Scripps Research FY2022 Annual Report

Scripps Research | Annual Report 2022 Visit us at scripps.edu

2022

Dear friends, Throughout the 2022 fiscal year, our nonprofit biomedical research institute has continued its trajectory of excellence. Our esteemed faculty received national and global recognition for their groundbreaking work. Most notably, early last fiscal year, neuroscientist Ardem Patapoutian, PhD, was awarded the 2021 Nobel Prize in Physiology or Medicine for his research on how our body senses touch and other mechanical stimuli. What’s more, in the 2023 fiscal year, chemist K. Barry Sharpless, PhD, won the 2022 Nobel Prize in Chemistry. These back-to-back Nobels awarded to Scripps Research scientists exemplify the transformative research taking place at our institute.

In our labs, researchers pursue critical investigations each day with the potential to impact a wide range of diseases. This past year, for example, our scientists continued working toward the development of a universal flu vaccine through discoveries like identifying an antibody that recognizes a broad array of flu viruses. Meanwhile, one research study from our institute in 2022 made extraordinary strides in advancing our knowledge of human vision and age-related macular degeneration by reviving human eyes hours after death.

The Year in Review I am so proud to help support our scientists in advancing knowledge in the biosciences and pioneering novel tools and techniques with applications across the spectrum of science, medicine and industry.

M E R E D I T H J O H N S T ON | VICE PRESIDENT OF PHILANTHROPY, SCRIPPS RESEARCH

At Calibr, the drug discovery division of Scripps Research, drug candidates for a variety of diseases are in development. One of those is a first-in-human clinical trial of the switchable CAR-T platform, which reported promising results against devastating cancers. Across campus, scientists at the Scripps Research Translational Institute are harnessing the latest technology to design studies to improve an individual’s access to health data and understanding of their own health and risks for disease. One such study determines users’ genetic risk for coronary artery disease—a leading cause of death in the U.S. In fiscal year 2022, the Scripps Florida campus—established in 2004 in Jupiter, FL, with a primary focus on basic biomedical research and drug discovery—underwent a transition. Scripps Research entered into an agreement with University of Florida on April 2, 2022, at which time Scripps Research transferred all assets associated with the 30-acre Scripps Florida campus to University of Florida.

During the integration, Scripps Research sought to ensure Jupiter campus’ outstanding research programs and significant investment in Florida continued without interruption.

I am extremely grateful to all those who have invested in our institute’s success and contributed to these impressive breakthroughs in science and medicine. In fall 2022, we hosted our inaugural Celebration of Gratitude—an event designed specifically to honor our exceptional community of donors and celebrate the progress fueled by their support. Additionally, we launched our giving society, The Science Trust at Scripps Research. This group brings together passionate and dedicated individuals who understand basic research’s monumental impact on advancing science and medicine.

To everyone who has supported Scripps Research, please accept our deepest thanks. In the following report, you will find some highlights from the last fiscal year (October 1, 2021, through September 30, 2022). I hope you enjoy this brief look into the past year and are encouraged by the many achievements and discoveries happening at our institute.

Meredith Johnston Vice President, Philanthropy

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2022 by the Numbers* Fiscal Year 2022: October 1, 2021 - September 30, 2022 Endowment Performance Year-Over-Year

2019

2020

2021

2022

Philanthropic Endowment value

$ 181,126

$ 198,445

$ 237,834

$ 204,676

Philanthropic Endowment growth

8%

10%

20%

-14%

Scripps Research is obligated to preserve the purchasing power of our endowment by spending only a fraction of its value each year. Spending significantly more would privilege the present over the future in a manner inconsistent with an endowment’s fundamental purpose of maintaining intergenerational equity—providing a critical and stable source of support for our scientists for generations to come. Consistent with many of our peers, Scripps Research targets an annual endowment payout of 5% of market value. The endowment grew at an average rate of 6% over the last four years despite negative market volatility in 2022. Scripps Research’s executive leadership and the Board of Directors continually engage with our investment advisors on asset allocation and manager selection in order to generate steady returns over time in excess of our endowment payout. The broader macro market dynamics have improved recently; as a result, the portfolio has experienced a 12.8% return in the 2023 fiscal year to date through June 30, 2023.

