StartUp Health Magazine 2021 Q4

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ISSUE 08

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Health ers Transform !

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"We built Nightingale from the beginning so that it could address global challenges."

-Teemu Suna CEO, Nightingale [Nasdaq: Health.He]

Sami upgrades Brazilian health insurance Health innovation funding doubles YoY

NIGHTINGALE SHINES The Finnish company's powerful at-home blood testing kits could redefine preventative health around the world.

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FOUNDERS’ LETTER

Start Local, Go Global

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One of the most exciting developments in health innovation is the growing wave of startups emerging from dozens of new health hubs around the world. We’ve worked to accelerate this trend over the past decade by making investments in Health Transformers spanning 27 countries and six continents; from Helsinki to São Paulo, we are thrilled that more

Cyclica CANADA Drug Discovery

1DOC3 COLOMBIA Telemedicine

Nightingale FINLAND Preventative Health

InnovaRx GAMBIA Primary Care Sami BRAZIL Health Insurance

Medebound CHINA Telemedicine

Us2.ai SINGAPORE AI Diagnostics

StartUp Health companies come from 27 countries across six continents.

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Health Transformers are starting local, then going global. In the After Covid world, we see an extraordinary opportunity to exponentially accelerate this global impact.

When we launched StartUp Health in 2011, not only did we see the pressing need to transform health across the US, we realized there was no one responsible for the transformation of health at global scale. No government, company, or foundation was focused on organizing long-term global collaboration to solve the most universal human challenge of all: how to improve the health and wellbeing of all people, everywhere.

We soon realized that the only way to do so was to help build a global ecosystem to focus on this challenge. Our health moonshot vision was born and ever since we’ve been organizing Health Transformers to solve big health challenges that impact billions of people.

With 7.5 billion people in the world – most with limited or no access to quality care – creating solutions to address the health of humanity is a moral imperative. What’s so striking however, is how few investors yet realize how big of an opportunity it is to think exponentially and systemically about the health impact that can be made at global scale.

Some of the world’s wealthiest families have pledged fortunes to solving important global challenges and there are governments, foundations, and NGOs tackling pieces of the puzzle for sure. But judging by the still nascent institutional funding for earlystage healthcare startups in global markets, too few investors seem to have assessed the tremendous opportunity to invest globally. We plan to help change this dramatically over the next decade.

Healthcare is, of course, regional; and in terms of fundamentals like regulatory process, business models, and care delivery realities, locality certainly matters. But as we have seen in other industries facing complex challenges from banking to mobile, it’s possible to leverage technology, rethink business models, and deliver essential value in order to leapfrog legacy systems and solve big problems. Using this playbook – across the world – let’s do the same for healthcare and accelerate global impact.

Steven Krein CEO, Co-founder & Managing Partner

Unity Stoakes President, Co-founder & Managing Partner

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In This Issue 2 Founders' Letter 5 Editor's Letter 6 Health Transformer News 12 Meet the Newest Health Transformers 14 Sami 20 De Oro Devices 24 BUA FIT 29 Spect 33 Affectifi 38 TAG 42 Now Performance 46 MindTrace 51 Diagnostikare 56 EyeCareLive 60 Eczemadoc 64 Neuralert 68 Medi-Ops 72 Synapsin StartUp Health News 74 Nightingale's Next Move 81 Meet StartUp Health Investors 88 StartUp Health Partners with HLTH 90 Jamey Edwards Tapped as COO StartUp Health Insights 92 2021 Year-End Funding Report 106 Health Moonshot Snapshots

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EDITOR-IN-CHIEF Logan Plaster DEPUTY EDITOR Jennifer Hankin CONTRIBUTING EDITORS Nicole Kinsey Lauren Schafer

EDITOR’S LETTER

For the Benefit of All

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There are two concepts in medical research that put the pace of health innovation in context. The first is knowledge translation (KT). This refers to the length of time it takes for what we’ve learned through medical research to reach common clinical practice. For years we’ve pegged that number at 17 years.

This is the reality that many health innovators live in. They have a breakthrough in hand but face hurdle after hurdle in implementation in the form of outdated regulations, bureaucratic hospital systems or disincentivized insurance providers.

But there’s another concept in clinical research: “for benefit” – as in why researchers might stop a clinical trial. In a blinded clinical trial, one group will get the therapy being studied while another will receive a placebo. Sometimes, in the course of the trial, it’s discovered that the therapy being studied is so beneficial that researchers agree it would be unethical to withhold that therapy from the placebo group. Scientists in this situation understand that when you know you have the cure in hand, you have an ethical obligation to share it, and share it quickly.

Within the StartUp Health portfolio are innovations, therapies and platforms that will literally save lives and change the world. Consider Us2.ai and Aidar Health, which each received FDA approval last year, which are making chronic disease diagnostics accessible.

Or how Cityblock and Devoted Health are bringing high-tech care to vulnerable populations. In this issue of StartUp Health Magazine there are startups saving people from blindness (Spect and EyeCareLive), helping people avoid depression and suicide (TAG and Affectifi), and giving Parkinson's patients the ability to walk (De Oro). The list goes on and on (which is why we share so many stories on our blog, YouTube channel and podcast).

We don’t have time for life-saving health innovations to take 17 – or even seven – years to go from proven research to helping real patients. When decision-makers in the healthcare market learn what really works, we need to move with a sense of moral urgency like a researcher ending a trial “for benefit.”

We’re seeing the benefits of health innovation in some limited populations. Now let’s open up our aperture and make the bold collaborative moves necessary to make those health advancements available to the world at global scale.

Logan Plaster Editor-in-Chief startuphealth.com 5

Health Transformer News at a glance A selection of portfolio company headlines from the fourth quarter of 2021.

For daily health moonshot news, follow StartUp Health on Twitter @startuphealth and read the StartUp Health Insider newsletter startuphealth.com/insider 6 StartUp Health Magazine / GLOBAL Issue 6 IMPACT

How Hoy Health Is Trying to Improve Latino Health Equity Lifestores co-founders Bryan Mezue (L) and Andrew Garza in Lagos, Nigeria.

Lifestores Selected for the Google for Startups Black Founders Fund in Africa GOOGLE FOR STARTUPS 10/1/21

Babyscripts Among the DC-Area Startups That Raised Funding in September

WASHINGTON BUSINESS JOURNAL 10/5/21

SyncThink Scores FDA Clearance for AI System to Aid Concussion Diagnosis MOBIHEALTHNEWS 10/6/21

Devoted Health Raises $1.2 Billion, With Plans to Expand Across the Country BOSTON GLOBE 10/8/21

CNBC 10/11/21

Fastest Growing & Innovative Companies Program – Mocingbird PROVIDENCE BUSINESS NEWS 10/20/21

Joint Academy’s Programme to Help Millions With Back Pain HEALTHCARE GLOBAL 10/20/21

Ido Schoenberg & Roy Schoenberg, co-CEOs of Amwell (NYSE: AML), acquirers of StartUp Health company Conversa Health, recognized as two of the 100 Most Influential People in Healthcare for 2021 MODERN HEALTHCARE

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HEALTH TRANSFORMER NEWS // AT A GLANCE

SageSurfer Selected as Platinum Award Winner at 12th Annual MassChallenge Showcase & Awards MASSCHALLENGE 10/28/21

Valera Raises $15M for HighAcuity Mental Healthcare MEDCITY NEWS 11/5/21

$58M RAISED Aver Raises $58M Led by Cox Enterprises, Rebrands as Enlace Health HIT CONSULTANT 11/5/21

Naheed Kurji CEO & Co-founder of Cyclica

Cyclica Named as One of Canada’s Top Ten Growth Companies by the CIX CANADIAN INNOVATION EXCHANGE 10/30/21

COVID-19 Boosts Demand for 'Silver' Tech Ventures Like CarePredict SOUTH FLORIDA BUSINESS JOURNAL 11/4/21

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Humana to Offer Virta Health's Diabetes Care Platform for Self-Funded Employer Plans FIERCE HEATHCARE 11/9/21

DarioHealth (Nasdaq: DRIO), the acquirer of StartUp Health company wayForward, entered the digital musculoskeletal market with launch of Dario Move FIERCE HEALTHCARE

Epicured Helps Make Your Holiday Meals Healthier This Year ABC 15 11/16/21

From Emergencies to Moonshots, Can Cyclica Use AI to Help Find the Next Blockbuster Drug?

FORBES 11/17/21

$77M RAISED Cala Health Scores $77M to Expand Its Tremor-Fighting Wearable to New Conditions FIERCE BIOTECH 11/17/21

Romy Antoine CEO & Founder One Stop Wellness

One Stop Wellness Wins Big Bang Texas Pitch Competition

How Black Tech Entrepreneurs – Such as Kevin Dedner of Hurdle and Erica Plybeah of MedHaul – Are Tackling Healthcare's Race Gap NPR 11/29/21

DALLAS INNOVATES 11/17/21

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HEALTH TRANSFORMER NEWS // AT A GLANCE

San Francisco-Based Spect Raises Seed Funding in Battle Against Blindness SAN FRANCISCO BUSINESS TIMES 11/30/21

Femtech Startup Babyscripts Secures Additional $7.5M for Virtual Maternity Care Solution HIT CONSULTANT 11/30/21

Katherine Grill, PhD CEO & Founder Neolth

Sift Healthcare Selected as a Health Tech Finalist for the Wisconsin Inno Fire Awards 2021 MILWAUKEE BUSINESS JOURNAL 11/26/21

Small Companies Are Taking on the World: Us2.ai Wins 2021 APAC FedEx Small Business Grant Contest FORBES 12/13/21

R$ 111M RAISED Brazil's Sami, a Health Plan for SMEs, Raises BRL 111 Million in Series A Extension LATIN AMERICA BUSINESS STORIES 12/14/21

Forbes 30 Under 30 2022 – Education: Katherine Grill, PhD, of Neolth FORBES 12/1/21

The Next 1000 2021: Tatyana Kanzaveli, CEO & Co-founder of Open Health Network FORBES 12/15/21

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Co-founders of Quit Genius (L-R) Drs. Maroof Ahmed, Sarim Siddiqui & Yusuf Sherwani

Healthcare and Biotech Startups That Are Set to Take Off in 2022, According to Top Investors: Babyscripts BUSINESS INSIDER 12/20/21

How Quit Genius's Founder Saw the Value of Remote Care for Addiction Treatment Long Before the Pandemic TECHCRUNCH FOUND PODCAST 12/20/21

Sami Inkinen of Virta Health Weighs in on What's Missing From Apple Watch as a Health Device FINANCIAL TIMES 12/30/21

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Meet the newest

Health Transformers Each issue we introduce you to the inspiring founders we invested in this past quarter. Their work addresses a range of health moonshots, from Children's Health to Brain Health. Learn how you can back Health Transformers at healthmoonshots.com

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SAMI DE ORO DEVICES BUA FIT SPECT AFFECTIFI TAG NOW PERFORMANCE MINDTRACE DIAGNOSTIKARE EYECARELIVE ECZEMADOC NEURALERT MEDI-OPS SYNAPSIN

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HEALTH TRANSFORMERS Vitor Asseituno, MD, President & Co-founder (L) Luis Guilherme Berardo, CEO & Co-founder (R) sami@startuphealth.com

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MEET THE HEALTH TRANSFORMERS

Sami, the Brazilian Health Insurance Company Making Care Tech-Enabled and Affordable Vitor Asseituno, MD, and Luiz Guilherme Berardo are using telemedicine, big data, and free gym memberships to create a new healthcare paradigm in Brazil.

ACCESS TO CARE MOONSHOT VINTAGE: 2021/Q4 SAMISAUDE.COM.BR

In Brazil, universal healthcare has been codified as a constitutional right since 1988 when the government established The Sistema Único de Saúde (SUS) or Unified Health System. By and large, Brazilians take great pride in this public health safety net, which provides free care to all, including foreigners passing through.

That is, if you can get an appointment.

At the risk of making a generalization, when you try to create one cohesive health system for 210 million people in a country as diverse as Brazil you’re bound to be overstretched and underfunded. In Brazil’s case, it isn’t uncommon for patients to wait six months for a doctor’s appointment and two years for surgery. What’s worse, people wait without knowledge about when

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they’ll get care or where they stand in line.

Predictably, and as we’ve seen in other countries, these frustrations with universal healthcare led Brazil to a two-tiered health system where approximately 20% of the population buys private healthcare insurance in an American-style market. The majority of people with private insurance receive it through an employer.

But in Brazil, even those who can afford private insurance face a daunting problem: high inflation. With medical inflation as high as 20% year over year, even if you’re part of the privileged few who can afford private healthcare today, wait two or three years and you’ll probably get priced out like everyone else.

On paper, healthcare in Brazil is a human right. It’s also the second largest market for private health insurance worldwide next to

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MEET THE HEALTH TRANSFORMERS / SAMI

the US. But if the systems created cannot deliver healthcare in any reasonable timeframe, and the private systems are impossibly expensive, does that promise of healthcare even exist?

So how do you make healthcare affordable and accessible to hundreds of millions of people? That’s a billion-dollar macro health challenge, and Brazil is by no means alone in facing it. Enter Vitor Asseituno, MD, and Luiz Guilherme Berardo, co-founders of Sami. Their team in São Paulo is building a new kind of insurance company, one that uses digital health tools and primary care gatekeepers to reduce costs and open up access to care to all Brazilians. With their recent $15M series A and $19.8M follow-on, they’re one step closer to achieving their health moonshot of creating what they call “virtual Kaiser Permanente.” origin story

Growing up in São Paulo, Brazil, Vitor Asseituno knew he wanted to work at the intersection of tech and health. He studied computer programming and then went to medical school to become a family doctor.

In 2012, in his final year of med school, he went to San Francisco and interned for Rock Health, the digital health consulting and investment firm. It was the era of Obamacare, “Meaningful Use,” and a new wave of value-based businesses. These were the early days of digital health in the United States, and Asseituno had a front-row seat. As he sat through demos and watched pitches, he knew he was seeing the future

of health, and that that future could bring hope to Brazil.

When he returned to São Paulo, Asseituno organized the country’s first major digital health conference. It was a time of gathering and sifting ideas and tools in order to figure out what would work in their unique context. The conference was a success, and as a result, Asseituno was offered the job of CEO at a faltering medical trade show company. This wasn’t the health tech move he’d expected, but he knew he could use the opportunity to sharpen his skills as an executive. After three years, he turned the company around and sold it to one of the largest trade show organizers in the world.

Along the way, Asseituno also started a digital health accelerator. He and his team assessed 400 digital health companies, investing in seven, with one achieving a significant exit. That experience taught him a

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Sami is unique in the way it has incorporated exercise into its value-based business model. Sami partnered with GymPass, a breakout fitness startup from Brazil, to give every Sami member access to gyms and fitness classes. And since they’re paying the tab, Sami has full access to gym attendance data, which is then sent back to the patient record.

To their knowledge, Sami is the first value-based insurer to utilize fitness data to this degree.

crucial lesson. Each of these companies had what he’d describe as a “nice tool” to solve a niche problem. And they were all struggling. Not because they weren’t great ideas, but because they were overly reliant on free pilots and exclusive contracts with riskaverse payers. He decided then and there to take a different route. When he struck out with his own digital health company, it wasn’t going to be a “point solution” selling a niche product no one had ever heard of (or budgeted for). He was going to take a macro approach and innovate from the top down, selling something everyone understood: insurance. By being the “mothership,” he’d be able to incentivize innovation and connect the data the way he wanted.

To take on this massive task, Asseituno teamed up with Luiz Guilherme Berardo, a serial health entrepreneur who had also

spent a period of his professional life working in the United States. In Brazil, Berardo founded a healthcare startup for post-acute care and then worked to build a Brazilian version of the CVS MinuteClinic. The two set about studying innovative insurance companies like Oscar, Bright Health, and Alan to see how they could bring a new tech-enabled, value-based payer to Brazil.

Apparently, the pre-work paid off. Asseituno and Berardo were able to launch Sami successfully during the COVID pandemic, and raised more than $36M, some of the largest health tech fundraises in Brazil’s history. under the hood

Sami is all about the latest and greatest in health tech, but at the end of the day, it’s an insurance company. And that’s by design. Fifty million Brazilians buy health insurance each year, says Berardo. The idea with Sami was to create a recognizable, easy-to-sell product in a well-defined market, and then innovate from within.

One thing that makes Sami unique is that they’re digital-first by design. Today, at Sami, around 55% of clinical events get solved digitally. Whether it’s via video telemedicine, a mental health app, or secure text, Sami has the digital infrastructure to take care of most problems quickly and remotely.

“That changes the cost structure radically,” says Berardo. “It also improves engagement and trust and improves your medical loss ratio. It’s a virtuous cycle.”

Speaking of cost, Sami is already competitive with the biggest insurers in Brazil, even though they aren’t operating at scale. startuphealth.com 17

MEET THE HEALTH TRANSFORMERS / SAMI

Once they grow, says Berardo, they’ll be able to bring their costs down significantly, a key component to improving access.

Sami cuts out the middleman and aligns financial incentives by employing some of their own physicians. In addition to working with 10 “in-network” partner hospitals and employing a remote telemedicine workforce, Sami employs physicians at a walk-in primary care center in São Paulo.

When a patient engages with Sami, the first thing they do is contact their primary care provider. In designing the company, Asseituno and Berardo were insistent on this “gatekeeper” structure. Rather than having patients call directly to a specialist, with Sami, they have to go through a family doctor who coordinates care. This is an essential step in managing costs, says Asseituno.

“Healthcare costs are so hard to control,

so we have to be as prudent as possible. The gatekeeper helps to manage that journey efficiently,” says Asseituno.

Sami is also unique in the way it has incorporated exercise into its value-based business model. Sami partnered with GymPass, a breakout fitness startup from Brazil, to give every Sami member access to gyms and fitness classes. And since they’re paying the tab, Sami has full access to gym attendance data, which is then sent back to the patient record. To their knowledge, Sami is the first value-based insurer to utilize fitness data to this degree. Other value-based care organizations encourage their members to “get healthy;” Sami gives them a gym membership and automatically tracks how often they go. They currently track more than 1000 gym sessions a week.

Rather than selling to insurance brokers, Sami sells directly to small- and medium-

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sized businesses. They’ve also found a hungry market in independent workers.

The gig economy is strong in Brazil, and these solo-preneurs previously had no way to access quality health insurance. why we’re proud to invest

There are a lot of reasons to be excited about the work Dr. Asseituno, Berardo, and the rest of the Sami team are doing in São Paulo. At a 10,000 foot level — because this is a big-picture kind of company — we love how bold their vision is.

Why nibble at the edges of health innovation when you can be the insurer, provider, and point solution all rolled into one coordinated business? Why suffer the slow “death of a thousand pilots” when you could be the institution running the pilots?

But it isn’t enough to have bold ideas.

Asseituno and Berardo bring a unique set of skills to the table that bring these dreams within reach. They combine experience in front-line medicine, finance, entrepreneurship, and insurance, plus they’ve built up a star advisory team, including leaders from some of the world’s most innovative health insurance companies.

At StartUp Health we talk a lot about the potential for leapfrog innovation. One of the reasons we’re proud to back Sami is that they’ve embraced this concept more than any company we’ve met. Asseituno and Berardo came to the United States and studied health tech companies that were succeeding. They freely admit that they’ve modeled parts

of Sami after companies like Oscar and Bright Health. But they’ve also seen where these companies have failed and are using that knowledge to their advantage.

“We said, let’s copy what’s working and change what isn’t,” says Asseituno.

Finally, we’re bullish on Sami because they’re already having a major impact, in spite of launching during COVID-19.

In their first year of operation, they’re looking at having more than 6,000 members, which outpaces their global peers Bright Health, Clover, Devoted Health, and Alan. Plus, Sami’s medical loss ratio (a calculation that indicates how much an insurer spends on administrative costs vs. patient care) also outperforms these peers.

The Sami team is on a massive health moonshot mission to radically lower cost, increase access, and upgrade health quality in Brazil. Not satisfied with being a health tech “curiosity,” they’ve gone all-in to disrupt the entrenched health insurance industry. On one hand, they’re following in the footsteps of other innovative health insurance companies. But in other ways, they’re leaping beyond them, learning from their mistakes in order to build a brighter future for Brazil. If they succeed, they’ll fundamentally change healthcare in their country, for the good of all. Please join us in welcoming the Sami team to StartUp Health.

4 SAMI@STARTUPHEALTH.COM

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HEALTH TRANSFORMERS Sidney Collin, CEO & Co-founder William Thompson, Co-founder deoro@startuphealth.com 20 StartUp Health Magazine / GLOBAL IMPACT

MEET THE HEALTH TRANSFORMERS

NexStride, by De Oro Devices, Is Giving People With Parkinson’s the Gift of Mobility CEO and Co-founder Sidney Collin has invented a novel device that helps people with Parkinson’s overcome ‘freezing of gait,’ a debilitating symptom that causes dangerous falls and affects millions of people worldwide.

BRAIN HEALTH & ALZHEIMER'S MOONSHOT VINTAGE: 2021/Q4 GETNEXSTRIDE.COM

Often with healthcare startups, there’s a direct problem at hand and then there’s the much bigger health moonshot challenge. The micro leads to the macro and the mission is critical to the moonshot. Such is the case with the most recent addition to the StartUp Health portfolio, De Oro Devices, maker of NexStride.

This story starts with a very specific challenge that is at once simple and profound.

Around the globe, there are 10 million people struggling with Parkinson’s disease.

Parkinson’s, which is the fastest-growing neurodegenerative disease in the world, attacks the central nervous system and affects movement, often causing tremors.

