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Tackling the Complexity of Autophagy

Our scientists combine state-of-the-art tools with the speed of machine learning to study phenotypic changes that distinguish behaviors of dysfunctional from healthy cells. We are boosting autophagy to address genetically validated, but previously undruggable targets with the goal of overcoming the historical challenges of treating severe neurodegenerative diseases.
An image of neurons from Nine Square Therapeutics

Our Founders

Nine Square was founded by life sciences venture capital firm ATP and renowned scientists at the University of California, San Francisco (UCSF). Our approach is based on the unique premise of converging phenotypic image-based cell profiling, computational molecular modeling, and chemistry with clinical research to develop more effective drugs, faster.

Management Team

Our interdisciplinary team of scientists and biotech leaders is committed to reshape the treatment of debilitating and life-threatening neurodegenerative diseases, including Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and lysosomal storage disorders.

Board of Directors

Spiros Liras, Ph.D.

Nine Square Therapeutics
Apple Tree Partners (ATP)

Seth Harrison, M.D.

Apple Tree Partners (ATP)

James B. Summers, Ph.D.

Pharmaceutical Research and Strategy Advisor

Matthew P. Jacobson, Ph.D.

Nine Square Therapeutics
Apple Tree Partners (ATP) 
University of California, San Francisco

John Hood, Ph.D.

Endeavor Biomedicines

Steve Altschuler, Ph.D. and Lani Wu, Ph.D. (Observers)

Nine Square Therapeutics
University of California, San Francisco

Scientific Advisory Board

Sami Barmada, M.D., Ph.D.

SAB Member

Aimee Kao, M.D., Ph.D.

SAB Member

Roberto Zoncu, Ph.D.

SAB Member

Robert Edwards, M.D.

SAB Member

James B. Summers, Ph.D.

SAB Member

About Us

OUR SCIENCE

LEGAL

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Robert Paul, M.D., Ph.D.

Chief Executive Officer

Robert has more than 20 years of experience in research and clinical development for neurological diseases. He joined Nine Square Therapeutics as CEO in January 2022 after serving as the chief medical officer of Alector, a pioneer in immuno-neurology. Robert came to Alector from Genentech, where he held leadership roles in the company’s Early Clinical Development organization from 2009 to 2016. Prior to working at Genentech, Robert was a neurologist at the University of Munich and a consultant at Boston Consulting Group.

Robert holds an M.D. and Ph.D. from Ludwig-Maximilians Universität München in Germany and is a board-certified neurologist.

Matthew P. Jacobson, Ph.D.

Chief Scientific Officer

Matthew P. Jacobson, Ph.D., is a co-founder of Nine Square Therapeutics and a member of Nine Square’s Board of Directors. Matt is a leading authority in computer-aided drug design and computational structural biology and biophysics and the author of over 200 research publications. He is Professor Emeritus in the Department of Pharmaceutical Chemistry at UCSF and is also a co-founder of Global Blood Therapeutics, Relay Therapeutics, Terremoto Biosciences, and Circle Pharma. Matt is also a venture partner at Apple Tree Partners.

Matt earned his Ph.D. in physical chemistry at MIT and completed postdoctoral research at Oxford and Columbia. As a faculty member at UCSF, he received the NSF CAREER Award, an Alfred P. Sloan Fellowship and several UCSF School of Pharmacy teaching awards. He has served on the editorial boards of several journals, including Biochemistry, PLoS Computational Biology, and Structure.

Mark Rosen, Ph.D.

Vice President and Head of Chemistry

With more than 20 years research and early drug development, Mark joined Nine Square Therapeutics in 2021 to oversee the medicinal and computational chemistry, DMPK, screening, and other drug discovery activities. Prior to joining Nine Square Therapeutics, he held leadership roles in big pharma and at small companies, including Johnson & Johnson, Akebia Therapeutics, Verge Genomics, and Regulus Therapeutics. Mark also co-founded the Johnson & Johnson spinout company, Aetheria Therapeutics in 2014. He has served as an elected member of the American Chemical Society, San Diego Executive Board, the Susan G. Komen grant review board, and as a graduate student advisor for the UCSD Academia/Industry advisory program.

