varegacestat (AL102) / Immunome - LARVOL DELTA

Exposure-Response (ER) Analyses to Support the Recommended Dose of Varegacestat (VAR) for Patients (Pts) With Desmoid Tumors (DT) (ESMO 2026) - No abstract available

Clinical • Desmoid Tumors • Oncology • Sarcoma

RINGSIDE Phase 3 Study of Varegacestat in Desmoid Tumors: Primary Results and T2-weighted Signal Intensity Changes (ESMO 2026) - No abstract available

P3 data • Desmoid Tumors • Oncology • Sarcoma

Detailed Safety Analysis of Varegacestat Treatment for Desmoid Tumors in the RINGSIDE Phase 3 Trial (ESMO 2026) - No abstract available

Clinical • P3 data • Desmoid Tumors • Oncology • Sarcoma

Patient reported outcomes (PROs) with varegacestat versus placebo (PBO) in progressing desmoid tumors: Results from RINGSIDE Part B (ESMO 2026) - No abstract available

Clinical • Patient reported outcomes • Desmoid Tumors • Oncology • Sarcoma

Initial results of phase II/III trial of AL102 for treatment of desmoid tumors (DT) (ESMO 2022) - P2/3 | "Table: 1488MO Summary of Treatment-emergent Adverse Events (TEAEs) by Patient *Deemed unrelated to study drug by investigator Conclusions Safety findings to date show no indication for discontinuing any of the three dosing cohorts. Efficacy, patient reported outcome and additional safety data will be presented at the conference."

P2/3 data • Desmoid Tumors • Oncology • Sarcoma

RINGSIDE: A phase 3 randomized, placebo-controlled trial of varegacestat for treatment of progressing desmoid tumors. (ASCO 2026) - P2/3 | "VAR demonstrated statistically significant and clinically meaningful antitumor activity and pain relief, achieving the highest ORR reported in a Phase 3 trial of systemic DT therapy, with no new safety signals. RINGSIDE phase 3 trial outcomes. LS, least square; SE, standard error."

Clinical • P3 data • Desmoid Tumors • Oncology • Sarcoma

Pipeline Highlights: Varegacestat (Businesswire) - "Immunome plans to submit a Marketing Authorization Application to the European Medicines Agency for varegacestat by the end of 2026."

EMA filing • Desmoid Tumors

Immunome, Inc…announced the U.S. Food and Drug Administration (FDA or the Agency) has accepted its New Drug Application (NDA) for varegacestat, an investigational, oral, once-daily gamma secretase inhibitor (GSI), for the treatment of adults with desmoid tumors. (Businesswire) - "The FDA assigned a Prescription Drug User Fee Act (PDUFA) target action date of April 28, 2027...The NDA is based on results from the Phase 3 RINGSIDE trial evaluating varegacestat in patients with progressing desmoid tumors."

FDA filing • PDUFA • Desmoid Tumors

Ayala Pharmaceuticals to Accelerate Development of AL102 for the Treatment of Desmoid Tumors in Pivotal Phase 2/3 Study (GlobeNewswire) - "Ayala Pharmaceuticals, Inc...announced the completion of its end-of-Phase 1 meeting with the U.S. Food and Drug Administration (FDA) on AL102, a potent, selective, oral gamma secretase inhibitor (GSI), for the treatment of desmoid tumors. The FDA has agreed, based on data from AL101 and AL102 studies including durable responses observed in patients with Desmoid tumors, to proceed with a Phase 2/3 pivotal study, which can potentially be used as a registrational study. Ayala expects to initiate the pivotal Phase 2/3 RINGSIDE study in adult and adolescent patients with desmoid tumors in the first half of 2021....initial interim data read-out from part 1 and dose selection expected by mid-2022 with part 2 of the study to commence immediately thereafter."

FDA event • P2/3 data • Trial status • Desmoid Tumors • Oncology

Ayala Pharmaceuticals Announces Updated RINGSIDE Phase 2 Results at 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - P2/3 | N=192 | RINGSIDE (NCT04871282) | Sponsor: Ayala Pharmaceuticals, Inc. | Ayala Pharmaceuticals...announced updated results from Phase 2 (Part A segment) of the RINGSIDE study evaluating AL102 in desmoid tumors. The results are summarized in an abstract published today for the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. More detailed results will be featured in a poster session at ASCO on Saturday, June 3....In the evaluable patient population, partial responses were observed in 50% of patients (i.e., 6 out of 12) in the 1.2 mg QD group, 23.1% of patients (3/13) in the 4 mg BIW group, and 45.5% of patients (5/11) in the 2 mg BIW group. Responses were assessed by blinded independent central review (BICR). In the intention-to-treat (ITT) population, partial responses were observed in 43% of patients (i.e., 6/14) in the 1.2 mg QD group, 21.4% of patients (3/14) in the 4 mg BIW group, and 36% (5/14) in the 2 mg BIW group. Responses were assessed by BICR."

