Moleculin Doses First Patient in Pivotal, Adaptive Phase 3 MIRACLE Trial
Moleculin Biotech (MBRX) has initiated patient dosing in its pivotal Phase 3 MIRACLE trial, evaluating Annamycin combined with Cytarabine (AnnAraC) for treating AML patients who are refractory to or relapsed after induction therapy.
The global approval trial, conducted across the US, Europe, and Middle East, features an adaptive design with two parts. Part A will randomize 75-90 subjects (1:1:1) to receive high dose cytarabine with either placebo, 190 mg/m2, or 230 mg/m2 of Annamycin. Part B will enroll approximately 220 additional subjects.
The company expects preliminary data unblinding from the first 45 subjects in H2 2025, with a second unblinding anticipated in H1 2026. Annamycin holds Fast Track Status and Orphan Drug Designation from FDA for R/R AML treatment, plus Orphan Drug Designation for soft tissue sarcoma and from EMA.
Moleculin Biotech (MBRX) ha avviato la somministrazione di farmaci ai pazienti nel suo trial pivotale di Fase 3 MIRACLE, che valuta Annamycin combinato con Cytarabine (AnnAraC) per il trattamento di pazienti con AML che sono refrattari o hanno avuto una recidiva dopo la terapia di induzione.
Il trial di approvazione globale, condotto negli Stati Uniti, in Europa e in Medio Oriente, presenta un design adattivo con due parti. La Parte A randomizzerà 75-90 soggetti (1:1:1) per ricevere una dose elevata di citarabina con placebo, 190 mg/m2 o 230 mg/m2 di Annamycin. La Parte B recluterà circa 220 soggetti aggiuntivi.
L'azienda prevede di ottenere dati preliminari dai primi 45 soggetti nel secondo semestre del 2025, con un secondo sblocco previsto nel primo semestre del 2026. Annamycin ha ottenuto lo stato di Fast Track e la designazione di farmaco orfano dalla FDA per il trattamento dell'AML R/R, oltre alla designazione di farmaco orfano per il sarcoma dei tessuti molli e dalla EMA.
Moleculin Biotech (MBRX) ha iniciado la dosificación de pacientes en su ensayo pivotal de Fase 3 MIRACLE, que evalúa Annamycin combinado con Cytarabine (AnnAraC) para tratar a pacientes con AML que son refractarios o han recaído después de la terapia de inducción.
El ensayo de aprobación global, realizado en los EE. UU., Europa y Medio Oriente, presenta un diseño adaptativo con dos partes. La Parte A aleatorizará de 75 a 90 sujetos (1:1:1) para recibir una dosis alta de citarabina con placebo, 190 mg/m2 o 230 mg/m2 de Annamycin. La Parte B inscribirá aproximadamente a 220 sujetos adicionales.
La empresa espera datos preliminares de los primeros 45 sujetos en la segunda mitad de 2025, con un segundo desbloqueo anticipado en la primera mitad de 2026. Annamycin tiene el estatus de Fast Track y la designación de medicamento huérfano de la FDA para el tratamiento de AML R/R, además de la designación de medicamento huérfano para sarcoma de tejidos blandos y de la EMA.
Moleculin Biotech (MBRX)는 AML 환자를 치료하기 위해 Annamycin과 Cytarabine (AnnAraC)을 결합한 임상 3상 MIRACLE 시험에서 환자 투약을 시작했습니다. 이 환자들은 유도 요법 후에 내성 또는 재발한 환자들입니다.
미국, 유럽 및 중동에서 진행되는 글로벌 승인 시험은 두 부분으로 나뉘는 적응형 설계를 특징으로 합니다. A 부분에서는 75-90명의 피험자를 무작위 배정(1:1:1)하여 고용량의 시타라빈과 함께 위약, 190 mg/m2 또는 230 mg/m2의 Annamycin을 투여받게 합니다. B 부분에서는 약 220명의 추가 피험자를 등록할 예정입니다.
회사는 2025년 하반기에 첫 45명의 피험자에 대한 초기 데이터 공개를 예상하고 있으며, 2026년 상반기에는 두 번째 공개가 예상됩니다. Annamycin은 R/R AML 치료를 위한 FDA의 신속 심사 지위 및 희귀 의약품 지정을 보유하고 있으며, 연조직 육종에 대해서도 희귀 의약품 지정을 받았습니다.
Moleculin Biotech (MBRX) a lancé l'administration de traitements aux patients dans son essai pivot de phase 3 MIRACLE, qui évalue Annamycin en combinaison avec Cytarabine (AnnAraC) pour le traitement des patients atteints de LMA qui sont réfractaires ou ont rechuté après une thérapie d'induction.
L'essai d'approbation mondiale, mené aux États-Unis, en Europe et au Moyen-Orient, présente un design adaptatif en deux parties. La Partie A randomisera 75 à 90 sujets (1:1:1) pour recevoir une dose élevée de cytarabine avec soit un placebo, 190 mg/m2, ou 230 mg/m2 d'Annamycin. La Partie B recrutera environ 220 sujets supplémentaires.