About 80% of people suffering from Parkinson’s have experienced or will experience what’s called “freezing of gait.” This is when the individual suddenly cannot walk forward, feeling as though their feet

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are glued to the floor or stuck in a box of cement. This sudden onset of immobility is one of the most debilitating symptoms of Parkinson’s because it’s both emotionally frustrating and dangerous. Not only is the person unable to go about their life, their normal daily routine, but since the freezing of gait can happen without warning, it’s a leading cause of falls.

Thankfully there is a solution. A body of research — and an army of physical therapists — have discovered that we can trick the brain and “unfreeze” a person’s gait by using visual and auditory cues. Something as simple as a line of tape on the floor and a steady beat clapped by hand can help the patient tap into a different part of the brain and allow them to restart their movement.

The problem is that these visual-auditory tools have been locked in the clinic when what patients really need is help at home or on the go. This is representative of startuphealth.com 21

MEET THE HEALTH TRANSFORMERS / DE ORO DEVICES

a broader industry challenge of translating the best research and clinical practice from the clinic to daily at-home usefulness.

With their startup, De Oro Devices, Sidney Collin, William Thompson, and their team are tackling the specific issue of “freezing of gait” while also opening up an avenue for bringing a range of well-designed tools to market, devices that bridge the gap from research to practice and make everyday life better for seniors. origin story

For as long as she can remember, Sidney Collin has been obsessed with how the brain works, how the body works, and how the two interact. That obsession led her to pursue a biomedical engineering degree at Cal Poly, in San Luis Obispo, and work for a brain-computer interface company in France.

Towards the end of her time at Cal Poly, Collin was introduced to an elderly man named Jack who was suffering from Parkinson’s disease. Jack brought Collin into his world and showed her the daily struggles of living with Parkinson’s, in particular, the “freezing of gait” challenge that left him glued to the floor, or worse, taking a spill.

He was having success using visual and auditory cues to “unfreeze” his gait at his physical therapist’s office, and since he was a former engineer, he knew that a device could be built that replicated this technology at home and on the go. He knew that if he could get a portable version of this therapy tool, it would give him freedom of movement. He just needed to inspire the right entrepreneur.

Sidney was hooked. She grabbed anoth-

er engineering student and set about building a device for Jack. Three months later she had a prototype that changed Jack’s life almost immediately.

“For Jack, who freezes up every three or four steps, it really was the difference between being able to get up and go to the bathroom, or walk into the kitchen, or being confined to a wheelchair,” says Collin.

Once they made the device for Jack, he brought Collin to a support group where she met dozens of people with Parkinson’s who needed the same product. She knew they were on to something big, so she launched De Oro Devices and began developing the manufacturing framework for their first product, called NexStride. under the hood

NexStride is a small black box that can be easily mounted on a cane, walker, or walking poles. About the size of your palm, this device sends out a green laser line that runs perpendicular to the person walking forward. The device can be swiveled to place this green line right in front of the person’s feet or a few feet out ahead.

NexStride also comes with a built-in metronome with adjustable pace and volume. The combination of the visual cue of the green line and the auditory cue of the steady beat has the effect of re-establishing communication pathways between the brain and the body when a freezing episode occurs.

“The first time I used NexStride it was amazing because the laser light went on and it was like a “go” signal,” says Earl, a man with Parkinson’s who shared his experience in a testimonial video. “I just

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stepped over it. I could take four or five steps no problem.”

Some people only freeze up in certain situations, like one man Sidney worked with who had trouble walking when he was on a hike. The portability of the NextStride device allowed him to strap it to his hiking poles and stay mobile no matter the terrain.

The NexStride was designed from scratch by Sidney Collin and her team and they’ve worked with a US-based manufacturer to build the devices domestically.

The results have been powerful.

“My wife hops up and is ready to go with NexStride,” says Roger McBride a caregiver who shared his story on the company’s website. “Before she would freeze up, get the walker out in front of her, and she would fall down. She has zero falls with NexStride.” why we’re proud to invest

Sidney Collin is a wonderful contradiction. She’s in her mid-twenties, as bright as they come, yet she is dedicating her youthful energy and intelligence to some of the quiet frustrations and daily challenges of our elderly population. We’re excited to invest in Collin and her vision because she’s smart enough to design new tools from scratch and young enough to believe anything is possible.

We’re also bullish on De Oro Devices because it addresses a startling gap in the market. While reams of research are being published about Parkinson’s, basic daily challenges have gotten less attention.

“What really blows my mind,” says Collin, “is that while this freezing of gait is

one of the most debilitating symptoms of Parkinson’s, there really hasn’t been a solution for it. Medications don’t help.

Neurostimulation doesn’t really help.” And Parkinson’s patients are just the beginning.

There’s published research showing that these same visual-auditory cues are helping in areas like stroke rehab, multiple sclerosis, and cerebral palsy.

“There’s a much bigger impact that this product can have. Just looking at the current product and use cases, it’s about 26 million people globally,” says Collin. “At our price point of $499, that’s a total market of $13B with this one product alone.”

Finally, we’re proud to back Collin and her team because their health moonshot vision goes way beyond one device and one challenge. This team recognizes that there’s a larger gap that needs to be filled, that of creating a suite of products that meet people where they’re at as they age.

“A lot of the money goes into cures, which is admirable,” says co-founder Will Thomson, “but we’re focusing on solutions to help people now, with specific symptoms.”

“There’s a huge need to create tools that allow people to retain and regain their mobility at home,” says Collin.

NexStride is just the first device by De Oro Devices that helps people thrive with independence as they age. We can’t wait to see what they build next. Join us as we welcome them to the StartUp Health family.

4 DEORO@STARTUPHEALTH.COM

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MEET THE HEALTH TRANSFORMERS

BUA FIT Is Using Social Tech and an Online Marketplace to Connect Consumers With Outdoor and Online Trainers As a rugby player and a serial entrepreneur, it was a natural fit for David Stapleton to address the needs of the fragmented outdoor fitness market. Now, with their marketplace of passionate trainers and consumers, Stapleton and his team are looking to scale BUA FIT beyond the UK, helping people everywhere live a healthier, more active lifestyle.

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NUTRITION & FITNESS MOONSHOT VINTAGE: 2021/Q4 BUAFIT.CO.UK

HEALTH TRANSFORMER David Stapleton, CEO & Co-founder (L) buafit@startuphealth.com

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Growing up in Kildare, Ireland, David Stapleton loved two things most of all: playing outside and making

money.

“I’ve been obsessed with business and fitness my whole life,” he says in a winsome brogue.

As a kid in boarding school, Stapleton heard his teachers complain about how un-

comfortable their chairs were. So he purchased better ones at wholesale and sold them to his teachers for a profit. When he was 19 he built a tech platform that digitized the process of buying Christmas trees, targeting high-net-worth individuals in Dublin. When he wasn’t working on his business — or studying business at University — he was playing rugby. For many years, Stapleton played the sport at a semi-

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MEET THE HEALTH TRANSFORMERS / BUA FIT

professional level.

In 2011, he moved to London to try his hand as a financial broker. It was a poor fit — he was an entrepreneur at heart — and he took refuge at the gym. There, his entrepreneurial brain kicked in once again and he identified a market gap. First, as a consumer, he got frustrated with how laborious it was to find great outdoor fitness opportunities. Every trainer had a new business process he had to learn. Then, he befriended a fitness trainer who was trying to get his business off the ground. He watched as his friend’s business ultimately failed due to high rents and complex administrative burdens.

So Stapleton went into startup mode and started to solve the problem any way he could. First, he set up a WhatsApp group where he could connect outdoor fitness trainers with consumers. Then he began using Eventbrite to coordinate fitness events for people around London. Finally, realizing that he was onto a real business idea that tapped into his personal passions, he found a technical co-founder and dove in head-first. The two bootstrapped the business on the side for two years, 11 months and then launched BUA FIT officially through Google for Startups in 2019.

“I’m putting everything into BUA, and I’m loving the journey,” says Stapleton. challenge

Fitness gyms and studios have their place, but for David Stapleton, who spent decades rucking and mauling on the rugby pitch, there’s nothing like training outdoors. Whether it’s a high-intensity training (HIIT) session or a kickboxing boot

camp, he just prefers to get fit in the open air. And Stapleton isn’t alone. Around the world, there are millions of people who prefer to train outdoors.

“It’s better for your mental health, you burn more calories, you get more vitamin D, it reduces blood pressure, and it’s just more fun,” says Stapleton.

Outdoor training can also be more accessible to people who are beginning their fitness journey, or who just feel intimidated by the gym environment.

“One in three people in the United Kingdom are considered physically inactive,” says Stapleton. “A huge driver of that sedentary life is that gyms are intimidating and fitness studios are expensive and lack diversity of classes. They’re not for everyone. For instance, we service teenage girls in North London who are recovering from mental health issues. They’re never going to get that care in a gym setting.”

Because the fitness market has focused its funding and innovation on gym facilities and studio classes, outdoor fitness has remained a fragmented market. Every boot camp or yoga trainer who meets clients at the park is their own business, which means they have to wear the hats of marketer, web designer, and business development. As a result, trainers spend time and money on admin when they could be helping clients stay healthy.

On the consumer side, because of the fragmented market, people struggle to find the right classes at the right time. They have to have a separate business relationship with every trainer, and each scheduling program and billing apparatus comes with its own learning curve. As if getting fit and

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Outdoor training can be more accessible to people who are beginning their fitness journey, or who just feel intimidated by the gym environment.

"One in three people in the United Kingdom are considered physically inactive,” says Stapleton. “A huge driver of that sedentary life is that gyms are intimidating and fitness studios are expensive and lack diversity of classes."

staying healthy weren’t hard enough.

What if an online platform could connect consumers with outdoor trainers in such a way as to increase access for consumers and help trainers focus on what they do best? Enter BUA FIT. under the hood

With BUA, which means victory in Gaelic, people can log onto the web-based platform and within seconds find classes from a variety of independent trainers.

With a couple of clicks, they can book a session outdoors and online and pay digitally, anything from boxing to yoga, from boot camps to meditation.

For those who like market comparisons, BUA looks a bit like “ClassPass for outdoor fitness.” But there’s an important differentiator, says Stapleton. “Where ClassPass is more of a booking platform, BUA is more a blend of eCommerce and

social technology which is developing a stickiness in the community. We have consumers and trainers hanging out on the platform, which means trainers can create an authentic content marketing strategy (supplying real-world advice to consumers) and customers are just one click away from moving from chat to purchase.” On the trainer side, BUA’s platform makes it easy to market classes, communicate with potential clients, and collect payment.

BUA has logged more than 300,000 engagements on the platform even though the community is under 5,000 members currently.

“That engagement piece is one of our biggest strengths,” says Stapleton. “The strategy isn’t to have vanity metrics around user numbers, but to have engaged users whose lives are being changed.”

Another thing that makes BUA unique is that they’ve worked with various city councils around London to find nontraditional workout spots. Whether it’s a downtown rooftop, a platform on the River Thames, or a patch of concrete under the London Bridge (Stapleton’s personal favorite), BUA takes consumers beyond parks and into urban spaces that keep them excited and engaged.

“We’re not just delivering a fitness class, we’re delivering an experience.”

When COVID hit, Stapleton moved up the launch of their virtual platform, called BUA Live. This platform was purposebuilt by co-founder Sam Woodbridge in order to solve problems they were seeing in other online fitness classes. For instance, when people join a virtual fitness class, they often turn off their own video feed for pristartuphealth.com 27

MEET THE HEALTH TRANSFORMERS / BUA FIT

The online fitness industry is hot, but outdoor fitness is still in its early stages and BUA FIT has a first-mover advantage in the marketplace model in the UK. With their communitycentric model that blends memorable experiences with well-compensated trainers, we see this platform having legs far beyond the UK.

vacy. But that’s a recipe for injury, says Stapleton, because the trainer isn’t monitoring the person’s form. Instead, Woodbridge designed a platform that allows the user to turn off their video feed for the class while still being visible to the trainer. BUA Live has served Sport of England, Starbucks, and has hosted fitness classes for 14,000 women at the Women In Technology 2021 event. why we’re proud to invest

A lot of time, energy, and capital are spent trying to invent cures for diseases, and rightly so. But many healthcare problems — like those subtle-yet-deadly heart disease and type 2 diabetes — can be helped using old-fashioned exercise. We’re proud to be investing in a startup that’s going upstream to tackle healthcare issues early, long before a person needs pharmaceuticals or a hospital stay.

We’re proud to support Stapleton and

his team because they’ve found a markettested way to increase access to fitness classes. For the millions of people who feel intimidated by gyms, or simply can’t afford them, outdoor fitness is an amazing first step towards a healthier life.

We’re also bullish on BUA because they’re making life better for trainers and aligning financial incentives. By helping trainers get out from under-exorbitant facility fees and the administrative burden that slows them down, BUA can dramatically increase their earning potential.

Stapleton’s vision is that BUA trainers will make more money than those on Peloton, and he believes that the BUA model can make professional trainers into millionaires.

“BUA means victory in Gaelic and when either trainer or consumer sign up to the platform they’re both one step closer to victory in building their fitness business or achieving their fitness goals,” says Stapleton.

The online fitness industry is hot, but outdoor fitness is still in its early stages and BUA FIT has a first-mover advantage in the marketplace model in the UK. With their community-centric model that blends memorable experiences with wellcompensated trainers, we see this platform having legs far beyond the UK and we look forward to seeing their growth. Join us in welcoming BUA FIT to the StartUp Health family.

4 BUAFIT@STARTUPHEALTH.COM

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MEET THE HEALTH TRANSFORMERS

ACCESS TO CARE MOONSHOT VINTAGE: 2021/Q4 GETSPECT.COM

Spect Is Fighting Blindness With a New Portable Eye Camera and Teleophthalmology Platform Millions of people are at risk of vision loss from diabetic retinopathy, yet they lack access to specialty eye care.

Spect is making this care simple, accessible, and affordable by enabling eye diagnostics at home and through primary care providers.

HEALTH TRANSFORMERS Michael Ricci, CEO & Co-founder Ankur Gupta, MD, Co-founder Michael Leung, Co-founder Theodore Leng, Co-founder spect@startuphealth.com

Today, one in three Americans are diabetic or pre-diabetic. Globally, that number stands near a half billion, according to the WHO. In the best-case scenario, when a person is diagnosed with diabetes (typically type II), they’re under the care of a primary care physician. That provider will likely recommend diet, exercise, and medications to manage the disease. They’ll also tell the patient they should get their eyes checked regularly because diabetes often leads to eye damage called diabetic retinopathy, which can cause vision loss and blindness.

Diabetic retinopathy is incredibly

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common. At some point, nearly one out of three people with diabetes will experience it. The good news is that if it’s caught early it can be managed and vision protected.

The problem is the gap between primary care and specialty eye care. Far too few people with diabetes get the eye exams they need to protect their vision. It’s estimated that about 60% of the people who need an annual eye exam don’t get one. That’s because they have to be conducted by an eye care specialist like an ophthalmologist or optometrist, which means they’re a hassle to schedule and can be expensive.

Plus, there is only about one ophthalmologist for every 17,000 Americans. The numbers are much lower elsewhere around the world.

The situation gets even more dire when you go upstream and consider how many people with diabetes don’t have a relationship with a primary care physician. These folks are disconnected from the healthcare system and often don’t even know that their eyes are in danger. Then there are the millions of people who have related diseases that lead to vision loss and blindness, who also lack access to specialty eye care. Put together, an estimated 80 million people in the US general population have vision loss due to disease.

Michael Ricci and Michael Leung, cofounders of Spect, have taken on this problem using a combination of hardware and data-driven software. They’ve designed an easy-to-use eye camera that can be deployed by healthcare staff in-clinic or at home. It’s an approach that makes eye-saving exams fast, accessible, and affordable, and it’s catching on quickly.

origin story

When Ankur Gupta was a child spending his summers in India, he spent time with his grandfather who was a local physician. He’d watch as his grandfather took care of a seemingly endless stream of patients from their town. Many of them came with vision loss or eye damage, but he lacked the tools for a proper eye exam, and didn’t have any eye specialists to refer them to. Necessity being the mother of invention, the doctor rigged a makeshift eye camera using a cell phone and did the best he could for his patients.

That experience stuck with Gupta, and years later, after studying engineering at Stanford, he got the opportunity to do something about it. He teamed up with fellow Stanford engineer Michael Leung and ophthalmology professor Theodore Leng and the three decided to build a better portable eye camera on top of existing iPhone technology, so that more people could get the eye care they needed. Thus, Spect was born.

The startup, still very much in stealth mode, caught the attention of Michael Ricci, a serial entrepreneur who’d worked on three digital health startups, including RecoveryOne, backed by 7wireVentures.

Ricci could tell that Spect had the right foundation for a successful startup.

“In my time running healthcare startups I’ve learned as much about what doesn’t work as what does,” says Ricci. “You can’t just throw technology at healthcare. You have to understand workflow. I could see Spect had that right.”

But it wasn’t just the business opportunity that drew him in. Diabetes and vision

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loss hit home and offered a chance for Ricci to do some serious good in the second act of his career.

“We tend to take eyesight for granted,” says Ricci. “My mother was a borderline diabetic, and my close friend was a severe diabetic. I watched the mood swings and depression that came along with his loss of vision. I have another friend who has lost his eyesight completely due to diabetes.

We’ve seen it firsthand. It’s hard not to, given the numbers.”

Ricci’s passion for saving people from blindness — and for reaching underserved populations — led him to become a Spect consultant and then CEO. Now he’s leveraging his experience to scale the business. under the hood

Spect can be divided into three components: hardware, software, and data. The hardware consists of specialized optics and electronics that enable the camera on the smartphone to take retinal images. It’s portable, easy to use, and internet-connected.

Spect calls it the Stethoscope for the Eye™.

At first, the Spect business model had them putting this camera in primary care offices. The idea was to have nurses and techs use it for a quick eye exam while they were gathering vitals like weight and blood pressure. That concept was working, and then COVID hit and primary care offices shut down. So Spect took their product fully remote, leveraging telemedicine to ensure it would work seamlessly for healthcare staff visiting patients in the home.

Whether in a clinic or in the home, Spect works like this. Whoever is using the camera is guided from start to finish in

"In my time running healthcare startups I’ve learned as much about what doesn’t work as what does,” says Ricci. “You can’t just throw technology at healthcare. You have to understand workflow. I could see Spect had that right.

taking usable — called “gradable” — images. “Up, down, a little left … perfect!”

These directions, sent through the device’s speakerphone, are provided in real time by a Spect-trained navigator. The images are then graded asynchronously by eye specialists (ophthalmologists and optometrists) in Spect’s telemedicine network. Spect boasts that more than 95% of the images they capture are gradable, compared with 50–60% using current cameras on the market.

The final assessment acts as a screening tool, either giving the patient a clean bill of eye health or offering the data needed to refer them to a specialist for more care.

Spect can teach a nurse or medical assistant to use the camera in about 15 minutes, and they can do the training entirely remotely. It takes about three minutes to complete a scan if you’re new and one minute if you’ve got some experience.

Spect is a prescribed service, ordered by a doctor, but it’s designed to extend the doctor’s reach. Their first large customer deployed the device using home health aids.

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were disconnected from the healthcare system and for whom going into the office for proper eye care was a significant hurdle.

While most of the patients were above the age of 40, some of them had never had an eye exam in their life. why we’re proud to invest

When we met Ricci and the Spect team, the first thing that got our attention was the beautiful simplicity of their vision. At the end of the day, regardless of hardware or software, they’re on a mission to save the eyesight of millions of people who currently can’t access the care they need. Few things are more life-changing than saving someone from blindness. Tools like Spect have the potential to improve the health and wellbeing of millions of people around the world.

Another reason we’re bullish on Spect is that they’ve nailed down a business model that makes their device and platform incredibly accessible. Other companies have waded into the remote eye exam market, but they’ve required users to buy bulkier cameras that cost anywhere from $5,000 to $10,000 or more. By building their tech onto a smartphone infrastructure and using a SAAS subscription model, Spect offers the device for free and makes the per-use cost extremely low. Practically any company or clinic can get up and running with remote eye exams with almost no upfront costs.

Another aspect we love about Spect is how its ease-of-use opens up access to care for vulnerable populations. Millions of people are disconnected from traditional primary care and rely on home health aids

and population health initiatives. Now, with just 15 minutes of training, community health workers of all kinds can extend the benefits of eye exams into underserved communities.

Spect is also a win for primary care doctors like Ankur Gupta’s grandfather. Not only can these physicians provide better care, but they gain a new line of revenue.

Spect eye exams are recognized and coded exams that are reimbursable by insurance.

By helping primary care doctors begin to offer eye exams, Spect is also helping them increase their quality rating as measured by the federal government, which in turn increases their rate of reimbursement for Medicaid and Medicare patients.

“It’s a fairly big financial benefit to them to have this arrow in their quiver,” says Ricci.

Finally, we are proud to invest in Spect because diabetic retinopathy is just the beginning. The information being captured

by Spect’s eye camera opens up a whole new world of health data. This is a noninvasive, zero-radiation test that can help understand a range of health concerns, like neurological deficits, blood pressure, heart disease, cancers, and Alzheimer’s disease.

Spect’s health moonshot vision is already making waves and has gotten the attention and support of Y Combinator, American Diabetes Association, Johnson & Johnson Innovation, Medtech Innovator, and StartX. Now, we’re proud to welcome them into the StartUp Health family and support them in their next exciting chapter.

4 SPECT@STARTUPHEALTH.COM

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MEET THE HEALTH TRANSFORMERS

ThinkHuman, by Affectifi, Uses Shows on Netflix and Disney to Teach Social-Emotional Skills Melissa Cesarano, PhD, and Ilya Lyashevsky, PhD, have designed a way to teach emotional intelligence that’s entertaining and backed by science.

