StartUp Health Magazine Issue 14: The Network Effect

the Network Effect

Unlock the compounding potential of Health Moonshot Communities

"After a grueling couple of years, the last couple of months have been transformational. The StartUp Health community is literally the reason why we're in this position! You guys are awesome."

Katharine Barnard, PhD Co-founder, Spotlight-AQ

T1D Moonshot Community

The Power of Joining Mission-Aligned Networks

SSince 2011 when we launched StartUp Health we’ve been guided by this unifying principle: Health Transformers multiplied by the Network Effect equals Achieving Health Moonshots. At first glance, it may seem the multiplying force of network effects is the key variable, but it’s not. The real power lies in the purpose behind the networks—our Health Transformers and their health moonshot missions.

Health Transformers are mission-driven innovators taking on bold challenges like eradicating Alzheimer’s or ending diabetes. What sets them apart isn’t just their expertise or groundbreaking technology—it’s their unwavering commitment to a mission fueled by purpose.

We unite these brilliant minds in Health Moonshot Communities, creating a constellation of innovation around a dedicated health challenge. Together, they navigate obstacles more easily, collaborate more effectively, and share wisdom to avoid costly mistakes.

Imagine a single beam of light shining into the night sky. It’s bright, but its reach is limited, cutting through only a small patch of darkness. Now, picture thousands of beams of light scattered across the sky, shining independently— each illuminating a small area but still disconnected from one another. Together, they are bright, but fragmented.

But what happens when those beams are aligned? When they are focused toward a single, shared purpose, something extraordinary happens. They merge, creating a powerful, unified force that can light up the entire sky.

This is the power of a purpose-driven network. It’s not just about bringing people together—it’s about aligning them around a bold, shared mission that transforms individual

Steven Krein CEO & Co-founder

efforts into something far greater than the sum of its parts.

Today, thousands of healthcare innovators, doctorpreneurs, and scientists are working tirelessly to bring transformative health solutions to the world. These bright stars are full of potential, yet many are navigating the complex, often isolating universe of the health industry alone. Too many are working in silos, grappling with the enormous challenges of innovation without enough support.

Network effects aren’t just theoretical— they are a practical, essential ingredient for leapfrogging progress. We’ve seen this time and again over the past 14 years: when Health Transformers collaborate, share insights, or make the perfect introduction at just the right moment, the entire network benefits.

Yet the most powerful force driving this network forward is purpose. When a community of innovators is united by a shared mission, network effects are supercharged. Purpose transforms connection into collaboration, and collaboration into lasting, collective impact.

If you’re a founder working on your own health moonshot and want to join a community of like-minded Health Transformers, we’d love to meet you. Connect with us at startuphealth.com.

Unity Stoakes President & Co-founder

EDITOR-IN-CHIEF

Logan Plaster

DEPUTY EDITOR

Jennifer Hankin

CONTRIBUTING EDITORS

Nicole Kinsey, Lauren Schafer

EDITOR’S LETTER

Harmonics of Innovation

RRecently I interviewed Nathan Intrator, PhD, a member of StartUp Health’s Alzheimer’s Moonshot Community, about his company Neurosteer. He and his team have developed a brain scanning device that could be groundbreaking for folks with Alzheimer’s disease (read the full story on page 92). Before launching Neurosteer, Nathan studied dolphins and bats and became an expert in how their brains processed signals. That led to a discovery about human brains. To explain it to me, he conjured the image of an orchestra.

If you’re sitting in the orchestra pit right next to the second chair violinist, you’re going to get a narrow understanding of the music. If, instead, you sit in the middle of the concert hall, your ears will take in every instrument at once, giving you a blended, holistic experience. This, says Nathan, is how brain signals work, and is why listening to the “harmonics” in the brain, not merely individual signals, results in better brain analysis.

His story has stuck with me, and is a reminder of what makes the ordinary extraordinary among our global community of founders. Let me explain.

In this, our fourteenth print edition of StartUp Health Magazine, we added a new section. It’s a “where are they now” send up, only instead of talking about child actors from the 80s we’re looking at the startups we profiled in the last two issues. We asked companies to share big milestones since we featured them a year ago. We got responses like “integrated new hardware into the platform,” and “had a successful pre-FDA meeting,” and “landed a new distribution partner.” Read them all on page 118.

These may not seem like juicy headlines if taken alone. They’re just single notes. And yet, taken collectively, they are extraordinary because they’re part of a longer song. The startup journey is arduous, with peaks and valleys and only by stopping to celebrate the milestones – small as they may seem – can we appreciate the grander picture.

They’re also extraordinary because they’re part of an orchestra playing the same tune. When the daily milestones of startup life occur within a supportive network that is working towards the same health goals, that progress is placed in context and is amplified. Each individual note – the second chair flute or the T1D app – might sound small on its own. But taken as a whole, harmonizing and amplifying, the rhythm of progress becomes something else, something strong, meaningful and effective. A song that can change the world.

Logan Plaster Editor-in-Chief

Join a Health Moonshot Community

Entrepreneurship can be lonely at times, especially when the stakes are as high as they are in health. But the game-changing breakthroughs? They come from unprecedented collaboration— the kind that rewrites the rules, redefines what’s possible, and connects you to something far bigger than yourself.

Currently accepting applications for the following health moonshots

Alzheimer’s & Related Dementias

Type 1 Diabetes

Addiction & Opioid Crisis

Cardio-Metabolic Health

End Cancer

Food Is Medicine

Longevity & Healthy Lifespan

Mental Health

Oral Health

Rare Disease

Respiratory Health

Women's Health

HEALTH MOONSHOT HEADLINES, AT A GLANCE

HEALTH TRANSFORMERS IN THE NEWS

For daily news from the StartUp Health community of founders, follow us on social media @startuphealth and subscribe to the StartUp Health Insider newsletter startuphealth.com/insider

Innovative Solutions For Maternal Mental Health – An Interview with Anne Wanlund, CEO & Cofounder of Canopie FORBES

8/21/24 Devoted Health Raises $112M

FIERCE HEALTHCARE

8/20/24

Toronto-Based RetiSpec Uses AI to Detect Alzheimer’s Through Eye Exams

BLOOMBERG

8/14/24

NICH Is Scaling Enhanced Care Management Services for Higher Risk Youth Through PATH Funding

CALIFORNIA DEPARTMENT OF HEALTH CARE SERVICES

8/13/24

MIIST Therapeutics

Prescription-Only Nicotine Replacement Therapy (NRT) Could Ease Cravings Faster

REUTERS

8/9/24

Blood Tests Like ALZpath's for Dementia ‘Highly Accurate’ and Could Become Gold Standard Method of Flagging Disease, Finds Study

DAILYMAIL

7/30/24

RetiSpec Secures

C$13.8 Million to Detect Alzheimer’s Early Through Retinal Imaging

BETAKIT

7/26/24

The Best User Experience Design of 2024: Careteam Technologies Is Humanizing Digital Healthcare

FAST COMPANY

7/23/24

Spotlight-AQ Wins ADA Innovation Challenge for Mental Health Intervention

DIABETES TIMES

7/18/24

Medicare Could Soon Start Covering Digital Mental Health Therapies Like Arcade Therapeutics

FAST COMPANY

7/16/24

In order to engage the limited English proficiency Latino community, MiSalud Health begins with onsite health screenings to build trust.

Cindy Blanco Ochoa, CEO & Co-founder of MiSalud Health, Selected as a Rising Star in the 2024 Diversity Leaders in Healthcare Awards

MODERN HEALTHCARE

7/15/24

DocGo and Spect Teaming Up to Bring Vision Screening to the People

OPHTHALMOLOGY TIMES

7/11/24

Cityblock Expands Footprint in North Carolina

through Alliance Health Partnership

FIERCE HEALTHCARE

7/10/24

Zinnia: Reducing Stress for People Living with Dementia — and Their Caregivers

AGETECH COLLABORATIVE FROM AARP

6/20/24

Lazzaro Medical wins $2.4M SBIR grant from National Institutes of Health

BIZ WEST

6/10/24

Unpluq Helps Adults and Teens Cut Screen Time

BBC

6/8/24

Mediktor Acquires

Conversational AI Platform Sensely to Enhance Global Footprint

HIT CONSULTANT

6/5/24

9amHealth Executives Talk New Spanish Language Service, Inclusivity, and Accessibility in Healthcare in New Interview

FORBES

6/4/24

Help-Full Won the 2024 SF Design Week Award in Health and Wellness

SAN FRANCISCO DESIGN WEEK AWARDS

6/3/24

Virtual Talking Circles to Prevent Suicide: Televeda's Innovative App Seeks to Reach Native American Vets at Risk

MILITARY.COM

5/25/24

Postpartum Pelvic Digital Health Solution MUTU System Demonstrates Significant Impact and Value in NHS Evaluation

FEMTECH INSIDER

5/13/24

Babyscripts Teams up with Lyft to Provide Transportation to Maternal Health Services

FIERCE HEALTHCARE

5/15/24

Sift Healthcare Collects $20M for Medical Billing Tools

AXIOS 5/9/24

Time 100 Health: Venkat Shastri, Founder of ALZpath

TIME

5/2/24

As Part of the Inaugural National Cancer Prevention and Early Detection Month, Biden Cancer Moonshot Announces Gabbi Among New Actions to Strengthen Preventive Cancer Care and Expand Accessibility of Cancer Screenings

WHITE HOUSE 5/1/24

A Smart Cookie: Joydays Makes Better Snacks for People with Diabetes

SMARTBRIEF

4/25/24

World's Best Digital Health Companies 2024: care. coach, Diagnostikare, Joint Academy, Particle Health & Virta Health

NEWSWEEK

4/25/24

How to Go Slow to Go Fast with Sami Inkinen of Virta Health

INC. 4/24/24

Arizona Startup NEXT Life Sciences Is Working on Making Birth Control for Men a Reality

NPR 4/23/24

Zero Overdose and Pear

Suite Join Forces to Curb

Opioid Epidemic

MOBIHEALTHNEWS

4/4/24

Avanlee Care Is on Inc.'s 2024 Female Founders 250 List INC.

3/31/24

Forbes 30 Under 30 2024: Science & Healthcare: Scan.com Co-founders

FORBES

3/31/24

Pelago, Provider of Virtual Substance-Use Therapy, Raises $58 Million

WALL STREET JOURNAL

3/28/24

New York City Football Club Announces Epicured as Official Nutrition Solutions Partner

NEW YORK CITY FC

3/21/24

Mass General Brigham and Avo Partner for Rapid Response Care Workflows

MOBIHEALTHNEWS 3/6/24

Salvo Health Secures

$5 Million to Expand Wraparound GI Care Model

HIT CONSULTANT 3/1/24

Supporting the Alzheimer's Moonshot

From Gates Ventures to ADDF, get to know some of the newest additions to StartUp Health's mission-driven impact boards.

Meryl Comer is the Co-founder of UsAgainstAlzheimers and Vice Chair of Women's Health Access Matters (WHAM).

In your book "Slow Dancing with a Stranger," you detail how Alzheimer's profoundly affected your life and

led you to advocacy work. Tell us about that.

Comer: My husband's Alzheimer's diagnosis was devastating, especially as he was a brilliant NIH chief whose cognitive decline was a constant struggle. Despite a prognosis of five years, he lived for 24 years, during which I felt increasingly powerless.

Advocacy became crucial for me. It was a way to regain some control and make a difference, leading to significant increases in Alzheimer's research funding. This work not only pushed for better policies but also helped shift federal perceptions of the disease and highlighted its impact on women as patients and caregivers. Two thirds of the victims of Alzheimer's disease are women, and we're two thirds the caregivers. We need to tease out the difference between men and women, as research is beginning to reveal that women may experience the disease differently, such as having a higher risk profile if the disease is on the maternal side and showing more precipitous drops in cognitive function compared to men.

Craig Ritchie, PhD leads Scottish Brain Sciences, has led major Alzheimer's cohort studies, and holds an academic position at the University of St Andrews.

How has the understanding of Alzheimer's disease evolved over the years?

Ritchie: Over the past 15 to 20 years, our understanding of Alzheimer's disease has advanced significantly. Initially, many drug trials failed because we didn't fully grasp the complexities of the disease. We now understand that Alzheimer's disease and Alzheimer's dementia are not the same. Alzheimer's disease refers to the early, asymptomatic phase where

changes in the brain might occur years before symptoms develop. Alzheimer's dementia, on the other hand, is the clinical syndrome characterized by noticeable symptoms in later life. This distinction has helped refine research and treatment approaches, focusing on the disease’s early stages rather than just the symptomatic phase.

What is the current state of early detection in Alzheimer's research?

Ritchie: Early detection in Alzheimer's research has made great strides. Studies like Prevent and EPAD are leading the way by identifying individuals who are at risk of developing Alzheimer's before symptoms appear. These studies use advanced techniques such as brain imaging, blood tests, and spinal fluid analysis to detect early changes in the brain. The goal is to identify potential problems well in advance, which could allow for earlier intervention. This proactive approach is critical as it opens up possibilities for

preventative strategies and more personalized care.

How do you see tech advances improving life for people with Alzhiemer's?

Ritchie: Innovation is crucial in both Alzheimer's research and treatment. Technological advancements are providing new ways to support individuals with dementia. For example, smart home technologies and devices like Alexa are helping people maintain their independence and cognitive function for longer. Additionally, there’s a growing recognition that beyond drug treatments, lifestyle changes and managing other health conditions are important. Innovations also include developing accessible tools—such as apps and algorithms—that make resources more visible and usable. Overall, these innovations contribute to creating more dementiafriendly environments and improving the quality of life for those affected.

INDUSTRY SHAPERS: THE STARTUP HEALTH IMPACT BOARD

Kristina Malzbender is the Associate Director of Health and Life Sciences at Gates Ventures.

Where do you see opportunity for strategic collaboration in Alzheimer's?

Malzbender: If we can combine the efforts that are being made by these companies developing blood tests with companies developing digital cognitive assessments and companies developing

novel therapeutics and get them together to think about some of these implementation challenges, that would be hugely impactful. We need to redefine the whole patient care workflow.

What challenges do you see in taking cutting-edge diagnostic tools and therapies from the lab to widespread clinical use?

Malzbender: With some Alzheimer's innovations, like blood tests, we’re waiting on FDA approval and broad accessibility. Some tests are available but not scalable enough. In terms of the digital cognitive assessments, one challenge has just been the lack of consensus about the tools, which each have different advantages. We’re faced with the challenge of how do we actually get

all of those advances into clinical care and implement them and get them reimbursed.

How does your personal experience [with your grandfather's Alzheimer's diagnosis] influence your vision for the future of patient care?

Malzbender: This experience inspired me to focus my career on Alzheimer’s and neurodegeneration. Patients like my grandfather often end up going to their doctor and going through all of these cognitive tests and still end up with opaque diagnoses of cognitive impairment but no understanding of what's causing it or what can be done. This just reinforces the need for better biomarkers and better diagnostics.

"Two thirds of the victims of Alzheimer's disease are women, and we're two thirds the caregivers. We need to tease out the difference between men and women, as research is beginning to reveal that women may experience the disease differently."

-Meryl Comer

Aishu Sukumar contributes to several Alzheimer’s initiatives at Gates Ventures, leading efforts including the Diagnostics Accelerator (DxA) program in partnership with the Alzheimer’s Drug Discovery Foundation (ADDF).

What drew you to working on Alzheimer's disease?

Sukumar: When I was in college, one of my close friends’ parents was diagnosed with early-onset Alzheimer's, and I got to see just how absolutely devastating it can be. There wasn’t much my friend could do but watch her mother slowly descend into dementia. Being the

only child of a single parent, the entire burden fell on my friend. This made me reflect on how this is probably the reality for millions of people and how only now we're starting to scratch the surface on solutions.

Tell us about the Diagnostics Accelerator (DxA)?

Sukumar: The Diagnostics Accelerator was established with the Alzheimer's Drug Discovery Foundation (ADDF), and Gates Ventures is one of its funders. Through the DxA we support everything from early-stage researchers who are working in biomarker identification and discovery, all the way to late-stage companies who are focused on bringing these solutions to market. We recognized that there’s NIH and NIA funding for early-stage research and VCs and hedge funds and other investors who invest in these companies where the risk is relatively lower and return is higher. And there was this kind of gap that

needed to be filled in areas like Alzheimer’s where the path to treatment was less clear and the risk was higher. And we felt that this is where philanthropy can make a difference.

If you could get a few companies around a table to collaborate, who would be there?

Sukumar: Imagine if you could take a company focused on these bloodbased biomarkers and someone focusing on digital tools and bring them together for this even stronger multimodal marker. Maybe you can detect the disease earlier, maybe it can be more accurate or push the performance to the next level. What I like to also think about is beyond just diagnostics to the entire Alzheimer's disease care continuum. From tools for supporting caregivers to education and awareness.

Each issue we introduce you to the inspiring founders who have joined the StartUp Health community. Are you a passionate founder ready to accelerate growth by joining a like-minded Health Moonshot Community? Get started today at startuphealth.com/membership

Kernel’s New Infrared “Helmet” Could Make Brain Health Analysis Simple and Affordable

After years of R&D, CEO Ryan Field, PhD, and his team of engineers and designers are introducing an exciting new piece of hardware. This brain scanning device, modeled after a snowboard helmet, uses safe infrared light to dynamically measure oxygen levels in the brain. The ready-to-wear form factor and cloud-based analysis means that this brain health scan can be performed anywhere, by almost anyone.

EEvery year millions of people make a pilgrimage to their primary care doctor’s office for an annual physical. At these perfunctory visits, we expect to get certain information. How is my cholesterol? Is it any lower since I started that new diet? How about my blood pressure? The list goes on.

As people age beyond 50, 60, and 70, these visits become even more important, with new concerns arising each year. Many people use their annual doctor visit to bring up concerns about their brain health, usually because they are experiencing some memory loss. These are often the signs of mild cognitive impairment (MCI), which is experienced by 10% to 20% of people over 65.

But unlike lung health and heart health, primary care doctors can’t provide patients with much data on their present and future brain health. Do I actually have MCI or am I just having an off day? Am I on the road to Alzheimer’s or dementia? Would I benefit from starting an early intervention medication? Today, clinicians rely heavily on pen and paper tests – or digital versions of them – to do their best to address these questions. Some of these questions could be answered more completely with a functional MRI (fMRI), but this process is so costly and onerous that precious few ever get sent for one. The millions of other patients who simply would like an in-depth datapoint on their brain health vitals are left out in the cold. And millions of people with brain-related illnesses are diagnosed far too late.

That all could change thanks to a startup called Kernel, which joined StartUp Health’s Alzheimer’s Moonshot in 2024.

ORIGIN STORY

Like many health tech startups, Kernel’s story began with an individual who encountered a particular health challenge and a major roadblock in care. In this case it was tech entrepreneur Bryan Johnson experiencing a 10-year bout with depression. Throughout his battle he’d visit specialists and was disappointed by the lack of data. How was his brain actually performing? How was it responding to treatment or therapy? It was a black box. And if it was a black box for him, a well-resourced technophile, how much more so was it for the hundreds of millions of people with hurdles to care?

Where this origin story differs from others is that this particular founder sold his tech company for $800 million dollars. That meant that when he decided to develop a new tool for affordable, accessible brain analysis, he had the capital to do it right.

Johnson hired a dream team of engineers, designers, and brain experts, pulling top talent from Qualcomm, Oakley, Intel, Harvard, Caltech, and SpaceX, and gave them the time and funding needed to invent something truly novel. That team included Ryan Field, the company’s current CEO, who was originally hired to build a new kind of optical sensor. Field spent his career building optical and chemical sensor systems, including a stint designing systems for autonomous cars. When

he was offered a chance to apply his PhD work to one of the biggest and most impactful challenges of our time – brain health – it was a dream come true.

Kernel’s R&D took five years and a lot of money before the team felt like they’d accomplished their mission. But it was well worth the effort, says Field.

“We spent over $50 million in R&D. A lot of money went into the tech nology build, and it's one of the things that differen tiates us. There's no other company in the world that has a measurement capability like ours.”

Now, after six years of development, Kernel is bringing their research and new product to life in the real world.

anyone. When Field is at industry events, he often has one in his backpack and encourages people to try it on or have a demo.

Looking inside the helmet, Field compares Kernel to a pulse oximeter in how it uses light to measure oxygen in the blood. Kernel’s optical sensors measure oxygen in the brain by sending small amounts of infrared light through the skull. The light is scattered throughout the brain and then returns to the source to provide data.

UNDER THE HOOD

At first glance, the Kernel product looks like an ordinary helmet and is worn in a similar way. Just place it on the head and you’re ready to scan. That ease of use is part of the magic of the product. What’s hidden beneath this apparent simplicity is a complex technology stack for performing detailed measurements of the brain. Unlike brain scan devices like fMRI that require special rooms and speciallytrained attendants, this “helmet” can be placed on a patient’s head by pretty much

“Where we've done something really unique is we measure how long each individual photon spends in the head,” says Field. “Detecting that is tough, but it allows us to separate what's happening in the brain from what’s happening in the scalp.” The result is a dynamic map of the oxygen in the brain.

“Whenever you're doing something, like thinking really hard, you engage all these neurons in the prefrontal cortex in the front of your brain, and you see that they demand fresh, oxygenated blood,” says Field. “So we measure where the blood oxygen is moving in the brain to know what parts of the brain are active at any instant in time.”

Based on how those levels change,

“We spent over $50 million in R&D...it's one of the things that differentiates us. There's no other company in the world that has a measurement capability like ours.”

-Ryan Field, CEO of Kernel

Kernel can tell a lot about the individual, including how cognitively healthy they are.

“You can think of it almost like measuring the fuel efficiency (MPG) of a car, but for the brain,” says Field. “We can measure how much effort the brain uses to do a job. Brains that have to work harder to perform a task may show early signs of illness.”

According to Field, Kernel’s product is safe to use.

“The amount of light that we use to measure the brain is so small that you can buy laser cat toys on Amazon that are more dangerous.”

WHAT’S NEXT

Kernel is moving into an exciting new phase as it comes off the successful completion of a pilot clinical trial aimed at showing that their device can correctly identify mild cognitive impairment. The next phase of the company is turning their successful research into a simple, repeatable product and clinical process that can be run end-to-end in under ten minutes.

Key to their go-to-market strategy is Kernel’s hardware plus algorithm approach. Traditionally, brain scanning hardware has been prohibitively expensive. Kernel has slashed this cost, and plans to lease devices to healthcare providers and then charge for algorithmic analysis on a per-scan basis. That high-volume opportunity on the reimbursable scanning fees means Kernel can drive down hardware costs even more, making each individual test more accessible.

Put simply, Kernel is building towards a not-too-distant reality where patients can come in for their annual wellness visit and, as a part of their regular vitals, get a Kernel brain health scan. That means more people can understand the trajectory of their brain health and, where appropriate, begin to take action. With new therapies for diseases like Alzheimer’s becoming available, these preventative health measures are more important now than ever before. CONTACT KERNEL@STARTUPHEALTH.COM

Oben Health Brings Preventative Health to the Barbershop

Enlisting barbers as community healthcare workers, Peter Njongwe of Oben Health (pictured on next page) hopes to screen more Black men for hypertension and put them on a path toward better health.

PPeter Njongwe, CEO & Co-founder of Oben Health, wants to improve access to healthcare by meeting people where they are — and barber-

shops seem like the right place to start. He hopes that lives will be saved through barbershop screenings for cardiovascular conditions. For him, the mission is personal. “My brother passed away from uncontrolled hypertension at age 36,” says Njongwe. He went to bed and never woke up, leaving a wife and two children behind. “If my brother had gotten screened for hypertension, I think he would still be alive,” says Njongwe, who considered his older brother as a father figure. “This haunts me until today.”

