Pursuing a radically different approach to treating neurodegenerative disease

Our approach: “Fix broken proteins”

Origami’s approach is to (1) focus on genetic diseases, (2) use small molecule therapeutics to fix the mutant disease-causing protein, (3) leverage the natural history of the disease to select which patients to treat, when to intervene and what clinical outcomes to measure and (4) demonstrate therapeutic benefit in the clinic.

Our Technology

Proteins arising from genes with mutations may have an altered shape (also called conformation), resulting in defective protein processing and a subsequent cascade of deleterious consequences. Origami is discovering small molecule Kinetic Conformation Stabilizers (KiCoS) to (1) Reshape the protein, (2) Restore normal function and (3) Renew and maintain physiological balance and health.

Disease Areas

Huntington’s Disease (HD)

HD is caused by a trinucleotide repeat expansion in the Huntingtin gene (HTT) that causes an expanded stretch of a single amino acid, glutamine, in the Huntingtin protein (HTT). A causal link exists between this known mutation and the clinical manifestations.

brainHuntington’s disease (HD) is a fatal hereditary, neurodegenerative disorder that results in a loss of cognitive, behavioral and physical control.

compassionHD slowly diminishes the affected individual’s ability to walk, think, talk and reason.  Symptoms usually appear in an individual between 30 and 50 years of age and progress over a 10 to 25 year period.  Eventually, a person with HD becomes totally dependent upon others for his or her care.

chartMore than 60,000 people in the United States and Europe are currently symptomatic with HD and another ~250,000 at risk for HD.  Each child of a person with HD has a 50% risk of having the disease.

pillsAlthough medications can relieve some symptoms in certain individuals, research has yet to find a means of conquering or even slowing the deadly progression of HD.

Our Company

Founded in 2015, Origami Therapeutics Inc. is a discovery stage company pursuing a radically different approach to treat neurological diseases. We are using small molecule kinetic conformation stabilizers (KiCoS) to “fix broken proteins” that cause disease to restore normal function rather than addressing symptoms or eliminating toxic proteins. Origami plans to generate a pipeline of small molecule therapeutics that prevent or delay the onset and the progression of neurodegenerative diseases to improve the quality of patients’ lives.


Beth J. Hoffman, Ph.D. is Founder, President and CEO

Beth J. Hoffman, Ph.D. is Founder, President and CEO of Origami Therapeutics, Inc. Prior to Origami, she was the Vice President, Discovery Biology for Vertex Pharmaceuticals, Inc. Her most significant contributions included the launch of two first-in-class drugs for Cystic Fibrosis (Kalydeco, Orkambi,) with a current market of >$1.5B. These therapeutics created a paradigm shift in the Cystic Fibrosis (CF) field by focusing on the underlying cause of the disease using small molecules to modulate protein folding and conformation. During her tenure she directly contributed to the label expansions for Orkambi, enlarging its market and increasing sales to over $1 billion. In addition, she led the research generating a novel non-opioid pain therapeutic, now entering Phase 3 development, and 2 other protein folding programs to preclinical proof of concept.

At Origami, Dr. Hoffman is leveraging lessons learned from her efforts at Vertex San Diego and 20 years of CNS drug discovery to create a new approach to drug discovery for neurodegenerative diseases by “fixing broken proteins”.  Prior to Vertex, she was a Research & Development executive at Amgen and Eli Lilly.  She has led and overseen programs from target identification to Phase II proof-of-concept and has managed numerous collaborations with biotech and academic institutions. She has made major contributions to 27 assets that have advanced to the clinic in CF, neurology, pain and psychiatry.

In the non-profit sector, Dr. Hoffman serves on the Board of Directors for the San Diego Chapter of the Huntington’s Disease Society of America (HDSA). Dr. Hoffman received an A.B. in Molecular Biology from Wellesley College, a Ph.D. in Cell Biology from the Johns Hopkins University and was Chief of the Molecular Pharmacology Unit at the National Institute of Mental Health, Bethesda, MD.

Leslie J. Schulze, CPA, CGMA is Co-Founder and CFO

Leslie J.  Schulze, CPA, CGMA is Co-Founder and CFO of Origami Therapeutics, Inc. She has made significant contributions towards acquiring and effectively managing VC financing (>$130M), non-dilutive funding (government contracts and grants totaling >$90M), mergers and acquisitions (sales totaling >$700M, including managing a $56M development budget for Phase 3-NDA drug development), asset sales (totaling >$400M) and a corporate collaboration (up to $1.2B in milestones and royalties) throughout her 10+ year career as a senior biotech executive in start-up pharmaceutical R&D organizations.  She has successfully built multiple streamlined operations teams from the ground up as a co-founder of Rempex Pharmaceuticals, Inc. and as one of the early employees at Mpex Pharmaceuticals, Inc. Ms. Schulze founded Cornerstone Business Solutions, Inc. in 2014 to provide CFO-level finance, accounting, and operations consulting services to start-up biotech companies.

In the non-profit sector, Ms. Schulze founded and serves on the Board of Directors for a public charity, Create Joy Project, who’s mission is to provide financial support to other 501(c)(3) organizations.  Ms. Schulze received her Bachelors of Accountancy from University of San Diego and is a Certified Public Accountant and Chartered Global Management Accountant.


 David H. Crean
David H. Crean, Ph.D., MBA

David H. Crean, Ph.D., MBA is a Managing Director & Partner at Objective Capital Partners where he leads the firm’s investment banking transactions with life science and healthcare clients. Dr. Crean has in excess of 25 years of life sciences R&D and corporate development transactional experience in the pharmaceutical industry responsible for leading mergers, acquisitions, licensing and collaborations, and establishing corporate strategy. Dr. Crean holds FINRA Series 79 and Series 63 licenses and is a Registered Investment Banking Representative of BA Securities LLC, Member FINRA SIPC.

Dr. Crean also serves as a business advisor for several early stage life science companies, is a limited partner with Mesa Verde Venture Partners Fund, on the Board of Directors for the Association for Corporate Growth (ACG) in San Diego, Capital Development Committee for BIOCOM, and a member of San Diego Venture Group (SDVG) and Corporate Directors Forum.  Recently, he was recognized and awarded Thought Leader of the Year and Advisor of the Year in 2017 for his advisory guidance to executives in life sciences deals.  Dr. Crean is also active in the non-profit sector where he serves in leading Board roles for Solutions for Change, Alzheimer’s Association and Altus Charter Schools of San Diego.

Dr. Crean holds a Masters of Business Administration (MBA) Degree with a finance concentration from Pepperdine University Graziadio School of Management. Additionally, he holds a Doctorate of Philosophy (Ph.D.) Degree in Biophysics and a Masters of Science (MS) Degree in Oncology from the State University of New York at Buffalo. Dr. Crean also earned a Bachelor of Science (BS) Degree in Biology/ Pre-Med from Canisius College.

Steven Finkbeiner, M.D., Ph.D.

Steven Finkbeiner, M.D., Ph.D., is Director, Taube/Koret Center for Neurodegenerative Disease Research and the Center for Systems and Therapeutics at the Gladstone Institutes, Investigator, Roddenberry Stem Cell Center and Professor, Neurology and Physiology, University of California, San Francisco. He is best known for his pioneering work on neurodegenerative diseases. Dr. Finkbeiner invented robotic microscopy, a new form of imaging that has helped unravel cause-and-effect relationships in amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease), Huntington’s, Parkinson’s, Alzheimer’s and other neurodegenerative diseases. He has used his robotic microscope to resolve the long-standing puzzle in Huntington’s disease. Dr. Finkbeiner studies the molecular mechanisms that are responsible for learning, memory, and neurodegeneration.

In conjunction with Bay Area philanthropists, Dr. Finkbeiner established the Taube/Koret Center in 2009 to accelerate development of drug therapies for patients suffering from conditions such as Huntington’s disease. At Gladstone, he also directs the Hellman Family Foundation for Alzheimer’s Disease Research Program. Dr. Finkbeiner has received numerous awards including the Lieberman Award, the Taube/Koret Prize and the Award for Outstanding Research Achievement from Nature Biotechnology.  He is a member of the American Neurological Association, the Society for Neuroscience, the Society for Cell Biology and the Biophysical Society.

Dr. Finkbeiner is Associate Editor of Autophagy and serves on the editorial board of the Journal of Huntington’s Disease. He earned a bachelor’s degree from Wheaton College and both an MD and a PhD in neuroscience from Yale University.

Lucia Mokres, DVM

Lucia Mokres, DVM is a Biotechnology Entrepreneurial Consultant based in the Bay Area, specializing in helping early stage companies with novel technology gain traction and develop an investable technology and business model. Prior to establishing her consultancy, she was the Chief Medical Officer of EpiBiome, Inc., a precision microbiome engineering company that employs a genomics approach to profiling complex microbial communities, and deploys bacterial viruses to selectively eliminate problematic bacteria without the use of small-molecule antibiotics in humans, animals, and plants. In this role she leveraged her clinical, research, and industry background to provide medical oversight and strategic direction for all clinical development activities, defined regulatory strategy, supported marketing and business development activities, and served as the medical point of contact for external stakeholders. She was a key participant at investor pitches, and was an invited speaker both nationally and internationally on the challenges faced by venture-backed, early stage companies working to gain drug approval. She led EpiBiome through the iCorps program (UCSF), the Springboard Accelerator program, and supported the team through the Illumina Accelerator, Johnson and Johnson JLABS, and the California Life Sciences Institute FAST Advisory Program.

Prior to joining EpiBiome, she served as a Principal Clinical Scientist and medical advisor at Evalve (acquired in 2010 by Abbott Vascular), supporting medical safety and development of the MitraClip, a minimally invasive device used to reduce mitral regurgitation without the need for open heart surgery. Prior to joining Evalve, she served as a Program Specialist at Hantel Technologies, a contract medical device engineering and manufacturing firm, serving as a liaison between clients and internal departments, and managing timelines and budgets for projects ranging from single person startups to Fortune 500 companies. She completed her postdoctoral fellowship at Stanford University School of Medicine in the Department of Pediatrics.

Origami Therapeutics, Inc.

A resident company of JLABS @ San Diego

Lab Address:
3210 Merryfield Row
San Diego, CA 92121

Mailing Address:
3525 Del Mar Heights Road, Suite 938
San Diego, CA 92130

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