Erasca has backed up bullish claims about its pan-RAS drug having a best-in-class profile, publishing phase 1 data that an analyst said reveal a “home run profile.” But with a patient dying and Revolution Medicines issuing a legal threat, the biotech’s share price plummeted in premarket trading.
The data come from two phase 1 dose-escalation trials of ERAS-0015, a pan-RAS molecular glue. Erasca pooled data from its U.S. trial and Joyo Pharmatech’s study in China, both of which tested ERAS-0015 in patients with RAS-mutant solid tumors. Revolution recently published phase 3 data on its rival pan-RAS inhibitor, daraxonrasib, but Erasca has argued (PDF) a higher binding affinity sets its asset apart.
Erasca’s phase 1 data provided early evidence to support its claims of best-in-class efficacy. The biotech reported a 40% response rate in 20 patients with KRAS G12X-mutated pancreatic cancer who received a pharmacologically active dose of ERAS-0015 as a second-line treatment.
In a presentation published last month, Erasca named the 19.6% response rate in a daraxonrasib trial as the benchmark for its pancreatic cancer readout. The biotech defined differentiated efficacy as beating Revolution’s benchmark by at least 10 percentage points.
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Erasca reported the pancreatic cancer data alongside its results from non-small cell lung cancer patients with KRAS G12X-mutated tumors. At pharmacologically active doses, 62% of the 37 people who received ERAS-0015 as a second-line therapy responded to the treatment. Erasca benchmarked the data against a 37.5% response rate on daraxonrasib and again targeted a 10-percentage-point improvement.
Going into the readout, Erasca said it needed both a 10-percentage-point improvement in the response rate and an edge on at least two safety and tolerability attributes to hit its “paradigm-shifting scenario.” The biotech claimed advantages on all five safety and tolerability attributes, pointing to data on rash and gastrointestinal events and evidence ERAS-0015 is tolerable in a combination to make its case.
Evercore ISI analyst Jon Miller said in a note to investors that the readout met the “home run profile” he set out last week. Yet Erasca’s share price dropped 46% to $10.23 when the markets opened on Tuesday. The analyst suggested the death of a patient as a potential explanation for the stock drop.
The patient, a 66-year-old man with metastatic pancreatic cancer, went to the emergency room with grade 3 pneumonitis, a type of lung inflammation, about one month after starting on ERAS-0015. The physicians discontinued ERAS-0015 and administered high-dose steroids and infliximab. The patient died after requesting the withdrawal of supportive care.
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The investigator told Erasca he thought “that if the patient had continued supportive care, then it might have been a different outcome,” CEO Jonathan Lim, M.D., said on a call with analysts to discuss the data Monday. Pneumonitis is a rare side effect of many cancer drugs, Lim said, and no grade 4 or 5 cases have occurred on ERAS-0015. The patient progressed to grade 5 because care was withdrawn, Lim said.
Evercore ISI’s Miller observed that “it’s tough to conclude what the true rate of pneumonitis is” at this point. The analyst will be watching the adverse event profile, but said “I find it hard to ignore the rest of the data even given this event.” Erasca is pushing ahead, with data from monotherapy dose expansion and combination dose escalation cohorts scheduled for publication in the first half of next year.
The biotech will work toward the readouts while contending with the fallout of its decision to directly compare ERAS-0015 to daraxonrasib, even though such cross-study comparisons can be unreliable. In a letter sent by its lawyers Friday, Revolution accused Erasca of “improperly” comparing preclinical data on the two molecules. Days later, Erasca compared clinical data on the drug candidates.
Revolution also alleged that ERAS-0015 infringed one of its patents and that the Chinese scientists who invented Erasca’s drug candidate stole its trade secrets. Erasca said it believes the assertions in the letter are without merit and intends to contest the allegations.
