2023-2024 Annual Publication

NEXT GENERATION MEDICINES

JONATHAN S. STAMLER, MD

President and Co-Founder, Harrington Discovery Institute

Robert S. and Sylvia K. Reitman Family Foundation Chair of Cardiovascular Innovation

Distinguished University Professor Professor of Medicine and of Biochemistry

Case Western Reserve University

University Hospitals Health System

DEAR COLLEAGUES,

It has been an eventful year. In biotech, gene editing, RNA, and AI technologies took center stage, and treatments for diabetes and obesity improved the lives of many. Meanwhile, at Harrington, we launched new programs in rare disease and brain health, and we advanced our mission and impact.

The Institute’s Center for Major Diseases, our foundational physician-scientist program, is effectively combining grant and seed funding for potential new treatments. It has high-quality science, a strong infrastructure, and good volume. Today, the industry recognizes our grant awards as signatures of creativity and therapeutic potential, and better yet, therapeutics are hitting milestones. Meanwhile, our Center for Brain Health Medicines can point to exciting advances in Huntington’s, ALS, and Alzheimer’s. This includes two first-in-human clinical trials, reflecting how treatments for neurodegenerative conditions are becoming increasingly possible (and likely).

In 2023, we expanded our partnership with the University of Oxford by launching the Therapeutics Accelerator (the Accelerator) with former UK Prime Minister David Cameron as founding Chair of the Oxford-Harrington Rare Disease Centre Advisory Council. The Accelerator will receive support from a new partnership between University Hospitals, University of Oxford, and investment company Oxford Science Enterprises. It will operate a unique non-profit/for-profit model bolstered by an initial commitment of up to $250 million to identify, fund and advance innovative projects from academic partners in the US, UK, and Canada. It has a goal of 40 rare disease medicines in clinical trials by 2034, and our

Therapeutics Development Advisors are eager to support it with their expertise.

Harrington’s seed fund has made ten catalytic investments in companies to date, and we have co-invested with many venture capital groups. Further, we have a fruitful partnership with Advent Life Sciences, a leading fund that invests in select companies arising from within and outside the Harrington network. We also anticipate that Oxford Science Enterprises, with its mission to create a science-business ecosystem for Oxford-Harrington technologies, will add significant capital to rare disease discoveries.

With so much activity and progress, we also can point to successes! Results are strong, with 201 medicines in the making, coming from 71 academic institutions, 39 companies launched, 21 medicines in the clinic, and 15 licenses to pharma. We owe the fact that we have raised nearly a billion dollars to the vision, care, sponsorship, and commitment of our impact donors and partners. Together, we all share a mission to accelerate promising discoveries into medicines for unmet needs and thus to shape the future of medicine.

Sincerely,

TABLE OF CONTENTS

2-3

A letter from Jonathan S. Stamler, MD

President and Co-Founder, Harrington Discovery Institute

6-7

Our Impact

8 The Philanthropic Flywheel

Ronald G. Harrington

Philanthropist and Entrepreneur

9 Advisory Councils

10-11

A New Transatlantic Rare Disease Therapeutics Accelerator

12-13

Retinal Gene Therapy Offers Hope for Those with Blinding Diseases

Jean Bennett, MD, PhD and Albert Maguire, MD 2023 Harrington Prize Co-Recipients

14-15

Discovering Pathways for Knocking Out Cancer

Arlene Sharpe, MD, PhD

2024 Harrington Prize Recipient

16

Back to Basics: 2023 Scientific Symposium

17

Singular Mission: 2024 Scientific Symposium

18-19

Harrington Scholar Programs

20 Meet Our Scholars

21 Congratulations New Scholars

OUR INNOVATION CENTERS

Won Jin Ho, MD

Maximilian Konig, MD

Berge Minassian, MD 27 Michael Pacold, MD, PhD

Anthony Rosenzweig, MD 29 Jeffrey Schelling, MD 30 Ming-Ru Wu, MD, PhD

Timothy Yu, MD, PhD

Scholar Spotlight: Barry Coller, MD

Moving an Antiplatelet Activation Treatment Toward FDA Approval

Scholar Spotlight: Jeannie Lee, MD, PhD

Advancing a Drug Prototype to Treat Rett Syndrome

Giving Spotlight: James and Susan Ratner Alzheimer’s Disease in the Family

Harrington Scholars 2013-2024

SUCCESS METRICS

201

39 MEDICINES IN THE MAKING INSTITUTIONS SUPPORTED

71

15 LICENSES TO PHARMA COMPANIES LAUNCHED

21 MEDICINES IN THE CLINIC

OUR IMPACT

INSTITUTION WITH HARRINGTON SCHOLAR(S)

“Harrington Discovery Institute has ac hieved incredible momentum. Donors really understand now what research scientists can do with their gif ts. They see medicines, patients, and successes.”

RONALD G. HARRINGTON

Philanthropist and Entrepreneur

THE PHILANTHROPIC FLYWHEEL

business entrepreneurs, distinguished researchers and professors, and many

family could imagine committing capital,” Mr. Harrington said.

mention the family’s billion-dollar goal for capital commitments to the new institute. On that wintry evening in Cleveland, the Harringtons thought it was too big and distant a goal to promote. But make no mistake, raising a billion dollars to support the scientists moving early medical discoveries toward patient benefit was their goal. Mr. Harrington would not mention it publicly, but privately, his family had their sights firmly set on it.

Fast forward 12 years. Harrington Discovery Institute is now partnered with world class institutions (such as University of Oxford and Morgan Stanley) and with world leaders including the former UK prime minister David Cameron, renowned

helping drive the overall growth of Harrington Discovery Institute and its affiliates. Top venture capital firms have launched new funds to accelerate the impact of Harrington-related discoveries. And Morgan Stanley has provided a unique worldwide platform called Morgan Stanley GIFT Cures in which family offices can donate to Harringtonrelated cures in development.

The organization has tremendous momentum, and philanthropists and impact investors have committed nearly $1 billion to Harrington Discovery Institute, monies that go toward cures that otherwise would not exist. The Harringtons are overjoyed by the momentum. “It’s the best way our

Mr. Harrington compares such momentum to a philanthropic flywheel, a comparison he gleaned from one of his favorite books, Good to Great, by Jim Collins. “With this flywheel,” Mr. Harrington said, “there’s no single action or donor that is creating success. Its many actions, programs, projects, innovations, steps, decisions, researchers, leaders, and donors, and together they’re turning the flywheel, creating sustained success.”

The Harringtons passionately believe that patients everywhere deserve the philanthropic flywheel. “We can get many more treatments and cures that could ultimately benefit millions of patients,” said Mr. Harrington.

ADVISORY COUNCILS

HARRINGTON REGIONAL LEADERSHIP ADVISORY COUNCIL

David Doll Morgan Stanley Council Chairperson

Dee Haslam Haslam Sports Group

Ralph Della Ratta Citizens Financial Group

Jim Ratner RMS Investment Group, LLC

Rob Durham HKM Direct Marketing Communications

Bob Reitman Riverbend Advisors

Brian Gale I.D. Images

Gregory Skoda Chair Emeritus MarCom

HARRINGTON INTERNATIONAL ADVISORY COUNCIL

Ron Harrington CEO, Biomotiv Council Chairperson

Dee Haslam

Haslam Sports Group Campaign Cabinet Executive Sponsor

John F. Crowley President & CEO

Biotechnology Innovation Organization (BIO)

Joe Kanfer CEO GOJO Industries (ret.)

Brenda Garza Philanthropist

Jill Harrington The Harrington Family Foundation

Vicki Tifft Entrepreneur

Jonathan Stamler, MD President Harrington Discovery Institute

OXFORD-HARRINGTON RARE DISEASE CENTRE ADVISORY COUNCIL

David Cameron

The Rt Hon the Lord Cameron of Chipping Nor ton

Former Prime Minister, United Kingdom Council Chairperson

John F. Crowley President & CEO

Biotechnology Innovation Organization (BIO)

Sir John Bell President Ellison Inst. of Technology, Oxford

Baroness Nicola Blackwood Chair Genomics England

Ron Harrington CEO Biomotiv

Jonathan Stamler, MD President Harrington Discovery Institute

A NEW TRANSATLANTIC RARE DISEASE

THERAPEUTICS ACCELERATOR

On a gray October day in 2023, UH CEO Cliff Megerian, Dr. Stamler, and Ron Harrington stood on the campus of the University of Oxford to sign a sweeping, new agreement. The signing event celebrated a co-funding and co-investment agreement among University Hospitals, University of Oxford and investment company Oxford Science Enterprises (OSE), and it officially launched a new therapeutics accelerator. Also present for the launch events were David Cameron, former Prime Minister of the UK; Sir John Bell, then Regius Professor of Medicine at Oxford, Irene Tracey, Vice-Chancellor of the University of Oxford, Jim Wilkinson, Chief Financial Officer of OSE, and Professor Matthew Wood, the Director and Chief Scientific Officer of the Oxford-Harrington Rare Disease Centre. Dr. Stamler stated, “This represents a major step forward toward finding the best medicines that improve outcomes for the millions of individuals and families affected by rare diseases.”

PARTNERS CONTRIBUTE WORLD-CLASS CAPABILITIES

The Therapeutics Accelerator (the ‘Accelerator’) is part of the Oxford-Harrington Rare Disease Centre (OHC). Formed in 2019, the OHC enables Oxford and Harrington to work together on rare diseases. It combines Oxford’s groundbreaking rare disease research with Harrington’s expertise in therapeutics development. With over 250 principal investigator scientists working on over 350 rare diseases, Oxford has unrivaled scientific leadership and resources. For its part, Harrington Discovery Institute has proven successes in moving breakthrough discoveries out of academic labs and into clinical development and has put 19 medicines in the clinic in twelve short years.

The OHC created the Accelerator to identify, fund and advance breakthrough discoveries from the UK, US, or Canada and deliver new treatments for those suffering from rare

diseases. It is expected to advance a pipeline of therapies toward new spinout companies and is backed by up to $250 million in funding. Alongside monies for breakthrough projects, the OHC pairs the projects with expert drug developers who collectively have hundreds of years of pharma experience and proven track records of bringing new drugs to market.

FAST-MOVING ADVANCES IN RARE DISEASE

The Accelerator aims to deliver 40 new, potentially life-changing therapies for rare diseases into clinical trials over the next 10 years and earn multiple approvals from regulators in key markets. It has a big nut to crack—over 400 million people worldwide live with a rare disease, and approximately 50 percent are children. There is, however, an incredibly exciting aspect of contemporary rare disease discovery and development, specifically the speed with which the genetics and

genomics landscape is improving. Former Prime Minister David Cameron, whose son suffered from an ultra-rare disease and who is now chairing the Advisory Council of the Oxford-Harrington Rare Disease Centre, said “Breakthroughs such as the use of genomics opened my eyes to how much we could know about rare diseases.”

