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
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Insights
The collaboration between GenFleet Therapeutics and BeiGene Switzerland GmbH to initiate a phase Ib/II trial for diffuse large B cell lymphoma (DLBCL) represents a significant step in addressing the unmet medical needs of relapsed/refractory DLBCL patients. The combination of GFH009, a CDK9 inhibitor and BRUKINSA® (zanubrutinib), a BTK inhibitor, is a strategic approach to target the disease from multiple pathways.
Given the high incidence of non-Hodgkin's lymphoma in China, the outcome of this trial could have substantial implications for the treatment landscape. The current standard, R-CHOP, leaves a considerable patient segment progressing to a more challenging stage of the disease. The trial's success could potentially lead to a new standard of care, which would be a notable advancement in the field.
It is essential to monitor the safety profile of the combination therapy, as the introduction of novel treatments often brings about concerns regarding adverse effects. However, the preclinical data indicating downregulation of anti-apoptotic proteins and increased apoptosis markers provide a scientific rationale for the combination's potential efficacy.
The initiation of this trial is a strategic business move for GenFleet, as it could position the company as a front-runner in the DLBCL treatment market in China. With a substantial patient population and the potential for a new therapy to capture market share from the current standard R-CHOP, the financial implications for GenFleet could be significant.
Investors should note that the trial's success could lead to increased valuation of GenFleet due to the expanded therapeutic portfolio and potential market exclusivity in this niche. However, it is important to consider the competitive landscape, as other companies may also be developing novel treatments for DLBCL. The collaboration with BeiGene, which is providing the clinical drug supplies of BRUKINSA®, suggests a shared risk and resource investment that could benefit both entities if the trial is successful.
Long-term, the success of this trial could set a precedent for future combination therapies in oncology, potentially leading to a paradigm shift in treatment approaches and a more personalized medicine framework.
The economic impact of improving treatments for DLBCL cannot be understated, considering the high prevalence and the associated healthcare costs. The development of more effective therapies could reduce the long-term economic burden on healthcare systems, especially in China where DLBCL represents a significant portion of new non-Hodgkin's lymphoma cases annually.
From a health economics perspective, the investment in innovative therapies like the GFH009 and BRUKINSA® combination could lead to cost savings through reduced hospitalizations, lower rates of progression and potentially improved survival outcomes. However, the cost-effectiveness of the treatment will be a important factor in its adoption. It will be important to balance the price of new treatments with their clinical benefits to ensure that they are accessible and do not impose an undue financial burden on patients and the healthcare system.
Under the terms of the agreement, GenFleet will conduct an open-label, single-arm and multi-center (10 hospitals in
The trials of GFH009 treating peripheral T-cell lymphoma and acute myeloid leukemia have entered into phase II stage in
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
3. Current status and progress of lymphoma management in
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
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
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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FAQ
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