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

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 & SAFETY OF THE BRUTON TYROSINE KINASE (BTK) DEGRADER BGB-16673 IN PATIENTS WITH RELAPSED/REFRACTORY WALDENSTRÖM MACROGLOBULINEMIA (WM): ONGOING PHASE (PH) 1 CADANCE-101 STUDY RESULTS (EHA 2025) - P1/2 | "Data from this ongoing study demonstrate that the novel BTK degrader BGB-16673 was well tolerated and continued to show substantial antitumor activity in pts with heavily pretreated BTK inhibitor-exposed R/R WM, including those with BTK, CXCR4, and TP53 mutations."

Clinical • IO biomarker • Anemia • Atrial Fibrillation • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Neutropenia • Oncology • Respiratory Diseases • Septic Shock • Thrombocytopenia • Waldenstrom Macroglobulinemia • BTK • CXCR4 • MYD88 • TP53

BTK-A428D IS A CROSS-RESISTANT MUTATION TO BOTH BTK INHIBITORS AND DEGRADERS (EHA 2025) - "BTK-A428D is a mutation that exhibits cross-resistance to multiple BTK degraders (BGB-16673, NX-2127, NX-5948, Abbv Compound 1) and inhibitors (ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib) both in vitro and in vivo, as supported by evidence from multiple aspects. In the future, BTK-A428D mutated cancer cells may be treated by other targeted therapies."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • PLCG2

Diagnosis and Management of Waldenstrom's Macroglobulinemia (ICML 2025) - "The cBTK-i zanubrutinib shows greater response activity and/or improved progression-free survival in WM patients with wild-type MYD88, mutated CXCR4, or altered TP53. New or emerging options for patients progressing on c-BTKi include pirtobrutinib, BGB-16673, venetoclax, and sonrotoclax. Combinations of BTK inhibitors with chemoimmunotherapy and BCL2 antagonists have advanced. Algorithms for patients with treatment-naïve and previously treated WM based on genomics, disease characteristics, and co-morbidities are discussed."

IO biomarker • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • BCL2 • CXCR4 • MYD88 • TP53

Updated Efficacy/Safety of the Bruton Tyrosine Kinase (BTK) Degrader BGB-16673 in Relapsed/Refractory (R/R) CLL/SLL: Results From the Ongoing Phase 1 CaDAnCe-101 Study (ICML 2025) - No abstract available

Clinical • P1 data • Chronic Lymphocytic Leukemia • Lymphoma • Small Lymphocytic Lymphoma • BTK

The BTK degrader BGB-16673 and the BCL2 inhibitor sonrotoclax shows anti-tumor activity as single agents and in combination in marginal zone lymphoma models (ICML 2025) - No abstract available

Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology

Updated Efficacy & Safety of BTK Degrader BGB-16673 in Patients (Pts) with Relapsed/Refractory Waldenström Macroglobulinemia (R/R WM): Ongoing Phase 1 CaDAnCe-101 Results (ICML 2025) - No abstract available

Clinical • P1 data • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia

UPDATED EFFICACY/SAFETY OF BRUTON TYROSINE KINASE DEGRADER BGB-16673 IN PATIENTS WITH RELAPSED/REFRACTORY INDOLENT NHL: ONGOING PHASE 1 CaDAnCe-101 RESULTS (ICML 2025) - P1/2 | "These data demonstrate that the novel BTK degrader BGB-16673 is tolerable and shows durable responses in heavily pretreated patients with FL and, particularly, MZL, including those receiving a prior BTKi. CaDAnCe-101 enrollment continues for patients with FL and MZL."

Clinical • P1 data • Follicular Lymphoma • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • BTK

Diagnosis and Management of Waldenstrom's Macroglobulinemia. (PubMed, Hematol Oncol) - "The cBTK-i zanubrutinib shows greater response activity and/or improved progression-free survival in WM patients with wild-type MYD88, mutated CXCR4, or altered TP53. New or emerging options for patients progressing on c-BTKi include pirtobrutinib, BGB-16673, venetoclax, and sonrotoclax. Combinations of BTK inhibitors with chemoimmunotherapy and BCL2 antagonists have advanced. Algorithms for patients with treatment-naïve and previously treated WM based on genomics, disease characteristics, and co-morbidities are discussed."

IO biomarker • Journal • Review • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • BCL2 • CXCR4 • MYD88 • TP53

Robust Early Results in CLL and WM with Potentially First-in-Class BTK Degrader (Businesswire) - P1 | N=621 | CaDAnCe-101 (NCT05006716) | Sponsor: BeiGene | "As the most clinically advanced BTK degrader, BGB-16673 continues to show potential in patients with various hematological malignancies. Updated data from the ongoing Phase 1 CaDAnCe-101 study of BGB-16673 in R/R CLL/SLL and R/R Waldenström macroglobulinemia (WM) showed substantial antitumor activity and a tolerable safety profile across heavily pretreated populations...R/R CLL/SLL (Oral Presentation S158):ORR: 84.8% across all dose levels and 93.8% at the recommended phase 2 dose of 200mg; R/R Waldenström Macroglobulinemia (Oral Presentation S231):ORR: 84.4%; major response rate: 75.0%; very good partial response rate (VGPR): 31.3%"

P1 data • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia

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=27 | Not yet recruiting | Sponsor: BeiGene

New P1 trial • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

BeiGene Showcases Strength of Hematology Portfolio at EHA 2025 with New Data Highlighting BRUKINSA’s Leadership and Next-Generation Innovation (BeiGene Press Release) - "BeiGene, Ltd...announced it will share data across a range of hematologic malignancies at the European Hematology Association (EHA) Congress in Milan, Italy, June 12–15. BeiGene has 31 abstracts accepted at EHA 2025, with four selected for oral presentations, featuring data from its best-in-class Bruton’s tyrosine kinase (BTK) inhibitor BRUKINSA (zanubrutinib) and its investigational pipeline assets – a next-generation BCL2 inhibitor, sonrotoclax, and BTK protein degrader, BGB-16673."

Clinical data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Mantle Cell Lymphoma • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia

BeiGene Announces First Quarter 2025 Financial Results and Business Updates (Businesswire) - "Sonrotoclax (BCL2 inhibitor): Continued enrollment of global Phase 2 trial for the treatment of Waldenström’s macroglobulinemia. Sonrotoclax BGB-11417-202: Filed in China for the treatment of relapsed/refractory (R/R) CLL. Sonrotoclax CELESTIAL-RR MCL BGB-11417-302: Achieved first subject enrolled for Phase 3 trial for the treatment of R/R MCL. Sonrotoclax CELESTIAL-TN CLL BGB-11417-301: Achieved last subject enrolled for Phase 3 trial for the treatment of treatment-naïve (TN) CLL. BGB-16673: Initiated Phase 3 trial compared to physician’s choice (IR/VR/BR) for treatment of R/R CLL."

China filing • Enrollment status • Trial status • Chronic Lymphocytic Leukemia • Waldenstrom Macroglobulinemia

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 BTK Inhibitors (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: BeiGene

New P3 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

A Study to Evaluate the Safety and Efficacy of BGB-16673 Compared to Pirtobrutinib in Adults With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (clinicaltrials.gov) - P3 | N=500 | Not yet recruiting | Sponsor: BeiGene

New P3 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

A Study of How [14C]-BGB-16673 is Absorbed, Broken Down, and Removed From the Body After a Single Oral Dose in Healthy Participants (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: BeiGene | Recruiting ➔ Completed

