Irving Weissman, M.D. Director, Institute of Stem Cell Biology and Regenerative Medicine
Director, Stanford Ludwig Center for Cancer Stem Cell Research and Medicine
Professor of Pathology and Developmental Biology
Co-Founder and Board Member, Forty Seven Inc
Co-Founder, President & CEO
Stanford University School of Medicine
Normal and Neoplastic Stem Cells
Neil Kumar, Ph.D. Chief Executive Officer and Founder, BridgeBio Pharma
Chief Executive Officer, Eidos Therapeutics
Targeting Genetic Disease at its Source
Genetic diseases affect 25 million Americans and countless more across the globe. Because genetic medicine is still in its adolescence, the space contains vast unmet needs and many grievous conditions. These diseases are also often targetable via precision medicine ñ one can characterize the source of the disease, define the mechanism, and drug the molecular pathophysiology at its source.
BridgeBio Pharma is dedicated to finding and efficiently developing novel, genetically targeted therapies. Led by experienced scientists, drug developers and investors, BridgeBio combines deep research and development expertise with a corporate model that efficiently distributes central resources across multiple subsidiary companies, each of which develops a specific drug. The company has a portfolio of 17 targeted genetic drugs that run from preclinical to late-stage trials with the underlying premise that a more efficient drug development ecosystem is in patients' best interests. These programs span multiple therapeutic areas including oncology, dermatology, mitochondrial disease, and cardiology. The fruits of this model are apparent in the work being done at subsidiary Eidos Therapeutics for patients with Transthyretin (TTR) Amyloidosis.
TTR Amyloidosis is a rare, devastating disease without an FDA-approved therapy which presents in two forms - a cardiomyopathy leading to progressive heart failure, and a polyneuropathy resulting in degeneration of sensory and motor function. Current treatment options for each focus upon symptom management and do not address the underlying source or mechanism of disease.
TTR amyloidosis is brought on by the genetically-driven destabilization of a common blood borne tetramer (TTR), resulting in its disassociation into monomers, which then aggregate into amyloid fibrils and deposit in tissues where they cause disease. Eidos Therapeutics is developing a drug candidate, AG10, to treat this amyloidosis by stabilizing the TTR tetramer in the blood, halting the disease's progression. AG10, conceived to mimic a saving mutation seen in nature that stabilizes TTR, has shown promising efficacy thus far, and will enter Phase II trials this spring.
Hing Sham, Ph.D.
Senior Vice President of Research Global Blood Therapeutics
A major driver of the pathophysiology of sickle cell disease (SCD) is polymerization of deoxygenated haemoglobin S (HbS), which leads to sickling and destruction of red blood cells (RBCs) and end-organ damage. Pharmacologically increasing the proportion of oxygenated HbS in RBCs may inhibit polymerization, prevent sickling and provide long term disease modification. We report that GBT440 (Voxelotor), a small molecule which binds to the N-terminal α chain of Hb, increases HbS affinity for oxygen, delays in vitro HbS polymerization and prevents sickling of RBCs. Moreover, in a murine model of SCD, GBT440 extends the half-life of RBCs, reduces reticulocyte counts and prevents ex vivo RBC sickling. Importantly, oral dosing of GBT440 in animals demonstrates suitability for once daily dosing in humans and a highly selective partitioning into RBCs, which is a key therapeutic safety attribute. Thus, Voxelotor is currently in clinical trials to explore its potential as a disease-modifying agent in sickle cell patients, and has been granted the Break Through Designation by the FDA.
Dr. Sham joined GBT in July 2014 as senior vice president, chemistry and was appointed senior vice president, Research in May 2016. He has significant experience and accomplishments in pharmaceutical research and discovery. Prior to GBT, he served as head of research and development at iOneWorldHealth/Path.org (PATH), a non-profit pharmaceutical development organization. Prior to that, he served as senior vice president of research and head of chemical sciences at Elan Pharmaceuticals, Inc., where he led the chemistry team in the discovery of two clinical candidates for the treatment of Alzheimer's disease. Before that, he worked at Abbott Laboratories Inc., where he and his team discovered and advanced 10 clinical candidates spanning cardiovascular disease, HIV, oncology and diabetes. His 24-year tenure at Abbott Laboratories culminated in his appointment as a distinguished research fellow in global pharmaceutical discovery division.