2019台灣生技月 Bio Taiwan 生物科技大展

2019 台灣生技月 南港展覽館

講師

Yingli Ma

Session 3 – Advances in Precision Medicine
Date: 25 July (Thursday)  09:00 – 12:00
Venue: 3F, Bldg. A, CTBC Financial Park, Ballroom A
 


 

Yingli Ma

Directory of Discovery Research
Amgen

 
Yingli Ma Ph.D., currently works at Amgen Asia R&D Center. Having 10 years’ pharma-biotech drug discovery experience with rapidly increased responsibilities, Dr. Ma leads up to 30 scientists with diverse expertise in structural biology, biophysics, modeling and AI, antibody discovery, in vitro and in vivo pharmacology, GPCR biology and medicinal chemistry. Dr. Ma is responsible for Amgen Shanghai Research site discovery research activities with delivery of small molecule and biologics hits and leads to support Cardiometabolic Diseases and Neuroscience. Dr. Ma is also responsible for technology evaluation and scouting, capability expansion through strategic external collaboration, site operational excellence and general business development.
Prior to joining Amgen in 2014, Dr. Ma was Principal Scientist and Structural Chemistry group leader of Platform Technology Science (2011-2014) and Senior Scientist of Informatics and Structural Biology (2009-2011) at GSK.
Dr. Ma has authored several publications and patents.


Session Speech Title & Synopsis:
Drugging the undruggable: Personalized Oncogenic inhibitor 

Somatic activating mutations of RAS family members are tumor driver mutations found in an estimated 21% of all cancers. Oncogenic KRAS mutations at residues G12, G13, and Q61 represent the most common RAS mutations found in solid malignancies. The prevalence of KRAS p.G12C tumors is 14% of lung adenocarcinoma (including NSCLC), 3–5% of colorectal carcinoma (CRC), and 2% of numerous other solid tumors, representing an unmet medical need. We have developed AMG 510, an orally bioavailable, covalent inhibitor of KRASG12C with potent biochemical and cellular activity, and robust in vivo efficacy. AMG 510
inhibited SOS-catalyzed nucleotide exchange of recombinant mutant KRASG12C/C118A but had minimal effect on KRASC118A, which is wildtype at position 12. In cellular assays, AMG 510 covalently modified KRASG12C and inhibited KRASG12C signaling as measured by phosphorylation of ERK1/2 (p-ERK) in all KRAS p.G12C-mutant cell lines tested but did not inhibit p-ERK in cell lines with various other KRAS mutations. AMG 510 also selectively impaired viability of KRAS p.G12C mutant cell lines but did not affect cell lines with other KRAS mutations. In vivo pharmacodynamic assays demonstrated dose- and time-dependent inhibition of KRASG12C signaling in human pancreatic and NSCLC tumor xenografts. Covalent modification of KRASG12C by AMG 510 was measured by mass spectrometry and correlated with p-ERK inhibition in tumors. AMG 510 significantly inhibited the growth of KRAS p.G12C xenografts and resulted in tumor regression. Combination treatment of AMG 510 with standard-of-care and targeted agents demonstrated enhanced tumor growth inhibition compared to either single agent.