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