Huge and fast-moving advances in fundamental science mean that the pace of getting genetic information about patients with rare diseases is fast and getting faster. Genetic treatment platforms can be both curative and programmable in that the same platform can be the basis for cures for highly related conditions. This feature of treatment platforms can shorten timelines and decrease costs dramatically. Dr. Wood said, “Of the 40 treatments we aim to develop in ten years, I would expect probably 80 percent to be genetic and therefore programmable. Once we successfully develop one, the next two, three, and four should be easier.”

SIGNIFICANT CAPITAL COMMITMENTS

A key partner of the OHC is Oxford Science Enterprises (OSE), an investment entity affiliated with the university and committed to translating scientific breakthroughs into commercially successful businesses. OSE will commit seed capital to the most promising projects, and Ed Bussey, its CEO, said his organization is eager to make investments and help improve patient outcomes for people impacted by rare diseases. What’s more, the OHC is in the process of raising a sizeable new impact fund to commit additional monies to the most promising rare disease innovations. The fund is expected to play a role similar to that which Advent Life Sciences (a leading venture capital firm) plays for promising major disease projects through the Advent-Harrington Impact Fund.

•Dr. Jonathan Stamler, Dr. Cliff Megerian, Lord Cameron, Ron Harrington

•Dr. Jonathan Stamler, Prof Irene Tracey, Dr. Cliff Megerian, Jim Wilkinson

•Sir John Bell

•Lord Cameron, Jill Harrington, Nancy Harrington, Ron Harrington

STREAMLINING CLINICAL REGULATIONS IN THE UK

Regulation does not always keep pace with science and business. With that in mind, the OHC Therapeutics Accelerator expects to help set a global science and innovation agenda for rare disease. Together with the Medical and Healthcare products Regulatory Agencies (equivalent to the FDA in the US), Genomics England, the Association of the British Pharmaceutical Industry, and Mila’s Foundation, the OHC has formed the Rare Therapies Launch Pad. The group aims to streamline clinical regulations to make it quicker and less costly to get new rare disease therapies to patients.

UK regulators are aware that existing regulations were devised long ago for small molecule drugs benefiting large patient populations, whereas genetic drugs today are developed for small patient populations. Currently, both must go through the same barriers, including multi-year, expensive animal safety studies. “What we are working to determine,” said Wood, “is what we will do instead—what will be safe and acceptable to regulators, who want to innovate and evolve their regulations to meet enormous, unmet patient need.”

Photos above are from the October 2023 Accelerator Launch. Shown from L to R:

THE 2023 HARRINGTON PRIZE FOR INNOVATION IN MEDICINE

RETINAL GENE THERAPY OFFERS HOPE FOR

THOSE WITH BLINDING DISEASES

The husband and wife team of Dr. Albert Maguire and Dr. Jean Bennett will probably never star in a Hollywood “rom-com”: the two met while dissecting a human brain in a neuroanatomy class. For the patients who will benefit from the duo’s groundbreaking translational research into gene therapy for inherited retinal diseases, however, the important fact will be that they did meet—not how. The result has been more than 30 years of professional and personal collaboration that has literally helped bring sight to the blind.

“Jean had been working at the National Institutes of Health doing transgenesis, which is a form of gene transfer, and I was working in a retinal degeneration lab as a medical student,” says Dr. Maguire. “What really struck me is that most of the diseases we were looking at were Mendelian, meaning one gene caused the disease. And I thought, ‘If we can isolate pieces of DNA, take them out of one

organism and put them back into a different one, why can't that be used as an approach to treating a genetic disease?’ I threw that out to Jean and she said, ‘Why don't wetry it?’ And away we went.”

Dr. Bennett says that simple notion may have been a little naïve, however, because the first gene that caused retinal degeneration wouldn’t even be identified for several years.

“But I was really interested in the idea of gene therapy, and Al and I both thought that the retina would be a great target: it's easy to expose because it's an epithelial layer, there’s a very small amount of tissue involved, and it's physically easy to get a reagent or a drug to cover the entire surface,” she says.

Drs. Maguire and Bennett continued their research in the lab for years, and

were eventually rewarded with a stunning “eureka moment.” It came while working with three dogs that had been born blind with a type of Leber’s congenital amaurosis (LCA), a rare blindness caused by the lack of a functional gene. To evaluate the response to their experimental gene therapy in a large animal eye, the researchers delivered the missing gene to the dogs’ eyes.

“Within two weeks I received a call from the animal caretakers,” Dr. Bennett recalls. “They said, ‘These dogs can see!’ And sure enough, the dogs were running around, wagging their tails, catching balls. It was staggering.”

The striking success with the dog model of LCA provided support for human clinical trials, and the Bennett-Maguire team was the first in the United States to initiate a Phase III in vivo gene therapy clinical trial for a genetic disease. Results from their trials were the first

(LEFT) JEAN BENNETT, MD, PhD

F.M. Kirby Emeritus Professor of Ophthalmology and Cell and Developmental Biology

University of Pennsylvania Perelman School of Medicine

(RIGHT) ALBERT MAGUIRE, MD

F.M. Kirby Professor of Molecular Ophthalmology

University of Pennsylvania Perelman School of Medicine

to demonstrate reversal of blindness in children with LCA, and in 2017 resulted in FDA approval of gene therapy to the eye, followed in 2018 by the first gene therapy product approved worldwide for a retinal disease (Spark Therapeutics’ Luxturna (voretigene neparvovec-rzylz)), and the first recombinant viral vector approved in the United States to be delivered directly to the target tissue in humans.

Building on their work in LCA, Drs. Bennett and Maguire initiated a clinical trial for a second inherited retinal degeneration, choroideremia. In doing so, they opened a path from the laboratory to the clinic in additional blinding diseases.

The Bennett-Maguire body of work has inspired numerous other academic and biotechnology groups to initiate gene therapy clinical trials for different forms of blinding disease. There are now dozens of gene therapy clinical trials that have been initiated for retinal disease, with more than half a dozen in (or recently having completed) Phase III.

Their work has done nothing less than change medical practice. Instead of doctors telling patients “there is nothing we can do” to treat inherited blindness, patients are now genotyped. Those with the mutation that may make them candidates for Luxturna are referred for potential treatment, and those with

other genetic forms of blindness learn about clinical trials for which they might qualify.

“Individuals born blind due to genetic disease now have hope that there will one day be a treatment for their condition,” Dr. Bennett says.

THE HARRINGTON PRIZE FOR INNOVATION IN MEDICINE , established in 2014 by Harrington Discovery Institute and the American Society for Clinical Investigation (ASCI), honors physician-scientists who have moved science forward with achievements notable for innovation, creativity and potential for clinical application.

THE 2024 HARRINGTON PRIZE FOR INNOVATION IN MEDICINE

DISCOVERING PATHWAYS

FOR KNOCKING OUT CANCER

Over the past three decades, evolving understandings of the signals that control immune system responses have led to the development of immunotherapy drugs, including pembrolizumab and nivolumab, which are used to treat cancer. Called immune checkpoint inhibitors, these drugs neatly overcome covert manipulation of the body’s defensive on/off processes by cancer cells.

“A healthy immune system can protect the body from disease,” says Arlene Sharpe, MD, PhD, Kolokotrones University Professor and Chair of the Department of Immunology at Harvard Medical School. She has been at the forefront of immunoinhibitory pathway study and discovery, contributing novel understandings that have helped launch a revolution in cancer treatment.

Dr. Sharpe’s groundbreaking scientific discoveries defined the signaling

pathways involving checkpoint proteins PD-1 (programmed death 1) and CTLA-4 (cytotoxic T-lymphocyte associated protein 4) on the surface of T cells. The work laid the foundation for development of immune checkpoint inhibitor drugs that target PD-1 and related pathways.

Inspired by the vision of vastly improving patient experience and treatment outcomes, Dr. Sharpe has employed advances in molecular biology to identify essential roles that different molecules play in regulating immune responses. The experience has led her to call tumors “the smartest immunologists” because they have figured out how to exploit inhibitory pathways to evade eradication by the immune system.

TWO PATHWAYS

In partnership with her husband, Gordon Freeman, PhD, Professor of Medicine at Dana-Farber Cancer Institute and Harvard Medical School, also a renowned

molecular biologist and immunologist, Dr. Sharpe shed light on the web of interactions between cancer cells and immune cells.

“I generated a knockout of CTLA-4, which had been a mystery molecule,” Dr. Sharpe recalls. “Was it stimulating immune responses or inhibiting them? We showed in knockout (genetically altered) mice that if the molecule was missing, they developed what looked like an autoimmune disease. We continued looking for more molecules that were cousins of the B7-1 and B7-2 proteins— the binding partners for CTLA-4. That led us to PD-L1 (and PD-L2) molecules. We spent a lot of time understanding that pathway.”

The scientists found PD-L1 on cancer cells as well as immune cells. That meant that cancer was hijacking the protein to prevent elimination by the immune system. Blocking PD-L1 would enhance immune

ARLENE SHARPE, MD, PhD

Kolokotrones University Professor Chair, Department of Immunology, Harvard Medical School

INTEGRATED APPROACHES, COMBINATION THERAPIES

“Today we are studying the entire neighborhood, Dr. Sharpe explains. “Genetic make-up may reveal why immunotherapy can have autoimmunelike side effects in some people and not others. Age, obesity, and an individual’s microbiome all impact treatment responses to checkpoint inhibitors, as do tumor microenvironments. Finding answers in those areas will help us understand prognostic and diagnostic considerations for new types of drug combinations for

Remarking that the pace of novel immunotherapies has quickened dramatically in the 21st century, Dr. Sharpe says, “I feel incredibly fortunate. It’s rare for somebody to discover something and see in their lifetime that it’s led to a therapy— and that’s what it’s really all about. We've made some strides, but there's a lot more to do.”

“I am truly honored to receive the 2024 Harrington Prize for Innovation in Medicine. This acknowledgment is deeply meaningful. I am thrilled to see novel cancer therapies emerge from understanding how the immune system works.”

University of Pennsylvania

University of Southern California

BACK TO BASICS

2023 SCIENTIFIC SYMPOSIUM

The 10th Annual Harrington Scientific Symposium was held May 24-25, 2023, and was the first in-person Symposium since May 2019.

“I think of this Symposium as bringing us 'back to the basics' of Harrington— the basics of coming together to connect, inform, and accelerate the discoveries that can change the face of medicine,” said Jonathan S. Stamler, MD, President and co-Founder, Harrington Discovery Institute, during the Symposium’s opening presentations.

In his remarks, Harrington Project founder Ronald G. Harrington spoke about

2023 SCIENTIFIC ADVISORY BOARD

William G. Kaelin Jr., MD

Andrew Marks, MD

Jeremy Nathans, MD, PhD

Michael Welsh, MD

Indiana University School of Medicine

Harrington Discovery Institute’s evolution and the factors that have led to its success including its capacity for innovation, a culture of innovation, the right people and partners, and shared values.