Thank you to our generous supporters whose philanthropy empowered our scientists to pursue groundbreaking discoveries in 2022. Your gifts ensure scientific progress can continue uninterrupted.

Launched in fiscal year 2022, The Science Trust at Scripps

Through digital and print communications, thousands of our

Research—with 241 members as of September 30, 2022—

friends and advocates stay connected to the vital scientific

recognizes our phenomenal community of supporters who

progress happening at Scripps Research and the impact

are committed to accelerating life-changing science at our

philanthropy has on the innovative work across our campus.

institute. Annual support of $1,000 or more qualifies donors

Total Revenue Year-Over-Year

2019

2020

2021

2022

External Research Funding

$ 340,637

$ 336,998

$ 381,750

$ 345,052

Royalty, Licensing, and Other

$

30,931

$

31,270

$

71,071

$

317,071

Philanthropy

$

24,810

$ 23,440

$

37,698

$

27,608

Investment Income

$

11,981

$

22,531

$ 46,606

$ (68,896)

Total Revenue

$ 408,359

$ 414,239

$ 537,125

$ 620,835

for membership.

Since the inception of our efforts to endow fellowships

In fiscal year 2022, total institute revenue continued to increase, despite a lower investment income return. Our institute received significant returns in royalties and licensing income as a result of seminal research conducted across the institute in preceding years. Included in our 2022 return of $317M were royalties associated with the work of Scripps Research scientists in the creation of COVID-19 vaccines as well as the development of numerous medications, such as ozanimod (an immune-modulating therapy) and tafamidis (the first FDA-approved treatment for transthyretin amyloid cardiomyopathy).

at the Skaggs Graduate School of Chemical and Biological Our institute continues to invite people from around the globe

Sciences, 73 doctoral students have received endowed

to engage with the extraordinary science underway at

fellowships. Scripps Research is in the midst of endowing

Scripps Research, and, in fiscal year 2022, 4,554 attendees

the full graduate program to ensure each student can focus

joined us for events, learning firsthand the ways researchers

on pursuing their research without financial concerns.

are shaping a healthier tomorrow.

* In Thousands 2

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A Year in Review

2022

Nobel Prize Science Ardem Patapoutian, PhD, holder of the Presidential Endowed Chair in Neurobiology, won the 2021 Nobel Prize in Physiology or Medicine for his groundbreaking research that solved the long-standing mystery of how the body senses touch and other mechanical stimuli.

Another extraordinary year of science changing life

Throughout the 2022 fiscal year, Scripps Research scientists contributed key insights into human health and disease, developed potential new drugs and vaccines, and received global acclaim for their work.

And, just after the close of the institute’s fiscal year, K. Barry Sharpless, PhD, the W.M. Keck Professor of Chemistry, received the 2022 Nobel Prize in Chemistry for his invention of click chemistry, an ingenious method for building molecules.

This was his second Nobel, making him one of only two scientists to ever receive two Nobel Prizes in Chemistry.

Alcohol Use Disorder Marisa Roberto, PhD, the Schimmel Family Chair, and her team showed—in animal models and human brain tissue—how the neurotransmitter noradrenaline goes awry with alcohol dependence and addiction. Their findings suggest that blocking some brain cells from sensing noradrenaline could help treat alcohol use disorder.

The Roberto lab also found that anxiety occurring during withdrawal from excessive alcohol use may be driven in part by the release of the immune protein, CSF1, in the brain.

Targeting CSF1 may also be a good strategy for treating alcohol use disorder.

Overturning previous scientific thought, Candice Contet, PhD, showed that a signaling molecule, corticotropin-releasing factor, was not linked with alcohol dependence or alcohol withdrawal. The discovery leads to new understanding of alcohol withdrawal in the brain.