In 1986 Robert Fulghum published the book All I Really Need to Know I Learned in Kindergarten. It sold seven million copies, but you really didn’t need to crack it open to get the gist. Some of life’s most critical skills are also the most basic.

Seemingly simple knowledge can be profound.

For example: emotional regulation.

Young children are often shown pictures of people who have frowns, grins or tears and then are asked to identify those emotions and talk about them. Decades of research in social-emotional learning (SEL) have shown us that these lessons — knowing how to pause and identify the emotions of the people around you — are foundational skills that lead to empathy and greater mental resilience.

But these aren’t just skills for five-year-

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HEALTH TRANSFORMERS Melissa Cesarano, PhD, President & Co-founder Ilya Lyashevsky, PhD, CEO & Co-founder affectifi@startuphealth.com

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olds. You don’t have to be a social scientist to know that people of all ages and backgrounds struggle with empathy, and with emotional regulation. We see the results every day in politics, on the news, and around our own dinner tables. The struggle to empathize was worsened by COVID-19 as the pandemic pushed people apart physically, but the core challenge has been there all along.

Yes, we’re in the middle of a mental health crisis, and anxiety, depression, and suicide are at dangerous levels. But beneath that, underpinning our collective mental wellbeing is a need for greater emotional intelligence. Addressing that means going beyond soft science, beyond cheezy “edu-tainment” repackaged from kindergarten lessons. It means using a data-driven approach and research-based methodologies.

This is precisely what Melissa Cesarano, PhD, and Ilya Lyashevsky, PhD, set out to do when they founded Affectifi, maker of ThinkHuman. origin story

For co-founders Melissa Cesarano and Ilya Lyashevsky, there’s no real division between art and science.

When Cesarano was doing her undergrad at the University of Pennsylvania, she majored in cognitive neuroscience and minored in poetry. She also fell in love with comedic acting and joined Bloomers, the college’s all-female sketch comedy group. It didn’t take long for her worlds to collide.

“As I studied cognitive science I kept seeing how the scientific concepts played

themselves out in the art that I was immersing myself in,” says Cesarano. One minute she’d be in class learning about mirror neurons — brain cells that allow people to learn empathy through imitation — and the next she’d take the stage and see how those neurons fire in real life.

Along the way she used her poetry to distill these ideas and put the connections, she was making into words.

Ilya Lyashevsky was making similar connections in New York City. By day he was working in computer science at a tech

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company. By night he wrote works of fiction that explored the complex emotional lives of his characters.

“Why am I writing?” Lyashevsky recalls asking himself. “I’m trying to say something about the human condition.

There’s this educational side of the arts, and it centers on emotion, understanding who we are, and why we behave the way we do. Art is great, but my real goal is to help people with that understanding of the self and others.”

These parallel strands of thought about

the intersection of art, emotion, and cognition landed Cesarano and Lyashevsky in a PhD program at Columbia University. They teamed up while working on their dissertations and later created a course at Columbia Teachers College on the cognitive underpinnings of emotion.

But teaching teachers was just the entry point. The two wanted to move upstream and find innovative ways to bring socialemotional learning to young people. The idea was to make SEL so accessible and palatable for teenagers that it could bestartuphealth.com 35

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come a preventative measure, not just a band-aid given to teens who were already suffering.

To accomplish this the duo founded Affectifi and in 2019 they received a grant from the National Science Foundation (NSF) to create ThinkHuman, a way to layer social-emotional learning on top of popular programming on Netflix and Disney Plus. under the hood

ThinkHuman, by Affectifi, is a straightforward concept. It layers social-emotional lessons on top of entertaining shows from your favorite streaming channel. It works like this.

When a user wants to improve their emotional intelligence they start by downloading the ThinkHuman browser extension. Then they dial up their favorite streaming service (Netflix and Disney Plus are currently covered, and Peacock is on its way). On the streaming platform, ThinkHuman TV provides a curated list of titles spanning diverse genres and interests. When the user hits play on one of these shows, the platform kicks into gear.

Let’s say you’re watching Star Wars Episode IV. Princess Leia comes on screen and gives Darth Vader a withering look.

The movie pauses automatically and a multiple choice question pops up on the screen. “What emotion label best describes Leia’s actions?” The questions range in style based on the show and the moment, but they all require the viewer to pause and consider the emotional landscape on screen and, by extension, within themselves.

Viewers can watch their way through specific modules based on core concepts in social-emotional learning. They get rewarded along the way and can even earn certificates by completing a series of shows and questions.

Behind the scenes, ThinkHuman is powered by a system of emotion mapping. Cesarano and Lyashevsky and their team of researchers map popular narratives based on emotion science principles.

In the future, this will also allow educators to dial up a specific emotion, like gratitude, and show students what that looks like across a range of diverse — and entertaining — narratives.

“For a long time in social-emotional learning there’s been something of a lack of consensus on what you teach and how you teach it,” says Lyashevsky. “We believe it’s essential to build foundational emotion knowledge, and we can do that by teaching people the science of emotions — giving them a real understanding of how emotions work. And we want to do it in a way that is connected to authentic examples of emotions and behavior.”

That core concept, which they call “Deep Emotional Learning” is designed to be an ongoing part of life — vs. a quick fix — as people build the habits and train the muscles around emotional regulation. why we’re proud to invest

In the world of health startups, mental health presents a bit of a contradiction.

On one hand, the challenges of depression and anxiety, and suicidal ideation are so great that it seems there could never be enough solutions. On the other hand,

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Teaching teachers was just the entry point. The two wanted to move upstream and find innovative ways to bring social-emotional learning to young people. The idea was to make SEL so accessible and palatable for teenagers that it could become a preventative measure, not just a bandaid given to teens who were already suffering.

it’s a crowded market for startups, and separating the signal from the noise can be difficult. We’re proud to back Affectifi because they’re using a truly unique approach to go upstream and tackle the building blocks of mental health early. It’s a highly-researched, data-driven methodology that we haven’t seen before, and which hones in on an underserved population: teenagers.

We’re also proud to back Cesarano and Lyashevsky because of the health moonshot scale of impact that a tool like ThinkHuman could bring to the world.

“When you begin to understand how fundamental these skills are, like empathy and emotional regulation, you realize that this is a society-transforming project,” says Lyashevsky. “It’s not just about anxiety and depression. It’s about politics. It’s about our justice system.

Everything comes down to what people understand about themselves and other people.”

We’re also bullish on ThinkHuman

because it builds on one of the market’s fastest-growing sectors: streaming entertainment. By linking their tools to such widely sought-after content, ThinkHuman massively increases its potential for distribution and impact. As the company grows, there’s no limit to the number of shows their team can map and make available within their learning modules.

We can imagine a future where ThinkHuman collaborates directly with streaming services, and emotion mapping is built in from the beginning like closed captioning is today.

Finally, the industry is taking note. Affectifi has already secured some initial school customers and has run a successful pilot at Teachers College as well as at Columbia University, where undergraduates have proven to be a particularly motivated user group. And they’re making inroads with mental health professionals, who like how ThinkHuman offers a fun way for patients to “practice” core concepts between sessions. They’re collaborating with Richard Lane, a worldrenowned researcher in emotional awareness, and they’re on the road towards a second NSF grant. At the same time, they’re in partnership discussions with multiple organizations across the edtech, media, and wellness spaces.

We’re incredibly excited to see how founders Cesarano and Lyashevsky will use their unique backgrounds in art and science to shape mental health through social-emotional learning. Join us in welcoming them to the StartUp Health family.

4 AFFECTIFI@STARTUPHEALTH.COM startuphealth.com 37

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On TAG TV, Mental Health Professionals Bring In-Session Wisdom to the Masses After a divorce left him depressed and desperate, media entrepreneur Erik Nielsen found a therapist who helped him face his past and begin to heal. Now, with TAG, he’s built a way to scale the tools of therapy, improving access to mental healthcare while lowering costs for all.

At StartUp Health we’ve written at length about the macro challenges within the mental health market. At the top of the funnel there’s the scale of the problem. According to the National Institutes of Health (NIH), one in five US adults lives with a mental illness of some kind. This massive number has created a need for more accessible solutions, and tele-mental health companies have proliferated as a result, a trend accelerated

by COVID-19.

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MENTAL HEALTH & HAPPINESS MOONSHOT VINTAGE: 2021/Q4 WATCHTAG.TV

But there are multiple complicating factors beyond the scale of the mental health crisis. The first is affordability.

Generally, when it comes to healthcare services covered by insurance, the 80/20 rule applies. Eight out of ten healthcare providers are covered by insurance and the other 20% are not — think cash-pay services like elective surgery or concierge medicine. In the mental health space, those numbers are reversed. About 80% of mental health providers are not covered by insurance and patients have to pay high rates in cash. As a result, in the United States alone, tens of millions of people report they need mental health services but don’t get it because of cost. That’s the kind of barrier to care that costs lives.

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And the hurdles to care get even higher.

In poor and rural communities, even if the care is affordable, there might not be any healthcare providers available. Just like there are food deserts and pharmacy deserts, there are mental healthcare deserts.

Finally, there’s the issue of stigma. In many communities, seeking mental healthcare is still looked down upon and people end up suffering alone.

That feeling of being alone, it turns out, is the icing on this cake that no one wants to eat. A person can overcome all of the hurdles to receiving care for a mental health challenge and yet still be left with the pain of feeling alone in their struggle.

There is a sense that ‘no one understands what I’m going through’ because it all stays in the therapist’s office. Of course, the therapist knows the truth: that thousands of people are working through the same issues, but they’re just not talking about it.

The scale of our current mental health crisis compounded by issues of affordability, access, and stigma have created a perfect storm. That storm has in turn sparked a wave of health innovation that goes beyond tele-therapy. Enter Erik Nielsen, CEO & Founder of TAG, an interactive platform that makes the tools and strategies from in-person therapy available to the masses in an engaging, data-driven way. origin story

Like so many health tech founders, Erik Nielsen started TAG because it was personal for him.

Nielsen was working as a successful

advertising exec when, at 35, he went through a rough divorce. The experience rocked him in ways he couldn’t understand and left him in such a deep depression that he could barely keep his head above water. At the same time, he was launching The Saffron Project, a digital marketing company that grew from two people to 30 and landed clients like Oprah, FedEx, and P&G. None of the business success dulled the pain.

He reached out for help and first landed in the office of a psychiatrist who began trying him on different antidepressants, seeing what might be effective.

“That game is ‘trial and error’ because everyone reacts differently,” says Nielsen, shaking his head. “There’s nothing wrong with medication, but the process of finding the right medication is really challenging.” None of the medications worked for him. Instead, he fell into an even deeper hole and had suicidal thoughts for months.

Finally, three years after the divorce was finalized, Nielsen reached out to a therapist. In these sessions he began to have breakthroughs and dig down into the root causes of his depression.

He was so encouraged by what he was learning — much of it rooted in cognitive behavioral therapy (CBT) — that he couldn’t help sharing it with people around him. With his experience in advertising, product development, and game design, it wasn’t long before he came up with an idea for bringing these mental health lessons to the broader world.

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an alpha product, a proof of concept.

After getting great initial feedback, TAG solidified as a bona fide company and they were off to the races.

“For me, this is totally personal,” says Nielsen. “There were so many years of pain and anguish and despair. Your brain just goes to the dark. If I’d had something like TAG, I wouldn’t have been in that awful place. I wouldn’t wish that on my worst enemy.”

HEALTH TRANSFORMER Eric Nielsen, CEO & Founder tag@startuphealth.com

under the hood

TAG has a straightforward framework.

A real person — not an actor — agrees to share their specific struggles with mental health on video. These “storytellers” are people who have dealt with everything from bipolar disorder to depression to trauma. They look at the camera and share their challenges and experiences in a transparent way that is rare in mental health.

Watching the storytellers has the immediate positive effect of helping people realize they’re not alone. But that’s just the first layer. At important moments during the person’s story, the video pauses and a licensed therapist from TAG comes on the screen. Not unlike the way a coach might pause and analyze a game film for their team, the therapist walks through the experiences being shared and highlights important points. They identify nuances and themes and then offer practical tools and coping strategies to the viewers.

This is more than just a taped therapy session, though that can have value as well.

The therapists are specifically tasked and trained to extrapolate the lessons within

a session to a larger audience, so that more people can benefit. The therapist is looking at the camera, directing their attention to you, the audience. In this way, the therapist lets the audience know that they’re not alone and gives them immediate tools to apply in their lives.

“We’re trying to take what is normal, dry science and package it in a completely different and engaging way, so that people can get informed and learn the techniques,” says Nielsen.

The next phase for TAG, says Nielsen, will be to add in a layer of AI and gamification. Instead of a linear progression through one story and one therapist’s commentary, the therapist’s wisdom will be chunked into modules that can be moved around. You’ll watch a segment, then answer some questions, and then you might be taken to a different scenario or therapist. This more nuanced approach to scaling therapy builds on Nielsen’s experience as a board game designer.

TAG has a partnership with the Uni-

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versity of Texas at Austin, working with the founder of the university’s Anxiety Lab. They’ve developed a model that TAG is weaving into their product that allows users to track their mood and progress week to week. They’ll then combine that information with reported data on the platform to deliver content recommendations, not unlike recommended shows on Netflix.

“We’re complementary to therapy, versus competing with it” says Nielsen. “If we do our job right, people will be much more likely to connect with a therapist when they need it. We’re upstream a bit, trying to head off a crisis before it happens and deliver the benefits of therapy much earlier.” why we’re proud to invest

When we met Erik Nielsen it quickly became obvious that he had that all-important combo of market expertise and personal passion. Nielsen knows media, business, and product development, having scaled up a digital marketing firm and worked with top-tier clients. Balanced with this experience is the gut punch of his personal bout with deep depression.

That period of his life, and the upswing he experienced from therapy, fuels his mission every day.

We’re also excited to back Nielsen and his TAG team because they’re leveraging the platform for the vulnerable populations. There are more than 1 million suicide attempts each year in the US alone and the biggest risk group is in ages 18– 25. It’s Nielsen’s plan to use revenue from their enterprise subscriptions to offer free

therapy to at-risk groups.

“It’ll eventually be crowd-funded healthcare for the most at-risk patients,” says Nielsen. He uses the example of a school shooting. After a traumatic event like this, Nielsen envisions immediately offering all of the students free access to the platform, to run through modules around trauma, anxiety, and grief.

We love that Nielsen is thinking differently about scalable mental healthcare.

We often think of therapy sessions as being so unique and each person’s problems as theirs alone. However, mental health therapists by and large learn the same set of tools for dealing with these challenges.

There’s a consensus on how to counsel and guide people through mental health crises. With platforms like TAG we can remove some of the mystery of therapy and share those strategies directly with the world.

There are thousands of mental health apps on the market that are basically the user interacting with the algorithm. Then there are a host of new, great telemedicine companies focused on mental health. But TAG lives in a unique space, bridging the worlds of automation and personal therapy.

We’re excited to watch as Nielsen increases TAG’s user base and builds out platform functionality because we believe it could be an important piece in multiple health moonshots, bridging access, cost, and mental health. Please join us in welcoming TAG to the StartUp Health portfolio.

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TAG@STARTUPHEALTH.COM

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CHILDREN'S HEALTH MOONSHOT VINTAGE: 2021/Q4 NOWPERFORMANCE.COM

Now Performance Is Using Wearable Tech to Get Kids Active and Healthy Former baseball coach Nik Edmondson was troubled when he saw how many kids were quitting sports just to sit on the couch and look at screens. With his startup, he’s leveraging the best elements in video games to incentivize active play that’s healthy and fun.

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The statistics on childhood physical activity are grim: 80% of young people in the US are classified as "inactive," scoring the US a D- on a global health report card in the area of activity levels.

Nine out of ten children in the United States fail to meet the recommended daily activity time of 60 minutes, says the CDC. It's not hard to see the connection between statistics like these and the 19.3% childhood obesity rate, or the growing prevalence of type 2 diabetes in adolescents. Lack of physical activity correlates to a long list of health risks: heart disease, high blood pressure, high cholesterol, stroke, certain cancers, osteoporosis, depression and anxiety, and raises the risk of premature death.

Clearly, the stakes are high. How do you get and keep young people moving? What factors contribute to an inactive lifestyle and what factors can shift someone towards activity? One big, obvious culprit is screen time. A 2019 study by the Common Sense Media found that 8- to 12-year-olds in the United States now use screens for entertainment for an average of 4 hours, 44 minutes a day, and 13- to 18-year-olds are on screens for an average of 7 hours, 22 minutes each day. The pandemic has exacerbated the problem as schools have gone remote and parents struggle to find affordable child care in the midst of closures and need to rely on screen time to entertain a child while they work.

While organized sports provide a source of physical activity for some kids, not everyone has access to those types of programs. And even with access, participation steeply drops off after age 13, as competi-

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tion gets tougher and other activities and interests take precedence. Interestingly, the number one reason young people who stop a sport give is that "it's no longer fun." Kids want to play and when a sport no longer feels like play, they look somewhere else for fun, like a video game console. origin story

Nik Edmondson saw this pattern play out time and time again as a baseball coach.

He'd have kids be enthusiastic members of a team from age 6–12, only to hang up their gloves at 12 to spend their free time playing Xbox. Edmondson, a former Division 1 baseball player with a MA in Sports Psychology, became fixated on figuring out how to stem the tide of kids moving from the field to a couch. He knew from his own experience as a player and coach that performance is linked to the right mindset.

Kids, just like adults, need the right motivation.

"I started asking the question, 'What motivates kids to get up and be active and healthy?' And I asked it in a lot of different ways, trying not to assume I knew the answer." Over time an answer started to take shape, an answer that was both simple and complex: kids want to have fun. Organized sports stopped being fun for a lot of kids as they grew older and it became more competitive. Gym class wasn't any better as it was often fraught with embarrassment and bullying and did little to encourage a love of movement (see this Atlantic article "Gym Class Is So Bad, Kids Are Skipping School to Avoid It"). Compared to intense practices for a game where you might get to bat once, video games were easy, available, and low pressure, a way to decompress after startuphealth.com 43

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a long day at school. They provide a sense of autonomy and control, a brief moment where the young person calls the shots.

Edmondson felt like he was starting to see the bigger picture about why kids left sports and what kind of motivation they needed to stay in. But he felt frustrated by the limited amount of impact he was able to have as a coach.

"I started looking at how technology could scale up the impact we could have with greater numbers of young people.

And I found a group of people to look into this with me. What we did is say, 'If kids care about video games, how do we create a big video game with activity?'"

Using his connections with the Little League world, Edmondson and his growing team, called Now Performance, set up a series of physical games for players (sprints, pitching speed, hitting speed) where they received metrics. Then, Now Performance received a grant to do the same thing with a Boys & Girls Club and it was a runaway success. The kids loved receiving quantifiable feedback on their performance: a number they could improve, just like a score on a level in their favorite video game.

This grant was followed by a series of fortunate events: the Boys & Girls Club program got the attention of WHO researchers who were looking into setting up a smartwatch for kids that tracked and encouraged activity. They asked for Now Performance's help, which became the seed of what the company is today.

Then, through his coaching work, Edmondson connected with a tech CEO who mentored him at just the right moment. That advisor connected Edmondson

HEALTH TRANSFORMER Nik Edmondson, CEO & Founder nowperformance@startuphealth.com

with the people and resources he needed to bridge the gap from baseball coach to health tech CEO (or as the Now Performance website puts it: Head Coach/GM). under the hood

Currently, Now Performance is in test drive mode (spring training, if you will), partnering with GENYOUth, a nationally-recognized youth wellness organization.

Through a partnership with Moto Watch, Now Performance is able to give kids free watches with the app installed. The app is a closed system, providing information privacy and safety for the students using it, as well as visibility for parents. The watch tracks each person's activity, awarding them points for movement that they can use to claim rewards through the app.

"We are keeping it simple at first by using steps as an activity metric to start so we can really uncover motivation without overcomplicating it. We always go back to our core question of 'What motivates kids to be active?'"

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Some of the enjoyable aspects of video games-autonomy, a level playing field, and individualism-get kids using the app, and the rewards system motivates them to keep it up. Now Performance is constantly finetuning its reward system based on feedback so that they understand what truly inspires the kids to persevere. Rewards could be digital, physical, or even altruistic: kids have the opportunity to donate, gift, or use their points to help others and the planet.

It's all about win-win partnerships; Now Performance is currently working with a global sportswear retailer on a pilot to reward kids with gift cards, but the options are endless.

"We are excited to create win-wins and do it in a sustainable and healthy way for the entire youth health ecosystem," says Edmondson. "Young people can do almost anything they want (within context) with a certain regimen, a certain structure. What you need is the right motivation, the right focus."

Now Performance is taking it slow and doing it right, listening to their users and building a platform that truly motivates them. When Edmondson talks about his company, he can't help but sound like the coach he is, laying out how they will achieve each next step through persistence and intentionality. We have little doubt that they will knock it out of the park. why we’re proud to invest

When we first met Nik Edmondson and his team at Now Performance, the first thing that caught our attention was their passion for children's health. At StartUp Health, we've been tracking global invest-

ment into the Children's Health Moonshot for a decade, and our takeaway is that there needs to be a lot more of it. Children's health initiatives often get short-changed in the allocation of healthcare resources.

But every health issue a child faces, from general fitness to type II diabetes to depression, will mature into an adult problem.

We're proud to back a startup like Now Performance that understands the vital nature of addressing health problems early in life.

We're also bullish on Now Performance because the positive ripple effect of active, healthy children is massive and global.

Turning the tide on inactivity in youth means attacking heart disease, diabetes, anxiety, and stroke, just to name a few. If an ounce of prevention is worth a pound of cure, going upstream to build healthy habits in children is like solid gold.

