Moleculin Receives European Medicines Agency Approval to Expand Phase 3 MIRACLE Clinical Trial
- EMA approval granted for all nine EU countries requested, significantly expanding trial reach
- Patient dosing has already commenced with first data readout on track for H2 2025
- Annamycin has Fast Track Status and Orphan Drug Designation from both FDA and EMA
- Trial addresses significant unmet need in R/R AML, particularly for venetoclax regimen failures
- Company must present additional nonclinical GLP studies before initiating Phase 3 portion
- Minor protocol differences between US and EU need harmonization
- Large number of additional subjects (220) required for Part B of the trial
Insights
EMA's approval for MBRX's Phase 3 AML trial across nine EU countries accelerates enrollment timeline with key data expected H2 2025.
Moleculin's EMA approval to expand their pivotal Phase 3 MIRACLE trial across nine additional EU countries represents a significant operational achievement that substantially enhances their patient recruitment capabilities. The trial evaluates Annamycin combined with cytarabine (AnnAraC) for relapsed/refractory acute myeloid leukemia (R/R AML) patients, with particular focus on venetoclax regimen failures – a population with notably poor outcomes using current therapies.
The adaptive trial design is particularly sophisticated, allowing for preliminary efficacy analysis at just 45 patients, with this first data readout expected in H2 2025. This accelerated timeline for preliminary data is unusual and strategically valuable, potentially providing early efficacy signals that could influence investor confidence well before full enrollment completion.
What's technically notable is the trial's two-part structure (Phase 2B/3) with dose-optimization in Part A (testing 190mg/m² and 230mg/m² Annamycin doses versus placebo) followed by expansion in Part B with the optimal dose. This aligns with FDA's Project Optimus initiative for dose optimization in oncology. The EMA approval includes a reasonable condition to present nonclinical GLP study results before initiating Part B, which shouldn't meaningfully impact timelines.
Annamycin's regulatory designations (Fast Track Status and Orphan Drug Designation from FDA and EMA) provide potential advantages including expedited review and extended market exclusivity if approved – crucial benefits for a late-stage biotech company navigating the final stages of development.
Adds nine additional countries to the Company’s ongoing pivotal Phase 3 trial; Authorization granted in all EU countries requested
Enrollment and dosing underway in Phase 3 clinical trial (the “MIRACLE” trial) evaluating Annamycin for the treatment of R/R AML; Interim data readout expected in the second half of 2025
Subjects targeted for the “MIRACLE” trial include venetoclax regimen failures where outcomes with currently available therapies are considered dismal
HOUSTON, May 12, 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 the European Medicines Agency (EMA) has approved its Clinical Trial Application (CTA) to conduct 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”). The study is 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) and is approved in all nine countries submitted in the European Union (EU). This Phase 3 “MIRACLE” trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) is a global approval trial, including sites in the US, Europe and the Middle East.
“EMA approval of the MIRACLE trial protocol is a huge milestone for us. Although we’re already seeing recruitment in our first non-EU country, we believe that this expansion into the EU really supercharges our recruitment potential,” said Walter Klemp, Chairman and CEO of Moleculin. “Importantly, when combined with the sites we are opening in the US, this approval from the EMA, along with the individual country committee and/or ethics approvals, for Belgium, Czechia, France, Germany, Italy, Lithuania, Poland, Romania, and Spain positions us to remain on track with our expected enrollment and data milestones.”
Mr. Klemp continued: “Being accepted in all nine of the countries for which we submitted, we believe indicates the magnitude of the need for a better answer for R/R AML patients, especially venetoclax regimen failures where the outcomes from currently available therapies are considered dismal in published studies. While there are minor differences between the US and EU protocols with the FDA and EMA, respectively, we do not view these as a barrier to conducting the study and are working to harmonize the protocols as appropriate. We are grateful for the international collaboration and believe it underscores the significant unmet need in R/R AML and the potential of Annamycin to provide a much needed second line treatment option. We remain focused on driving enrollment and patient dosing and look forward to reporting initial data on the first 45 subjects in the second half of 2025.”
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 will yield 30 subjects treated with Annamycin (190mg/m2 and 230 mg/m2) and 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.
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 protocol.
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 clinicaltrials.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 is initiating 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 timing of the release of the initial data on the first 45 subjects in the trial and the Company’s ability to harmonize 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 testing and when will MBRX release interim data?
Which European countries approved Moleculin's Phase 3 MIRACLE trial?
How many patients will be enrolled in MBRX's MIRACLE Phase 3 trial?
What regulatory designations does Moleculin's Annamycin have?
What doses of Annamycin will be tested in the MBRX MIRACLE trial?