Jean Bennett, MD, PhD, co-recipient of the 2023 Harrington Prize for Innovation in Medicine, shared the groundbreaking translational research she and co-recipient Dr. Albert Maguire, conducted to restore sight in inherited genetic diseases.

Robert Lefkowitz, MD Investigator, HHMI Duke University Medical Center

Nobel Laureate Robert Lefkowitz, MD provided reflections on his career and major discoveries for Symposium guests over dinner at Severance Hall.

The Harrington model was highlighted in a panel discussion with Harrington Rare Disease Scholar, Justin Ichida, PhD, and Harrington Investment Advisory Board members Drs. John Rice and Graeme Martin, and Vice President of Therapeutics Development Dr. Diana Wetmore.

The Scholar Experience presentation was given by twice-awarded Harrington Scholar, Ben Gaston, MD. Dr. Gaston, a pediatric pulmonologist, presented his work, which accelerates ventilator weaning for patients with COVID-19 lung infection.

TO ALL OUR PANEL MEMBERS!

2023 THERAPEUTICS DEVELOPMENT CENTER

Stephen Brenner, PhD

Jim Bryson, PhD

Dennis Klinman, MD, PhD

George Trainor, PhD

2024 SCIENTIFIC ADVISORY BOARD

Barbara Kahn, MD

Andrew Marks, MD

Jeremy Nathans, MD, PhD

Michael Welsh, MD

2024 THERAPEUTICS DEVELOPMENT CENTER

Jim Bryson, PhD

Debra Bowes, MBEE

Dennis Klinman, MD, PhD

George Trainor, PhD

Jean Bennett, MD, PhD

Justin Ichida, PhD

Benjamin Gaston, MD

SINGULAR MISSION

2024 SCIENTIFIC SYMPOSIUM

Leaders in medicine, science, academia and industry convened in Cleveland, Ohio for the 11th Annual Harrington Scientific Symposium May 22-23, 2024. United by a shared mission of curing diseases, attendees heard from innovators whose breakthroughs are elevating the standard of care for patients across disease areas.

Harrington Discovery Institute President and co-Founder Jonathan Stamler, MD told the audience “we now see an increasing academic and industry recognition of the efficiency and effectiveness of our model.” Harrington Project founder Ronald G. Harrington built on Dr. Stamler’s remarks

SAVE THE DATES :

MAY 21-22, 2025

MAY 20-21, 2026

by sharing updates on key initiatives, including the launch of two new advisory councils.

Daniel Skovronsky, MD, PhD, Executive Vice President at Eli Lilly and Company, delivered the Keynote Address on "Harnessing Incretin Biology to Improve Human Health," which highlighted the tremendous advancements in the treatment of diabetes and obesity.

The 2024 Harrington Prize recipient, Arlene Sharpe, MD, PhD, from Harvard Medical School, shared reflections on her scientific career and groundbreaking work in immunology, which has led to new cancer

therapies. Harrington Rare Disease Scholar Ed Grabczyk, PhD, LSU Health Sciences Center, shared his experience working with the Harrington team who connected him to an industry partner for the further advancement of his work with DNA repeat expansion disorders.

Symposium attendees also heard from Ali Rezai, MD, Executive Director of the WVU Rockefeller Neuroscience Institute. A renowned neuroscientist and neurosurgeon, Dr. Rezai presented his work in ultrasound technology that has transformed the treatment of neurological and mental health conditions.

“My lab has been palpably energized by the rigor and pace of our Harrington project and how the unique infrastructure of advising and c ollaboration, through standing meetings and the yearly Harrington Symposium, has enabled such remarkable progress.”

LOREN WALENSKY, MD, PhD Dana-Farber Cancer Institute 2022 Harrington Scholar-Innovator

Ed Grabczyk, PhD

LSU Health Sciences Center

Ali Rezai, MD

Rockefeller Neuroscience Institute, West Virginia University

Arlene Sharpe, MD, PhD

Harvard Medical School

Daniel Skovronsky, MD, PhD

Eli Lilly and Company

HARRINGTON SCHOLAR PROGRAMS

Our Scholar Award programs support physicians and scientists in their development of new medicines to address unmet medical need. Our current programs are listed below by Innovation Center.

MAJOR DISEASES

HARRINGTON SCHOLAR-INNOVATOR AWARD

Supports physician-scientists whose research has the potential to change the standard of care in medicine. Each year, Harrington Discovery Institute’s Scientific Advisory Board reviews applications from outstanding physician-scientists and selects those whose discoveries embody innovation, creativity and potential for clinical impact. ELIGIBILITY: MD OR MD/PhD; US AND CANADA.

HARRINGTON-MSTP SCHOLAR AWARD AT CASE WESTERN RESERVE UNIVERSITY

In partnership with Case Western Reserve University (CWRU)

Supports Medical Scientist Training Program (MSTP) students whose research shows innovation and creativity, and the potential for progressing from scientific discovery to a medical therapy.

ELIGIBILITY: MSTP STUDENTS AT CWRU.

BRAIN HEALTH MEDICINES

ADDF-HARRINGTON SCHOLAR AWARD

In partnership with the Alzheimer’s Drug Discovery Foundation (ADDF)

Supports research efforts that seek to prevent, treat, or cure Alzheimer’s disease, related dementias and cognitive decline associated with aging. ELIGIBILITY: MD OR PhD; US, CANADA AND UK.

BRAIN HEALTH MEDICINES SCHOLAR AWARD

Supports researchers whose work aims to treat, prevent or cure Alzheimer’s disease and related dementias. ELIGIBILITY: MD OR PhD; US, CANADA AND UK.

RARE DISEASES

OXFORD-HARRINGTON RARE DISEASE SCHOLAR AWARD

In partnership with the University of Oxford through the Oxford-Harrington Rare Disease Centre

Supports researchers who are advancing promising rare disease discoveries from academic labs into clinical practice. ELIGIBILITY: MD OR PhD; US, CANADA AND UK. FOR MORE INFORMATION: HarringtonDiscovery.org/Funding

MEET OUR SCHOLARS

CONGRATULATIONS NEW SCHOLARS

These scholars have been recently awarded and will be profiled in our next annual publication.

MAJOR DISEASES

2024 HARRINGTON SCHOLAR-INNOVATORS

DEMETRIOS BRADDOCK, MD, PhD

Yale University

JULIANE BUBECK WARDENBURG, MD, PhD

Washington University St. Louis

CHRISTOPHER HOLLEY, MD, PhD

Duke University

ANDREW HSIEH, MD

Fred Hutchinson Cancer Research Center

DEEPAK NIJHAWAN, MD, PhD UT Southwestern

RUSSELL PACHYNSKI, MD

Washington University St. Louis

DAVID RALEIGH, MD, PhD University of California, San Francisco

JULIE SABA, MD, PhD University of California, San Francisco

CARLOS SUBAUSTE, MD Case Western Reserve University

JORDAN WINTER, MD University Hospitals Cleveland Medical Center

BRAIN HEALTH MEDICINES

2024 ADDF-HARRINGTON SCHOLARS

ROSEMARY JACKSON, PhD

University of Dundee

TIMOTHY RICHARDSON, PhD

Indiana University

2024 BRAIN HEALTH MEDICINE SCHOLAR

LI GAN, PhD

Weill Cornell Medicine

RARE DISEASES

2024 OXFORD-HARRINGTON RARE DISEASE SCHOLARS

JACQUELYN BOWER, PhD University of North Carolina at Chapel Hill

LOUIS CHESLER, MD, PhD Institute of Cancer Research

CHARLES GERSBACH, PhD

Duke University

XIANXIN HUA, MD, PhD University of Pennsylvania

MICHELE JACOB, PhD

Tufts University School of Medicine

BOWEN LI, PhD

University of Toronto

MICHAEL PACOLD, MD, PhD

New York University

CARLO RINALDI, MD, PhD University of Oxford

TIMOTHY YU, MD, PhD

Boston Children’s Hospital

HAIYAN ZHOU, MD, PhD University College London

A NOVEL THERAPEUTIC FOR

PROTEINURIC KIDNEY DISEASE

FOCUS : Targeting a calcium-activated potassium channel to reduce kidney podocyte injury

A hallmark of most chronic kidney disease is proteinuria, where high levels of protein spill into an individual’s urine. Hypertension, diabetes, and primary proteinuric kidney diseases damage kidney podocytes, epithelial cells that serve as the final barrier to urinary protein loss. Using a genetic model of proteinuric kidney disease, Dr. Campbell has identified a calcium-activated potassium channel, KCa3.1, which becomes upregulated in injured podocytes and shows potential as a druggable target.

“We uncovered the role of KCa3.1 through transcriptomic profiling of genes that were dysregulated in an experimental model of podocyte injury,” explains Dr. Campbell. “We then performed target validation with human biopsy tissue from patients with proteinuric kidney disease, as well as cell-based functional assays and rodent disease models.”

With Harrington support and guidance in lead compound optimization, Dr. Campbell and his team are conducting proofof-concept testing with small molecules that inhibit KCa3.1 function. He hopes to demonstrate target engagement and efficacy.

“We are working toward an early-stage treatment to slow disease progression and, ultimately, to be part of a comprehensive management plan supporting overall kidney and cardiovascular health,” Dr. Campbell says.

Podocytopathies and their associated proteinuric kidney conditions account for 90% of all end stage kidney disease in the US, costing $20 billion annually. Hardest hit are African-Americans, who comprise more than 35% of dialysis patients, despite comprising only 13.5% of the population. Latino and Native Americans are vulnerable, also. With the Food and Drug Administration’s (FDA’s) recent acceptance of proteinuria reduction as a surrogate endpoint for protection from kidney function decline in some kidney disease indications, timing is good for new therapeutic drug development.

“Harrington’s expertise and project management support are amazing,” says Dr. Campbell. “We are optimistic about making a positive impact for patients with high unmet clinical need.”

Irene and Dr. Arthur M. Fishberg Professor of Medicine and Professor of Pharmacological Sciences and inaugural Director of the Mount Sinai Center for Icahn School of Medicine at Mount Sinai

“Our Harrington team is critical to lead compound generation

JACQUES GALIPEAU, MD

Don and Marilyn Anderson Professor in Oncology

Associate Dean for Therapeutics Development

University of Wisconsin School of Medicine and Public Health

Director, UW Program for Advanced Cell Therapy

University of Wisconsin – Madison

BANISHING DIABETES WITH A

“LIVING THERAPY” APPROACH

FOCUS : Gene editing to express a fusion protein for pancreatic islet graft tolerance

In hyperglycemia (diabetes), endocrine “islet” cells in the pancreas produce insufficient insulin or cannot use it effectively. Currently, no cure exists, and for 37 million Americans with Type 1 and Type 2 forms of the disease, pharmaceutical insulin becomes a lifeline. Dr. Galipeau and his team are working on restoring normal pancreatic functioning using a genetically-engineered, tolerogenic islet graft approach, with the aim of developing a diabetes cure.