Mark holds a Ph.D. in Organic Chemistry from the University of California, Irvine and a B.S. in Chemistry from the University of California, San Diego. 

Tina Schwabe, Ph.D.

Vice President and Head of Biology

Tina has more than 20 years’ experience as a neuroscientist and cell biologist. She joined Nine Square Therapeutics in August 2021 to lead its biology function, overseeing assay development, functional compound validation, disease model development and testing, and the establishment of the company’s cell profiling platform. Tina came to Nine Square from  Alector, where she lead the team that discovered three novel first-in-class antibody therapeutics targeting innate immune cells in the brain. Tina holds a Ph.D. from the University of Hohenheim, completing postdoctoral fellowships at Rockefeller University and Stanford University. She earned a Master’s degree in Biology from Leipzig University.

Sethu Sankaranarayanan, Ph.D.

Vice President, Preclinical and Translational Sciences

Sethu has more than 20 years’ experience in translational sciences. He joined Nine Square Therapeutics in October 2022 to lead efforts to build the preclinical, translational biomarker platform and clinical disease validation across  programs. Prior to Nine Square Therapeutics, Sethu held scientific leadership positions at Escape Bio, Annexon, Bristol-Myers Squibb and Merck. He led the discovery and development of small molecule and antibody-based therapies from early discovery to clinical target-engagement studies in areas including neurodegeneration, ophthalmology and autoimmune disease.

Sethu has a Ph.D. in Neuroscience from Washington State University with post-doctoral research  completed at Max-Planck Institute at Heidelberg and the Weill Medical College at Cornell University.

Kristine Gordon, PMP

Senior Director, Head of Program Management
and Operations

Kristine brings more than 20 combined years’ experience in research and program management in the life sciences to  Nine Square Therapeutics, which she joined in July 2022. Prior to Nine Square, Kristine led the Program and Alliance Management function at Frontier Medicines and served as a project manager for the Centers for Therapeutic Innovation at Pfizer. Before moving into program and project management, Kristine began her career as a scientist in the laboratory of Dr. Mary-Claire King at the University of Washington. She went onto joing the preclinical research team at Seattle Genetics, now Seagen, where she contributed to the advancement of multiple antibody-drug conjugate programs in oncology.

Kristine has a B.S. in Cell and Molecular Biology from the University of Washington and Project Management Professional certification from the Project Management Institute.

Spiros Liras, Ph.D.
Nine Square Therapeutics
Apple Tree Partners (ATP)

Spiros is co-founder of Nine Square Therapeutics and venture partner at Apple Tree Partners (ATP). He brings to ATP his decades-long career leading scientific innovation and discovery at some of the world’s foremost pharmaceutical companies. At ATP, Spiros  co-founded its portfolio companies Nereid Therapeutics (Cambridge, MA) , Initial Therapeutics (San Francisco, CA), Evercrisp Biosciences (Berkeley, CA), Deep Apple Therapeutics (San Francisco, CA), and Apertor Pharmaceuticals (Alameda, CA).

Prior to ATP, Spiros established and led the External Portfolio Innovation unit within Research and Development at Biogen. Prior to Biogen, he was vice president of Medicinal Chemistry at Pfizer, where he led teams to deliver clinical pipelines in disease areas including cardiovascular, metabolic and neuroscience. Under his leadership, his divisions explored cutting edge drug discovery concepts including selective protein translation inhibition, design of macrocycles for drug discovery in tough target space, allosterism, and tissue targeting design strategies for the delivery of small molecule, oligonucleotide therapeutics and other modalities.

Spiros earned a Ph.D. in Organic Chemistry from Iowa State University and completed postdoctoral studies at the University of Texas at Austin. Spiros is an adjunct professor in the Department of Pharmaceutical Chemistry at the University of California, San Francisco.