Peter Njongwe, CEO & Co-founder

CHALLENGE

Since starting Oben Health, Njongwe has been turning his grief into action. “Our initial target is Black and Brown men,” says Njongwe. “They’re one of the least engaged populations when it comes to health,” he adds. Research shows that Black adults are more likely to die from cardiovascular disease than other racial groups and that one in five Black adults miss routine and necessary preventative screenings. Njongwe found himself frustrated with the normalization of hypertension and high blood pressure within his community. “‘Oh yeah, it’s fine. Nothing’s gonna happen.’ It’s just so normal to hear that,” says Njongwe.

Njongwe understands the reluctance to visit a clinic for health screenings. “No one enjoys going to see a doctor or being at a clinic,” says Njongwe. There are also structural barriers that make it hard for folks to go to the doctor such as taking time off work, transportation, childcare, etc. But with advances in technology, he is surprised that more creative solutions haven’t been found. “Why is chronic disease getting worse in this community? Why is it not getting better?” he asks. Through research and discussions with partners, Njongwe found that it wasn’t a lack of tools preventing progress. “It was access and support of community-basedoutpatient clinics (CBOCs),” he says.

WHAT THEY BUILT

There are about 280,000 barbershops in the US according to Njongwe, 100,000 of which serve their target audience. “On

average, men go to the barbershop about once a month,” he says. “A clinic would kill to have those numbers.” Oben Health is committed to providing digital support to community-based organizations involved in place-based services, such as the barbershop and community health worker models. Although these organizations spearhead the implementation of these innovative services, Oben Health’s role is to boost operational efficiency through automation and offer real-time data insights into their effectiveness. This partnership seeks to deepen our understanding of interactions within community settings (like barbershops) and enhance care coordination and case management for individuals diagnosed with cardiovascular disease, ensuring they receive prompt treatment.

Before the establishment of Oben Health, Roots Community Health Center had already implemented a barbershop healthcare model known as the Cut Hypertension Program. The organization was looking for a technology partner

to support the demands associated with expansion of their barbershop model. At that time, Njongwe was embarking on his own path. He had pursued computer science and entrepreneurship in college and gained experience in product management and behavior design through his work with tech startups. With his background, Njongwe founded Oben Health, driven by a similar ambition to address cardiovascular disparities. However, he recognized a gap in his expertise, particularly in clinical and community-based experiences. This realization led to an exploratory partnership between Oben Health and Roots Community Health Center.

To bridge the gap between barbershops and primary care homes, Oben has been collaborating with CBOCs and community members to enhance support for existing community-based clinical service workflows and data management. Additionally, they are providing extra tools to improve the execution of placebased services. For their initial use case, they are developing a digital platform to support a CBOC that employs barbers as community health workers, utilizing existing reimbursement models for community-based services (currently, in California, this rate is $26 for every 30-minute interaction).

The goal is to empower community spaces and foster better health outcomes through a supported digital environment. “I tell my barber probably much more than I tell my partner, and that’s a reality for most men,” observes Njongwe. “How can we support that sacred space in ad-

dressing community needs?” Barbershops often host health-related discussions, and with the training and encouragement, barbers can direct these conversations towards actionable health measures, such as taking blood pressure measurements. The incentives for barbers go beyond financial rewards. “We aim to provide real-time visualization of how community health workers, like barbers, can positively impact the health and wellbeing of the communities they serve,” says Njongwe.

WHERE THEY ARE IN THE PROCESS

Oben Health is currently building technology to streamline the interaction between a barber, clients/patients, and a team of professionals responsible for managing the care of any at-risk individuals. “We’re building tools to automate the reporting segments of this,” says Njongnwe, who is experimenting with audio intake and scribes. “We don’t want the CHWs to be burdened with any administrative processes,” he says.

Critical to the Oben’s success is supporting the integration of clinical services in community spaces, such as the barbershop space. Supporting patients in receiving services in places they are comfortable and trust is important. The CBOCs they are working with are deploying pharmacists to go directly into the shops to treat patients with uncontrolled hypertension. “If you just refer a patient to go see a primary care provider, you’re going to have people falling off,” says Njongwe, who is working on a platform to support communication between patients, pharmacists,

case managers, a care team, and payors. Much of this is backend infrastructure, but the company is also working on an app that patients will use to enroll in a placebased service that provides a care plan, health education, and opportunities for interaction with their care team (including CHWs).

Currently, Oben Health is working with four other healthcare companies. Revenue is generated by collecting between $1,500 and $3,500 per patient per year, paid by managed care organizations and health systems. Oben Health hasclosed a pre-ssed round, continues to grow their team, and are gearing up for a major product launch and partnership with a health system in the next quarter.

OUR TAKE

“I really think community spaces are excellent spaces to access preventative care,” says Njongwe. With advances in technology, clinics no longer need to be the only nodes for healthcare. Oben Health is forward-looking by empowering existing community spaces and leveraging technology to improve preventive care within a population that has been historically overlooked in care delivery design. Oben Health’s system is efficient, original, and just in both its design and execution.

Although Oben Health is focused on hypertension in the Black community, the technology they are developing shows potential for application to other conditions, like cholesterol or mental health, and other spaces, like nail salons or churches. They are designing technology with an eye toward adaptability — a “plug-andplay model that supports bringing care to where people are,” says Njongwe.

Oben Health’s holistic data — which is continually updated whenever someone engages with the app — and their innovative use of technology to bring healthcare to community spaces promises to serve as a model for the future of preventative care and a tool to tackle some of our nation’s most intractable health problems. CONTACT OBEN@STARTUPHEALTH.COM

Moneta Health Provides Early Brain Health Therapy You Can

Access Over the Phone

Serial healthtech entrepreneur Paul Campbell and bioengineer Jen Flexman, PhD, have teamed up to bring an AI-powered earlyintervention Alzheimer’s treatment to market, one that brings hope to patients and caregivers through a familiar medium and is covered by Medicare.

A“At the core of Moneta Health is my mom,” says Paul Campbell.

Campbell had been working in digital health since 2010 when his mother, a former nurse, said something to him that now feels prophetic. She looked at his work – a startup that Campbell pitched as a mental health coach in your pocket – and she told him his next big venture should be something that helped seniors.

Fast forward a few years and Campbell’s mother was diagnosed with early dementia.

“Unfortunately, the healthcare system offered little hope and limited early-intervention treatment options, especially non-drug alternatives,” Campbell wrote recently online. “There was also a lack of personalized education and support for families and caregivers. I realized very quickly that millions of people around the world are going through the same thing.”

In 2021, Campbell met Jen Flexman, PhD, and the wheels began to turn. Flexman did a PhD in bioengineering and got immersed in neuroscience. She worked with a team of engineers and radiologists to study the aging brain by analyzing large imaging datasets. She moved into the world of commercialization with Canada's largest diagnostic lab and then joined Babylon Health during an incredibly rapid period of growth for the company.

Flexman was at the nexus of a telehealth revolution, but she saw a flaw. Too many of these app-based platforms were being created for relatively healthy young people. Where did that leave seniors who

Paul Campbell, CEO & Co-founder

actually use the vast majority of healthcare services?

In Paul Campbell, Flexman found an industry veteran with a passion for dementia care and a track record for building successful startups. The two set their sights on developing an early-intervention behavioral therapy platform for Alzheimer’s disease and related dementias (AD/RD).

UNDER THE HOOD

Generally, patients will come to Moneta Health after having received an initial diagnosis of mild cognitive impairment (MCI) or early dementia.

“Getting those diagnoses is very emotional and what compounds that negative experience is that a lot of physicians don’t

provide many options for what you can do next,” says Flexman.

Moneta aims to be the standard of care for this scenario, the go-to accessible cognitive rehabilitation therapy resource for any physician – likely a primary care physician or a neurologist – diagnosing early cognitive decline.

Patients are referred to Moneta by a provider. The Moneta program is a recurring monthly course of treatment and is covered by Medicare. The first step in the patient experience is meeting with one of Moneta’s therapists by phone.

“We have an amazing, compassionate team of speech language pathologists who are specialized in dementia and cognitive impairment,” says Flexman. “They will really spend a good amount of time doing cognitive testing and understanding the patient and their daily life.” Patients often come with specific concerns, like no longer being able to remember names or the steps in their favorite recipes, and Moneta’s therapists can quickly begin working on a plan tailored to their needs and, if needed, those of their caregiver.

So far so good. But here is what might be Moneta’s elegantly simple secret sauce. The entire program is handled over the phone, with a powerful technology platform behind the scenes. Not an app, not a webpage. It doesn’t even require a smartphone. Any landline will do. For the Moneta team, virtual care was essential – many patients are in so-called neurology deserts without access to high-quality care. But it was also essential to lower the barrier to entry as much as possible. Many

Jennifer Flexman, PhD COO & Co-founder

seniors lack the devices or the internet bandwidth for virtual care.

After the therapist completes a cognitive assessment with the patient, they begin receiving calls from Moneta’s AI voice assistant, Mona™. The patient is prompted through a traditional phone call – no need to remember to log in to anything, ever –to complete the cognitive restorative and compensatory activities set out by their therapist. If a patient misses a call or wants to do extra practice, no problem: they can simply call Mona back at any time.

“There's a huge clinical benefit to being able to do these activities on your own time, rather than simply waiting for when

a therapist is available to do it with you,” says Flexman.

Moneta’s programs can target specific cognitive deficits, like short-term memory or language. They also provide education on strategies for improving cognitive function in daily life.

Patients participate in the program for an average of two months, getting intensive care from therapists, and then they can be transitioned to a maintenance program, interacting primarily with Mona, the AI assistant.

“We definitely want to support a patient journey that is not just one and done,” says Flexman. “This is a chronic condition. It's neurodegenerative. People have different stages of decline that they need help with, and we want to be there every step of the way with the individual.”

For patients, the Moneta program offers a path to greater independence. Moneta’s early results show a statistically significant increase in patients' average quality of life score and other cognitive measures. In the words of one patient, “I learned to deal with one task at a time and to give my complete attention to that task rather than multitasking. I also learned to be patient with myself.” Other individuals report more self esteem and the confidence to navigate communication with family and friends more effectively.

OUR TAKE

Moneta Health is like physical therapy for the brain, delivered through a traditional phone call for maximum accessibility.

It’s an elegantly simple sounding idea, but the Moneta team has a few important things going for them that make us particularly excited to support them.

In Campbell and Flexman, they have a powerful combination of experience, combining digital health operational ability with engineering and deep knowledge of neurodegeneration.

They’re also very smart in their go-tomarket strategy. By showing strong early results in terms of improving cognitive function and patient quality of life (with more trials to come), they’re securing big name referring partners. They’re also tapping into known reimbursement codes, so that they can generate revenue to feed product development.

And, as we have found to be so important in this market of long sales cycles, Moneta’s team has the personal passion necessary to commit long term. Campbell is doing this for his mom and so many moms like her.

Under the leadership of Paul Campbell and Jen Flexman, PhD, Moneta Health has the potential to become an essential piece of the care continuum for Alzheimer’s and other dementias.

CONTACT

MONETA@STARTUPHEALTH.COM

Goodbye Wasted Insulin: InsulinSaver Helps People with Diabetes Keep Their Medications Effective

Sibling co-founders Hanna and Oskar Dahl have joined forces to build an easy-touse device that alerts people dependent on insulin when their medications have been exposed to too much heat or too much cold.

MMost people with Type 1 diabetes and many with Type 2 have to inject themselves with insulin every day, sometimes up to five times a day. Every dose requires thought as the individual measures their blood sugar and actively uses the insulin to keep their glucose within a healthy range.

This daily medication dance causes serious decision fatigue. According to one study, people with insulin-dependent diabetes have to make an average of 180 more decisions per day compared with people without the disease.

But that’s not all. Unlike most pills that are taken daily for chronic diseases, insulin is a bit delicate. Specifically, it can become ineffective if it comes in contact with hot or cold temperatures.

So what do you do if you have diabetes and you bring your insulin to the beach on

a hot day? Or accidentally leave it in your car on a cold day? Or what if you live in a country without electricity? If you’re concerned that your insulin has been damaged by heat or cold, you have two choices: throw it out or use it and roll the dice.

Taking ineffective insulin is a disaster waiting to happen. Imagine taking a carefully dialed dose of insulin before bed in order to counteract a heavy meal, only to find out in the middle of the night that the dose did nothing. You could end up in the hospital. On the flip side, imagine throwing away expensive insulin every time you worry that it’s been exposed to too much heat or too much cold.

Most people have accepted this costly, dangerous reality as part of the challenge of diabetes. But when Hanna Dahl realized how much insulin she was wasting due to temperature swings, and how much uncertainty the problem was adding to her life, she decided to take action.

ORIGIN STORY

Hanna Dahl, who lives in Sweden, was diagnosed with Type 1 diabetes at age 10. As a college student she fell in love with traveling. She’d pack a backpack, get a train ticket, and be off to a new country.

She was well acquainted with the problem of exposing her insulin to high and low temperatures, but the problem came to a head on a trip to Italy in 2017. She stored her insulin in a fridge in a hotel room, and then after swapping the insulin into her pen, she noticed her blood sugar rising. She gradually increased the doses, thinking she had an infection. She kept getting worse. She got dehydrated, got a headache, and felt nausea. She got to the point where she was doubling her normal dose but still had high blood sugar.

Finally, her travel partner realized that foods were partially freezing in the hotel fridge and that the insulin must have become inactive. She survived the episode but it left her shaken. And determined.

When she got back to Sweden, Hanna laid the problem out for her brother, Oskar, who was running an engineering consultancy. He started to workshop the problem. It turned out to be a bigger technical challenge than expected, says Oskar. Insulin goes bad quickly when it’s too hot or cold, and so any kind of alert system had to be well calibrated.

“It doesn't change shape, color, or taste,” says Oskar. “When it’s too cold, it’s just, boom, inactive. And you have no way of knowing.”

Their first breakthrough came in the form of new micro-computers. Oskar realized that these new micro-processors could survive on a cell battery, thus making their prototype possible.

Hanna and Oskar labored quietly on their device – a smart temperature monitor that is purpose-built for insulin – even re-

ceiving CE Mark approval in Europe. But they didn’t think much of its larger market potential until they attended ATTD, a major conference on diabetes technology.

“We went to ATTD expecting nothing,” says Oskar. “But we were completely overwhelmed by interest from physicians, nurses, and patients. We had people from Brazil standing in line to buy the device. That’s when I knew this could be something real. After that event, we realized this could actually help a lot more people.”

“We went there with something like 100 samples,” says Hanna. “We thought we’d give out 20 of them. We were out in 10 minutes.”

From that moment forward, Hanna and Oskar shifted their thinking entirely, from a small startup focused on one person’s problem, with a single market focus, to a scalable company with the potential for global distribution.

UNDER THE HOOD

InsulinSaver is a continuous temperature monitor the size of a small pocket calculator that is meant to be stored next to insulin. The device is calibrated specifically for

insulin, and gives the user warnings if their insulin has been exposed to harmful high or low temperatures.

The key word there is “harmful.” The device is smarter than a typical portable temperature monitor that has a maximum and minimum temperature alarm, Oskar notes.

“We're evaluating the temperature in a smart way, and we will not produce an alarm just because of a temporary spike or dip in temperature.” Since he lives in Sweden, Oskar gives the example of a skier carrying insulin in their jacket. They might open up their coat for 10 seconds and expose the insulin to extreme cold temperatures for a moment. But InsulinSaver is smart enough to know that there hasn’t been enough sustained cold to ruin the medication.

It was essential to Oskar and Hanna that their device work without cables or apps, so you can just throw it in your gobag or in the fridge near your meds, and it will do its job. They purposefully chose to keep all of the functionality on the device itself, so they were never constrained by an uncharged phone or a weak bluetooth connection.

FINAL WORD

InsulinSaver is another entry into the list of medical devices that appear elegantly simple but serve a major patient need.

We’re excited to support Hanna and Oskar and the InsulinSaver team because they’re tackling the dual goals of improving outcomes and cutting costs. Having insulin-dependent diabetes is expensive – for individuals, companies, and nations.

Preserving effective insulin and avoiding unnecessary waste can save millions. At the same time, and more importantly, ensuring that insulin is active and effective every time will save lives.

InsulinSaver can also save brain space, and that’s a precious commodity for someone with diabetes. Having diabetes and being insulin dependent means making decisions all day and worrying about your blood glucose levels constantly. Having a smart tool that assures you that your insulin is effective to use takes one worry off the table.

InsulinSaver also has the added benefit of making people smarter about their insulin storage. For Hanna that meant realizing that the window sill where she liked to set her insulin pen got too hot from the sun. As she got alerts throughout her week, she modified her behavior and now has a much more accurate understanding of how and where to safely store her insulin.

The future appears bright for this small Swedish team. They’ve partnered with a big distributor in Germany and have made inroads in France, the two largest European markets.

Finally, we love InsulinSaver because, in true Scandinavian fashion, they want to keep their device affordable for all. There are some clear and exciting applications for their work in low-resource settings, where people with diabetes may not have access to refrigeration.

Zinnia’s

Smart

Take on

Slow

TV

Brings

Comfort to People with Dementia and Their Caregivers

Co-founders Allyson Schrier and Bill Uniowski

Allyson Schrier combined her experience as a caregiver with her career in tech to solve a persistent problem for people living with Alzheimer’s disease and related dementias and their overextended caregivers. Her research-backed take on “therapeutic TV” has won the company an enthusiastic initial user base, and their team is poised to scale.

LLike so many innovations in healthcare, and especially in the world of dementia, Zinnia was born out of personal experience. In this case it began when Allyson Schrier’s husband was diagnosed with frontotemporal dementia at the age of 47.

“It’s a particularly nasty form of dementia because it generally results in a wholesale personality change,” says Allyson. “People lose their executive functioning and things like empathy can go out the window. He had been just the sweetest guy, and yet as the disease progressed he would become completely enraged because he could no longer button his shirt or listen to music.”

His condition progressed to the point where Schrier had to move him into a longterm care facility. That’s when her eyes were opened to a new problem in dementia care, one that was making life harder for both patients and caregivers in an already stressful situation.

THE CHALLENGE

What Schrier discovered was that it was common practice to park people with cognitive decline in front of a television for hours on end, with the assumption that it was a way to entertain, distract, or pacify them. From the very start, Schrier knew that the opposite was in fact true, and that something needed to change.

“Early on in the disease my husband was able to say he didn’t want to watch something or simply leave the room, but as his dementia grew worse he became trapped in front of the television. I would show up and he would either be agitated about what he was watching, or he’d seem lost.”

The television was not only causing more agitation, thought Schrier, but it was a huge missed opportunity for something positive. That’s when the wheels started turning on an idea. What if she could create a new kind of video content, something specifically designed to help folks suffering from dementia, while also easing the burden on their caregivers?

THE DIY DAYS

Schrier went into research mode. She read the available research (there wasn’t much) and immersed herself in the world of Alzheimer’s caregiving. She even got certified to train Alzheimer’s caregivers. What she learned was that the best video content for this patient population had a few important characteristics: it was slow paced, low on plot, and had no confusion between fact and fiction.

Using these simple parameters, Schrier started DIYing content for her husband

using her iPad and iPhone. At first they were simple videos about their children and their vacations. But they worked. So much so that she began asking herself some bigger questions. How could she improve the quality of the videos and then get them into a lot more hands? Luckily, Schrier had a bit of prior experience solving big technical problems.

Before her children were born, Schrier worked as the head of technology for the Experience Music Project, a unique position that had her acting as the personal technology manager for Microsoft cofounder Paul Allen. What Allen dreamed up, Schrier brought to reality, and the job instilled in her the belief that with the right team, even the wildest ideas were possible.

“It's only ridiculous if you can't find the right people to build it,” says Schrier.

The first “who” that Schrier turned to was Frank Lee, an accomplished designer who’d worked at Apple, Mozilla, and Microsoft. Friends introduced Schrier to Lee, and the idea resonated with him almost immediately. “Let’s do it,” he told her.

Lee turned around and recruited Bill Uniowski to the cause. Uniowski was an experienced media tech executive who’d lost two grandparents to dementia. He heard Schrier’s story and was hooked. A talented visual artist and filmmaker, Berenice Freedome, rounded out the initial team.

For four years the four labored on Zinnia as a side passion project, meeting once a week to develop and improve their content. Schrier would visit homes and facilities where people were caring for people with Alzheimer’s. She’d show them the vid-

eos they were developing and watch how people responded – and then iterate and iterate again.

THE INFLECTION POINT

The COVID lock-downs in 2020 shut down Schrier’s patient visits but ended up giving the project an unexpected shot in the arm. The team decided to throw their content on a website for free in the hopes that people would find value and share some feedback. The response was powerful.

“What we started discovering from the feedback was that these videos had a therapeutic potential that we hadn’t fully appreciated,” says Schrier. She and her team decided to conduct a two-year research project at the University of British Columbia and Vancouver General Hospital where they tested Zinnia in longterm and acute-care settings. Among other things, they discovered that Zinnia videos

had the potential to decrease the overreliance on antipsychotic drugs within dementia care facilities.

“Antipsychotics are not meant to be used for people with dementia, yet they're used all the time because it’s a quick fix and calms people down,” says Schrier. “We have had people reach out and share amazing stories about how Zinnia videos were able to calm patients down who’d previously relied on drugs. So much so that their care plan was changed, with Zinnia added as a first course of action. The researchers at UBC found the same thing.”

Zinnia’s next inflection point came when they were chosen for the Techstars Future of Longevity Accelerator in January 2023.

“We believed in our content, but until we were chosen for Techstars, I’m not sure we believed in ourselves as a company,” says Uniowski.

UNDER THE HOOD

With a product as seemingly simple as Zinnia, the details are everything. That’s where Chief Designer Frank Lee and Chief Creative Officer Berenice Freedome come in. Lee makes the user experience seamless while Freedome makes sure every video is aesthetically pleasing and tells a compelling – if simple – story.

Zinnia’s videos range from topical videos that engage the mind – while remaining slow paced and clear – to calming videos of pets and nature, to “activity of daily living” videos that encourage positive actions in patients, like drinking water or using the bathroom. The team painstakingly plans

every detail from color to sound to image speed. The Zinnia team has made their videos available on a broad array of devices, including streaming platforms like Roku.

OUR TAKE

There are a lot of reasons we’re excited to have Allyson Schrier, Bill Uniowski, and the Zinnia team in StartUp Health’s Alzheimer’s Moonshot. First, Schrier is exactly the kind of founder we look for to join the Health Transformer community. She’s got amazing technical experience and she has a fire to change the status quo. Her positive energy and attitude in the face of this devastating disease are infectious. She’s also attracted an all-star team to take the project to the next level.

We’re also bullish on Zinnia because it’s aimed at helping patients and caregivers alike. Schrier’s experience with her husband gave her a deep passion for dementia family caregivers, who bear such a heavy emotional load that they’re said to be six times more likely to get dementia themselves. Recently the Zinnia team did a survey of caregivers who were subscribed to their platform and 80% said that the videos reduced their own stress.

Schrier and her team are bringing moments of peace and little nuggets of joy into very stressful and strained situations, and that’s a beautiful thing. With their clinical research and the amazing team they’ve formed, we think Zinnia is poised to scale and have an even greater impact.

CONTACT

ZINNIA@STARTUPHEALTH.COM

ALZpath Is Powering a New Wave of Blood-Based Alzheimer’s Tests

With their renowned scientific team, ALZpath is leading the charge on a new breakthrough in Alzheimer’s detection: blood-based biomarkers designed around the p-tau217 antibody.