P2 data • Desmoid Tumors • Oncology • Solid Tumor

Ayala Pharmaceuticals Presents Updated AL102 Results from Phase 2 Clinical Trial in Desmoid Tumors at ESMO Congress 2023 (GlobeNewswire) - P2/3 | N=192 | RINGSIDE (NCT04871282) | Sponsor: Ayala Pharmaceuticals, Inc. | "Ayala Pharmaceuticals, Inc...announced that new data from the RINGSIDE study evaluating its lead investigational candidate AL102 for the treatment of desmoid tumors (DT) are being presented today at the European Society for Molecular Oncology (ESMO) Congress 2023, taking place October 20th to 24th in Madrid, Spain....1.2 mg once daily achieved ORR of 83% per RECIST in the evaluable population as assessed by MRI BICR (Blinded Independent Central Review); ORR per RECIST was 64% in evaluable patients across the 3 dose arms (n=36)....First Partial Responses (PRs) observed at 16 weeks and 21 additional PRs and 1 Complete Response across all dose arms; Early and deep volume (-52%) and T2 signal intensity (-58%) reductions within 16 weeks after starting 1.2 mg once daily."

P2 data • Desmoid Tumors • Oncology • Solid Tumor

Immunome Announces Detailed Phase 3 RINGSIDE Data for Varegacestat in Adults with Progressing Desmoid Tumors at the 2026 ASCO Annual Meeting (Businesswire) - "Varegacestat demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs. placebo, with an 84% reduction in the risk of disease progression or death (hazard ratio [HR] = 0.16, 95% confidence interval [CI]: 0.071, 0.375; p<0.0001)....Among responders treated with varegacestat, median time to response was 8.2 months (range: 2.6–28.0 months) vs. 16.7 months (range: 8.1–30.2 months) for responders receiving placebo. Varegacestat achieved a statistically significant improvement in change in worst pain intensity score at week 12, as assessed with the Gounder/Desmoid Tumor Research Foundation Desmoid Tumor Symptom/Impact scale."

P3 data • Desmoid Tumors

A Relative Bioavailability and Bioequivalence Study of Varegacestat in Healthy Participants (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Immunome, Inc.

New P1 trial

Hidradenitis suppurativa and HS-like cutaneous adverse events associated with γ-secretase inhibitors (SID 2026) - "Seventeen studies met inclusion criteria, including 11 clinical trials, 4 case reports, and 2 cohort studies evaluating nirogacestat, crenigacestat, varegacestat, MK-0752, RO4929097, LY3056480, and semagacestat. While explicit diagnoses of HS were uncommon, GSIs were frequently associated with follicular and inflammatory cutaneous adverse events that overlap with HS phenotypes. These findings support a role for γ-secretase malfunction in HS pathogenesis and suggest that HS or HS-like disease may be under-recognized in patients receiving γ-secretase inhibitors."

Adverse events • Acne Vulgaris • Alzheimer's Disease • CNS Disorders • Dermatitis • Dermatology • Desmoid Tumors • Hidradenitis Suppurativa • Immunology • Infectious Disease • Sarcoma

Pipeline Highlights: Varegacestat (Businesswire) - "(i) Immunome plans to submit a Marketing Authorization Application to the European Medicines Agency for varegacestat by the end of 2026; (ii) Data from RINGSIDE, the global, Phase 3, randomized, placebo-controlled trial of varegacestat in patients with progressing desmoid tumors, have been selected for presentation in an oral abstract session at the 2026 ASCO Annual Meeting."

EMA filing • P3 data • Desmoid Tumors

Immunome Announces Submission of New Drug Application to U.S. FDA for Varegacestat for the Treatment of Adults with Desmoid Tumors (Businesswire) - "The NDA is supported by positive results from the global, randomized, double-blind, placebo-controlled Phase 3 RINGSIDE trial of varegacestat in patients with progressing desmoid tumors....Detailed Phase 3 RINGSIDE data selected for oral presentation at the 2026 ASCO Annual Meeting."

