Dizal Reports Promising Hematology Data at ASH 2025 with JAK1 Inhibitor Golidocitinib and Dual BTK/LYN Inhibitor Birelentinib
核心洞察
Dizal (搜索) presented new clinical data at ASH 2025 for two hematology compounds targeting T-cell and B-cell lymphomas with encouraging efficacy results.
Golidocitinib, a JAK1 (搜索)-only inhibitor, demonstrated high response rates across multiple T-cell lymphoma indications, including 94.1% ORR in newly diagnosed PTCL when combined with CHOP (搜索).
Birelentinib (搜索), a non-covalent LYN (搜索)/BTK (搜索) dual inhibitor, achieved 84.2% ORR in heavily pretreated CLL/SLL patients and received FDA Fast Track Designation.
Dizal (搜索) (SSE:688192) unveiled compelling new clinical data for its hematology pipeline at the 67th American Society of Hematology (ASH) Annual Meeting, showcasing the potential of two targeted therapies addressing significant unmet needs in T-cell and B-cell lymphomas. The biopharmaceutical company presented updated results for golidocitinib, a Janus kinase 1 (JAK1 (搜索)) only inhibitor, and birelentinib (搜索), a non-covalent LYN (搜索)/BTK (搜索) dual inhibitor.
Golidocitinib Shows Strong Activity Across T-Cell Lymphoma Spectrum
Newly Diagnosed PTCL Results
Golidocitinib demonstrated exceptional efficacy when combined with CHOP (搜索) chemotherapy in newly diagnosed peripheral T-cell lymphoma (搜索) (PTCL) patients. Two dosing regimens showed robust antitumor activity with manageable safety profiles.
The 75mg daily dose with CHOP (搜索), followed by 150mg maintenance therapy, achieved an objective response rate (ORR) of 94.1% and a complete response (CR) rate of 64.7%. Notably, 85% of patients remained on treatment by the data cutoff date. The higher 150mg daily dose with CHOP, also followed by 150mg maintenance, produced an ORR of 88.9% and CR rate of 61.1%.
Durable Responses in Relapsed/Refractory Disease
Updated 2-year follow-up data from the MD Anderson Cancer Center cohort of the multinational pivotal trial JACKPOT8 Part B revealed sustained efficacy for golidocitinib monotherapy in relapsed or refractory PTCL (r/r PTCL). The treatment achieved an ORR of 53.8% and CR rate of 46.1%, with median progression-free survival (PFS) reaching 37.9 months and a 2-year PFS rate of 58.3%.
Activity in Rare PTCL Subtypes
Golidocitinib showed compelling clinical activity in heavily pretreated patients with rare T-cell malignancies. In relapsed or refractory T-cell and NK-cell large granular lymphocyte leukemia (搜索) (r/r T-LGLL), the drug achieved an ORR of 92.3% and CR rate of 61.15%. Remarkably, 100% of STAT3 (搜索)-wildtype patients responded to treatment.
In treatment-naïve monomorphic epitheliotropic intestinal T-cell lymphoma (搜索) (MEITL), golidocitinib combined with CHOP (搜索) demonstrated profound antitumor activity with an ORR of 85.7% and CR rate of 71.4%, representing a significant therapeutic advance over conventional chemotherapy.
Addressing High-Risk PTCL-Associated HLH
For patients with r/r PTCL-associated hemophagocytic lymphohistiocytosis (搜索) (HLH), golidocitinib-based regimens showed dual anti-HLH and antitumor efficacy, achieving rapid clinical improvement and an ORR of 46.7%. Most patients achieved systemic and hematologic recovery with manageable safety profiles.
Birelentinib Overcomes BTK Inhibitor Resistance
Addressing Treatment Resistance Mechanisms
Chronic lymphocytic leukemia (搜索)/small lymphocytic lymphoma (搜索) (CLL/SLL) patients face significant challenges with BTK (搜索) inhibitor resistance. Two primary resistance mechanisms have been identified: BTK-dependent mutations and non-BTK pathway-mediated resistance. While BTK-dependent resistance is well-characterized, the emergence of kinase-impaired BTK mutations highlights the growing importance of non-BTK pathways.
Birelentinib (搜索) is designed to block both BTK (搜索)-dependent and BTK-independent BCR signaling pathways. Updated follow-up data presented at ASH demonstrated potent anti-tumor efficacy with manageable safety profiles in heavily pretreated CLL/SLL patients.
Clinical Efficacy Results
At the recommended Phase 3 dose of 50mg once daily, birelentinib (搜索) achieved an ORR of 84.2%. Tumor responses occurred regardless of prior BTK (搜索) inhibitor, BCL-2 (搜索) inhibitor, or BTK degrader treatment, and in patients with both kinase-proficient and kinase-impaired BTK mutations. The antitumor efficacy proved durable, with no new safety concerns identified during follow-up.
Regulatory Recognition and Development Status
Both compounds have received significant regulatory recognition. Golidocitinib was approved by China's National Medical Products Administration (NMPA) in June 2024 for treating adult patients with r/r PTCL, making it the first and only JAK1 (搜索) inhibitor approved for this indication. The drug also received FDA Fast Track Designation for r/r PTCL treatment in February 2022.
Birelentinib (搜索) received FDA Fast Track Designation in August 2025 for treating adult patients with relapsed/refractory CLL/SLL who have received at least two prior lines of therapy, including a BTK (搜索) inhibitor and a BCL-2 (搜索) inhibitor. A global multicenter Phase III study in r/r CLL/SLL is currently ongoing.
Historical Efficacy Data
Previous data from golidocitinib's pivotal studies showed robust and durable anti-tumor efficacy. At the August 31, 2023 data cutoff, the drug demonstrated an ORR of 44.3% in r/r PTCL patients, with all subtypes benefiting and common subtypes exceeding 40% ORR. More than 50% of patients with tumor remission achieved complete response, with a CR rate of 23.9%. The median duration of response reached 20.7 months, and median overall survival was 24.3 months as of February 2024.