Earlier in September 2024, a Breakthrough Therapy Designation (BTD) has been granted to XNW5004 by the Center for Drug Evaluation (CDE) of the NMPA based on its groundbreaking Phase II study data in relapsed/refractory PTCL. This BTD designation provided a faster and more efficient pathway to expedite the development of XNW5004 and to shorten the review process for market approval. In addition, XNW5004 has also demonstrated superior efficacy in relapsed/refractory follicular lymphoma (FL) regardless EZH2 mutation status.
Currently, Evopoint has established a dual development strategy for XNW5004 including XNW5004 as a monotherapy and in combination with other drugs, pushing XNW5004 in a more competent position:
XNW5004 as a monotherapy in hematological malignancies
A single-arm, Phase II pivotal study and a registrational Phase III study of XNW5004 as a monotherapy in relapsed/refractory PTCL have been initiated. The milestone of First Patient In (FPI) has been achieved in both studies.
XNW5004 in combination with chemotherapy in hematological malignancies
The goal of the Phase Ib/II study approved by NMDA this time is to investigate the potential of XNW5004 in combination with first-line chemotherapy as a first-line treatment in treatment-naïve PTCL patients.
Therapeutic potential of XNW5004 in solid tumors
In prostate cancer, XNW5004 is the first EZH2 inhibitor to be investigated in combination with enzalutamide for the treatment of castration-resistant prostate cancer (CRPC) in China. The preliminary results of the ongoing study demonstrate a significantly longer progression-free survival (PFS) in patients treated with XWN5004 in combination with enzalutamide.
“The approval of this important clinical study evidenced the start of the development of XNW5004, a new-generation EZH2 inhibitor, in the field of PTCL as the first-line therapy. The unique epigenetic mechanism of action of XNW5004 may provide new insights to address the issue of drug resistance in cancer,” said Mr. Meijie Le, the co-founder and CEO of Evopoint, “Evopoint is concurrently advancing the development of XNW5004 in hematologic malignancies and solid tumors, and continues to explore more potentials of this molecule at the same time, hoping to bring new treatment options to more cancer patients as soon as possible.”
About XNW5004
XNW5004 is a substrate-competitive, selective, small-molecule inhibitor of EZH2 solely developed and proprietary to Evopoint. Clinical study results of XNW5004 have demonstrated excellent anti-tumor efficacy of XNW5004 in lymphoma, suggesting the potential of XNW5004 as a new treatment option for lymphoma patients. Meanwhile, XNW5004 has also demonstrated manageable safety profile and outstanding anti-tumor activities in several preclinical models, both in vivo and in vitro.
About EZH2
EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2). It inhibits the transcription of target genes through tri-methylation of histone H3 lysine 27 (H3K27me3) and participate in the regulation of cell cycle, cell aging, cell differentiation, tumorigenesis and other pathological/physiological processes. It has been reported that EZH2 is over-expressed in PTCL. Combination of EZH2 inhibitor with CHOP/CHOEP, the current treatment option to PTCL, may synergistically improve the outcome of treatment in PTCL.
About Breakthrough Therapy
A breakthrough therapy is an innovative drug or modified drug intented to prevent or treat serious life-threatening diseases or conditions that have no effective treatment options, or for which sufficient evidence is available to demonstrate a significant clinical advantage over existing therapies. The CDE will prioritize review process of innovative drugs designated as breakthrough therapy, which significantly shortens the time for drug market approval.
