varegacestat (AL102) / Immunome - LARVOL DELTA

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

Pipeline Highlights: Varegacestat (Businesswire) - "Immunome expects to report topline data for the Phase 3 RINGSIDE Part B study before the end of 2025."

P3 data • Desmoid Tumors

A Varegacestat Hepatic Impairment Study (clinicaltrials.gov) - P1 | N=44 | Active, not recruiting | Sponsor: Immunome, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology

A Phase 1 Mass Balance Study of Varegacestat (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Immunome, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Jul 2025 ➔ Mar 2025 | Trial primary completion date: Jul 2025 ➔ Mar 2025

Trial completion • Trial completion date • Trial primary completion date

A Cardiac Liability Study of Varegacestat in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Immunome, Inc. | Active, not recruiting ➔ Completed

Trial completion

Repurposing nirogacestat, a gamma secretase enzyme inhibitor in desmoid tumors. (PubMed, Future Oncol) - "GS enzyme inhibitors such as semagacestat and avagacestat were explored in AD but the studies were paused because of adverse events attributed to their influence on the Notch pathway.Crosstalk between Notch and Wnt signaling pathways created a potential role for GS inhibitors in the treatment of malignancies such as glioblastoma multiforme, pancreatic, and breast cancers. Emphasis was placed on patient-reported outcomes (PRO) including the DT-specific tool, GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom Scale (GODDESS).Nirogacestat received Food and Drug Administration (FDA) approval in November 2023 for management of progressive, unresectable, recurrent, or refractory DT. Further studies are underway to investigate other GS inhibitors such as AL-102 in the management of DT."

Journal • Review • Alzheimer's Disease • Brain Cancer • Breast Cancer • CNS Disorders • Desmoid Tumors • Glioblastoma • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • APP

Immunome Reports Second Quarter 2025 Financial Results and Provides Business Update (Businesswire) - "Pipeline Highlights: Varegacestat: (i) Immunome expects to report topline data for the Phase 3 RINGSIDE Part B study before the end of 2025...; (ii) The European Medicines Agency granted Orphan Drug Designation to varegacestat in July 2025. Varegacestat previously received Orphan Drug Designation from the U.S. Food and Drug Administration in November 2023."

Orphan drug • P3 data: top line • Desmoid Tumors

Change in T2-weighted signal intensity, change in tumor volume, and exposure-response analysis in the RINGSIDE phase 2 study of varegacestat in patients with desmoid tumors. (ASCO 2025) - P2/3 | "Substantial early and rapid reductions in T2W and TV on MRI preceded eventual RECIST responses in adults with DT treated with varegacestat. These data add to a growing body of work showing T2W and TV may play a role in evaluating treatment response in DT. Future research should evaluate the prognostic or predictive value of these imaging techniques in DT and standardization to allow for use in clinical management of DT patients."

Clinical • P2 data • Desmoid Tumors • Oncology • Pain • Sarcoma

Subgroup analysis of the phase 2 part of the RINGSIDE phase 2/3 trial of varegacestat for treatment of desmoid tumors. (ASCO 2025) - P2/3 | "Comparable, objective tumor responses to oral varegacestat therapy were shown in all subgroups examined. These findings support continued evaluation of all desmoid tumor patients independent of subgroups in the ongoing, double-blind, randomized, placebo-controlled Phase 3 study of varegacestat (RINGSIDE NCT04871282). Varegacestat response in subgroups."

P2/3 data • Addiction (Opioid and Alcohol) • Desmoid Tumors • Oncology • Pain • Sarcoma • CTNNB1

Immunome Reports First Quarter 2025 Financial Results and Provides Business Update (Yahoo Finance) - "Pipeline Highlights: (i) Varegacestat:...Immunome expects to report topline data for RINGSIDE Part B in the second half of 2025...; (ii) IM-3050: Immunome received IND clearance for IM-3050 in April 2025 and expects to initiate a Phase 1 clinical trial in the second half of 2025."

IND • New P1 trial • P3 data: top line • Desmoid Tumors • Solid Tumor

A Phase 1 Study to Examine the Effects of Itraconazole After Single Dose Administration of Varegacestat (AL102) to Healthy Participants (clinicaltrials.gov) - P1 | N=22 | Completed | Sponsor: Immunome, Inc. | Active, not recruiting ➔ Completed

Trial completion

A Cardiac Liability Study of Varegacestat in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Immunome, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

A Phase 1 Mass Balance Study of Varegacestat (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Immunome, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

Immunome Reports Full Year 2024 Financial Results and Provides Business Update (Businesswire) - "Pipeline Highlights: Varegacestat: Full enrollment for the Phase 3 RINGSIDE Part B study of varegacestat for the treatment of desmoid tumors was completed in February 2024, and Immunome expects to report topline data for RINGSIDE Part B in the second half of 2025."

Enrollment closed • P3 data: top line • Desmoid Tumors

A Varegacestat Hepatic Impairment Study (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: Immunome, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology

A Cardiac Liability Study of Varegacestat in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Immunome, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

A Cardiac Liability Study of Varegacestat in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Immunome, Inc.

New P1 trial

A Phase 1 Study to Examine the Effects of Itraconazole After Single Dose Administration of Varegacestat (AL102) to Healthy Participants (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Immunome, Inc. | Trial completion date: Jan 2025 ➔ Apr 2025

Trial completion date

A Phase 1 Mass Balance Study of Varegacestat (clinicaltrials.gov) - P1 | N=6 | Recruiting | Sponsor: Immunome, Inc.

New P1 trial

A Phase 1 Varegacestat Hepatic Impairment Study (clinicaltrials.gov) - P1 | N=44 | Not yet recruiting | Sponsor: Immunome, Inc.

New P1 trial • Hepatology

Immunome Provides Pipeline Update in Advance of Presentation at the 43rd Annual J.P. Morgan Healthcare Conference (Businesswire) - "The presentation will cover Immunome’s pipeline of targeted therapeutics, including varegacestat (formerly known as AL102), a once-daily oral gamma secretase inhibitor in the Phase 3 RINGSIDE clinical trial for the treatment of desmoid tumors. Immunome expects to report topline data in the second half of 2025....Immunome also announced the FDA clearance of its IND submission for IM-1021, a ROR1-targeted ADC. Immunome anticipates submitting an IND for IM-3050, its FAP-targeted radioligand therapy, by the end of the first quarter of 2025."

IND • P3 data: top line • Desmoid Tumors

A Phase 1 Study to Examine the Effects of Itraconazole After Single Dose Administration of Varegacestat (AL102) to Healthy Participants (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Immunome, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

A Phase 1 Study to Examine the Effects of Itraconazole After Single Dose Administration of Varegacestat (AL102) to Healthy Participants (clinicaltrials.gov) - P1 | N=22 | Recruiting | Sponsor: Immunome, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open