TThere around 55 million people living with dementia globally and the numbers are skyrocketing. Some estimates project we’ll hit 140 million people by 2050, and that’s likely under-reporting due to poor diagnostic tools. In short, the scope of the Alzheimer’s problem is massive and growing rapidly. There are new therapies, clinical trials and lifestyle changes that can help people with Alzheimer’s but that requires that they get an accurate and timely diagnosis. Today the gold standard for diagnosing Alzheimer’s involves complicated workups, expensive scans and painful

Chad Holland, CEO

spinal taps. It’s the opposite of the famous “triple aim” in healthcare; it’s costly, painful and inaccessible.

In this series we’ve shared news about a range of startups working to shift this narrative by offering low cost, non-invasive early diagnostics for Alzheimer’s disease. One of the most exciting and noteworthy of these developments are tests that can detect Alzheimer’s from a simple blood panel. Leading the charge on the science behind these breakthrough blood tests is ALZpath, one of the newest members of StartUp Health’s Alzheimer’s Moonshot.

ORIGINS

ALZpath was founded in 2020 by Venkat Shastri, Phd, Eric Reiman, MD, and Jerre Stead. Their vision from the beginning was to transform Alzheimer’s disease diagnosis through industry-leading scientific discoveries.

That research led them to p-tau217.

For people not working in Alzheimer’s disease and related dementias (AD/RD), that will sound like scientific gibberish. But for those inside the AD/RD research community, p-tau217 is something worth shouting from the rooftops. At this year’s Alzheimer’s Association International Conference (AAIC) in Philadelphia, ptau217 was one of the most talked about breakthroughs, and ALZpath was front and center with their research.

So what is p-tau217 and what has ALZpath built? Let’s back up for a moment. In order to detect Alzheimer’s disease through a blood test we must first identify the signs (or surrogates) for brain pathology and then measure them accu-

rately. Both of these steps have proven challenging.

One of the greatest breakthroughs in Alzheimer’s research has been the discovery that by measuring phosphorylated tau 217 (ptau-217) in the blood we can get a picture of how much amyloid beta protein has accumulated in the brain, which tells us a lot about brain pathology.

Over the last few years the ALZpath team built on the scientific community’s p-tau217 discoveries, leveraging its abililty to measure brain proteins that have crossed the blood-brain barrier and entered the bloodstream. Precision measurement is essential to this work because only the tiniest molecules can bridge the blood-brain barrier.

Their work has earned the ALZpath team wide recognition in the Alzheimer’s community and has set them up for their next phase of business. In 2024, in order to transition from research and publishing to broad commercialization, ALZpath brought on seasoned CEO Chad Holland (pictured left), who’d spent years developing products in rare disease, and has worked on cutting edge gene therapies related to neurodegeneration. For Holland, ALZpath represents a chance to change the course of one of the world’s most devastating diseases, which hits home both professionally and personally.

“Alzheimer's has impacted my family, my extended family, and so many others,” says Holland. “Our thesis is that earlier diagnosis saves lives, so what we are bringing to the table is a more precise and accessible diagnostic solution.”

GOING TO MARKET

Bringing ALZpath’s discoveries to market is a relatively complicated undertaking – it’s different from building a telemedicine company or digital therapeutic. The ALZpath founding team worked for years discovering the relationship between ptau217 and Alzheimer’s disease, and yet that discovery in itself wasn’t a product they could sell. Holland thinks of it more as intellectual property that becomes extremely valuable in the hands of the right drug development partner.

“Our culture is to say that we don't have all the answers,” says Holland, “but we can be a great partner because we understand the needs of drug developers, biotech companies and diagnostic companies. This field is going to evolve; how can we help? This method is fairly democratic,” he adds. “We want many others to be able to use our discoveries in their drug development process.”

ALZpath recently announced a partnership with Roche which cemented the company’s vision for working with the world’s leading pharmaceutical companies, rather than competing as a drug platform company themselves.

For Roche and others, ALZpath will produce highly precise and accurate plasma for use in the development of Alzheimer’s disease blood tests. This approach lets ALZpath focus on the science, and on building a team that can see over the horizon at the next molecule, the next discovery.

“We have an absolutely outstanding founder team,” says Holland, “and our sci-

entific advisory board is the who's who of blood based biomarkers for neurodegenerative diseases and Alzheimer's specifically.” That board includes Henrik Zetterberg, who is working directly with the FDA to set standards for blood-based Alzheimer’s tests, as well as the co-authors of the current leading JAMA paper on blood-based Alzheimer’s tests.

WHAT’S NEXT

While ALZpath has entered the market working on Alzheimer’s biomarkers, their science-first approach and strong collaboration model suggest that Alzheimer’s is just the beginning.

“We're not just going to be a p-tau217 company going forward,” says Holland. “I think we're just at this early part of the convergence of neuroscience and medicine and drug development. Over the next five to ten years, we'll really start unlocking some of those puzzles, and we'll figure out there might be different types of treatments for different folks.”

With its industry-leading advisory board and recent partnerships with Roche, Beckman Colter and ADDF, ALZpath is poised to power a new wave of blood-based biomarkers while also forging ahead with novel research, solving all new challenges. Join us in welcoming ALZpath to StartUp Health’s Alzheimer’s Moonshot. CONTACT

ALZPATH@STARTUPHEALTH.COM

LAKKA Health is Revolutionizing

Medical

Devices from the Ground Up

LAKKA Health intends to reinvent the wheel. Well, maybe not the wheel, but at least the standard medical devices that the industry has been using for years without any major innovation. The company is currently developing two products, including devices to measure blood pressure and sudden drops in blood sugar levels, but their sights are much broader.

SSami Lakka, CEO and founder of LAKKA Health, believes that when it comes to common medical devices, the industry is following the old track. “A lot of the medical devices that we use at the moment have remained unchanged for decades,” says Lakka. “Sure they may have a sleeker plastic enclosure but the parts inside that really matter are essentially the same.

Take the blood pressure monitor, for example. It consists of a cuff, a pump, and a pressure sensor that measures blood pressure by squeezing an artery. “That’s been a traditional way of measuring for century or so,” he states.

When it comes to measuring blood sugar levels, there may be more products on the market, but again, Lakka sees a critical lack of innovation in the underlying technology: it’s either a blood prick or a CGM device.

“Large medical device companies are often reluctant to disrupt their existing market or portfolio”, Lakka remarks. Unconcerned with innovating on devices that they deem to be working just fine, these large companies are typically not forward looking with their sights on new products and new technologies. “This leaves a lot of room for smaller companies like us to play in the field and hopefully bring something new,” declares Lakka. His company finds unacknowledged opportunities where they can reinvent existing technology.

HOW IT WORKS: SIIRING

When LAKKA Health decided to rethink the standard blood pressure monitor (which is “as big as a laptop,” says Lakka) they had the patient’s convenience in mind. The product they are developing - Siiring - measures blood pressure from the finger and is small enough to fit inside of one’s pocket. To reach this solution the company had to challenge the centurylong dependence on air pressure. “There’s nothing in the actual measurement process that necessitates the use of air pressure,” comments Lakka. “There's room for innovation.” Their device uses mechanical shape memory alloy (SMA) actuation and highly sensitive force sensors to detect blood pressure. The measurement is conducted through a squeezing action whereby thin wire contracts when stimulated by a current. With this approach there is no need for air pressure and the large and noisy equipment that goes along with it.

The Siiring allows users to measure whenever they want, whether at home or in an office, as the device is small and silent. Measurements and readings are accessed through a mobile app. The product is useful for individuals with high blood pressure who might need to take their measurements multiple times a day to identify trends or adjust medications. This consumer-centric approach to design is central to LAKKA’s ethos. From a business standpoint, they want to provide their customers with innovative products that allow individuals affordably to manage their own health.

HOW IT WORKS: SOKRU

For another of LAKKA’s innovations, dogs served as inspiration. From 2014 to 2015 Lakka, who has a PhD in measurement and information technology, was working at the University of Michigan as a post-doctoral researcher and started to become interested in wearable medical devices. Around the same time, he was also reading academic studies about how service dogs are used to assist people who have Type 1 diabetes. Their acute sense of smell allows the dogs to recognize gas compounds emitted from the body when an individual’s blood glucose drops. This research left him with a technical question: can technology mimic the olfactory cells of a dog and measure when someone’s blood sugar levels are reaching dangerous levels?

The team at LAKKA Health began looking at existing sensing technologies and started developing their own that

could take very sensitive measurements of volatile organic compounds (emitted gasses) when someone is experiencing hypoor hyperglycemia. Their technology can detect very low concentrations of these VOCs due to a patented temperature cycle operation that uses a temperature ramp to enhance the sensitivity and crossselectivity of the sensor.

After creating a prototype of the device, a friend of Lakka’s informally tested it. A Type 1 diabetic, he put himself into a hypoglycemic state with the sensing technology nearby and it worked. They soon began optimizing the device, which they named Sokru, by streamlining the devices that went into it, developing software apps to help it run, and creating hardware so that people could wear it. Last year, they completed their first clinical trial in Switzerland at Diabetes Center Berne.

This novel device could monitor one’s glucose non-invasively, unlike finger pricking or continuous glucose monitoring devices. The idea is that Sokru, which can be attached to one’s body or placed in a room, sounds an alarm when a person’s glucose levels begin to plummet and metabolic responses produce VOCs. Lakka claims that Sokru responds faster than CGMs but he doesn’t think that they will replace this legacy technology. He believes it will be beneficial to people who lack access to CGMs and need something to safeguard them from extreme fluctuations in blood glucose levels. It’s also helpful at night when a child or an adult is sleeping, which is when over 50 percent of hypoglycemic conditions occur.

WHERE THEY ARE IN THE PROCESS

Currently, the focus is on further developing Siiring in collaboration with Global Health Labs, Inc. This partnership began in July 2024, with the goal of having a fully functional device by November. The upcoming version will be suitable for demonstrations and pilot testing. So far, measurements conducted with the Siiring prototype have been successful, showing accuracy comparable to traditional blood pressure monitors.

OUR TAKE

As a Finnish company, Lakka claims that innovation is in their DNA. “We’re a country of five and a half million people,” reminds Lakka. If your company makes a device only for Finland, “you’re going to die,” he states, and if you try to enter the international market “it has to be innovative because there are so many large US companies that can create existing devices in a very lean way.” Their two devicesSiiring and Sokru - highlight their creative and inventive approach to reimagining common medical devices. We’re excited to sees how Lakka and his team apply their ethos of invention – and of questioning the status quo – to more aspects of healthcare delivery.

CONTACT

LAKKA@STARTUPHEALTH.COM

TELL Is Building the Leading Voice Biomarkers for Latin America

Fernando Johann, PhD, and his team are bringing groundbreaking voice analysis research to patients through their AI-driven platform. With a strong focus on native Spanish and non-English speakers, TELL is focusing on making early Alzheimer’s detection more accessible. You can tell a lot about a person from the way they speak. For centuries doctors have been trained to listen closely to their patients' voices for signs of illness, as subtle changes like slurring and tremors can be a sign that something is going on beneath the surface.

YOver the years science has tripled down on this idea, going deeper and deeper into the connection between speech and our brains, muscles, and respiratory system.

What once might have been casually called “listening closely” or “performing a good history and physical” has blossomed into a robust academic field for voice biomarkers. Technology has allowed researchers to go far beyond the abilities of a human ear and detect changes in the voice that are so subtle they may predict disease

Fernando Johann, PhD CEO & Co-founder

many years in the future.

One of the great applications for digital voice biomarkers is in the early detection of Parkinson’s and Alzheimer’s disease. Well published research suggests that AIassisted voice analysis can be incredibly useful in these diagnoses, while also having the benefit of being one of, if not the most, accessible and non-invasive detection methods possible.

So far so good. Here’s the problem. For many years, the research that forms the foundation of voice digital biomarkers for Alzheimer’s has been stuck in academia.

Researchers have used it, but it has not scaled and has not achieved its potential for opening up access to care.

That’s where TELL comes in.

ORIGIN STORY

About 15 years ago Adolfo García, PhD, started researching neurodegeneration and language. Over time he became a leading academic voice, particularly in Latin America, on the connection between speech and the brain. He published prolifically and had a vision for how this work could transform patients’ lives

through early disease detection.

But that didn’t happen.

Year after year, even as he made new discoveries, his studies never seemed to make it beyond the realm of research. That began to change when he met Facundo Carrillo, who had completed a PhD in computer science on the topic of natural language processing. By putting their heads together, they were able to build the MVP of a product that brought Garcia’s research into a usable digital format. They distributed it to twelve of their colleagues, who started using the app in research and

TELL Co-founder Adolfo Garcia, PhD, speaks with StartUp Health at AAIC.

clinical scenarios.

The initial response was very positive, and the duo was approached by a life science fund in Argentina that was interested in scaling the technology. They needed a seasoned CEO to bridge the worlds of technology and business and tasked engineer-turned-VC Fernando Johann, PhD, with the task of finding this right-fit executive. The more Johann worked on the project – and reflected on the loss of his own two grandmothers to Alzheimer’s –the more he realized that he might be the man for the job. Everyone agreed, and TELL kicked into high gear.

UNDER THE HOOD

TELL can take different forms, depending on the application, so it’s good to start with what’s happening beneath the surface. The foundation is a body of voice data that’s constantly growing and improving through dozens of academic collaborations. These collaborations are training TELL’s AI models, making them smarter and smarter.

These AI models have the ability to be used in the analysis of a single voice, at a single moment in time. They also have the ability to analyze changes in one voice over time, and provide longitudinal trend data, grading a person’s voice against their own personal benchmarks. This personal benchmarking – understanding how a person’s voice has altered from their norm, not the global norm – begins to look a lot more like personalized medicine, says Johann.

There are three types of tasks that are

typical to a TELL assessment. The first is called “spontaneous elicitation” and it’s a spontaneous prompt that requires you to think on the spot. For example, “tell me about your morning routine.” Then they have “guided elicitation” where the individual responds to a fixed prompt, like describing an image. Finally they have “forced elicitation” which is focused on the person’s mechanical abilities, like, “say the letter R until you run out of air.”

Within these categories, the actual questions are customizable to each patient population.

“Voice biomarkers are a match made in heaven for everyone,” says Johann. “Voice is the most robust way of accessing the body non-invasively. Voice allows for increased engagement in treatment. Voice allows for early signs of behavior change. For example, in Parkinson's, the fluctuation is part of the actual condition. So we could actually report that you are at this part of the cycle. You are at this part of the cycle, and you would go and do other testing. It's a great tool to justify the trip to the doctor's office.”

Unlike some Alzheimer’s tests, TELL’s voice analysis is a measure of subtle disease symptoms that already exist, not a prediction of what may come later.

TELL has a unique potential for adding to the global world of knowledge around speech, because of their access to native Spanish speakers. For Johann this “human data acquisition” piece of the project gives the project even greater importance.

“We have a competitive advantage in Latin America because we are the only

model trained in Spanish by Spanishspeaking participants.”

Their focus on Latin America also means that Johann and his team are addressing a region of extreme need, with an eye towards radical accessibility. There are very few geriatricians and neurologists available in Latin America, and TELL has the potential to break open brain health diagnostics for millions of people. TELL can be deployed over any VOIP (voice over IP) phone line, like a WhatsApp or Zoom call.

“In the future this benchmarking could even be done at the DMV, just like you test your eyes and ears,” says Johann.

FINAL WORD

Fernando Johann, PhD, and his team at TELL bring an exciting and fascinating new dimension to StartUp Health’s Alzheimer’s Moonshot. They open the door to an entire field of study – voice biomarkers – and add that knowledge to the collective progress being made in blood biomarkers, eye tracking, and even brain stimulation.

We appreciate TELL’s vigorous academic approach. They are continually making new studies and leading their field in research.

“We are publishing quarterly,” says Johann. “And we are creating new biomarkers almost every quarter.”

We’re also bullish on TELL because they’ve already successfully landed major research collaborations, currently deploying their technology with 22 institutions. That gives them a firm foundation, helping

them grow their data set without spending a lot of money.

The use cases for TELL are broad, and their early non-academic partners have ranged from the Davos Alzheimer’s Collective (with a project in Kenya) to a pharmaceutical company in Brazil.

In the field of voice biomarkers, there is talk, says Johann, that in five to 10 years we will have passive analysis of speech happening through technology like Alexa and Google Home and your smartphone. There are obviously privacy concerns attached to that dream, and we’re not there yet, but that’s where Johann sees TELL heading.

Perhaps the most exciting thing of all is the potential for TELL to aid clinical trials and increase the speed of development of brand new Alzheimer’s treatments.

“We are developing the best microscope out there [for voice analysis]. We want others to use it so they can be the heroes that cure this disease.”

CONTACT

TELL@STARTUPHEALTH.COM

How Ilios Therapeutics Is Pioneering a Novel Approach to Treating Neurodegenerative Conditions by Generating Multifunctional Molecules

The human brain, a three-pound universe of tangled neurons and electrical impulses, holds the mysteries of our consciousness, memories, and very sense of self. Yet, this magnificent organ is tragically susceptible to a class of diseases known as neurodegenerative disorders. Alzheimer's, Parkinson's, ALS –these conditions rob individuals of their cognitive abilities, motor functions, and ultimately, their lives.

Luca Giani, CEO & Co-founder

AAlzheimer's disease, the most common form of neurodegeneration, afflicts an estimated 5.5 million Americans and is projected to balloon to nearly 14 million by 2050. It's a thief of minds, progressively stripping away memories and leaving behind a shell of the person you once knew.

The scientific understanding of

Alzheimer's is constantly evolving, but one thing is clear: it's not a singular disease with a single cause. Three processes in the brain are believed to play key roles in neurodegeneration: misbehavior of different proteins, and chronic stress factors coming from oxidative stress, and neuroinflammation. These three processes are interconnected and require simultaneous modulation.

The traditional approach to drug discovery focused on developing drugs with a single target, like clearing plaques or reducing inflammation. However, these attempts have yielded limited success. The paradigm of one-target, one-drug has fallen short and might not be enough to navigate the complexity of the disease.

ORIGIN STORY

Luca Giani, the CEO & Co-founder of Ilios Therapeutics, understands the devastation of neurodegenerative diseases all too well. Witnessing his grandfather succumb to Alzheimer's ignited a personal fire within him. This was further stoked when he was diagnosed with a brain tumor himself and faced the possibility of cognitive decline. Thankfully, surgery proved successful, but the experience left an indelible mark.

"I had a wakeup call through these personal experiences," says Giani. "I decided that I would dedicate the rest of my life to work so that as many people as possible can use their brain for as long as possible."

Giani’s background in venture creation and the biotech industry fueled his entrepreneurial spirit. He saw the need for an innovative approach to neurodegenerative disease treatments by recognizing the multi-factorial complexity of neurodegeneration head-on. This vision gave birth to Ilios Therapeutics.

Ilios’ academic co-founders include renowned professors in the field of Alzheimer’s, and current scientific efforts are advanced by a team of drug discovery experts, with experience in medicinal

chemistry, neurobiology, neuropharmacology, and drug development.

Ilios is also fortunate to have been supported by renowned fellowships, such as the Harvard Blavatnik Fellowship in Life Science Entrepreneurship, the Harvard Belfer Fellowship, as well as leading accelerators such as MassBio Drive, Nucleate, and MassChallenge. These resources provide access to cutting-edge research facilities and expertise, which will accelerate Ilios' progress.

UNDER THE HOOD

Ilios isn't following the traditional, single-target approach. Instead, they're pioneering a new frontier in drug discovery: multifunctional therapeutics.

Their platform leverages naturally occurring molecules that have shown potential against neurodegenerative processes, but which, by themselves, cannot be turned into drugs because of efficacy of pharmacological limitations. Ilios is the old name of Troy, and the Ilios chemistry platform brings together naturally-occurring components into a single molecule, optimized – like the Trojan horse – to get into the brain and modulate the three key drivers of disease. This "multifunctional molecule" is designed to simultaneously target the three key culprits in Alzheimer's: protein misfolding, oxidative stress, and neuroinflammation.

"We're reverse-engineering the equation," explains Giani. "Instead of screening millions of molecules hoping for a hit, we start with elements that have already shown promise against these processes."

COO

This approach offers several advantages. First, it's more efficient, streamlining the drug discovery process. Second, by targeting multiple factors simultaneously, Ilios aims to achieve therapeutic effects that can be translated to effective medicines for patients. A single drug with a multifunctional activity holds potential compared to a “cocktail” of different medications targeting individual factors, potentially reducing side effects, drug-drug interactions, compliance issues, and a more straight-forward regulatory pathway.

THE EARLY RESULTS

Ilios is in the preclinical stages of development, but the potential is becoming clear: the team has already built the chemistry platform that can rapidly merge naturally-occurring components into single molecules. And several of these proprietary molecules have shown multifunctionality and potential to increase po -

tency through iterative chemistry. In the next twelve months, Giani is most excited about creating lead candidates – molecules that have successfully navigated the initial screening process. These candidates will then undergo further testing and optimization before potentially moving to clinical trials.

The road to a commercially available treatment is long and arduous, but the initial results are encouraging. Ilios' approach has the potential to revolutionize the treatment landscape for ALS, Alzheimer's, and other neurodegenerative diseases. By targeting multiple hallmarks of the disease simultaneously, Ilios' multifunctional drugs could slow or even halt disease progression. This could offer patients a chance to maintain cognitive function and independence for longer, significantly improving their quality of life.

The fight against neurodegenerative diseases is a marathon, not a sprint. But with its innovative approach and a passionate team driven by personal connection, Ilios Therapeutics is offering a beacon of hope in this labyrinthine battle. Their success has the potential to not only change the lives of millions but also pave the way for future advancements in treating other complex diseases. Imagine a world where a new generation of multifunctional drugs tackles a variety of conditions by addressing their underlying causes.

CONTACT ILIOS@STARTUPHEALTH.COM

Lisa Paborsky, PhD,

Esya Labs is Putting a New Spin on the Brain Health Diagnostics

After a traumatic illness left her temporarily paralyzed, cofounder Dhivya Venket decided to use her experience as a business strategist to tackle the problem of neurodegeneration. Now, with Esya Labs, she’s attempting to flip the typical R&D narrative, focusing on collaborative, multiomic solutions rather than the work of one brilliant scientist or lab.

MMost startups are born in an office, around the kitchen table, or on the back of a napkin. Esya Labs was born in a hospital bed. But that’s getting ahead of ourselves.

Dhivya Vankat began her career in 2003 as a consultant for Accenture. She learned the ropes and then rapidly came to realize that her passion was to build her own business, not merely help someone else with theirs.

So just four years later, Dhivya took the leap and started her own boutique con-

sulting firm, eventually earning the business of blue chip clients like Vodafone, HSBC, Best Buy, and Barclays.

When asked why she branched out on her own so early in her career, Venkat points to her grandfather.

“He was an entrepreneur in India, and even when I was a little baby, he'd take me into the office,” she recalls. “He worked in the agricultural sector, making paddy threshers, sugar cane crushers, motor pumps and other agricultural machinery. I'd see him working in the factory, handling meetings, and that became the norm. You take problems and you find solutions for them. That’s my ethos.”

That ethos might have kept Venkat in the financial sector had it not been for one very traumatic event that left her bedridden and paralyzed.

In 2016 Dhivya took part in a quadrathon, a race where participants do four marathons in four days. She flew back to India right after the race and quickly fell ill. Two days later she woke up to discover that she couldn’t move her lips on one side or close her eyes. Her face was partially paralyzed. She thought she was having a stroke. The hospital treated her for meningitis and she stayed in intensive care for 11 days. Eventually physicians settled on a diagnosis of Ramsay Hunt and she was given a 30% chance of recovery.

While lying in the recovery room, Dhivya’s problem solving mindset kicked back into gear. She shifted from the micro – her own struggle with neurological deficits like memory loss – to the macro. Why, she wondered, was there no diagnostic

tool, no screening test, for neurodegeneration? Why was there no clear way of testing if you have brain inflammation? After all, we have well-studied panels for heart health, lung health, and kidney health. Why not the brain?

