Moleculin Biotech (MBRX) Status Update summary

Key clinical insights and unmet need

• Significant unmet need remains in relapsed/refractory AML, with survival often less than three months and limited effective therapies available, especially for patients without targetable mutations.

• Annamycin, a novel anthracycline, has shown a 50% complete remission (CR) rate in second-line AML patients, compared to an average 21% CR rate for currently approved targeted therapies.

• The drug is non-cardiotoxic, allowing higher cumulative dosing and broader use, including in patients previously treated with anthracyclines.

• Annamycin demonstrates activity in both fit and unfit patients, with no observed cardiac impairment even at doses far exceeding traditional anthracycline limits.

• The drug’s mechanism avoids cross-resistance with other AML therapies, including cytarabine and venetoclax, and may inhibit MCL-1, a key resistance factor.

Phase III Miracle trial design and expectations

• The pivotal Miracle trial uses an adaptive design, comparing two Annamycin dosing regimens plus HiDAC to HiDAC plus placebo, with early unblinding after 90 patients to select the optimal dose.

• Historical HiDAC CR rates are well established at 17-18%, providing a reliable control for comparison; Annamycin’s performance in second-line patients is nearly three times higher.

• The trial will enroll both fit and unfit patients, aiming for broad applicability and faster recruitment.

• First patient is expected in Q1 2025, with midpoint blinded data anticipated by late 2025 and unblinded data in mid-2026.

• A CR rate above 30% at interim analysis would be considered a strong indicator of success, with overall survival and MRD negativity as important secondary endpoints.

Clinical and strategic implications

• Annamycin’s lack of cardiotoxicity and MDR1 independence may allow its use in broader AML populations and potentially in other cancers.

• The FDA has agreed to allow dosing above traditional anthracycline limits based on safety data from 84 patients.

• The initial regulatory strategy targets approval for Annamycin in combination with HiDAC for relapsed/refractory AML, with plans to expand to other indications and settings.

• The estimated cost for phase III part A is around $60 million.

• Durable, deep remissions (MRD negativity) and the ability to transition patients to transplant or maintenance are seen as key clinical outcomes.