Seth Harrison, M.D.
Apple Tree Partners (ATP)

Seth Harrison is a founder and managing partner of Apple Tree Partners (ATP), where he oversees $2.65 billion in committed venture capital. Since starting the firm in 1999, Seth has launched or invested in more than 30 companies focused on delivering cutting-edge therapies for unmet medical needs, with 19 now public or acquired. Prior to ATP Seth was a venture partner at Sevin Rosen Funds and a general partner at Oak Investment Partners.

Seth received an M.D. and MBA from Columbia University, completing a surgery internship at the Presbyterian Hospital in the City of New York. He earned an A.B. from Princeton University. He served on the board of the International Partnership for Microbicides from 2002-2010.

Robert holds an M.D. and Ph.D. from Ludwig-Maximilians Universität München in Germany and is a board-certified neurologist.

James B. Summers, Ph.D.
Pharmaceutical Research and Strategy Advisor
During more than 30 years with Abbott and AbbVie, Dr. Summers held various senior R&D leadership positions, including vice president of neuroscience research, where he led efforts located in Ludwigshafen, Germany, Lake County, IL and Cambridge, MA, focused on the discovery of new drugs for the treatment of Alzheimer’s and Parkinson’s diseases, pain and psychiatric disorders. Under his leadership, the teams advanced more than 20 compounds into clinical development. Currently Dr. Summers serves as a board member and advisor to several biotechnology companies. He is also a venture partner with the Dementia Discovery Fund. Dr. Summers earned a Bachelor of Science in Chemistry, summa cum laude, from Denison University and a Doctorate in Organic Chemistry from Harvard University.
Matthew P. Jacobson, Ph.D.
Nine Square Therapeutics
Apple Tree Partners (ATP)
University of California, San Francisco

Matthew P. Jacobson is a co-founder of Nine Square Therapeutics, a venture partner at Apple Tree Partners (ATP), and a biotech entrepreneur who has co-founded several other successful companies including Global Blood Therapeutics, Circle Pharma, and Relay Therapeutics. A Professor Emeritus in the Department of Pharmaceutical Chemistry at University of California San Francisco, he is a leading authority in computer-aided drug design and computational structural biology and biophysics. His research interests include docking against homology models and flexible protein binding sites, membrane permeability, antibody modeling, mechanisms of protein regulation by post-translational modifications, allostery, and pH. He is author of more than 200 research publications, the recipient of an NSF CAREER award and an Alfred P. Sloan Fellowship, and holder of several patents. Software written by Matt and his collaborators is widely used in the pharmaceutical industry.

Matt earned a Ph.D. in physical chemistry from the Massachusetts Institute of Technology in 1999 and did his postdoctoral work at Oxford University and Columbia University.

John Hood, Ph.D.
Endeavor Biomedicines

John is a 20-year veteran of the life sciences community in California and has founded and led several successful biotechnology companies. He is currently founder, chief executive officer and executive chairman of Endeavor Biomedicines, which was funded in 2021 to develop novel therapeutics for oncology and idiopathic pulmonary fibrosis. John has founded and led several other successful biotechnology companies including the now Bristol-Myers-Squibb-owned Impact Biomedicines, of which he was Founder and CEO.

He began his career in 2001 as director of research at TargeGen, where he co-discovered fedratinib, a treatment option approved worldwide for myelofibrosis, and led a team identifying small molecule therapeutics for cancer and eye disease. John is an inventor on more than 100 patents and author of more than 50 scientific articles.

He received a Ph.D. in Medical Physiology and a B.S. in Biochemistry from Texas A&M University.

Lani Wu, Ph.D., and Steve Altschuler, Ph.D. (Observers)
Nine Square Therapeutics
University of California, San Francisco

Lani and Steve are co-founders of Nine Square Therapeutics and professors in the Department of Pharmaceutical Chemistry at the University of California, San Francisco . They together tackle systems-level questions in biology, disease and pharmacology in their laboratories at UCSF, where they developed a research program that combines experimental biology, data sciences and modeling to attack fundamental problems in cell biology and drug discovery. They entered systems biology and pharmacology through Rosetta Inpharmatics, a biotech startup. Their research careers started in mathematics at the interface of analysis and geometry, in which they found diverse applications, including the Poincaré Conjecture, robotics and computer graphics. They transitioned to engineering at Microsoft, co-leading an invention team that developed machine learning approaches to improve human-computer interactions in areas including computer vision, social networking and noisy speech recognition.  

