Dizal Unveils New Data on DZD8586 for B-cell Non-Hodgkin Lymphoma at 2024 ASH Meeting

DZD8586 Demonstrates Promising Anti-Tumor Efficacy and Manageable Safety Profile in B-NHL Patients

SHANGHAI, Dec. 9, 2024 – Dizal, a biopharmaceutical company focused on innovative treatments for cancer and immunological diseases, has shared the latest findings from a pooled safety and efficacy analysis of its drug, DZD8586, for patients with B-cell non-Hodgkin lymphoma (B-NHL). This data was recently presented at the 66th American Society of Hematology (ASH) Annual Meeting.

DZD8586 is a non-covalent blood-brain barrier (BBB) penetrant LYN/BTK dual inhibitor designed to treat B-NHL. The pooled analysis incorporated data from ongoing phase 1/2 clinical trials involving patients who had either progressed after previous treatments or were intolerant to them. By October 20, 2024, the study included 61 patients for the efficacy analysis and 84 patients for the safety analysis.

Anti-Tumor Efficacy:
In patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), DZD8586 demonstrated an overall response rate (ORR) of 57.9% at doses of 50 mg or higher. Notably, responses were seen in patients previously treated with both covalent and non-covalent BTK inhibitors as well as Bcl-2 inhibitors. The drug also showed effectiveness in cases with classic BTK resistance mutations (C481X) and BTK "dead" mutations. Preliminary anti-tumor activity was also observed in patients who had been treated with pirtobrutinib, even those with the T474I mutation.

The drug exhibited significant anti-tumor activity in other B-NHL types, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone B-cell lymphoma (MZL), and central nervous system lymphoma (CNSL).

Safety:
The primary dose-dependent side effects observed were thrombocytopenia and neutropenia, both of which were manageable in a clinical setting.

Pharmacokinetics (PK) and Pharmacodynamic Biomarkers:
DZD8586 displayed a dose-proportional PK profile and dose-dependent modulation of pharmacodynamic biomarkers. In patients with CNSL, the Kpuu, CSF values at steady state were 1.21 and 0.98, respectively, indicating high penetration into the central nervous system.

Dr. Xiaolin Zhang, CEO of Dizal, highlighted the challenges in treating B-NHL, noting that many patients eventually develop resistance to BTK inhibitors due to C481X and BTK loss-of-activity mutations. DZD8586, targeting both BTK-dependent and BTK-independent pathways, has shown promising anti-tumor activity and a favorable safety profile in these difficult-to-treat cases, including CLL/SLL and other B-NHL types.

Bruton's Tyrosine Kinase (BTK) inhibitors have marked a significant advancement in the treatment of B-cell lymphomas. However, resistance mechanisms, such as the C481X mutation and BTK independent pathways, pose ongoing challenges. The C481X mutation prevents covalent BTK inhibitors from binding effectively, leading to treatment failures. The loss or reduction of BTK enzyme activity represents another resistance mechanism currently lacking targeted therapy options.

DZD8586 was developed as a dual LYN/BTK inhibitor with high selectivity against other TEC family kinases and full BBB penetration. By blocking BTK and LYN, it aims to overcome resistance to existing BTK inhibitors by targeting both BTK-dependent and independent BCR-signaling pathways.

About DZD8586:
DZD8586 is an oral, highly selective, non-covalent LYN/BTK dual inhibitor targeting both BTK-dependent and independent B-cell receptor signaling pathways, with full BBB penetration. Pre-clinical studies indicated a favorable safety profile and effective inhibition of B-NHL cell growth. A study involving healthy volunteers has been completed to assess clinical safety and PK/PD correlation. Ongoing global phase I/II trials are evaluating DZD8586’s safety, tolerability, pharmacokinetics, and anti-tumor efficacy in patients with recurrent or refractory B-NHL. Preliminary results from these trials suggest that DZD8586 has favorable PK properties, a good safety profile, and promising anti-tumor efficacy.

About Dizal:
Dizal is a biopharmaceutical company dedicated to innovating and commercializing novel treatments for cancer and immunological diseases. Committed to addressing unmet medical needs, the company leverages translational science and molecular design to develop groundbreaking new medicines. Dizal has established a competitive international portfolio, with two leading assets in pivotal global studies that have already launched in China.