FDA filing • P3 data • Desmoid Tumors

A Varegacestat Hepatic Impairment Study (clinicaltrials.gov) - P1 | N=35 | Completed | Sponsor: Immunome, Inc. | Active, not recruiting ➔ Completed

Trial completion • Hepatology

Full-year 2025 Financial Results (Businesswire) - "In-process research and development expenses for the year ended December 31, 2025, were $10.0 million, reflecting a development milestone associated with reporting positive topline results for the Phase 3 RINGSIDE trial of varegacestat...Immunome reported a net loss of $212.4 million for the year ended December 31, 2025."

Commercial • Desmoid Tumors

New Drug Application submission for varegacestat in patients with desmoid tumors planned for 2Q 2026 (Businesswire) - "Immunome plans to share additional data from the RINGSIDE trial at an upcoming major medical conference."

FDA filing • P2/3 data • Desmoid Tumors

How have gamma-secretase inhibitors changed the treatment landscape for desmoid tumors? (PubMed, Expert Opin Pharmacother) - No abstract available

Journal • Desmoid Tumors • Fibrosis • Oncology • Sarcoma • Solid Tumor

Immunome Announces Positive Topline Results from Phase 3 RINGSIDE Trial of Varegacestat in Patients with Desmoid Tumors (The AI Journal) - "Registrational trial met primary endpoint, with varegacestat significantly improving progression-free survival vs. placebo (hazard ratio = 0.16, p<0.0001); Trial also met all key secondary endpoints, with varegacestat delivering an objective response rate of 56%; Varegacestat was generally well tolerated with a manageable safety profile; New Drug Application submission to U.S. FDA planned for Q2 2026"

FDA filing • P3 data: top line • Desmoid Tumors

Immunome…announced the company will host a conference call and webcast on Monday, December 15, 2025 at 8:30 am ET to disclose the topline results from the global pivotal Phase 3 RINGSIDE trial of varegacestat, an investigational, oral, once-daily gamma secretase inhibitor, in patients with progressing desmoid tumors (Businesswire)

P3 data: top line • Desmoid Tumors

ANALYSIS OF CHANGES IN T2-WEIGHTED SIGNAL INTENSITY AND TUMOR VOLUME AND EXPOSURE-RESPONSE IN THE RINGSIDE PHASE 2 STUDY OF VAREGACESTAT FOR DESMOID TUMORS (CTOS 2025) - P2/3 | "Substantial early and rapid reductions in T2W and TV preceded subsequent varegacestat responses by RECIST in adults with DT, adding to evidence that T2W and TV may play a role in evaluating DT treatment response"

P2 data • Desmoid Tumors • Oncology • Sarcoma

SUBGROUP ANALYSIS OF THE PHASE 2 PART OF THE RINGSIDE PHASE 2/3 TRIAL OF VAREGACESTAT FOR TREATMENT OF DESMOID TUMORS (CTOS 2025) - P2/3 | "Objective tumor responses to oral varegacestat were seen in all subgroups examined. These findings support continued evaluation of varegacestat for DTs in the ongoing, double-blind, randomized, placebo-controlled RINGSIDE Phase 3 study (NCT04871282)"

P2/3 data • Desmoid Tumors • Oncology • Sarcoma • CTNNB1

Initial Results from a Phase 1 Dose-Escalation Study of WVT078, a BCMA×CD3 Bispecific Antibody, in Combination with WHG626, a Gamma-Secretase (GS) Inhibitor, in Patients with Relapsed and/or Refractory Multiple Myeloma (ASH 2023) - P1 | "Introduction: WVT078, a potent anti–B-cell maturation antigen (BCMA)×anti-CD3 bispecific antibody (BsAb), is being investigated as a single-agent and in combination with a GS inhibitor (GSI), WHG626 (AL102), in patients (pts) with relapsed and/or refractory (r/r) multiple myeloma (MM). WVT078 combined with WHG626 has an acceptable safety profile and shows preliminary evidence of clinical activity at highest doses tested. PD biomarker analysis supports postulated mechanism of action of WHG626 combined with WVT078. This is the first clinical report on combination of BCMAxCD3 BsAb and GSI in r/r MM."

Clinical • Combination therapy • IO biomarker • P1 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Multiple Myeloma • Musculoskeletal Pain • Neutropenia • Oncology • Pain • Pneumonia • Renal Disease • Respiratory Diseases • Septic Shock