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Phase 3 data for a gamma secretase inhibitor called varegacestat “looks like a knockout,” Evercore analysts wrote Dec. 15.\n Immunome’s investigational oral therapy has slashed the risk of disease progression or death by 84% for patients with desmoid tumors, data one analyst describes as a “near best-case outcome.”The phase 3 win centers around Ringside, a global study that recruited 156 patients to receive either 1.2 mg daily of Immunome’s varegacestat or placebo until disease progression or death. Varegacestat, a gamma secretase inhibitor (GSI), was also tied to key secondary successes, building up a body of data that “looks like a knockout,” Evercore ISI analyst Cory Kasimov wrote Dec. 15.The findings have Immunome eying a new drug application submission, with an FDA filing expected in the second quarter of next year, according to a Dec. 15 company release.Immunome’s stock has risen 25% from $19.57 per share to $24.54 as of 10:35 a.m. ET today. Zooming in on Ringside, varegacestat significantly improved progression-free survival compared to placebo, showing an 84% reduction in disease progression or death risk, hitting the study’s primary target and delivering what Evercore\'s Kasimov dubbed “very strong topline results.”Varegacestat also delivered an objective response rate (ORR) of 56% based on RECIST v1.1 as compared to a 9% response rate for placebo.This tops the 41% ORR seen in phase 3 development for the current standard of care, Ogsiveo, a GSI sold by Merck KGaA\'s SpringWorks.Immunome’s asset also achieved statistically significant improvements over placebo in reducing tumor volume and pain intensity, the Washington-based biotech said.   Varegacestat was generally well tolerated, with most adverse events of grades 1 or 2 severity, according to Immunome. The most common adverse events occurring in the treatment arm were diarrhea and fatigue, the biotech said.While the adverse event profile looks favorable compared to Ogsiveo, Evercore\'s Kasimov said he\'s interested in more detailed safety data, citing the lack of information in the release about ovarian toxicity, a side effect that can limit treatment for women. Plus, rates of low-grade alopecia were much higher for varegacestat than Ogsiveo in phase 2 development, but no data on the measure were provided today, the analyst wrote.Immunome said it plans to share more data at an upcoming medical meeting. Immunome picked up varegacestat from Ayala Pharmaceuticals last year for $50 million in cash and stock. Should the investigational oral treatment—formerly known as AL102—live up to the hype, Ayala could receive milestone payments of up to $37.5 million.At the time of the deal, Immumone said “data from clinical trials have shown AL102 may be more effective in treating desmoid tumors” than SpringWorks’ Ogsiveo, which secured FDA approval at the end of November 2023.Desmoid tumors are non-cancerous, soft tissue tumors that are prone to recurrence. The tumors are rare, with around 1,000-1,650 Americans diagnosed annually. The condition is known to cause debilitating pain and deformities.“Desmoid tumors can have a devastating physical and emotional impact on patients given their unpredictable nature and the limitations of current treatment options,” Mrinal Gounder, M.D., sarcoma medical oncologist and drug development specialist at Memorial Sloan Kettering Cancer Center, and primary investigator for Ringside, said in the release.“The progression-free survival benefit, high response rate and reduction in tumor volume with varegacestat in the Ringside trial are striking,” Gounder continued. “These findings elevate the role of GSIs and confirm varegacestat could become standard of care in the treatment of desmoid tumors.” Ringside’s phase 3 findings reveal the potential varegacestat has to deliver “best-in-class results in a convenient, once-daily, oral medicine that may help patients reclaim their lives,” Immunome CEO Clay Siegall, Ph.D., said in the release.Siegall took the top spot at the clinical-stage company in 2023 after resigning from his CEO position at oncology powerhouse Seagen in 2022 following an arrest for alleged domestic violence.At the time, the biotech executive was charged with fourth-degree misdemeanor assault and spent 33 hours in jail. The charge was later dismissed due to “insufficient evidence to support filing charges,” according to The Seattle Times.

Immunome’s rare tumor drug succeeded in a Phase 3 study, setting the company up for an FDA submission by the end of next June. Researchers said Monday that the drug, called varegacestat, reduced the risk of disease progression or death by 84% in patients with desmoid tumors, a rare condition that tends to occur in younger adults. In the 156-patient study, 56% of those who took varegacestat responded to the drug, compared to 9% of individuals who received a placebo. The results were highly statistically significant, with a p-value of p<0.0001 in both progression-free survival and objective response rate. Immunome’s stock price $IMNM rose about 25% Monday morning. Immunome said it plans to ask the FDA for an approval in the second quarter of next year. On an investor call Monday morning, company executives said varegacestat could also be eligible for priority review. If approved, varegacestat would compete against Merck KGaA’s Ogsiveo. Immunome is led by CEO Clay Siegall, who resigned from Seagen in 2022 in the wake of an arrest related to domestic violence allegations by his then-wife. Siegall denied the allegations and did not face charges due to “evidentiary reasons” and “insurmountable inconsistencies,” according to the prosecutor, located in the Seattle suburbs. After leaving Seagen, Siegall joined the private biotech Morphimmune in 2023. Less than four months later, Morphimmune reverse merged with Immunome, taking the latter company onto the Nasdaq. Seagen was subsequently acquired by Pfizer in 2023 for $43 billion. Desmoid tumors can occur in any part of the body, but are not cancerous and do not metastasize, according to the Mayo Clinic . The tumors are usually aggressive and appear most often in the abdomen, causing swelling, pain and potential organ damage. Immunome estimates about 1,000 people are diagnosed with desmoid tumors every year in the US. There is only one other FDA-approved treatment for desmoid tumors. Ogsiveo was originally developed by Pfizer and spun out into orphan disease biotech SpringWorks Therapeutics in 2017. Ogsiveo was approved in late 2023, and SpringWorks was acquired by Merck KGaA earlier this year. Ogsiveo’s study induced a 71% reduction in the risk of disease progression or death and an objective response rate of 41%, according to data published in the New England Journal of Medicine. Both Ogsiveo and varegacestat are gamma secretase inhibitors. Leerink analyst Andrew Berens said in a note to investors Monday morning that the results represented the best-case scenario for Immunome. “Varegacestat appears to be the best-in-class GSI with the potential to capture the majority of the desmoid tumor market,” he wrote. Berens projected peak sales of $783 million by 2034. Side effects occurred as expected, Immunome said, and most were mild or moderate. The most common adverse events were diarrhea (82%), fatigue (44%), rash (43%), nausea (35%) and cough (34%). Immunome is planning to launch the drug on its own and not seek a partner, executives said on Monday’s conference call. The company estimates that only one in 10 desmoid tumor patients are currently taking a gamma secretase inhibitor.