sonrotoclax (BGB-11417) / BeOne Medicines - LARVOL DELTA

BGB-11417-101: Study of Bcl-2 Inhibitor Sonrotoclax (BGB-11417) in Participants With Mature B-Cell Malignancies (clinicaltrials.gov) - P1 | N=437 | Active, not recruiting | Sponsor: BeOne Medicines | Trial completion date: Aug 2027 ➔ May 2027 | Trial primary completion date: Aug 2027 ➔ May 2027

IO biomarker • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Oncology

BGB-21447, a next generation Bcl-2 inhibitor, shows high potential in Bcl-2 overexpressing B cell non-Hodgkin lymphomas (NHL) cancers in preclinical studies (AACR 2026) - "In this study, we evaluate the potential of BGB-21447, a next-generation Bcl-2 inhibitor structurally distinct from sonrotoclax (BGB-11417), mainly in DLBCL/B-NHL via preclinical studies. Cell viability was assessed by CTG assay in vitro. These findings indicate that BGB-21447 is a Bcl-2 inhibitor with substantially greater potency than venetoclax and strong potential in indications such as DLBCL where venetoclax has suboptimal efficacy. Clinical trials are needed to validate these results."

IO biomarker • Preclinical • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

Sonrotoclax (BGB-11417), a selective Bcl-2 inhibitor, demonstrates better efficacy than Venetoclax (Ven) and Lisaftoclax (APG-2575) in hematological cancer cells, xenografts, and human bloods (AACR 2026) - "Son demonstrates significant advantage over Ven and Lisa in preclinical studies, including better efficacy in Bcl-2-dependent cancers, against Bcl-2-G101V and BTK resistance mutations, and enhanced target engagement in human whole blood. These highlight Son's great potential in addressing unmet needs in hematologic malignancies."

Clinical • IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CASP3

A Study to Investigate the Relative Bioavailability and Food Effect of a Fixed-Dose Combination Tablet Containing Zanubrutinib and Sonrotoclax (BG-71332) in Healthy Adults (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: BeOne Medicines | Active, not recruiting ➔ Completed

Trial completion

Updated Interim Results of Sonrotoclax + Dexamethasone in Patients With t(11; 14)-Positive Relapsed/Refractory Multiple Myeloma (R/R MM): An All-Oral Treatment (IMS 2025) - P1/2 | "Sonrotoclax (sonro; BGB-11417), a next-generation BCL2 inhibitor, is a more selective and pharmacologically potent inhibitor of BCL2 than venetoclax, with a shorter half-life and no drug accumulation. This ongoing study showed that the all-oral combination of sonro + dex is tolerable, with low rates of infection and hematologic toxicity, and promising efficacy, with an ORR of 81% in the 640-mg cohort, in this t(11; 14)-positive R/R MM population. Additional tx combinations with sonro are being investigated."

Clinical • CNS Disorders • Fatigue • Hematological Malignancies • Infectious Disease • Insomnia • Multiple Myeloma • Pancreatic Cancer • Pneumonia • Respiratory Diseases • Respiratory Syncytial Virus Infections • Sleep Disorder • Solid Tumor

Sonrotoclax (BGB-11417) monotherapy in patients with Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) previously treated with a bruton tyrosine kinase (BTK) inhibitor: Early results from A phase 1/2 study (ASH 2025) - P1/2 | "Sonrotoclax (BGB-11417), a next-generation B-cell lymphoma 2 (BCL2) inhibitor, is a more selective and pharmacologically potent inhibitorof BCL2 than venetoclax, with a shorter half-life and no drug accumulation. Preliminary results indicate that once daily sonrotoclax 320 mg monotherapy is welltolerated in patients with R/R MCL previously treated with a BTK inhibitor. Clinically meaningful benefits,including median DOR of 15.8 months, were seen in patients with high unmet needs and advanced,aggressive disease. These results support sonrotoclax as a promising treatment option for patients withR/R MCL."

Clinical • Monotherapy • P1/2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Disorders • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Pneumonia • Respiratory Diseases

Sonic: Escalated inpatient ramp-up of sonrotoclax in CLL/SLL and MCL (ASH 2025) - P2 | "Sonrotoclax (BGB-11417) is apromising next generation Bcl-2 inhibitor with better potency and specificity than venetoclax, a firstgeneration Bcl-2 inhibitor, in pre-clinical studies...Patients with a prior othermalignancy within the past 2 years are excluded.Objectives:Primary Objectives:To examine the safety and tolerability of an escalated ramp-up of sonrotoclax (BGB-11417) followinginitial debulking with zanubrutinib or rituximab in patients with treatment-naïve or R/R CLL/SLL andpatients with R/R MCL.To assess safety by measuring the frequency of adverse events (AEs), including episodes of laboratoryand clinical TLS.To evaluate the feasibility of reaching a target dose of sonrotoclax 320mg daily on day 12 +/- 2 daysfollowing a 4-day inpatient ramp-up of sonrotoclax.Secondary Objective:To estimate the efficacy of an escalated ramp-up of sonrotoclax followed by 1 year of combinationtherapy (with either zanubrutinib or rituximab) by assessing the overall..."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Richter's Syndrome • Small Lymphocytic Lymphoma

