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

Rhea-AI Summary

GenFleet Therapeutics collaborates with BeiGene Switzerland for a combination study in DLBCL patients, aiming to provide innovative therapies for relapsed/refractory cases. The agreement involves a phase Ib/II trial of GFH009 and BRUKINSA® targeting DLBCL, a prevalent form of non-Hodgkin's lymphoma in China. The trial marks the first combination study by a Chinese biotech in this field, with promising results from previous trials of GFH009 in other lymphomas.

Oncology Clinical Research Analyst

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.

Pharmaceutical Market Analyst

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.

Healthcare Economist

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.

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

What is the focus of the collaboration between GenFleet Therapeutics and BeiGene Switzerland?

The collaboration aims to conduct a combination study of GFH009 (CDK9 inhibitor) and BRUKINSA® (zanubrutinib, BTK inhibitor) in treating diffuse large B cell lymphoma (DLBCL) patients.

What is the significance of the trial led by Henan Cancer Hospital and Fudan University Shanghai Cancer Center?

The trial involves prominent institutions in China and marks the first combination trial by a Chinese biotech to target DLBCL using CDK9 and BTK inhibitors.

What are the key findings from the trials of GFH009 in other lymphomas?

Previous trials of GFH009 in peripheral T-cell lymphoma and acute myeloid leukemia showed significant downregulation of anti-apoptotic proteins and promising responses among patients.

How does GFH009 demonstrate its anti-proliferation effects?

Preclinical research showed that GFH009 induces dose-dependent increase in apoptosis markers like cleaved caspase-3 and cleaved PARP in tumor cell lines.

Who is the Chief Executive Officer of GenFleet Therapeutics?

Jiong Lan, Ph.D., serves as the Chief Executive Officer of GenFleet Therapeutics.