“Our invention concept is based on how placenta allows pregnancy to continue even though the mother and the baby in her womb are separate organisms,” explains Dr. Galipeau. “We copied nature by synthetically encoding a gene for PIDO, a synthetic fusion protein consisting of programmed death-ligand 1 (PD-L1) and indoleamine dioxygenase (IDO) that allows transplanted tissue to evade immune response. In our diabetic mouse model studies, pancreas islet allografts gene modified to express PIDO were not rejected even though no immunosuppressive drugs were given. The grafts

reversed hyperglycemia and, importantly, remained functionally viable long term.”

Harrington support and guidance is enabling the team to test clinical grade human stem cells engineered to make PIDO protein and differentiate into synthetic islet cells in mice. Based on previous cross-species animal modeling studies, Dr. Galipeau is optimistic. The process also has significant advantages over other recent experimental graft technologies designed for immune tolerance.

“PIDO-equipped islets, which are tolerated, avoid immunosuppression complications, and can be produced at high volume, could standardize the therapy and make off-the-shelf grafts a reality for diabetics,” Dr. Galipeau says. “We hope to fill a void in tolerogenic immunotherapy and dramatically change the lives of millions of individuals.”

“The market and industry knowledge Harrington provides perfectly suits our needs.”

A KNOCKOUT TREATMENT

FOR PANCREATIC DUCTAL CANCER

FOCUS : Inhibiting PTPN22 to enhance antitumor immunity

The fourth leading cause of cancer deaths worldwide, metastatic pancreatic ductal adenocarcinoma (PDA) has few treatment options. Dr. Ho and his team have harnessed the immune system in animal models in a way that raises new hope. They found a viable target for overcoming resistance to immunotherapy that could be leveraged in comprehensive treatment strategies for PDA and potentially, other cancers.

“Our findings show that Protein Tyrosine Phosphatase Non-receptor Type 22 (PTPN22)—a key regulator of T-cell receptor (TCR) signaling that leads to tumor growth in pancreatic and breast cancers is a druggable target,” Dr. Ho says. “In experiments with mouse models, we observed that when PTPN22 signaling is absent, immune system function is strengthened. Subsequently, we tested a novel small molecule agent, L1, to inhibit PTPN22 and we found the same effect.”

Dr. Ho and his team have developed an assay to better understand PTPN22 expression in other human cancers and are working to further characterize it through their access to Johns Hopkins University’s robust biorepository of cancer specimens. With Harrington assistance, the next translational step they hope to achieve is L1 optimization. Because L1 synergizes with a class of drugs already on the market and in use for chemotherapy, it has strong potential for augmenting anticancer immunity and greatly improving patient outcomes.

“Harrington is a bridge between our increasing knowledge of PTPN22 inhibition and defining the most opportune disease models and medicinal chemistry,” Dr. Ho says. “We are very excited to advance our work with Harrington’s guidance and expertise.”

WON JIN HO, MD Assistant Professor of Oncology

Johns Hopkins University

“Our Harrington team helps us understand each step of the innovation process.”

MAXIMILIAN KONIG, MD

Assistant Professor of Medicine Division of Rheumatology

Johns Hopkins University

ENGINEERING AN ARMY TO FIGHT

ANTIPHOSPHOLIPID SYNDROME

FOCUS : Deploying chimeric autoantigen T-cell receptor technology

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder that causes blood clots and pregnancy complications, including repeated miscarriages. Existing treatments—commonly lifelong therapy with blood thinners—do not address the underlying autoimmune problem and often fail. Rheumatologist, Maximilian Konig, MD, and his team have developed a way to reprogram the immune system to stop the autoimmune attack without suppressing its vital functioning.

The groundbreaking approach, called CATCR (chimeric autoantigen T-cell receptor, pronounced “catcher”), involves immune cell engineering similar to CAR-T cell technology except that the scientists genetically edit the T-cell receptor directly, turning them into precise weapons against rogue B cells that drive APS.

“In patients suffering from APS, a small subset of B cells becomes self-reactive—they recognize and attack an abundant

plasma protein called beta-2-glycoprotein I (B2GPI),” explains Dr. Konig. “These rogue B cells also make the autoantibodies that cause blood clots and pregnancy loss in APS. Armored with CATCRs, we have shown that a very small number of re-engineered T-cells can eliminate the B2GPI-reactive B cells while sparing all normal B cells to fight infection.”

With Harrington support, Dr. Konig is refining structural characteristics and functions of CATCR-T cells while conducting efficacy and safety studies in humanized models.

“Having a team of experts in drug manufacturing, regulatory affairs, and commercial development is a major advantage in advancing CATCR,” Dr. Konig says. “We hope to leverage this technology to treat patients with APS first, and eventually design precision cellular therapies for various other autoimmune and rheumatic diseases.”

“Our Harrington advisory team is ensuring our therapeutic vision is realized.”

STOPPING LAFORA DISEASE

IN ITS TRACKS

BERGE

MINASSIAN, MD

Division Chief, Pediatric Neurology

Jimmy Elizabeth Westcott Distinguished Chair in Pediatric Neurology

University of Texas Southwestern

FOCUS : A divalent siRNA drug to treat a rare, fatal epilepsy

The most severe form of human epilepsy, Lafora Disease (LD), cruelly strikes patients in adolescence, progressing to continuous seizures during every waking moment of their shortened lives. Today’s treatment is primarily palliative and aimed at reducing seizures. Dr. Minassian, a pediatric neurologist who began investigating LD genetics in the mid-1990s, is testing a unique, divalent siRNA-based approach in mouse models with potential for transforming and saving human lives.

“Lafora Disease results from mutations of two genes, EPM2A and EPM2B, which encode for the Lafora and Malin proteins,” explains Dr. Minassian. “The proteins are integral to storing and releasing cellular

glycogen molecules to make glucose for fueling body and brain functions. Normally, glycogen chains are shaped for solubility in the surrounding cellular fluid, enabling access by enzymes for glucose production. In LD, the chains lengthen and twist together, becoming insoluble. They precipitate occlusions of glycogen-derived particles called Lafora bodies. Glucose production is disrupted, ultimately leading to seizures.”

Collaborating with a University of Massachusetts genetics team, Dr. Minassian is testing divalent small interfering RNAs (siRNAs) to replace Laforin and Malin functions. Targeting and downregulating the glycogen synthase enzyme with siRNAs prevents

glycogen chain deformity and particle accumulation. Normal glucose production and whole brain functioning is restored.

“If we can prevent abnormal glycogen accumulation in the mouse models for months at a time, we potentially can develop an annual therapy for commercialization,” he says. “My Harrington team has expertise in that area, which is invaluable for this project.”

Halting this horrific disease with a drug is tantamount to a cure, Dr. Minassian believes. “I want to help make a fundamental difference in families’ lives by eliminating Lafora Disease in as many cases as we can,” he says.

“Harrington’s wealth of drug development and business knowledge allows me to focus on experiments and my patients.”

MICHAEL PACOLD, MD, PhD

Assistant Professor

Department of Radiation Oncology

New York University

FOCUS : Targeting the CoQ10 headgroup synthesis pathway in pancreatic cancer

Coenzyme Q10 (CoQ10) has a bit of a Jekyll-and-Hyde personality. It is found in every cell in the body and is essential for mitochondrial electron transport chain activity, the source of energy at the cellular level. However, increased CoQ10 synthesis enables uncontrolled cellular proliferation in malignancies.

CoQ10 consists of a lipophilic tail and a quinone headgroup. The biosynthesis pathways for the tail are known, but those in the headgroup are largely undefined. By delineating and targeting the headgroup synthesis pathway, Dr. Pacold and his colleagues hope to improve the understanding and treatment of cancer and other diseases driven by uncontrolled cellular proliferation.

Dr. Pacold found that 4-hydroxyphenylpyruvate dioxygenase-like (HPDL), an orphan dioxygenase, is responsible for the reaction that represents the first committed step in the mitochondrial CoQ10

headgroup synthesis pathway. He and his team are investigating the target engagement of lead compounds with the goal of developing HPDL inhibitors, and also examining how HPDL inhibitors attenuate cellular proliferation.

“Our work with Harrington is to take this first step of the headgroup synthesis pathway and basically throw a wrench into the works,” Dr. Pacold said.

The team chose to apply their findings to pancreatic cancer because it appears that pancreatic cancer cells, which live in an extremely low oxygen environment, cannot lose as much CoQ10 as normal cells.

“With other cells you can cut the amount of CoQ10 production and they do just fine. But if you reduce the CoQ10 in the pancreatic cancer cells they don’t like it. Why that is we don’t yet know,” he said.

“Harrington is very much a hybrid between the best of academia and the best of industry. It gives you access to the best of the medical industry with excellent consultants and project managers who have brought products to market, combined with the risk-taking of academia.”

EXERCISE-INSPIRED TARGETS

TO PROMOTE HEART HEALTH

FOCUS : Aiming at lncExACT1 to repair and regenerate cardiomyocytes

Cardiologist, Anthony Rosenzweig, MD encounters many diseased hearts. Curious to deeply understand what makes hearts healthy, he and his team conducted genomic studies to compare RNA pathways in cardiomyocytes (muscle cells) in exercised healthy hearts and diseased hearts of mouse models. They identified and validated a pathway driven by a noncoding RNA molecule they named lncExACT1 (pronounced “link exact one” for long noncoding Exercise-Associated Cardiac Transcript). lncExACT1 increases in human and animal hearts in disease, where overexpression induces pathological growth and heart failure. It decreases in the exercised hearts, however, and its chemical inhibition promotes cardiomyocyte repair and regeneration. With Harrington support,

the team hopes to demonstrate further proof of concept, validating lncExACT1 in cell models of human heart disease.

“lncExACT1 signaling through the downstream effector, DCHS2, acts as a master switch,” explains Dr. Rosenzweig. “We hope that targeting that switch in patients who can’t exercise sufficiently themselves and turning it off can capture some of the benefits of exercise and improve heart function and decrease the burden of heart disease.”

Interventions such as modified nucleic acid antisense drugs, approved by the US Food and Drug Administration (FDA) for other indications, can effectively inhibit lncExACT1 in animal models. Dr. Rosenzweig and his

team are now testing drug candidates to inhibit lncExACT1 in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes.

“If we can mimic the effects of exercise through this druggable target, we can improve heart function,” Dr. Rosenzweig says. “Our Harrington team’s support and drug development expertise are essential as we refine lncExACT1 inhibition strategies—foundational to preclinical large animal studies and future clinical trials of lncExACT1 inhibition in heart disease.”

