Immunome Submits NDA for Varegacestat in Desmoid Tumors After Positive Phase 3 RINGSIDE Trial

Immunome Inc. (NASDAQ:IMNM) has submitted a New Drug Application to the U.S. Food and Drug Administration for varegacestat, an oral, once-daily gamma secretase inhibitor for treating adults with desmoid tumors. The submission follows positive topline results from the global pivotal Phase 3 RINGSIDE trial, which the company initially reported in December 2025.

The Phase 3 RINGSIDE trial enrolled 156 patients with progressing desmoid tumors who were randomized to receive varegacestat 1.2 mg daily or placebo. The study met its primary endpoint of improving progression-free survival, demonstrating an 84% reduction in the risk of disease progression or death compared to placebo, with a hazard ratio of 0.16 (95% CI: 0.071, 0.375; p<0.0001). The confirmed objective response rate based on RECIST v1.1 was 56% with varegacestat versus 9% with placebo (p<0.0001), as assessed by blinded independent central review. An exploratory analysis showed a median best change in tumor volume of negative 83% with varegacestat compared to positive 11% with placebo.

The trial met all key secondary endpoints, including statistically significant improvements in landmark tumor volume reduction and worst pain intensity compared to placebo. The CEO noted that the study included approximately 10 endpoints across primary, secondary, and tertiary measures, and the drug "won on all of them."

Varegacestat was generally well tolerated with a manageable safety profile consistent with the gamma secretase inhibitor class. The most common adverse events in the treatment arm were diarrhea (82%), fatigue (44%), rash (43%), nausea (35%), and cough (34%). Most events were grade 1 or 2.

Data from the RINGSIDE trial has been selected for oral presentation at the American Society of Clinical Oncology Annual Meeting scheduled for May 29 to June 2 in Chicago.

The company plans to submit the NDA in Q2 2026, though the CEO stated during a recent investor discussion that Immunome expects to file "within the next few months" and expressed hope the FDA would move quickly based on the results. The CEO noted that first submissions often take about six months due to manufacturing and quality documentation requirements, and said the team is working to accelerate the process.

On the commercial opportunity, the CEO cited approximately 1,600 new cases per year in the U.S. and around 11,000 prevalent patients seeking therapy annually, with an estimated prevalence pool of nearly 30,000. Based on pricing set by the existing marketed product in the category, the CEO stated that a roughly 3,000-patient treated population could represent a billion-dollar market opportunity.

Regarding differentiation from the existing therapy Ogsiveo, which has the same mechanism of action, the CEO argued that varegacestat could offer advantages including a higher objective response rate and median tumor regression, pain relief data to be presented at conferences, and once-daily dosing compared with twice-daily dosing for the competitive product, which could improve compliance.

Desmoid tumors are aggressive non-metastatic soft tissue tumors affecting approximately 1,000 to 1,650 people diagnosed annually in the United States, with about 10,000 to 11,000 actively managed patients. The tumors can cause debilitating pain, deformity, and organ damage.

Immunome is building a targeted oncology pipeline centered on cell-surface targeting agents (antibody-drug conjugates and bispecifics) and small molecules. The company's ADC lead, IM-1021 (ROR1-targeting), has shown early objective responses at multiple dose levels in Phase 1, with trial expansion to U.S. and European sites while the company explores an accelerated approval path in lymphomas.