GenFleet and BeiGene Enter into Trial Collaboration for a Potentially First-in-class Combination Therapy to Initiate Phase Ib/II Study of GFH009 (CDK9 inhibitor) and BRUKINSA® (zanubrutinib) Treating Diffuse Large B Cell Lymphoma

SHANGHAI, March 28, 2024 /PRNewswire/ -- GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, today announced it has entered into a clinical trial collaboration and supply agreement with BeiGene Switzerland GmbH to start a combination study of GFH009 (CDK9 inhibitor) and BRUKINSA^® (zanubrutinib, BTK inhibitor) in a multicenter phase Ib/II trial treating diffuse large B cell lymphoma (DLBCL). The first patient was dosed in the trial led by prominent Henan Cancer Hospital and Fudan University Shanghai Cancer Center.

Under the terms of the agreement, GenFleet will conduct an open-label, single-arm and multi-center (10 hospitals in China) study of the combination therapy to evaluate the safety and efficacy among relapsed/refractory DLBCL patients. BeiGene will provide clinical drug supplies of BRUKINSA^®(zanubrutinib) for this trial. This study will be the first combination trial conducted by a Chinese biotech to combine CDK9 inhibitor and BTK inhibitor targeting DLBCL.

China's National Cancer Center reports that around 100,000 patients are newly diagnosed non-Hodgkin's lymphoma per year in China, with DLBCL patients accounting for 40-50% of new cases. Currently, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is the standard of care in the first line setting for DLBCL globally, but 30-40% of DLBCL patients ultimately progressing into relapsed/refractory stage need more effective treatments.

The trials of GFH009 treating peripheral T-cell lymphoma and acute myeloid leukemia have entered into phase II stage in China and the U.S. respectively. Numerous patients achieved complete or partial response, and significant downregulation of anti-apoptotic proteins such as MYC, MCL1 were observed among patients.

Preclinical research demonstrated GFH009's anti-proliferation effects on various tumor cell lines; the expression level of apoptosis markers including cleaved caspase-3 (CC3) and cleaved PARP increased dose-dependently with GFH009 treatment. According to academic publications, the treatment of CDK9 inhibitor in combination with BTK inhibitor resulted in accelerated induction of cleaved CC3 (the key protein in the cancer-cell killing mechanism of cytotoxic T lymphocytes).

"We are delighted to reach this agreement to move forward the innovative combinational therapy. We appreciate BeiGene's recognition of GenFleet's R&D capabilities and GFH009's clinical potential. GFH009 has shown a promising activity in monotherapy trial and BRUKINSA^®(zanubrutinib) has been approved in scores of markets worldwide; we hope to explore more innovative therapies for relapsed/refractory DLBCL patients with our mutual efforts." stated Jiong Lan, Ph.D, Chief Executive Officer of GenFleet.

References：

1.Development and validation of a sensitive UPLC–MS/MS analytical method for GFH009 in rat plasma and its application to toxicokinetics studies, Biomedical Chromatography, 2023

2. Epidemiology of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the United States and Western Europe: population-level projections for 2020–2025, Leukemia & Lymphoma, 2021

3. Current status and progress of lymphoma management in China, International Journal of Hematology, 2018

About GFH009 & CDK9

As a family of serine & threonine kinases, the cyclin-dependent kinase (CDK) family plays an important role in cell cycle regulation and transcription; CDK9 activity is inversely correlated with the overall survival rate of patients with multiple tumors. Data from phase I trial and the preclinical research of GFH009 were posted at the 2002 Annual Meeting of the American Society of Hematology. GFH009 monotherapy is well tolerated with preliminary clinical activity in patients with relapsed/ refractory lymphomas.

According to preclinical research, GFH009 reduces the expression of downstream oncogenes required for rapid cellular division and protein expression through specific, short-lived inhibition of CDK9. With more than 100 times selectivity over other CDK subtypes, this depletion via GFH009 inhibition of CDK9 likely deprives oncogene-addicted cancer cells of crucial survival signals, leading to senescence and death. GFH009 also exhibits strong anti-proliferative activities in multiple human cell lines, effectively inhibits the growth of tumor in various xenograft models and significantly improves survival of tumor bearing animals.

GFH009 has been granted with both fast track and orphan drug designation from the FDA for the treatment of adult patients with relapsed/refractory (r/r) peripheral T-cell lymphomas (PTCL) and r/r acute myeloid leukemia (AML). GenFleet received IND approval in 2020 for the GFH009 monotherapy to proceed into phase I trial treating patients with r/r hematological malignancies. In 2022, GenFleet and SELLAS Life Sciences Group (Nasdaq: SLS) entered into an exclusive license agreement across all therapeutic and diagnostic uses worldwide outside of Greater China (the Chinese mainland, Hong Kong, Macau and Taiwan).  

About BRUKINSA^® (zanubrutinib)

BRUKINSA^®(zanubrutinib) is a small molecule inhibitor of BTK designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

About GenFleet Therapeutics

GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies, is dedicated to serving significant global unmet medical needs in oncology and immunology. Based on the deep understanding of disease biology and translational medicine, GenFleet's proprietary and fully integrated R&D platform highlights multiple cutting-edge products with novel mechanisms and global IP.

Since its inception in 2017, GenFleet has built up industry-leading capabilities and expertise in developing novel drug candidates - both small molecules and biologics. Its pipeline includes over 10 programs, many of which have entered multi-regional clinical trials across China (including Taiwan), the United States, Europe and Australia. To date, GenFleet has over 5 clinical studies encompassing IND stage to phase II studies and completed co-development partnerships with numerous publicly listed companies worldwide.

GenFleet is expected to progress additional programs into the clinic, as well as transition from a clinical stage biotech company into a commercial stage biopharmaceutical company in the next 3-5 years.

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SOURCE GenFleet Therapeutics