Moleculin Biotech, Inc., a clinical-stage pharmaceutical company with drug candidates targeting difficult-to-treat tumors and viruses, has published data from a completed European phase 1 MB-105 clinical trial assessing the safety and efficacy of annamycin as a single agent for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML).
‘Results of the Phase 1 Liposomal Annamycin Study for the Treatment of Relapsed or Refractory AML Patients After Induction Therapy’ was published in the Journal of Cancer Research.
The authors of the published manuscripts include Wolfram Dempke (Moleculin’s chief medical officer of Europe), John Paul Waymack (Moleculin’s chief medical officer) and Waldemar Priebe (chair of Moleculin – scientific advisory board), as well as the Polish investigators of the MB-105 experiment.
Walter Klemp, chairman and CEO of Moleculin, said: “These preliminary data provide an important foundation for our AML program and are informative to guide our clinical development strategy for Annamycin in combination with Cytarabine for the treatment of AML. We continue to be optimistic about the potential of annamycin to provide patients with a non-cardiotoxic treatment option.”
About the MB-105 Moleculin study
MB-105 is the company’s multicenter, open label, complete dose escalation study, which was performed to determine the maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D) of annamycin as a single agent for the treatment of patients with AML after induction therapy. A total of 20 subjects aged between 24 and 76 years with a mean age of 64.5 years were enrolled at five clinical trial sites in Europe. The mean number of previous treatments for all subjects was four (range 1–18). Of the 20 enrolled subjects, 17 received the full dose for three consecutive days per protocol.
Overall response rate of 80%.
As previously announced, the final results of MB-105 align with the overall safety profile of annamycin and the observations made in previously completed and ongoing clinical studies evaluating annamycin. In addition, as detailed in the paper, among the eight subjects treated in the final dose cohort (240 mg/m), five were evaluated for efficacy and there was one PR (partial response) and three CRi (complete response with incomplete recovery of peripheral blood count) among these five subjects, representing an overall response rate (ORR) of 80% in the final cohort.
For purposes of this clinical trial, CR means the subject’s bone marrow blasts are reduced by 5% or less (with CRi meaning CRs where there is incomplete recovery of the white blood cell and/or platelet count), and PR means the subject’s bone marrow blasts are reduced by 50% and result in an explosion count of 25% or less.
Annamycin showed no evidence of cardiotoxicity based on a review of cardiotoxicity biomarkers, LVEF, and ECHO GLS evaluation. This property distinguishes the drug from all other anthracyclines which have shown limited or no cardiotoxicity to date and distinguishes it as a very promising anticancer agent. It retains the ability to poison TOPO-IIα (topoisomerase II) and can also overcome mdr-1-related resistance mechanisms in leukaemic blasts, as demonstrated in its parent compound.
Based on safety and dose data from two successfully completed phase 1 trials, Moleculin began an ongoing phase 1/2 trial evaluating annamicin in combination with cytarabine (Ara-C) for the treatment of subjects with refractory or relapsed AML after induction therapy (MB-106).
Annamycin currently has Fast Track Status and Orphan Drug Designation from the US Food and Drug Administration (FDA) for the treatment of soft tissue sarcoma lung metastases and the treatment of relapsed or refractory AML.