Moleculin Biotech (MBRX) Study Update summary

Clinical background and unmet need

• Annamycin is a novel anthracycline designed to address the lack of advancement in this drug class for AML over the past 50 years.

• Current AML therapies benefit only about 40% of patients, leaving nearly 60% with limited options due to relapse or resistance.

• Annamycin has shown more than double the complete remission rate compared to existing treatments for relapsed or refractory AML.

• The drug demonstrates efficacy regardless of prior therapy, genotype, or mutation, with 78% of responders achieving MRD negativity.

• 89% of complete remissions occurred in patients with difficult-to-treat cytogenetics and mutations.

Recent clinical results and regulatory feedback

• Combined second and third-line subjects (N=14) showed a 50% complete remission rate and a median remission durability of 7 months.

• No cardiotoxicity was observed in 84 patients, as confirmed by independent cardiology review and FDA divisions.

• FDA agreed to allow U.S. AML patients to be treated above the current lifetime anthracycline dose limit, expediting U.S. clinical development.

• The FDA's Project Optimus initiative influenced the trial design to compare two dosing regimens (190 mg/m² vs. 230 mg/m²).

MIRACLE phase III trial design and endpoints

• MIRACLE is an adaptive phase III trial, initially randomizing 75 patients to HiDAC plus placebo, 190 mg/m², or 230 mg/m² Annamycin.

• The optimal dose will be selected based on safety, pharmacokinetics, and efficacy from the first 75 patients.

• The primary endpoint is complete remission at one month, with secondary endpoints including durability of remission.

• The trial will focus on second-line subjects, with a follow-up MIRACLE-II trial planned for third-line patients.

• FDA allows patient crossover after 30 days, aiding recruitment and reducing risk for control group participants.