Lani and Steve are pioneering members of the Bauer Fellows Program at Harvard University and the Green Center for Systems Biology at University of Texas Southwestern Medical Center, and visiting faculty at Mathematical Scientists Research Institutes in Berkeley and Google Brain in Mountain View.

Sami Barmada, M.D., Ph.D.
SAB Member

Sami is the Angela Dobson Welch and Lyndon Welch research professor and associate professor of Neurology at University of Michigan and director of the University’s Michigan Brain Bank. Sami’s research focuses on combining basic biology with translational research and technology development to investigate unanswered questions in neurodegenerative diseases. His lab uses innovative technologies and methods involving fluorescence microscopy, computer science and engineering, bioinformatics, genome engineering and molecular biology to investigate critical abnormalities in RNA and protein metabolism in ALS and FTD.

Sami received his Ph.D. in the Medical Scientist Training Program at Washington University in St. Louis, where he investigated prion diseases. He went on to train with some of the premier clinicians and scientists in neurodegenerative diseases, such as Bruce Miller and Cathy Lomen-Hoerth while at University of California, San Francisco for his neurology residency. Throughout residency and postdoctoral fellowship, Sami worked with Steve Finkbeiner at the Gladstone Institutes, where he established one of the first human neuronal models of familial ALS and FTD.

Sami serves on the executive advisory board of the Robert Packard Center for ALS Research and scientific advisory boards of the Live Like Lou Foundation and Synapticure, Inc. He takes an active role in their efforts to raise awareness of ALS.

Aimee Kao, M.D., Ph.D.
SAB Member

Aimee is the John Douglas French Foundation Endowed professor at the University of California San Francisco School of Medicine and associate professor of Neurology at the University’s Weill Institute for Neurosciences. Aimee’s laboratory studies the basic mechanisms underlying neurodegenerative disorders. She is an expert in the diagnosis and treatment of age-related cognitive conditions such as Alzheimer’s disease, Lewy body disease and frontotemporal lobar degeneration.An award-winning scientist, Aimee She maintains an active clinic at UCSF’s Memory and Aging Center. At UCSF, she teaches medical students and serves as a research mentor to UCSF undergraduates for both theSummer Research Training Program (SRTP)and San Francisco Building Infrastructure Leading to Diversity (SF BUILD) program. Aimee also co-chairs the Neuroscience graduate program’s Diversity, Equity and Inclusion Committee.

Aimee completed her internship at the Beth Israel Deaconess Medical Center, residency in neurology at University of California, San Francisco, where she was chief resident, and received fellowship training in behavioral neurology and molecular genetics. She holds an MD and Ph.D. from the University of Iowa Carver College of Medicine and BS fromBrown University. She joined the UCSF faculty in 2007.

Roberto Zoncu, Ph.D.
SAB Member

Roberto is a professor of Molecular Therapeutics in the Department of Molecular and Cell Biology at the University of California, Berkeley. Prior to UC Berkeley, Roberto was a postdoctoral fellow at MIT’s Whitehead Institute, where he worked in Dr. David Sabatini’s laboratory. Roberto combined biochemical and microscopy-based assays to understand how lysosomes govern the signaling activity of the master growth regulator, mTORC1 kinase, and how these organelles generally function as metabolic signaling centers. For his doctoral studies, Roberto joined Dr. Pietro De Camilli’s laboratory. He used advanced microscopy and chemical genetic techniques to interrogate how a class of phospholipids known as phosphoinositides control endocytic vesicle traffic and maturation.

Roberto holds a Ph.D. in Cell Biology at Yale University. He studied molecular biology at the University of Pisa in Italy.

