Mood check
AACR leaders thank Congress
Angus Chen/STAT
Last year, President Trump’s budgets included dramatic cuts to the National Institutes of Health, giving NIH funded scientists a scare and prompting outcry from scientific leaders including those at AACR. Congress firmly rejected those cuts last year, and increased the NIH budget for fiscal year 2026. In response, at this year’s AACR opening ceremony, AACR CEO Margaret Foti thanked Congress for standing up for science, with a callout for members of the Senate Appropriations Committee.
Earlier this month, Trump proposed a $5 billion cut to the NIH for 2027, which Foti called unacceptable during her opening remarks. “Our purpose is clear. Our mission is urgent. And our commitment is unwavering. We cannot allow our lifesaving mission to be adversely affected by the Administration’s plan to cut NIH funding by 20% for fiscal year 27,” she said.
data
Revolution Medicines’ KRAS targeting drug delivers strong results
Today Revolution Medicines, called RevMed for short, delivered data for zoldonrasib, which targets lung cancers that test positive for a particular mutation, called G12D.
The overall response rate was 55%, according to an abstract published Saturday. Faisal Khurshid, an analyst at Jefferies, the investment bank, wrote in a note to investors that the drug’s safety profile was also incredibly strong. He noted that only 3% to 5% of patients with non-small cell lung cancer carry a G12D mutation, and that this drug has been “less of a focus” given the attention one of the company’s other drugs, daraxonrasib, has drawn. Khurshid called the drug “an important lever” for the company.
RevMed’s CEO Mark Goldsmith called the results one of three “exciting stories” the company has at AACR this year, with more data coming on Tuesday. Zoldonrasib also had a 93% disease control rate in the cohort thus far and, while overall survival data aren’t mature yet, Goldsmith noted that the cohort is showing a median progression-free survival of 11.1 months. “If you compare that to standard of care, you’re talking about 4.5 months,” he said. “A dramatic increase. We don’t have median OS yet, but landmark value of 73% at 12 months. That tells us where things are going.”
long read
The story behind the KRAS revolution
These drugs didn’t just come out of nowhere. In a deeply reported feature, Angus tells the story of how they emerged from a biotech game of greased watermelon. KRAS is recognized as one of the most commonly mutated oncogenes, representing roughly a third of all solid tumors, making it an attractive target to drug, if the chemistry could be done.
For decades, KRAS was considered “undruggable” as an intracellular protein with a flat surface. UCSF’s Kevan Shokat was the first to uncover the chemistry needed to covalently bond a small molecule to the G12C mutant KRAS, which worked to inhibit the “off” state of KRAS. The trouble with the first generation of inhibitors based on that chemistry was resistance formed rapidly, partly because of the lack of “on” state activity.
Later, Greg Verdine, a Harvard University scientist, invented a new method to drug RAS by designing a “molecular glue,” small molecules that can form protein-drug complexes that can then contact a flat target. That was the technology for the RevMed compounds, which the company acquired with its purchase of Verdine’s biotech Warp Drive Bio in 2018. (Verdine will speak at STAT’s live event Tuesday.)
“We put our whole company” on refining that technology, Goldsmith told STAT. “We have a very talented team. The single most important thing was none of their compounds were orally bioavailable. They were injecting. That was a no go. We converted them chemically through insights into oral compounds, and we increased the potency.”
The results of that chemistry are anything but arcane – Angus spoke to one patient, a 36-year-old gymnastics manager named Leanna Stokes – who credits the drug with transforming her life and allowing her to live far longer than most patients with her diagnosis.
Read the story here.
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