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A Year in Review (continued)

ALS (Amyotrophic lateral sclerosis) An experimental drug co-developed in the lab of John Griffin, PhD, began a Phase 2 clinical trial in patients with ALS. The goal of the trial is to prove the safety of the drug and its effectiveness against ALS.

Anxiety Chemist Ryan Shenvi, PhD, along with his laboratory team, developed a method to synthesize a chemical found in the bark of the rainforest tree Galbulimima belgraveana. They found the chemical binds to opioid receptors in the brain and may have utility as a new antidepressant or anti-anxiety drug.

Cancer Calibr, the drug discovery division of Scripps Research, reported promising results from a first-in-human clinical trial of its switchable CAR-T platform. In the phase 1 study for patients with B-cell malignancies, a class of blood cancers, 7 of 9 patients responded and 6 of 9 had a complete response. The novel CAR-T cell therapy leverages patients’ own immune cells to treat cancer, putting the cells under the control of a molecular “switch” that seeks to mitigate potential life-threatening side effects that have hampered the use of cell therapies to date.

Katja Lamia, PhD, further illuminated the link between chronic circadian disruption and increased lung cancer growth in animal models by pinpointing a family of genes whose activity was increased when changes to sleeping cycles disturbed the daily rhythm of body temperature. The findings could help protect vulnerable groups, such as shift workers and others with irregular schedules.

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COVID-19 COVID-19 Working with his team at the Scripps Research Translational Institute and other collaborators, Kristian Andersen, PhD, developed an algorithm for the early detection of SARS-CoV-2 variants in wastewater, a tool that was quickly adopted by many public health labs.

2022

Scientists led by Raiees Andrabi, PhD, characterized 30 antibodies that recognize a wide variety of coronaviruses —these antibodies successfully block not only all the SARS-CoV-2 variants tested but also other related viruses.

In a preclinical study, a nanoparticle-based COVID-19 vaccine developed in the lab of Jiang Zhu, PhD, elicited immune responses suggesting very potent and broad protection against SARS-CoV-2. This new approach could greatly outperform other COVID-19 vaccines.

The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, awarded Scripps Research $67 million to lead a major new antiviral drug development center, known as the Center for Antiviral Medicines and Pandemic Preparedness (CAMPP).

Eye Disorders

By restoring the light-sensing function of human retinas hours after death, Anne Hanneken, MD, and collaborators generated an unprecedented trove of data on the physiology of human vision and revealed a new way to study age-related macular degeneration and other eye disorders.

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A Year in Review (continued)

ALS lateral sclerosis) Heart(Amyotrophic Disease A team led by Ali Torkamani, PhD, developed a smartphone app that can calculate users’ genetic risk for coronary artery disease. Their study showed that at-risk users who downloaded the app were much more likely to start using statins or other cholesterol-lowering therapies, compared to those with low-risk scores.

The three-year observational results of a direct-to-participant clinical trial led by Steven Steinhubl, MD, found that people who wore heart rhythm-recording patches for early detection of atrial fibrillation (AFib) had a lower rate of stroke, heart attack or other major vessel-blocking blood clots, when compared to a control group.

Influenza Collaborating with other labs, Andrew Ward, PhD, discovered a new antibody in the blood of some people that can recognize a broad variety of flu viruses. The discovery is another step toward the development of a universal flu vaccine.

Metabolic Disorders Ardem Patapoutian, PhD, working with Li Ye, PhD, the AbideVividion Chair in Chemistry and Chemical Biology, discovered new sensory neurons that carry a stream of messages from adipose tissue to the brain. Their findings could eventually be co-opted to treat obesity or metabolic disease.

A collaboration between teams in the labs of Luke Wiseman, PhD, and Enrique Saez, PhD, showed that an experimental compound called IXA4 tested in obese mice activated a natural signaling pathway, protecting them from harmful obesity-driven metabolic changes, which normally lead to diabetes.

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Neurodegenerative Disease

2022

A team in the lab of Hahn Professor of Neuroscience Hollis Cline, PhD, discovered hundreds of proteins being transported throughout the healthy brain in small membrane-enclosed sacs, revealing a new form of communication between brain cells. The findings could lead to better understanding of neurological conditions such as Alzheimer’s and autism spectrum disorder.