We're also excited to back Edmondson and his team because they are uniquely positioned and have a Health Transformer mindset. Edmondson's time as a coach taught him how to build and motivate a team. It prepared him for overcoming obstacles and persevering to the goal. He and his team are using this mindset to tackle each aspect of this health challenge in turn, step by step, asking the right questions and listening carefully to the answers. Now Performance has been smart about forming partnerships in order to scale, and their approach has already garnered the attention of multiple national organizations. Now, we're excited to support them in their next chapter. Join us in welcoming Now Performance to the StartUp Health family.

4 NOWPERFORMANCE@STARTUPHEALTH.COM startuphealth.com 45

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MindTrace Is Improving Brain Surgery Outcomes Through Behavioral Mapping Brad Mahon, Max Sims, and Hugo Angulo are building tools that help brain surgeons understand how procedures will impact a patient’s core functions, like speech and memory. It’s a new approach that bridges cognition and anatomy at the point of care.

HEALTH TRANSFORMERS (L-R) Max Sims, CEO & Co-founder Hugo Angulo, CTO & Co-founder Brad Mahon, PhD, CSO & Co-founder

BRAIN HEALTH & ALZHEIMER'S MOONSHOT

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VINTAGE: 2021/Q4 MINDTRACE.COM

Imagine going to the doctor because your right hand has been tingling and receiving the scariest news of your life. It’s cancer. In your brain. And they need to operate as soon as possible.

As if that wasn’t bad enough, there’s more. You learn that since the surgeons will be operating in an area of the brain that supports core functions like the abilities to skillfully use your hands and produce language (they call these “eloquent” areas), there is a risk that removing the tumor could damage parts of your brain that help you function. The ordeal could cause a cognitive deficit that makes you less, well, YOU. Now, there have been tools and strategies in existence for decades to try to work this problem, to protect people’s minds during surgery so that they can walk out of the hospital the same person they walked in. One approach involves “awake surgery” and it goes something like this: Local anesthetic is applied to the scalp in the location where the surgery will occur. The patient is put under general anesthesia and their skull carefully opened, exposing the brain. Then the person is woken up. Because the scalp has been numbed and the brain has no feeling, they can remain awake and aware without pain or discomfort, for hours.

The surgeon then begins a process of electrically stimulating specific parts of the brain while evaluating the real-time performance of the patient on sensory, motor and cognitive tests.For instance, while a specific point in the brain is temporarily “turned off ” through electrical stimulation, another member of the clin-

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ical team might show the patient a word or picture on a notecard and see if they can recognize it. By doing so, they’re able to pinpoint where certain functions exist in that patient’s brain. No two brains are exactly alike in their geography; in fact there can be up to a two centimeter difference in where certain cognitive functions are located in the brain, from one patient to the next.

Here’s where the modern challenge comes into play. How can clinical teams plan a route to remove the most tumor while at the same time ensuring the highest possible quality of life post-surgery?

To tackle that problem, surgeons need new tools to integrate data and translate information into evidence that can be used during clinical decision making. Today, brain surgeons rely heavily on a suite of brain mapping techniques that provide high-resolution information about the functional and structural organization of each specific patient’s brain. Those data are collected pre-operatively, whenever possible, at all major medical centers as part of standard of care. Those pre-operative images give the surgeons a very clear picture of the patient’s brain and where a tumor sits within it. What’s needed now is an upgraded suite of tools that helps translate all of that information into evidence at the point of care in the surgical suite. It is the difference between knowing where something is in the brain (the status quo) and having an evidence-based prediction about how removing a given area of the brain will affect a patient’s future language or motor function — a sort of Google directions for brain surgery.

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individual’s cognitive function in a way that can be brought right into the surgical suite, and that utilizes data from other patients in real-time. No more holding up flashcards, no more lost data.

And that is where MindTrace comes in. origin story

Brad Mahon was working at the University of Rochester when he first witnessed the opportunities for innovation around the surgical management of brain tumor and epilepsy patients. As a psychology professor specializing in neuroscience, he built his academic career on a research program that involved pre-, intra- and post-operative cognitive testing in brain tumor and epilepsy patients.

Throughout his time in Rochester, Mahon worked closely with Dr. Webster H. Pilcher, Chairman of the Department of Neurosurgery. Mahon and Pilcher had shared NIH and NSF grants to support their academic research, and collaborated on building a Translational Brain Mapping program to foster innovations that lead to better patient outcomes. “Every time we do an operation, we have an opportunity to learn something new about the brain,” says Dr. Pilcher, who specializes in the care of patients requiring complex brain mapping and awake surgery.

“We want to deliver the best care to our patients and to ensure they have the best possible outcomes. This means treating the person and not just the disease–and in neurosurgery, this means doing everything we can to protect each patient’s mind while addressing their specific surgical needs.”

Through his experience as a basic scientist working with surgeons such as Dr. Pilcher, Mahon came to recognize two core needs. The first was that there was no established technology or system for the cognitive and brain imaging data his team was collecting before surgery to be most effectively utilized by surgeons at the point of care. The second involved the opportunity to innovate the way that data was collected and accessed in real time during awake brain surgery.

The pieces began to come together when Mahon met Max Sims, who was double majoring in business and neuroscience at Rochester. Sims worked with Mahon in the lab for two years as a fulltime researcher, testing brain tumor and epilepsy patients before, during, and after surgery. As they studied each brain, they became more convinced that they could improve how cognitive functions are mapped in the brain in a neurosurgical context and help bring a more nuanced picture of the brain into the surgery suite.

They decided to take their idea on the road to test whether the opportunities for innovation they were seeing at one academic center were generalizable across the country. They traveled the United States and had hundreds of conversations with brain surgery teams at 15 different medical centers. The answer was a resounding yes, which gave them the confidence to pursue MindTrace as a business.

“It’s a space that is ripe for innovation,” says Mahon, “because even at the top facilities for cancer and epilepsy treatment, in the context of incredibly advanced methods for non-invasive and invasive

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started building out a tech team at Carnegie Mellon.

Today, they’re building up their medical advisory board and prepping for their first meeting with the FDA. They raised about $600K in their pre-seed stage and are looking ahead to a seed round. under the hood

brain mapping, it is not uncommon for someone to be holding up a piece of paper with words or pictures and doing the test completely manually. And, even if the testing is digital, that data remains siloed from other information about the patient, and siloed from informing the care of future patients. All of that information is being used in the moment, but then it’s disappearing.” Mahon and Sims realized that MindTrace could develop the tools to digitize this entire process. By doing so, the data generated from one patient can inform care decisions about future patients, and in potentially any operating room in the world.

Core to their challenge was how to scale. They knew they could improve cognitive mapping for 50–60 patients a year, but how could they grow to help thousands of neurosurgery patients a year? For that they’d need a new platform driven by artificial intelligence and machine learning. So they moved to Pittsburgh and

MindTrace is a SaaS platform that organizes all of the behavioral and neuroimaging data that is collected before, during, and after a brain surgery. Put another way, they’re combining the knowledge gained from pre-operative neuropsychology assessments with anatomical scans like MRI and CT. That allows MindTrace to overlay — and fuse in 3D — all of the relevant neuroimaging and behavioral data into a single 3D visualization. That image can then be used by the surgeon to evaluate their surgical options, both before the first incision and in real time as the surgery unfolds.

Once it “co-registers” the neuroimaging and behavioral information into one platform, MindTrace will be able to simulate surgical plans and actually predict postoperative cognitive outcomes. That means a new type of evidence-based planning about how to surgically treat brain cancer and medically refractory epilepsy, while optimizing the post-operative quality of life of the patient.

To explain how this added data helps the surgeon, Sims extends the analogy to navigation. Imagine a Google Map. For the last couple decades, we’ve had anatomical navigation for brain surgery. That status quo is like using a two dimensional startuphealth.com 49

MEET THE HEALTH TRANSFORMERS / MINDTRACE

map of roads and highways and then manually charting one’s planned course.

Of course, for geographical navigation we now have google maps, which tells you the implications of taking one route over another. Mind Tracing, says Sims, will tell clinical teams the implications for a patient’s future mental function of taking one approach in a surgery compared to another. “We want to be able to tell the brain surgeon how a decision could change the expected neurocognitive performance of the patient, in real time, during surgery so that the surgical team can use that information in real time as new type of evidence.” why we’re proud to invest

Some innovations in health are more technical and specialized than others.

MindTrace’s product is highly technical and their initial market of awake brain surgeries is in the low thousands per year.

But that’s part of the strength of what they’re doing. We’re incredibly proud to back this team because they’re patiently and carefully laying the groundwork for massive future impact. The first step is to hone the algorithm in awake brain surgery where they can get direct causal feedback. Then they can build a tool for a broader population and help hundreds of thousands of people with brain injuries, like stroke patients just as one example.

Mahon’s got one word to describe this approach.

“If there’s one core value to MindTrace, it’s integrity,” says Mahon. “In the space in which we’re working, we understand the need that every step of our journey

must be based in scientific validity, because that is our lived experience in the academic work out of which MindTrace grew. We want to build and scale MindTrace as quickly as we can, but no quicker and without haste. We must proceed carefully, so that our clinician collaborators understand and recognize that our products and features will work exactly as intended.”

The industry has already responded positively. For their work helping make sure people walk out of surgery the same person they walked in as, MindTrace won the first-place prize of LifeX Labs at Pittsburgh Life Science Greenhouse’s Accelerator program. As Mahon’s longtime collaborator Dr. Pilcher put it, “What is inspiring about this technology is the ability to harness the insights gained from the care of today’s patient to inform the care of tomorrow’s patient, and to do this at scale, across clinicians, medical centers, and time” Finally, we’re proud to support the team at MindTrace because they understand that it’s not enough to simply live longer.

It’s how we live that defines our humanity.

Their tools change the focus away from a simple calculation of life years to protecting the things that matter most. It’s about thriving as we age and protecting the parts of ourselves that make us who we are. That’s a health moonshot mission we can get behind. Join us in welcoming Brad Mahon, Max Sims, Hugo Angulo, and the rest of the MindTrace team to the StartUp Health family.

4 MINDTRACE@STARTUPHEALTH.COM

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Diagnostikare Is Making AIPowered Virtual Healthcare a Reality in Mexico Brothers Rafael (L) and Rodrigo López, MD, combined their experience in tech, business, and medicine to upgrade healthcare delivery in Mexico City and beyond.

ACCESS TO CARE MOONSHOT VINTAGE: 2021/Q4 DIAGNOSTIKARE.COM

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Mexico, like so many nations, faces the challenges of a fragmented healthcare system.

On paper, it’s a two-tier system where a privileged few (about 7%) have private insurance, and everyone else is covered by public institutions or pay for healthcare expenses on their own. But the high cost of private care and the long wait times for public aid have created a de facto third tier: self-care by way of your local pharmacy. Or, worse, they get no healthcare at all — over 33 million people (almost 28% of the population) lack access to public or private healthcare services.

Imagine, for instance, that you’re an employee of a mid-sized company in Mexico. The company isn’t providing any private insurance, so when you come down with flu-like symptoms, your only option is the public clinic. But the wait times are such that your flu will be long gone by the time a doctor can see you. So instead you pull out your phone, Google “flu symptoms and medications” and then walk to your neighborhood pharmacy. If you’re lucky, you’ll talk to a healthcare provider for a few minutes, but more likely you’ll remember what you took last time you felt this way and just buy some medicine and hope for the best.

There are many situations where this path of self-care — bypassing insurance and public and private hospitals or clinics — works out fine. However, taken at scale this becomes a serious health problem.

When tens of millions of people don’t have access to basic primary care services or preventative medicine, the downstream impact is predictably negative. It means

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that no physician is watching the patient over time, tracking the progression of illness. It means that serious chronic diseases are left unmanaged (Mexico ranks #2 in the world for obesity). It means that patients take the wrong medications, relying on past experience rather than the consultation of a trusted physician. It’s a style of healthcare that’s episodic, reactive, and divorced from patient data.

Of course, healthcare can also be fragmented within well-financed private institutions. It happens when data is siloed and providers don’t communicate.

Imagine now that you’re someone who has recently gained a lot of weight and you’re concerned about your health. You schedule an appointment to talk to your primary care doctor who tells you need to set an appointment with a nutritionist to get a specialized meal plan. A month later the nutritionist realizes that beneath the weight gain is a struggle with anxiety, so you’re sent back to the GP, who then gives a referral to a therapist. The process takes hours of logistical planning and months of waiting. Even when there’s insurance coverage and well-meaning providers, the walls we’ve built in health can keep us from delivering holistic, preventative care in a timely manner.

These challenges are experienced in fragmented healthcare systems all over the world. What makes Mexico unique is that it is home to nearly 130 million people and is the second-largest economy in Latin America. Indeed, it’s a top 15 economy in the world, suggesting that it is uniquely situated for disruption in healthcare. To meet this moment, co-founders Rafael

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and Rodrigo López built Diagnostikare, a virtual-first healthcare platform designed for patients, and built on actionable data, that makes it easy for Mexican employers to provide holistic, preventive healthcare. origin story

Brothers Rafael and Rodrigo López have always been close, but they never thought they’d work together. Rafael, the elder by almost three years, studied information systems engineering and then worked his way up the corporate ladder.

His career in management consulting and corporate strategy took him to the United States and then to London for a time.

Rodrigo stayed in Mexico and became a general surgeon physician, following in the footsteps of the brothers’ grandfather, a renowned gynecologist. In his work Rodrigo experienced both private and public healthcare which gave him a front-row view of Mexico’s broken healthcare system.

“In Mexico we have almost no focus on preventative medicine or the promotion of health,” says Rodrigo.

His frustration about Mexican healthcare would often bubble up at the dinner table when the brothers were reunited over the holidays. Rafael was always ready to dissect the issues, talking late into the night about the need for preventative care and a data-driven approach to health.

They’d dream about what good they could do if they combined their expertise. But it was just talk.

That is, until a serendipitous bout of the flu changed everything.

In 2018, Rafael was living and work-

ing in London when he was invited by the National Health Service (NHS) to take part in a new virtual healthcare initiative. He swapped his local GP for an online patient portal and called it a day.

Then, just a few short months later, Rafael found himself laid up with the worst flu of his life. It was all he could do to log in to the new healthcare platform online and he was ecstatic when he realized he could talk to a doctor and get medications ordered from the comfort of his bed. The illness kept him bed-bound for five days, but when he emerged, it was with a fire in his gut. As soon as he was able, he called up his brother.

“This is happening! This is now a reality in the UK!” he recalls telling Rodrigo.

They talked feverishly about how this virtual care technology, which was becoming a concrete reality in the world’s most developed countries, could be adapted for the Mexican context. They went into heavy research mode, one on the business side and the other in the clinic. ‘What was the right business model for Mexico?’ asked Rafael. For Rodrigo: ‘How did patients feel about virtual care?’ Their early feedback was exciting enough to make Rafael pack his bags and move back home to Mexico. Soon after, Diagnostikare was born, and the two began testing their hypotheses in local primary care clinics and small businesses under Rafael’s watchful eye. under the hood

With Diagnostikare, Rafael and Rogrigo López have built an omni-channel digital health platform aimed at making it startuphealth.com 53

HEALTH TRANSFORMERS (L-R) Rodrigo López, MD, Co-founder Rafael Lopez, CEO & Co-founder diagnostikare@startuphealth.com

easier for patients in Mexico to get highquality care when they need it. The platform uses artificial intelligence to collect and analyze patient data and then suggest the best course of action in terms of how and where the patient should receive care.

Diagnostikare works directly with employers, baking their service in as an employee health benefit. Here’s how it works for patients.

Once a person logs into Diagnostikare on a desktop or mobile device, they’re given a brief questionnaire that covers a basic health history. That process takes about a minute and generates a health profile that can streamline care going forward. Next, the patient has access to a menu of services. If they’re currently feeling ill, they

can work through an online triage tool or choose to talk to a physician straight away. The platform makes it possible for patients to move seamlessly between verticals like primary care, nutrition coaching, and mental health. It also gives them access to an ecosystem of real-world complementary services like medication fulfillment and delivery and lab testing. Lab tests are then interpreted by physicians on the platform and integrated into the patient’s profile, leading to recommendations for the patient’s health.

Diagnostikare is built primarily to address low-complexity, high-incidence acute conditions — low-hanging fruit that when taken in aggregate has massive public health implications. These are the

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daily conditions — like cold, flu, anxiety, depression, and weight gain — where people were traditionally paying out of pocket or forgoing treatment entirely. But Diagnostikare has also partnered with local specialists, like cardiologist and gastroenterologists, for when care needs to be kicked to the next level.

In terms of how they employ physicians, Diagnostikare works like a clinic. They recruit and assess individual providers and then slot them into a shift schedule. This more centralized model for virtual care helps the team control clinical quality and streamline delivery processes. In addition to providing daily patient care, Diagnostikare supplies top-level de-identified business intelligence to employers to better understand the health and wellbeing of their employees. why we’re proud to invest

When we met Rafael and Rodrigo López we were reminded that we invest just as much in the “who” as the “what.”

In this team we find both the principle of complementary unique abilities as well as long-term commitment.

“My side of the business is operations and management and Rodrigo is responsible for putting himself in the patient’s shoes. No one can do that better than him,” says Rafael.

That division of labor and knowledge means that when Diagnostikare hits hurdles, the founders can quickly delegate.

That means faster innovation and a more cohesive team.

We’re also bullish on Diagnostikare because Mexico is in the midst of a leapfrog

moment.

“Mexico in recent years has proven to be a land of opportunity in terms of the digital transformation of almost every industry,” says Rafael. “Fintech has taken off, creating new opportunities for healthcare.”

A key ingredient in this market transformation is the meteoric rise of the internet-connected smartphone.

“You’ve got people who have never been in front of a computer, but they’ve got a smartphone,” says Rafael. “They’re on social media, know how to order food online, and even have a digital wallet for making payments.”

Because people have leaped over personal computers and into mobile phones, it’s possible for healthcare in Mexico to not only become virtual but fully portable, and Diagnostikare is purpose-built for that evolution.

Finally, we’re proud to support the López brothers because their solution has massive health moonshot potential. By making preventive health accessible and by using data and artificial intelligence to scale care, Diagnostikare can address the biggest population health challenges facing the world. If we use new technology to scale healthcare interventions, fighting epidemics like obesity and hypertension, millions of people can live longer, healthier lives.

4 DIAGNOSTIKARE@STARTUPHEALTH.COM

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EyeCareLive Is Making Comprehensive Eye Exams Accessible and Affordable Through AI-Powered Telemedicine After decades in Silicon Valley working on operating systems and cloud computing, Raj Ramchandani decided to focus his knowledge on improving health. Now, he and his team are partnering with J&J to decentralize eye health and make important non-invasive eye exams available to the masses.

Philosophers and poets have called the eye “the window of the soul.” But ask an optometrist and they’ll tell you they’re even more than that; the eyes are a window into your health. According to the American Academy of Ophthalmology, a comprehensive eye exam can give early warning of diabetes, high blood pressure, Lyme disease, and some cancers. (Here are 20 surprising things an eye exam can reveal). All of this from a non-invasive test, no radiation or blood draw required.

Here’s where we run into the first market challenge: not enough people are getting comprehensive eye exams. Can you remember your last exam that went beyond a vision test for wearing glasses? No? You’re not alone. Around 150 million Americans could have benefited from an annual eye exam last year but didn’t get one. Narrowing the focus slightly, according to the CDC, 46 million Americans were at high risk for vision loss but didn’t visit an eye

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HEALTH TRANSFORMER Raj Ramchandani, CEO & Co-founder eyecarelive@startuphealth.com

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doctor last year.

There are two predictable reasons for this lack of eye exams. First: out of sight, out of mind. When our teeth ache or look a bit yellow or are shifting out of position, we call the dentist. But our eyes more or less work — until they don’t. There’s been a lack of education around the importance of eye health and as a result, the majority of people forgo eye exams until they have a visible problem.

The second challenge is cost. Tens of millions of people lack health insurance that covers eye exams which means they have to pay hundreds of dollars out of pocket. If it’s not urgent, or if money’s tight, that exam gets pushed off for another year. The problem is that eye conditions are often silent until they become emergencies.

Even if a person knows they should get regular eye exams, and even if they can afford it, there’s the issue of basic access.

It can take weeks to make an appointment and then they require patients to take hours out of their workday. Again, if you’re not experiencing an eye emergency, these logistical headaches might be enough to push your eye exam off another year.

Into this gap steps Raj Ramchandani, CEO and Founder of EyeCareLive, who is combining new eye exam technology with telemedicine infrastructure to make comprehensive eye exams accessible and affordable. origin story

In 1996, Raj Ramchandani traveled from his home in Pune, India, to San

Francisco to work at Sun Microsystems.

He was put to work on the company’s operating system, but it wasn’t long before he took an entrepreneurial detour. Sun started an ambitious internal incubator program to cultivate startups in the hopes of future-proofing the company. Ramchandani was tapped to help start the program, which ultimately collaborated with over 4000 startups from 50 countries. That experience gave him an education in every aspect of tech startups, and how Sun’s technology fit into the equation. He saw firsthand what ingredients led to a breakout success and what ideas and teams were doomed to fail.

Fourteen years after Ramchandani arrived in San Francisco, Sun Microsystems was bought by Oracle in a now-infamous deal worth $5.6B. He took it as a sign to move on to his next adventure and in 2010 he launched his own cloud computing company, Cumulogic. He ran the company for five years, working with enterprise partners like Citrix, before selling it off.

Ramchandani had played an important role at a legendary tech company, then he’d built and sold his own tech startup.

When the dust settled and he looked around, he wasn’t sure what his next act should be. Then, as luck would have it, it was time for his annual eye exam.

Ramchandani had a special relationship with his optometrist, a man named Dr. Moshe Mendelson. He met him shortly after coming to America and had been seeing him every year for 22 years.

He wasn’t your average eye doctor, says Ramchandani. The long-time Silicon Valstartuphealth.com 57

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ley resident had an insatiable curiosity and was always taking part in clinical trials.

“It’s very unusual for a doctor to be that tech savvy,” says Ramchandani. “He understands the future and what is coming more than any doctor I’ve ever met.”

Each year they’d meet for a routine exam and spend the visit discussing tech, health, and new business models. So when Ramchandani sat down in his exam room after selling off Cumulogic, Dr. Mendelson didn’t waste any time before asking, “What are you going to do next?”

They bounced around ideas about telemedicine, of bridging their worlds of health and cloud platforms. Dr. Mendelson pitched the idea of telemedicine for eye care and Ramchandani’s interest was piqued. Telemedicine was still in its infancy and relegated mostly to primary care. Specialty areas of health were still untapped.

The seed of an idea took root and together, the two decided to build EyeCareLive, a company that utilizes the information from the eye scan to its full potential.

They set out to build a company that uses the best in cloud technology, AI, and telemedicine to make eye exams affordable and accessible.

Ramchandani has always enjoyed his work in tech, but now, he says, he’s found his passion.

“Our belief is that vision care can become more accessible, affordable, and scalable by digitally transforming the industry,” says Ramchandandi. under the hood

EyeCareLive applies a hub-and-spoke

telemedicine model to optometry, with artificial intelligence thrown in to help scale the operation.

Imagine you’re one of the millions of people who needs an eye exam but hasn’t gotten one recently. You walk into your grocery store and see an EyeCareLive kiosk. The sign says you can get a comprehensive eye exam plus a pair of prescription glasses for $79. That’s cheaper than you’d see anywhere else, plus you don’t have to take the time of making a doctor’s appointment.

An EyeCareLive attendant — not an optometrist — walks the patient through the eye exam using industry-leading equipment. The images of the eye are sent to the cloud and made available on the EyeCareLive platform for a remote optometrist to review. Up to this point, the availability of optometrists had been a bottleneck for eye exam services. The decentralized model allows them to be more efficient with their time and talents.

“Now a doctor can scale faster and broader, rather than being tied to one location,” says Ramchandani. “Our platform has been used by thousands of eye care professionals to provide virtual care to over five million patients.”

Once the optometrist dials in remotely, they’re able to operate the equipment if necessary and provide a full eye health report. The patient can walk out with a diagnosis, a prescription, glasses — whatever is needed.

This first phase of EyeCareLive, which has been rolled out at a few retail store locations in the United States, consists of high-quality remote eye exams plus expert

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analysis on the cloud platform. The next phase, says Ramchandani, is to add a layer of artificial intelligence that will review each eye image and automatically flag potential problems not only related to vision but overall health. This will make the reviewing optometrist even more efficient and allow the technology to be scaled affordably. why we’re proud to invest

Over the last two years we’ve watched the mass adoption of telemedicine and virtual health. The first movers in the space have been primary care, urgent care and remote patient monitoring, but now it’s time to expand the technology to all areas of health. Eye health is an important and logical next step for decentralized healthcare and Raj Ramchandani and his team are well-positioned to capture that momentum.

We’re bullish on EyeCareLive because every challenge we’ve listed in this article is going to get much bigger in the coming

years. As our population ages, the need for regular eye exams is going to increase.

According to the CDC, the number of blind and visually impaired people in the United States is going to triple by 2050.

And that’s just one of many sub-populations that will benefit from this service.

Another reason we’re proud to back EyeCareLive is that they’re building the kinds of partnerships they’ll need to scale nationally. Their biggest investor ($6.4M to date) is J&J, who reached out proactively to Ramchandani when they saw their platform in action. For a startup seeking to have a footprint in high-traffic retailers nationwide, institutional partners like J&J are essential.

Finally, we’re excited to back Ramchandani because he’s building the kind of scaleable health platform that could eventually move the needle on the Access to Care and Cost to Zero Health Moonshots. By building AI into the eye exam review process and decentralizing physicians (which are the most expensive piece of the exam equation) the cost of eye care will get cheaper and it will be available in more places. It doesn’t take much imagination to envision these kiosks in stores around the world, helping millions of people manage their eye health quickly and affordably.

“Our belief is that vision care can become more accessible, affordable, and scalable by digitally transforming the industry,” says Ramchandandi.

Join us in welcoming Raj Ramchandani and the EyeCareLive team to the StartUp Health portfolio.

4 EYECARELIVE@STARTUPHEALTH.COM startuphealth.com 59

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Eczemadoc Is Giving One of the Most Pervasive Skin Conditions a Digital Health Upgrade Three physicians used their own battles with eczema as a catalyst to build the world’s first end-to-end digital health app for the 550 million people around the world who suffer from the condition. By allowing symptom tracking, advanced analytics, and personalized coaching, the team believes that they can make eczema a problem of the past.

ACCESS TO CARE MOONSHOT VINTAGE: 2021/Q4 ECZEMADOC.CO.UK

Eczema. It’s that frustrating, chronic skin condition characterized by red, dry, itchy skin.

It’s a common problem, perhaps more common than most people realize. Around 550 million people around the world suffer from it. And they suffer mostly in silence.

Why suffer in silence? Because it’s itchy skin, eczema isn’t exactly grabbing head-

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HEALTH TRANSFORMERS Dr. Haroon Ahmad, CEO & Co-founder Dr. Noreen Akram, CMO & Co-founder Dr. Niall Jawad, CPO & Co-founder eczemadoc@startuphealth.com

lines or demanding massive R&D investment. When people tell their doctor they have dry, itchy skin, they’re usually given a laundry list of creams and home remedies to try, in the hopes that one will work. It’s a haphazard trial-and-error approach lacking in data that leaves patients frustrated and disillusioned with healthcare. After a few attempts at remedies, most people just settle in for their life as a chronic eczema sufferer.

Eczema sufferers experience a flare-up every one in three days, and for the most part, they don’t know why. Eczema flareups can be caused by anything from stress to diet to sleep to weather. Because it’s so hard to predict when they’ll have a bad day, patients are always on the back foot, reacting to the problem instead of preventing it.

But it’s more than an annoyance. Eczema goes deeper than the skin, often impacting patients’ ability to sleep, work, and socialize. People with this condition can get to a point where they just don’t want to leave their home for fear of a flareup. They’re uncomfortable, they’re embarrassed, they’re anxious. Sadly, most people accept their fate, assuming nothing will ever improve.

As eczema sufferers and physicians, Ha-

roon Ahmad, Niall Jawad, and Noreen Akram had a unique lens into the problem. They’d become disillusioned with the management of eczema and other chronic conditions. Today, with Eczemadoc, they’re creating a tech-enabled, data-driven platform to help people with chronic skin conditions get healthy skin and reclaim their lives. origin story

Haroon Ahmad has suffered from severe eczema for as long as he can remember. His flare-ups were highly visible, causing red, bumpy outbreaks on his face, neck, and arms. He’s naturally outgoing by nature, but the fear of a visible flare-up pushed him into the shadows. In fact, he was a grown man before he felt confident enough to speak in public.

While studying at medical school he was able to finally get to grips with the condition. He was pleased to discover that by paying closer attention to his eczema and following evidence-based practices, he was able to reduce the problem significantly. It was during this period that he met his co-founders Akram and Jawad who had also suffered from the condition.

Something shifted for them during their third year of medical school. It was during their first rotation in a hospital that they began to see the system’s flaws and how senior doctors were struggling under the weight of a bureaucratic system.

They went from eager, aspiring doctors to individuals whose eyes had been opened to the shortcomings of the healthcare system.

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traditional mold,” says Ahmad. “We saw a lot of problems in health that were just being passed by. There was talk about preventative health and patient-centric care, but we weren’t seeing that in action.”

Casting about for answers, Haroon decided to get a management degree, Jawad taught himself to program, and Akram worked to validate a medical device as part of a neuroscience degree. That’s when things clicked into place. These experiences tapped into their natural entrepreneurial bent and shifted their mindsets.

Where before they felt like disillusioned victims of the healthcare system, they were now inspired to change healthcare from the inside out.

Taking this mentality into the final year of med school, they quickly honed in on a challenge to address: eczema. It was impacting hundreds of millions of lives, benefited from specialist knowledge, and had been neglected in the digital health revolution.

Their back-of-the-napkin concepts about a tech-enabled eczema platform materialized quickly and it wasn’t long before the three were winning pitch competitions, gaining early financial support from their university, and being backed by reputable academic institutions. Those early wins gave the co-founders the confidence they needed to dive in fully and launch Eczemadoc whilst still working as junior doctors. under the hood

Ahmad calls Eczemadoc “the FitBit for eczema management.” What he means is that the app-based platform enables pa-

tients to track their condition easily, understand it in more detail, and manage it more effectively.

It works like this: The patient opens up the Eczemadoc app and is prompted to journal about their skin condition. It starts with a 30-second survey, questions like, “Where is eczema affecting you today?” “How severe are your symptoms?” and “How have you been sleeping?”

The data captured on the app is then used to provide bespoke insights and analysis to help patients understand when they have flare-ups and why. Perhaps their flare-ups correlate with poor sleep or stressful situations. That mapping helps the patient move from reactive to proactive management.

According to Ahmad, the team has amassed the world’s most comprehensive content library for eczema care. They analyzed more than 200 academic papers and distilled them into around 100 lessons.

That enables them to push out bite-sized wisdom about what causes eczema and how to manage it, based on the individual patient and situation. When it comes to eczema, knowledge truly is power. Research has shown that just providing good knowledge to patients can reduce flareups by as much as 45% and improve quality of life by 78%.

Another important piece of the platform is habit change. Eczema can cause an addiction to itching and, conversely, an addiction to itching can cause eczema. It’s termed the itch-scratch cycle, and studies have shown that 70% of the time that an eczema sufferer feels the urge to scratch, that urge is habitual and not based on a

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change in their skin. The Eczemadoc team realized that if they could target the itching habit, they could cut off the skin irritation before it starts. So Eczemadoc has built a 30-day habit reversal program called ItchX that helps people break their scratching habit. Research has shown that this methodology can eradicate chronic eczema in 90% of patients.

The next phase of development will allow the company to leverage the data collected to conduct teledermatology consultations, introduce advanced tracking capabilities, and eventually predict the cause of eczema flare-ups to deliver truly preventative therapy. why we’re proud to invest

When we first met Haroon, Noreen, and Niall, we knew that they had a special combination of expertise and personal knowledge. They were the right team for this project. As life-long eczema sufferers, they knew the subject intimately. They’ve dedicated years of medical training into reading eczema literature, allowing them

to empathize with their end users. They also have a diverse set of skills that will allow them to bring the company to market sustainably.

We’re also proud to back Eczemadoc because they’re bringing the best of digital health to a massive community of patients who have, until now, been suffering in silence. Dry, red, itchy skin flare-ups might seem like a minor ailment to those who haven’t experienced it, but the condition harms sleep, stunts growth, and causes anxiety, depression, and loneliness.

The team has proven that eczema is treatable with the right data and education, and this global community deserves access to that care.

Finally, we’re bullish on Eczemadoc because the time is right to bring every specialty area of health into the modern world of virtual, data-driven, tech-enabled care. Thanks to COVID-19, we’ve experienced a revolution in virtual care and remote patient monitoring. The next phase is to extend these benefits to more niche communities of patients, with specialized tools and understanding. Eczema is one more important piece of this digital health evolution and will help millions live fuller lives.

We are excited to see how Haroon, Niall, and Noreen will open up access to care for millions of eczema sufferers and use their data-driven approach to improve dermatology writ large. Join us in welcoming them to the StartUp Health portfolio.

4 ECZEMADOC@STARTUPHEALTH.COM

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Neuralert’s First-in-Class Wearable Detects Stroke Quickly So Brain Function Can Be Saved It can take five hours or more to detect a stroke when a patient is in the hospital, a delay that can result in debilitating brain damage. Neuralert’s easy-to-deploy wearable uses arm movement to detect stroke in as little as 15 minutes.

When a clot blocks the flow of blood to a person’s brain, things go downhill quickly.

We call this a stroke, and it can cause brain damage within minutes. It’s the number one cause of disability in the United States and the number three cause of death. More than a billion people living in the world today will have a stroke in their lifetime. Chances are, you know someone who’s suffered a stroke, or you will.

Fortunately, when a person is experiencing a stroke, they get a few warning signs.

They might have one side of their face go numb and droop, have trouble speaking, or struggle to move their arms in a coordinated way. Today, many people are trained to recognize these signs and when they see them, they call a doctor or head straight to the emergency department.

In stroke care, there’s a saying that “time is brain.” In emergency medicine it is taught that every 10-minute delay between arrival at the emergency department and starting stroke treatment can cost a patient eight weeks of healthy life. Thankfully, there are

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HEALTH TRANSFORMERS Eric Corkhill, CEO Steven Messé, MD, Co-founder James Weimer, PhD, Co-founder neuralert@startuphealth.com

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amazing treatments available for stroke, and most emergency departments follow strict, swift protocols for getting these patients the care they need. Patients who come into the emergency department with a life-threatening stroke are often saved, with many able to go home the next day with no ill effects.

Now, here’s the rub. As many as 17% of all strokes take place while patients are already in the hospital. You might think that this would put them at an advantage for stroke detection because they’re surrounded by healthcare providers and medical equipment. It turns out that the opposite is true. Because a patient in the hospital is lying down and hooked up to machines, the usual signs of stroke are much harder to detect. It’s nearly impossible for rounding nurses, who are already over-extended, to detect facial droop or speech difficulty if the patient is masked and intubated.

The result is that according to one study in the United States, the median time to detect a stroke in a hospital setting was five hours. In another study out of Montreal, the median time was 10 hours. When “time is brain” and two million brain cells die every minute during a stroke, this is a serious problem. Enter Neuralert, a new technology designed to detect in-hospital stroke within 15 minutes, so patients can get life-saving treatment started in time. origin story

Neurologist Steven Messé was tired. He was tired of being called into his hospital at the University of Pennsylvania only to find a patient with preventable brain dam-

age from a stroke. He knew that if he’d discovered their stroke just a few hours earlier, he could have treated it and discharged them home healthy. Instead, they were going to need six months or more of rehab to relearn how to speak and walk.

He had the seed of an idea. Since asymmetrical movement of the arms is a key indicator of stroke, what if he could use a wearable on the wrist to detect this motion? He teamed up with James Weimer, a PhD in biomedical engineering and signal processing, who had developed an algorithm to do just this kind of work.

Prior efforts to use arm asymmetry to detect stroke had failed because there are multiple causes of arm asymmetry such as favoring one arm over another while eating or talking on a phone. That creates a high false alarm rate. Dr. Weimer developed an algorithm that interprets asymmetry movements in order to weed out these false alarms and understand when a stroke is actually occurring.

The two collaborators started their clinical validation journey at the University of Pennsylvania in 2019, with a study of 200 bed-bound patients at risk of stroke. They used the study to refine the algorithm and make sure that it could catch stroke the way they expected. Then, in 2021, in a different cohort of patients, they refined the algorithm even more, getting down to a 15-minute detection time.

At this point, Drs Messé and Weimer knew they were on to something big, and that they’d need help scaling it. So they brought on serial entrepreneur and seasoned CEO Eric Corkhill. Corkhill has been in digital health since 1980 and startuphealth.com 65

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has been involved in startups since 1997.

Asked why he was so interested in the opportunity, Corkhill had a quick answer: “1.2 billion living today will have a stroke.

The ability to help that many people gets me up in the middle of the night, thinking about how we can get to market faster and help more people. This isn’t just a startup, it’s a mission.” It’s also very personal: Corkhill’s mother-in-law died of a stroke.

Neuralert is focusing on a very specific initial market, which is patients coming out of high-stroke-risk cardiovascular surgery or procedures. There are around two million of these procedures done in the US each year, and some of the procedures have a stroke incident rate as high as 10%. To reach these patients, Neuralert is focusing first on Joint Commission accredited stroke centers. They have the knowledge and resources to provide topquality stroke care, if they are able to catch in-hospital strokes quickly enough. These centers are good early partners because they also quickly comprehend the problem and the costs associated with delayed stroke detection. under the hood

The Neuralert is a sleek black device that looks like a Fitbit but without the strap. Instead, the main hardware is secured to the patient’s wrist using a traditional hospital bracelet. That means the nurses don’t have to learn new hardware or have additional supplies lying around.

They can put it on a patient’s wrist and walk away.

Where some medical devices need to be worn for days, weeks or longer to es-

tablish a personal baseline, the Neuralert starts detecting strokes within 15 minutes. When it comes to training, since the last thing they wanted to do was add a burden to the nurses, Neuralert’s motto is “five and bye.” If Neuralert can’t get a nurse up to speed with how to strap on the device and understand the alerts in five minutes, they’ve failed, says Corkhill.

When the Neuralert system detects a stroke, it automatically sends a secure text to assigned staff members, alerting the nurse to immediately perform a neurological check. Neuralert is currently able to detect a stroke in as little as 15 minutes and has a median false alarm rate of one per day. That factor is crucial for alarmfatigued nurses and staff. By comparison, the gold standard for heart monitoring gives a false alarm three to five times a day.

“When there’s only one false alarm a day, the nurse is going to pay close attention when the device goes off,” says Corkhill.

Under the normal care paradigm, when a nurse suspects a stroke, they have to make a decision as to whether to contact the on-call neurologist. This can be a difficult call to make, especially if the stroke signs are less than clear, and it’s the middle of the night. The Neuralert device offers a way to support the nurse’s assessment, and with such a low false-positive rate, the nurse can have confidence in their decision to alert the on-call physician.

Neuralert comes with dashboard software that allows nurses to see all the devices currently in use, who they are assigned to, and their associated activity and battery life. Currently the device and alert

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Neurologist Steven Messé was tired. He was tired of being called into his hospital at the University of Pennsylvania only to find a patient with preventable brain damage from a stroke. He knew that if he’d discovered their stroke just a few hours earlier, he could have treated it and discharged them home healthy. Instead, they were going to need six months or more of rehab to relearn how to speak and walk.

operate entirely independently of other hospital systems, but in the future, Neuralert will send its signal via bluetooth to a central hub in the patient’s room which is part of the bedside monitor. The data will flow seamlessly into the electronic health record. why we’re proud to invest

When we met Corkhill and the Neuralert team, it was immediately clear that this is all about impact. Everyone has a story of a loved one or friend who has been impacted by a stroke. These are mothers, fathers, sisters, and brothers who can either continue living healthy lives or be severely disabled. If the Neuralert team succeeds at scale, they can prevent tens of millions of people from a loss of independence, quality of life, or even death. What better mission could a startup be on?

We’re proud to back a team that has

gone the distance in terms of clinical validation. They’ve spent years conducting studies and publishing peer-reviewed papers on in-hospital strokes, and in refining their algorithm. Their next step is FDA approval. Because they are the first to use asymmetry on the wrist to detect stroke in this manner, they’re going down the de novo path with the FDA beginning in early 2022. They’ll conduct a study at three different hospitals, ranging from academic to community, using the Neuralert bands to detect stroke with real patients. The study will take up most of 2022 and, if everything goes as planned, they’ll be buttoning up their FDA approval in 2023.

Finally, we’re excited to back Neuralert because it is health moonshot entrepreneurship at its best. Co-founder Dr. Steven Messé saw a terrible problem — people becoming disabled from strokes that were treatable. So he combined his extensive neurology experience with an expert collaborator in signal processing, to help solve the problem, and created a life-giving device that never existed before. With commitment, capital and collaboration, the Neuralert team can change the world.

That’s a journey we’re proud to get behind. Join us in welcoming Eric Corkhill, Dr. Steven Messé, Dr. James Weimer, and the Neuralert team to the StartUp Health family.

4 NEURALERT@STARTUPHEALTH.COM

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Medi-Ops Is Upgrading Hospital Transport Logistics, So Blood, Organs, and Patients Arrive on Time, Every Time Rylan Stone was working as an EMT when he witnessed the inefficiency and waste in the healthcare transport business. Now, with custom software and a network of contractors, he’s saving lives and lowering costs.

Much has been written about the front door of the healthcare system and its implications for healthcare cost and quality.

But what about the foundation that keeps that front door standing tall? In healthcare there’s an unseen logistics infrastructure that keeps pharmacy shelves stocked, medical instruments clean, and a thousand other things every hour of night and day. Some parts of this infrastructure operate smoothly; others feel held together by bubblegum and string.

Take, for example, a patient who needs a blood transfusion in the middle of the night. The blood is across town at a blood bank. How does that precious cargo arrive where it is needed in a timely manner? In most facilities, a medical tech is tasked with calling an ambulance company that is on contract with the hospital. Then, after a few minutes or a few hours, a couple of EMTs arrive in an ambulance to make the drop.

Here’s the problem. The tech ordering the

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HEALTH TRANSFORMERS Rylan Stone, CEO & Founder mediops@startuphealth.com

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blood has too little information to make a smart transport decision. One, they don’t have visibility on transport options. Do they need a helicopter, an ambulance, or would a sedan do the trick? Two, they don’t see transport availability. It could be that one ambulance company is backed up by three hours while another is standing by. Or, perhaps there are so few ambulances on call that pulling one out of rotation for a non-emergency blood transport would leave critical patients in danger.

They also don’t have a way to see and compare pricing. A 10-mile transport of a blood product in a full lights-and-siren ambulance might take about 10 minutes yet the cost could be upwards of $3,000.

