BGB-21447 / BeOne Medicines - LARVOL DELTA

Preliminary results from a phase 1/1b first-in-human study of BGB-21447, a next-generation BCL2 inhibitor, in patients with B-cell non-Hodgkin lymphoma (ASH 2025) - P1 | "Initial first-in-human data demonstrate that BGB-21447 is well tolerated in heavilypretreated patients with B-NHL. The safety profile is as expected; as with other BCL2 inhibitors,hematologic toxicities are the most common all-grade and grade ≥3 TEAEs observed. Antitumor activity isencouraging, with ORRs of 38% and 33% observed in patients with FL/MZL and DLBCL, respectively.Enrollment in BGB-21447-101 is ongoing."

Clinical • First-in-human • IO biomarker • P1 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Leukopenia • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Richter's Syndrome • Thrombocytopenia

Trial in progress: a phase 1 dose-escalation study evaluating BGB-21447 (BCL2 inhibitor) in combination with fulvestrant with and without BGB-43395 (CDK4 inhibitor) in patients with previously treated HR+/HER2− metastatic breast cancer (SABCS 2025) - P1 | "Patients with prior BCL2i exposure are excluded.Primary objectives are to assess the safety and tolerability of BGB-21447 in combination with fulvestrant, with or without BGB-43395, and to determine the maximum tolerated dose, maximum administered dose, and recommended dose for expansion of both the doublet and triplet combination. Secondary objectives are preliminary antitumor activity (objective response rate, duration of response, and time to response per Response Evaluation Criteria in Solid Tumors v1.1), characterization of the PK (single dose and steady state), and the preliminary effect of food on PK.This study is currently recruiting patients, with sites open across Australia, China, and the United States (Part A only)."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • BCL2L1 • CDKN2A • ER • HER-2

BGB-21447-101: A Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies (clinicaltrials.gov) - P1 | N=112 | Active, not recruiting | Sponsor: BeiGene | Recruiting ➔ Active, not recruiting

Enrollment closed • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2

BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: BeiGene | N=92 ➔ 120

Enrollment change • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BCL2

A Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies (clinicaltrials.gov) - P1 | N=112 | Recruiting | Sponsor: BeiGene | N=85 ➔ 112 | Trial completion date: Oct 2026 ➔ Apr 2027 | Trial primary completion date: Mar 2026 ➔ Apr 2027

Enrollment change • Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2

BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=92 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BCL2

BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=92 | Not yet recruiting | Sponsor: BeiGene

New P1 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BCL2

A Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies (clinicaltrials.gov) - P1 | N=85 | Recruiting | Sponsor: BeiGene

Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2

Phase 1 Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies (clinicaltrials.gov) - P1 | N=66 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • BCL2

Phase 1 Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies (clinicaltrials.gov) - P1 | N=66 | Not yet recruiting | Sponsor: BeiGene

New P1 trial • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • BCL2