BridgeBio and Amgen Unite on Combination Therapy for Advanced Solid Tumors

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BridgeBio Pharma announced that it had inked a non-exclusive clinical partnership with Amgen to study a combination of its BBP-398 with Amgen’s Lumakras (sotorasib) in advanced solid tumors with the KRAS G12C mutation. BBP-398 is a potentially best-in-class SHP2 inhibitor, while Lumakras is a KRASG12C inhibitor.

The two companies will initiate a Phase I/II trial that will include a dose escalation portion followed by dose expansion and optimization. Under the terms of the deal, BridgeBio will sponsor the study and Amgen will produce a global supply of Lumakras.

BridgeBio developed BBP-398 with The University of Texas MD Anderson Cancer Center’s Therapeutics Discovery division. It is an SHP2 inhibitor; SHP2 is a protein-tyrosine phosphatase that combines growth factor, cytokine and integrin signaling with the downstream RAS/ERK MAPK pathway. This regulates cellular growth and survival. They hope that by combining SHP2 inhibition with KRASG12C inhibition in KRAS SG12C mutations, the combination will prevent oncogenesis and overactive cellular development.

“Overactivity of the MAPK pathway is a significant cause of many types of difficult-to-treat cancers and by combining these two agents, we aim to reduce the oncogenic potential of tumors cells,” said Frank McCormick, Chairman of Oncology at BridgeBio. “Building on our collaborations with Bristol Myers Squibb and LianBio, we are excited to be working with Amgen on this new collaboration. By harnessing the power of BBP-398 as a potentially best-in-class SHP2 inhibitor with Lumakras, we are hopeful that we will be able to provide substantial relief for cancer patients in need. We will continue to pursue additional collaborations that we believe hold promise for patients.”

KRAS mutations are observed in about 17% of malignant solid tumors. BridgeBio is currently running a Phase I trial of BBP-398 in solid tumors driven by mutations in the MAPK signaling pathway, including RAS and receptor tyrosine kinase genes.

Lumakras is indicated for adults with non-small cell lung cancer (NSCLC) that has spread to other parts of the body or can’t be removed by surgery, and where the tumor has an abnormal KRAS G12C gene, and who have received at least one previous treatment for cancer. It was approved in May 2021, and in the third quarter of 2021, the company reported it had brought in $36 million for the quarter and a total of $45 million since its launch.

“Lumakras has been prescribed by over 500 oncologists in both academic and community setting,” stated Murdo Gordon, Amgen’s Commercial Operations Chief at the time. “A majority of clinical laboratories have updated their testing reports to reflect KRAS G12C as an actionable mutation, and approximately 75% of patients with non-small cell lung cancer are now being tested for the mutation at the time of diagnosis.”

In July 2021, BridgeBio announced a clinical collaboration with Bristol Myers Squibb to study BBP-398 with BMS’s checkpoint inhibitor Opdivo (nivolumab) in advanced solid tumors with KRAS mutations. That deal includes a Phase I/II trial with the two drugs together and Opdivo, BBP-398 and a KRASG12C inhibitor as a triplet combination. The costs of clinical development are shared between the two companies.

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