Other key contributors to this work include Dr. Haobo Li of Massachusetts General Hospital, and Drs. Jon and Christine Seidman of Harvard Medical School.

ANTHONY ROSENZWEIG, MD

Professor of Internal Medicine-Cardiology and of Pharmacology Director, Michigan Medicine Frankel Institute for Heart & Brain Health University of Michigan

“The Harrington advisors are also helping us consider the most appropriate clinical indications and study populations.”

JEFFREY SCHELLING, MD

Professor of Physiology & Biophysics and Medicine

Case Western Reserve University

A NEW TARGET TO SLOW

DIABETIC KIDNEY DISEASE PROGRESSION

FOCUS : FATP2 small molecule inhibitors to treat diabetic kidney disease

his team have characterized apical FATP2 as the major transporter of fatty acid reabsorption, and have found that global FATP2 deletion in mice resulted in a dramatic reduction in plasma glucose, improved kidney histology, normalization of glomerular filtration rate and greater

“Targeting FATP2 is a completely different approach than existing therapies,” Dr. Schelling said. “Although it may not be a cure for diabetic kidney disease, it potentially represents a new option to prevent patients from progressing to end-

“Harrington Discovery Institute has been incredibly helpful by providing a team of people with unique skills that I don’t have as an MD investigator.”

REPROGRAMMING CANCER CELLS INTO

CANCER FIGHTERS

FOCUS : Turning melanoma cells against themselves as the next-generation immunotherapy

A powerful cancer-fighting gene therapy platform that can detect cancer cells and then “reprogram” those cells to produce anticancer therapeutics could usher in a new era in the detection and treatment of melanoma and other common cancers.

According to Dr. Wu, many cancer researchers aim to target transcription factors, which initiate and regulate the process of tumor formation.

“If you think of the body’s cells as machines, each machine would have around 1,800 knobs (transcription factors) that could be adjusted to make it perform a certain way,” Dr. Wu explained. “Hence, transcription factors are the main culprits that drive tumor formation. However, they are structurally dynamic, making them challenging to target.”

Dr. Wu and his colleagues have developed a programmable Synthetic Transcription-factor Activity Responsive (STAR) gene

circuit platform that can turn aberrant transcription factor activity into therapeutic response. Dr. Wu’s lab is leveraging the STAR gene circuit to educate patients’ own immune systems to kill tumor cells. Gene circuits (highly engineered DNA sequences that work together), delivered systemically, are activated by the presence of cancer-specific transcription factors. The cancer cells are then forced by the activated gene circuits to produce cancer-fighting immunomodulators.

“We were able to develop a comprehensive sensor library that covers almost all known human transcription factors, and this sensor platform has turned out to be a very good weapon to distinguish tumor cells from normal cells,” Dr. Wu said.

In mouse models in vivo, STAR has elicited a strong immune response against melanoma. This therapy also holds promise for ovarian, prostate, and breast cancer, Dr. Wu added.

“Harrington connects me with experts who can give me direct feedback from a pharmaceutical company's leadership perspective, which is very useful.”

‘KNOCKING DOWN’

BAD GENES

FOCUS : Gene- and allele-specific therapies for developmental epileptic encephalopathies

The diagnosis of developmental epileptic encephalopathies (DEEs) can be heartbreaking for new parents. DEEs are frequently associated with infantile-onset, drug-resistant seizures and severe cognitive and other neurodevelopmental impacts.

Children with certain types of DEEs have negative chromosomal mutations, or alleles, in a critical central nervous system channel that is responsible for modulating neuronal excitability. RNase H-activating antisense oligonucleotides—short snippets of RNA that can be designed to change levels of

gene expression—can be used to induce selective, allele-specific reduction of mutant mRNAs. This reduces the amount of the mutant allele and improves the function of the remaining (non-mutated) allele.

With support from Harrington Discovery Institute, Dr. Yu and his team are seeking to develop a portfolio of drugs that could be used to treat children with DEEs. The challenge, Dr. Yu noted, is to safely “knock down” the bad copy of a gene while leaving the good copy of the gene intact. A portfolio is required because targeting

the mutated gene copy depends on the presence of certain genetic markers. As different patients may have different markers, any two patients with DEEs might require different drugs.

“Our goal is to develop these drugs, and then to launch the first clinical trials for kids with DEEs who require this allelespecific approach,” Dr. Yu said. “It’s a very challenging task. This concept has been around for many years, but yet to make it into clinical practice for this patient population. We are hoping to change that.”

TIMOTHY YU, MD, PhD

Physician and Research Investigator Boston Children’s Hospital

“Harrington’s network of experts are wonderful thought partners in helping us tackle the scientific, clinical and regulatory challenges to be solved.”

“Academia and industry are two separate worlds Harrington acts as a bridge between them.”

WILLIAM WULFTANGE, MSTC

Medical Scientist Training Program Doctoral Candidate Case Western Reserve University School of Medicine

PREDICTING CAR-T CELL TREATMENT

EFFICACY AND SAFETY

FOCUS : A novel human tissue-on-a-chip approach

Although chimeric antigen receptor T cell therapy (CAR-T) shows promise for fighting CD-19 leukemias, it has serious challenges. The approach is tremendously expensive, and it carries risk of immune effector cell-associated neurotoxicity syndrome (ICANS).

William Wulftange is developing novel, human tissue-on-a-chip assays for predicting CAR-T cell therapy safety and efficacy prior to patient treatment.

CAR-T personalized medicine involves drawing T cells from a patient, genetically modifying them, then reinfusing them to detect and attack target antigens on cancer cells. By replicating the narrowing channels of human microvasculature onto a tiny wafer, Mr. Wulftange can see how naïve and engineered T cells travel through a model environment.

Tissue-on-a-chip reveals—with high precision—T cell functionality, including interactions with proteins and binding to blood vessel walls. With a few thousand T cells, the test platform can deliver

multiple answers in about three hours, a huge advantage for clinicians with patients awaiting treatment.

Leveraging the expertise of the Gurkan Biomanufacturing and Microfabrication and the Tesar Neuroscience labs at Case Western Reserve University, along with support and strategic assistance of Harrington Discovery Institute, Mr. Wulftange is optimizing the technology and preparing for commercialization.

Timely success of this versatile platform can set a precedent for future clinical CAR-T cell therapy assays, positioning the technology at the forefront of adoptive T cell treatment development.

“With the novel and translational nature of tissue-on-a-chip assays, we believe we can capture a significant space in the patenting landscape,” Mr. Wulftange notes. “Our hope is that this technology one day helps lower cost and risk of groundbreaking cancer treatments.”

A SYSTEMS APPROACH TO MULTIFACTORIAL CONDITIONS

FOCUS : Systems pharmacology therapeutics for retinal diseases

Degeneration of photoreceptor cells, the retinal pigment epithelium and other cell types in the retina is the underlying cause of vision loss in progressive retinal diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy and glaucoma; a large majority of these cases (up to 90%) have only minimally effective or no treatment options available.

According to Dr. Luu, conventional treatments targeting singular disease pathways have not been successful because these diseases are multifactorial. Therefore, he and his team have pursued a systems pharmacology approach.

“Systems pharmacology holds promise as a safe and highly efficacious therapeutic approach for mitigating complex neurodegenerative disorders through synergistic modulation of multiple pathways underlying retinal health and function,” Dr. Luu explained. “In preclinical studies we have demonstrated the efficacy of our SP3 therapeutic platform, based on systems pharmacology, which improved both retinal structure and function across a variety of genetic and environmental disease models.”

With support from Harrington Discovery Institute, Dr. Luu and his team are now focusing on formulation and manufacturing

of the SP3 oral medication as a prelude to human clinical trials for degenerative retinal diseases.

“The data that we have supports broad efficacy,” Dr. Luu said. “Beyond retinal disease we hope to achieve validation of the systems pharmacology platform in treating a variety of neurodegenerative conditions, with clinical trials started for dementia, multiple sclerosis and other indications. Ultimately, I am optimistic our efforts will culminate in an entire class of broad-spectrum therapies representing a new standard of care for acute and chronic disorders associated with aging, stress and/or neurodegeneration.”

JENNINGS LUU

Medical Scientist Training Program Doctoral Fellow

Case Western Reserve University School of Medicine

“The support we’ve received from Harrington has been instrumental in facilitating our pre-IND studies, helping to accelerate the transition of our research from the pre-clinical to the clinical stage.”

AN UNREALIZED

THERAPEUTIC TARGET

FOCUS : Treating Alzheimer’s disease by targeting astrocytes

Non-neuronal glial cells play a vital role in the nervous system by providing physical and chemical support to neurons. In the brain, the most abundant type of glial cells, called astrocytes, have historically been viewed solely in that support role and as passive bystanders in neurodegeneration.

Recent studies, however, have identified a pathological state of toxic reactive astrocytes as a major contributor to neurodegeneration and disease progression in Alzheimer’s disease, making astrocytes an unrealized opportunity as a cellular therapeutic target.

“Astrocytes normally support healthy brain function,” Dr. Tesar said. “But we and others have now shown that in many neurodegenerative diseases astrocytes can switch into a harmful state that increases nerve cell loss and contributes to progressive neurodegeneration.”

Dr. Tesar’s lab has developed a powerful cellular platform to mimic the formation and function of toxic reactive astrocytes. He and his team have tested thousands of drugs for their ability to block the formation of toxic astrocytes, and identified a promising class of drugs that inhibit the epigenetic effector histone deacetylase

3 (HDAC3). In mouse models, inhibition of HDAC3 blocks toxic reactive astrocyte formation, favors a beneficial astrocyte phenotype, and promotes neuroprotection.

With the support of Harrington Discovery Institute, Dr. Tesar and his team are focused on optimizing and advancing new therapeutics that can inhibit HDAC3.

“We think that this project is going to allow us to identify the best-in-class molecules to move forward as therapeutics targeted at HDAC3,” Dr. Tesar said. “If successful, this could be a launching point for pushing our program forward into clinical development.”

PAUL TESAR, PhD

Professor, Department of Genetics and Genome Sciences

Case Western Reserve University School of Medicine

“The ADDF-Harrington program brings fresh technologies, ideas and approaches to a problem, and helps open doors to comprehensive ultimate solutions.”

THINKING OUTSIDE THE

NEUROLOGIC BOX

DONALD WEAVER, MD, PhD, FRCPC, FCAHS Senior Scientist University Health Network

“Harrington is more than just funding. They also bring expertise and advice to the table and that saves both time and money.”

FOCUS : Exploring how the immune system contributes in Alzheimer’s disease

Much Alzheimer’s disease (AD) research focuses on protein misfolding in the brain, which is linked to the toxic accumulation of soluble amyloid-beta oligomers. However, the role of the immune system in the etiology of AD is often overlooked.

“In an attempt to better understand the inherent complexity of Alzheimer's disease, we are focusing on it more as an immune disorder and trying to understand how and why the immune system in the brain goes awry,” Dr. Weaver said.

