Moleculin Doses First EU Patient in Phase 3 Pivotal MIRACLE Trial for Treatment of Acute Myeloid Leukemia

Rhea-AI Summary

Moleculin Biotech (Nasdaq: MBRX) has reached a significant milestone in its Phase 2B/3 MIRACLE trial by dosing the first EU patient for its AnnAraC treatment targeting relapsed/refractory acute myeloid leukemia (R/R AML). The trial has active recruitment sites in the US, Spain, Ukraine, Georgia, and Romania.

The adaptive design study will evaluate AnnAraC (Annamycin combined with cytarabine) across 75-90 subjects in Part A, with an initial data unblinding planned for the first 45 subjects in 2H 2025. Part B will involve approximately 220 additional subjects. The company expects to complete the second unblinding in 1H 2026.

Annamycin holds Fast Track Status and Orphan Drug Designation from both FDA and EMA for various indications, highlighting its potential significance in treating hard-to-treat cancers.

Positive

• Active recruitment across multiple countries indicates strong investigator interest
• Fast Track Status and Orphan Drug Designations from both FDA and EMA
• Accelerated timeline for initial data unblinding expected in 2H 2025
• Strong early enrollment with two subjects already enrolled at first Spain site

Negative

• EMA requires additional nonclinical GLP studies before initiating Phase 3 portion
• Complex trial design with multiple stages and dose levels may extend timeline
• Substantial patient recruitment still needed (265-310 total subjects required)

Insights

Oncology Clinical Trials Expert

Moleculin's Phase 3 AML trial reaches EU enrollment milestone, supporting timeline for critical data readout in 2025.

Moleculin's announcement marks a significant operational milestone in their pivotal Phase 2B/3 MIRACLE trial for Annamycin (naxtarubicin) in relapsed/refractory acute myeloid leukemia (AML). The immediate enrollment of two patients at their first Spanish site signals strong investigator interest and likely reflects the urgent unmet need in second-line R/R AML, where treatment options remain limited.

The trial's adaptive design is particularly noteworthy. The study incorporates two planned interim analyses - first at 45 subjects and again at 75-90 subjects. This approach allows for earlier efficacy signals and potential dose optimization between the 190 mg/m² and 230 mg/m² Annamycin arms when combined with high-dose cytarabine (HiDAC). This design aligns with FDA's Project Optimus initiative, which emphasizes dose optimization rather than maximum tolerated dose.

The global expansion across multiple European countries (Spain, Ukraine, Georgia, Romania) alongside US sites strategically accelerates enrollment timelines. Management's projection to complete the 45-patient initial analysis by late 2025 appears increasingly feasible given this multi-region approach. The trial's double-blind, placebo-controlled methodology provides the robust evidence generation needed for potential regulatory submissions.

Annamycin's regulatory designations (Fast Track Status and Orphan Drug Designation from both FDA and EMA) provide potential advantages in review timelines and market exclusivity. The conditional EMA approval requiring additional non-clinical GLP studies before Part B introduces a potential regulatory checkpoint, though this appears to be a manageable requirement rather than a significant obstacle.

Spain site opens with two R/R AML subjects enrolled; One treated

On track to recruit 45 subjects in 4Q25 for initial data unblinding

HOUSTON, Sept. 08, 2025 (GLOBE NEWSWIRE) -- Moleculin Biotech, Inc., (Nasdaq: MBRX) (“Moleculin” or the “Company”), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat cancers and viral infections, today announced that it has enrolled the first two subjects, and treated one, in the European Union (EU) in its pivotal Phase 2B/3, multi-center, randomized, double-blind, placebo-controlled, adaptive design study of Annamycin in combination with cytarabine (also known as “Ara-C” and for which the combination of Annamycin and Ara-C is referred to as “AnnAraC”) for the treatment of adult patients with acute myeloid leukemia (AML) who are refractory to or relapsed (R/R) after induction therapy (R/R AML). This Phase 3 “MIRACLE” trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) is a global approval trial, including sites in the US, the EU, and other parts of Europe.

“We now have active sites recruiting in the US, Spain, Ukraine, Georgia, and Romania with more sites expected to come online by the end of September. For our first site in Spain to have opened up with two subjects enrolled, we believe, indicates the unmet need in treating second line R/R AML,” said Walter Klemp, Chairman and CEO of Moleculin. “All of this, importantly, supports our goal to recruit the first 45 subjects for Part A before the end of 2025 for which efficacy and safety will be unblinded.”

The MIRACLE study is a Phase 2B/3 clinical trial whereby data from the 2B portion will be combined with the Phase 3 portion for purposes of measuring its primary efficacy endpoint. MIRACLE is subject to appropriate future filings with and potential additional feedback from the FDA and their foreign equivalents, utilizes an adaptive design whereby the first 75 to 90 subjects will be randomized (1:1:1) in Part A of the trial to receive high dose cytarabine (HiDAC) combined with either placebo, 190 mg/m² of Annamycin, or 230 mg/m² of Annamycin, which Annamycin doses were specifically recommended by the FDA in the Company’s end of Phase 1B/2 meeting.