In the end she recovered physically, but the experience left an indelible mark. She’d found a mission worthy of her time and experience.

LAUNCHING ESYA LABS

Dhivya dived into the problem of neurodegeneration and soon she was workshopping it with a family friend, Prof. Yamuna Krishnan, PhD. One conversation led to another until they figured out that the professor’s work on lysosomal storage disease had a direct link to Alzheimer’s. Prof. Krishnan invented an award-winning technology that could measure the ionic composition of lysosomes / endosomes in a way that had never been done before. This turns out to be relevant to Alzheiemer’s because lysosomes are like the garbage disposal units in our cells and it is this endo-lysosomal pathway that is dysregulated in most neurodegenerative diseases, including Alzheimer's. It appeared very promising that Dr. Krishnan’s work could be foundational to a new blood test for Alheimer’s Disease. The company Esya Labs was born to bring that idea to fruition, with Krishnan and Venkat as co-founders.

This was 2019 and there wasn’t a simple blood test for detecting dementia. Most companies were working on tests that required cerebrospinal fluid (CSF) from a

lumbar puncture.

But this initial discovery that launched Esya was just the foot in the door. Once Dhivya began raising money for Esya and stepping further into the world of neurodegeneration, she realized there was a much bigger opportunity – to build the world’s first and best brain health panel. The world didn’t just need a single pathway for detecting Alzheimer’s, it needed a broader approach to brain health that was multiomic, meaning it's an integrated approach combining multiple areas of biology, like genes, proteins, etc

UNDER THE HOOD

“We started off as a skin-based test, then moved into blood, then realized a single lysosomal single marker wasn't sufficient,” Venkat explains. “We then added targeted proteomics, transcriptomics, genetics, and now we have a fine tuned assay that combines key markers and lysosomal data to enable us to understand onset of dysfunction, 15-20 years before developing the symptoms for Alzheimer's.”

To outsiders, it might seem obvious for a brain health company to take a multiomic approach to diagnostics. We all appreciate at some level how complex our brains are. However, it is actually a differentiator for Esya Labs that they are working from the problem backwards. More common in neuroscience is to take the specific work of a brilliant PhD or lab and try to make it fit the market. Esya represents a tech-agnostic framework for combining leading diagnostics related to neurodegeneration. That mindset also makes Esya more future-

proof as they are designed to continually evolve their methodologies.

"Many in this field are fixated on a single hypothesis, often tied to their PhD or life's work. They believe it's the only solution and focus solely on bringing it to market. However, with my business background, I approach it differently: I start with the problem and explore all available solutions to address it effectively."

That same business-forward approach also plays into Venkat’s view on the competitive landscape. There are so many parts to the Alzheimer’s Disease value chain, she explains. Esya’s model would lean heavily on collaborations and strategic partnerships in order to create more of a one-stop solution.

Today, Esya Labs measures five key proteins that are dysfunctional, and combines that data with an understanding of cellular dysfunction to get a molecular signature that allows them to give patients a risk scoring for neurodegeneration. Their vision is to roll this out at the primary care level so that neurodegeneration can be caught early – and inexpensively – and patients can have an informed conversation about lifestyle changes and therapeutics with their doctor. Dhivya has raised $2 million to date and is raising again soon to move into the next phase of lab research, and to work through the FDA process

Pelex’s New Device Uses Biofeedback to Make Pelvic Floor Rehab Accessible and Affordable

Leveraging a powerful combination of a non-invasive medical device and virtual pelvic floor physical therapy, Pelex offers personalized, home-based treatments for a broad range of pelvic floor disorders. With successful clinical tests and ongoing studies, Pelex is committed to fostering a cultural shift, empowering women to prioritize their pelvic health.

NNearly a decade ago, Jeremy Wiygul, MD, a pediatric and reconstructive urologist, decided to find a solution for a health condition he frequently dealt with at work – urinary leakage. One of the primary treatments for this condition is pelvic floor rehabilitation. The procedure usually involved a massive, six-foottall device that showed the patients Kegel exercises on a screen – basically a form of biofeedback – and tracked their muscle activity as they performed the exercises. While the procedure was effective, it

had to be conducted at the doctor’s office, which often wasn’t accessible in non-urban areas. So Dr. Wiygul started looking for ways to make the huge device compact and inexpensive.

Meanwhile, Dr. Wiygul’s wife, like every other mother out there, was also struggling with pelvic floor strength problems post-childbirth. These issues could be treated through the same type of biofeedback device that Dr. Wiygul was attempting to build for children. So, she asked him, “Why not make this available for women?” All of a sudden, an enormous market opened up.

“My wife used to complain about her symptoms. And I was like, let's have you seen by someone, let's get you treated,” says Dr. Wiygul. “But we had a hard time finding someone. If a urologist's wife has a hard time getting access to this kind of care, I can't imagine how hard it is for everyone else.” His wife was one of the first people to use the device successfully, and the positive response in her symptoms told him they were on the right track.

ORIGIN STORY

Dr. Wiygul began exploring the market for women in the postnatal period and found numerous products in the market designed to strengthen the pelvic floor but none that came with proper guidance.

“If people have never been shown how to use the device, they could end up hurting themselves because not all pelvic floor disorders are the same,” says Dr. Wiygul. “Sometimes, you need the pelvic floor relaxed, while other times, it requires

strengthening.”

This prompted Dr. Wiygul to modify his solution and make it a combination of technology and personalized treatment, the first of its kind in the market. He wanted to recreate the clinical experience at home for his users. So he added a pelvic floor physical therapist to the equation (through a virtual clinic model), who would provide coaching and guidance to complement the patient's self-guided device use at home.

Once the guidance part was taken care of, Dr. Wiygul started looking at the other gaps in the market and addressing them one by one. He found that similar devices and treatment options available to women in the postnatal period were invasive. This made a lot of women put off treatment. So, he made his product non-invasive.

Dr. Wiygul also realized that a form of treatment called neurostimulation could be performed through the same patient interface. Most other devices that offered stimulation targeted muscle, but the muscular stimulation wasn’t as effective as the neuro stim. So Dr. Wiygul decided to leverage neurostimulation and target a novel nerve for certain disorders of the pelvic floor, like chronic pelvic pain and dyspareunia (painful intercourse). These were conditions that no one had been able to successfully target before non-invasively, and with this new approach, Pelex could treat up to 90% of all pelvic floor disorders.

After numerous trials, Dr. Wiygul and his team successfully developed a beta prototype that implemented the biofeedback

technology, featuring a patient interface resembling a saddle, a specific sensor array (fully patented part of their intellectual property), and a smartphone application where the interactions happen. They successfully ran a round of clinical trials using their beta prototype and the biofeedback technology. They were able to amass overwhelmingly positive feedback, with close to an average of 50% reduction in symptoms across all subjects.

“We have had users tell us if they could have access to this all the time, they would use it all the time. I remember a couple of study participants saying they didn’t want to give the device back and asking me if they could keep it. Participants liked the idea, and they found the smartphone application to be very good at explaining how to set the whole thing up. Also, it made perfect sense to people that this is something that is built to be used in the privacy and comfort of your home rather than during an appointment with a specialist,” says Dr. Wiygul.

UNDER THE HOOD

Pelex took a basic technology that has been around for decades – biofeedback –and modified it by integrating neurostimulation. They also made treatment noninvasive and more accessible for people suffering from pelvic floor disorders.

There are two parts to their device. The first is a saddle with electrodes embedded in it, and the second is a smartphone app connected to the saddle via Bluetooth. For the biofeedback component, when a user sits on the saddle, the electrodes capture

Jeremey Wiygul, MD CEO & Founder

the signals and deliver them to the app, which shows the user their own muscle contractions and guides the user in performing the exercises properly. For the neurostimulation therapy, electrical impulses are delivered to the pudendal nerve via an array of stimulation electrodes. These sessions are also set and controlled by the smartphone app and are performed separate from the biofeedback therapy.

All the data generated through the device is gathered and stored in a HIPAAcompliant manner on a third-party cloud platform. Over time, this data can be used to analyze how a specific treatment plan works for a specific user and tailor regimens based on individual needs, creating a personalized pelvic floor care plan.

Pelex has successfully run clinical tests on the device with the biofeedback technology, demonstrating the device’s intuitive usability. The signal capture was also found to be highly efficient, ensuring ac-

curate data collection and analysis.

Currently, Team Pelex has begun the second round of clinical investigation: a three-arm study comparing the device alone, the device with virtual pelvic floor physical therapy, and the virtual pelvic floor physical therapy alone. The anticipated results are expected to highlight the superior effectiveness of Pelex’s device in conjunction with physical therapy as opposed to either alone.

“There have been multiple studies comparing people who are taught pelvic floor exercise by a trained professional and people who were given the same training along with an in-office device and asked to follow the same regimen for four weeks. Those given the device consistently got better outcomes as compared to those receiving pelvic floor physical therapy alone, with a substantial improvement of around 30%,” says Dr. Wiygul. “There is also a significant added benefit to using a device than just doing Kegel exercises alone. This goes to the very basis of biofeedback, where somehow representing your own body processes allows you to control those processes better than not seeing them represented in one form or fashion.”

After the study concludes, Pelex will be poised for FDA submission and approval. The FDA Class II designation would set Pelex apart in a market flooded with wellness devices. It allows them to make specific claims about treatment that others cannot. This clinical differentiation is crucial in the market where consumers seek evidence-based solutions and guidance from their physicians. Hence, Pelex's

primary sales channel will be through doctors' offices, in contrast to generic devices available through mainstream online platforms.

LAST WORDS

Pelex is committed to reshaping the narrative around women’s health. For Dr. Wiygul and his team, improving the lives of mothers post-birth is personal.

“The stigma around something like leakage is that it's not that big of a deal. But these pelvic floor issues can snowball into situations that keep a woman from being able to be confident at work, pursue her dreams, and can affect her overall quality of life,” says Dr. Wiygul. “We also know, through the testimony of our study participants, that women with these conditions feel very vulnerable even talking about it. Our goal is to make getting treatment as easy as flipping a switch.”

With their novel device and platform –which bring the clinical standard of care into the home – Pelex aspires to foster a cultural shift where women are encouraged to prioritize their pelvic health. Their goal is to empower women to receive the care they deserve without compromising their priorities. And we’re proud to support Pelex as a member of the StartUp Health community. CONTACT

MindAhead Offers Digital Alzheimer’s Therapy Through a Clinical Trial-Backed Behavior Activation Program

With MindAhead, serial entrepreneur Nina Kiwit and her team are bringing to market an Alzheimer’s digital therapy that leverages behavioral activation. This therapeutic strategy – one of the most effective methods for slowing cognitive decline – focuses on restoring a person’s ability to do the things they enjoy in life.

WWhen a patient comes into their doctor’s office with forgetfulness or other selfreported symptoms of “mild cognitive impairment,” the current standard of care falls flat. It’s not the physician’s fault, they just don’t have many tools in their toolbox for early stage cognitive decline. Usually the response from the healthcare provider is to simply watch and wait until things get worse.

Which, for many people, is exactly what will happen.

It’s estimated that 20% of people over 65 have mild cognitive impairment. And according to the Mayo Clinic, around 10% to 15% of people with MCI develop de-

mentia each year, compared with 1% to 3% in the general population of aging adults.

Left on their own, people concerned about cognitive decline turn to the myriad apps on the market or simply Google their way to a pseudo-answer. Or they do nothing at all. Some of the most prominent apps that target early stage dementia or mild cognitive impairment use something called cognitive stimulation therapy or cognitive test therapy. These often focus on in-app exercises, like math problems or puzzles. The problem, according to Nina Kiwit, CEO & Co-founder of MindAhead, is that these exercises mainly make the patient better at the specific activity at hand.

“It doesn't really train your brain in a way to prevent dementia,” says Kiwit. “You learn the task itself.”

For Kiwit, a serial entrepreneur and digital health expert based in Berlin, that problem begged for an answer.

ORIGIN STORY

Nina Kiwit studied economics in Germany, but after school fell in love with the startup life. She worked at big startups in eCommerce but quickly realized she wanted to have a more lasting impact in the world. She got an advanced degree in digi-

tal health at the Hasso Plattner Institute and Mount Sinai New York and dove into electronic health records and machine learning. She has served as COO of multiple digital health startups.

While working with a subsidiary of Roche, Kiwit met Manuel Kraus, who had trained in psychology and had founded the app Stresscoach. Kraus had been on a parallel path, in many ways. He started out in traditional business, working with tech startups, and then began yearning for more. He wanted to scale companies to improve lives, not just for financial gain. Looking back, he roots that desire in his experience watching his grandmother slowly decline into dementia. For years he felt helpless. There was no clear diagnosis and nothing concrete he could do to help besides show up and try to make her life a little better.

That frustration became an inspiration, and when Kraus met Kiwit, he was primed to tackle the problem of slowing the progression of mild cognitive impairment.

UNDER THE HOOD

Kiwit and Kraus, along with their cofounders Pasquale Fedele (CTO) and Patrick Fissler, PhD (CSO), have built an app designed to be prescribed to patients diagnosed with mild cognitive impairment. The app guides users through brain teasers and physical activities that improve brain function. The short-term objective (three to six months) is a measurable increase in quality of life. The two-year goal is to bend the curve on cognitive decline and slow the progression towards dementia. Where MindAhead differentiates its

MindAhead is launching their product in Germany first, which has advantageous digital health reimbursement laws. This could give the company an onramp to revenue, setting them up for larger European markets and the United States.

therapeutic approach is in the use of behavioral activation therapy, a strategy that has been tested and proven effective in the treatment of depression. The therapies focus on helping people become more active in life again and perform activities that are enjoyable or personally meaningful to them.

While well understood in depression therapy, behavioral activation therapy is a relatively new concept for treating earlystage cognitive disorders. In 2018, researchers in the United States conducted

a large-scale clinical study in which they adapted the approach for older people with cognitive impairment and dementia. The results were eye-opening. With behavioral activation therapy only about 1% of patients showed significant cognitive decline within two years, the percentage for patients without this program was over 9% in the same period.

“There is no other digital therapy that uses the behavioral activation approach for dementia. It is a unique approach designed to give back some degree of control over the rate of cognitive decline,” says neuroscientist Patrick Fissler, PhD, who is one of the co-founders of MindAhead.

The app includes an AI assistant named after Barry Rovner, MD, the doctor who proved the efficacy of the therapy in the United States.

So far, MindAhead’s results have been positive. The team tested the platform with more than 50 patients and then conducted a clinical trial with another 50. They’re expecting results from their most recent study this autumn.

With a patient population struggling with cognitive impairment, ease of use is paramount for the app. Kiwit and Kraus have made sure that their app has simple controls, large fonts, and visual support. They’ve also stressed user testing, inviting folks with MCI in to review the app at every stage.

FINAL WORD

We don’t have a cure for dementia, unfortunately. But we do know how to slow it down, and the team at MindAhead want

to put the best tools for doing so in everyone’s hands.

One of the interesting things about MindAhead that we believe gives them an advantage is that they’re launching their product in Germany first, which has advantageous digital health reimbursement laws. This could give the company a robust onramp to revenue, setting them up for larger European markets and the United States.

MindAhead has also been strategic in building technical partnerships. Most recently, NeuroSys from Ulm became a founding member of the project, developing a physician portal that connects the dots between a consumer-facing app and care in the clinic. They’ve also seen early traction with an investment from RoX (Roche Pharma).

Finally, we’re proud to support MindAhead because they’re meeting an unmet need in a population where the stakes are incredibly high. The sweet spot for MindAhead is patients aged 60, with an upper limit around 75. That’s a massive population of people who, if their dementia is delayed or stopped, if their health is managed, have literally decades of high quality life to live. If MindAhead can delay cognitive decline for folks in their 60s, that means seeing children and loved ones graduate high school, get married, have children. These are massive years and we need more scalable tools to preserve them.

ToxGenSolutions Zeroes in on microRNA for the Early Detection of Alzheimer’s

The Dutch company has created a device that can detect early signs of Alzheimer’s, and they’re on their way to developing a preventative drug.

IIn 2019 Maria Tsamou, PhD, the Chief Scientific Officer at ToxGenSolutions, obtained human blood samples at a Greek hospital from people with mild cognitive impairments to test for a microRNA profile that her team thought might be associated with the early onset of Alzheimer's disease (AD). All the results from her tests of the experimental group

were positive – but she also got positive Alzheimer’s results from almost half of the control group, who were considered healthy during the visit. They were discouraged by what they saw as false positives in the control group and felt the experiment was a failure. Then Tsamou, in an effort to get greater clarity, discussed the results with a professor working with the same group of patients. She learned that there were early samples available from the same group taken during a four-year study. It turned out that a meaningful percentage of the seemingly healthy patients who had tested positive for Alzheimer’s in the control group had gone on to develop full Alzheimer’s disease. Their diagnostic tool had worked after all and better than expected.

“We opened up a bottle of champagne and started celebrating the success,” says Erwin Roggen, PhD, CEO & Co-founder of ToxGenSolutions. “We believed we were doing the right thing,” he says. “That’s how it picked up.”

THE CHALLENGE

ToxGenSolutions started with the hypothesis that an AD diagnosis happens far too late for any meaningful intervention. “By the time people are diagnosed with AD their brain looks like Swiss cheese,” says Roggen. He describes the process of a typical AD diagnosis: a patient experiencing forgetfulness usually begins with a questionnaire administered by a physician, which results in a score that might provide a diagnosis of cognitive impairment. Typically, a patient is asked to return a few

“We opened up a bottle of champagne and started celebrating the success,” says Erwin Roggen, PhD, CEO & Co-founder of ToxGenSolutions. “We believed we were doing the right thing.”

months later for a follow-up appointment, which can sometimes stretch into a year. Eventually, when the physician is confident that something is wrong, a lumbar puncture is administered to test for proteins in the patient’s cerebrospinal fluid. If the results are positive the patient then undergoes MRI or PET scans. “It can take a year or two before one is actually diagnosed,” says Roggen.

THE SOLUTION

ToxGenSolutions is developing a diagnostic device that can measure microRNAs in a drop of blood and identify signs of AD within moments. In addition, it can anticipate the disease six years before onset, and they’re hoping they can move that window to 10 or 15 years before onset.

They are not stopping at the development of just this device, which will be submitted to medical agencies for approval later this year. Roggen leads an international team based in the Netherlands focused on three major goals: early detection of AD, production of a device for doing

so, and administration of a therapy.

“We want to use our insight from the diagnostics and the computational part, first, to identify patients as soon as possible, and then to develop potential preventative drugs,” says Roggen. “It doesn't make sense to have an early diagnosis if you don't have any drug to treat it.”

HOW IT WORKS: EARLY DETECTION OF ALZHEIMER'S DISEASE

MicroRNAs are small molecules that exist within genes or between genes and can fine-tune their expression. When a chemical from an environmental factor hits a cell, both the genes and the microRNAs are affected, resulting in either an upregulation or downregulation of the gene.

Whereas one’s genes and chromosomes are fixed, microRNAs are expressed in a moment and are constantly changing. ToxGenSolutions zeroed in on microRNA as a key arbiter between genes and environmental chemicals, responsible for the onset of a disease like Alzheimer’s, which is caused by the interplay between genetic and environmental factors. “AD is not a problem of pathologic genes, but dysregulated genes,” says Roggen.

Early in their research, ToxGenSolutions found some microRNA molecules that were only present in patients with mild cognitive impairments and were different from the microRNA molecules present in Alzheimer’s patients.

With their device, they can analyze blood, tears, or hypodermal fluid for their microRNA patterns that they have associated with early cognitive decline and con-

Erwin Roggen, PhD CEO & Co-founder

fidently predict whether or not a person will develop mild cognitive impairment or Alzheimer’s disease.

HOW IT WORKS: DEVELOPING A DRUG

Now that ToxGenSolutions has discovered a microRNA profile associated with pre-Alzheimer’s disease, they are considering how to hack into the processes and pathways between microRNAs and genes. They’re looking at the impact of environmental chemicals with the hopes of using a drug to control the interplay between microRNA and gene expression.

They are convinced that their solution is an improvement on models of therapy that use stem cells or monoclonal antibodies. “We could do what they did with Parkinson's disease years ago where they injected stem cells and saw an improvement but then the cells started dying, of course, because if you don’t remove the reason why the original cells are dying,

new cells will die as well,” says Roggen.

Furthermore, Roggen sees the monoclonal antibody approach, often favored by pharmaceutical companies, as risky. “With Alzheimer’s disease and dementia in general and so many other chronic diseases, chronic inflammation is a driver. It’s a risk factor to add an antibody onto a cluster of proteins or a bacteria or virus because the first thing that happens is an inflammatory response that starts the immune response,” says Roggen.

“We want to work with a chemical solution that will pass the blood-brain barrier and not trigger an inflammatory response,” says Roggen. They are encouraged by developments in cancer research where microRNA therapy is being used to stop processes and kill cancer cells.

WHERE THEY ARE IN THE PROCESS

Although ToxGenSolutions has already developed a diagnostic device for identifying a microRNA profile associated with the development of Alzheimer’s disease, they are still on a journey toward creating a drug to prevent AD. “We have identified model drug targets, and we are putting them in a computer system and screening them against 50,000 chemicals,” says Roggen. Many of these chemicals are repurposed, including chemicals that may have been on the market and tested in clinical trials but didn’t work as expected.

ToxGenSolutions has an agreement with an Australian company that has human brain organoids, which bring together human brain cells in a 3D structure. They will use this to test whether their

chemicals are toxic. For the drugs that they determine to be safe and non-toxic, ToxGenSolutions will take them apart and induce neurodegeneration with environmental chemicals. “Then we will give the drug and see if it can stop and preferably reverse the process,” says Roggen. Once they have a drug, they’re confident that it will be immediately effective. “MicroRNAs react within 30 minutes after you introduce a drug,” says Roggen. They expect to reach this milestone by 2028 at the earliest.

OUR TAKE

ToxGenSolutions is an ambitious company already on the path to tackling Alzheimer’s disease. Their diagnostic tool could radically reduce the timeline of diagnosis and create opportunities for early treatment. Their research around microRNA therapy shows promise at altering the underlying causes of Alzheimer’s by targeting the interaction between genes and environmental chemicals. Furthermore, their ambitions extend beyond AD. They are building a database with the microRNAs of all diseases with a chronic vector, like Alzheimer’s and Parkinson’s. “We’re building a very big network to show the interaction and pathways between microRNAs, genes and different diseases,” says Roggen. “It is our dream to find the one golden bullet that can address all these chronic diseases.”

CONTACT

TOXGEN@STARTUPHEALTH.COM

Stem Pharm is Revolutionizing Drug Discovery for Brain Diseases

A team of scientists and entrepreneurs have developed a superior “brainin-a-dish” platform that makes the development of therapeutics for diseases like Alzheimer’s and epilepsy much more likely to succeed.

Neurological diseases, such as Alzheimer’s, epilepsy, and brain cancer are devastating conditions with limited treatment options.

Pharmaceutical companies using traditional drug development methods have struggled to develop effective therapies for these conditions in part because the hu-

man brain is so complex. Specifically, the brain cells needed to do research have been so difficult to isolate and culture in the lab that neuroscience researchers have been forced to rely heavily on mice and rats. The results, historically, have been less than successful.

That’s where a startup out of Madison, Wisconsin hopes to change the game. By developing a superior “brain-in-a-dish” technology, they aim to revolutionize neuroscience drug discovery, ultimately creating their own therapeutics for widespread brain conditions.