According to Dr. Weaver, microglia, the resident immune cells of the brain, represent

one of the key mediators of enhanced immune-mediated neuroinflammatory responses in AD. The normal spectrum of microglial responses is intended to promote bacteria/virus elimination, tissue repair and functional recovery. In neurodegenerative disorders, however, the microglia become excessively pro-inflammatory and release neurotoxic factors.

Dr. Weaver and his colleagues have found that by blocking Transient Receptor Potential Melastatin 2 (TRPM2), a receptor on the surface of microglia, they can dramatically lessen microglial proinflammatory activation with minimal effect

on beneficial anti-inflammatory activation. They are seeking to develop a small molecule therapeutic agent which will be effective at reducing or shutting down the negative aspects of microglia.

“The beta amyloid approach to treating Alzheimer’s disease as primarily a neurologic disorder is not dead, but by no means is it the whole story,” Dr. Weaver said. “We need other approaches and other avenues, and the immune system and microglia are the front runners in these approaches.”

AN

AHA(1) MOMENT

FOR TAUOPATHIES

FOCUS : Reducing Tau aggregation in Alzheimer’s disease

Researchers know the rewarding feeling of an “aha moment,” when a significant discovery is made. Such a moment is usually figurative, but in the case of Dr. Blair and a collaborative team searching for new therapies to treat Alzheimer’s disease, it was also literal.

Dr. Blair, lead investigator, and co-principal investigator Brian Blagg, PhD, professor of chemistry and biochemistry at the University of Notre Dame, have demonstrated that the activator of Hsp90 ATPase activity (Aha1) promotes the assembly of tau fibrils that contribute to Alzheimer’s disease.

They have found that levels of Aha1 correlate with tau pathology in Alzheimer’s disease, while other groups have shown that Aha1 interacts directly with tau in neurons and higher Aha1 is associated with worsened neuronal health—all of which supports targeting Aha1 as a therapeutic approach for Alzheimer’s. The team has

(LEFT) LAURA BLAIR, PhD

Associate Professor, Department of Molecular Medicine

University of South Florida

(RIGHT) BRIAN BLAGG, PhD

Professor of Chemistry and Biochemistry

University of Notre Dame

developed Aha1/Hsp90 disruptors that reduce tau aggregation in recombinant and cellular models, and is seeking to characterize the in-vivo properties of their lead compound to understand its binding to Aha1 and prepare for additional optimization.

“We hypothesized that breaking up the interactions between Aha1 and Hsp90, these proteins that together promote the aggregation of tau, will slow down that accumulation and be beneficial for patients that have Alzheimer's disease and other related tauopathies,” Dr. Blair said.

She added that there are about 25 other neurodegenerative diseases categorized as tauopathies where tau aggregation occurs and is a part of the damage in the brain.

“We think that there is potential for many individuals to benefit from a tau-targeted therapy such as this,” Dr. Blair said.

“Harrington Discovery Institute has given us critical feedback about potential biomarkers because having a validated biomarker is going to be very important as we move forward.”

MAKING AN IMPACT

SCHOLAR SPOTLIGHT

MOVING AN ANTIPLATELET ACTIVATION TREATMENT TOWARD FDA APPROVAL

Advancing a new therapeutic all the way to market usually follows a winding path with side excursions that can increase the chances of success.

For Barry Coller, MD, Physician In Chief and Vice President For Medical Affairs at Rockefeller University and 2015 Harrington Scholar-Innovator, the drug development path has been like that. It’s also been part of his career-long interest in platelets, the tiny components of blood that initiate blood coagulation.

“Normally, blood flows easily through blood vessels,” Dr. Coller explains. “But the minute there’s vascular injury, platelets begin sticking to the damaged vessel lining. They have receptors for the proteins present in the lining that causes them to adhere and other receptors that cause them to aggregate.”

IDENTIFYING THE TARGET

Dr. Coller’s platelet research contributed to identifying the platelet integrin αIIbβ3, also called glycoprotein IIb/IIIa (GPIIb/ IIIa), as a receptor involved in platelet

aggregation. Targeting this receptor for anti-clotting therapy, he developed key monoclonal antibodies to inhibit platelet aggregation. Then, working with scientists at Centocor, an early biotechnology startup, he helped develop abciximab, based on a derivative of one of these antibodies. In 1994, abciximab was approved by the Food & Drug Administration (FDA) for use before, during, and immediately after coronary artery procedures, such as angioplasty (with or without stent placement) to prevent clotting. Since then, more than five million patients worldwide have been treated with the drug.

TIME IS OF THE ESSENCE

Although “door-to-balloon” times for angioplasty have improved, Dr. Coller recognized an unmet need for an antiplatelet therapeutic to start working before the patient reaches the hospital. If successful, it could buy time and save precious myocardial tissue from lasting damage, particularly for patients with ST-Segment Elevated Myocardial Infarction (STEMI), the most severe type of heart attack in which blood cannot get through

an artery, and downstream heart muscle is permanently damaged.

By 2015, he had developed a small molecule called RUC-4 in collaboration with Marta Filazola, PhD, Dean of the Graduate School of Biomedical Sciences at Mount Sinai School of Medicine and Craig Thomas, PhD, at the National Institutes of Health Division of Preclinical Innovation. Dr. Coller also received a Harrington ScholarInnovator grant to assess the potential of RUC-4 as a treatment of STEMI.

ADJUSTING COURSE

Initially, the proposed route of administration was intramuscular (IM). Input from Dr. Coller’s Harrington Therapeutics Development Center advisors, Paul Williamson, MD, and Perry B. Molinoff, MD, and pharmacokinetics expert, Martin Graham, PhD, changed that to subcutaneous (SC, or under the skin) administration, opening up the potential of using an autoinjector.

“The SC route is less invasive than IM and might prevent inadvertent injury to

large blood vessels and nerves during an ambulance ride,” says Dr. Williamson.

Pharmacokinetic testing in animal models during Dr. Coller’s Harrington project predicted that administering RUC-4 via the SC route would deliver the high, rapid blood levels necessary to achieve a fast therapeutic response. Subsequently, RUC-4 was licensed by Rockefeller University to CeleCor Therapeutics and development continued.

Another consideration arose during the Harrington project—cost reimbursement for medication given during ambulance transport. Harrington commissioned a detailed analysis of the reimbursement landscape for drugs administered in

an ambulance, which proved extremely valuable in commercialization planning.

FUTURE POSSIBILITIES

BARRY COLLER,

MD

David Rockefeller Professor

Physician In Chief and Vice President For Medical Affairs

The Rockefeller University 2015 Harrington Scholar-Innovator

Dr. Coller envisions one day using modern electrocardiogram technology where a patient experiencing chest pain or other STEMI symptoms could transmit data from a home ECG device directly to a physician for confirmation. The patient could then self-administer the drug, or it could be given upon ambulance arrival by medical technicians.

“Speed is key—after onset of confirmed symptoms, the earliest treatment that would open a clogged artery would save the most heart muscle,” Dr. Coller emphasizes. “This is the biggest determinant of outcome and

recovery in a patient that survives STEMI–RUC-4 has the potential to achieve that. We hope that it can improve outcomes for patients worldwide.”

PHASE 3 CLINICAL TRIAL

Currently, RUC-4 (generic name, zalunfiban) is being tested in the Phase 3 CeleBrate study (NCT04825743), which is scheduled to recruit 2,499 STEMI patients who receive the drug while in the ambulance or upon arrival to the emergency department. The multicenter study is being conducted in the Netherlands, France, Romania, Hungary, Czech Republic, and Canada and also is scheduled for Mexico and the United States.

“The Harrington program was crucial for the development of zalunfiban. My advisor, Dr. Paul Williamson, provided access to experts in multiple disciplines, which led to us to reconsider the route of administration and initiate reimbursement strategies.”

ADVANCING A DRUG PROTOTYPE TO TREAT RETT SYNDROME

Rett syndrome is a rare chromosomal disorder that occurs almost exclusively in girls. It usually manifests itself between six months and 3 years of age, with symptoms that include motor abnormalities, severe seizures, absent speech and autism.

Rett is caused by mutations on the X chromosome, specifically on the MECP2 gene, which is crucial for neuronal development. Females have two X chromosomes, but only one is expressed in any cell, and the other is inactive.

In Rett girls, every affected cell harbors a normal but dormant copy of MECP2 on the inactive X chromosome.

Dr. Lee has been pursuing research into alleviating the disease by reactivating that dormant chromosome to restore MECP2 protein to the brain. It has been a long road, but Dr. Lee and her colleagues have persevered and are making exciting strides as they work to develop a drug prototype to treat the disease.

A FATEFUL PHONE CALL

Dr. Lee’s involvement in Rett syndrome research dates back to 2009, when she received a call from Monica Coenraads, founder and CEO of the Rett Syndrome Research Trust.

“Monica wanted to know if we would be interested in turning on the MECP2 allele from the inactive X chromosome to treat Rett syndrome,” Dr. Lee said. “When Monica asked me that question, the field did not believe that the inactive chromosome could be reactivated. But we had made some preliminary observations and believed it was possible, so we started to dig deeper and deeper.”

Thirteen years later, Dr. Lee and her team are involved in two preclinical lines of investigation, both of which are being supported by Harrington Discovery Institute. The first is a mouse model that is establishing proof of concept for a proposed “therapeutic cocktail,” and the

second is developing a therapeutic that would be suitable for humans.

“We have screened a number of candidates, and we now have two or three dozen that I would consider to be good for further development,” Dr. Lee said. “It’s good news that we have a lot of candidates that can work in a cellular model, but we want to whittle that down to two or three that we will test for safety and efficacy in nonhuman primates. Those are the next steps before we could go into the clinic.”

A HOLISTIC APPROACH

Dr. Lee is quick to credit the contributions of Harrington Discovery Institute to her Rett research program.

“We’ve had other foundation support, but Harrington Discovery Institute provides a team of experts and takes a holistic approach that is very different from any other funding agency,” she said.

SCHOLAR SPOTLIGHT

what the first clinical trial is going to look like. I’ve never done this before, and I don’t think I would be able to look that far ahead without Harrington’s input.”

Ultimately, Dr. Lee wants the message to Rett girls and their families to be loud and clear: There’s hope.

“We’re hopeful that within the next two to three years, with Harrington’s continued support, our drug will be in the clinic and we’ll be able to make a meaningful impact for the girls and their families,” she said.

JEANNIE

LEE, MD, PhD Professor of Genetics

Massachusetts General Hospital 2018 Harrington Rare Disease Scholar

“I don’t think we would have made as much progress as we have without Harrington Discovery Institute. And it certainly would not have gone at the rate that it has without their support and everything they brought to the project.”

