BMS-986458 / BMS - LARVOL DELTA

BMS-986458, a first-in-class, highly selective, and potent ligand-directed degrader (LDD) of B-cell lymphoma 6 (BCL6) combined with T-cell engagers (TCEs) demonstrates preclinical synergistic antitumor efficacy for the treatment of B-cell non-Hodgkin lymphoma (NHL) (ASH 2025) - P1/2 | "3 daysafter hPBMC injection, mice were randomized in 4 groups (8–9 per group): vehicle, BMS-986458 (5 mg/kgBID PO), glofitamab (glofit; 1 µg/mouse IV QW), and combination (BMS-986458+glofit)... In vitro anti-tumor response to BMS-986458 + 3 CD20xCD3 TCEs (glofit, epcoritamab, andmosunetuzumab) was evaluated in 3 cell lines... Combining BMS-986458 with TCEs results in synergistic T cell-driven tumor cell killing acrossmultiple DLBCL models. In vivo, using a hPBMC mouse DLBCL model, BMS-986458+glofit demonstratedsynergistic antitumor efficacy, and increased infiltration of CD3 T cells into the tumor microenvironment.No evidence of T-cell activation based on HLA-DR expression or plasma-measured cytokines wasobserved with BMS-986458±glofit. In vitro studies showed synergy was observed irrespective of CD20fold-induction following BMS-986458 treatment, and was also observed in models lacking BCL6expression, indicating that additional immune mechanisms may be..."

Preclinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL6 • CD20 • CD4 • CD69 • CD8 • CRBN • CXCL8 • IFNG • IL10 • IL1B • IL2 • IL4 • IL6 • TNFA

BMS-986458, a first-in-class, bifunctional cereblon-dependent ligand-directed degrader of B-cell lymphoma 6 (BCL6) in patients with Relapsed/Refractory (R/R) non-Hodgkin lymphoma (NHL): Updated results from the Phase 1 dose escalation study (ASH 2025) - P1/2 | "27 pts (52%) remain on therapy, and 25(48%) have discontinued (progressive disease, n=15; AE, n=7; advanced to transplant, n=2; withdrawal bypt, n=1). Conclusions BMS-986458 was well tolerated and shows promising efficacy in pts with heavily pre-treatedR/R DLBCL and FL, supporting its continued development for the tx of NHL."

Clinical • IO biomarker • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • High-grade B-cell lymphoma • Immunology • Lymphoma • Musculoskeletal Diseases • Musculoskeletal Pain • Neutropenia • Non-Hodgkin’s Lymphoma • Osteoarthritis • Rheumatology • Thrombocytopenia • BCL2 • BCL6 • CRBN • CXCL8 • IL10 • IL6 • TNFA

BMS-986397, a first-in-class casein kinase 1α (CK1α) degrader in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS): A phase 1 dose escalation study (ASH 2025) - P1 | "Two (3.8%) patients discontinued from treatment due to death fromTEAEs (not related to BMS-986458) of pneumonia and septic shock. Treatment with BMS-986397 monotherapy resulted in high response rates in R/R HR-MDS patients (CRR:57.1%) and modest activity in R/R AML (ORR: 12.1%). The most common TEAEs were grade 3/4 cytopeniasthat led to dose interruptions or reductions. The MTD was not reached."

Clinical • P1 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • Targeted Protein Degradation • Thrombocytopenia • GDF15 • TP53

Updated results from dose-escalation study of BMS-986458 monotherapy in heavily pre-treated relapsed or refractory non-Hodgkin lymphoma (Abstract #480) (Businesswire) - "Bristol Myers Squibb...reinforces its hematology leadership...at the 67th American Society of Hematology (ASH) Annual Meeting....BMS-986458, an investigational ligand-directed-degrader targeting BCL6, continued to show promising preliminary efficacy and acceptable tolerability in patients with heavily pre-treated R/R DLBCL and FL, with mainly low-grade adverse events. Strong antitumor activity was confirmed, with an ORR of 65% (54% in DLBCL and 80% in FL) and a CRR of 21% (7% in DLBCL and 40% in FL). Data support continued development of BMS-986458 as a monotherapy or combination therapy for non-Hodgkin lymphoma (NHL)."

