GenFleet Starts Phase Ib/II Trial of GFH009 (Highly Selective CDK9 Inhibitor) Treating Patients with Relapsed/Refractory Peripheral T-cell Lymphomas (PTCL)

SHANGHAI, Oct. 10, 2023 /PRNewswire/ -- GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, today announced the first subject was dosed in a phase Ib/II trial of GFH009 (a highly selective CDK9 inhibitor) treating relapsed/refractory PTCL (peripheral T-cell lymphomas) patients. Designed to enroll a total of 95 patients, this multi-center (close to 40 hospitals in China), open-label, single-arm study will include the prominent Sun Yat-Sen University Cancer Center and the First Affiliated Hospital of Zhengzhou University.

The phase I, multi-center trial of GFH009 monotherapy for relapsed/refractory hematological malignancies has completed its dose escalation portion in both China and the US. Preliminary results demonstrated favorable safety/tolerability and promising clinical efficacy of GFH009. Complete or partial responses were observed in acute myeloid leukemia and lymphoma patients; 4 PTCL patients were observed with clinical response including one in a continuous treatment for over 48 weeks. The recommended phase II dose (RP2D) has been determined to be 100 mg once per week based on all safety, pharmacokinetics, pharmacodynamics, and efficacy data.

There are approximately 100,000 newly diagnosed non-Hodgkin's lymphoma（NHL）patients per year in China, with PTCL patients accounting for over 20% of new cases. Within the histologically and clinically heterogeneous group of PTCL, patients in most subtypes (other than ALK-positive ALCL patients) are relatively chemo-resistant and are less responsive to autologous stem cell transplants. There is significant room for improvement in terms of prognosis and overall survival rate in recurrent/refractory PTCL patients after first-line treatment. Based on current studies, the functional dependence on MCL1 and the amplification or copy-number gain of MYC observed in many PTCL cell lines are correlated to poor prognosis. Clinical trials of GFH009 demonstrated significant reduction in the expression of proto-oncogenes such as MYC, MCL1, and PCNA in patients with hematological malignancies including PTCL.

"GFH009 is GenFleet's first clinical-stage asset for hematological malignancies in a global multi-center trial. Currently there is significant unmet medical need in recurrent/refractory PTCL; studies from GFH009 have confirmed its potential in combating the disease. Following on GFH009's favorable safety profile and preliminary efficacy in phase I trial, we are planning to explore more studies of GFH009 monotherapy and combination therapies for global patients." stated Yu Wang, M.D., Ph.D., Chief Medical Officer of GenFleet.

GenFleet received IND approval in 2020 for the GFH009 monotherapy (NCT04588922) to proceed into phase I trial treating patients with relapsed/refractory hematological malignancies. In 2022, GenFleet and SELLAS Life Sciences Group (Nasdaq:SLS) entered into an exclusive license agreement across all therapeutic and diagnostic uses. Conducted by SELLAS, the phase IIa clinical trial of SLS009 (GFH009) with venetoclax and azacitidine is ongoing in the US treating r/r AML patients.

References:

1.     Targeting CDK9 with selective inhibitors or degraders in tumor therapy: an overview of recent developments, 2023, Cancer Biology & Therapy 
2.     Current status and progress of lymphoma management in China, 2018, International Journal of Hematology
3.     SELLAS Announces First Patient Dosed in Phase 2a Clinical Trial of GFH009 in Acute Myeloid Leukemia, 2023
4.     VIP152, a Selective CDK9 Inhibitor, Induces Complete Regression in a High-Grade B-Cell Lymphoma Model and Depletion of Short-Lived Oncogenic Driver Transcripts, MYC and MCL1, with a Once Weekly Schedule, 2021, Blood 

About CDK9 and GFH009

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 and an AML patient observed with complete remission (with no minimal residual disease) lasting for over 8 months.

According to preclinical research, GFH009 reduces the expression of downstream oncogenes required for rapid cellular division and protein expression through specific 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.

About PTCL (peripheral T-cell lymphomas)

The incidence of PTCL in Asia is substantially higher compared with western countries. The most common PTCL subtypes in China include NK/T-cell lymphoma (NKTCL), PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL).

Currently, CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP with etoposide remain the most commonly used first-line treatment for PTCL. Autologous stem cell transplantation (AUTO-HSCT) may follow as a consolidation therapy for eligible patients. Based on retrospective studies, ALK-positive ALCL patients have the most favorable prognosis after applying CHOP-based regimens. However, the prognosis of relapsed/refractory PTCL patients was poor, and the median overall survival was less than 6 months. In recent years, the development of targeted drugs provided new options for patients with relapsed and refractory PTCL.

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 region), 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.