Sandra Encalada, PhD, the Arnold and Arlene Goldstein Associate Professor of Molecular and Experimental Medicine, demonstrated how toxic aggregates form inside brain cells and how to block this cell-killing process associated with prion diseases. Her discovery may have significance for other neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases.

To support her research, the National Institute on Aging, part of the National Institutes of Health, awarded Encalada a $4.1 million grant.

Stuart Lipton, MD, PhD, holder of the Step Family Foundation Endowed Chair, and his team showed how blocking a key cellular cleanup system leads to the buildup and spread of abnormal protein aggregates in the brain.

The discovery offers a clear and testable hypothesis about the progression of Parkinson’s and may lead to new treatments.

Stroke

The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, awarded the first $4 million tranche of a potential $20 million in direct funding for a large “phase three” clinical trial of an experimental stroke drug—3K3A-APC—invented in the lab of John Griffin, PhD. The drug has demonstrated strong brain-protecting effects in animal models of stroke.

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A Year in Review (continued)

Institute Accolades

2022 Three Scripps Research faculty were elected to the National Academy of Sciences, one of the highest honors awarded to scientists. The election of Hollis Cline, PhD, Jane Dyson, PhD, and James Williamson, PhD, brings the number of institute faculty memberships in the National Academies of Sciences, Medicine and Engineering to 30.

Facts at a glance Some of the most brilliant minds in the world join forces at Scripps Research:

Scientists here have won 6 Nobel awards The faculty currently includes

Scripps Research garnered 17 places on the 2021 Highly Cited Researchers list published annually by Web of Science, the world’s largest publisher-neutral citation index. Researchers on this list rank among the top one percent of citations in their field over the prior decade.

2 MacArthur Fellows Chemists at Scripps Research have won 6 Wolf Prizes

30

The Skaggs Graduate School of Chemical and Biological Sciences received another top-10 ranking by U.S. News & World Report.

The school’s chemistry program ranks 6th in the nation and the biological sciences program ranks 9th.

memberships

We educate and train the scientific leaders of tomorrow: The Skaggs Graduate School of Chemistry and Biological Sciences at Scripps Research is consistently ranked among the ten best graduate programs of its kind in the nation

by U.S. News & World Report.

in the National Academy of Sciences, Engineering and Medicine

Scripps Research added new financial leadership to the Institute in June 2022 by appointing Caroline Moon* as Chief Financial Officer. * Caroline Moon was also promoted to Chief Operating Officer in 2023.

Scientific teams collaborate across disciplines to improve human health:

175+

Every day, Scripps Research makes an impact nationally...

faculty members

working to advance scientific knowledge

Our drug discovery division, Calibr has in its pipeline

50+ potential medicines

15

50+ 1,100+ $ 295M active spin-off companies

U.S. patents

in annual federal and state grant expenditures

...as well as globally

FDA-approved drugs and vaccines have arisen from our discoveries Our Translational Institute is reaching underserved groups via digital technologies and site-less clinical trials.

Our scientists address diseases OF THE WORLD’S affecting

85%

Faculty earned 13 spots on the 2022 Highly Cited Researchers list (representing the top 1% in the world)

Ranked

#1 10

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POPULATION

in the world for our impact on innovation

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What can I do?

At Scripps Research, our deep commitment to our mission and emphasis on innovation enable us to lead the way for nonprofit biomedical research institutes.

We are sustainably conducting world-class scientific research and translating our discoveries into new medicines and treatments that are reshaping the future of human health each day. We’d love to partner with you.

Learn more Visit our website at scripps.edu to take a virtual peek inside our labs to see what we’ve been working on. Through our institute website and podcast, you’ll meet dedicated faculty members and research associates and learn about their scientific journeys. On the Scripps Research YouTube channel, you can watch recorded presentations that match your areas of interest. And when you sign up for our free monthly e-newsletter, you’ll never miss a “Eureka!” moment.

