DiTech Pharmaceuticals' Innovative Drugs Garner Promising Results in Lymphoma Research at ASH Annual Meeting

Introduction

DiTech Pharmaceuticals (stock code: 688192.SH) recently announced that two of its investigational new drugs, Golixetinib and DZD8586, have been selected for presentation at the 65th Annual Meeting of the American Society of Hematology (ASH). The studies, focused on lymphoma, highlight the groundbreaking advancements made by DiTech Pharmaceuticals in this field. The ASH Annual Meeting is the largest international academic conference in hematology, showcasing cutting-edge research from around the world. The event is scheduled to take place from December 9 to 12, 2023, in San Diego, United States.

Golixetinib: The First JAK1 Inhibitor in the Lymphoma Field

Golixetinib is the world's first and currently the only highly selective JAK1 inhibitor in the lymphoma field to have reached the New Drug Application (NDA) stage. It is being investigated for the treatment of relapsed/refractory (r/r) peripheral T-cell lymphoma (PTCL). The ASH Annual Meeting will feature two related studies on Golixetinib.

The pivotal global multicenter Phase II clinical trial (Part B of JACKPOT8) for r/r PTCL met its primary endpoint, with an objective response rate (ORR) of 44.3% as assessed by an independent review committee (IRC). This ORR is consistent with the preliminary analysis results previously presented at the 2023 ASCO Annual Meeting, surpassing existing treatment options by nearly twofold. Golixetinib demonstrated good safety and tolerability, offering a potential breakthrough in the treatment of r/r PTCL. Detailed survival data will be presented in an oral session at the 2023 ASH Annual Meeting.

After receiving standard frontline therapy, approximately 40% of complete response (CR) patients and 80% of partial response (PR) patients in PTCL experience disease relapse or progression within two years. The prognosis for these patients is poor, and there is a lack of standard maintenance therapy. Results from a Phase II clinical trial (JACKPOT26) demonstrate that Golixetinib, as a maintenance/consolidation therapy, is safe and effective following initial tumor response. The latest efficacy and safety data from this study will be presented at the conference.

DZD8586: First-in-Class LYN/BTK Dual Target Inhibitor

DZD8586 is a novel, fully penetrant LYN/BTK non-covalent dual target inhibitor that can cross the blood-brain barrier. It is being developed for B-cell non-Hodgkin lymphoma (B-NHL). Preclinical research and a Phase I clinical trial analysis of DZD8586 have been selected for presentation at the ASH Annual Meeting.

While BTK inhibitors have shown clinical efficacy in treating B-NHL, the issue of drug resistance remains a significant challenge. The mechanisms of resistance can be BTK-dependent or non-BTK-dependent. Currently, there is no drug available that can simultaneously address both mechanisms of resistance, underscoring the need for a safe and effective treatment for relapsed or refractory (r/r) B-NHL.

Preclinical studies have demonstrated that DZD8586 can effectively block both BTK-dependent and non-dependent B-cell receptor (BCR) signaling pathways, inhibiting the growth of various B-NHL subtypes. Moreover, DZD8586 has shown complete penetration of the blood-brain barrier in animal models, indicating its potential to overcome the issue of resistance observed with existing BTK inhibitors.

DZD8586 exhibits strong inhibition of both LYN and BTK targets while maintaining excellent selectivity. It has demonstrated significant inhibitory activity against C481S mutant BTK and BTK mutations associated with resistance to Pirtobrutinib (LOXO-305). Additionally, it effectively suppresses the proliferation of diffuse large B-cell lymphoma (DLBCL) cells.

Currently, DZD8586 is being evaluated in two Phase I clinical trials (TAI-SHAN1 and TAI-SHAN5) for r/r B-NHL globally. Preliminary results from these studies have shown encouraging pharmacokinetic (PK) characteristics, safety, and anti-tumor activity. The latest efficacy and safety analysis from these studies will be presented for the first time at the ASH Annual Meeting.

Conclusion

DiTech Pharmaceuticals' innovative drugs, Golixetinib and DZD8586, have demonstrated promising results in lymphoma research. Golixetinib, as the world's first JAK1 inhibitor in the lymphoma field, has shown potential as a breakthrough therapy for r/r PTCL. DZD8586, a first-in-class LYN/BTK dual target inhibitor, holds promise in overcoming drug resistance in r/r B-NHL. The selectionfor presentation at the prestigious ASH Annual Meeting highlights the significance of these advancements in the field of hematology and underscores DiTech Pharmaceuticals' commitment to developing effective therapies for patients with lymphoma. Further data presented at the conference will provide additional insights into the efficacy and safety profiles of these investigational drugs, potentially paving the way for improved treatment options and better outcomes for lymphoma patients.