birelentinib (DZD8586) / Dizal Pharma - LARVOL DELTA

A Mass Balance Study of DZD8586 in Healthy Male Participants (TAI-SHAN15) (clinicaltrials.gov) - P1 | N=6 | Not yet recruiting | Sponsor: Dizal Pharmaceuticals

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

DZ2024B0002: A Phase 3 Study of DZD8586 versus Investigators Choice in r/r CLL/SLL (clinicaltrialsregister.eu) - P2/3 | N=55 | Recruiting | Sponsor: Dizal (Jiangsu) Pharmaceutical Co. Ltd.

New P2/3 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • BCL2

DZD8586 in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (TAI-SHAN9) (clinicaltrials.gov) - P2 | N=59 | Active, not recruiting | Sponsor: Dizal Pharmaceuticals | Trial completion date: Aug 2026 ➔ Dec 2026 | Trial primary completion date: Jan 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of DZD8586 in Adults With Primary Immune Thrombocytopenia (ITP) (TAI-SHAN11) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Dizal Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

A Phase 2 Study to Evaluate DZD8586 in Adults With ITP (TAI-SHAN11) (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Dizal Pharmaceuticals

New P2 trial • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

DZD8586 in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (TAI-SHAN9) (clinicaltrials.gov) - P2 | N=59 | Active, not recruiting | Sponsor: Dizal Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=180 ➔ 59 | Trial completion date: Apr 2028 ➔ Aug 2026 | Trial primary completion date: Oct 2027 ➔ Jan 2026

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Trial in progress: A phase II, multicentre study to evaluate the efficacy and safety of birelentinib (DZD8586) combination therapy in diffuse large B-cell lymphoma (TAI-SHAN12) (ASH 2025) - P1/2 | "The study consists of three arms: Arm 1: Birelentinib + R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for 6 cycles. Arm 2: Birelentinib + R-GemOx (rituximab, gemcitabine, oxaliplatin) for 8 cycles. Arm 3: Birelentinib + BR (rituximab, bendamustine) for 6 cycles...Pharmacokinetic analyses will be conducted as secondary objectives in both parts of the study. Patient enrollment for this study commenced in July 2025 and is currently ongoing."

Clinical • Combination therapy • P2 data • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • BCL2

Phase 1/2 studies of DZD8586 in CLL/SLL patients after COVALENT and non-COVALENT BTK inhibitors and BTK degraders – extended follow-up report (ASH 2025) - P1, P2 | "Durable tumor response was observed. The updated data will bepresented at the meeting."

Clinical • IO biomarker • P1/2 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Cough • Febrile Neutropenia • Hematological Disorders • Neutropenia • Respiratory Diseases • Small Lymphocytic Lymphoma • LYN • TP53

…follow-up data of birelentinib reported at this ASH Annual Meeting demonstrated potent anti-tumor efficacy with a manageable safety profile in heavily pre-treated CLL/SLL patients. (PRNewswire) - "At 50 mg QD (RP3D), birelentinib achieved an ORR of 84.2%. Tumor responses were observed irrespective of prior BTK inhibitor, BCL-2 inhibitor or BTK degrader treatment, and in patients with kinase-proficient or kinase-impaired BTK mutation. Antitumor efficacy proved durable, with no new safety concerns identified during follow-up."

Retrospective data • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

A Study of DZD8586 Versus Investigator's Choice in r/r CLL/SLL (TAI-SHAN6) (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Dizal (Jiangsu) Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

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

A Study of DZD8586 Combination in CLL/SLL (TAI-SHAN10) (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: Dizal (Jiangsu) Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

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

First Report of Phase 1 Studies of DZD8586, a BBB Penetrant LYN/BTK Dual Inhibitor, in Patients with B-Cell Non-Hodgkin Lymphoma (B-NHL) (ASH 2023) - P1, P1/2 | "Introduction Resistance to covalent (ibrutinib, acalabrutinib and zanubrutinib) and non-covalent BTK inhibitors (pirtobrutinib) is an emerging clinical challenge. The combination of BBB penetration, dual inhibition of LYN/BTK and potential to overcome C481S mutant CLL and other covalent BTKi resistant lymphomas suggest this may be a useful agent. Updated data will be presented at the meeting."

