Moleculin Biotech is advancing its lead drug candidate, Annamycin, towards a pivotal Phase 3 clinical trial for relapsed or refractory acute myeloid leukemia (R/R AML). The "MIRACLE" trial, designed with a possible accelerated approval pathway in mind, is slated to begin dosing patients in Q1 2025. This development follows promising data from the MB-106 Phase 1B/2 AML clinical trial, where the combination of Annamycin and cytarabine demonstrated a median durability of complete response composite (CRc) exceeding eight months.
Annamycin's Potential in AML Treatment
Recent discussions with key opinion leaders (KOLs) in AML have underscored Annamycin's potential to significantly alter the treatment paradigm for this aggressive hematological malignancy. A virtual AML KOL event highlighted the drug's unique mechanism of action and its ability to overcome multidrug resistance, a common challenge in treating R/R AML. Walter Klemp, Chairman and CEO of Moleculin, expressed enthusiasm about the upcoming MIRACLE trial and its potential to drive significant value for stakeholders.
MIRACLE Trial Design and Objectives
The MIRACLE trial will be a global study, including sites in the US, and will evaluate Annamycin in combination with cytarabine (AnnAraC) in patients with R/R AML. The trial is designed with an adaptive approach. Initially, approximately 75 to 90 subjects will be randomized to receive high-dose cytarabine (HiDAC) combined with either placebo, 190 mg/m² of Annamycin, or 230 mg/m² of Annamycin. An unblinding will then occur to select the optimum dose of Annamycin for the second part of the trial, where approximately 240 additional subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin. The selection of the optimum dose will be based not only on the overall balance of safety, tolerability, pharmacokinetics and efficacy, consistent with the FDA's new Project Optimus initiative.
Annamycin Development Program: Expected Milestones
- 4Q 2024: Contracting with MIRACLE trial sites and IRB approval
- 1Q 2025: First subject treated in MIRACLE trial
- 4Q 2025: Recruitment and overall efficacy rate update (n=45)
- 2H 2026: Interim efficacy and safety data (n=90) unblinded and Optimum Dose set for MIRACLE trial
- 2027: Begin enrollment of 3rd line subjects in MIRACLE2
- 2027: Enrollment ends in 2nd line subjects
- 2028: Primary efficacy data for 2nd line subjects in MIRACLE
- 2028 2H: Begin submission of a Rolling New Drug Application (NDA) for the treatment of R/R AML for accelerated approval on primary endpoint of CR from MIRACLE
Annamycin for Soft Tissue Sarcoma Lung Metastases
In addition to its AML program, Moleculin is also evaluating Annamycin as a monotherapy for soft tissue sarcoma (STS) lung metastases. Enrollment in the Phase 2 portion of the U.S. Phase 1B/2 clinical trial is complete. The study database is locked, and the clinical study report is being written and should be completed in early 2025 and will be released in detail at that time.
Financial Update
For the third quarter of 2024, Moleculin Biotech reported a research and development expense of $4.9 million, compared to $3.3 million for the same period in 2023. As of September 30, 2024, the company had cash and cash equivalents of $9.4 million, which is expected to fund planned operations into the first quarter of 2025.
