Moleculin Biotech completes Part A enrolment in AML MIRACLE trial

Moleculin Biotech has completed enrolment in Part A of the MIRACLE trial, its pivotal Phase 2/3 study of Annamycin combined with cytarabine (AnnAraC) in adults with relapsed or refractory acute myeloid leukaemia (R/R AML). The Houston-based company said 89 subjects have been enrolled, with one additional subject in screening at the time of announcement, and that the programme remains on track for a comprehensive data readout in the first quarter of 2027.

Part A is a randomised, double-blind comparison of two doses of AnnAraC against a control arm of cytarabine plus placebo, with all arms assessed after a single cycle of therapy. Moleculin noted that the single-cycle design means absolute remission rates will be lower than those seen in multi-cycle historical benchmarks such as the MIRROS and CLASSIC I studies, and cautioned that the meaningful comparison will be the performance of the Annamycin arms relative to the concurrent control arm assessed on the same basis.

Trial composition and cardiotoxicity data

The company said it expects the final Part A population to be split approximately evenly between subjects previously treated with intensive 7+3 chemotherapy, broadly categorised as "fit" patients, and those previously treated with venetoclax-based regimens, broadly categorised as "unfit" patients. That balance has shifted from a roughly 70/30 fit-to-unfit split seen in the first 45 subjects. Walter Klemp, chairman and chief executive, said in a statement that the larger proportion of unfit subjects "represents a more challenging environment for achieving treatment responses" but should provide clinically important insight into Annamycin's utility across distinct patient populations.

Moleculin also reported that blinded data from MIRACLE continues to show a lack of cardiotoxicity, a property the company says differentiates Annamycin from conventional anthracyclines such as daunorubicin and idarubicin. Cardiotoxicity has long been a dose-limiting concern with anthracycline-class agents, and the company contends that Annamycin's structural design avoids the relevant mechanisms. Investors will want independent confirmation of that profile when unblinded safety data are reported alongside efficacy results in early 2027.

Competitive landscape and regulatory context

R/R AML is a high-need indication with limited approved options. Vyxeos (liposomal daunorubicin and cytarabine) and Idhifa (enasidenib) address specific genetically defined subpopulations, while CPX-351 and venetoclax-based combinations have reshaped frontline treatment but leave a substantial proportion of patients who relapse or are refractory. The shift toward venetoclax-containing first-line regimens means a growing portion of the R/R population has already failed that backbone, which is precisely the dynamic reflected in MIRACLE's evolving enrolment composition.

Several other investigational agents are in mid-to-late development in the same setting, including antibody-drug conjugates and targeted small molecules, making the differentiation profile of AnnAraC, particularly its cardiotoxicity absence and independence from resistance mechanisms, commercially relevant if the data read out positively.

Moleculin said the comprehensive Part A analysis will also guide dose selection for Part B of MIRACLE, the confirmatory expansion portion of the adaptive design. The company has previously noted FDA input into the trial design as part of its strategy to de-risk the approval pathway. A positive Q1 2027 readout would be the most significant clinical milestone in Annamycin's development history and would set the timeline for a potential regulatory submission, though the company cautioned it will require additional financing to advance the programme.