Bottom line: the techs are ordering what can be a very expensive and resourceintensive service without the data they need to make smart decisions. And, as it turns out, all the same problems apply to transporting organs for donation, surgical tools, and even patients themselves.

Into this gap has stepped Medi-Ops,

which is applying a tech-enabled supply chain approach to hospital transport.

Under CEO Rylan Stone, they’re helping hospitals make smarter, more cost-efficient decisions, so that life-saving deliveries arrive on time. origin story

Rylan Stone wasn’t your typical high school student. When he was 17 he enrolled in a community college near his home in Denver, Colorado, to become an EMT. Barely able to drive, he was by far the youngest person in the class. He didn’t know where it would lead, but he knew he wanted to help people, and fighting fires seemed like a good place to start.

When he was 18, Stone began riding all over Denver with a city EMS group. He met people in their hardest moments and had to grow up quickly.

“It was a lot, doing it young,” says Stone.

“I wouldn’t necessarily recommend it.

The stuff you’re exposed to is really hard.”

But the upside of being the young

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guy on the ambulance squad was that he didn’t take old ideas for granted. When he looked around and saw how broken and inefficient the EMS logistics system was, he immediately wanted to fix it. That came to a head one day when the team was called to transport blood to a hospital.

Whenever a hospital needed a blood delivery, Stone’s EMS team would be called up to make the drop. The process would tie up two trained EMTs and a full ambulance. Not only was that expensive, Stone realized, but he knew that every minute his team was driving this small box of blood across town they weren’t in the community, saving lives. He looked at the container of blood sitting in the back of the ambulance and an idea formed. He could transport that blood in an SUV faster and cheaper.

And so, at 18 — still in high school — Stone registered a company called MediOps and dubbed himself Director of Operations. Then he petitioned the State Patrol for permission to put lights on his Chevy Equinox SUV. They never asked for his age, and once they saw he’d developed all the necessary safety protocols, they gave him the go-ahead. Stone wired up the lights himself, added some MediOps decals to his car, and it was official.

Next, Stone began bidding on hospital transport contracts. It took him 10 months of daily emails, phone calls, and letters but eventually he landed a 30-minute meeting that resulted in the company’s first contract. He started taking calls for blood transport within the week.

Medi-Ops was operational.

From that humble beginning Stone has

grown Medi-Ops to an operation that can transport blood, organs, and patients across the country by car, ambulance, helicopter, or plane. Most importantly, they’re developing the software necessary to knit the system together, making transport predictable, trackable, and efficient. under the hood

When a hospital tech needs to order a hospital transport, whether it’s a blood product from a local blood bank or an organ from across the country, they pull up the Medi-Ops system and plug in their request. Medi-Ops receives the request and matches the needs to the available resources. Which vehicle or operator would be best suited to the request at hand?

What delivery method would be most effective? Those questions get handled on the back-end so that the hospital dispatcher gets the most efficient option.

The seemingly simple task of matching the right vehicle to the right job can save a lot of money. Remember that 10-minute ambulance trip that could cost upwards of $3,000? At Medi-Ops, doing the same trip in an SUV costs around $300. The same logic goes for transporting patients.

If they’re paying $250 for a wheelchair van when all they needed was a Lyft, they can save hundreds of dollars. The next evolution will be for Medi-Ops to use artificial intelligence to automate this vehicle matching process.

Since they’re often carting precious specimens, like a heart for transplant, Medi-Ops is integrating into their software the ability to track the shipment’s temperature. So not only does the dispatcher

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and receiver see that the package is on the move, but they have confidence it’s safe and secure.

One important function of the MediOps system is its ability to connect smaller transport companies into one network.

There are thousands of mom-and-pop companies around the country that operate wheelchair vans and ambulettes. Each one is a unique business with its own hotline, rates, and rules. That makes for a very disorganized market.

“That’s good for us, because now we’re connecting all of these people,” says Stone.

“A small operator with two wheelchair vans can’t service a whole nursing home, but they can service two or three people a day. A nursing home doesn’t want to call 12 different companies to get one patient moved. The more operators there are, the more we can pull from.”

In the end, Medi-Ops is offering a modern, tech-enabled logistics framework — not unlike what has been rolled out successfully in other supply chain sectors — and tailoring it to the unique needs of the hospital system. why we’re proud to invest

We’re proud to back Medi-Ops because they’re saving lives, plain and simple. Under the old logistics framework, blood products had a 45% successful delivery rate. That means that nearly half the time that blood was shipped to someone in need, it didn’t arrive on time, or something happened in transit to compromise the package. By applying their datadriven framework, Stone estimates that the blood they’ve transported has saved

around 1,100 lives this year alone.

We’re also excited about Medi-Ops because they’re shining a light into an area of healthcare that had been siloed and data-poor for a long, long time. To bring efficiency and interoperability to the healthcare system, we have to operate on good data, delivered at the right time, in the right way. That means bringing techenabled solutions not just to the high visibility, front doors of healthcare, but to the foundation and structure as well.

Finally, we’re proud to back Rylan Stone because he thinks like a Health Transformer. Stone is barely old enough to order a beer at a bar, yet he could, with a phone call, charter a plane to carry a patient to an emergency heart transplant.

His youth is an asset. We need Stone, and other brilliant young entrepreneurs, to help identify what’s broken in healthcare because they aren’t tied to old ways of thinking. They aren’t satisfied with the status quo of inefficiency and waste.

They know we can do better, and have the energy and drive to create that better future. Stone is just getting started on his journey, but his mindset is exactly what we need to keep reimagining health and healthcare delivery.

We are excited to see how Rylan Stone and his team at Medi-Ops re-imagine hospital logistics and transport, saving lives and lowering the cost of care. Please join us in welcoming them to the StartUp Health family.

4 MEDIOPS@STARTUPHEALTH.COM

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MEET THE HEALTH TRANSFORMERS

Synapsin [Stealth] Is Developing a Novel Pharmacuetical for the Treatment of Alzheimer's Alzheimer's Disease (AD) is a progressive and fatal brain disorder that affects around 36 million people worldwide. That is expected to double over the next 20 years. Currently there are treatments to temporarily improve memory and cognition, but there are no effective treatments to prevent or cure the disease.

After decades in academic research in neurology and neurodegenerative diseases, Dr. Denis Dorsey discovered a compound called SPI-001. Working with Mark Kindy, PhD, Dorsey showed in pre-clinical animal research that SPI-001 held potential as a treatment for degenerative brain diseases. While Synapsin is still in stealth, they're currently building the team and raising the funds required to take the next steps to clinically validate their approach.

BRAIN HEALTH & ALZHEIMER'S MOONSHOT VINTAGE: 2021/Q4 CURRENTLY IN STEALTH

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HEALTH TRANSFORMERS Denis Dorsey, PhD, President & CEO Mark Kindy, PhD, Co-founder synapsin@startuphealth.com

Ready to Transform Health With Us?

StartUp Health’s investment platform fuels health moonshots To the Health Transformers of the World: We created StartUp Health to help you, the entrepreneur, thrive, scale and ultimately achieve health moonshots.

StartUp Health is investing in a global army of Health Transformers to achieve 12 Health Moonshots. Since 2011, we have invested in over 390 innovative health companies, and we’re just getting started.

Entrepreneurs, learn how to apply to StartUp Health at startuphealth.com/gettingstarted Investors, learn how you can back a diverse portfolio of private health innovation companies at healthmoonshots.com

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After an IPO, launching at-home test kits, and acquiring a genomics company, Nightingale is poised for global expansion.

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FEATURE

Nightingale Is Reinventing Preventative Health One Blood Draw at a Time Nightingale’s health moonshot is as big as they come. The Finnish startup, backed by StartUp Health in 2016, is helping people predict future disease risk so they can change the course of their health before it’s too late.

To do this, they’ve designed a way to analyze blood samples that pulls 250 times more data from that sample than a typical test. They then use artificial intelligence and machine learning to correlate that data with future disease risk. Finally, they serve that information back to the patient (not just their doctor) in a consumer-friendly app that makes it easy to take action. The icing on the cake? They’ve put it all together into a package that’s affordable enough for most people to buy, with plans to get even cheaper.

Recently, Nightingale took three major strides forward to expand this vision. They IPO'd on the Finnish Nasdaq (HEALTH. HE), which gave them capital to

scale globally. They rolled out at-home testing kits so anyone can benefit from Nightingale’s disease prediction regardless of their location. And they acquired Negen, a genomics company that will allow them to bake genetic information into their app and provide people with even more personalized health assessments. It’s been a sevenyear journey so far, with €50M invested, but according to CEO and co-founder Teemu Suna, this is Nightingale’s breakout moment. They’re ready to scale and begin seeing the global impact that they dreamed about from the beginning.

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Most people love the idea of preventative health. The trouble is that in order to prevent bad things from happening, you have to arrive before they occur. Today’s health paradigm is almost completely reactionary. We don’t think about a disease until we’ve tested positive for it. For that reason, Nightingale designed their firststartuphealth.com 75

“ENTREPRENEURSHIP IS ABOUT MAKING THE INVISIBLE VISIBLE. AT NIGHTINGALE, THE ‘INVISIBLE’ IS BUILDING A NEW PREVENTATIVE HEALTH SYSTEM GLOBALLY. MOST PEOPLE DON’T SEE IT. BUT I SEE IT, AND WE WILL MAKE IT VISIBLE.” Teemu Suna, CEO & Co-founder

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in-class blood test for healthy people, not those who are already sick.

“Take type II diabetes as an example,” says Nightingale CEO Teemu Suna. “It develops over decades, not overnight. And all the while, the body is giving signals at a molecular level that it is heading towards diabetes. Typically, a person will begin treating their type II diabetes when they test positive for the disease, not a moment sooner. But you can’t prevent anything if your only health metric is the test that tells you that you’re already positive.”

“A person can take the Nightingale test and discover that their risk of getting type II diabetes in the future is elevated. But this isn’t judgment day, it’s observation about how your lifestyle is treating your body. Then, armed with this information, you may decide to take action. Perhaps you improve your diet or begin to exercise. You can try this change for a month or two and then come back and test your blood again with Nightingale. That will show how the molecules in your body have reacted to the changes in your lifestyle. When you know the future risks, you can take action.”

For decades we’ve known that lifestyle choices contribute to chronic diseases.

There are literally millions upon millions of articles about eating healthy fats, which diet is good for your heart, and how many times a week you should get your heart pumping. But for the most part, we make all of these life adjustments in a vacuum.

Besides basic vitals like weight and blood pressure, we have little to no idea if our life changes are making us healthier. That’s where Nightingale is changing the game, says Suna.

“With Nightingale, really for the first time, you can know that your lifestyle changes are actually helping you. This is how you can learn about your own body, how you can optimize your future health trajectory. You can change the course of your life. A big part of health is in your hands. Not everything, of course, but a lot of health comes down to behaviors we can control.”

“People often think that a lifestyle intervention like this means they’re going to have to quit doing the things they love, like eating hamburgers or drinking beer. It’s not that black and white, and this is not what Nightingale is saying. I experienced this personally. I did the Nightingale test and saw that my lipid profile wasn’t optimal.

So I experimented with eating fewer carbs.

That improved my lipid levels. I didn’t know exactly what would be effective, but I did something manageable – eating fewer potatoes or having less rise – and my numbers improved. I just tweaked my lifestyle and measured again, and it worked. That taught me about my own body.”

In order for Nightingale to be able to pull so much data out of a single blood sample, and then correlate it with future disease risk, their molecular measurements have to be incredibly precise. The way it works is that they put each blood sample inside a high-frequency magnet, a technology called nuclear magnetic resonance or NMR. In the magnet, the molecules in the blood start to resonate. Because each of the molecules has its own unique resonance, and because all of the molecules are resonating at the same time, Nightingale can capture the signal from multiple molecules

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FEATURE: NIGHTINGALE'S NEXT MOVE

at once.

Next, they use their AI algorithms to transform that resonance signal into units that are useful in healthcare. Once they do that translation, the molecules finally start to mean something and Nightingale can begin to correlate them with health outcomes. The final health outcomes piece, where disease risk is predicted in logical, trackable numbers, is being built out by analyzing some of the world’s largest biobanks. The end-to-end nature of Nightingale’s platform is complex, but it’s holistic by design, says Suna.

“When we think about biotechnology, the challenge is in creating real value for people. Often biotech companies don’t think about that. They build the technology and that’s it. Our vision from the beginning has been to create an end-to-end solution. You have to have the world’s best biotechnology, but that’s not enough. You have to be able to process and communicate the information that helps people live healthier lives. The complexity of all the different components is kind of incredible.”

When Nightingale first launched their end-to-end blood test technology, they weren’t sure how people would respond, because it was so new. They started by offering it to a limited group in Finland, where they’re based. They wanted to test and see how people would respond to having more holistic preventative health information.

“We got a lot of people challenging us saying that people who are well won’t change their behavior,” says Suna. “They said people aren’t motivated unless they’re sick. We didn’t believe that. We believed

that people weren’t motivated to stay healthy because they hadn’t been given the right tools. So we wanted to test this hypothesis.” So they built a health clinic in Helsinki and started to sell the service.

They got a couple thousand people to try Nightingale, and the results more than confirmed Suna’s suspicion.

“The striking thing, out of many findings, was that people who we might have written off as lost cases made significant improvement. Half of that group, when they returned for a second test, made a major improvement and changed their risk levels. We got the group that is the least likely to change their lifestyle to change.

They were motivated by having the right information and right tools.”

Nightingale has been on a seven year journey of establishing and validating their technology, but it’s clear that they’re in a transition moment. In 2021, Nightingale took a major step forward by going public on the Helsinki stock exchange raising about €115M. The purpose of the raise, according to Suna, was to take their platform and scale it globally so that millions of people can benefit.

“We are building a global preventative health system. It’s such a big mission that we need to be well capitalized. We need the resources to bring this technology all around the globe. That’s why we went public. All the money we raised went into future growth.” Nightingale currently has labs running in Japan, the US, the UK, and Finland. They’ve launched their preventative health offering in Finland and Japan.

The company has also released an athome testing kit that makes their technology much more accessible. The move fol-

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lows the booming at-home testing trend part of your genetics. Your genes represent of companies like EverlyWell, but with a static data that we can measure once and major twist. incorporate into your health picture for “Companies are opening up the at- your whole life. This provides a sort of finhome testing market, but there’s a big dif- gerprint for your future health. But it is not ference. They are relying a judgment that you will on traditional blood be doomed to have a testing labs and technoldisease. The largest part IN 2021, NIGHTINGALE ogy. The breakthrough of your risk is defined by WENT PUBLIC ON with Nightingale is that your lifestyle. When we THE HELSINKI STOCK with our technology, acquired Negen we were you get our holistic, preable to combine these EXCHANGE, RAISING ventative analysis. We two things: your genetic ABOUT €115M, didn’t build Nightingale risk and your lifestyle TO TAKE THEIR primarily for doctors. risk. That allowed us to PLATFORM AND SCALE We built it for ordinary understand a person’s people. The current difuture risks, as well as IT GLOBALLY. agnostic testing industry what kinds of actions gives results in a kind of you could take to lower scientific code that no your risk levels. There normal person can understand or act on. are many companies that do genetic testing We measure many of the same biomark- and many that do blood testing. But we’re ers, but we deliver it in a way that you don’t putting these two things together in a new have to be a medical professional to get the way that’s groundbreaking.” value from the measurement. It needs to be The next major hurdle for Nightingale is understandable and actionable.” accessibility. The test is already relatively afIn early 2022, Nightingale acquired Ne- fordable – around €100 – but Suna’s vision gen, a Finnish company that specializes in is to make the price even more accessible. genomics. The goal is to use Negen’s tech“Our goal is to push the price of this adnology and framework to begin incorpo- vanced biotechnology down. We believe rating genetic data into the Nightingale that the value is created when this technolmobile app within the year. Suna sees this ogy is brought to the masses. This is one of as a critical next step in helping people our breakthroughs, that we’re able to bring understand their bodies and their health this technology to people at scale. Allowtrajectory. ing people to access this state-of-the-art “The Nightingale technology is mea- technology in the home is quite new and suring the dynamic state of the body, how exciting.” your lifestyle is manifested in your blood.

When you consider Nightingale’s future But, as we know, there are also aspects of prospects you can’t divorce them from the your health that you can’t control, that are company’s origins. When asked if there are startuphealth.com 79

FEATURE: NIGHTINGALE'S NEXT MOVE

any advantages to launching a global health startup from Finland, Teemu Suna smiles.

There are a few advantages to launching from a smaller country, he says.

“For one, since we’re a nation of around five million people, the only strategy is to go global. If you want to have impact, you have to plan for the international market.

That’s a massive benefit. We built Nightingale from the beginning so that it could address global challenges, not just those in Finland. That infuses how we think about software, pilots, partners, everything.”

“Also, people in Finland have a ‘go through the rock’ mindset. We call it ‘Sisu’ and for an entrepreneur it means that the challenges are just made to be solved. And there are plenty of challenges. When we go to raise funds internationally and we tell people we are from Finland, we are immediately the underdog. We know that, so we have to compensate by making sure our product and presentation is incredibly

good. We know we have to be more prepared than the competition.”

“I’ve been asked many times what entrepreneurship is. I’ve tried to summarize it, and I like to say that entrepreneurship is about making the invisible visible. At Nightingale, the ‘invisible’ is building a new preventative health system globally.

Most people don’t see it. It’s invisible. But I see it, and we will make it visible.”

“I believe that this preventative health thinking will revolutize primary care everywhere. And why shouldn’t every human benefit? If the price point is low enough, if it gives tools to people to take better care of themselves, and there are no side effects, why should anyone not benefit? It just makes sense in the big picture. The world is moving towards this direction, and Nightingale’s ability to accelerate the trend and make this happen is incredibly exciting.”

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NIGHTINGALE@STARTUPHEALTH.COM

STARTUP HEALTH MOONSHOTS IMPACT FUND MEET THE INVESTORS

ESTHER DYSON

StartUp Health Investor & Advisor

Join investors like Esther Dyson, Lee Shapiro, and Glen Tullman in backing the StartUp Health Moonshots Impact Fund. This fund, launched in 2021, makes it easy to back a diverse portfolio of early-stage health tech startups. healthmoonshots.com

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meet the investors

A Growing Community of Health Moonshot Investors Is Backing StartUp Health's Impact Fund Each issue we interview new investors in StartUp Health's Moonshot Impact Fund to learn what drives them, and why they believe in backing a diverse portfolio of Health Transformers. This issue we're featuring: STEFANO BINI, MD JON KAPLAN ASH NASHAD, MD ROB ODELL IRA BRIND

Dr. Stefano Bini is an award-winning clinical researcher and educator based at UCSF in San Francisco.

--Learn how you can join investors like Esther Dyson, Lee Shapiro, and Glen Tullman in backing the StartUp Health Moonshots Impact Fund at healthmoonshots.com

StartUp Health: Is there a particular pain point that you want to see entrepreneurs solve in the near future that you haven’t seen addressed?

Dr. Stefano Bini: Where I see the biggest appetite for solutions is around documentation and health records. From

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a physician’s perspective, this is the biggest pain point and the principal cause of burnout. Anybody who’s running a group of trained physicians knows it’s the amount of time that is being spent on clinical documentation that’s killing them, literally driving them into retirement and to leave what should be the most gratifying of all professions. Think about clinicians, nurses, physicians assistants — the entire healthcare team — as being a limited resource. For example, in the USA, we’re going to be 11,000 doctors short in the next five years. COVID-19 exacerbated that shortage in many ways. So now you have this incredibly valuable but limited resource that is hard to replace (it takes a decade to train a doctor), and you’re taking the total accessible time for that resource and cutting it in half. At least 30% of the clinical time is spent documenting. Documentation also takes up much of doctors’ free time and emotional bandwidth (it gets done at night and early mornings, taking time away from family and self care). All this time would otherwise be spent on patient care. So the opportunity is massive for AI applications like machine learning and NLP as well as “camera vision” and image recognition to address much of this unnecessary digital paper work and automate it.

StartUp Health: Why back the StartUp Health Moonshots Impact Fund?

Dr. Stefano Bini: I am not a professional investor, and I have limited funds

that I can provide and the way the new rolling fund was set up gave my wife and me access to something I didn’t previously have access to: a way to invest in a meaningful way in the digital health economy. This is one of the few ways I as an individual investor actually can have a small piece of a larger pie. I’ve been following the team here at StartUp Health ever since the early days of digital health. We’re actually talking about a decade ago when we first crossed paths, and I’ve always been impressed with their vision. This really humanistic approach to investing, where we’re looking to take on specific moonshots, and funding those people who are looking to approach those massive challenges in a way that is both financially responsible and aspirational.

StartUp Health: Advice for founders in the StartUp Health portfolio?

Dr. Stefano Bini: Challenge your assumptions, period. What may seem like a great business model changes once you actually talk to people who are in the business. I see this constantly, and I think it’s something that StartUp Health does extremely well. It provides its entrepreneurs with access to the kinds of people, like myself, who can give them honest feedback about what they are trying to do. If you don’t go deep in understanding the issue, you’ll never ask the questions that will get you to the point where you can identify the pain point that needs to be solved.

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StartUp Health: What drew you to StartUp Health?

Jon Kaplan is a longtime tech executive and former Chief Revenue Officer at Pinterest.

StartUp Health: Is there a sector within health that you’re particularly interested in–a specific health moonshot you’re passionate about?

Jon Kaplan: I’m drawn to bold and ambitious goals like curing disease, including ending Alzheimer’s. I just wonder if we’re at the beginning stages of applying technology to solve those problems in very different ways where they were not solved before. That’s very exciting to me. We’re only a couple of years into that journey so it’s probably a multi-decade, if not, century-long journey that we’ll be on, to be honest.

