DZD8586 / Dizal Pharma - LARVOL DELTA

Phase 2 study of DZD8586, a non-covalent BBB penetrant LYN/BTK dual inhibitor, as monotherapy in relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL; TAI-SHAN9). (ASCO 2025) - P2 | "DZD8586 showed promising anti-tumor activity and a manageable safety profile in patients with r/r DLBCL. 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 • LYN

Phase 1/2 studies of DZD8586 in CLL/SLL patients after covalent or non-covalent BTK inhibitors and BTK degraders. (ASCO 2025) - P1, P2 | " The data from two clinical studies, TAI-SHAN5 (NCT05824585) and TAI-SHAN8 (NCT06539182, CTR20240120), were pooled for the safety and efficacy analysis in patients with CLL/SLL... DZD8586 showed encouraging anti-tumor activity with a 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. PK/PD results confirmed dose/exposure-dependent pathway inhibition by DZD8586. 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 • Pneumonia • Respiratory Diseases • Small Lymphocytic Lymphoma • LYN

DZD8586: A Potential Novel Therapeutic Option for Patients with B-NHL (ACROFAN) - "A pooled analysis of two phase I/II studies of DZD8586 in CLL/SLL patients after treatment with covalent or non-covalent BTK inhibitors and BTK degraders (Abstract #7010) was selected for an oral presentation: An objective response rate (ORR) of 84.2% was achieved. Tumor response was observed in patients previously treated with BTK inhibitors and BCL-2 inhibitors, with response rates of 82.4% and 83.3%, respectively....Response was durable, with an estimated 9-month duration of response (DOR) rate of 83.3%."

Retrospective data • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

Dizal to Present Promising Clinical Data on Golidocitinib and DZD8586 for the Treatment of Lymphoma at the Coming International Hematology Conferences (PRNewswire) - "Dizal...announced that the latest data from eight hematologic malignancy clinical trials will be presented at the 2025 European Hematology Association (EHA) Congress and the 18th International Conference on Malignant Lymphoma (ICML). Notably, Dizal's two investigational drugs in lymphoma—golidocitinib and DZD8586—have collectively secured three oral presentations at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting, EHA Congress and ICML...The latest 2-year follow-up data from JACKPOT26, a prospective, multicenter Phase II study of golidocitinib, will be presented at both the upcoming EHA Congress and ICML, where it has been selected for an oral presentation...Two studies of DZD8586 have been selected for presentation at ASCO, EHA, and ICML....Results of a Phase II study of DZD8586 as monotherapy in relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) will be reported for the first time at the 2025 EHA Congress."

Clinical data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Indolent Lymphoma • Natural Killer/T-cell Lymphoma • Peripheral T-cell Lymphoma • Small Lymphocytic Lymphoma

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

Phase 1/2 Studies of DZD8586 in CLL/SLL Patients after Covalent or Non–covalent BTK Inhibitors and BTK Degraders (ICML 2025) - No abstract available

Clinical • P1/2 data • 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) - No abstract available

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

Dizal to Showcase Data in Hematologic Malignancies and Lung Cancer at ASCO 2025 (PRNewswire) - "DZD8586 study results in B-cell non-Hodgkin lymphomas (B-NHLs) were selected for oral and poster presentations. The analysis in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after covalent or non-covalent BTK inhibitors and BTK degraders was selected for oral presentation; Dizal will also present results from the ongoing Phase I/II study of DZD6008, a 4th generation EGFR TKI with full BBB penetration, in advanced EGFR mutation positive (EGFRm) non-small cell lung cancer (NSCLC)."

Clinical data • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Non Small Cell Lung Cancer • Small Lymphocytic Lymphoma

Dizal Announces DZD8586 and DZD6008 Presentations at 2025 ASCO Annual Meeting (PRNewswire) - "Dizal...announced today that results of its investigational drug candidates DZD8586 and DZD6008, have been selected for presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 30 – June 3, 2025, in Chicago. Oral and poster presentations of its DZD8586 study results in chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL) are selected by ASCO Scientific Program Committee. In addition, Dizal will present its 4th generation EGFR TKI clinical data in non-small cell lung cancer (NSCLC) during the conference."

Clinical data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Non Small Cell Lung Cancer

A Study of DZD8586 in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma (TAI-SHAN1) (clinicaltrials.gov) - P1/2 | N=17 | Completed | Sponsor: Dizal Pharmaceuticals | Recruiting ➔ Completed | N=386 ➔ 17 | Trial completion date: Oct 2027 ➔ Feb 2024 | Trial primary completion date: Apr 2027 ➔ Feb 2024

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

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

Dizal Presents Latest Data of DZD8586, a LYN/BTK Dual Inhibitor, in B-cell Non-Hodgkin Lymphoma at the 2024 ASH Annual Meeting (PRNewswire) - "The analysis pooled data from ongoing phase 1/2 clinical studies evaluating DZD8586 in patients with B-NHL who had progressed following, or were intolerant to, prior systemic therapies.... In chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL), the overall response rate (ORR) was 57.9% (≥ 50 mg) by data cutoff. Tumor response was observed in patients with prior treatment of covalent and non-covalent BTKi, and Bcl-2i. Tumor responses were observed in patients with classic BTK resistance mutations (C481X) as well as BTK 'dead' mutations....Significant tumor response was also observed in other B-NHL, 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)."