Sonrotoclax: Expiry of patents in US/EU/China/Japan related to composition-of-matter in 2039 (BeOne Medicines) - Annual Report 2025

Patent • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

COMBINATION TREATMENT WITH NOVEL BCL2 INHIBITOR SONROTOCLAX (BGB-11417) AND ZANUBRUTINIB INDUCES HIGH RATE OF COMPLETE REMISSION FOR PATIENTS WITH RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA (EHA 2025) - P1, P3 | "The phase 3 SYMPATICO study showed that combination therapy with venetoclax, a BCL2 inhibitor (BCL2i), and ibrutinib, a Bruton tyrosine kinase inhibitor (BTKi), had efficacy in patients (pts) with relapsed/refractory (R/R) MCL; however, treatment intolerance may impact its use. Sonrotoclax + zanu combination therapy was well tolerated and demonstrated encouraging antitumor activity, with a CR rate of 62.2%, and responses in pts previously treated with a BTKi. A registrational phase 3 study (NCT06742996) further assessing this combination with sonrotoclax 320mg is recruiting."

Clinical • Atrial Fibrillation • Cardiovascular • CNS Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Myelodysplastic Syndrome • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock

MRD-guided therapy of sonrotoclax (BGB-11417) + obinutuzumab (O) in patients with treatment-naive CLL: Initial results from an ongoing phase 1/1b study, BGB-11417-101 (ASH 2025) - P1 | "Introduction: The first-generation BCL2 inhibitor, venetoclax, is an effective treatment for CLL/SLL, but itsusage may be limited by toxicity. Sonrotoclax + obinutuzumab was generally well tolerated in patients with TN CLL/SLL, withno sonrotoclax discontinuations or deaths due to TEAEs. No laboratory or clinical TLS events occurredduring sonrotoclax ramp-up. Encouraging antitumor activity was observed with sonrotoclax 320 mg."

Clinical • IO biomarker • P1 data • Chronic Lymphocytic Leukemia • Genito-urinary Cancer • Hematological Malignancies • Neutropenia • Prostate Cancer • Richter's Syndrome • Solid Tumor • Thrombocytopenia • IGH

BGB-11417-303: A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CELESTIAL-RRCLL) (clinicaltrials.gov) - P3 | N=630 | Recruiting | Sponsor: BeOne Medicines

Trial initiation date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Initial phase 1b/2 study results with sonrotoclax (BGB-11417) in combination with carfilzomib and dexamethasone in patients with t(11; 14)-positive relapsed/refractory multiple myeloma (ASH 2025) - P1/2 | "Sonrotoclax (BGB-11417), a next-generation BCL2 inhibitor, is a more selective and pharmacologically potent inhibitor ofBCL2 than venetoclax, with a shorter half-life and no drug accumulation. Sonrotoclax + K + dex combination therapy demonstrated a tolerable safety profile andencouraging antimyeloma activity, with an 84% ORR and a 32% CR/sCR rate in heavily pretreated patientswith t(11; 14)-positive R/R MM. Enrollment in BGB-11417-105 is ongoing, and additional treatmentcombinations with sonrotoclax are being investigated."

Clinical • Combination therapy • P1/2 data • Acute Kidney Injury • Back Pain • Cardiovascular • CNS Disorders • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Insomnia • Multiple Myeloma • Musculoskeletal Pain • Nephrology • Pneumonia • Renal Disease • Respiratory Diseases • Sleep Disorder • Thrombocytopenia

BGB-11417-304: A Study to Investigate Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Acalabrutinib in Adults With Previously Untreated Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: BeOne Medicines | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

BGB-11417-303: A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CELESTIAL-RRCLL) (clinicaltrials.gov) - P3 | N=630 | Recruiting | Sponsor: BeOne Medicines

Trial initiation date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

BGB-16673-104: A Study to Investigate Safety and Effectiveness of BGB-16673 in Combination With Other Agents in Patients With Relapsed or Refractory B-Cell Malignancies (clinicaltrialsregister.eu) - P1/2 | N=99 | Recruiting | Sponsor: BeOne Medicines AG

New P1/2 trial • Hematological Malignancies • Oncology

BGB-11417-204: A Study to Investigate Sonrotoclax Combined With Zanubrutinib Versus Zanubrutinib Alone in Participants With Previously Untreated Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P2 | N=94 | Active, not recruiting | Sponsor: BeOne Medicines | Trial completion date: Jun 2030 ➔ Sep 2029 | Trial primary completion date: Oct 2027 ➔ Nov 2026

Monotherapy • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • BCL2

BGB-11417-303CLL-RR1: A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (clinicaltrialsregister.eu) - P2/3 | N=285 | Recruiting | Sponsor: BeOne Medicines AG

New P2/3 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Anticipated R&D Milestones (Businesswire) - "TEVIMBRA: Supplemental Biologics License Application submissions in U.S. and China for the treatment of adult patients with first-line HER2-positive GEA in combination with zanidatamab: 1H 2026; Japan regulatory action for the treatment of adult patients with first-line gastric cancer: 2H 2026...Sonrotoclax (BCL2 inhibitor): FDA regulatory action on New Drug Application as monotherapy treatment of adult patients with R/R MCL: 1H 2026; Phase 3 trial initiation for the treatment of adult patients with R/R multiple myeloma t(11;14): 2H 2026...BGB-16673 (BTK CDAC): Phase 2 potential accelerated approval submission (if data support) for the treatment of adult patients with R/R CLL: 2H 2026."

Approval • Filing • New P3 trial • Chronic Lymphocytic Leukemia • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Mantle Cell Lymphoma • Multiple Myeloma

Reinforcing Anti-BCMA CAR T-cells in t(11;14) Multiple Myeloma (EHA-EBMT-CART 2026) - "Here, we present a combinatorial approach integrating CAR T-cell therapy with small molecule BCL2-inhibitors such as Venetoclax and the second-generation agent Sonrotoclax. Additionally, overexpression of alternative anti-apoptotic proteins, such as MCL-1 and BCLXL, could provide an efficient rescue mechanism for CAR-T cells against BCL-2 inhibitor-induced apoptosis. Long-term restimulation assays will elucidate the impact of prolonged BCL2-inhibitor exposure on CAR T-cell phenotype and function."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Multiple Myeloma • BCL2L1 • IFNG • MCL1

ALLG NHL43: An open-label multi-centre international phase 2 trial to evaluate the safety and efficacy of two years fixed duration therapy with sonrotoclax in combination with the BGB-16673 and rituximab in patients with treatment naïve or BTKi naïve/intolerant Waldenström Macroglobulinemia (WM). (ANZCTR) - P2 | N=80 | Not yet recruiting | Sponsor: Australasian Leukaemia and Lymphoma Group

New P2 trial • Hematological Disorders • Lymphoma • Lymphoplasmacytic Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Waldenstrom Macroglobulinemia • CXCR4

Novel therapeutic strategies targeting resistance mechanisms in hematologic malignancies: from BCL2 inhibition to immunomodulatory approaches. (PubMed, Front Pharmacol) - "Main Findings: BCL2 inhibitors like venetoclax have achieved high response rates (ORR >70%) in CLL and AML but face resistance via MCL1/BCL-XL upregulation. Next-generation agents (e.g., sonrotoclax) and combinations address this...These strategies represent a paradigm shift toward precision medicine, but challenges like toxicity and biomarker-driven resistance persist. Future directions include AI-guided predictions and novel degraders like proteolysis-targeting chimeras (PROTACs)."

IO biomarker • Journal • Review • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Oncology • Targeted Protein Degradation • BCL2L1 • MCL1

A Study to Investigate the Relative Bioavailability and Food Effect of a Fixed-Dose Combination Tablet Containing Zanubrutinib and Sonrotoclax (BG-71332) in Healthy Adults (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: BeOne Medicines | Recruiting ➔ Active, not recruiting

Enrollment closed

CELESTIAL-TNCLL: An ongoing, open-label, multiregional, phase 3 study of sonrotoclax (BGB-11417) + zanubrutinib vs venetoclax + obinutuzumab for treatment-naïve (TN) CLL. (ASCO 2024) - P3 | "Background: The combination of venetoclax (ven), the first-generation BCL2 inhibitor, and ibrutinib, a BTK inhibitor, has demonstrated efficacy in patients with CLL (Wierda et al. Other secondary endpoints include PFS as assessed by investigator (INV); CRR by INV; rate of uMRD4 based on flow cytometry; overall response rate by IRC and INV; duration of response by IRC and INV; patient-reported outcomes; and safety and tolerability. Recruitment is ongoing."

Clinical • IO biomarker • P3 data • Chronic Lymphocytic Leukemia • Hematological Disorders • Neutropenia • TP53

An Open-Label, Single-Arm Study of Sonrotoclax Plus Zanubrutinib in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Without Disease Progression After First-Line BTK Inhibitor Therapy. (ChiCTR) - P=N/A | N=50 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

New trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

A Phase 1 Study with the Novel B-Cell Lymphoma 2 (Bcl-2) Inhibitor Bgb-11417 As Monotherapy or in Combination with Zanubrutinib (ZANU) in Patients (Pts) with CLL/SLL: Preliminary Data (ASH 2022) - P1a/1b | "Background/introduction: The effectiveness of Bcl-2 inhibitors as a treatment for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was established by the approval of venetoclax in pts with CLL/SLL across all lines of therapy. These preliminary data show BGB-11417, alone or in combination with ZANU, was well-tolerated in most patients. Grade ≥3 neutropenia was uncommon and manageable. Efficacy is supported by the rapid reduction in ALC during ramp-up, and early response data are promising."

Clinical • Combination therapy • IO biomarker • Monotherapy • P1 data • Chronic Lymphocytic Leukemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia