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Product Development

KRAS to the future; plus ARPA-H & EGFR: a BioCentury podcast

Jun 2, 2021 | 1:34 AM GMT

FDA’s approval of Amgen’s Lumakras represents so much more than the authorization of the first inhibitor again KRAS, once thought to be an “undruggable” target. In BioCentury’s latest podcast, BioCentury’s editors discuss how the target went from hard-to-drug to market and what the impact the KRAS G12C inhibitor could have for patients. They also discuss Zai’s deal for a rival KRAS inhibitor, the Biden administration’s ARPA-H initiative and what to expect from EGFR data at ASCO21.

Senior Editor Lauren Martz and Editor in Chief Simone Fishburn discuss why the approval of Lumakras sotorasib from Amgen Inc. (NASDAQ:AMGN) is so significant for the biotech industry and how Amgen and other companies have developed programs against KRAS so quickly.

Fishburn also explains why the approval was a “sentimental” one for many who have watched the journey of ras biology. “It’s a target that’s been known for so long. It probably was the first one to get the moniker of undruggable, which it obviously is not,” she said. “I think a lot of people really see this as a signature moment.”

Staying with KRAS, this week’s Deal in Focus zeroes in on Tuesday’s deal giving Zai Lab Ltd. (NASDAQ:ZLAB; HKEX:9688) rights in Greater China and Taiwan to small-molecule KRAS G12C inhibitor adagrasib (MRTX849) from Mirati Therapeutics Inc. (NASDAQ:MRTX). The deal, Executive Editor Jeff Cranmer says, is illustrative of how cross-border company Zai appears to be making larger and more ambitious deals and sets up a race in China between Zai and BeiGene Ltd. (NASDAQ:BGNE; HKEX:6160), which has rights to Amgen’s molecule.

Turning to Washington, Washington Editor Steve Usdin describes what the Advanced Research Projects Agency – Health is and assesses what the new agency can accomplish with $6.5 billion in three years. Usdin says that there is dispute over the merits of ARPA-H, but there is no doubt among its supporters and opponents that it will be created. He also discusses the role that Eric Lander, director of the White House Office of Science and Technology Policy, will have at the initiative.

“I wouldn’t bet against him here,” Usdin says of Lander, who founded the Broad Institute of MIT and Harvard. “I think that it’s quite likely that they’re going to create something that’s going to do some things that are going to be tremendously impactful. I think that how impactful it’s going to be is going to be a function of how it’s set up, whether it’s at NIH, how independent of NIH it’s going to be.”

On the product development front, Senior Editor Karen Tkach Tuzman says the upcoming meeting of the American Society of Clinical Oncology features a series of programs targeting resistance mechanisms faced by marketed therapies against EGFR.

The biggest focus, Tkach Tuzman says, is on EGFR-mutant non-small cell lung cancer (NSCLC), an indication where resistance to EGFR-targeting tyrosine kinase inhibitors (TKIs) often emerges, and where patients with certain mutations have historically been left behind. The landscape is rapidly changing for NSCLC with rare EGFR exon 20 insertion mutations, according to Tkach Tuzman, who says these mutations produce a conformational change in the receptor’s intracellular domain that renders tumors insensitive to traditional TKIs.

TARGETS
EGFR (ErbB1; HER1) - Epidermal growth factor receptor
KRAS (K-Ras) – KRAS proto-oncogene

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