GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, today announced the preliminary safety and efficacy data from the Phase I study of GFH009 monotherapy for treatment of relapsed/refractory hematological malignancies will be shared at the 2002 Annual Meeting of the American Society of Hematology (ASH) in New Orleans, Louisiana, on December 12, 2022.
Through a phase I, multicenter, dose-escalation trial (NCT04588922), GFH009 (a highly selective CDK9 inhibitor) monotherapy is well tolerated with preliminary clinical activity in patients with relapsed/ refractory lymphomas. No dose limiting toxicities were observed to date. 4 lymphoma patients with different histology achieved stable disease. One patient with peripheral T cell lymphoma (PTCL) at 9 mg dose level had tumor shrinkage with tumor burden decreased by 62% after 8 weeks of treatment. The study is currently ongoing.
"We are delighted to collaborate with GenFleet in the study of GFH009 as China’s first highly selective CDK9 inhibitor moving into clinical trial. We are pleased to report the initial promising phase I data and preliminary clinical activity of GFH009 monotherapy. We hope to explore more indications in following studies and observe encouraging results from potential combination therapies in the future." said Professor Jianxiang Wang, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences.
“GFH009 is GenFleet’s first clinical-stage program treating hematologic malignancies and the company’s first global multi-center clinical program granted with FDA’s IND approval. GenFleet entered into its first overseas out-licensing deal with SELLAS Life Sciences (NASDAQ: SLS) to co-develop GFH009 this year. We are planning for more monotherapy and combination studies and looking forward to presenting data from such studies in future academic conferences.”said Yu Wang, M.D./Ph.D., Chief Medical Officer of GenFleet.
First in Human (FIH) Study of GFH009, a Highly Selective Cyclin-Dependent Kinase9 (CDK9) Inhibitor, in Patients with Relapsed/Refractory (r/r) Hematologic Malignancies
Session Name: 626. Aggressive Lymphomas: Prospective Therapeutic Trials
This is a phase I, multicenter, dose-escalation trial of GFH009 enrolling patients with relapsed/refractory acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) and lymphoma. In the first part of the trial, GFH009 was administered intravenously twice per week. The primary objective was to evaluate the safety of GFH009 and dose limiting toxicities (DLTs).
As of 15 July 2022, 30 patients enrolled and no DLTs were observed to date. Four lymphoma patients (3 in 4.5 mg and 1 in 9 mg) achieved stable disease (SD) including one peripheral T cell lymphoma (PTCL), one diffuse large B-cell lymphoma, one Hodgkin lymphoma and one mucosa-associated lymphoid tissue (MALT) lymphoma. The patient with PTCL at 9 mg dose level had tumor shrinkage with tumor burden decreased by 62% after 8 weeks’ treatment. One MALT lymphoma patient achieved a durable SD of 41 weeks and is still on treatment. PK exposure increased in a dose-proportional manner as increasing dose from 2.5 mg to 22.5 mg. The mean half-life ranged from 14.9 h to 17.7 h.
GenFleet and SELLAS are also presenting the pre-clinical research results of GFH009 introducing its mechanism of action at 2022 ASH Annual Meeting on December 11th（In Vitro and In Vivo Studies Support GFH009, a Selective CDK9 Inhibitor, As a Potential Treatment for Hematologic Cancers，ID#:3477）. Treatment with GFH009 demonstrated anti-proliferative activity in hematologic malignancy cell lines.
Preclinical research indicates that GFH009 is a potent and highly selective CDK9 inhibitor with the ability to reduce expression of downstream oncogenes required for rapid cellular division and protein expression through specific, short-lived inhibition of CDK9. This depletion via GFH009 inhibition of CDK9 likely deprives oncogene-addicted cancer cells of crucial survival signals, leading to senescence and death.
About GFH009 & CDK9
As the first highly selective CDK9 inhibitor entering clinical stage in China, GFH009 is a potent and highly selective small-molecule inhibitor of CDK9 with more than 100 times selectivity over other CDK subtypes. Preclinical data have also suggested the potential anti-tumor effects of GFH009 in combination with BCL-2 inhibitors.
As a potent and highly selective small molecule CDK9 inhibitor, GFH009 exhibits strong apoptosis-inducing and anti-proliferative activities in multiple human cell lines and animal models of diseases. It effectively inhibits the growth of tumor in various xenograft models and significantly improves survival of tumor bearing animals.
As a family of serine & threonine kinases, cyclin-dependent kinase (CDK) family plays an important role in cell cycle regulation and transcription. CDK9 is one of the most potential targets for cancer therapeutics in the CDK family. Compared with non-selective CDK inhibitors, highly selective CDK9 inhibitors are advantageous in avoiding off-target toxicity against other CDK subtypes and reducing the risk of dose-limiting toxicity. Currently, no highly selective CDK9 inhibitors have been authorized with New Drug Application (NDA) approvals on the global market.
About SELLAS Life Sciences Group
SELLAS is a late-stage clinical biopharmaceutical company focused on the development of novel therapeutics for a broad range of cancer indications. SELLAS’ lead product candidate, galinpepimut-S (GPS), is licensed from Memorial Sloan Kettering Cancer Center and targets the WT1 protein, which is present in an array of tumor types. GPS has potential as a monotherapy and combination with other therapies to address a broad spectrum of hematologic malignancies and solid tumor indications. The Company is also developing GFH009, a small molecule, highly selective CDK9 inhibitor, which is licensed from GenFleet Therapeutics (Shanghai), Inc., for all therapeutic and diagnostic uses in the world outside of Greater China.