Moleculin Biotech announced additional positive interim safety and efficacy data from one of the Company's two ongoing open label, single arm Phase 1/2 studies of Annamycin for the treatment of relapsed or refractory acute myeloid leukemia (AML).

The Phase 1 portion of these clinical trials is designed to establish the safety of Annamycin and to determine the Recommended Phase 2 Dose to be used in the Phase 2 portion of the trials. While the Primary Endpoint of the Phase 1 portion is safety, a Secondary Endpoint is the assessment of efficacy generally defined as an improvement in bone marrow biopsy results sufficient to qualify patients for a potentially curative bone marrow transplant. The Company cautions not to place undue reliance on interim results.

The third cohort in Poland receiving a single dose of 180 mg/m2 in the Phase 1 dose escalation portion of the trial was completed with no adverse events and the trial will continue to the next cohort of 210 mg/m2. In the US trial, one patient has completed treatment in the second cohort at 120 mg/m2. This brings the total number of patients treated and evaluated at or above 120 mg/m2 to 10. An additional patient in the US has begun treatment at 120 mg/m2 but has yet to complete post-treatment evaluation. The interim results for these 10 patients are 1 CRi (defined as a complete response with incomplete recovery of white blood cells and/or platelets) and 2 partial responses ("PRs" or where bone marrow blasts are reduced 50% and to below 25%). One additional patient was bridged to bone marrow transplant (BT) based on a sufficient reduction in bone marrow blasts, bringing the total to 4 out of 10 patients at or above 120 mg/m2 who have demonstrated efficacy.

In the latest cohort in Poland, 1 of the 3 patients treated at 180 mg/m2 had a PR sufficient to qualify for a potentially curative bone marrow transplant. The results for all 3 patients were reviewed by the Safety Review Committee, which determined that no drug-related adverse events were observed that would prevent advancing the trial to the next higher dose level of 210 mg/m2. To date in the European trial, only one adverse event related to Annamycin has been reported; a patient experienced grade 2 mucositis (which resolved to grade 1 within 2 days). In the Company's parallel US clinical trial, one new patient (the first of cohort #2) achieved a "morphologically leukemia free state" or MLFS, which also constitutes a CRi, after receiving a single dose of 120 mg/m2.

The company is referring to Annamycin as a "next generation anthracycline," because it is designed to provide enhanced therapeutic benefits when compared with traditional anthracyclines (like doxorubicin) while reducing the potential for unwanted cardiotoxicity, or damage to the heart. This design intent has previously been validated with preclinical toxicology studies in animal models (as required by FDA) demonstrating Annamycin has little to no cardiotoxicity when compared with doxorubicin. Of the 14 patients treated thus far in both trials, none has shown any evidence of cardiotoxicity. This includes 7 patients in Poland who were treated at levels above the US maximum allowable cumulative anthracycline dose level (550 mg/m2), a limitation not imposed on our trial in Europe. If upheld in further studies, this lack of toxicity could be an important differentiator between Annamycin and the currently approved anthracyclines, for which cardiotoxicity is a well-known treatment limitation.

"The interim data from our early-stage clinical trials of Annamycin continues to meet or exceed our expectations, from both a safety and efficacy perspective," said Walter Klemp, Moleculin's Chairman and CEO. "We believe the activity we are seeing – with 40% of patients treated at or above 120 mg/m2 responding with CRi's, PR's and/or bridging to a potentially curative bone marrow transplant – is encouraging, especially since we have yet to reach a maximum tolerable dose. Although the data is preliminary, we are excited by the results to date, and to continue moving forward. Importantly, recruitment continues to be much faster in Europe than in the US. We believe this is because Europe has imposed fewer regulatory constraints on the level of anthracycline dosing allowed and because there are far fewer competing AML clinical trials in Poland, where our clinical testing sites are located."

"Although it is still early and the data are preliminary, I believe we may see that Annamycin has significant activity against relapsed and refractory AML," Dr. Robert Shepard, Moleculin's Chief Medical Officer for Annamycin said. "To have a 40% response rate this early in the dose-escalating process is very encouraging. And if the product ultimately is shown to have little or no cardiotoxicity – as the preliminary data suggest – there is a real potential for Annamycin to become the first approved anthracycline without a dose-limiting cardiovascular risk. The use of anthracyclines for induction therapy in acute leukemia is often, and unfortunately, limited if such treatment would put them over what is currently considered the 'lifetime maximum' anthracycline exposure (or 'maximum cumulative dose'). However, authorities in the EU took into account Annamycin's apparent lack of cardiotoxicity and have allowed us to demonstrate this in patients whose treatment would exceed this maximum cumulative dose. In fact, 7 of the 9 patients treated to date in Europe substantially exceeded that lifetime maximum based on their treatment with Annamycin and, of course, have shown no cardiotoxicity."

The Company is studying Annamycin in both the US and Europe in open label, single arm clinical trials to assess the safety and efficacy of Annamycin for the treatment of adults with relapsed or refractory acute myeloid leukemia. The US and European trials have the same study design, consisting of a Phase 1 intended to establish a "Recommended Phase 2 Dose" (RP2D), to which the studies will then proceed. The Phase 1 studies provide for escalating doses in cohorts of 3 patients each, with each successive cohort receiving the next higher dose level until "dose limiting toxicities" prevent further increases. Cohorts 1, 2 and 3 in Poland received a dose of 120, 150 and 180 mg/m2, respectively, and the results now permit moving to 210 mg/m2. Cohort 1 in the US started at 100 mg/m2, and the results supported moving to 120 mg/m2, at which 1 patient has now been treated and evaluated as having achieved a "morphologically leukemia free state" or MLFS, which also constitutes a CRi. Because one patient in US cohort 1 did not complete the evaluation protocol, a fourth patient was added to complete that cohort. Once the Company establishes an RP2D, the intent is for each trial to advance to a Phase 2 arm planned to assess the safety and efficacy of Annamycin in 21 additional patients.

The data reported here is preliminary as collected by independent CRO site monitors per standard practice and is subject to subsequent quality assurance review.

The US trial also differs from the European trial in that the FDA would like to review safety data relating to cardiotoxicity from patients treated prior to advancing beyond 120 mg/m2, as exceeding this dose level would require the patient to exceed the established lifetime maximum exposure to anthracyclines (presuming all anthracyclines are cardiotoxic). To date, 100% of all 14 patients treated in both the US and EU trials have shown no incidence of cardiotoxicity, including 7 patients out of 9 treated in Poland who exceeded the lifetime maximum anthracycline exposure level. The Company believes that the additional patient safety data gained from the European trial may also assist in the FDA's review of Annamycin's cardiac safety.

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