ORIGIN STORY

We pick up the Stem Pharm story over a

cup of coffee in Madison, the picturesque college town home to the University of Wisconsin (UW). This was a few years ago when Steven Visuri was an angel investor looking for investment opportunities. He sat down with the Stem Pharm co-founders, Bill Murphy, a UW professor, and Connie Lebakken, a cell biologist, who had just launched a company with technology from Dr. Murphy’s lab.

Both co-founders had close family members struggling with Alzheimer’s or dementia, and were passionate about using discoveries and talents to get closer to a cure. Visuri had lost his father-in-law to Alzheimer's disease in 2018, and his sister has dementia and primary progressive aphasia, a brain condition that slowly degrades the ability to communicate.

“I'm very passionate about coming up with a therapeutic that's going to address her disease and symptoms,” says Visuri.

Murphy and Lebakken are PhD-level scientists but Visuri recalls they also keenly understood the business and social impact opportunity in front of them.

Impressed by the team and inspired by the vision – of finding a cure for Alzheimer’s and other disorders of the brain – Visuri signed on with the hopes of bringing Stem Pharm’s research into the world of pharmaceutical drug discovery. Shortly after he joined the company the team also brought on Ryan Gordon, who added deep domain expertise in pharma commercialization.

UNDER THE HOOD

If scientists want to do brain research –

like discover a cure for Alzheimer’s – one thing they need is a proxy for the brain in the lab. So, they cultivate the cells necessary to approximate a piece of the brain in a petri dish. A newer approach taking hold in the field is to cultivate mixtures of brain cells together into a 3D structure, called neural organoids.

At the heart of Stem Pharm are a series of scientific breakthroughs related to these neural organoids.

“We and others will affectionately refer to this as brains-in-a-dish technology, but it is not a brain in a dish. Our platform approximates part of the function of the brain in a dish,” says Visuri. “In our case, we’re really good at modeling neuroinflammation. And the more you learn about it, the more you realize how complex that is.”

This is a rapidly emerging field today as dozens of teams from academic centers around the globe work to improve on the quality of neural organoids.

So what's unique about Stem Pharm’s approach? To put it simply, rather than simply housing neural organoids in a petri dish, they created a specific environment on which to grow the neural cells in a 3D structure. They build this structure on specialized synthetic biomaterials, and by doing so mimic the physiological environment of the brain and allow the growth of important cell types including neurons, astrocytes and microglia. The patents around their organoids and hydrogels give their work a helpful moat.

“By creating the right physical, chemical and cellular environment for these cells, we can coax microglia cells to behave more

like they're in the in vivo setting, that is, respond like they are in a human brain. That's what makes our model unique,” says Gordon.

“I think these complex models are probably the world's best way of studying neural inflammation in the laboratory,” says Visuri.

NEXT STEPS

Recent successes in Alzheimer’s therapeutics, like those announced this year by Eli Lilly, have heated up the space and increased interest in Stem Pharm’s work. According to Gordon and Visuri, one major opportunity is to work with leading pharma companies to use these superior brain organoids to develop treatments for brain diseases. And not just Alzheimer’s. These neural organoids are like “the goose that lays the golden egg,” says Visuri, because they can help researchers better understand all kinds of neural inflammation, which is related to a broader range of diseases.

Stem Pharm works with larger pharmaceutical companies, but they are focused on developing their own therapeutics. It’s R&D-heavy work that will require a fair amount of upfront investment, which is part of their current calendar. Thankfully, the team has been very successful at raising grant funding to date – about six million dollars in total.

They’ve got a long road ahead, and Stem Pharm is still a relatively small, scrappy team, but Gordon counts that as a strength.

“You can develop drugs to treat neural inflammation as it relates to Alzheimer's, Parkinson's, potentially ALS, MS, many, incredibly devastating neurologic diseases,” says Visuri. “It’s not a one-size-fits-all solution, but it’s a tremendous opportunity.” It’s helpful that each member of the leadership team has had startup company successes in pharma and life sciences and can bring those experiences to bear.

“I think this is where the innovation happens in drug discovery,” says Gordon. “Small companies, new approaches, intriguing technology, changing the way drug discovery is being done. I think it's just really exciting that there's so much opportunity with this technology to make a huge difference.”

We couldn’t agree more.

C. Light Is Using New Eye Movement Tech to Detect Alzheimer’s Early

Christy Sheehy-Bensinger, PhD, is on a mission to bring a non-invasive and affordable test to market that can give early indications of brain conditions like Alzheimer’s. Her academic work in eye movement tracking has opened up a world of opportunity for primary care physicians – who would gain a new tool in their toolbox – and for patients concerned about cognitive impairment.

DDiagnosing brain health issues, particularly neurodegenerative diseases like Alzheimer's and Parkinson's, can be a slow and frustrating process. Current methods often rely on expensive and invasive procedures like PET scans or lumbar punctures. These tests just aren’t practical for routine screening or preventative care, often leading to delayed diagnoses and missed opportunities for early intervention.

"Early detection is critical for managing neurodegenerative diseases," says Christy Sheehy-Bensinger, PhD, CEO & Founder of C. Light Technologies. "But current methods are simply not ideal for preven-

tative care. We need a faster, easier, and more accessible solution."

That “faster, easier, and more accessible” is key. There are a wide range of innovative solutions coming to market with the promise of early detection of Alzheimer’s, from scans to blood biomarkers to appbased tests. But these solutions are rarely available at the point of care when a concerned patient is talking about cognitive impairment with their primary care physician.

One highly-accessible way to get a window into brain health is by measuring eye movement, something doctors have been aware of for years. The problem is past methods haven't been sensitive enough to

detect the subtle changes associated with early-stage neurodegenerative diseases. C. Light Technologies' goal is to change that.

ORIGIN STORY

Like so many founders, Dr. SheehyBensinger’s connection to Alzheimer’s is personal. She has had multiple family members get diagnosed with the disease and she watched her Great Aunt Mary deteriorate before her eyes.

“I can remember visiting her in the nursing home when I was 10 years old. She had no idea who I was, even though we’d been grocery shopping for her and visiting for years.”

Dr. Sheehy-Bensinger’s grandmother also died from Alzheimer’s, her aunt from early-onset Alzheimer’s at the age of 60, and now her father has signs of mild cognitive impairment (MCI).

“Knowing I have this big family connection to Alzheimer’s motivates me to see how I can help expedite drug development and get care into the hands of patients.”

Those feelings, strong as they were, went somewhat dormant while SheehyBensinger threw herself fully into a PhD program at Berkeley. She studied vision science and did a post-doc in neurology. She spent years exploring a new way to measure eye movement, one based on microscopic movements in the back of the eye, instead of in the front.

She had a hunch that her work could be helpful in detecting conditions like multiple sclerosis, but over time she realized that there was a strong eye-brain connec-

tion as well, and suddenly her academic work brought her right back to her starting place: Alzheimer’s.

“It was a happy confluence of events that ultimately led C. Light back to brain health,” says Sheehy-Bensinger.

Her research into microscopic eye movements and their connection to various conditions caught the industry’s attention. So she formally launched a company called C. Light Technologies, jumped into a Berkeley accelerator, and then went on the fundraising trail, ultimately raising around $8 million to bring her vision to life.

UNDER THE HOOD

C. Light's flagship product is RetiTrack, a non-invasive device that uses a high-resolution camera to track eye movements at the photoreceptor cell level in the retina. These tiny movements, invisible to the naked eye, can provide valuable insights into oculomotor function with a future nod towards brain health.

"The key innovation lies in our ability to detect these subtle eye movements," explains Dr. Sheehy-Bensinger. "Our highresolution camera offers a much more sensitive measurement compared to traditional eye tracking methods. We bring previously invisible data to life."

The RetiTrack test itself is incredibly quick and user-friendly. It takes just 10 seconds to complete and requires minimal user effort. This makes it ideal for use in various settings, from primary care physician offices to potentially even retail locations. There is no puff of air, no eye

drops, and certainly no pain.

The RetiTrack is FDA 510-k cleared only as an eye movement monitor. Dr. Sheehy-Bensinger’s work connecting fixational eye movements to conditions like Alzheimer’s is currently in process and has yet to be proven with the FDA. You could describe RetiTrack as a device with a current capability, and a mission and vision for future impact.

FINAL WORD

It turns out the eyes aren’t just the window to the soul. They’re also a window into the brain. Thanks to the personal passion of founder Dr. Christy SheehyBensinger, combined with her unique academic work in vision science and neurology, we may be on the cusp of a new wave of non-invasive diagnoses.

If C. Light Technologies is successful in using subtle changes in eye movements for earlier diagnoses of neurodegenerative diseases, it could have a cascade of positive implications. It could lead to more timely intervention, which, when combined with new therapies, could lead to better long-term outcomes.

Early and accurate diagnosis can also expedite drug development by providing researchers with better tools to track disease progression and treatment efficacy.

Finally, RetiTrack's non-invasive and user-friendly nature makes it suitable for broader screening initiatives. This could allow for earlier identification of at-risk individuals and facilitate preventative measures.

Despite its promise, C. Light

Technologies acknowledges the challenges ahead. Dr. Sheehy-Bensinger mentions two key hurdles: clinician adoption and reimbursement.

"Encouraging clinicians to adopt a new technology can be challenging," says Dr. Sheehy-Bensinger. "We need to build trust and demonstrate the value RetiTrack can bring to patient care." On the reimbursement front, C. Light is working with a reimbursement strategist to secure insurance reimbursement for RetiTrack.

C. Light Technologies remains confident about the future. They are continuously refining their technology and developing algorithms to combine eye movement data with other biomarkers for enhanced predictive capabilities. Their vision is to integrate RetiTrack seamlessly into primary care settings, potentially offering a valuable tool for routine checkups.

"Imagine a future where an annual brain health assessment is as simple as an eye test," Dr. Sheehy-Bensinger concludes. "That's the future we're working towards at C. Light Technologies."

By leveraging the power of eye movements, C. Light Technologies is poised to transform brain health assessment, paving the way for earlier interventions and improved patient outcomes in the fight against neurodegenerative diseases. CONTACT CLIGHT@STARTUPHEALTH.COM

Michael Harris, PhD CEO & Co-founder

Novel Interventions in Children’s Healthcare (NICH) Serves Vulnerable Youth Struggling with Type 1 Diabetes

While many health interventions focus on helping the most engaged patients, seeing this as low hanging fruit for improving outcomes, the Novel Interventions in Children's Healthcare (NICH) team takes a different approach. They’ve created a platform and care strategy that tackles the most complex and costly patients with Type 1 diabetes. Their innovative program reduces costs and saves lives by meeting the holistic needs of vulnerable youth.

IIn 2011 Michael Harris, PhD, was flying to New Mexico, to visit family for Thanksgiving when he started putting together an idea to solve a persistent problem he had faced as a healthcare provider. In his diabetes clinic he encountered young people struggling to successfully manage their diabetes because of insurmountable social problems, including poverty, social isolation, lack of access to diabetes tech, instability in their families, among many other challenges. Many of these young people were repeatedly hospitalized and experiencing avoidable deterioration in their diabetes and overall health.

“I was really frustrated. I was seeing these young people in my diabetes clinic, and I really had nothing to offer,” says Harris. As he started brainstorming solutions, his focus turned to what seems to get people’s attention in healthcare more than anything else: money. “I was thinking about dollars because it seemed like people don’t invest in programs because they make sense or improve people’s lives and health, but because they have an ROI attached to it,” he says.

After returning to Oregon, he shared his idea with Kimberly Spiro, PhD, a friend who had a background working in intensive, community-based mental health programs in the foster care system. They brainstormed further, drawing from some notes Harris had jotted down on a napkin on the plane during his trip to Albuquerque; then Harris sent an email to the director of his lo -

cal Medicaid office, pitching the idea with the enticement that it could save Medicaid money.

Harris proposed to provide intensive community-based services to youth with diabetes and other chronic and complex medical conditions who also experience significant system and social challenges. It would require a buy-in from Medicaid, but Harris assured Medicaid that the savings from avoiding repeat hospitalizations would far outweigh the investment. To Harris’s surprise, they immediately wanted in.

Harris and Spiro soon began to pilot Novel Interventions in Children’s Healthcare (NICH), which serves young people living with diabetes and other complex and chronic conditions who are considered high risk, high needs, and most importantly high costs. Currently, NICH serves around 160 young people at any given time in hospitals throughout all of Oregon and at two sites within California’s Bay Area (Stanford University and University of California – San Francisco). The program has proven effective in improving the health outcomes of young people and saving the system money. The average cost savings from the year prior to a patient enrolling in NICH to the year of enrollment is $30,000 with an additional reduction of $15,000 to $20,000 in Medicaid paid claims the year after discharge.

THE PROBLEM

As the Clinical Director, Spiro is well aware of the problems facing NICH’s

patients. In addition to contending with complex and chronic medical conditions like diabetes, these young people also face significant social challenges such as unstable housing, lack of access to phones or internet, and poverty. Many of them have parents that suffer from their own health problems, mental health issues, or substance abuse problems. Some of their parents are incarcerated or can’t keep stable employment because of their child’s regular medical appointments. And then, there are also parents that don’t speak English, making it near to impossible to navigate the healthcare system.

“The hospital tries to connect these patients with community services but when you are living in survival mode, you have no time or energy to connect to the resources that exist in the community,” says Spiro. “There's this breakdown between the hospital and the community with no infrastructure to address the true challenges these families experience on the daily, and these kids are just slipping through the cracks."

The cost of treating these young people at hospitals is very high. “Young people come into our institution repeatedly for avoidable reasons that cost the system a disproportionate amount of healthcare expenditures,” says Harris. NICH focuses on serving the top 5% of children and adolescents who account for 48% of medical expenditures.

Harris recalls one young person who exemplifies the gravity of their mission. “We had a young teen with Type 1 dia -

betes who I had seen in clinic and had unsuccessfully petitioned for a contract for NICH services with the insurer. This young person was on the autism spectrum and living with grandparents who had custody because the youth’s parents died in a car accident years ago. This young person’s grandfather was the primary caregiver, and the grandmother was on hospice, however, both grandparents were in failing health. When the grandfather had an acute medical emergency and was life-flighted from their rural community to a hospital in Portland, this young person was left alone with the grandmother. Unfortunately, the teen died of diabetic ketoacidosis (DKA) while the grandfather was at the hospital. We’re not serving a population that will be fine with the status quo. We are serving our highest risk, highest needs, and highest cost youth.”

THE SOLUTION

Spiro tells another story of a patient – this one with a more hopeful ending. This young woman lives with Type 1 diabetes and couldn’t live with her mother who had substance abuse problems. She was sent to live with her grandmother in a single-wide trailer in rural Oregon, where her situation quickly deteriorated. “She assaulted a principal, she was running away regularly, and had multiple DKAs,” says Spiro. With the help of NICH, she was able to stabilize her health through regular check-ins to make sure she was monitoring her blood-sugar levels and giving herself

insulin. “She earned rewards for doing those things and we were able to get her on a Dexcom and eventually access to a pump,” says Spiro, adding that Medicaid often waits for a patient to meet requirements around self-regulation before providing access to healthcare technology. With the support of her NICH interventionist her A1C levels dropped by two points, her school situation stabilized, and she was able to continue living with her grandmother. “Without NICH she was on the verge of ending up in foster care, further impacting her quality of life and costing the system even more money,” says Spiro.

This intensive, hands-on approach is central to NICH. “The problems of these young people are not successfully managed with more medical care. The solution is getting into their lived experience and understanding the true drivers of a deterioration of their health,” says Harris. NICH provides daily contact either in person or through personalized technology, 24/7 family access, and intensive home-and-community-based services, typically for one year. “The most important thing we do is build relationships with people who have lost trust in the system,” says research director David Wagner.

Interventionists, who each have caseloads of eight patients, do most of this on-the-ground relationship building. Many of the interventionists are bilingual and representative of the communities they serve.

Spiro describes their solution as a two-

pronged approach. The first step involves stabilizing the lives of their patients and then building skills in helping the families more successfully navigate the broken system. Interventionists also share with medical providers, school staff, and others the unique ways of supporting each family that will lead to the most success.

FINAL WORD

NICH is improving the lives of vulnerable young people while saving money for the healthcare system, including payors and hospitals alike. “We see a 30% reduction in youth experiencing admission for diabetes when they’re in the program and a 50% reduction in youth that need to be admitted for DKA,” says Wagner.

Other benefits of the program include overall improvement of health among patients, improvement of care, reduction of provider burnout, and a reduction in health inequities among youth of color. “We feel incredibly passionate about doing this work, but only after focusing on the money were we able to get this lifesaving program to our most vulnerable youth,” says Harris. “By bringing the patients’ stories into the boardroom we’re making it incredibly hard for decisionmakers to say “no” in doing the right thing for the most vulnerable.”

CONTACT

NICH@STARTUPHEALTH.COM

RetiSpec’s AI-Driven Eye Test Detects Alzheimer’s Early

Eliav Shaked’s passion to solve critical challenges in Alzheimer’s led him to new research connecting brain health to retinal imaging. His company has now raised a $10M Series A from strategic investors Topcon Healthcare and Lilly.

For many years, the early aaof Alzheimer’s disease felt pointless. Why inform someone that they were at risk of the

disease, or already showing signs of decline, if there was nothing you could do for them?

That reality has shifted dramatically in the last decade. There are now multiple FDA-approved disease-modifying therapies on the market that can slow the disease and extend quality years of life. As a result, more and more people want to understand their current brain health – and what’s in store for them in the future – yet health systems have been slow to address the demand.

Current methods for the detection of Alzheimer’s are extremely limited. In fact,

Eliav Shaked, CEO & Co-founder

if a person goes to their primary care doctor (their most likely first stop) with complaints of potential mild cognitive impairment, they’ll probably just be told to watch and wait: ‘Come back next year and we’ll see how you’re doing.’

Other methods for diagnosis are invasive, expensive, and stigmatizing. For instance, people who are fearful of getting evaluated for Alzheimer’s disease are likely to avoid discussing their concerns about their brain health with their doctor. For the few people who live close enough to a large urban area to get a lumbar puncture for suspected Alzheimer’s – an extremely helpful diagnostic tool – there’s still a hesitance because it’s painful and challenging to coordinate.

What if early Alzheimer’s detection was easy, painless, and could be performed at a primary care office or at an annual eye exam?

Enter RetiSpec.

ORIGIN STORY

Eliav Shaked has always been a problem solver. He began his career as a biomedical

engineer and focused on the intersection of technology and medicine. He worked for a few years at startups focused on noninvasive monitoring, mainly for vital signs of the brain, and then it was time to carve his own entrepreneurial path. In 2015 he took part in Singularity University.

“The goal for the program was to build companies that would impact a billion people in the next decade,” says Shaked. The experience lit a fire, but he wasn’t sure what problem to solve.

Around this time, a family friend was diagnosed with Alzheimer's disease. There was nothing Shaked could do, in spite of his knowledge of healthcare and technology, and the pain and frustration of that fact hit him hard.

He threw himself into Alzheimer’s. He discovered new research that was coming out of the University of Minnesota about how the eye could be a window into early Alzheimer’s detection. He studied spectral imaging and sharpened a theory for how it could be leveraged in new ways to detect this disease.

But all of that was an easy warmup compared to what came next. Shaked applied to and was accepted into MassChallenge in Boston. He and his wife had to sell most of their belongings, cash out their savings, pack their life into a suitcase, and live out of an AirBnB for five months.

“The goal in Boston was to ask the right questions to the right people. There was a lot of mentorship involved. I made a lot of mistakes, but it empowered me to keep on going,” says Shaked.

He not only succeeded in the program,

but emerged with a company and device that could help millions of people. He also landed some of the most revered healthcare brands in Boston as interested partners.

UNDER THE HOOD

RetiSpec has created a completely noninvasive process that uses eye imaging to detect Alzheimer’s disease. They leverage already existing equipment – the fundus camera that can be found in any eye doctor's office – and take a picture of the retina at the back of your eye.

The magic of RetiSpec is in understanding that the retina is neural tissue. It’s the one point in the body where you can noninvasively see – or at least get a great proxy for – what's happening in the brain.

A fundus camera, like any standard digital camera, captures three wavelengths of color: red, green, and blue. RetiSpec takes that standard sensor off of the fundus camera and replaces it with a hyperspectral sensor that can capture and analyze 100 wavelengths of color. Then they use deep learning models to process that information, which allows them to identify signs that correlate with Alzheimer's disease.

OUR TAKE

There are a lot of reasons we’re excited to welcome RetiSpec into StartUp Health’s Alzheimer’s Moonshot. First, we love that they’re already attracting the kinds of partners they’ll need in order to get to market and scale. RetiSpec just closed their Series A with participation from Topcon Healthcare, the leading player in the eye care space, and Eli Lilly and Company, a leader in advanc-

ing research of therapies and diagnostics for people with Alzheimer’s disease. This raise is about a lot more than money – it’s about having the right people on the bus in order to grow quickly.

We’re bullish on RetiSpec because their clinical results have been promising. They’re showing strong performance for prediction of Alzheimer’s pathology, compared with the gold standard of PET, cerebral spinal fluid, and emerging blood tests. They continue to conduct clinical trials, which are aided by the fact that participants can be recruited easily at any eye care office.

And finally, we love RetiSpec simply because it makes Alzheimer’s testing easy and accessible. Once in the market, the RetiSpec test can be made available in any primary care or eye care office, in any community regardless of income level. Given today’s demographic demands and the challenges faced by overburdened hospitals, that accessibility piece is more critical than ever.

Sensulin’s Biotech Dream Team Is Bringing the Lowest-Cost Smart Insulin to Market

The idea of glucose-responsive insulin has been bandied about for decades. Could a new insulin formulation automatically level out high and low glucose levels such that a person dependent on insulin only needed to take one shot a day? CEO Mike Moradi (pictured) has assembled a team with the experience necessary to make this dream a reality — and at an accessible price point.

SSensulin’s idea to create a “smart insulin” (glucoseresponsive insulin or “GRI”) is not new. Three of the company’s co-founders were toying around with the idea in the 1990s and 2000s, and the concept has existed in academia for some time. What sets Sensulin apart is their dream team of diabetes researchers and the use of an already-approved insulin as the basis for its formulation, which will help bring glucose-responsive insulin to market.

Their team has a successful exit track record and a combined century of experience in diabetes research and biotechnology. Dan Bradbury, their Chairman & Founder, was the CEO of Amylin, which developed the first GLP-1 drugs. In 2012 Amylin was acquired by AstraZeneca and BMS for $7 billion, which is still the largest exit in the diabetes sector. Chris Rhodes, PhD, their CTO, was the CEO & Founder of Drug Delivery Experts, and as a newly minted post-doc he invented the Technosphere inhalable delivery system, which is the only non-injectable insulin approved by the FDA. He also worked at Amylin as the head of drug delivery for nearly a decade. Mike Moradi, CEO & co-founder, cofounded Nanosource, a nanotechnology company acquired by Dupont.

In addition to their professional work, the team also has personal knowledge of diabetes. Both of Moradi’s parents are insulin dependent. In his late 20s — when he noticed that a whole generation of his family was being diagnosed with Type 2 diabetes — he moved from working in advanced materials and semiconductors to the natural sciences, in hopes of having an impact on diabetes research. Jon Brilliant, Sensulin’s CFO, also has family members impacted by the disease. His youngest child was diagnosed with Type 1 diabetes, which has since become a professional area of focus, along with cancer and mental health.

THE CHALLENGE

People with Type 1 diabetes typically take insulin shots four to six times a day. “There’s a cognitive burden one carries when diagnosed and told there’s a drug that can save your life but if you don’t manage it properly it can also kill you," says Brilliant. "Think about the burden of that. You can never escape it.”