Clinical • P1 data • Atrial Fibrillation • B Cell Non-Hodgkin Lymphoma • Cardiovascular • Chronic Lymphocytic Leukemia • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Musculoskeletal Pain • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Secondary Central Nervous System Lymphoma • Thrombocytopenia • LYN

Preclinical Study of DZD8586, a Non-Covalent LYN/BTK Dual Inhibitor with Excellent BBB Penetration, for the Treatment of B-Cell Non-Hodgkin Lymphoma (B-NHL) (ASH 2023) - "TMD-8-IbruR cells carrying the C481S mutation were generated by stepwise induction of increasing concentrations of Ibrutinib...In cell lines expressing C481X and pirtobrutinib resistance mutations, DZD8586 demonstrated concentration dependent anti-proliferative effects, with similar GI50s among cells carrying different BTK mutations...The Kpuu,CSF of DZD8586 in rat and monkey were 1.2 and 1.3, respectively, suggesting its excellent BBB penetration in humans. Conclusion DZD8586 is a novel non-covalent LYN/BTK dual inhibitor, which could overcome resistance mutations to the approved covalent and non-covalent BTK inhibitors, and derive clinical benefit to patients with DLBCL and CNSL by blocking both BTK-dependent and BTK-independent signaling pathways with excellent BBB penetration."

Preclinical • B Cell Non-Hodgkin Lymphoma • Brain Cancer • Chronic Lymphocytic Leukemia • CNS Lymphoma • CNS Tumor • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • LYN

Phase 1/2 Studies of DZD8586, a Non-Covalent BBB Penetrant LYN/BTK Dual Inhibitor, in BTK Inhibitor Resistant Chronic Lymphocytic Leukemia (CLL) and Other B-Cell Non-Hodgkin Lymphoma (B-NHL) (ASH 2024) - P1/2 | "Paradoxically, the dominant clinical resistance mutations to non-covalent BTK inhibitor such as pirtobrutinib cause loss of or much diminished BTK enzyme activity, suggesting a BTK-independent resistance mechanism. PK/PD results confirmed dose-dependent pathway inhibition by DZD8586, with good BBB penetration. Enrolment continues, and updated data will be presented at the meeting."

IO biomarker • P1/2 data • Atrial Fibrillation • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Cardiovascular • Chronic Lymphocytic Leukemia • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Marginal Zone Lymphoma • Musculoskeletal Pain • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Secondary Central Nervous System Lymphoma • Thrombocytopenia • LYN

A Study of DZD8586 Combination in CLL/SLL (TAI-SHAN10) (clinicaltrials.gov) - P2 | N=66 | Not yet recruiting | Sponsor: Dizal (Jiangsu) Pharmaceutical Co., Ltd.

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

A Phase 3 Study of DZD8586 Versus Investigator's Choice in r/r CLL/SLL (TAI-SHAN6) (clinicaltrials.gov) - P3 | N=250 | Not yet recruiting | Sponsor: Dizal (Jiangsu) Pharmaceutical Co., Ltd.

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

DZD8586 Combination Therapy in Patients With Diffuse Large B-cell Lymphoma (TAI-SHAN12) (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: Dizal Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The U.S. FDA Granted Fast Track Designation to Dizal’s Birelentinib for Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (Dizal Pharma Press Release) - "Dizal...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to its Birelentinib (DZD8586) for the treatment of adult patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor....The Fast Track Designation is supported by data from a pooled analysis of two phase I/II studies of birelentinib in CLL/SLL patients previously treated with covalent/non-covalent BTK inhibitors and BTK degraders."