P1 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma

Bristol Myers Squibb Data at ASH 2025 Showcase Potential of Hematology Pipeline and Build Momentum for Next Generation Portfolio (Businesswire) - "Data from the company’s targeted protein degradation and cell therapy research platforms, as well as other hematology programs, will highlight development across key disease areas including multiple myeloma, lymphomas and myeloid diseases."

Clinical data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Large B Cell Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Transplantation

BMS-986458 a Potential First-in-Class, Highly Selective, Potent and Well Tolerated BCL6 Ligand Directed Degrader (LDD) Demonstrates Multi-Modal Anti-Tumor Efficacy for the Treatment of B-Cell Non-Hodgkin's Lymphoma (ASH 2024) - P1/2 | "In summary, the robust cell intrinsic mechanism of BMS-986458 across BCL6-expressing NHL tumors together with its stimulation of CD20 surface expression and the immunomodulatory impact on Tfh populations, demonstrate that BCL6 degradation using BMS-986458 has the potential to be highly efficacious and represents a novel mechanism of action for NHL therapy. Collectively, this evidence supports its current clinical investigation as an orally dosed single agent or in combination with an anti-CD20 agent (NCT06090539), providing a potential first-in-class chemo-free therapeutic option for B-cell NHL patients."

Clinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • BCL6 • CRBN

BMS-986458, A FIRST-IN-CLASS, BIFUNCTIONAL CEREBLON-DEPENDENT LIGAND-DIRECTED DEGRADER (LDD) OF B-CELL LYMPHOMA 6 (BCL6) IN PATIENTS WITH R/R NHL: INITIAL PH 1 RESULTS (ICML 2025) - P1/2 | "BMS-986458 was well-tolerated and showed promising preliminary efficacy in pts with heavily pre-treated R/R DLBCL and FL, supporting its continued development for the treatment of NHL."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CRBN

BMS-986458, A FIRST-IN-CLASS, BIFUNCTIONAL CEREBLON-DEPENDENT LIGAND-DIRECTED DEGRADER (LDD) OF B-CELL LYMPHOMA 6 (BCL6) IN PATIENTS WITH RELAPSED/REFRACTORY NON-HODGKIN LYMPHOMA: INITIAL PH 1 RESULTS (EHA 2025) - P1/2 | "BMS-986458 was well-tolerated and showed promising preliminary efficacy in pts with heavily pre-treated R/R DLBCL and FL, supporting its continued development for the treatment of NHL."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Immunology • Lymphoma • Musculoskeletal Pain • Oncology • Osteoarthritis • Pain • Rheumatology • Targeted Protein Degradation • BCL2 • BCL6 • CRBN

BMS-986458 BCL6 LDD: (Businesswire) - P1/2 | N=273 | NCT06090539 | Sponsor: Bristol-Myers Squibb | "Abstract #4160340: First clinical findings were presented from the dose-escalation part of the first-in-human, multicenter, open-label study of BMS-986458 in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). Initial results evaluating 31 heavily pre-treated patients treated with BMS-986458 were promising and support continued development for the treatment of NHL; BMS 986458 was well-tolerated, with the most common treatment-related adverse events (TRAEs) being grade 1/2 arthralgia (19.4%) and fatigue (16.1%); no grade ≥3 treatment-related cytopenias or treatment-related discontinuations were observed; Antitumor activity was evident from the first dose level in DLBCL and FL patients."

P1/2 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Non-Hodgkin’s Lymphoma

A Study to Assess BMS-986458 Alone and in Combination With Anti-lymphoma Agents in Relapsed/Refractory Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1/2 | N=273 | Recruiting | Sponsor: Bristol-Myers Squibb | Phase classification: P1 ➔ P1/2

Combination therapy • Phase classification • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study to Assess BMS-986458 Alone and in Combination With Anti-lymphoma Agents in Relapsed/Refractory Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1 | N=273 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study to Assess BMS-986458 Alone and in Combination With Anti-lymphoma Agents in Relapsed/Refractory Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1 | N=273 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

Combination therapy • New P1 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology