tacabrutideg (BGB-16673) / BeOne Medicines - LARVOL DELTA

BTK/BCL2 dual targeting enhances apoptosis in marginal zone lymphoma: preclinical activity of tacabrutideg (BGB-16673) and sonrotoclax. (PubMed, Haematologica) - "Combination studies included sonrotoclax, venetoclax, bendamustine, lenalidomide, rituximab, selinexor, and tazemetostat.Tacabrutideg showed single-agent activity in MZL cell lines, inducing BTK degradation and suppression of BCR signaling, MYC targets, and oxidative phosphorylation. Its biological effects largely overlapped with those of zanubrutinib while maintaining complete target degradation...Tacabrutideg demonstrates potent preclinical activity in MZL as a single agent and in combination regimens. Together with the superior activity of sonrotoclax, these findings provide a strong rationale for the clinical evaluation of dual BTK degradation and BCL2 inhibition in patients with MZL."

Journal • Preclinical • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • BCL2 • BCL2L1 • BTK • MCL1 • PLCG2

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple-Ascending Doses of Tacabrutideg (BGB-16673) in Adults With Chronic Spontaneous Urticaria and in Healthy Participants (clinicaltrials.gov) - P1 | N=58 | Recruiting | Sponsor: BeOne Medicines | Completed ➔ Recruiting | N=34 ➔ 58 | Trial completion date: Apr 2026 ➔ Nov 2026 | Trial primary completion date: Apr 2026 ➔ Nov 2026

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

PRELIMINARY EFFICACY AND SAFETY OF THE BRUTON TYROSINE KINASE (BTK) DEGRADER BGB-16673 IN PATIENTS WITH RELAPSED OR REFRACTORY (R/R) INDOLENT NHL: RESULTS FROM THE PHASE 1 BGB-16673-101 STUDY (EHA 2024) - P1/2 | "Preliminary data from this ongoing, first-in-human study of the novel BTK degrader BGB-16673 demonstrate atolerable safety profile and antitumor activity in heavily pretreated patients with NHL, including those with BTKinhibitor-resistant disease."

Clinical • IO biomarker • P1 data • Atrial Fibrillation • Cardiovascular • Fatigue • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hypertension • Indolent Lymphoma • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • Respiratory Diseases • Septic Shock • Targeted Protein Degradation • Waldenstrom Macroglobulinemia • BTK

PRELIMINARY EFFICACY AND SAFETY OF THE BRUTON TYROSINE KINASE (BTK) DEGRADER BGB-16673 IN PATIENTS WITH RELAPSED OR REFRACTORY (R/R) CLL/SLL: RESULTS FROM THE PHASE 1 BGB-16673-101 STUDY (EHA 2024) - P1/2 | "Emerging data from this ongoing, first-in-human study of the novel BTK degrader BGB-16673 demonstrate atolerable safety profile and antitumor activity in heavily pretreated patients with CLL/SLL, including those withBTK inhibitor-resistant mutations."

Clinical • P1 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • CNS Disorders • Endocrine Cancer • Fatigue • Hematological Disorders • Hypertension • Infectious Disease • Musculoskeletal Pain • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Solid Tumor • Targeted Protein Degradation • Thyroid Gland Carcinoma • BTK • IGH • TP53

Preliminary Efficacy and Safety of the Bruton Tyrosine Kinase Degrader BGB-16673 in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Results from the Phase 1 CaDAnCe-101 Study (ASH 2024) - P1/2 | "Responses were seen at the lowest dose, as well as in patients previously treated with a cBTKi, ncBTKi, double- (cBTKi and BCL2i) and triple- (cBTKi, BCL2i, ncBTKi) exposed patients, and in patients with and without BTK mutations. Conclusions : Emerging data from this ongoing, first-in-human study demonstrate that the novel BTK degrader BGB-16673 has a tolerable safety profile and shows promising and deep overall responses in heavily pretreated patients with R/R CLL/SLL, including those with prior BTK inhibitor treatment and BTK resistance mutations."

Clinical • IO biomarker • P1 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Fatigue • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Small Lymphocytic Lymphoma • Targeted Protein Degradation • BTK • IGH • TP53

Preliminary Efficacy and Safety of the Bruton Tyrosine Kinase Degrader BGB-16673 in Patients with Relapsed or Refractory Waldenström Macroglobulinemia: Results from the Phase 1 CaDAnCe-101 Study (ASH 2024) - P1/2 | "One patient had IgM flare at initial response assessment and went on to develop PR. Conclusions : Early data from this ongoing, first-in-human study demonstrate that the novel BTK degrader BGB-16673 has a tolerable safety profile and shows promising antitumor activity in heavily pretreated patients with BTK inhibitor–exposed R/R WM, including those with BTK and CXCR4 mutations."

Clinical • IO biomarker • P1 data • Atrial Fibrillation • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Neutropenia • Oncology • Otorhinolaryngology • Respiratory Diseases • Septic Shock • Sinusitis • Targeted Protein Degradation • Waldenstrom Macroglobulinemia • BTK • CXCR4 • MYD88

UPDATED EFFICACY AND SAFETY OF THE BRUTON TYROSINE KINASE (BTK) DEGRADER BGB-16673 IN PATIENTS (PTS) WITH RELAPSED OR REFRACTORY (R/R) CLL/SLL: RESULTS FROM THE ONGOING PHASE (PH) 1 CADANCE-101 STUDY (EHA 2025) - P1/2 | "Data from this ongoing study demonstrate that the novel BTK degrader BGB-16673 has a tolerable safety profile and shows robust and deepening responses in pts with heavily pretreated R/R CLL/SLL, including those with prior BTKi tx and BTKi mutations."

Clinical • IO biomarker • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • CNS Disorders • Fatigue • Febrile Neutropenia • Hematological Disorders • Hypertension • Infectious Disease • Neutropenia • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Septic Shock • Small Lymphocytic Lymphoma • Subarachnoid Hemorrhage • BTK • IGH • TP53

Updated efficacy and safety results of the Bruton tyrosine kinase (BTK) degrader BGB-16673 in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) from the ongoing phase 1 CaDAnCe-101 study (ASH 2025) - P1/2 | "Data from the ongoing CaDAnCe-101 study demonstrate that the novel BTK degrader BGB-16673 has a tolerable safety profile and shows robust and deepening responses in patients with heavilypretreated R/R CLL/SLL, including those with prior BTK inhibitor treatment and BTK mutations. The 200-mg dose of BGB-16673 is being evaluated in phase 2 and 3 studies in patients with R/R CLL/SLL."

Clinical • P1 data • B Cell Lymphoma • Chronic Lymphocytic Leukemia • CNS Disorders • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Respiratory Diseases • Small Lymphocytic Lymphoma • Thrombocytopenia • BTK • IGH • PLCG2 • TP53

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 Tacabrutideg and rituximab in patients with treatment naïve or BTKi naïve/intolerant Waldenström Macroglobulinemia (WM). (ANZCTR) - P2 | N=50 | Not yet recruiting | Sponsor: Australasian Leukaemia and Lymphoma Group | N=80 ➔ 50

Enrollment change • Hematological Disorders • Lymphoma • Lymphoplasmacytic Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Waldenstrom Macroglobulinemia • CXCR4

BGB-16673, a Potent BTK Degrader in Human Blood and Cancer Cell Lines, Shows High Selectivity in Both Proteomics and Kinome Panel Analysis (SOHO 2026) - "BGB-16673 is a potent BTK degrader with high selectivity across key blood cell types by proteomic profiling. Both degraders reduce TEC in platelets, while BGB-16673 shows markedly higher selectivity of kinase inhibitions than NX-5948. The clinical relevance of these selectivity profiles warrants further validation."

Preclinical • Hematological Malignancies • Lymphoma • Oncology

Updated efficacy and safety results of the Bruton tyrosine kinase degrader BGB-16673 in patients with relapsed/refractory indolent non-Hodgkin lymphoma from the ongoing phase 1 CaDAnCe-101 study (ASH 2025) - P1/2 | "These data demonstrate that the novel BTK degrader BGB-16673 is tolerable and showsclinically beneficial responses in heavily pretreated patients with FL and, particularly, MZL, includingthose who received a prior BTK inhibitor. CaDAnCe-101 enrollment continues for patients with FL andMZL."

Clinical • P1 data • Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Febrile Neutropenia • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Respiratory Diseases • BTK

BGB-16673, A BRUTON TYROSINE KINASE (BTK) DEGRADER, IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) WALDENSTRÖM MACROGLOBULINEMIA (WM): A PHASE 1 CADANCE-101 STUDY UPDATE (EHA 2026) - P1/2 | "Responses deepened over time, with early evidence of response durability. The phase 2 portion of the study is actively enrolling ."

Clinical • IO biomarker • P1 data • Atrial Fibrillation • Cardiovascular • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Waldenstrom Macroglobulinemia • BTK • CXCR4 • TP53

BGB-16673, A BRUTON TYROSINE KINASE (BTK) DEGRADER, IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA (CLL/SLL): A PHASE 1 CADANCE-101 STUDY UPDATE (EHA 2026) - P1/2 | "Summary/Conclusion These data demonstrate that the novel BTK degrader BGB-16673 continues to have a manageable safety profile with durable responses in pts with R/R CLL/SLL, including in pts with difficult-to-treat CLL/SLL. BGB-16673 (200 mg) is being evaluated in ongoing phase 2 and 3 studies in pts with R/R CLL/SLL."

Clinical • IO biomarker • P1 data • Chronic Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Respiratory Diseases • Small Lymphocytic Lymphoma • Thrombocytopenia • BTK

Phase I CaDAnCe-101 trial update: Tacabrutideg for R/R CLL/SLL (Lymphoma Hub) - "Patients had a median of four prior lines of therapy. Any grade treatment-emergent adverse event (TEAE) occurred in 97.0% of patients; Grade ≥3 TEAEs occurred in 62.7%, including Grade ≥3 infections in 35.8% and Grade ≥3 neutropenia in 25.4%. Grade ≥3 treatment-related TEAEs occurred in 34.3% of patients, while treatment-related TEAEs led to discontinuation in 6.0%; no treatment-related deaths occurred. The overall response rate (ORR) was 85.1% across doses and 94.1% in patients receiving the RDFE (200 mg tacabrutideg; n = 17), with a median duration of response (DoR) of 20.7 and 20.6 months, respectively."

P1 data • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

Second Quarter 2026 Business Highlights: Hematology (Businesswire) - "Tacabrutideg (BTK CDAC): Achieved last patient enrolled for Phase 3 CaDAnCe-303 (China-only) study (BGB-16673-303) in post-BTKi R/R CLL. BG-75202 (KAT6 A/B inhibitor): Achieved first patient enrolled into monotherapy cohort for Phase 1 study for the treatment of adult patients with acute myeloid leukemia."

Enrollment closed • Enrollment open • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia

BGB-16673-104: A Study to Investigate Safety and Effectiveness of BGB-16673 in Combination With Other Agents in Participants With Relapsed or Refractory B-Cell Malignancies (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: BeiGene | N=170 ➔ 80

Enrollment change • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CaDAnCe-104: A Study to Investigate Safety and Effectiveness of BGB-16673 in Combination With Other Agents in Participants With Relapsed or Refractory B-Cell Malignancies (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: BeOne Medicines

New P1/2 trial • Hematological Malignancies • Oncology

Zanubrutinib, Obinutuzumab, Sonrotoclax (BOSon) or BGB-16673, Obinutuzumab, Sonrotoclax (DOSon) in TN CLL/SLL (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Massachusetts General Hospital | N=40 ➔ 80

Enrollment change • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • BCL2

BGB-16673-104: A Study to Investigate Safety and Effectiveness of BGB-16673 in Combination With Other Agents in Participants With Relapsed or Refractory B-Cell Malignancies (clinicaltrials.gov) - P1/2 | N=170 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study to Investigate Safety and Effectiveness of BGB-16673 in Combination With Other Agents in Participants With Relapsed or Refractory B-Cell Malignancies (clinicaltrials.gov) - P1/2 | N=170 | Not yet recruiting | Sponsor: BeiGene

New P1/2 trial • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple-Ascending Doses of BGB-16673 in Adults With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P1 | N=35 | Completed | Sponsor: BeiGene | Recruiting ➔ Completed

Trial completion • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria • BTK

CaDAnCe-303: A Study of BGB-16673 Compared to Investigator's Choice in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Covalent Bruton Tyrosine Kinase (BTK) Inhibitors (clinicaltrials.gov) - P3 | N=153 | Active, not recruiting | Sponsor: BeOne Medicines | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

BGB-16673 VERSUS IDELALISIB + RITUXIMAB (R), BENDAMUSTINE + R, OR VENETOCLAX + R RE-TREATMENT IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA: THE PHASE 3 CADANCE-302 TRIAL (EHA 2026) - P1/2, P3 | "Reused with permission. Results N/A Summary/Conclusion N/A"

Clinical • IO biomarker • P3 data • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Leukemia • Lymphoma • Prolymphocytic Leukemia • Richter's Syndrome • Small Lymphocytic Lymphoma • TP53

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple-Ascending Doses of BGB-16673 in Adults With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P1 | N=34 | Completed | Sponsor: BeiGene | Active, not recruiting ➔ Completed

Trial completion • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

PROTEOLYSIS-TARGETING CHIMERA (PROTAC) TARGETING BRUTON TYROSINE KINASE (BTK) DEGRADATION IN MANTLE CELL LYMPHOMA (EHA 2026) - "Notably, compared with BGB-16673 and NX-2127, C23 not only efficiently degraded BTK but also induced the degradation of IKZF1 and IKZF3. Summary/Conclusion The C23 BTK-PROTAC inhibits MCL cells with BTK variants resistant to BTK-inhibitors in vitro and in vivo models. BTK-PROTAC C23 is a potential therapy of BTK-inhibitor resistant MCL."

Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Targeted Protein Degradation • BTK • IKZF1 • IKZF3