Moleculin AML trial holds 37% blinded CRc in venetoclax-failed patients
Moleculin Biotech has reported updated blinded interim data from Part A of its pivotal Phase 2/3 MIRACLE trial, showing that a composite complete remission rate of 37% has held steady across a patient population that has grown progressively harder to treat.
With 62 subjects now evaluable, the blinded complete remission (CR) rate stands at 24% and the composite complete remission rate (CRc) at 37%. Of those 62 patients, 30 had previously received a venetoclax-based regimen. Within that subgroup, the blinded CR and CRc rates were 23% and 37% respectively, essentially the same as the overall evaluable cohort. Published salvage remission rates following first-line venetoclax failure are approximately 13%, with median overall survival of around 2.4 months, according to a retrospective single-centre analysis cited by the company (Maiti et al., Haematologica, 2021).
Because the analysis remains blinded, the figures include subjects randomised to the control arm and are expected to sit below the unblinded Annamycin-arm results. At the June 2026 interim analysis of 45 evaluable subjects, the unblinded CRc reached 50% and 57% in the two Annamycin dose cohorts versus 29% for the control arm. The two datasets are not directly comparable.
Trial progress and cardiac safety profile
Enrollment has reached 74 of the 90 planned Part A subjects, with final treatment expected in September 2026. Comprehensive unblinded Part A data are on track for December 2026 to February 2027, after which the company will seek to transition into the adaptive design's Part B. Moleculin said it continues to observe no evidence of cardiotoxicity, measured via ejection fractions and adverse event reporting, a characteristic the company positions as a key differentiator for Annamycin against conventional anthracyclines such as daunorubicin and idarubicin, which carry well-documented risks of cardiomyopathy.
Walter Klemp, chairman and chief executive of Moleculin, said: "That it has held in a narrow band while the population became measurably harder to treat is what gives us added confidence as we approach the completion of Part A."
Annamycin holds FDA Fast Track Status and Orphan Drug Designation for R/R AML, as well as Orphan Drug Designation from the EMA. Composition-of-matter patent protection runs through 2040, with potential extension to 2045.
Competitive and regulatory context
R/R AML after venetoclax failure is one of the most underserved niches in haematologic oncology. Standard second-line options, including FLAG-IDA and CPX-351, deliver limited and short-lived responses in this population, and no agent has yet secured a specific regulatory indication for post-venetoclax relapse. The unmet need has drawn interest from several development-stage programmes, including menin inhibitors such as revumenib (Syndax), which received accelerated FDA approval in late 2024 for NPM1-mutant or KMT2A-rearranged R/R AML, and which is being explored in venetoclax-failure settings in combination studies. However, menin inhibitors address a molecularly defined subset, whereas Annamycin is being evaluated across an unselected R/R population.
The MIRACLE protocol's single-cycle design is a structural consideration for regulators and clinical readers. The company has noted that historical benchmarks, including MIRROS and CLASSIC I, permitted multiple cycles of treatment, which is likely to temper direct cross-trial comparisons. The December-to-February unblinded readout will be the data event that matters: it will carry the full 90-subject dataset, a randomised control arm evaluated on the same single-cycle basis, and sufficient safety information to inform a Part B transition decision and regulatory discussions on both sides of the Atlantic.