Fast track • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

DZD8586 Combination Therapy in Patients With Diffuse Large B-cell Lymphoma (TAI-SHAN12) (clinicaltrials.gov) - P1/2 | N=150 | Not yet recruiting | Sponsor: Dizal Pharmaceuticals

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

PHASE 1/2 STUDIES OF DZD8586 IN CLL/SLL PATIENTS AFTER COVALENT OR NON-COVALENT BTK INHIBITORS AND BTK DEGRADERS (ICML 2025) - P1, P2 | "DZD8586 showed encouraging anti-tumor activity with well-tolerated and manageable safety profile in heavily pre-treated CLL/SLL patients, including patients with prior covalent BTKi, non-covalent BTKi, BTK degrader and Bcl-2 inhibitor treatment. The updated data will be presented at the meeting."

Clinical • IO biomarker • P1/2 data • Chronic Lymphocytic Leukemia • Lymphoma • Small Lymphocytic Lymphoma

PHASE 2 STUDY OF DZD8586, A NON-COVALENT BBB PENETRANT LYN/BTK DUAL INHIBITOR, AS MONOTHERAPY IN RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: TAI-SHAN9 TRIAL (ICML 2025) - P2 | "DZD8586 demonstrated promising anti-tumor activity and a manageable safety profile in patients with r/r DLBCL at dose of 50 mg and 75 mg QD. Updated data will be presented at the meeting."

Monotherapy • P2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

PHASE 1/2 STUDIES OF DZD8586 IN CLL/SLL PATIENTS AFTER COVALENT OR NON-COVALENT BTK INHIBITORS AND BTK DEGRADERS (EHA 2025) - P1, P2 | "The data from two clinical studies, TAI-SHAN5 (NCT05824585) and TAI-SHAN8 (NCT06539182, CTR20240120), were pooled for efficacy and safety analysis in patients with CLL/SLL. DZD8586 showed encouraging anti-tumor activity with well-tolerated and manageable safety profile in heavily pre-treated CLL/SLL patients, including patients with prior covalent BTKi, non-covalent BTKi, BTK degrader and Bcl-2 inhibitor treatment. The updated data will be presented at the meeting."

Clinical • IO biomarker • P1/2 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Infectious Disease • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Small Lymphocytic Lymphoma

PHASE 2 STUDY OF DZD8586, A NON-COVALENT BBB PENETRANT LYN/BTK DUAL INHIBITOR, AS MONOTHERAPY IN RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: TAI-SHAN9 TRIAL (EHA 2025) - P2 | "DZD8586 demonstrated promising anti-tumor activity and a manageable safety profile in patients with r/r DLBCL at dose of 50 mg and 75 mg QD. Updated data will be presented at the meeting."

Monotherapy • P2 data • Atrial Fibrillation • B Cell Lymphoma • Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Thrombocytopenia

DZD8586 Overcomes Multi-Drug Resistance in…B-NHL (The Manila Times) - P2 | N=180 | TAI-SHAN9 (NCT06539195) | Sponsor: Dizal Pharmaceuticals | "A Phase II study of DZD8586 monotherapy in relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) will also be presented at EHA and ICML....At recommended phase 2 doses (RP2Ds) of 50 mg and 75 mg QD, DZD8586 monotherapy demonstrated promising anti-tumor activity in r/r DLBCL. The majority of patients showed target lesion shrinkage, with a CRR of 35.5%. Complete responders showed durable responses, with 81.8% of patients remaining in response and the median DoR was not reached. Notably, it showed efficacy in both GCB and non-GCB subtypes, supporting its broad therapeutic potential."

P2 data • Diffuse Large B Cell Lymphoma

DZD8586 Overcomes Multi-Drug Resistance in CLL and other B-NHL (The Manila Times) - P2 | N=155 | TAI-SHAN8 (NCT06539182) | P1 | N=230 | NCT05824585 | Sponsor: Dizal Pharmaceuticals | "In heavily pretreated CLL/SLL, DZD8586 achieved an ORR of 84.2%. Tumor response with a manageable safety profile was observed irrespective of prior covalent/non-covalent BTKi, BTK degrader, or BCL-2 inhibitor treatment, and in patients with classic BTK resistance mutations (C481X) as well as other BTK mutations, including kinase-dead mutations. No drug-related bleeding, atrial fibrillation, or major cardiac events observed."

P1 data • P2 data • Chronic Lymphocytic Leukemia • Non-Hodgkin’s Lymphoma