But I’m hopeful.

Jon Kaplan: I had a chance to meet the team early on and I was compelled by the vision.

I was involved in StartUp Health’s first fund. Some of the early examples of types of companies that they were investing in made a lot of sense in terms of the application of technology to healthcare. I felt a good connection to StartUp Health and appreciated how they vetted companies based on the actual technology.

It’s been great to see the great performance of the fund. Importantly, you can see these companies getting acquired by bigger companies, you can see partnerships that have been a part of this journey as well, which I think is a validation of the approach. Good results, good partnerships, and seeing companies actually get acquired and absorbed into bigger companies. This tells you that the companies that they invest in are solving the problem that they intended to solve.

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Ash Nashed, MD, is a retired emergency physician and the CEO & Founder of Adiant, a digital media technology company.

StartUp Health: Where do you see the greatest possible impact on health globally?

Dr. Ash Nashad: Preventive care is something that’s really underutilized in the US. We have the technology available today. If you could do a total body MRI of everybody every couple of years you would diagnose so many diseases — the only problems are cost and false positives. For example, if you can detect cancer very early it’s a game-changer. You reduce the reliance on chemo and can have surgery instead. It’s a massive, massive resource saver in the ecosystem as well.

StartUp Health: Why invest in StartUp Health?

Why the Moonshots Impact Fund?

Dr. Ash Nashad: I like the moonshot concept because it implies you’re being ambitious and looking for real game-changers and that’s what healthcare needs. I like that you’re investing in a broad range of companies — the deals I’ve done, a lot of them I thought weren’t going to be the one, ended up being the one. I don’t know what’s going to be successful! I like that you have a diverse fund and I can invest in that diversity, and I don’t have to worry about one versus the other. I like that you’re looking for real gamechanger companies.

StartUp Health: What’s one piece of advice that you would give to a startup or founder today?

Dr. Ash Nashad: If you’re passionate about something and you believe in it, persistence and tenacity are critical. It takes years and sometimes many different failures in order to be successful.

Rob Odell is a longtime entrepreneur and investor with deep expertise in insurance, fin tech, and real estate.

StartUp Health: How would you describe your philosophy as an investor?

Rob Odell: Initially it was mainly an opportunity to make money! But at this point in my life, I like companies that can improve our quality of life, and that can eventually make a profit or have an exit. I’m kind of a riskaverse person by nature, but somewhere along the way I realized that if you want to do something great, you have to take risk. There’s a coach for the Cardinals that says, “No risk it, no biscuit.”

Rob Odell: I like to leverage talent. Over the past 10–15 years our current company grew from three people to around 65. There’s only so many hours in the day, so if you find other entrepreneurs with different skill sets than yours, you can add ingredients and make a better cake. That’s something that drew me to StartUp Health. Additionally, smart people attract smart people, so if you look at the people either on the StartUp Health advisory board or on the companies, at the end of the day your experience is going to be rewarded. You’re going to do good things.

StartUp Health: What’s a piece of advice you’d give to a startup founder today?

Rob Odell: You need persistence, common sense, and a sense of urgency.

StartUp Health: What drew you to StartUp Health initially?

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roadmap that works.

StartUp Health: What particular areas of health are you interested in?

Ira Brind has been investing for 40 years and has a seat on many trustee boards, including Thomas Jefferson University and the Philadelphia Museum of Art. StartUp Health: How would you describe yourself as an investor?

Ira Brind: I’ve got to start with the most important driver for me which is the who, never the what. I try to invest in people that I think are going to win and figure it out. That means whatever they start with, they’re going to react to the marketplace, learn from what the marketplace tells them, and go forward. After the ‘who’ I move to the ‘what.’ It has to be interesting and the problem has to be worth solving, but rarely is the business plan the

Ira Brind: The health moonshot that I think interests me the most, because it’s a problem that hasn’t been solved, is brain health and dementia. To me it’s worthwhile to really find solutions because there are not many yet. We’re making great strides — not fast enough, not big enough — but great strides in disease and vaccines, and we’re making some progress in cancer.

Another place we haven’t made progress, and the only major industry that has not been disrupted by technology, is in the delivery of healthcare.

Not the development of medicines, but the delivery of healthcare. It’s pretty much the same as 10–20 years ago. You get on the phone and hope someone answers.

Another frontier in healthcare that will develop and be extremely important over the next 10–20 years is moving healthcare to the home.

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It will be out of the hospitals — never totally, but it is more effective and less expensive to send healthcare doctors and experts to the home.

You’ll see more and more of that StartUp Health: Was there anything about StartUp Health's latest impact fund that made you want to continue to support startups?

Ira Brind: I think it developed the StartUp Health model, not only creating the ecosystem to drive forward health moonshots, but also creating vehicles where they can invest in selective startups and help the companies have a greater impact than they had before. Also, in StartUp Health, you have an unparalleled group of peers that the other CEOs should rush to take advantage of.

STARTUP HEALTH MOONSHOTS IMPACT FUND MEET THE INVESTORS

NAN GARDETTO

StartUp Health Investor

Join investors like Nan Gardetto, Lee Shapiro, and Glen Tullman in backing the StartUp Health Moonshots Impact Fund. This fund, launched in 2021, makes it easy to back a diverse portfolio of early-stage health tech startups. healthmoonshots.com

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StartUp Health and HLTH Announce Partnership to Convene World’s Health Transformers Working to Achieve Health Moonshots StartUp Health @ ViVE 2022 and HLTH 2022 will unite the global ecosystem of health innovators, entrepreneurs, and investors.

StartUp Health, a global organization dedicated to achieving health moonshots, rolled out a multi-year partnership with HLTH, the leading platform bringing together the entire health ecosystem, to host StartUp Health at ViVE and HLTH annual events beginning in 2022.

Since 2011, StartUp Health has regularly gathered thousands of CEOs, investors, and entrepreneurs from around the world who are focused on achieving health moonshots. ViVE, the industry’s new health information technology event, merges the leadership of CHIME and the digital marketplace of HLTH to create a technology event focused on the business of transformation in healthcare.

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“The best way to solve health moonshots — the world’s largest health challenges — is to unite the people and organizations from around the world dedicating their lives to achieving them,” said Unity Stoakes, Co-founder & President of StartUp Health. “We’re excited to partner with HLTH and invite even more entrepreneurs, investors, and those working in public and private sectors who want to speed up health innovation to access StartUp Health’s global army of Health Transformers.

The partnership offers another annual opportunity to drive moonshot ideas forward and makes sense for our mutual evolution.”

Rich Scarfo, President of HLTH commented, “StartUp Health’s plan for achieving health moonshots is incredibly inspiring and their global army of Health Transformers offers hundreds of examples of the impact that’s possible from transformative health innovation."

REGISTER: startuphealth.com/vive2022

Rich Scarfo President of HLTH -On HLTH We started HLTH in 2018 and it's really an executive event, a trade show, and a retreat, all wrapped in one. Everything from the caliber of speakers to the food to the evening's entertainment was designed to be experiential.

The HLTH Difference When people arrive, we want them to focus on dealmaking. Standing around a booth for three days is not our vibe.

We focus on return on investment. For startups we have our Funding Founders program, which hosts several thousand curated, scheduled meetings between CEOs and VCs. Then we have our Hosted Buyer program, which brings together industry buyers and companies that have opted in.

On Partnering with StartUp Health Partnering with StartUp Health is a natural fit because of its media component, the reach into the worlds of VC and life sciences and startups. But most importantly, we share an understanding of the importance of advancing health for all.

Keith Fraidenburg EVP & COO of CHIME -On CHIME The College of Health Information Management Executives is a professional association serving the needs of around 5000 healthcare CIOs and other senior digital health leaders.

How COVID Put a Spotlight on CHIME COVID showed us that the industry is capable of accelerating technologies like telehealth that for decades had so many barriers to implementation.

On Partnering with HLTH at ViVE To truly accelerate innovation, you have to have all the right players at the table.

CHIME specializes in health innovation from the provider perspective while HLTH brings together many other stakeholders in the ecosystem.

On the Importance of In-Person Events While we've accelerated our ability for members to meet virtually, there is a great desire to meet in person, safely.

I've heard from CHIME members who feel incredibly alone in their challenges, and who would benefit from sitting down with a colleague face to face.

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StartUp Health Appoints Jamey Edwards as Chief Operating Officer Health Transformer with proven track record of scaling healthcare businesses joins StartUp Health’s leadership and mission to achieve health moonshots.

For years we at StartUp Health have known Jamey Edwards as the visionary CEO and Co-founder of Cloudbreak Health (which merged with UpHealth and went public via SPAC in 2021). He’s been an active member of the Health Transformer community, offering his wisdom and experience on Circles (our peer-coaching platform), in our Slack community, and at the StartUp Health Festival. Now, we’re incredibly excited to announce that Edwards has officially joined the StartUp Health leadership team as Chief Operating Officer.

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F

He’ll be putting his 25 years of experience in healthcare, investment banking, and private equity to work scaling StartUp Health’s moonshot platform as we expand our Health Transformer community. This is just the first of many exciting new hires we’ll be announcing in 2022, so stay tuned.

“We’ve been collaborating with Jamey for several years as a leader within our Health Transformer community and he is one of the most batteries-included entrepreneurs we know," said Steven Krein, CEO and Co-founder of StartUp Health.

"His expertise in scaling healthcare companies makes him uniquely qualified to help expand our health moonshot platform.”

“Jamey’s track record as a serial entrepreneur and battle-tested leadership in digital health is a huge asset to StartUp Health and our entire community of Health Transformers,” said Unity Stoakes, President and Co-founder of StartUp Health.

“I am excited to be part of StartUp Health’s important mission to improve the health of billions of people around the world over the coming decades and inspired by our strategy to solve the biggest health challenges of our time,” said Jamey Edwards. “Being able to write my next chapter as part of an organization with one of the most innovative platforms in existence for value creation in healthcare is a dream come true.”

As a serial entrepreneur, Jamey Edwards has founded, co-founded or led companies in the hospital management, physician outsourcing, and telemedicine space. Until 2021 he was the CEO

& Co-founder of Cloudbreak Health, a leading unified telemedicine company currently performing millions of encounters per year in over 2,000 healthcare venues nationwide. Cloudbreak’s mission is to #HumanizeHealthcare by leveraging technology to resolve health disparities and ensure health equity for underserved patients across the country. Cloudbreak was recognized as one of the top entrepreneur driven companies in the nation 3x by Entrepreneur Magazine, a Patrick Soon-Shiong Innovation award winner, and as a finalist in the E&Y Entrepreneur of the Year program.

Jamey has been recognized throughout healthcare as a thought leader and was named a HIMSS Changemaker, a Top 40 Health Transformer by MM&M magazine, a Medika Life Top Healthcare Digital Influencer, and one of the Top 10 Influential People in Digital Pharma by Pharmaceutical Technology. He has been a featured speaker at conferences across the country including HIMSS, the American Telemedicine Association, DOCSF, and SoCal Bio, among others.

Philanthropically, Jamey is a Board Member with the Los Angeles Chapter of the American Heart Association, the Partners in Care Foundation, PinkSocks. life, a Steering Committee Member for Scale Health, part of the Global Visioneering Health Brain Trust for the XPrize, an Advisory Board Member of the Los Angeles Kings Hockey Organization, and a member of the Santa Monica Bay Chapter of the Young Presidents Organization.

You can engage with Jamey on Twitter & Instagram: @JameyEdwards startuphealth.com 91

StartUp Health Insights | 2021 YEAR END REPORT

2021 Year-End Insights Report: $44B Raised Globally in Health Innovation, Doubling Year Over Year

For the latest in health innovation funding go to startuphealth.com/insights-reports 92 StartUp Health Magazine / GLOBAL IMPACT

Thanks to a wave of mega deals in the United States, England, India, and China, health innovation funding has reached heights that would have seemed impossible just a year or two ago. Plus, acquisitions are up 50%, and more than 20 companies went public.

94 Total Funding Year Over Year

100 Top Deals (Non-US)

97 Top Deals (US)

102 Innovation Hubs

98 Average Deal Size

105 Most Active Investors startuphealth.com 93

StartUp Health Insights | 2021 YEAR END REPORT

F

For more than a decade StartUp Health has been monitoring the digital health landscape and tracking market data globally. Back in 2011, when there was around $2B being invested in

health tech, we wrote about the nascent potential of the market. Digital health was barely a topic of conversation and telemedicine was struggling to gain traction. But we knew that with global collaboration, entrepreneurship and, yes, much

10 Years of Global Health Innovation Funding Total Raised

Total Deals

552

603

582 498

393

$7.1B

$2.3B 2012

$8.2B $6.1B

$2.8B 2013

2014

2015

2016

94 StartUp Health Magazine / GLOBAL IMPACT

Source: StartUp Health Insights | startuphealth.com/insights. Note: Report based on publicly available data through 12/31/21 on seed (incl. accelerator), venture, corporate ventur

more capital, we could achieve historic gains in health. We could, in fact, achieve health moonshots that previous generations thought were impossible.

Now, as we end 2021, the conversation has shifted completely. We just closed the

books on a year that hit $44B in health innovation funding globally. That’s more than a 20x increase in 10 years. To call that number record-breaking would be an understatement — we’ve seen recordbreaking funding numbers nearly every

$44B

990 841

805

797 732

$22B

$15.4B

$14.3B

$11.8B

2017

2018

2019

2020

2021 startuphealth.com 95

re, and private equity funding only. Companies tracked in StartUp Health Insights may fall under multiple moonshots and therefore will be represented throughout the report.

StartUp Health Insights | 2021 YEAR END REPORT

year since we started tracking. What we’re seeing now is a doubling of funding.

2021 saw twice as much funding as 2020 ($22B), which itself was a 50% increase over 2019 ($14B). This new, accelerating growth rate shifts our expectations for the future.

It’s obvious to most observers what happened in 2020 to take digital health investing from steady growth to doubling year over year. The tipping point aligns almost perfectly with the WHO’s announcement in early 2020 that COVID-19 had reached pandemic status. But it’s worth remembering that this wasn’t a foregone conclusion. First, investors went very quiet and markets went on ice.

In March and April of 2020, major news outlets projected that the digital health market would cool off.

But that’s not what happened. By all observations, fear gave way to optimism and investors shifted their focus from self protection to bold action on health. From that point on we witnessed a truly historic shift in investment priorities towards virtual healthcare, telemedicine, remote patient monitoring, and other next-gen health solutions. mega deals continue to dominate

One funding trend we’ve been tracking for a few years is the rise of the health innovation mega deal. It’s not a new phenomenon; we’ve been noting the increase in deals over $100M for at least four years.

But the trend just keeps accelerating and the deal totals keep ballooning. A couple of years ago it was notable to have a health

innovation deal top $100M. This year there were multiple deals over $400M and one from the StartUp Health portfolio, Devoted Health worth $1.2B. As this chart shows, a decade ago average deal size was around $2M. Now the average deal size is $16M, an 8x increase.

Thankfully, deals aren’t just getting bigger — we’re also seeing more of them. This year we tracked 990 total deals, compared to 797 in 2020. But most growth is coming from the top, resulting in a market that is inordinately impacted by a small number of mega deals occurring in the most-funded cities in the world. This is a well-documented trend across venture capital, and it has the potential to skew our perception of market growth overall.

In health innovation, total funding numbers are important metrics, but they need to be balanced against total deal counts, regional totals, and measurable global impact.

Total deal count is an important measure of entrepreneurial activity, and one we’ll continue to watch closely. We believe that to achieve health moonshots it’s not enough to back a few unicorns. As an industry we need to invest in entrepreneurs at scale, at every stage, so that the best ideas and products have a chance to emerge. follow the money: analyzing top deals

Every quarter we publish our list of the top 10 largest health innovation deals in the US and outside the US. While these lists are only a slice of the pie, they give us a window into the priorities of the

96 StartUp Health Magazine / GLOBAL IMPACT

Top Health Innovation Deals (US) Company

Function

Devoted Health

Patient Empowerment

$1.2B

Noom

Wellness

$540M

Ro (fka Roman)

Patient Empowerment

$500M

Commure

Patient Empowerment

$500M

Mindbody

Wellness

$500M

Insitro

Personalized Health

$400M

XtalPi

Research

$400M

Olive

Admin Workflow

$400M

Hinge Health

Personalized Health

$400M

Cityblock Health

Population Health

$400M

world’s largest investors. It can shed light on where there is growing confidence and market optimism. Here are a few observations from 2021’s top deals list.

With their $1.2B raise, Devoted Health (which StartUp Health backed in 2019) has broken through the ceiling, redefining what’s possible in health tech

Amount Raised

funding. No health innovation company has ever raised this much before, especially not a company focused on improving healthcare for the elderly. As long time supporters of Todd and Ed Park, co-founders of Devoted Health, we think this investment bodes well for the shifting priorities of the industry towards vulnerstartuphealth.com 97

StartUp Health Insights | 2021 YEAR END REPORT

able populations and preventative population health.

The largest raise of the fourth quarter was a $500M deal for Mindbody, which some have described as the OpenTable for fitness. Wrapped into this raise was

the acquisition of ClassPass, which further solidified that this is a year for market consolidation. To better understand the significance of the Mindbody raise, we talked to David Stapleton, CEO and founder of BUA FIT, a UK-based social

Global Health Innovation Funding Average Deal Size, Year Over Year

$4.7M

$4.4M

$4.0M

$2.0M

$2.0M

2012

2013

2014

2015

2016

98 StartUp Health Magazine / GLOBAL IMPACT

Source: StartUp Health Insights | startuphealth.com/insights. Note: Report based on publicly available data through 12/31/21 on seed (incl. accelerator), venture, corporate ventur

marketplace for outdoor and online fitness that StartUp Health backed in 2021.

“We’re seeing a strong tailwind in the global wellness market, which is forecasted to top $7 trillion by 2025,” says Stapleton. “I think this is the start of a lot more

M&A activity in the fit-tech and wellness industry.”

The second largest raise of the fourth quarter went to Hinge, which raised $400M to grow its digital platform for back and joint pain. At a $6.2B valuation,

$16M

$10M

$7.3M $6.3M

$4.6M

2017

2018

2019

2020

2021

startuphealth.com 99

re, and private equity funding only. Companies tracked in StartUp Health Insights may fall under multiple moonshots and therefore will be represented throughout the report.

StartUp Health Insights | 2021 YEAR END REPORT

Top Health Innovation Deals (Outside the US) Company

Country

Amount Raised

CMR Surgical

England

$600M

Medlinker

China

$514M

PharmEasy

India

$500M

Miaoshou Doctor

China

$465M

Keep

China

$360M

PharmEasy

India

$323M

KRY

Sweden

$312M

Oxford Nanopore

England

$270M

Quanta Dialysis Technologies England

$245M

Miaoshou Doctor

$232M

China

this raise makes Hinge one of the most valuable digital health companies in the world. Not unlike the Devoted Health raise, investors’ interest in Hinge suggests a shift towards elder care and taking preventative health much more seriously.

“Between Hinge and Sword, two of the biggest raises in digital health this year

were attributed to musculoskeletal conditions (MSK), which is a strong testament to how big the problem and market are,” says Jakob Dahlberg, CEO and co-founder of Joint Academy, which has digitized joint pain therapy based on best practices from Sweden. “There are upwards of 100M people in the US with chronic or

100 StartUp Health Magazine / GLOBAL IMPACT

acute musculoskeletal problems, and we potential to find financial opportunity have only treated a few hundred thou- while building greater health equity. sand patients. We are still early and there is so much important work left to do.” diversity at the top Another trend in the top deals list We analyzed the top 50 health innois that mega deals are now happening vation deals (deals over $200M) for the around the globe. For many years, the top year to see what we could learn about deals we tracked outside the US were a investor priorities. One takeaway is that fraction of the size of those coming out while many investors have made public of San Francisco and New York. Not any- statements about their intention to invest more. This year all ten in Black and female top deals outside the founders — populaWE JUST CLOSED THE US were over $200M, tions historically left BOOKS ON A YEAR THAT including $600M for out of the VC money HIT $44B IN HEALTH CMR Surgical, $823M pool — we’re not seeINNOVATION FUNDING for PharmEasy (coming that representation GLOBALLY. THAT’S MORE bined across two backat the highest echelons THAN A 20X INCREASE to-back raises), and just yet. In our list of IN 10 YEARS. TO CALL $697M for Miaoshou top 50 deals of 2021, THAT NUMBER RECORDDoctor out of China. only 2% of funding BREAKING WOULD BE AN Historically, we’ve went to companies UNDERSTATEMENT separated top deals bewith Black founders. tween the US and outThings are improvside the US, because a ing on that front: acsingle global list would have skewed too cording to Crunchbase, funding for Black heavily towards cities like San Francisco, startup founders quadrupled in 2021. Yet ignoring important growth happening in these entrepreneurs still received only other markets. This year we’re beginning 1.2% of the record $147B in venture capito see a shift. For the first year ever, two of tal invested in all US startups through the the year’s top deals outside of the United first half of 2021.