The protocol for the MIRACLE trial allows for the unblinding of preliminary primary efficacy data (Complete Remission or CR) and safety/tolerability of the three arms at 45 subjects, in addition to the conclusion of Part A (at 75 to 90 subjects). The first early unblinding is expected to yield 30 subjects treated with Annamycin (190mg/m² and 230 mg/m²) in combination with HiDAC and 15 subjects treated with just HiDAC plus placebo. The Company expects to reach the first unblinding (45 subjects) in the second half of 2025, in addition to the second unblinding, which is expected in the first half of 2026. This accelerated estimated timeline is due in part to the positive response the Company received in meetings during December with potential investigators regarding recruitment for the trial.

As previously announced with regard to the EU, the clinical trial approval with EMA was granted under the condition that the Company present results of appropriate nonclinical GLP studies before initiating the Phase 3 portion (Part B) of the study. Results will be submitted as a substantial modification to the existing approved CTA.

For Part B of the trial, approximately 220 additional subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin (randomized 1:1). The selection of the optimum dose will be based on the overall balance of safety, pharmacokinetics and efficacy, consistent with the FDA’s new Project Optimus initiative.

Patient dosing has commenced, and the initial data readout is on track for the second half of 2025. For more information about the MIRACLE trial, visit clinicaltrials.gov and reference identifier NCT06788756. Additionally, the clinical trial in the EU is on euclinicaltrials.eu and the reference identifier there is 2024-518359-47-00. 

Annamycin, also known by its non-proprietary name of naxtarubicin, currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the EMA.

About Moleculin Biotech, Inc.

Moleculin Biotech, Inc. is a Phase 3 clinical stage pharmaceutical company advancing a pipeline of therapeutic candidates addressing hard-to-treat tumors and viruses. The Company’s lead program, Annamycin, is a next-generation highly efficacious and well tolerated anthracycline designed to avoid multidrug resistance mechanisms and to lack the cardiotoxicity common with currently prescribed anthracyclines. Annamycin is currently in development for the treatment of relapsed or refractory acute myeloid leukemia (AML) and soft tissue sarcoma (STS) lung metastases.

The Company has begun the MIRACLE (Moleculin R/R AML AnnAraC Clinical Evaluation) Trial (MB-108), a pivotal, adaptive design Phase 3 trial evaluating Annamycin in combination with cytarabine, together referred to as AnnAraC, for the treatment of relapsed or refractory acute myeloid leukemia. Following a successful Phase 1B/2 study (MB-106), with input from the FDA, the Company believes it has substantially de-risked the development pathway towards a potential approval for Annamycin for the treatment of AML. This study remains subject to appropriate future filings with potential additional feedback from the FDA and their foreign equivalents.

Additionally, the Company is developing WP1066, an Immune/Transcription Modulator capable of inhibiting p-STAT3 and other oncogenic transcription factors while also stimulating a natural immune response, targeting brain tumors, pancreatic and other cancers. Moleculin is also engaged in the development of a portfolio of antimetabolites, including WP1122 for the potential treatment of pathogenic viruses, as well as certain cancer indications.

For more information about the Company, please visit www.moleculin.com and connect on X, LinkedIn and Facebook.

Forward-Looking Statements

Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties. Forward-looking statements in this press release include, without limitation, the ability of the Company to recruit the first 45 subjects from Part A before the end of 2025, the timing of the release of the initial data on the first 45 subjects in the trial and the Company’s ability to reconcile the US and EU protocols with the FDA and EMA, respectively. Moleculin will require significant additional financing, for which the Company has no commitments, in order to conduct its clinical trials as described in this press release, and the milestones described in this press release assume the Company’s ability to secure such financing on a timely basis. Although Moleculin believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. Moleculin has attempted to identify forward-looking statements by terminology including ‘believes,’ ‘estimates,’ ‘anticipates,’ ‘expects,’ ‘plans,’ ‘projects,’ ‘intends,’ ‘potential,’ ‘may,’ ‘could,’ ‘might,’ ‘will,’ ‘should,’ ‘approximately’ or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including those discussed under Item 1A. “Risk Factors” in our most recently filed Form 10-K filed with the Securities and Exchange Commission (SEC) and updated from time to time in our Form 10-Q filings and in our other public filings with the SEC. Any forward-looking statements contained in this release speak only as of its date. We undertake no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events.

Investor Contact:
JTC Team, LLC
Jenene Thomas
(908) 824-0775
MBRX@jtcir.com

FAQ

What is the MIRACLE trial studying for Moleculin (MBRX)?

The MIRACLE trial is studying AnnAraC (Annamycin combined with cytarabine) for treating adult patients with relapsed or refractory acute myeloid leukemia (R/R AML). It's a Phase 2B/3 global approval trial being conducted in the US, EU, and other European locations.

When will Moleculin (MBRX) release initial MIRACLE trial data?

Moleculin expects to release the first unblinded data from 45 subjects in the second half of 2025, with a second unblinding planned for the first half of 2026.

How many patients will be enrolled in MBRX's MIRACLE trial?

The trial will enroll 75-90 subjects in Part A and approximately 220 additional subjects in Part B, for a total of 295-310 patients.

What regulatory designations does Moleculin's Annamycin have?

Annamycin has Fast Track Status and Orphan Drug Designation from the FDA for R/R AML treatment, plus Orphan Drug Designation for soft tissue sarcoma. It also has Orphan Drug Designation from the EMA for R/R AML.

Which countries are participating in Moleculin's MIRACLE trial?

The trial has active recruitment sites in the United States, Spain, Ukraine, Georgia, and Romania, with more sites expected to open by the end of September 2025.