WVT078 / Novartis - LARVOL DELTA

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

A Study of WVT078 in Patients With Multiple Myeloma (MM) (clinicaltrials.gov) - P1 | N=56 | Terminated | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Terminated; The decision was made for business reasons and was not based on any safety or tolerability concerns

Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of WVT078 in Patients With Multiple Myeloma (MM) (clinicaltrials.gov) - P1 | N=56 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jan 2024 ➔ Sep 2024 | Trial primary completion date: Jan 2024 ➔ Sep 2024

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of WVT078 in Patients With Multiple Myeloma (MM) (clinicaltrials.gov) - P1 | N=56 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=90 ➔ 56

Enrollment change • Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

Preclinical discovery and initial clinical data of WVT078, a BCMA × CD3 bispecific antibody. (PubMed, Leukemia) - P1 | "20 patients (60.6%) experienced cytokine release syndrome. WVT078 has an acceptable safety profile and shows preliminary evidence of clinical activity at doses tested to date."

Clinical data • IO biomarker • Journal • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

Preclinical discovery and initial clinical data of WVT078, a BCMA × CD3 bispecific antibody (Leukemia) - P1 | N=53 | NCT04123418 | Sponsor: Novartis Pharmaceuticals | "WVT078...binds to BCMA with subnanomolar-affinity. It was selected based on potent T cell activation and anti-MM activity in preclinical models with favorable tolerability in cynomolgus monkey. In the ongoing first-in-human phase I dose-escalation study (NCT04123418), 33 patients received intravenous WVT078 once weekly at escalated dosing. At the active doses of 48–250 µg/kg tested to date (n = 26), the overall response rate (ORR) was 38.5% (90% CI: 22.6–56.4%) and the complete response rate (CRR, stringent complete response + complete response) was 11.5%, (90% CI: 3.2–27.2%)."

P1 data • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

PRECLINICAL DISCOVERY AND EARLY FINDINGS FROM THE PHASE 1, DOSE-ESCALATION STUDY OF WVT078, A BCMA-CD3 BISPECIFIC ANTIBODY, IN PATIENTS WITH R/R MULTIPLE MYELOMA (EHA 2022) - P1 | "In the phase 1 study, WVT078 exhibited an acceptable safety profile and preliminary evidence of clinical activity. Clinical evaluation of WVT078 as a single agent and in combination with a gamma secretase inhibitor is ongoing."

IO biomarker • P1 data • Preclinical • Anemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Neutropenia • Oncology • TNFA

Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to BCMA-targeting bispecific antibody treatment (IMW 2022) - P2 | "Of the patients who received cilta-cel, 3 had prior teclistamab, and 1 each had prior AMG 420, AMG 701, PF06863135, and WVT078. Cilta-cel induced favorable responses, DOR, and PFS in heavily pretreated MM patients with prior anti-BCMA BsAb exposure. These initial results may inform treatment plans, including sequencing and washout periods between agents targeting BCMA."

Clinical • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Infectious Disease • Inflammation • Movement Disorders • Multiple Myeloma • Novel Coronavirus Disease • Oncology • Parkinson's Disease • Pneumonia • Respiratory Diseases • Subarachnoid Hemorrhage

A Study of WVT078 in Patients With Multiple Myeloma (MM) (clinicaltrials.gov) - P1; N=90; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Apr 2022 ➔ Dec 2023; Trial primary completion date: Apr 2022 ➔ Dec 2023

Clinical • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Ayala Pharmaceuticals Reports Third Quarter 2021 Financial Results and Provides Business Update (GlobeNewswire) - "Phase 1 Trial of AL102 in Combination with Novartis’ BCMA Targeting Agent, WVT087 for the Treatment of Relapsed/Refractory Multiple Myeloma Continues to Progress: Enrollment progresses as planned in the Phase 1 combination trial of AL102 with Novartis’ investigational anti-B-cell maturation antigen (BCMA) agent, WVT078, for the treatment of relapsed and/or refractory (R/R) multiple myeloma (MM)....Cash and cash equivalents were $40.8 million as of September 30, 2021, as compared to $42.0 million as of December 31, 2020."

Commercial • Enrollment status • Hematological Malignancies • Multiple Myeloma • Oncology

Ayala Pharmaceuticals Announces First Patient Dosed in Phase 1 Clinical Trial of AL102 in Combination with BCMA Targeting Agent, WVT078, in Patients with relapsed/refractory Multiple Myeloma (GlobeNewswire) - “Ayala Pharmaceuticals, Inc…announced the dosing of the first patient in the ongoing Phase 1 clinical trial evaluating its potent investigational gamma secretase inhibitor (GSI), AL102, in combination with Novartis’ investigational anti-B-cell maturation antigen (BCMA) agent, WVT078, for the treatment of patients with relapsed and/or refractory multiple myeloma (MM).”

Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of WVT078 in Patients With Multiple Myeloma (MM) (clinicaltrials.gov) - P1; N=90; Recruiting; Sponsor: Novartis Pharmaceuticals; N=41 ➔ 90

Clinical • Enrollment change • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of WVT078 in Patients With Multiple Myeloma (MM) (clinicaltrials.gov) - P1; N=41; Recruiting; Sponsor: Novartis Pharmaceuticals; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open