GenFleet Therapeutics, a clinical-stage biotechnology company developing cutting-edge therapies in oncology and immunology, announced that U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) for SLS009 (GFH009) for the treatment of adult patients with relapsed/refractory (r/r) peripheral T-cell lymphomas (PTCL). This designation was supported by data from the phase I, multi-center trial of GFH009 (highly selective CDK9 inhibitor) which met all key study objectives. Earlier in October, GFH009 was granted with FDA’s Orphan Drug Designation for the treatment of acute myeloid leukemia (AML).
The phase I, multi-center trial of GFH009 monotherapy for r/r hematological malignancies has completed its dose escalation portion in both China and the US. Clinical trials of GFH009 demonstrated significant reduction in expression of proto-oncogenes such as MYC, MCL1 among patients with hematological malignancies including PTCL. Four PTCL patients（36.4%）were observed with clinical response including one in a continuous treatment for over 56 weeks. GenFleet has started its phase Ib/II trial of GFH009 treating r/r PTCL in close to 40 sites in China.
“GFH009 was granted for FDA’s Orphan Drug Designation and Fast Track Designation within a month, representing important milestones in the product’s overseas development. That also demonstrates the product’s clinical potential and market prospects. Currently GenFleet and its partner SELLAS are conducting the next phase of trials in China and the US respectively. We look forward to positive data from more studies in GFH009’s development.” stated Yu Wang, M.D.,Ph.D.，Chief Medical Officer of GenFleet.
Fast Track is a process designed by the FDA to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. It was initially included in the Food and Drug Administration Modernization Act and later revised as part of the Food and Drug Administration Safety and Innovation Act. Programs with FTD are eligible for more frequent interactions with FDA to discuss the candidate’s development plan, as well as a rolling review of NDA or BLA to facilitate Accelerated Approval and Priority Review if relevant criteria are met.
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. 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. All patients failed other venetoclax-based therapies and have been enrolled to date at the 45 mg (safety) dose level in the trial; the first patient enrolled has achieved a complete response in a continuous treatment for over four months.
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, 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.
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 various targeted drugs provided new options for patients with relapsed and refractory PTCL.