Retrospective data • Chronic Lymphocytic Leukemia • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Small Lymphocytic Lymphoma

DZD8586 in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (TAI-SHAN9) (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Dizal Pharmaceuticals

New P2 trial • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

DZD8586 in Patients With Relapsed or Refractory CLL/SLL (TAI-SHAN8) (clinicaltrials.gov) - P2 | N=155 | Recruiting | Sponsor: Dizal Pharmaceuticals

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

TAI-SHAN5: DZD8586 in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=230 | Recruiting | Sponsor: Dizal Pharmaceuticals | Not yet recruiting ➔ Recruiting | N=20 ➔ 230

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

Dizal Impresses with Its Differentiated Hematological Oncology Portfolio at 2023 ASH (PRNewswire) - P1 | N=20 | NCT05824585 | P1/2 | N=386 | NCT05844956 | Sponsor: Dizal Pharmaceuticals | "At 2023 ASH, the pooled analysis from the two studies were debuted. The results revealed that DZD8586 showed encouraging anti-tumor activity with manageable safety and favorable PK profile in heavily pre-treated B-NHL patients. Highlights of the study findings include...ORR of 64.7% across all dose levels, 71.4% at 50 mg; Tumor response in different subtypes, including DLBCL (ORR 83.3%), CNSL, and CLL; ORR of 50% in patients resistant to BTKi treatment"

Retrospective data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Non-Hodgkin’s 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...Methods TAI-SHAN1 (NCT05844956; CTR20220558) and TAI-SHAN5 (NCT05824585) are phase 1 dose escalation and expansion studies in patients with r/r B-NHL...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 • 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 • 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 • Brain Cancer • Chronic Lymphocytic Leukemia • CNS Lymphoma • CNS Tumor • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • LYN

Dizal Impresses with Its Differentiated Hematological Oncology Portfolio at 2023 ASH (PRNewswire) - "Preclinical studies have shown that DZD8586 can overcome resistance mutations observed with approved covalent and non-covalent BTK inhibitors. DZD8586 has exhibited potent inhibition of cell growth by blocking both BTK-dependent and BTK-independent signaling pathways...It is hypothesized that blockage of BTK pathway alone is not sufficient to bring meaningful clinical benefit in DLBCL. DZD8586 shows strong inhibition of LYN and BTK phosphorylation and achieves superior anti-tumor efficacy in DLBCL and chronic lymphocytic leukemia (CLL) models than selective BTK inhibitors....DZD8586 indicated CNS penetration with the potential to treat CNSL."

Preclinical • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies

Dizhe Pharmaceutical plans to establish a joint venture with Gaofa Group to carry out the research, production and marketing of two self-developed innovative drugs [Google translation] (STCN) - "...Dizhe Pharmaceuticals...announced that the company plans to jointly invest in the establishment of a joint venture with Wuxi Gaofa Investment Development Group Co., Ltd. and/or its affiliates (referred to as 'Gaofa Group'). The two parties signed a 'Cooperation Framework Agreement' to develop, produce and sell drugs containing the compound golidocitinib and the compound DZD8586 in the field of topical treatment of atopic dermatitis, vitiligo, chronic spontaneous urticaria and alopecia areata. Among them, Dizhe Pharmaceutical invested 700 million yuan, with a shareholding ratio of 87.5%; Gaofa Group invested 100 million yuan, with a shareholding ratio of 12.50%."

Licensing / partnership • Alopecia • Atopic Dermatitis • Immunology • Vitiligo

Dizal Highlights Its Advances in Hematological Portfolio at 2023 ASH, Featuring Breakthroughs in Lymphoma Treatment (Businesswire) - "Dizal today announced that it will have four presentations from its hematological oncology pipeline, including golidocitinib and DZD8586, at the 65th American Society of Hematology Annual Meeting and Exposition (2023 ASH, San Diego). Its global multicenter pivotal study of golidocitinib (JACKPOT8 PARTB) has been selected for oral presentation....Dizal will release the latest results from two clinical studies: the full analysis of the multinational pivotal study of golidocitinib (JACKPOT8 PARTB) in r/r PTCL and a phase 2 study evaluating golidocitinib as a maintenance therapy in patients with PTCL after first-line systemic therapy (JACKPOT26)....Dizal will report its preclinical data as well as the ongoing clinical study results in B-NHL."

P1 data • P1/2 data • P2 data • Preclinical • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

TREATMENT OF B-CELL MALIGNANCIES WITH DZD8586 THROUGH OVERCOMING BOTH BTK-DEPENDENT AND BTK-INDEPENDENT RESISTANCE (ICML 2023) - P1 | "Introduction: Two types of clinical resistance mutations, the C481S mutation, and BTK loss-of-activity mutations, have been identified to covalent (ibrutinib, acalabrutinib, and zanubrutinib) and non-covalent BTK inhibitors (pirtobrutinib). DZD8586 is a promising investigational drug which could overcome BTK-dependent and BTK-independent resistance. In the ongoing clinical study, DZD8586 showed good safety profile and encouraging anti-tumor efficacy in heavily pre-treated r/r B-NHL patients. The updated data will be presented at the conference."

CNS Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of DZD8586 in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=386 | Recruiting | Sponsor: Dizal Pharmaceuticals

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

DZD8586 in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Dizal Pharmaceuticals

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