States (CMR Surgical in England and We also note that only 10% of the top PharmEasy in India) rank in the top 10 50 health deals went to companies with deals overall. We can’t emphasize enough female founders, and that number trims how important this move is. Investing down dramatically to 2% when we filter in health moonshots means addressing for solo female founders. To make meanhealth challenges on every continent, not ingful change in healthcare, where womjust the ones with the largest, most lucra- en are not only major recipients of care, tive healthcare markets. Every human on but also primary purchasers, we’ll need the planet is in need of the health inno- to see a lot more money invested into vations being developed today, so inves- female-led businesses. tors who expand their footprint have the At StartUp Health, we take these issues startuphealth.com 101

StartUp Health Insights | 2021 YEAR END REPORT

Hubs of Health Innovation (US) City/Region

Funds Raised

2021 Total Deals

San Francisco

$11.9B

200

New York City

$7.5B

164

Boston

$4.4B

70

Los Angeles

$1.1B

41

Denver

$670M

16

Seattle

$642M

19

Columbus

$598M

7

Baltimore

$561M

7

San Diego

$515M

11

Austin

$509M

21

of representation into account with every investment we make. In 2021, 7% of the founders we backed were Black, and 21% were women. While these numbers are ahead of industry standards, we’ll be the first to say that we have a lot more work to do. hubs of innovation

While San Francisco, New York City,

and Boston continued to dominate our list of health innovation hubs, second tier markets like Seattle, Columbus, Baltimore, and San Diego made a solid showing in 2021. It should be noted that health investing skews so heavily towards the top three cities that in 2021, San Francisco, New York, and Boston accounted for a combined $23.8B, more than half (55%) of the total amount raised globally for the year and 45% of the

102 StartUp Health Magazine / GLOBAL IMPACT

Hubs of Health Innovation (OUS) City/Region

Funds Raised

2021 Total Deals

London Metro

$2.3B

47

Mumbai

$1.1B

7

Beijing

$1.0B

3

Guangzhou

$697M

2

Toronto

$605M

20

Paris

$501M

13

Tel Aviv Metro

$466M

25

Stockholm

$420M

3

Dublin

$313M

3

Porto

$299M

3

total deals for the year.

Outside the US, London and Tel Aviv dominated in deal activity, with London metro seeing a massive $1.7B increase in funding (369%) between 2020 and 2021.

Toronto and Paris continue to be active hubs for health innovation, with 20 and 13 deals respectively, while Mumbai and Beijing each hit the billion dollar mark for funding.

acquisition activity

2021 saw 110 total acquisitions in health innovation, up from 71 in 2020.

That’s more than a 50% increase in acquisition activity, bolstered by a few massive deals in the final quarter of the year. Notably from the StartUp Health portfolio were Conversa Health’s acquisition by Amwell (NYSE: AMWL), the telemedicine leader, and wayForward’s acquisition startuphealth.com 103

StartUp Health Insights | 2021 YEAR END REPORT

by DarioHealth (NYSE: DRIO). Historic levels of fundraising set off a strong year for acquisitions and we predict this will continue at a steady clip in 2022. ipos and spacs

In 2021, a record 24 companies sought to grow by taking the plunge into the public markets, either through a traditional IPO or a SPAC. Notably for the StartUp Health portfolio, next gen blood testing startup Nightingale went public on the Finnish stock exchange in March (HEX: Health.He). By comparison, In 2020 we counted only seven digital health IPOs and two SPACs. Overall, in this list we’re observing a healthy diversity in the types of companies that are going public, everything from decentralized clinical trial platforms to online therapy companies to maternal/neonatal health platforms. most active investors

Topping our list of most active investors in health innovation are familiar names like General Catalyst, Tiger Global, and GV. But perhaps more interesting is to take the chart back five years and see how rapidly deal activity has grown for these firms. Notably, Tiger Global and Oak had zero investments in the space as recently as 2017. Every firm has doubled, tripled (or 8x’d) their investment volume in just a few short years. In 2021, the most active investor in the market, General Catalyst, took part in four times as many deals as the most active investor in 2017, Khosla Ventures.

conclusion

As exciting as the last two years of growth have been in health innovation investing, at StartUp Health we still believe we’re at the beginning of the wave. We believe that to achieve the health moonshots of our time, like curing cancer and bringing the cost of healthcare to zero, we’re going to need to fundamentally change how we prioritize health. That means allocating capital where it’s needed most. The cures and conveniences in health being funded today are still available to too few people. Improving health and wellbeing is a global challenge, and the geography of our funding needs to match that reality.

Funding health innovation in the United States, Israel, and the United Kingdom isn’t enough. We need to see a renewed focus on health access and quality across every continent. And that’s going to require a whole new wave of investment — and a health moonshot mindset — beyond even this year’s historic funding numbers.

This report was written and designed

by Logan Plaster based on data collected and managed by Tara Salamone, Nicole Kinsey, and Jennifer Hankin. Additional analysis by Anne Dordai and Priya Reddy.

Report based on publicly available data through 12/31/21 on seed (incl. accelerator), venture, corporate venture, and private equity funding only. Companies tracked in StartUp Health Insights may fall under multiple moonshots and therefore will be represented throughout the report.

104 StartUp Health Magazine / GLOBAL IMPACT

Most Active Investors Investor

2021

2020

2019

2018

2017

General Catalyst

40

20

4

6

6

Tiger Global Management

27

8

4

2

0

GV (fka Google Ventures)

20

16

11

6

6

F-Prime Capital

19

8

11

10

8

Khosla Ventures

19

19

12

14

10

Andreessen Horowitz

19

12

5

6

3

Oak HC/FT

18

13

4

8

0

Optum Ventures

17

18

8

4

2

Insight Partners

16

9

2

6

3

Flare Capital Partners

15

7

3

6

7

Founders Fund

15

11

8

11

9

startuphealth.com 105

Health Moonshot snapshots

106 StartUp Health Magazine / GLOBAL IMPACT

ACCESS TO CARE COST TO ZERO DISEASE PREVENTION & CURES END CANCER WOMEN’S HEALTH CHILDREN’S HEALTH NUTRITION & FITNESS BRAIN HEALTH & ALZHEIMER’S MENTAL HEALTH & HAPPINESS HEALTHY LONGEVITY & AGING ADDICTION & OPIOID CRISIS PANDEMIC RESPONSE

108 110 112 114 116 118 120 122 124 126 128 130

startuphealth.com 107

HEALTH MOONSHOT

Access to Care Together we can deliver quality care to everyone regardless of location or income

Javier Cardona CEO & Co-founder 1DOC3

PORTFOLIO SPOTLIGHT

Toyin Ajayi, MD President & Co-founder Cityblock Health

Founded in 2017, Cityblock Health is a transformative, value-based healthcare provider for Medicaid and lower income Medicare beneficiaries. They partner with community-based organizations and health plans to deliver medical care, behavioral health, and social services virtually, in-home and in communitybased clinics. Modern technology is at the core of the model, with custom-built tools to support care team operations and member interactions. Cityblock currently serves 70k members across four major US metro areas and partners include EmblemHealth, ConnectiCare, CareFirst, and Tufts Health Plan. The company was named a 2021 CNBC Disruptor 50.

Data as of 12/31/21. Sample of portfolio company investments and may not be representative of larger portfolio.

108 StartUp Health Magazine / GLOBAL IMPACT

144

ACTIVE PORTFOLIO COMPANIES

NOTABLE PORTFOLIO INVESTMENTS 2021

2020

2019

2018

(Acquired by Press Ganey) 2017

2015

2014

(Acquired by AmWell) 2013

(Acquired by Press Ganey)

(Acquired by Sharecare & Generali)

“StartUp Health is my home base as a founder.

StartUp Health has provided exposure to investors and customer that I’d never have gotten on my own. They’ve given me support to accelerate faster and with more confidence.”

-Troy Bannister CEO & Founder, Particle Health

startuphealth.com 109

HEALTH MOONSHOT

Cost to Zero Together we can reduce the cost of care to “zero”

Ed Park CEO & Co-founder Devoted Health

PORTFOLIO SPOTLIGHT

Bill Nordmark CEO Enlace Health

Enlace Health (fka Aver) delivers industry-leading, end-to-end solutions – from pilot to total risk – for all value-based care initiatives.

To date, the company has analyzed 300B claims with 20% average savings, and a 7:1 payback ratio.

Clients include some of the largest payors and EHR providers. In Q4 2021, the company raised $58M led

by Cox Enterprises to accelerate the scale and deployment of its new Enlace Health brand.

Data as of 12/31/21. Sample of portfolio company investments and may not be representative of larger portfolio.

110 StartUp Health Magazine / GLOBAL IMPACT

76

ACTIVE PORTFOLIO COMPANIES

NOTABLE PORTFOLIO INVESTMENTS 2021

2020

2019

2018

2017

2015

2014

2013

“I can’t even count on two hands the number of times in the last 18 months that someone – an investor, business partner, mentor – said ‘be a part of StartUp Health.

It’s where it’s at.’ So we are, and we’re thrilled about it.”

-Brad Artery President & COO, Mocingbird startuphealth.com 111

HEALTH MOONSHOT

Disease Prevention & Cures Together we can rid the world of disease

Naheed Kurji CEO & Co-founder Cyclica

PORTFOLIO SPOTLIGHT

Lynda Brown-Ganzert CEO & Founder Curatio

Curatio develops private social health networks using AI and peer support.

Available in 15 languages and currently used in 102 countries, Curatio is the only global privacy and regulatory compliant social platform designed specifically for healthcare. Published clinical evidence shows that 80% of Curatio users had improved health behaviors and adherence, an increased interest in self-management, and improved social integration. Notable partnerships include Novartis US, Abbvie, Bioscript Solutions, Providence Health Care, and Simon Fraser University.

Data as of 12/31/21. Sample of portfolio company investments and may not be representative of larger portfolio.

112 StartUp Health Magazine / GLOBAL IMPACT

56

ACTIVE PORTFOLIO COMPANIES

NOTABLE PORTFOLIO INVESTMENTS 2021

2020

2019

2018

2017

(Acquired by Labcorp) 2016

2014

2013

(Acquired by FamilyTreeDNA)

“We wouldn't be where we are today without the help of StartUp Health. They introduced us to our Series A investor and have made many intros to companies that became really important customers of ours, driving seven figures in revenue.”

-Josh Stein Co-founder, Adheretech startuphealth.com 113

HEALTH MOONSHOT

End Cancer Together we can end cancer as we know it

Kaitlin Christine CEO & Founder Gabbi

PORTFOLIO SPOTLIGHT

Nikhil Pooviah, MD Co-founder Elly Health

Elly is an app that delivers personalized audio experiences to improve the lives of patients, including those with cancer.

Users engage with content around disease education, exercise, meditation and sleep practices, symptom management, and fellow patient stories. ​​Clinical research has demonstrated that patients improved their quality of life by ~15% and patient activation by ~40% after 30 days using Elly.

Their Phase I clinical study in oncology showed that Elly achieved $9k per patient per year in predictive cost savings, 86% user retention rate with user engagement of 2x per day, and an NPS score of 79.

Data as of 12/31/21. Sample of portfolio company investments and may not be representative of larger portfolio.

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18

ACTIVE PORTFOLIO COMPANIES

NOTABLE PORTFOLIO INVESTMENTS

2021

2020

2019

2018

2016

2014

“We were in the process of rolling out and preparing a launch of the world’s first blood-based, multi-cancer detection system. That launch brought us to a lot of questions, where StartUp Health was tremendously helpful.”

-Jo Bhadki CEO & Founder, Quantgene startuphealth.com 115

HEALTH MOONSHOT

Women's Health Together we can improve the health of every woman

Jill Angelo CEO & Founder Gennev

PORTFOLIO SPOTLIGHT

Anish Sebastian CEO & Co-founder Babyscripts

Babyscripts is the most comprehensive and clinically validated maternity program to help manage expecting moms virtually, before and after birth. The Babyscripts technology is a combination of a smartphone app and internet-connected medical devices delivered via their “Mommy Kit,” which remotely monitors patients and allows providers to risk-stratify care, offering specific experiences to manage different risk conditions (e.g. diabetes, hypertension). Babyscripts works with more than 75 health systems in 32 states and the company is monitoring 250k women each year. Babyscripts has raised $26M to date.

Data as of 12/31/21. Sample of portfolio company investments and may not be representative of larger portfolio.

116 StartUp Health Magazine / GLOBAL IMPACT

19

ACTIVE PORTFOLIO COMPANIES

NOTABLE PORTFOLIO INVESTMENTS 2021

2020

2019

2015

2013

2018

“The coverage provided to us was a major plus, our investors found us via the online article and the magazine article.

Your coverage gave us a 'blue check' and the investors now on our board are wellknown leaders with the industry.”

-Sheena Franklin CEO & Founder, K’ept Health

startuphealth.com 117

HEALTH MOONSHOT

Children's Health Together we can ensure that every child has access to high-quality care

Stephanie Canale, MD CEO & Founder Lactation Lab

PORTFOLIO SPOTLIGHT

Javier Evelyn CEO & Founder Alerje

Alerje is a Detroit-based company developing digital tools for food allergy management, impacting over 220M people worldwide. In Summer 2021, Alerje was granted a utility patent for their flagship epinephrine auto-injector smartphone case combo, in both the US and abroad, and received a Phase I SBIR grant from the National Science Foundation. Funds from the SBIR grant will be used to develop an OIT platform that collects, stores, analyses, and distributes clinically relevant data to build a bridge between patients and their care teams.

Data as of 12/31/21. Sample of portfolio company investments and may not be representative of larger portfolio.

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15

ACTIVE PORTFOLIO COMPANIES

NOTABLE PORTFOLIO INVESTMENTS 2021

2020

2019

2018

2017

2013

“We traveled from Australia to attend the StartUp Health Festival, and the minute we arrived we knew we were home with an amazing cohort of valuealigned entrepreneurs and stakeholders all solving big complex problems. The two days enabled us to establish global collaborative opportunities that will shape our company’s progress.”

-Danny Hui CEO & Founder, sameview

startuphealth.com 119

HEALTH MOONSHOT

Nutrition & Fitness Together we can ensure access to food, water and a healthy lifestyle

Shireen Abdullah CEO & Founder Yumlish

PORTFOLIO SPOTLIGHT

Victor Penev CEO & Co-founder Edamam

Edamam organizes the world’s food knowledge and provides nutrition data services and value-added solutions to health, wellness, and food businesses.

Using a proprietary semantic technology platform, it delivers real-time nutrition analysis and diet recommendations via APIs. Edamam has built the most extensive recipe database in the industry with 5M+ recipes and 800k individual foods, each tagged for 40+ diets and 130+ nutrients to address over 200 chronic conditions. More than 90k companies have subscribed to their APIs and partners and clients include Amazon, Food Network, McCormick, Microsoft, and Nestle.

Data as of 12/31/21. Sample of portfolio company investments and may not be representative of larger portfolio.

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23

ACTIVE PORTFOLIO COMPANIES

NOTABLE PORTFOLIO INVESTMENTS 2021

2020

2019

2018

2016

2014

2013

(Acquired by Zimmer Biomet)

“StartUp Health is such a credible resource for investors, entrepreneurs, and healthcare professionals. They’ve built a great culture, which is no small task. The team is authentic and passionate about what they do and it comes through in every encounter we have.”

-Aubrey Sawyer President & Co-founder, inHealth startuphealth.com 121

HEALTH MOONSHOT

Brain Health & Alzheimer’s Together we can unlock the mysteries of the brain to improve health and wellbeing

Sidney Collin CEO & Co-founder De Oro Devices

PORTFOLIO SPOTLIGHT

Renee Ryan CEO Cala Health

Cala Health is on a mission to transform the standard of care for patients living with chronic diseases using non-invasive wearable neuromodulation therapies.

Their lead product, the Cala Trio, is the only non-invasive prescription therapy for essential tremor. In Q4 2020, the FDA granted Breakthrough Device Designation to Cala Trio for the treatment of action tremors in the hands of adults with Parkinson’s disease.

The company recently raised $77M in new funding from investors including Ascension Ventures and Dolby Family Ventures.

Data as of 12/31/21. Sample of portfolio company investments and may not be representative of larger portfolio.

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17

ACTIVE PORTFOLIO COMPANIES

NOTABLE PORTFOLIO INVESTMENTS 2021

2020

2019

2017

2016

2014

“Pitching at the Health Transformer Showcase was a highlight for us this year. The opportunity to present our solution to an audience finely attuned to the digital therapeutics sector has been invaluable: the number of follow-up meetings that resulted from the event are a testament to that fact.”

-Amir Bozorgzadeh CEO & Co-founder, Virtuleap

startuphealth.com 123

HEALTH MOONSHOT

Mental Health & Happiness Together we can connect mind, body, and spirit in the pursuit of wellbeing

Thomas Tsang, MD CEO & Co-founder Valera Health

PORTFOLIO SPOTLIGHT

Raj Amin CEO & Co-founder Wise Therapeutics

Wise Therapeutics uses breakthrough neuroscientific research to improve mental health through casual, accessible mobile games. Their first product is an app called Personal Zen. With a decade’s worth of NIH-backed clinical R&D, Wise is the first to apply mobile gamebased cognitive training techniques to therapeutic areas such as anxiety, distress, and addiction. To date, they’ve published seven RCTs with 288 patients studied in published trials. Research collaborators and partners include NIH, NAMI, NYU Langone Health, and Soterix Medical.

Data as of 12/31/21. Sample of portfolio company investments and may not be representative of larger portfolio.

124 StartUp Health Magazine / GLOBAL IMPACT

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ACTIVE PORTFOLIO COMPANIES

NOTABLE PORTFOLIO INVESTMENTS 2021

2020

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(Acquired by Dario Health)

“I want to thank StartUp Health for the 1,2 publicity punch that Help-Full received recently. About a dozen inquiries came in from investors, large healthcare payors, and health systems from the media coverage.”

-Jenny Gallagher CEO & Co-founder, Help-Full

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HEALTH MOONSHOT

Healthy Longevity & Aging Together we can add 50 healthy years to every human life

Satish Movva CEO & Founder CarePredict

PORTFOLIO SPOTLIGHT

Bob Wise CEO Solius

SOLIUS uses advanced light science as a revolutionary way to treat and prevent disease by stimulating the production of hormones, such as vitamin D, which are critical for supporting human health.

They’re currently developing their second product — an at-home device that will have the same level of efficacy as their commercial product, at a fraction of the size and cost. Trials show that their light science produces 10 times more vitamin D than the sun, but with 100 times less energy. SOLIUS has been awarded a Medical Device License by Health Canada and is currently operating in Canada, aiming for US FDA approval later this year.

Data as of 12/31/21. Sample of portfolio company investments and may not be representative of larger portfolio.

126 StartUp Health Magazine / GLOBAL IMPACT

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ACTIVE PORTFOLIO COMPANIES

NOTABLE PORTFOLIO INVESTMENTS 2020

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(Acquired by Sharecare & Generali)

“Health Transformer Circles has been one of the most helpful experiences I’ve had as an entrepreneur. It’s a safe place to share some of our deepest emotions together — the joy of our companies and also the insecurities, fears, and uncertainties that need to be addressed.”

-Beth Sanders CEO & Founder, LifeBio

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HEALTH MOONSHOT

Addiction & Opioid Crisis Together we can end addiction and the opioid epidemic

Rachel Trobman CEO & Founder Upside Health

PORTFOLIO SPOTLIGHT

Yusuf Sherwani, MD CEO & Co-founder Quit Genius

Quit Genius is the world’s first digital clinic for tobacco, alcohol, and opioid addictions. Their model allows employees and health plan members to access a proven treatment program 100% remotely. Quit Genius is the only digital addiction program validated in a randomized-controlled trial (RCT) and six peer-reviewed studies. Their academic partners include Imperial College London and Cambridge University. To date they’ve enrolled hundreds of thousands of participants across multiple geographies and industries, and their partners include NHS, Corning, and Yokohama. In July 2021, they raised a $64M Series B.

Data as of 12/31/21. Sample of portfolio company investments and may not be representative of larger portfolio.

128 StartUp Health Magazine / GLOBAL IMPACT

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ACTIVE PORTFOLIO COMPANIES

NOTABLE PORTFOLIO INVESTMENTS 2021

2020

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2013

“I’m proud to be part of the StartUp Health community of Health Transformers.

There is so much to learn from other entrepreneurs and time is so limited. Every week someone will share their story, their learnings, and their struggles.”

-Emilio Goldenhersch CSO & Co-founder, The Mind Company

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HEALTH MOONSHOT

Pandemic Response Together we can prevent, mitigate, and manage pandemics

Cristian Pascual CEO & Co-founder Mediktor

PORTFOLIO SPOTLIGHT

Kim Gandy, MD, MPH CEO & Founder Play-it Health

Play-it Health provides education and remote patient monitoring in a rich communication and incentive platform, achieving some of the highest engagement and adherence rates in the industry. They offer a comprehensive virtual care solution that allows one to move from tracking symptoms through spot checking vitals to continuous remote patient monitoring. Notable partners include Duke University Health System, University of Nebraska Medical Center, and Universal Software Solutions.

Additionally, in light of COVID-19, they’re working with with UC Merced to address vaccine hesitancy in the student body and surrounding community.

Data as of 12/31/21. Sample of portfolio company investments and may not be representative of larger portfolio.

130 StartUp Health Magazine / GLOBAL IMPACT

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ACTIVE PORTFOLIO COMPANIES

NOTABLE PORTFOLIO INVESTMENTS 2021

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(Acquired by AmWell) 2016

2014

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(Acquired by AmWell)

“The StartUp Health Festival probably saved us a year of networking. Being able to connect with industry leaders and influencers — everyone from a global CEO to the CIO of pharma company to a hospital system CEO to our peers who we can share intelligence with — was invaluable.”

-Jonathan Dariyanani President & Founder, Cognotion

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FLORENCE NIGHTINGALE pioneered healthcare reforms that revolutionized nursing and paved the away for global impact.

In 2020, to mark the 200th anniversary of her birth, the WHO declared it the Year of the Nurse and Midwife.

"How very little can be done under the spirit of fear."

FLORENCE NIGHTINGALE

Dream Impossible

At StartUp Health we help Health Transformers achieve health moonshots.

Learn more at healthmoonshots.com 132 StartUp Health Magazine / GLOBAL IMPACT