Connect with us Join the Scripps Research community via social media for current updates and to learn more about what we do. Better yet, help us spread the word about our work by sharing with your friends and networks.

Make a gift Ensure our scientists are able to continue their research without interruption.

Philanthropic support from our friends and advocates allows us to think creatively, shift quickly and move swiftly toward the next life-changing discovery. Make your gift online at give.scripps.edu or reach out to our Office of Philanthropy.

Chairman John D. Diekman, PhD Founding Partner, 5AM Ventures Ron Burkle Founder, The Yucaipa Companies Founder and Chairman, Ronald W. Burkle Foundation Gerald Chan, ScD Co-founder, Morningside Tom Daniel, MD Chairman, LocanaBio Inc. Mark Edwards Founder and Managing Director, Bioscience Advisors, Inc. Peter C. Farrell, PhD, DSc Founder and Chairman, ResMed Benedict Gross, PhD Professor Emeritus, Mathematics, Harvard University Professor, Dept. of Mathematics, UCSD Sherry Lansing Co-founder, Stand Up To Cancer Founder, The Sherry Lansing Foundation Lillian Lou, PhD President and Program Director, The John C. Martin Foundation Claudia S. Luttrell President, The Skaggs Institute for Chemical Biology Mark Pearson Founder and CEO, Altamont Pharma Co-founder and Vice Chairman, Drawbridge Realty Trust

Office of Philanthropy 10550 N. Torrey Pines Road, TPC-2 La Jolla, CA 92037 (800) 788-4931 philanthropy@scripps.edu

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Administrative Leadership

Board of Directors

Jen Rubio Co-founder and CEO, Away Co-founder, The David C. Butterfield and Alfonso D. Rubio Memorial Foundation

Herbert Wertheim, OD, DSc, MD (hc) Founder and CEO, Brain Power Incorporated Co-founder, Dr. Herbert and Nicole Wertheim Family Foundation Peter Schultz, PhD Vice Chair of the Board President and CEO, Scripps Research L.S. “Sam” Skaggs Presidential Chair Ardem Patapoutian, PhD Faculty Board Appointee Professor, Department of Neuroscience Presidential Endowed Chair in Neurobiology, Scripps Research Board Observer Stewart Butterfield Co-founder and CEO, Slack Co-founder, The David C. Butterfield and Alfonso D. Rubio Memorial Foundation

Peter Schultz, PhD President and CEO L.S. “Sam” Skaggs Presidential Chair Caroline Moon Chief Operating Officer Eric Topol, MD EVP, Director, Scripps Research Translational Institute The Gary and Mary West Chair of Innovative Medicine Emilie Broderick VP, Academic Planning Chinh Dang Chief Information Officer Chris Emery VP, Marketing and Communications Melina Fairleigh VP, People Morgan Hoffman VP, Facilities, Construction and Engineering Meredith Johnston VP, Philanthropy Jared Machado, CPA VP, Treasury and Corporate Finance Marshall Olin, Esq. General Counsel

In Memoriam Christopher T. Walsh, PhD Harvard Medical School

Academic Leadership Phil Dawson, PhD Dean, Graduate and Postdoctoral Studies Donna Blackmond, PhD Chair, Chemistry The John C. Martin Endowed Chair in Chemistry Dennis Burton, PhD Chair, Immunology and Microbiology James & Jessie Minor Chair in Immunology Ian Wilson, DPhil Chair, Integrative Structural and Computational Biology Hansen Professor of Structural Biology Hugh Rosen, MD, PhD Chair, Department of Molecular and Cellular Biology Pearson Family Chair James Paulson, PhD Chair, Molecular Medicine Cecil H. and Ida M. Green Chair of Chemistry Marisa Roberto, PhD Vice Chair, Molecular Medicine Schimmel Family Chair Hollis Cline, PhD Chair, Neuroscience Hahn Professor of Neuroscience

Scripps Research | Annual Report 2022 Visit us at scripps.edu