CEO & Co-Founder: Stephen Bloch, MD

Co-Founder: Paul Fonteyne, MBA

Scientific Founder: Stephen Strittmatter, MD, PhD, Yale University 2020 Harrington Scholar-Innovator

Allyx Therapeutics takes a novel approach to preserve and protect synapses for people living with neurodegenerative diseases. Its lead compound, ALX-001, is a first-in-class oral therapy with a unique mechanism of action at mGluR5, which has been shown to be essential for mediating synaptic dysfunction and loss caused by multiple misfolded proteins. Clinical programs are currently underway in Alzheimer’s disease (Phase 1b nearing completion; Phase 2 anticipated to begin Q1, 2025) and Parkinson’s Disease (Phase 1b underway). Founded in 2019 by a group of Yale scientists, seasoned biopharma industry executives, and venture capitalists, Allyx raised a Series A financing in 2021 from a group of biotech investors including Harrington Discovery Institute.

For more information, visit allyxthera.com.

“In the Alzheimer’s disease ecosystem, venture philanthropists like Harrington Discovery Institute fills a critical gap in funding new therapeutics for patients. Harrington is a key partner in financing Allyx Therapeutics’ clinical trials to show Allyx’s novel treatments protect neuronal synapses and memory in Alzheimer’s disease.”

STEPHEN BLOCH, MD

INVESTMENT SPOTLIGHT RARE RESPIRATORY DISEASES

Executive Chair: David Hipkiss

Co-Founders:

Professor Eric Alton, Imperial College

Dr. Chris Boyd, University of Edinburgh

Professor Deborah Gill, Oxford University

Professor Uta Griesenbach, Imperial College

Professor Steve Hyde, Oxford University

Dr. Gerry McLachlan, University of Edinburgh

AlveoGene is a gene therapy company created and funded by Oxford Science Enterprises, Harrington Discovery Institute at University Hospitals, and Old College Capital in partnership with six leading scientists from the world renowned UK Respiratory Gene Therapy Consortium (GTC). The GTC was founded in 2001 to catalyze the application of pioneering research to gene therapy development and manufacturing related to cystic fibrosis and other respiratory diseases, and originated at Imperial College London and the Universities of Oxford and Edinburgh. Alveogene is developing therapies to address rare respiratory diseases using a novel lentiviral gene therapy platform designed for inhaled delivery—InGenuITy®

For more information, visit alveogene.com.

“It has been a first year of continual achievement for AlveoGene. Leveraging our inhaled gene therapy platform, InGenuITy®, the team has generated compelling world leading data with AVG-001 (AATD) and AVG-002 (SP-B Neonatal Surfactant Deficiency). These data support their next stages of clinical translation and ultimate approval of first-in-class inhaled gene therapies with the potential to transform outcomes for patients with rare respiratory diseases.”

DAVID HIPKISS

GIVING SPOTLIGHT ALZHEIMER'S DISEASE IN THE FAMILY

Cleveland-based real estate development entrepreneur, Jim Ratner began a deeply personal association with Harrington Discovery Institute shortly after learning that his brother, renowned scientist, Mark Ratner, PhD, was diagnosed with Alzheimer's disease.

“I knew almost nothing about Alzheimer’s,” Jim says. “Learning that Mark has the disease felt intensely tragic—as if a plague descended on our family. I never thought something like that would happen to someone in my family, let alone someone with a mind capable of such complex and pioneering scientific work.”

Jim had many questions. Why do some and not others get the disease? What are the treatment options? What is going to happen next? As the illness progressed, it was obvious little could be done to slow the degenerative process. He turned to friend and University Hospitals physician, Dan Simon, MD.

“Dan is someone I've had the privilege of knowing since he came to Cleveland and then became involved with Harrington. I highly value his opinion and work because his judgments are always based on fact,” Jim says.

Dr. Simon, a practicing cardiologist with University Hospitals, is the Chief Academic Officer of UH and recruited Jonathan Stamler, MD, to Cleveland.

“When Jonathan came to Cleveland from Duke University, I knew he was here to do something major,” Jim relates. “When they unveiled the Harrington Discovery Institute, it was obvious that it was an important initiative. After Mark’s diagnosis, I saw Harrington as a great opportunity to support research in an area where I had personal and direct experience.”

FOCUS AND SYNERGY

According to the Alzheimer’s Association®, nearly 7 million Americans are living with the disease. By 2050, this number is projected to rise to nearly 13 million.

Jim strongly believes that getting the edge on Alzheimer’s requires unprecedented effort.

“Many diseases that once were incurable or considered unstoppable were cured eventually, and significant interventions—such as the COVID-19 vaccination—show how fast progress can be made with great effort and dedication of resources, both intellectual and financial,” he says. “I see this with Harrington’s approach to Alzheimer’s, but it's the same thing with each disease they are working on—the hands-on effort, the search for the best talent and most innovative solutions, plus worldwide partnerships that complement their capabilities.”

GREAT FOR THE REGION

Harrington Discovery Institute is a unique addition to Northeast Ohio’s reputation for premier medical innovation, Jim believes.

“My wife, Susie, and I had never seen anything like their model,” he relates. “Harrington does not seek cures necessarily but aims to advance new treatment for diseases where there is great unmet need. They have made brain health medicines a major priority. This is important because you can disperse your resources too widely and not have adequate focus on any single area.”

That the Harrington approach could lead to the most promising treatments for patients is a bright spot for the Ratners.

“I continue to hope and believe Harrington will make a difference— maybe not for my brother, but for many people,” he says. “That’s how you repair the world and make it a better place.”

“There are all kinds of signs. At first, you're in denial, and then that no longer works. The reality is too punishing. And then you go looking for treatment. Everybody goes down that road."

JIM RATNER

BRAIN HEALTH MEDICINES SCHOLAR AWARD

The Brain Health Medicines Center at Harrington Discovery Institute supports novel research that aims to treat, prevent or cure Alzheimer’s disease and related dementias.

Applications to the Scholar Award program can be submitted at any time and will be reviewed at the end of each quarter and awarded on a rolling basis.

Successful applicants will receive:

• $100,000 with appropriate justification for one year

• Potential to renew for a 2nd year based on milestones achieved

• Dedicated Project Manager for the duration of the award

• Drug development, commercial strategy and business development suppor t from Harrington’s Therapeutics Development Center exper ts

• Opportunity to qualify for up to $400,000 in additional funding and drug development suppor t

Eligibility: MD or PhD researchers in the US, Canada and the UK operating their own independent lab.

For questions about this funding opportunity, please email Questions@HarringtonDiscovery.org.