“Living with chronic diabetes is a complex math problem,” says Moradi. Individuals must time their insulin injections with their meals and try to match up the peak PK curves of the insulin with their digestive curves. For the 537 million diabetes patients worldwide, it’s a process that involves a fair amount of guesswork, trial by error, and adjustments — and mistakes can be costly to one’s health.

If a person with diabetes spends too much time in hyperglycemia (marked by high levels of glucose in the bloodstream) long-term effects can arise, such as eye

and kidney disease. Hypoglycemia can be deadly for patients and the average person with Type 1 diabetes goes to the ER once per year, which is half the cost of treating the disease, according to Moradi.

THE SOLUTION

Sensulin’s glucose-response insulin takes the guesswork out of diabetes management by meeting both baseline and mealtime needs with a single injection. Whereas a person with diabetes is always living between the peaks and valleys of hyperglycemia and hypoglycemia, Senuslin helps to calm these waves through its chemical makeup that can recognize imbalances in glucose levels and respond by either bringing blood sugar levels up or down. “This takes the guesswork out of a very complex disease,” says Moradi.

Brilliant sees Sensulin as an interim step toward a cure for the disease. “I don’t think there will be a cure in my daughter’s lifetime,” he says. “We don’t even know what causes Type 1 at this point and reprogramming the autoimmune system is not an easy journey,” he adds. But moving to one shot a day would be a big step forward. “I think there’s a continuum toward the cure and we’re playing an advancing role towards those next steps.” Moradi adds “Even in a world where a cure exists, the world still needs better and cheaper insulins.”

Reducing costs is another major motivating factor for Sensulin. “The innovations that will be truly game changing will be super low cost and widely available,” says Moradi. He hopes that Sensulin will be available worldwide and save patients con-

siderable money. He adds, “There is always room in the market for the low-cost producer, though our real goal is to be best-inclass. If we are also first-in-class, that is the icing on the cake.”

HOW IT WORKS

“Sensulin is sort of like a chemical pancreas,” says Moradi. “When blood sugar is high, it releases more insulin. When blood sugars return to normal, it releases less, much like a healthy human pancreas.” The solution is achieved by clever chemistry. “It’s a very elegant solution to a very complex problem,” says Brilliant.

Sensulin does not use chemicallymodified insulin, which distinguishes it from other glucose responsive insulin. The company sees this as a significant advantage, which they anticipate will lead to a faster and cheaper FDA approval process and a lower price when it hits the market. Other GRIs are considered “New Chemical Entities” by the Food & Drug Administration and other regulatory bodies globally, which requires more stringent clinical trials with many more patients and longer timelines.

Ananth Annapragada, their chief scientist, first developed something that appeared to work in rats in his academic labs. The technology they initially licensed was inhalable insulin but the linker (sort of like a glue between the liposomes) was toxic. “Challenge number one was to take something that worked as an inhalable drug and repurpose that as a subcutaneous injectable,” says Moradi. This required a new route of administration and finding new

linkers. This initial research was funded by the National Institutes of Health, the National Science Foundation, and private foundations and investment.

WHERE THEY ARE IN THE PROCESS

In 2021 the company raised a $4M Series A round of capital that helped them hit key research milestones. Currently, they are at a point of transition, moving from a research and development preclinical team to a clinical team. They are gearing up for another set of pig studies to show further scientific proof of concept in a large animal setting before moving to a human clinical setting. “The roadmap is there,” says Moradi. They are currently seeking further funding to bring them into this next stage of development.

OUR TAKE

Sensulin’s ambition to reduce insulin injections to once-per-day would greatly improve the quality of life for patients. It promises to reduce hospitalization for hyperglycemia, lower the cost of treatment, and lighten the burden for people with diabetes through a smart insulin that can regulate glucose levels without the stress of hypervigilance. We’re hopeful about this cost-aware solution that could be widely accessible, and we’re honored to join this world-class team toward achieving this goal as a member of our T1D Moonshot Community.

ADmit Therapeutics Has Developed a Breakthrough Alzheimer’s Biomarker Test Based on Epigenetics

Under CEO Marta Barrachina, PhD, ADmit Therapeutics has developed a promising new blood test for the early detection of Alzheimer’s disease that could help make Alzheimer’s clinical trials more efficient and effective. Most people think about Alzheimer’s disease as a series of visible symptoms, like memory loss and mood changes.

MThese symptoms exist on a spectrum, and when a person – or their loved one –notices the early signs of these symptoms, they might go to their primary care physician and get a diagnosis of mild cognitive impairment (MCI).

Patients with an MCI diagnosis have no idea if their small signs of decline are harbingers of full blown Alzheimer’s or dementia. In decades past, this wasn’t a huge issue, because there was precious little that could be done to slow the progression of the disease. In some cases, it felt like less knowledge was better. But that’s all changing. Today there are

Marta Barrachina, PhD CEO & Co-founder

therapeutics and treatments that can slow the progression of Alzheimer’s, and there is even serious work being done on a cure. Pharmaceutical companies are going all-in on Alzheimer’s clinical trials, but these studies come with huge enrollment challenges.

According to a white paper put out by UCS Schaffer, “Alzheimer’s trials tend to be slower to enroll participants, take longer to complete, and are more expensive than trials in most other therapeutic categories. In fact, approximately 99% of eli-

gible patients are never referred to or consider participating in an AD clinical trial.”

One of the barriers to Alzheimer’s clinical trials is that screening for appropriate patients is expensive and time-consuming. To date, screening has included MRIs, PET scans, and spinal taps. Adding insult to injury (spinal taps are painful and not tolerated by everyone) preclinical Alzheimer’s trials have a screening failure rate – the percent of subjects who go through screening but don’t meet the enrollment criteria – of 88%.

A group of scientists in Spain are on a mission to change this paradigm – and help pharmaceutical companies develop therapies faster – by making Alzheimer’s testing more accurate and predictive.

ORIGIN STORY

Marta Barrachina is a biochemistry PhD who began her career at the Bellvitge Biomedical Research Institute in Barcelona. She worked her way up the academic ladder, as a principal investigator and then on a team with renowned neuropathologist Isidro Ferrer.

But she had discoveries of her own to make about the biochemistry of the brain. So she went to the source, analyzing postmortem human brains from biobanks.

Through their work, Dr. Barrachina and her team successfully identified a series of epigenetic biomarkers that link mitochondrial activity to Alzheimer’s disease. The reason this was important, explains Barrachina, is that mitochondrial dysfunction has been described as one of the first events in the progression – or

etiopathogenesis – of Alzheimer’s disease, happening even prior to the appearance of beta amyloid and tau proteins. As their findings are related to mitochondrial DNA, they have been viewed as promising biomarkers for the disease.

Their discovery opened the door to the possibility of predicting Alzheimer’s progression years in advance, by looking at activity at the cellular level, rather than waiting for physical signs of plaque to show up on the brain. It’s a prognosis, or disease forecast, not merely a snapshot of current symptoms.

Barrachina presented her findings to her innovation unit, and they pushed her to validate and patent it – and then share it with the world.

She knew that she was on to something special, something that could change patients lives by giving them early detection for cognitive diseases. But she also knew how easy it was for research to get lost in peer-reviewed journals.

“Our results were quite robust, but I saw clearly that if I didn't do that change in my professional career, that our findings wouldn't reach patients,” says Barrachina. So she got an MBA and found two cofounders who could help her bring her discoveries to market.

“My motivation and the motivation of my team is the clinical impact. I'm aware that I have to assure the return of investment to my current investors, but the motivation is not a business motivation.”

UNDER THE HOOD

For ADmit, it all starts in the mito -

chondria, which Barrachina explains are “like the lungs of the cells. It's where the energetic metabolism occurs.” This is where the very first events of nearly all neurogenic diseases take place, “because without energy, the neuron or the glial cells cannot survive.”

After concluding their first clinical validation, ADmit was able to predict the progression of Alzheimer's disease and dementia in patients with mild cognitive impairment. In patients with early memory loss complaints, they were able to categorize patients into those who will progress to Alzheimer’s disease dementia or those who won’t.

“Based on our data, we can predict up to 14 years before the appearance of Alzheimer's dementia,” says Barrachina. “We have better results – accuracy, sensitivity, specificity – than current scans.”

Just how much better is what Barrachina will be proving out in their next clinical validation and in their FDA process.

OUR TAKE

Marta Barrachina, PhD, and her team at ADmit are on the cusp of the kind of scientific breakthrough that could completely change how we look at Alzheimer’s. Current options for visualizing Alzheimer’s disease, like the PET scan, give patients a snapshot of a moment in time but don’t offer much information on what’s to come. Patients get a diagnosis not a prognosis. And with more and more therapies coming to market that can slow the progression of Alzheimer’s, catching

it early can gain a person years of quality life.

Patients will also be pleased to be able to gain data on disease progression through a blood test. ADmit positions itself as a good first line of defense, democratizing access to Alzheimer’s testing by sidestepping costly PET scans and highly invasive spinal taps.

But it’s not just about individual patient care. ADmit’s breakthrough is even more useful at a macro-pharmaceutical level. They believe that their test could improve the ease and accuracy of the Alzheimer’s disease testing required during clinical trials, thereby making those trials significantly more successful.

Barrachina and her team are currently working on CE Mark approval in Europe and are holding meetings with the FDA. Their team of 11 has raised $10 million and counts among their advisors Dr. Russell Swerdlow, considered the father of the theory of the mitochondrial cascade in Alzheimer’s disease.

The next task is to increase their sample size with more patients from the United States. Much of the hard science has been done, the discoveries patented. Now Barrachina and her team have to complete validation studies and start shouting their story from the rooftops.

DiabetesWise Is Helping People with Diabetes Thrive Through Unbiased Device Reviews

Korey Hood, PhD, and his team –in collaboration with Stanford University, people with diabetes, and other stakeholders – created a platform that helps people living with diabetes take control of their health with confidence and clarity through transparent and comprehensive device reviews.

IImagine being diagnosed with Type 1 diabetes (T1D) while pursuing your PhD in the field of Type 1 diabetes. That irony is Korey Hood’s story, and the spark for DiabetesWise.

“Being diagnosed with the same disease I was researching seemed like a strange coincidence. But looking back, I think it was a calling that gave me some extra passion for doing the work,” says Hood.

Being a clinical and health psychologist, Hood was no stranger to the clinical rules of taking insulin. But it was after he was diagnosed that he started realizing the real challenges of having diabetes. From choosing the right CGM to deciding whether an insulin pump was the best option, Hood was overwhelmed by the endless decisions that had to be made. Unfortunately, there wasn’t a place where he could get unbiased

Korey Hood, PhD, Founder

information or compare different devices to understand how those devices could fit into his life.

That gave rise to one big question in Hood’s mind – if he, a diabetes researcher, couldn't find unbiased information online about basic diabetes questions, particularly around medical devices, what hope was there for the person without an insider view?

ORIGIN STORY

This problem gave Korey, a professor and a staff psychologist at Stanford University,

the spark of an idea for a digital platform that would educate people with diabetes about the options they had to manage their condition.

Millions of people in the United States are affected by diabetes or are on their path to developing the condition. Among those who rely on insulin, around 5-6 million people struggle with effective management because access to diabetes devices, such as insulin pumps and continuous glucose monitors (CGMs), is often concentrated in urban areas.

So, leveraging his expertise in clinical research studies, Hood joined forces with three other experts to bring DiabetesWise to life. They pitched their idea to the Helmsley Charitable Trust and received support for the next five years through a $4M grant. The funding helped them work independently of commercial interests, focusing solely on creating an educational platform accessible to everyone.

As often happens with startups, solving one problem unearthed another. After the DiabetesWise platform was deployed, Hood began gaining insights into the different groups of people with diabetes who still couldn’t have their problems solved through his platform. These were essentially people who relied on primary care physicians for diabetes management. The challenge was that these primary care physicians didn’t always have the expertise or resources to provide comprehensive care, leaving many individuals without ready access to the tools that could significantly improve their diabetes management and overall wellbeing.

Korey also learned that these challenges were more pronounced for individuals residing in remote or rural areas, where the limited healthcare infrastructure and geographical barriers made it difficult for them to manage their condition effectively.

Then, Hood and his team started developing a professional version of DiabeteWise for healthcare providers that would help them better match people with diabetes to the right devices.

A short while after launching both platforms, Hood and his team conducted clinical trials involving around 500 people with diabetes to measure DiabetesWise’s impact. Their goal was to see if DiabetesWise would encourage more discussions about diabetes devices with healthcare providers and lead to more people adopting them.

“We could tell just across the first couple of months that people were accessing it and that they were using it as a tool to share information or handouts that they had with their providers and start on that process,” says Hood.

UNDER THE HOOD

DiabetesWise was designed after drawing inspiration from models like Consumer Reports. Developed by a small team of fulltime members who dedicate their efforts to the platform and a larger advisory group of endocrinologists, psychologists, primary care practitioners, certified diabetes educators, and individuals living with diabetes themselves, the platform acts as a source of reliable and unbiased information.

On DiabetesWise, people with diabetes can compare treatments and devices – in-

cluding insulin pumps, connected pens, smart pens, automated insulin delivery systems, and emerging technologies – based on different features, free from the influence of device manufacturers’ agendas. It provides comprehensive information and resources for each device category, from guides on using them to tips for navigating insurance coverage.

In addition to its technology-focused content, DiabetesWise also emphasizes community and storytelling through its “Wisdom” section, where people share their personal experiences of starting and stopping devices and the reasons why. This helps people with diabetes make informed decisions about what devices would better fit their unique circumstances and lifestyle.

DiabetesWise Pro has a prescription assistance tool that streamlines the process of understanding and accessing diabetes management options, making it easier for healthcare providers to find the best device options for their patients.

When it comes to the business model, DiabetesWise operates with a dual focus: serving both direct-to-consumer needs and partnering with healthcare providers, clinics, and payers. While the core services are free to access for individuals with diabetes, the team is exploring avenues to collaborate with healthcare stakeholders to ensure sustainability and scalability. In the latter case, the DiabetesWise team is looking for people interested in supporting some of their services. For instance, they are exploring innovative strategies to embed prescription tools into electronic health records (EHRs) in order to stream-

line the process of prescribing diabetes management devices.

In addition, they are also considering partnerships with payers to bundle DiabetesWise with other services that could enhance patient support and education during critical moments, like when starting continuous glucose monitoring (CGM).

LAST WORDS

Born out of Stanford and developed by a team of professionals with backgrounds in healthcare, DiabetesWise stands out for its mission of providing unbiased resources and support for individuals managing diabetes. With their focus on devices, DiabetesWise stands alone as a trusted partner that can help any insulin-dependent individual figure out what tools are right for them. Whether they need to start, stop, or switch devices, DiabetesWise is ready to help.

We’re also bullish on DiabetesWise because it fosters community. The platform fosters engagement and interaction among its members, creating an environment where individuals can share their experiences, learn from one another, and find solidarity in their diabetes journey. With all these features, DiabetesWise is driving a positive change in the diabetes space and improving outcomes for individuals living with diabetes.

CONTACT

DIABETESWISE@STARTUPHEALTH.COM

Neurosteer’s Breakthrough hdrEEG™ Reimagines EEG with Its Better, Faster Approach to Analyzing the Brain

Under the direction of signal processing expert Nathan Intrator, PhD, Neurosteer’s team has created an affordable and accessible device that measures minute electrical brain activity. Their device can help patients and providers manage brain conditions more effectively and proactively.

TThe Neurosteer story begins with a resurrection. Or at least as close to one as you’ll likely hear about in medicine today.

Nathan Intrator, PhD, has been working as a researcher and professor in signal processing for two decades. He studied how the brain processes electrical signals, focusing on the inner sonar systems of bats and dolphins.

This work led Intrator to develop the initial hardware that could be affixed to an individual's forehead to directly measure electrical brain activity. Initially he focused on commercial applications such as studying pilots during flight simulation

and students with ADHD. It was all very academic and lived within the confined world of Tel Aviv University, until the day he received a call about a man in a coma.

The woman on the phone explained to Intrator that her husband had been in a coma for five years. The doctors had given up hope, assuming he’d remain in a vegetative state forever. But the woman had read about Intrator’s research and thought maybe, just maybe, there was something there that could help.

She asked him if he would try out his device on her husband to see if any brain signals could be detected. Intrator responded to the challenge and was eager to see whether sensing the brain with just one EEG channel could provide valuable information in this case. After attaching the electrode strip to the man’s forehead, they could immediately see varying brain activity. More importantly, when the man’s wife spoke to him or they played his favorite music, the level of brain activity increased in meaningful ways.

Intrator was intrigued. He hadn’t yet had much experience with comatose patients, but he was seeing a significant level of specific brain activity. Something real

was happening. Intrator speculated that the verbal and musical stimulation had a profound impact on the comatose brain. The wife, motivated by these findings, immediately jumped into action, asking people from their community to spend time with her comatose husband, reading to him, playing music, and finding other ways to stimulate his mind.

After about eight months, the man opened his eyes and woke up. He was able to speak, his mind was perfectly intact, and he was able to answer complex math questions (he was, after all, an engineer).

To the woman and her family, this felt like a miracle. To Intrator, it was a revelation, but for different reasons. It was proof

that his technology had a potentially enormous role to play in healthcare. It wasn’t enough to use it in purely academic signal processing studies. A tool that offered highly accessible brain activity monitoring could save lives. It could help people understand and treat diseases and conditions of the brain and improve the quality of life for millions.

THE CHALLENGE

A fair question at this point was: Weren’t there already other effective ways to measure brain activity?

When measuring brain activity, we usually consider electroencephalography (EEG) or functional MRI (fMRI).

EEG has been around for 100 years and involves having a technician spend about half an hour pasting 24-256 small electrodes on the surface of the scalp using a sticky conductive paste. Not particularly convenient or pleasant. EEG is also limited in what it can detect. In fact, according to Intrator, a traditional EEG could have missed the faint brain signals emitted by the man in the coma. For that signal detection level, patients would currently need one of the big medical scanners, such as an fMRI (which only measures blood flow as a proxy for brain activity rather than directly measuring electrical activity itself). However, such scanners are incredibly costly, labor intensive, and simply not practical. According to our healthcare system, minimal responsive patients (in coma) are not routinely tested with fMRI.

But let’s step back from the specialized case of the man in a coma and think about people with neurological disorders or those who have concerns about developing such conditions in the future. That’s millions of people globally, representing one of the fastest growing areas and, in the context of an aging population, critical areas of healthcare today.

People concerned about Alzheimer’s disease and related dementias face similar barriers to timely and disease-modifying treatment. They are sent to amyloid PET (a radioactive brain scanner) or to a CSF test (via an invasive spinal tap). While there may be blood-based biomarkers available in the near future, it is still not clear whether they will be sensitive enough at the very early stages of the disease, when

Nathan Intrator, PhD CEO & Co-founder

disease modification therapy will be most effective. Also, blood biomarkers are not able to indicate whether there is also a risk for vascular dementia, a condition that does not allow therapy with the latest drugs.

What if a new system using affordable specialized hardware and automatic assessment based on the latest advances in digital signal processing, could offer people a fast, easy, noninvasive assessment of brain function? Intrator set out to answer that question by launching Neurosteer and building a strong and diverse team that could bring this new technology to market.

UNDER THE HOOD

The first thing to notice about Neurosteer’s wearable device is that it is small and portable. It consists of a disposable adhesive electrode strip that easily af-

fixes to the forehead. The electrodes pick up the electrical brain activity and send the signals to a pocket-sized sensor, which then wirelessly transmits data to the cloud for signal processing and automatic assessment. The algorithms created for the device allow for rapid and highly advanced analysis of the brain signals, which are then displayed on a web-based dashboard and produce an assessment report.

When Intrator describes what makes Neurosteer’s signal processing unique, he uses the metaphor of a symphony orchestra. Specifically, you can listen closely and identify the sound of individual instruments.

Just as a symphony is played on different musical instruments, the symphony of brain wave activity plays out on a collection of what Intrator calls “functional neural networks.” Using Neurosteer’s digital signal processing, Neurosteer’s hdrEEG can distinguish the activity of the different networks in the same way a single human ear can distinguish between the instruments of an orchestra.

This is important as it enables looking at the whole “orchestra of the brain” by applying connectivity analysis between the different functional networks. Connectivity analysis performed with fMRI has shown changes a decade before symptoms of Alzheimer’s occur. Demonstrating timely detection of Alzheimer’s and later vascular dementia, based on functional connectivity changes, will be key milestones for Neurosteer.

FINAL WORD

Neurosteer’s team is well on its way to redefining how we look at the management of brain health. The device has already received FDA Class II clearance. They’ve conducted several pilot clinical trials and are working on enhancing those trials to obtain additional FDA clearances for various neurological disorders, including Alzheimer's, vascular dementia, and Parkinson's. They have also published multiple peer-reviewed papers; in particular, their work on Parkinson's demonstrated the significance of their connectivity analysis. Additionally, they are exploring collaborations with research institutions and pharma to advance affordable patient screening.

By offering a more efficient and accessible method for brain assessment, Neurosteer seeks to empower individuals to proactively manage their brain health and receive timely interventions.

Neurosteer began changing lives the day Intrator used it to identify that a man in a coma still had signs of life. But Neurosteer is just getting started. Their advanced signal processing means scientists and physicians will gain a new understanding of the brain, which will have many positive benefits. For starters, it will most likely help optimize screening and neurostimulation, improve drug selection, and support more efficient clinical trials.

Chekkit Health Tackles the Problem of Counterfeit Drugs with a More Integrated Supply

Using blockchain technology, founder Dare Odumade’s Nigerian company provides products with unique identifiers to trace their origin, movement and determine their authenticity. In addition, it enhances last-mile supply chain knowledge with AIdriven insights from consumer data, enriching brands with predictive demand analytics.

DDare Odumade, CEO & Founder of Chekkit, was looking for a way to use his technology skills to create solutions to key problems in Nigeria, his country of origin. Previously, he started two technology companies: a social media platform at his university and then a music streaming network that eventually led to a partnership offer from Warner Music Group. However, by 2017, he was eager to start something that could impact lives in a more tangible way. He zeroed in on the problem of counterfeit drugs.

“Counterfeit drugs were a problem

Dare Odumade, CEO & Founder

that was always there, that I always noticed,” says Odumade, citing a statistic that 500,000 people die each year in sub-Saharan Africa from counterfeit or substandard drugs. Around the world, that number is close to one million people, according to the World Health Organization. Counterfeit drugs fall into two main categories. There are fake drugs that contain less of or replaced active ingredients, which may be harmful. Then there are substandard drugs which come from the original manufacturers but have factory errors and abnormal composition or not enough active ingredients.

While he was thinking about how to tackle this problem, the issue came close to him when a friend, a nurse in Ghana, had a patient who died when his kidney ruptured after taking counterfeit antimalarial medication. “This was an affirmation of what I need to do,” says Odumade. “The problem hadn’t been solved for a long time and was still having this impact on lives.”

THE SOLUTION

In establishing Chekkit, Odumade developed a solution that tracks products and connects supply chains using blockchain technology. In developed nations, such as the United States, GS1based systems regularize barcodes and serial codes, guarantee consistency among products, and allow products to move efficiently and securely. Nigeria, and many other countries in the developing world, do not have the benefit of such infrastructure, which makes it difficult to trace the origin of drugs or any other packaged goods. Chekkit helps solve this problem.

HOW IT WORKS

Although barcodes identify products, they don’t go very far in determining whether a product is counterfeit or authentic. “A counterfeiter can make an identical product with identical packaging,” says Odumade. “Chekkit exists to provide unique identifiers and an electronic means of transferring them between parties.” In order to accomplish this, Chekkit produces a label for each

package (leveraging GS1’s global standard for serialization), which includes a cryptographic unique identifier in the form of a QR code, data matrix code, or pin. Consumers or vendors are able to scan this information or enter it into a system in order to determine its authenticity and manufacturers are able to trace their products beyond the distributor.