Robert Edwards, M.D.
SAB Member

Robert is the Cahill professor of Neurology and Physiology at the Weill Institute for Neurosciences at the University of California San Francisco School of Medicine. His work focuses on the molecular and cellular basis of neurotransmitter release and its role in Parkinson’s disease. In his research, he and his colleagues have identified several proteins implicated in Parkinson’s disease. Robert joined University of California, San Francisco from the faculty at University of California, Los Angeles. Among Robert’s many awards is the Established Investigator Award of the National Alliance for Research on Schizophrenia and Affective Disorders. He serves on editorial boards of several journals and the scientific advisory board of the Parkinson’s Foundation. He is a member of the National Academy of Medicine and the National Academy of Sciences.

He studied as a postdoctoral fellow with William J. Rutter after completing residency in clinical neurology at UCSF. Robert completed his M.D. at Johns Hopkins University School of Medicine and BA at Yale College. 

Michael Ehlers, M.D., Ph.D. Apple Tree Partners (ATP)
Mike is general partner and chief scientific officer at Apple Tree Partners (ATP), where he applies expertise gained through a successful career leading research and development at major biopharmaceutical companies. He co-founded ATP’s portfolio companies Intergalactic Therapeutics (Cambridge, MA), Aulos Bioscience (Cambridge, MA), Ascidian Therapeutics (Boston, MA), and Replicate Bioscience (San Diego, CA). Prior to ATP, Mike was executive vice president of Research and Development at Biogen, where he led discovery sciences, translational medicine, clinical development, and regulatory sciences with a focus on neurological, immunological, and rare diseases. He expanded and diversified Biogen’s clinical portfolio, transformed its R&D productivity, advanced more than 20 novel clinical candidates, and oversaw global filings and approvals of Spinraza™ (nusinersen), the first drug approved for spinal muscular atrophy. Prior to Biogen, Mike was senior vice president at Biotherapeutics and chief scientific officer of Neuroscience at Pfizer. While there, he created and advanced the neuroscience and rare disease portfolios,directed global development activities in biologics design, synthesis, and manufacturing, steered academic collaborations focused on immunology and oncology,and brought 22 compounds into the clinic.  Before entering industry, Mike was a professor and investigator at the Howard Hughes Medical Institute at Duke University Medical Center. Hee pioneered studies on neuronal organelles and the trafficking of neurotransmitter receptors. He has received numerous awards, authored more than 100 scientific papers, and served on multiple editorial and advisory boards for the National Institutes of Health, private foundations and many other organizations across industry, academia and government.h Mike holds an M.D. and Ph.D. from Johns Hopkins University School of Medicine and  a B.S. in Chemistry from California Institute of Technology.

Parkin

Parkin is an intracellular protein that regulates mitochondrial quality control by selectively promoting the degradation of dysfunctional mitochondria, and Parkin mutations are implicated in early-onset Parkinson’s disease (PD). Nine has small molecule candidates that promote Parkin activity in lead optimization for PD, and plans to nominate a clinical candidate by [date].

TRPML1

TRPML1 is a lysosomal membrane protein that promotes autophagy by releasing calcium ions from the lysosome, and defects in the TRPML1 pathway have been linked to autophagic disorders and amyotrophic lateral sclerosis (ALS). Nine Square is evaluating small molecule candidates that activate TRPML1 to treat ALS, and plans to nominate a clinical candidate by the end of 2023.
Robert Paul, M.D., Ph.D.
Chief Executive Officer

Robert has more than 20 years of experience in business and clinical development for neurodegenerative diseases. He joined Nine Square Therapeutics as CEO in January 2022 after serving as the chief medical officer of Alector, a leading immuno-neurology and immuno-oncology company. Robert joined Alector from Genentech, where he held leadership roles in the company’s Medical and Neuroscience Clinical Development organizations from 2009 to 2016. Prior to joining Genentech, Robert was a neurologist at the University of Munich and a consultant at Boston Consulting Group.

Robert holds an M.D. and Ph.D. from Ludwig-Maximilians Universität München in Germany and is a board-certified neurologist.