Immunome (IMNM) investor relations material

Study design and objectives

• RINGSIDE was a global, randomized, double-blind, placebo-controlled Phase 3 trial enrolling 156 patients with progressing desmoid tumors, randomized 1:1 to varegacestat or placebo, with crossover allowed upon progression.

• The primary endpoint was progression-free survival (PFS); key secondary endpoints included objective response rate (ORR), tumor volume reduction, pain intensity, duration of response, and safety.

• Eligibility criteria mirrored other large studies in this population.

• The study is the largest Phase 3 trial conducted in desmoid tumors to date.

• The trial includes an ongoing open-label extension phase.

Efficacy results

• Varegacestat achieved an 84% reduction in risk of disease progression versus placebo (PFS hazard ratio 0.16, p<0.0001).

• Confirmed ORR was 56% for varegacestat versus 9% for placebo (p<0.0001), the highest reported in a randomized desmoid tumor trial.

• Median best percentage reduction in tumor volume was 83% for varegacestat, compared to an 11% increase for placebo.

• All key secondary endpoints were met, including significant improvements in tumor volume reduction and pain intensity.

• Early and sustained separation of PFS curves was observed, with responses seen both early and late in treatment.

Safety and tolerability

• Varegacestat was generally well tolerated, with most adverse events being grade 1 or 2; most common were diarrhea (82%), fatigue (44%), rash (43%), nausea (35%), and cough (34%).

• Ovarian toxicity occurred in 55.6% of women of childbearing potential, with most recovering function; this rate is lower than previously reported for the GSI class.

• No deaths were observed in the study.

• Adverse events typically occurred early and stabilized or improved over time.

• Safety profile was consistent with the gamma secretase inhibitor class.