The complexity of the African market has made traceability elusive for both producers and consumers. In the current distribution model, manufacturers are left in the dark once their products are delivered to distributors. “The market is heavily fragmented and the only way to solve the problem of counterfeiting is to unify the market,” says Odumade, who sees a solution by developing infrastructure that unifies a supply chain from end to end. “African countries are beginning to mandate policies around traceability.”

Currently, three African countries mandate traceability as a standard (GS1-based) for bringing a product to the market and Nigeria is poised to become the fourth. Odumade sees this as a game changer for the implementation of Chekkit’s technology as a middleware that transfers product master data from the Manufacturing Authorisation Holder’s (MAH) Contract Manufacturers (CMOs) to the destination country’s repository. The company has received the first accreditation for traceability in Nigeria and is prepared to provide traceable information on packages in accordance with GS1 standards globally. “The timing is good,”

says Odumade. “I’m a visionary leader and I see possibilities in this part of the world for more streamlined structures and processes in the supply chain.”

Another challenge of implementing streamlined supply chain systems is that each company bringing products to the market has its own system of logistics. Chekkit works around this by providing a product nimble enough to plug into a variety of supply chain systems. For example, a manufacturer like Pfizer might use software such as an ERP extension to control their supply chain. Yet, within the ERP system there’s a space for track and trace, explains Odumade. “That’s where we plug in via APIs and ingest the existing serialization to log on our distributed ledger network to securely cryptograph the codes or generate new ones as requested by the MAH.” By producing or ingesting and printing traceable serial codes they provide secured unique identifiers and “last mile” traceability, extending beyond the warehouse via engagement with key supply chain stakeholders.

FURTHER APPLICATIONS

Depending on the goals of a particular company, Chekkit’s digital identifiers can be modified to provide direct links between consumers/retailers and producers.

Chekkit App and Mobile SDK allow consumers to verify products and give feedback, usually with some sort of incentive or reward (The Token Program). For companies or organizations, this

provides important insight into consumer behavior. Nivea used Chekkit’s labels and technology for an in-store reward campaign. Consumers verified the product using USSD, a global system for off-internet mobile communications, answered surveys, and received a free product. These survey responses (depending on the choice of questions), indicated the customers are pleased by the quality and availability but had concerns about affordability of the brand.

Odumade thinks this holds huge potential for business strategy, explaining that information about changes in demand gleaned directly from consumers can have significant financial repercussions and plans to amplify these AI-generated insights by matching these insights further with social media data related to each SKU tracked, thus generate demand predictions from the resulting patterns.

In a social campaign, water bottles were given out at a protest against police brutality. A QR code on the water bottle led protesters to an online survey where they could complete a survey about police brutality thereby educating organizers about the opinions and issues important to the protesters.

Although Chekkit started out by tackling the problem of counterfeit drugs and that remains their primary objective they discovered a much larger problem in the process. “Global supply chains are not interconnected,” says Odumade. “You don’t have an ability to go end to end with your products,”

While their initial focus has been Nigeria, Chekkit has serviced customers through partners in South Africa, Rwanda, Afghanistan, UAE, and India.

he adds. Whether identifying counterfeit drugs or allowing businesses to communicate directly with their consumers, Chekkit’s supply chain goes all the way from the producer to the end consumer as a digital infrastructure.

WHERE THEY ARE IN THE PROCESS

Currently, Chekkit is tracking more than 200M unique identifiers for 22 paying customers, including global pharmaceutical companies like Merck and smaller companies across Africa, the Middle East, and Asia.

Their system is fully operational. “We have a full solution that includes SaaS and APIs for serialization, meta-data customisation, and traces supply chain all the way down to the retailers and consumers with mobile app or SDK for integrations. Most of our customers have seen 1.2 times to 1.3 times increase in revenue since working with Chekkit,” says Odumade, adding that the service is currently set up to facilitate both distribution tracking (even discover product/ market diversions) and consumer engagement.

So far they have raised one million dollars and are leveraging their company for maximum reach and blitz-scaling. While their initial focus has been Nigeria,

they have serviced customers through partners in South Africa, Rwanda, Afghanistan, UAE, and India. They are looking to scale throughout Africa, Europe, the Middle East, and Asia, with an eye on India for its large drug manufacturing industry. Ultimately, they hope that the Chekkit digital identifier will be a signifier for authentic products, telling its history and provenance both within the pharmaceutical industry and beyond.

OUR TAKE

Nigeria, like much of Africa, is experiencing huge growth. “The aggressive growth of the market creates new complexities, which also creates opportunities,” says Odumade. Chekkit is taking on a foundational opportunity by streamlining supply chains and fostering a circular and sustainable economy as the leading digital infrastructure. In doing so, they are not only tackling counterfeit drugs but also providing technology and systems that show promise for revolutionizing the way packaged products are delivered and traced throughout the developing world.

CONTACT

CHEKKIT@STARTUPHEALTH.COM

Sinaptica’s Novel Approach to Alzheimer’s Leverages Electrical Brain Stimulation

Using precision neuromodulation therapy to electrically stimulate the brain, Sinaptica Therapeutics is able to slow the progression of Alzheimer’s, with impressive phase 2 results.

GGiacomo Koch, MD, PhD, and Emiliano Santarnecchi, PhD, have been working together for over a decade on issues related to Alzheimer’s and neuromodulation. At the Santa Lucia Foundation in Rome, Dr. Koch, a practicing neurologist and neuroscientist, works with Alzheimer’s patients as well as conducting research in his lab, while on the other side of the Atlantic, Dr. Santarnecchi – who directs the Precision Neuroscience lab at Harvard-MGH –uses neuroimaging and electrophysiology to develop diagnostic and therapeutic solutions for Alzheimer’s patients.

Their collaboration led to a groundbreaking study in which they proved that personalized noninvasive neuromodulation therapy for Alzheimer’s patients slowed the progression of the disease by 82% at six months. Sinaptica Therapeutics – the business entity now responsible for developing the therapy – claims they have unprecedented clinical trial efficacy.

“Our therapy works better than any drug that I’ve seen in 20 years,” says Ken Mariash, CEO, who previously worked as head of strategy at Boston Scientific’s $1B Neuromodulation Division.

THE PROBLEM

Alzheimer’s disease directly or indirectly touches millions of people, including those on Sinaptica’s core team. “I got to see the first-hand effects of Alzheimer’s on my grandmother,” says Mariash. He was also struck by its effect on his extended family. “I saw it swallow up my family in

a way that I could have never imagined,” he says.

Rich Macary, Sinaptica’s President, was working in the biotech space on rare diseases when a family member developed Alzheimer’s disease, which put him on a search for novel solutions, leading him to Drs Koch and Santarnecchi and eventually a new area of focus in his career.

Although Macary’s relative ended up in assisted living, he’s hopeful others will have a different story. He points to the phase 2 study by Sinaptica’s scientific co-founders that showed how neuromodulation therapy allowed Alzheimer’s patients to maintain activities of daily living (ADLs) over six months, whereas the sham cohort had diminished ADLs. “In the study, we saw full preservation of function, the thing we as caregivers and family members care about most, which can enable the patient to remain living independently,” says Macary. “I would do anything to have kept my loved one out of assisted living,” he adds.

Although the impact of Alzheimer’s disease is widely understood by the general public, treatment options have been lacking for decades, until two recent drug approvals that come with some efficacy and safety challenges. Sinaptica is forging a new path with a non-drug approach and a new disease target, separate from ‘the usual suspects:’ amyloid, an aggregate of misfolded proteins that form in the spaces between nerve cells; and tau, a protein that when abnormally formed causes the internal structure of neurons in the brain to fall apart. The scientific community

has “spent decades and billions of dollars targeting amyloid,” says Mariash, which Sinaptica believes is more of a covariant – just one aspect of the pathology of the disease. “We’re going beyond amyloid,” he says.

THE SOLUTION

Sinaptica Therapeutics posits that Alzheimer’s might be as much of an electrophysiological disease as a biochemical disease. “The brain is electric and operates as multiple overlapping networks. The Alzheimer’s brain shows dysregulation of the complex signaling in those networks, which is related to synaptic dysfunction. Excitation/inhibition imbalances and dysregulated oscillatory patterns (e.g. epileptiform activity) are well-known in AD. This suggests that neuromodulation can restore balance to the network and induc eneuroplasticity – strengthening synapses – thereby restoring network connectivity.”

The therapy process begins with a patient receiving an MRI and then a calibration session to personalize the therapy. Drs. Santarnecchi and Koch’s research took a big leap forward in 2015 when they realized they could personalize the therapy to hit the right network in the brain that is implicated in Alzheimer’s. “The brain works as a combination of networks,” says Dr. Santarnecchi. “We go after the default mode network (DMN), one specific network known to impact Alzheimer’s disease,” he adds. This network is the biggest cortical network in the brain, across which memories are integrated. Yet, each brain works differently,

so Sinaptica’s therapy begins by mapping out a custom blueprint of the brain so that the therapy can be targeted to the correct region for each patient.

Mariash likens the calibration process to active sonar: TMS (transcranial magnetic stimulation) pulses, and EEG (electroencephalography) ‘listens.’ “It’s better to understand a complex system by sending a perturbation to the system and see how the system responds,” says Dr. Santarnecchi. “When you send a magnetic pulse and listen to the brain you get very specific information,” he adds. With this information, it’s possible to create personalized weekly therapy that sends magnetic pulses to the targeted region of the brain.

During their therapy, patients spend 20 minutes sitting back in a reclining chair, with the neuromodulation system just behind their head. The therapy uses repetitive magnetic stimulation to generate electrical activity in the DMN in the brain via the precuneus. During the foundational phase 2 study, the results of which were published in Brain in 2022, patients who underwent this therapy once a week for six months showed over 80% slowing of disease progression relative to sham on the Clinical Dementia Rating Scale (CDR-SB, primary endpoint), Alzheimer’s Diseases AssessmentCognitive (ADAS-COG), Mini-Mental State Examination (MMSE), and Activities of Daily Living (ADCS-ADL, referenced earlier). The study conclusions show confidence in the potential of using precision neuromodulation to slow the

progression of cognitive and functional decline in Alzheimer’s.

Mariash draws a parallel to working out: “When you stimulate your muscle tissue by lifting a heavy object, you strengthen muscles.” By stimulating key parts of the brain involved in memory, neuromodulation strengthens those networks, new connections are made, and the progression of the disease lessens. It’s not a cure for Alzheimer’s, but rather a slowing of its momentum that can provide precious time and independence. “This disease is a freight train. We're working to slow it down,” says Macary.

WHERE THEY ARE IN THE PROCESS

Sinaptica holds a unique position as a startup company buoyed by compelling data from a phase 2 clinical trial and patented technology with FDA Breakthrough designation. They’re currently in the process of raising additional funds and replicating the phase 2 data in a phase 3 clinical trial that will follow patients for one year and include participants in about 20 sites throughout the US and EU. They are working with other Alzheimer’s experts to get broad input and interest in the design of the clinical trial and they are in frequent contact with the FDA through the TAP program, which gives extra level of access to the FDA for breakthrough devices.

Part of their work also involves convincing the wider medical community that advances in treatment for Alzheimer’s can include neuromodulation as well as drugs. “In Alzheimer's, neuromodulation

is just beginning to be acknowledged, and there is some skepticism” says Mariash. “But our therapy has its foundations in a $7B industry that's affecting all kinds of areas of medicine, from Parkinson's, to pain, to epilepsy, to rheumatoid arthritis, to depression…. Neuromodulation is a well-established space.” Sinaptica is on a path to introduce this non-pharmacological intervention for Alzheimer’s disease to the market.

OUR TAKE

Sinaptica Therapeutics presents groundbreaking data for slowing the progression of Alzheimer’s disease. Their therapy sidesteps the usual targets, instead using a personalized solution that focuses on the unique electrical makeup of a patient’s brain. It’s an original and effective approach that holds promise for extending the cognitive functions of people with Alzheimer’s. We’re excited to partner with them and seek creative solutions for tackling this disease.

CONTACT SINAPTICA@STARTUPHEALTH.COM

Pocket Clinic’s “Patch Pump” Simplifies Insulin Delivery with the First 7-Day Patch

Amir Omidvar, PhD, isn't your typical entrepreneur. A tinkerer since childhood, Dr. Omidvar has spent years learning how microelectromechanical systems (MEMS) can improve lives. Now, with his first-of-its-kind insulin “patch pump” he’s on the verge of removing the burden of daily insulin injections and revolutionizing how people maintain their blood sugar levels.

MMore than 537 million people worldwide live with diabetes, and millions of them rely on daily injections of insulin to survive. These injections come with a significant burden. There is the pain and discomfort of constant needle pricks, which become a source of anxiety, especially for young children. Studies show a significant portion of patients skip or delay injections due to needle phobia. Multiple daily injections also require meticulous planning. According to one study out of Stanford, people with diabetes have to make 180 more decisions per day, compared with someone without the condition. If that weren’t hard enough, traditional insulin injections are a financial strain, which creates a well-documented

access gap in effective diabetes management.

While some people with diabetes have benefited from modern insulin pumps, which adhere to your arm and deliver insulin when you need it, the majority still rely on daily injections. “We have been treating diabetes the same way since 1922,” says Amir Omidvar, PhD, founder of Pocket Clinic. “Although insulin is a lifesaver, it is not an easy drug to administer and causes overdose or underdose due to poor management and cost.”

Omidvar, a life-long inventor, looked around at multiple family members reliant on daily injections to manage chronic diseases and knew there had to be a better way.

ORIGIN STORY

Amir Omidvar, PhD, who was born in Iran and immigrated to Canada, watched as his grandmother was diagnosed with Type 2 diabetes and became insulindependent. He can distinctly remember how challenging it was for his mother and aunts to handle her insulin injections multiple times a day.

“It was really painful for them as well to inject and see the suffering because they needed to measure the glucose several times a day,” he says. “And they worried

Amir Omidvar, PhD CEO & Co-founder

about how to manage her glucose when she was asleep. Insulin is really tricky.”

After his grandmother's passing, Omidvar’s father was also diagnosed with Type 2 diabetes. Due to his inadequate management of the condition, he eventually became dependent on insulin as well.

Fueled by a desire to make a difference for his family and millions like them, Amir began envisioning a device that could discreetly and comfortably deliver medications like insulin while being financially accessible.

Omidvar’s academic work in Toronto proved to be a crucial piece of the puzzle. He studied micro-electromechanical systems (MEMS), an innovative technology that uses microneedles to deliver drugs through a painless patch.

Through his PhD project, Omidvar

developed the device, the algorithms, and the real-time data monitoring needed to use a MEMS device to deliver insulin effectively and affordably. As a serial medical device inventor, he’d also built up the manufacturing know-how necessary to bring a MEMS device to market. All that remained was to formalize a company –now called Pocket Clinic – and bring his innovation to the people.

UNDER THE HOOD

The Pocket Clinic "patch pump" represents a significant advancement in diabetes management, combining the benefits of traditional insulin injections and modern pumps while introducing distinct advantages. As the first insulin patch pump capable of delivering microdosing insulin for a full seven days, it dramatically extends the operational duration compared to today's pumps, which typically last two to three days.

The extended wearability helps maintain stable blood glucose levels, reduces the mental burden, minimizes human error associated with frequent device management, and lowers healthcare costs by decreasing the need for frequent replacements and clinical visits. Additionally, the Pocket Clinic Smart Injector collects valuable data that can be used to optimize treatment plans. Overall, this patch pump significantly improves the quality of life for insulin-dependent patients by making diabetes management more efficient and less intrusive.

The Pocket Clinic is also unique in its ability to be a pharma-agnostic platform.

The patch pump consists of two parts: The main pod is durable, rechargeable, secure, and reliable. The second part is a disposable cartridge with different capacities. That means that Pocket Clinic can build on its MEMS infrastructure to treat additional chronic illnesses in the future.

The Pocket Clinic "patch pump" is a compact solution that integrates an insulin pump and continuous glucose monitoring system. Utilizing advanced microneedle technology, this small and responsive patch efficiently administers insulin while continuously monitoring blood glucose levels. It features smart technology that automatically adjusts insulin delivery based on real-time blood sugar data, significantly simplifying diabetes management. This capability helps prevent dangerous fluctuations in blood sugar levels, enhancing both safety and ease of use.

Pocket Clinic’s go-to-market strategy is built on currently available billing codes, making it easy for clinicians to recommend the device. Omidvar’s plan is to partner with clinics and hospitals and increase access to their technology through insurance and public health programs.

WHAT’S NEXT

Amir Omidvar’s childhood experience wasn’t unique. Millions of people watch their relatives suffer from diabetes and the financial and physical burden of insulin injections. What made Omidvar unique, and set him up for success with Pocket Clinic, is his obsession with solving big problems, his deep domain expertise in

micro-electromechanical systems, and his ability to execute the manufacturing of a complex medical device.

Interestingly, while Omidvar is specially targeting the insulin injection market, which is the majority of people dependent on insulin, his patch pump is also taking aim at the insulin pump market. Their patented seven-day patch has the potential to revolutionize the entire landscape of insulin delivery, widening the potential market and vastly expanding their impact.

For all of these reasons, we’re bullish on Amir Omidvar, PhD, and the Pocket Clinic team and are excited to have them as part of our community as they bring their patch to market. And then, to see how they can build on this platform technology to deliver medication to more chronic disease patients in a way that is easy, painless, and affordable.

“In the end, people with diabetes don’t choose their disease,” says Omidvar. “Don’t they deserve to choose their treatment?”

CONTACT POCKETCLINIC@STARTUPHEALTH.COM

Diabetes Driving Pal Helps People with Diabetes Stay Safe Behind the Wheel in the Face of Low Blood Sugar Episodes

Helping people with diabetes live healthier, safer lives is a daily pursuit for Dr. Viral Shah (pictured). As a physician scientist and clinician specializing in diabetes at Indiana University, Dr. Shah spends his days immersed in the world of blood sugar management, new technologies, and patient care. Now, with his new app, he’s going beyond the walls of the clinic to help patients stay safe on the road.

IImagine hurtling down the highway, the wind whipping through your hair, the radio blasting your favorite song. It's a picture of freedom, a feeling of control. But for millions of people with Type 1 diabetes, this seemingly ordinary act of driving can harbor a hidden danger – low blood sugar episodes.

These episodes, characterized by a sudden drop in blood sugar levels, can cause a cascade of symptoms like dizziness, blurred vision, and impaired judgment. Behind the wheel, even a brief episode can be catastrophic.

Type 1 diabetes is an autoimmune disease that affects more than 8.4 million people globally. With T1D, the body can’t produce insulin, a hormone essential for regulating blood sugar levels. This constant state of insulin deficiency makes people with Type 1 highly susceptible to blood sugar fluctuations, with episodes of hypoglycemia (low blood sugar) occurring frequently. Pretty much everyone with T1D experiences low blood glucose almost daily and 70% of people with T1D experience at least one hypoglycemic episode while driving. Though early Type 2 diabetes is primarily managed through

lifestyle changes and medications, after 15-20 years of T2D, most people require insulin therapy to control blood sugar and can experience similar risks of hypoglycemia while driving.

FROM FRUSTRATION TO INSPIRATION: THE BIRTH OF DIABETES DRIVING PAL

The impetus for Diabetes Driving Pal arose from a simple observation.

"Many of my patients with Type 1 diabetes confided in me about experiencing low blood sugar episodes while driving," says Viral Shah, MD, an endocrinologist at Indiana University. He was shocked and concerned, but since he works as a clinical researcher, that wasn’t enough – he wanted more data points. Dr. Shah conducted a survey at the Barbara Davies Center in Colorado, his previous institution, and it revealed that a staggering 72% of respondents reported experiencing at least one low blood sugar episode while driving and even more concerning, 4% admitted to having had a vehicular accident due to low blood sugar in the previous two years. Interestingly, more than 90% of the survey population used continuous glucose monitors and/or insulin pumps. The study was published in the journal Diabetes Care.

Dr. Shah's survey, while geographically limited, paints a concerning bigger picture. If 4% of survey respondents in Colorado had accidents due to low blood sugar, this could translate to tens of thousands of accidents annually caused by hypoglycemia behind the wheel.

Frustrated by the lack of existing solutions and deeply concerned about the potential for tragedy, Dr. Shah knew he had to do something. He assembled a team of experts, including clinicians and an engineering professor. Together, they set out to create a technological safeguard for drivers with diabetes.

DIABETES DRIVING PAL: YOUR REALTIME COPILOT

The Diabetes Driving Pal app acts as a copilot for drivers with Type 1 diabetes. It will be designed to integrate with existing continuous glucose monitoring systems (CGMs), which provide real-time blood sugar readings. Here's how it works:

Tiered Alert System: Imagine a threetiered system, each level designed to gently guide you back into the safe zone. For slightly low blood sugar readings, the app provides a discreet alert, similar to standard CGM notifications. This is your chance to take a preventative sip of juice or a quick bite of food to raise your blood sugar.

Personalized Intervention: If your blood sugar continues to drop rapidly, the app kicks into a higher gear. Utilizing your pre-set preferences and location data, it suggests nearby options to raise your blood sugar levels, like a Starbucks or a convenience store with sugary snacks.

Emergency Action: In the most critical situations, where blood sugar plummets to a medically dangerous level, the app doesn't hesitate. It automatically calls a designated emergency contact or 911, ensuring you receive the help you need.

Shah and his team are aiming for a beta launch of the Diabetes Driving Pal app in Q4 2024.

This personalized, multi-layered approach is what sets Diabetes Driving Pal apart. "It's not a one-size-fits-all solution," explains Dr. Shah. "We empower users to customize their experience through settings, making it truly user friendly."

BEYOND THE HORIZON

While the initial focus is on improving safety for individual drivers with diabetes, Dr. Shah has a vision that extends beyond personal vehicles. He sees the app's functionality having a significant impact on the safety of entire fleets operated by companies like Uber, Lyft, and trucking companies.

This type of integration could not only safeguard drivers but also enhance passenger and public safety on the roads. Furthermore, by demonstrating a com-

mitment to driver health and wellbeing, companies could attract and retain top talent in a competitive marketplace.

Dr. Shah is early in his entrepreneurial journey and knows that achieving this ambitious vision requires collaboration. "We're actively seeking partnerships with fleet management companies, diabetes organizations, and insurance providers," he says. “We’re also building our internal team and are seeking tech developers and operators passionate about this space.” By building bridges between stakeholders, Dr. Shah hopes to be a key part of a comprehensive ecosystem that supports not just safe driving but holistic diabetes management.

CONTACT

DIABETESDRIVINGPAL @STARTUPHEALTH.COM

Founder Ben Tzeel wants people with diabetes to start living on their own terms. On social media, he’s the face of his tech-enabled nutrition coaching company and he embodies the ethos of a life unhindered by diabetes. In his videos and photos – widely viewed on TikTok and Instagram – he chronicles himself eating things like stadium food and banana pancakes all while managing his blood sugar levels and maintaining washboard abs. He gets to have his cake and eat it too – and he wants others to as well.

BBen Tzeel was diagnosed with Type 1 diabetes (T1D) at age seven. “The first thing I remember was just everyone saying no, you can't have this. You can't do this. You can't run around with your friends. You can't have the birthday treat,” says Tzeel. “I had a chip on my shoulder from the time I was eight or nine years old because I was constantly being told no.” His frustration came to a head when he was 12 years old and tried out for a traveling baseball team in his small Wisconsin town. He was thrilled to have thought he made the team and went out to get ice cream with his future teammates to celebrate. But after testing his blood sugar and finding his glucose extremely high, everything changed. Not only could he not have the ice cream, but he found out the next morning that he couldn’t join the team either. “I knew it had to be because of diabetes.”