L'entreprise s'attend à une première divulgation des données des 45 premiers sujets au second semestre 2025, avec une seconde divulgation prévue au premier semestre 2026. Annamycin bénéficie du statut de Fast Track et de la désignation de médicament orphelin par la FDA pour le traitement de la LMA R/R, ainsi que de la désignation de médicament orphelin pour le sarcome des tissus mous et de l'EMA.
Moleculin Biotech (MBRX) hat die Patientendosierung in seiner entscheidenden Phase-3-Studie MIRACLE begonnen, die Annamycin in Kombination mit Cytarabin (AnnAraC) zur Behandlung von AML-Patienten, die refraktär oder nach der Induktionstherapie rezidiviert sind, bewertet.
Die globale Genehmigungsstudie, die in den USA, Europa und dem Nahen Osten durchgeführt wird, weist ein adaptives Design mit zwei Teilen auf. Teil A randomisiert 75-90 Probanden (1:1:1), die hochdosiertes Cytarabin entweder mit Placebo, 190 mg/m2 oder 230 mg/m2 Annamycin erhalten. Teil B wird voraussichtlich etwa 220 zusätzliche Probanden einschreiben.
Das Unternehmen erwartet, dass die vorläufigen Daten von den ersten 45 Probanden im zweiten Halbjahr 2025 veröffentlicht werden, mit einer zweiten Veröffentlichung, die im ersten Halbjahr 2026 erwartet wird. Annamycin hat den Status eines Fast Track und die Orphan Drug Designation von der FDA für die Behandlung von R/R AML sowie die Orphan Drug Designation für Weichgewebesarkome und von der EMA erhalten.
- First patient dosed in pivotal Phase 3 trial, advancing clinical development
- Global trial expansion across US, Europe, and Middle East
- Fast Track Status and multiple Orphan Drug Designations from FDA and EMA
- Accelerated timeline for preliminary data readout
- Final trial results not expected until after H1 2026
- Large patient enrollment requirement (295-310 subjects) may extend timeline
- Success not guaranteed with adaptive trial design requiring multiple phases
Insights
This first patient dosing in Moleculin's Phase 3 MIRACLE trial represents a significant milestone in the company's development journey. The pivotal status of this trial means it's designed to potentially support regulatory approval if successful. For a micro-cap company (
The adaptive trial design is strategically advantageous, allowing for multiple data readouts and potential optimization of the Annamycin dose. The planned interim analysis after 45 subjects (expected H2 2025) provides a relatively near-term catalyst that could significantly impact the company's valuation and potential partnering opportunities.
Annamycin's regulatory advantages are substantial, with both Fast Track Status and Orphan Drug Designation from FDA and EMA Orphan designation for AML. These designations provide benefits including increased agency interaction, potentially accelerated review processes, and market exclusivity periods upon approval.
The global nature of the trial (US, Europe, Middle East) suggests the company is positioning for international commercialization while potentially accelerating enrollment through access to diverse patient populations. For relapsed/refractory AML patients who have failed induction therapy, new therapeutic options are desperately needed as this population typically has poor outcomes with existing treatments.
Moleculin's progression to Phase 3 represents a crucial inflection point that substantially derisks their lead program. The MIRACLE trial's structure offers multiple value-creating catalysts within a defined timeline – first readout in H2 2025 and second unblinding in H1 2026 – providing clear benchmarks for investors to evaluate progress.
For context, the AML therapeutics market is projected to expand significantly, driven by an aging population and the need for treatments beyond standard chemotherapy regimens. The relapsed/refractory setting addressed by Annamycin represents a particularly challenging area with effective options.
The combination approach (Annamycin with cytarabine) targets established treatment pathways while potentially addressing limitations of current therapies. If successful, this approach could position Moleculin's therapy as part of standard care for R/R AML patients.
Financially, launching a global Phase 3 program is substantial for a company of Moleculin's size. Investors should monitor cash runway as this expanded trial will increase burn rate. However, positive interim data could provide leverage for potential partnerships or financing on improved terms. The FDA's specific dose recommendations suggest constructive regulatory interaction, which further derisks the development pathway.
– Initial data readout on track for second half of 2025
HOUSTON, April 01, 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 viruses, today announced the first patient has been dosed in its Phase 3 pivotal trial evaluating 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 AML patients who are refractory to or relapsed 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, Europe and the Middle East.
“The start of patient dosing represents a huge milestone for Moleculin and importantly, the AML community,” commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin. “Our team remains focused on bringing clinical sites online in the U.S., Europe and Middle East and enrolling patients to build on this momentum. With the progress made to date, we expect to unblind preliminary data from the first 45 subjects in the second half of this year, a near-term, potentially value-driving milestone that will provide key insight as we continue to advance Annamycin’s development towards approval.”
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 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/m2) and HiDAC and 15 subjects treated with just HiDAC. 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.
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.
For more information about the MIRACLE trial, visit clinicaltrials.gov and reference identifier NCT06788756.
Annamycin 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 European Medicines Agency (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 anthracycline designed to avoid multidrug resistance mechanisms and to eliminate 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 is 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 achievements of each of the milestones in this press release. 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
When will Moleculin (MBRX) release initial data from the Phase 3 MIRACLE trial?
How many patients will be enrolled in MBRX's MIRACLE Phase 3 trial?
What regulatory designations does Annamycin have for MBRX's AML treatment?
What is the dosing structure in MBRX's Phase 3 MIRACLE trial?