Trial completion

An oral BTK degrader TGRX-3911 overcomes resistance conferred by kinase-proficient and kinase-impaired mutations (AACR 2025) - "TGRX-3911 potently inhibited proliferation of TMD8 parental cells and those harboring knock-in BTK mutations that are resistant to currently approved ibrutinib, zanubrutinib and/or pirtobrutinib, including C481S, T474I, L528W, V416L, A428D, T474I/C481S, T474I/L528W and C481S/L528W (IC50 from 0.4 to 9.9 nM). Remarkably, TGRX-3911 potently inhibited the A428D mutant which is still resistant to current BTK degraders, NX-5948, BGB-16673 and ABBV-101...By eliminating both the catalytic and scaffold functions of BTK, TGRX-3911 has the potential to overcome clinical resistance which can hardly be achieved by conventional BTKi. The potential clinical application of TGRX-3911 for patients with B-cell malignancies is worth exploring."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD86 • PLCG2

HP-002: A brain-penetrant PROTAC that demonstrated potent anti-proliferation activities on multiple BTK mutant (AACR 2025) - "In lymphoma cells e.g. REC-1 and TMD8, HP-002 demonstrated 2-digit pM IC50 with up to ~10-fold more potent than NX-5948 and BGB-16673. HP-002 is a potent and highly selective BTK degrader against BTK-WT and multiple BTK inhibitor-resistant mutations. Brain penetration was observed in the TMD8 xenograft tumor model with deeper BTK down-regulation on the HP-002 treatment and robust tumor growth inhibition. With no significant safety risk findings in the preliminary rat and NHP DRF studies, HP-002 is currently under IND-enabling development."

Late-breaking abstract • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • BTK • CRBN • GSPT1 • SALL4

The BTK degrader BGB-16673 shows anti-tumor activity in marginal zone lymphoma models (AACR 2025) - "Effect on cell viability was assessed by MTT assay after 5 days of exposure to increasing concentrations of compounds or DMSO (control) in MZL cell lines and in cell lines with secondary resistance to idelalisib (n.=2), copanlisib (n.=1), ibrutinib (n.=2), and copanlisib/venetoclax. Oxidative phosphorylation, commonly associated with resistance to multiple therapies, was repressed by BGB-16673 but upregulated by zanubrutinib.Conclusions. Its ability to degrade BTK protein and its antitumor activity position the BTK degrader BGB-16673 as a promising candidate for further development in MZL patients."

B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CRBN

BGB-16673, a BTK Degrader, in Patients With R/R CLL/SLL: Preliminary Phase 1 Results from CaDAnCe-101 (BSH 2025) - No abstract available

Clinical • P1 data • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

Effect of Phenytoin or Itraconazole on How BGB-16673 is Absorbed and Removed From the Body in Healthy Participants (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of BGB-16673 Compared to Investigator's Choice in Participants With Chronic Lymphocytic Leukemia Previously Exposed to Both Bruton Tyrosine Kinase (BTK) and B-cell Leukemia/Lymphoma 2 Protein (BCL2) Inhibitors (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

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

Effect of Phenytoin or Itraconazole on How BGB-16673 is Absorbed and Removed From the Body in Healthy Participants (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: BeiGene

New P1 trial

BeiGene Announces Fourth Quarter and Full Year 2024 Financial Results and Business Updates (Businesswire) - "Anticipate FDA and EC approvals of BRUKINSA tablet formulation in the second half of 2025; Anticipate an interim analysis of progression-free survival for the Phase 3 MANGROVE study in TN mantle cell lymphoma (MCL) in the second half of 2025; and Anticipate completing enrollment for the relapsed/refractory (R/R) follicular lymphoma portion of the Phase 3 MAHOGANY study in the second half of 2025. Sonrotoclax: Planned data readouts in R/R CLL and R/R MCL Phase 2 trials and potential accelerated approval submissions in the second half of 2025...Anticipate enrolling first subjects in global Phase 3 trials in R/R CLL and R/R MCL in the first half of 2025."

Approval • Clinical data • Enrollment status • FDA filing • New P3 trial • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Small Lymphocytic Lymphoma

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