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David Shen is Sr. VP of NGM Biopharmaceuticals a leading
expert with more than 20 years of experience in the antibody
and therapeutic protein field, and has a proven record of
advancing pipelines from discovery to proof-of-concept in
clinical stage to registration. Dr. Shen joined NGM in 2013
and was most recently Vice President, Global Head of
Biologics Development at TEVA Pharmaceuticals and
managed the innovative biologics, biobetters and biosimilars
portfolio across therapeutic areas. During his tenure, several
biologics/biosimilars were successfully approved, including
TBO-Filgrastim by FDA and Lipegfilgrastim by EMA. Prior
to TEVA, Dr. Shen was Executive Director, Biologics
Research and GlycoFi at Merck where he oversaw overall
biologics pipeline from discovery to preclinical development.
His professional career started at Amgen where he held
positions of increasing responsibility, including site-head for
the Protein Sciences Department in San Francisco, and was
critical in advancing more than eight antibody drug candidates
from research to clinical development and regulatory
approval, including evolucumab (anti-PCSK9), romosozumab
(anti-sclerostin) and denosumab (anti-RANKL). In addition,
he has developed the mammalian full IgG display technology
that is now widely used by the antibody field. Dr. Shen
graduated from East China University of Science and
Technology and received a Ph.D. from University of Toronto.
He completed post-doctoral training at the Whitehead
Institute for Biomedical Research.
Discovery of GDF15 Receptor (GFRAL/RET) and Its Novel Biological Pathway that Controls Body Weight and Its Clinical Applications
We have identified GDF15 as a potent hormone for potentially treating diabetes and weight loss. GDF15 regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses. In the course of pursuing its molecular mechanism, we have undertaken extensive biochemical, cell-based, and functional screenings, culminating in the discovery of GFRAL/RET as the cognate receptor for GDF15. By isolating GFRAL as the receptor for GDF15-induced anorexia and weight loss, we identify a mechanistic basis for the non-homeostatic regulation of neural circuitry by a peripheral signal associated with tissue damage and stress. Furthermore, we have co-crystalized GDF15 with its cognate receptor GFRAL to gain insight of detailed molecular interactions. We have then identified an array of antagonistic antibodies, including competitive, non-competitive and allosteric modulators. Co-crystal structures of antibodies with GFRAL further defined the nature of interactions of these modulators with GDF15 receptor; and this led us to have successfully generated antibodies intended for preventing weight loss in cancer cachexia. Presently GDF15 for treating diabetes and weight loss is in development by Merck through licensing, and antibody for GFRAL is in phase 1 clinical study by NGM.