LEARN MORE AND APPLY: HarringtonDiscovery.org/BrainHealthFunding

MAJOR DISEASES

2024 HARRINGTON SCHOLAR-INNOVATORS

DEMETRIOS BRADDOCK, MD, PhD Yale University

JULIANE BUBECK WARDENBURG, MD, PhD

Washington University St. Louis

CHRISTOPHER HOLLEY, MD, PhD Duke University

ANDREW HSIEH, MD

Fred Hutchinson Cancer Research Center

DEEPAK NIJHAWAN, MD, PhD UT Southwestern

RUSSELL PACHYNSKI, MD Washington University St. Louis

DAVID RALEIGH, MD, PhD

University of California, San Francisco

JULIE SABA, MD, PhD

University of California, San Francisco

CARLOS SUBAUSTE, MD Case Western Reserve University

JORDAN WINTER, MD University Hospitals Cleveland Medical Center

2023 HARRINGTON SCHOLAR-INNOVATORS

KIRK CAMPBELL, MD

Icahn School of Medicine at Mount Sinai

JACQUES GALIPEAU, MD University of Wisconsin – Madison

WON JIN HO, MD

Johns Hopkins University

MAXIMILLIAN KONIG, MD

Johns Hopkins University

BERGE MINASSIAN, MD

UT Southwestern

MICHAEL PACOLD, MD, PhD

New York University

ANTHONY ROSENZWEIG, MD University of Michigan

JEFFREY SCHELLING, MD

Case Western Reserve University

MING-RU WU, MD, PhD

Dana-Farber Cancer Institute

TIMOTHY YU, MD, PhD

Boston Children’s Hospital

2022 HARRINGTON SCHOLAR-INNOVATORS

BURTON DICKEY, MD

MD Anderson Cancer Center

DIANA FARMER, MD

University of California, Davis

JAMES HAGOOD, MD

University of North Carolina at Chapel Hill

LI LAN, MD, PhD

Massachusetts General Hospital

CAROLYN LEE, MD, PhD

Stanford University

MICHAEL LIN, MD, PhD

Stanford University

FRANCIS MCCORMACK, MD

University of Cincinnati

HarringtonDiscovery.org/Scholars

DAVID MYUNG, MD, PhD

Stanford University

BERND SCHNABL, MD University of California, San Diego

LOREN WALENSKY, MD, PhD Dana-Farber Cancer Institute

HANS-GUIDO WENDEL, MD

Memorial Sloan Kettering Cancer Center

2021 HARRINGTON SCHOLAR-INNOVATORS

JENNIFER CHEN, MD University of California, San Francisco

JOHN CHORBA, MD University of California, San Francisco

JOSEPH CONTESSA, MD, PhD Yale University

TOREN FINKEL, MD, PhD University of Pittsburgh

MARIA GRAZIA RONCAROLO, MD Stanford University

AARON SCHIMMER, MD University of Toronto

JILL SMITH, MD Georgetown University

XINNAN WANG, MD, PhD Stanford University

2020 HARRINGTON SCHOLAR-INNOVATORS

RIZWAN HAQ, MD, PhD

Dana-Farber Cancer Institute

MICHAEL HOLTZMAN, MD Washington University

KYU RHEE, MD, PhD Weill Cornell Medicine

STEPHEN STRITTMATTER, MD, PhD Yale University

DONALD WEAVER, MD, PhD, FRCPC, FCAHS University Health Network

TIMOTHY YU, MD, PhD Boston Children’s Hospital

2019 HARRINGTON SCHOLAR-INNOVATORS

ROBERT E. ANDERSON, MD, PhD University of Oklahoma

ROSA BACCHETTA, MD Stanford University

GERALD W. DORN, II, MD Washington University

JOACHIM HERZ, MD UT Southwestern

PAUL W. HRUZ, MD, PhD Washington University

PENG JI, MD, PhD Northwestern University

V. VINOD MOOTHA, MD UT Southwestern

DAWN M. WETZEL, MD, PhD UT Southwestern

T.C. WU, MD, PhD

Johns Hopkins University

ELLEN YEH, MD, PhD

Stanford University

2018 HARRINGTON SCHOLAR-INNOVATORS

SUNEET AGARWAL, MD, PhD

Boston Children’s Hospital

JEFFREY S. GLENN, MD, PhD

Stanford University

WAYNE I. LENCER, MD

Boston Children’s Hospital

ROBERT O. MESSING, MD University of Texas at Austin

VICTOR L. SCHUSTER, MD

Albert Einstein College of Medicine

BHUVANESH SINGH, MD, PhD

Memorial Sloan Kettering Cancer Center

DAVID B. SYKES, MD, PhD

Massachusetts General Hospital

MARC N. WEIN, MD, PhD

Massachusetts General Hospital

ADRIAN WIESTNER, MD, PhD

NHLBI/NIH

MONE ZAIDI, MD, PhD

Icahn School of Medicine at Mount Sinai

2017 HARRINGTON SCHOLAR-INNOVATORS

PAUL L. BOLLYKY, MD, PhD

Stanford University

AMBROSE L. CHEUNG, MD

Geisel School of Medicine at Dartmouth

GIULIO F. DRAETTA, MD, PhD

MD Anderson Cancer Center

SETH J. FIELD, MD, PhD

*University of California, San Diego

TODD D. GOULD, MD

University of Maryland School of Medicine

JOHN J. LETTERIO, MD

Case Western Reserve University

DAVID B. LOMBARD, MD, PhD University of Michigan

DARUKA MAHADEVAN, MD, PhD

*University of Arizona

DEEPAK NIJHAWAN, MD, PhD

UT Southwestern

STUART H. ORKIN, MD

Boston Children’s Hospital

DANIEL S. ORY, MD

Washington University

2016 HARRINGTON SCHOLAR-INNOVATORS

NUNZIO BOTTINI, MD, PhD

*La Jolla Institute for Allergy and Immunology

STANLEY N. COHEN, MD

Stanford University

BENJAMIN M. GASTON, MD

*Case Western Reserve University

RAMA K. MALLAMPALLI, MD

*University of Pittsburgh

M. PETER MARINKOVICH, MD

Stanford University

DAVID J. MILAN, MD

Massachusetts General Hospital

KEVIN D. NISWENDER, MD, PhD

Vanderbilt University

SUSAN P. PERRINE, MD

Boston University

ANN MARIE SCHMIDT, MD

NYU School of Medicine

GERALD I. SHULMAN, MD, PhD

Yale University

2015 HARRINGTON SCHOLAR-INNOVATORS

ROBERT A. BONOMO, MD

Case Western Reserve University

JOHN C. BURNETT, Jr., MD

Mayo Clinic

NICOLE CALAKOS, MD, PhD

Duke University

DAVID R. CLEMMONS, MD University of North Carolina

BARRY S. COLLER, MD

The Rockefeller University

XIANXIN HUA, MD, PhD University of Pennsylvania

RICHARD J. JOHNSON, MD University of Colorado

MARIKKI LAIHO, MD, PhD

Johns Hopkins University

GEOFFREY S. PITT, MD, PhD

*Duke University

IRA A. TABAS, MD, PhD

Columbia University

2014 HARRINGTON SCHOLAR-INNOVATORS

JAYAKRISHNA AMBATI, MD *University of Kentucky

DARREN R. CARPIZO, MD, PhD *Rutgers Cancer Institute of New Jersey

GARRET A. FITZGERALD, MD University of Pennsylvania

MARK S. HUMAYUN, MD, PhD University of Southern California

JOHN N. KHEIR, MD Boston Children’s Hospital

RAHUL M. KOHLI, MD, PhD University of Pennsylvania

IRINA PETRACHE, MD *Indiana University

DAVID H. ROWITCH, MD, PhD University of California, San Francisco

JEAN Y. TANG, MD, PhD Stanford University

DAVID WALD, MD, PhD Case Western Reserve University

2013 HARRINGTON SCHOLAR-INNOVATORS

MARC I. DIAMOND, MD *Washington University

ROGER A. GREENBERG, MD, PhD University of Pennsylvania

GEOFFREY C. GURTNER, MD, FACS Stanford University

RICHARD N. KITSIS, MD Albert Einstein College of Medicine

WOLFGANG B. LIEDTKE, MD, PhD Duke University

SANFORD D. MARKOWITZ, MD, PhD Case Western Reserve University

SCOTT A. OAKES, MD

*University of California, San Francisco

FEROZ R. PAPA, MD, PhD University of California, San Francisco

JONATHAN D. POWELL, MD, PhD

Johns Hopkins University

LARRY S. SCHLESINGER, MD *The Ohio State University

ROBERT B. WILSON, MD, PhD University of Pennsylvania

2023 HARRINGTON-MSTP SCHOLAR

JENNINGS LUU

Case Western Reserve University

2022 HARRINGTON-MSTP SCHOLAR

WILLIAM WULFTANGE

Case Western Reserve University

2021 HARRINGTON-MSTP SCHOLAR

DEREK WONG Case Western Reserve University

2020 HARRINGTON-MSTP SCHOLAR

YI FAN CHEN Case Western Reserve University

2016 OXFORDHARRINGTON SCHOLAR

VALENTINE MACAULAY, MD, PhD, FRCP University of Oxford

2015 OXFORDHARRINGTON SCHOLARS

HELEN MCSHANE, MD, PhD, FRCP University of Oxford

CLAUDIA MONACO, MD, PhD, FESC University of Oxford

2014 OXFORDHARRINGTON SCHOLAR

ALISON SIMMONS, MD, PhD University of Oxford

BRAIN HEALTH MEDICINES

2024 ADDF-HARRINGTON SCHOLARS

ROSEMARY JACKSON, PhD University of Dundee

TIMOTHY RICHARDSON, PhD Indiana University

2023 ADDF-HARRINGTON SCHOLAR

DONALD WEAVER, MD, PhD, FRCPC, FCAHS University Health Network

2022 ADDF-HARRINGTON SCHOLAR

PAUL TESAR, PhD Case Western Reserve University

2021 ADDF-HARRINGTON SCHOLAR

CHRISTIANE WRANN, DVM, PhD Massachusetts General Hospital

2020 ADDF-HARRINGTON SCHOLARS

PAUL FISH, PhD University College London

PAUL WORLEY, MD Johns Hopkins University

2019 ADDF-HARRINGTON SCHOLAR

EUGENIA TRUSHINA, PhD Mayo Clinic

2018 ADDF-HARRINGTON SCHOLAR

KEVIN HODGETTS, PhD Brigham & Women’s Hospital

2017 ADDF-HARRINGTON SCHOLAR

DIANNE M. PEREZ, PhD Cleveland Clinic Lerner Research Institute

2016 ADDF-HARRINGTON SCHOLARS

TRAVIS L. DUNCKLEY, PhD Arizona State University

SUNG OK YOON, PhD The Ohio State University

2015 ADDF-HARRINGTON SCHOLARS

CAROL A. COLTON, PhD Duke University

JERRI M. ROOK, PhD Vanderbilt University

2014 ADDF-HARRINGTON SCHOLARS

THOTA GANESH, PhD Emory University

CHIEN-LIANG LIN, PhD The Ohio State University

2024 HARRINGTON BRAIN HEALTH MEDICINES SCHOLARS

LAURA BLAIR, PhD University of South Florida Douglas Scholar

BRIAN BLAGG, PhD University of Notre Dame Douglas Scholar

LI GAN, PhD Weill Cornell Medicine

2022 HARRINGTON BRAIN HEALTH MEDICINES SCHOLARS

NABIL ALKAYED, MD, PhD Oregon Health and Science University Vinney Scholar

XIN QI, PhD Case Western Reserve University Vinney Scholar

2019 GUND HARRINGTON SCHOLAR

STEPHEN MARTIN, PhD University of Texas at Austin

2018 GUND HARRINGTON SCHOLARS

ZHENG-RONG LU, PhD

Case Western Reserve University

KRISHANU SAHA, PhD University of Wisconsin-Madison

2017 GUND HARRINGTON SCHOLARS

SHANNON E. BOYE, PhD University of Florida

RICHARD H. KRAMER, PhD University of California, Berkeley

SHIGEMI MATSUYAMA, PhD

Case Western Reserve University

THOMAS A. REH, PhD University of Washington

2016 GUND HARRINGTON SCHOLAR

DAVID M. GAMM, MD, PhD University of Wisconsin-Madison

2015 GUND HARRINGTON SCHOLARS

ALBERT R. LA SPADA, MD, PhD

*University of California, San Diego

KONSTANTIN PETRUKHIN, PhD Columbia University

DONALD J. ZACK, MD, PhD Johns Hopkins University

RARE DISEASES

2024 OXFORDHARRINGTON RARE DISEASE SCHOLARS

JACQUELYN BOWER, PhD University of North Carolina at Chapel Hill

LOUIS CHESLER, MD, PhD Institute of Cancer Research

CHARLES GERSBACH, PhD Duke University

XIANXIN HUA, MD, PhD University of Pennsylvania

MICHELE JACOB, PhD

Tufts University School of Medicine

BOWEN LI, PhD University of Toronto

MICHAEL PACOLD, MD, PhD New York University

CARLO RINALDI, MD, PhD University of Oxford

TIMOTHY YU, MD, PhD Boston Children’s Hospital

HAIYAN ZHOU, MD, PhD University College London

2021 HARRINGTON UK RARE DISEASE SCHOLARS

PIETRO FRATTA, MD, PhD University College London

ANGELA RUSSELL, DPhil University of Oxford

HELEN WALLER-EVANS, DPhil Cardiff University

WYATT YUE, PhD

*University of Oxford

HAIYAN ZHOU, MD, PhD University College London

2018 HARRINGTON RARE DISEASE SCHOLARS

ED GRABCZYK, PhD LSU Health Sciences Center in New Orleans

XIANXIN HUA, MD, PhD University of Pennsylvania

JUSTIN ICHIDA, PhD University of Southern California

JEANNIE LEE, MD, PhD Massachusetts General Hospital

JOHN MARSHALL, PhD Brown University

XIN QI, PhD

Case Western Reserve University

DANIEL R. SCOLES, PhD University of Utah

JAMES A. SHAYMAN, MD University of Michigan

COVID-19

2020 HARRINGTON SCHOLARS FOR CORONAVIRUS

MICHAEL BARRY, PhD Mayo Clinic

KATHERINE FITZGERALD, PhD University of Massachusetts

BENJAMIN GASTON, MD Indiana University

JEFFREY S. GLENN, MD, PhD Stanford University

ANASTASIA KHVOROVA, PhD University of Massachusetts

YULIA KOMAROVA, PhD University of Illinois

ANNE MOSCONA, MD Columbia University

MICHEL NUSSENZWEIG, MD, PhD

The Rockefeller University

JAMES REYNOLDS, PhD

University Hospitals of Cleveland/ Case Western Reserve University

JOSEPH VINETZ, MD Yale University

JAMES WELLS, PhD University of California, San Francisco

JAMES WILSON, MD, PhD University of Pennsylvania

IN MEMORIAM

CLARK W. DISTELHORST, MD

2015 Harrington Scholar-Innovator Case Western Reserve University

GAVRIL W. PASTERNAK, MD, PhD

2014 Harrington Scholar-Innovator Memorial Sloan Kettering Cancer Center