Tzeel credits that moment as a turning point. “Up until that time, I resented my diabetes, but then I realized if I'm going to do what I want to do in life, I have to work doubly as hard as everybody else,” says Tzeel. In high school, Tzeel began

working out and lifting weights and paying more attention to his diet, but it was a largely unguided pursuit. He would ask his care team for advice about how to live an active life but didn’t get many answers. “They’d tell me I have to figure it out and guess and check and see what happens,” says Tzeel.

Tzeel’s pursuit for answers led him to a PhD program where he began conducting diabetes research. However, after two years he was itching to share his insight with others and pivot away from academia to something more accessible. “Why not just switch gears, become a dietitian, become a diabetes educator, and get the information I’m researching out to people now?” says Tzeel.

THE SOLUTION

In 2018, armed with his degree in nutrition, registered dietitian credential, and having spent four years as strength coach already, and knowing “enough about how to read research properly to be dangerous,” Tzeel started developing his social media presence. He wanted to holistically cover nutrition, exercise, and blood sugar levels –what he terms “a holy trinity” that he didn’t

see others addressing – as a complete package. “What matters to me is the widespread adoption of this information,” says Tzeel.

On his social media channels, Tzeel’s entertaining antics are infused with educational content, providing tips and insight on living a satisfying life with diabetes. In his fully-virtual nutrition practice, he and his team of registered dietitians and diabetes educators build upon this educational model with one-on-one coaching meant to empower individuals to lead more healthy lives without banning all “fun” foods. “We will show you how to live your best life so that you are the healthiest, strongest, and best version of yourself,” their website states.

HOW IT WORKS

Tzeel’s social media presence and coaching company, Your Diabetes Insider, work hand in hand. Through social media, he has been able to educate widely about topics that he feels most diabetes care teams don’t adequately address, and in the meantime, he’s been able to create an audience and client stream for his company. “Social media led to the start of a sustainable business,” he says.

Tzeel grew his social media presence to more than 22,000 followers on Instagram and 127,000 on TikTok through a combination of first-person narratives, humor, and research-based educational content. At age 32, his youthful energy translates well on these platforms: he’s always in a flat-brimmed baseball cap, records his videos at home or out and about, and when he’s wearing any t-shirt at all, it’s often

By sharing his personal T1D journey and offering practical tips for living a full life in spite of the disease, Tzeel has built up a sizeable social media following.

emblazoned with a motivational phrase like “man up” or “hustle beats talent.” The fast edits and bold graphics of his videos are right at home on TikTok, where he has gained most traction. “TikTok is the fun platform,” says Tzeel. “If I can bring across messages and educate in a fun way, the message will really resonate with the diabetes community,” he says. He uses skits and punch lines to deliver messages that might otherwise be a bore to sit through – like the importance of subtracting fiber from net carb dosing.

Tzeel has the eyes and ears of a mostly young audience on social media and over the past five years, he has brought over

about 2,500 of them as clients at Your Diabetes Insider. He works with two other registered dietitians who, like him, are living with T1D and have exercise backgrounds. “If you don't live with diabetes yourself, it's very hard to understand what the day to day is like,” says Tzeel.

At Your Diabetes Insider, the registered dietitians work with clients to create personalized health plans for the patients with their top priorities in mind. “For people that want to make a change to their diet or exercise routine, we can give them a game plan so that they’re not floundering and guessing,” says Tzeel. Consistent virtual meetings, which can be weekly or monthly according to one’s needs, help clients set objectives, develop accountability, and learn about nutrition and lifestyle management. Tzeel wants to fill in the gaps for the things that should have been taught to people early in their diabetes diagnosis but weren’t.

At Your Diabetes Insider, Tzeel has made a point of building a team that combines expertise in T1D and nutrition with specialists who understand strength and conditioning. That allows them to address fitness concerns not covered by other T1D care teams. Tzeel mentions a client that wants to build muscle but has no idea what to do and his care team won’t tell him anything. “We can do that in an evidence-based way that makes sense and fits into his life as a person living with diabetes,” says Tzeel.

Accessibility is another major concern to Tzeel. His embrace of telemedicine renders the services of Your Diabetes

Insider available worldwide and cuts out commuting to a dietitian’s office and sitting around in a waiting room. “You sit there for an hour and a half waiting for your ten-minutes-of-glory appointment,” says Tzeel. “If we’re three minutes late, we’re profusely apologizing. We value our patients’ time,” he says.

Money, like time and location, is another barrier of accessibility that Tzeel creatively navigates. His educational resources on social media are free. The coaching services for Your Diabetes Insider are not, but he works hard to establish coverage from insurance companies when possible. “If we can take insurance for certain people in certain places, then hopefully that lowers the barriers,” says Tzeel.

OUR TAKE

Tzeel wants to grow Your Diabetes Insider to be the top diabetes dietitian practice in the country. His presence on social media has proven his ability to draw large audiences and his relevance to a young demographic that represents the future of diabetes. As a dietitian, he’s filling a gap by addressing diet, exercise, and diabetes management. We’re excited to partner with him as part of our T1D Moonshot Community to scale up his company and help even more people with diabetes live lives that feel fuller, less restricted, and healthier.

InsuLearn Uses Smarter Algorithms to Optimize Insulin Delivery

Arielle Messer and Dorian Goldman leveraged their background in biomedicine and mathematics to develop machine learning software that takes the guesswork out of diabetes care.

WWhen Arielle Messer, a seasoned machine learning scientist, was diagnosed with Type 1 diabetes, she was frustrated with the guesswork required to manage her condition. Despite having access to advanced tools like an insulin pump and CGM device, she found it difficult to make informed decisions about monitoring her insulin delivery given the shifting dynamics that affect glucose levels, such as diet, physical activity, and menstruation. In theory, the algorithms within her pump should have been harvesting her health data in order to effectively monitor insulin delivery. But as a machine learning scientist, she knew these algorithms weren’t doing their job very well. Determined to find a better way, she partnered with Dorian Goldman, a data scientist with a strong background in mathematics, to tackle this issue head-on.

THE CHALLENGE

Messer recalls a particular experience where the algorithms behind her insulin pump failed her, causing the pump to continuously deliver insulin over the course of 10 minutes while her blood sugar plummeted. “I almost died,” says Messer. “And that’s an FDA-approved algorithm.”

While the commercial algorithms currently on the market are black boxes that lack transparency, Messer and Goldman were able to infer that the algorithms running Messer’s pump had significant limitations in their methodology. “For example, we found out that the algorithm's forecast appears to rely on the ‘most likely glucose value’ in the next 60 minutes, not taking into account the patients' unique individual risk profile, and appears to lack adequate sensitivity to rapid declines in glucose,” says Goldman.

This severe hypoglycemic incident only compounded the doubts Messer initially had about the technology. “We were already working on this before but at that point, I was like, this is literally insane,” says Messer. “We want to create an algorithm that doesn’t do that, but in the case that it does, someone’s going to be calling you and asking if you’re okay and figuring out the problem. Accountability and transparency is essential for every decision an algorithm makes.”

Messer’s personal frustrations mirror a problem faced by people with diabetes around the world. Twenty five percent of people with diabetes had severe hy-

poglycemia in the past six months and inadequate pump algorithms are not doing enough to mitigate hypo- and hyperglycemia. Messer and Goldman identified six major problems with the current pump algorithms on the market: no personal adaptability or learning to account for physiological changes, such as illness; a 60-minute forecasting model that lacks responsiveness to rapid changes; lack of auto-correction; patient-guessed insulin parameters, like insulin sensitivity and carb rates; oversimplified linear models to estimate Insulin On Board; and last but not least, the use of “point estimates” of forecasted glucose used to make decisions which is dangerous in the presence of such noisy signals.

THE SOLUTION

As Messer was considering how to address this diabetes challenge she turned to Reddit to do some market research. She was intrigued and impressed by some of the open-source products created by the "we are not waiting" community, but realized that the lack of FDA approval and technical expertise required to use these algorithms would ultimately limit the number of people they can reach. Instead she started looking at her data from her pump and CGM device and was soon on her way to building a solution that was more savvy than the existing pump algorithms and took guesswork out of the equation.

When Goldman joined Messer in looking more closely at the problem, he

felt like it was something he could help solve. “In my PhD and postdoc I specialized in the calculus of variations and differential equations, with a focus on modeling and optimizing decisions in complex problems that arise in nature,” says Goldman. “I realized that the problem of insulin delivery can be addressed with these tools when augmented with modern machine learning methods, which I had spent the last decade mastering. Given Arielle’s background in biomedicine, we had the exact skills needed to build the best solutions to this problem.”

“Current pumps on the market have the ability to set certain parameters like insulin-to-carb ratio, insulin correction factor, and duration of action,” says Messer, but “all of these things are guesses that the patient or doctor makes.” For Goldman and Messer they wanted to solve this as a math problem and use the data that had “just been sitting there, collecting dust.” They felt that Messer’s data could be activated to set more accurate parameters. Looking closely at the data, they built something that used regression analysis, a statistical method to analyze the relationship between variables and predict the value of one based on others. In this case, they looked at the way Messer’s body reacted to insulin over the past month when she ate carbs. “I could determine that when I eat one carb, I would need to take a certain amount of insulin and I could say that with a level of confidence that can be computed,” says Messer.

INSULEARN IN BRIEF

This algorithmic product looks at a patient’s history and uses a combination of machine learning and stochastic control, a subset of variational calculus, in order to create a personally-tailored system of insulin delivery. It optimizes glucose homeostasis by predicting dosages based on real-time glucose data and it continually adapts to changes in a patient’s health profile, lifestyle, and treatment response.

This solution – which was used to set initial parameters for a meal – has since grown into a vision for a larger software solution: InsuLearn. This algorithmic product looks at a patient’s history and uses a combination of machine learning and stochastic control, a subset of variational calculus, in order to create a personally-tailored system of insulin delivery. It optimizes glucose homeostasis by predicting dosages based on real-time glucose data and it continually adapts to changes in a patient’s health profile, lifestyle, and treatment response.

HOW IT WORKS

InsuLearn harvests data from the patient’s pump and CGM device and uses machine learning to analyze that data in order to inform the pump of appropriate insulin dosages. The body’s response is then recorded back into the devices, creating a continuous loop between data, the algorithm, the pump, and the body. The algorithm is designed to adapt to metabolic shifts, including during sickness, and to tailor an ideal treatment model by uncovering consistent patterns in a patient’s longitudinal glucose trends. Ultimately, InsuLearn hopes that people with diabetes never have to think about their pump again.

WHERE THEY ARE IN THE PROCESS

Currently Messer and Goldman are developing a prototype based off of the technology that they first built for Messer. It’s a product that will initially only be for doctors as a way to figure out the parameters needed to initialize pump settings and update them over time. “That’s a good place for us to start,” says Messer, who adds that within two years they want to launch a product that can be used directly by patients and integrated with pumps. To reach that goal, they need to develop partnerships with companies that produce pumps and CGM devices. They’re not trying to replace the pump industry but make existing products work more effectively with their smarter software. They’re confident that companies will see value in their product, as many of them don’t have the

in-house expertise to create sophisticated software. “This is a business model we see in Europe where software companies have multiple pumps they are associated with,” says Goldman.

OUR TAKE

This product is poised to reduce the mental burden for people with diabetes by increasing their confidence in the devices meant to regulate their health. Through smarter software, InsuLearn can harness one’s health data to make insulin delivery more efficient and ultimately, safer. Arielle Messer and Dorian Goldman are an ideal team to address this challenge, given their complementary skill sets, passion, and experience. Messer is an expert in building machine learning models and has extensive experience developing algorithms for cancer treatment. Goldman has extensive tech leadership experience and brings a deep understanding of mathematics to solving complex technological challenges. Together, we’re confident they have the vision and expertise to transform the way software functions in insulin pumps..

One Year Later... Where Are They Now?

Each issue we introduce you to new members of the StartUp Health community. In this progress report, we check back in with the companies profiled in issues 12 and 13 and see how they've fared. We also asked them this bonus question: "What is one thing that helped you survive, sustain, or grow over the last 12 months?"

Ambrosia Systems

2023 Headline: Ambrosia Systems Is Designing an Affordable Non-Invasive CGM for Low-Resource Settings

2024 Update: "Our biggest achievement has been integrating FreeStyle Libre 3 into our platform and developing a new technology that predicts glucose levels up to 60 minutes in advance, significantly enhancing patient care and proactive diabetes management."

What helped you grow? "Continuous innovation and strong customer relationships have fueled our growth."

Diatech Diabetes

2023 Headline: Diatech Diabetes Upgrades Diabetes Care Through AIPowered Infusion Monitoring

2024 Update: "We had a very successful first FDA pre-submission meeting, we raised $150,000 in funding, launched a large national market survey with 600+ responses, and were one of the winners of the 2024 American Diabetes Association's Innovation Challenge."

What helped you grow? "Obtaining advising from veteran founders who faced similar challenges."

Difinity Solutions

2023 Headline: Difinity Solutions

Introduces the First Modular, Multi-Dose Emergency Medication Delivery System

2024 Update: "Following feedback with SMEs/FDA, we implemented a major design change. From an engineering and financial perspective, it was challenging but absolutely the right thing to do. We are better positioned than ever to deliver a true platform technology for medication delivery as a combination product."

What helped you grow? "100% the team. We came out stronger than before!"

2023 Headline: DreaMed Simplifies Diabetes Care via AI-Driven Recommendations

2024 Update: "We expanded in YNHHS to its family medicine clinics, raised a $3M financing round led by eHealth Ventures, and signed a data integration agreement with Abbott for our endo.digital platform."

What helped you grow? "The right dedicated team at the right time."

DreaMed

Enhance-D

2023 Headline: Enhance-d Delivers Digital Diabetes Management Tools Previously Reserved for Elite Athletes

2024 Update: "Hyper-focus on exercise! We listened to our early users and decided to focus in an area where they were not getting (much-needed) support from any other system. Feedback has so far been outstanding!"

What helped you grow? "A solid and resilient team, bootstrapping and small angel investors."

EqualityMD

2023 Headline: EqualityMD’s Digital Health Platform Is Changing How the LGBTQ+ Community Perceives & Receives Care

2024 Update: "Secured new channel distribution partners; completed three corporate fellowships; graduated from Halcyon’s inaugural social impact healthcare accelerator; finalized 'LGBTQ+ data pivot' which enables us to advance health equity at scale and provides exciting exit opportunities."

What helped you grow? "Steadfast support from the LGBTQ+ community."

GO-Pen

2023 Headline: GO-Pen Is Designing Safe, Reusable Insulin Pens That Are Accessible for All

2024 Update: "Engaged in active FDA and CE mark dialogues. Poised for global distribution addressing a growing demand driven by poor socioeconomic conditions."

What helped you grow? "Clear vision and a little help from our friends."

Greens App

2023 Headline: The Greens App Scales Diabetes Management with a Focus on Teens from Vulnerable Communities

2024 Update: "Greens Health has secured backing from Blue Cross Blue Shield for our approach to health equity and diabetes management. This achievement has been instrumental in validating our work and propelling our growth."

What helped you grow? "The startup community and team members are a constant source of encouragement."

The IndyGeneUs team has expanded operations in South Africa

HealthBook+

2023 Headline: HealthBook+ Empowers Patients with Personalized Health Data and Predictive Analytics

2024 Update: "HealthBook+ has overcome major bumps and has pivoted to focusing on DPC and concierge clinics where we have seen great early traction."

What helped you grow? "Deciding to pivot and be laser focused on DPC."

IndyGeneUs

2023 Headline: IndyGeneUS AI Is Bringing Genomic Medicine to Underrepresented Populations

2024 Update: "Secured an exclusive sequencing agreement with Africa's only certified biobank, Aurum Institute, enabling their South African team to sequence up to 3 million samples in their genomics lab in Johannesburg, South Africa."

What helped you grow? "Cultivating relationships in alignment with our mission and vision are paramount."

In-Range Animation

2023 Headline: In-Range Animation Uses Micro-Learning to Improve Diabetes Education

2024 Update: "In July, In-Range Animation began a project with DiabetesWise to educate people with Type 1 and Type 2 diabetes on insulin patch pumps. We are excited about the partnership and the opportunity to work with a fellow T1D Moonshot company."

What helped you grow? "Our focus narrowed from general diabetes education to device education."

Insulloc

2023 Headline: InsulLoc Is Combining AI and Computer Vision to Identify Safe Injection Sites for Insulin

2024 Update: "Won a European grant from EIT for clinical trials at Coimbra Hospital, Portugal. Started talking with a European key player in diabetes for using our app for their clients."

What helped you grow? "Keeping our expenses very low and our mindset high."

JoyDays

2023 Headline: Meet Joydays: All the Sweet without the Spike

2024 Update: "Working on how to reach the T2 diabetes consumer, who is less apt to change habits of what they buy on shelf. It's not about being on the diabetes shelf at Walmart, it's about getting their families to refer them or push them to purchase healthier items."

What helped you grow? "Starting to realize it was important to carve out time for myself, and prioritize that just as I would any meetings for my company that day. It has to come first."

MIIST got "incredibly strong" phase 1 clinical trial results and is poised for phase 2, says co-founder Dalton Signor.

MIIST

2023 Headline: MIIST Therapeutics

Brings a Modern Approach to Fighting Nicotine Addiction

2024 Update: "Our most significant achievement has been obtaining incredibly strong phase 1 clinical trial results in early '24. We are well capitalized to now advance our smoking cessation inhaler through phase 2 trials."

What helped you grow? "Have a culture that values execution, irrespective of the market."

Pramana Pharmaceuticals

2023 Headline: Pramana’s Biotech Discoveries Could Spark a Revolution in Type 1 Diabetes Management

2024 Update: "We’ve pivoted to focus on Latent Autoimmune Disease in Adults (LADA), driven by breakthrough preclinical data for a once-daily oral Hypoglycemia treatment. Our mission is to modulate the disease and prevent misdiagnosed patients from developing diabetes."

What helped you grow? "Enabling a mission driven team with resilience, tenacity and perseverance."

QuLab

2023 Headline: QuLab’s Nanotechnology Monitors Multiple Metabolites on One Minimally-Invasive Patch

2024 Update : "We have pivoted to Continuous Lactate Monitoring (CLM) for professional and recreational athletes and have obtained very promising safety and efficacy results in our First-in-Human trial for our CLM patch."

What helped you grow? "The continued support of our investors and our secured grants."

Replica Health

2023 Headline: Replica Health Is Simplifying Type 1 Diabetes Management with Conversational AI

2024 Update: "We've pivoted away from our consumer application being the primary focus, and have reoriented as a research lab building modular AI/ML components that are licensed by medical device and pharma companies. Super proud of each new partnership this year, and excited for what comes next!"

What helped you grow? "Adapting to market needs without forgetting our long term objectives."

Rezq Bio

2023 Headline: Rezq Bio’s Dendritic Cell Therapy Offers Hope in the Fight Against Autoimmune Disorders

2024 Update: "We've added a new application of our lead therapy to our portfolio. As it acts as a localized immunosuppressant, we are combining our therapy with islet cell implants/transplants to reduce the requirement for systemic immunosuppression. A study is upcoming with Dr. James Shapiro."

What helped you grow? "Team cohesiveness and trust has allowed us to survive and grow over the last 12 months."

Zinacare

2023 Headline: Zinacare Makes Healthcare More Accessible in Africa Through At-Home Testing Services

2024 Update: "By July of this year we’d already surpassed 2023 revenues and are on track to double our sales. We’ve started servicing B2B."

What helped you grow? "Honing in on our core revenue generator, which improved our product and operations, and ultimately our bottom line."

Network Like a Pro

Health innovation isn’t a solo sport. Not only does every founder need to build a fantastic internal team, but they have to actively cultivate a broad network of present and future investors, partners and buyers.

For the last seven years Nancy Mastroianni has been front and center at what is likely the most active and successful in-person networking operation in health tech. At HLTH, the conference that brings together the world of health innovation each year in Las Vegas, she orchestrates matchmaking programs via the Investor Connect lounge where thousands of investors, founders and would-be partners meet for the first time.

So, what separates a winning meet-up from one that falls flat? We dialed Nancy up to learn this and a few other nuggets of networking wisdom.

Nancy Mastroianni Head of Investors & Networks at HLTH

THERE ARE NO THROWAWAY MOMENTS

Getting on a shuttle bus? Standing in line for food? Sitting in a session? “Look at the badge to your left, to your right, and pay attention to who you're sitting next to,” says Mastroianni. “It’s incredible some of the people you’ll meet in the in-between moments if you’re open to a conversation.” Not a natural extrovert? Consider buddying up with a more outgoing person.

ASK BETTER QUESTIONS

If you struggle to start conversations with strangers, start with open-ended questions. "People in health tech often love to share their journey; for many people it’s very personal, so ask those deeper questions. Sometimes it’s something personal that launches a conversation, and ultimately can become a life changing connection.”

NAIL YOUR COMPANY STORY

Have a clear and concise elevator pitch ready to share with potential investors and collaborators. Have a pitch deck ready in case the moment arises, but you may or may not have time to present it. "Make sure you have a cohesive story, and that your materials look professional. But you don't have to give us a book."

FIND A MATCHMAKER

If you miss the sign-up deadline for the Investor Connect Lounge at HLTH, come by anyway. At this lounge, which is designed to facilitate

connections between investors and startups, there is a team of people who can help you make organic connections. “We’ve had incredible success with this more organic networking, and so now we encourage it and bake it into our strategy.”

FOCUS ON BUILDING RELATIONSHIPS

Often a networking meeting is only around 15 minutes. That’s not enough time to give a full pitch or answer every question, so focus on building a relationship so that you’re well positioned for a follow up meeting. “This meeting is just the beginning. Share

"Don't let the small stuff bog you down, because that negativity will be noticeable, and will hinder your opportunities."

your mission and vision in a way that leaves them wanting another meeting.” The goal is to establish a relationship and continue the conversation.

STAY POSITIVE AND APPROACHABLE

Networking doesn’t always go your way. Handling setbacks like a missed appointment with a positive and engaging persona can make a big difference in your networking success. "Don't let the small stuff bog you down, because that negativity will be noticeable, and will hinder your opportunities."

UTILIZE NETWORKING PLATFORMS

Leverage tools like HLTH's event app to connect with attendees, schedule meetings,

and filter for potential contacts. Also, make sure your information is correct in HLTH’s system, since they use those details in making connections. Make the most of the networking meeting areas. "The app has an incredible adoption rate for attendees. Your opportunity to engage with other people on the platform is excellent.”

TURN AN INVESTOR INTO A MENTOR

Even if they aren’t ready to invest in your idea, a lot of amazing people come to networking events ready to help founders out. Come curious, ask good questions, and you might find a mentor or advisor.

PACE YOURSELF

Networking events can be exhausting. Make sure to

take breaks, rest, and stay hydrated to maintain your energy and focus. “You don’t want to be wiped out when you need to be at your best. Consider going back to your room before the evening events to refresh yourself. Wear comfortable shoes and drink water!”

MINDSET OVER ATTIRE

Old school rules of attire have gone out the window, says Mastroianni. Business casual is perfectly acceptable, and investors are looking past the blazer and the shoes at the attitude and mindset of the person in front of them. “You should focus on being comfortable and professional. Ultimately it’s your story that’s going to impress them.”

Join a Health Moonshot Community

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Landing on the moon required the mission-aligned collaboration of more than 400,000 people from 20,000 companies. The same goes for health’s biggest challenges. Health moonshots require more than innovation— they demand collaboration on an unprecedented scale.

When you join a Health Moonshot Community, you’re joining forces with a powerhouse network of vision-aligned founders and entrepreneurs who are rewriting the rules, breaking barriers, and tackling the world’s most daunting health challenges. Members don’t just find it valuable; they call it priceless.