Moleculin Highlights Development Progress of Annamycin, Phase 2 Data Outperforms Billion-Dollar Assets in AML, Phase 3 Data Readouts in 2025 & 2026
Moleculin Biotech (MBRX) has received IRB approval for its pivotal Phase 3 'MIRACLE' trial of Annamycin in combination with cytarabine for R/R AML treatment. The trial's preliminary readouts are expected in H2 2025 (n=45) and 1H 2026 (n=~75-90), with potential NDA process starting in 2027.
Recent preliminary clinical results show Annamycin plus Ara-C achieved 60% CR/CRi in subjects relapsed/refractory to Venetoclax regimens, exceeding historical rates by more than 4 times. The Phase 1B/2 trial demonstrated a 50% Complete Remission rate and 60% CRc rate for 2nd line subjects, with median survival of 11.6 months for 2nd line subjects.
The MIRACLE trial will be conducted globally, utilizing an adaptive design with two parts. Part A will randomize 75-90 subjects, while Part B will include approximately 244 additional subjects. The company has engaged Catalyst Clinical Research as CRO for the trial.
Moleculin Biotech (MBRX) ha ricevuto l'approvazione dell'IRB per il suo importante studio di fase 3 'MIRACLE' che prevede l'uso di Annamycin in combinazione con citarabina per il trattamento della leucemia mieloide acuta (AML) refrattaria/recidivante. I risultati preliminari dello studio sono attesi nel secondo semestre del 2025 (n=45) e primo semestre del 2026 (n=~75-90), con un possibile avvio del processo NDA nel 2027.
Recenti risultati clinici preliminari mostrano che Annamycin più Ara-C ha raggiunto il 60% di CR/CRi nei soggetti recidivanti/refrattari ai regimi di Venetoclax, superando i tassi storici di oltre 4 volte. Lo studio di fase 1B/2 ha dimostrato un tasso di remissione completa del 50% e un tasso di CRc del 60% nei soggetti di seconda linea, con una sopravvivenza mediana di 11,6 mesi per i soggetti di seconda linea.
Lo studio MIRACLE sarà condotto a livello globale, utilizzando un design adattivo suddiviso in due parti. La Parte A recluterà 75-90 soggetti, mentre la Parte B includerà circa 244 soggetti aggiuntivi. L'azienda ha coinvolto Catalyst Clinical Research come CRO per lo studio.
Moleculin Biotech (MBRX) ha recibido la aprobación del IRB para su ensayo pivotal de fase 3 'MIRACLE' que evalúa Annamycin en combinación con citarabina para el tratamiento de la leucemia mieloide aguda (AML) resistente/recidivante. Se esperan los resultados preliminares del ensayo en el segundo semestre de 2025 (n=45) y el primer semestre de 2026 (n=~75-90), con un posible inicio del proceso NDA en 2027.
Los recientes resultados clínicos preliminares muestran que Annamycin más Ara-C lograron un 60% de CR/CRi en sujetos que recayeron/refractarios a regímenes de Venetoclax, superando las tasas históricas por más de 4 veces. El ensayo de fase 1B/2 demostró una tasa de Remisión Completa del 50% y una tasa de CRc del 60% en sujetos de segunda línea, con una supervivencia media de 11,6 meses para los sujetos de segunda línea.
El ensayo MIRACLE se llevará a cabo a nivel global, utilizando un diseño adaptativo dividido en dos partes. La Parte A randomizará de 75 a 90 sujetos, mientras que la Parte B incluirá aproximadamente 244 sujetos adicionales. La compañía ha contratado a Catalyst Clinical Research como CRO para el ensayo.
몰레큘린 바이오텍 (MBRX)는 Annamycin과 사이타라빈을 병용하여 R/R AML 치료를 위한 주요 3상 'MIRACLE' 시험의 IRB 승인을 받았습니다. 시험의 초기 결과는 2025년 하반기(밤=45)와 2026년 상반기(밤=~75-90)에 기대되며, NDA 프로세스는 2027년 시작될 수 있습니다.
최근 초기 임상 결과에 따르면 Annamycin과 Ara-C의 조합이 Venetoclax 요법에 대한 재발/불응환자에서 60% CR/CRi를 달성했습니다, 이는 역사적 비율보다 4배 이상 높습니다. 1B/2상 시험에서는 2차 치료 대상자의 전체 관해율이 50%, CRc가 60%였으며, 2차 치료 대상자의 중간 생존 기간은 11.6개월이었습니다.
MIRACLE 시험은 전 세계적으로 수행되며, 두 부분으로 나뉜 적응형 디자인을 사용할 것입니다. A파트에서는 75-90명의 환자를 무작위로 배정하고, B파트에서는 약 244명의 추가 환자를 포함할 것입니다. 이 회사는 시험을 위해 Catalyst Clinical Research를 CRO로 계약했습니다.
Moleculin Biotech (MBRX) a reçu l'approbation de l'IRB pour son essai pivot de phase 3 'MIRACLE' portant sur l'Annamycin en association avec la cytarabine pour le traitement de la LMA R/R. Les résultats préliminaires de l'essai sont attendus au deuxième semestre 2025 (n=45) et au premier semestre 2026 (n=~75-90), avec un processus NDA potentiel commençant en 2027.
Les récents résultats cliniques préliminaires montrent qu'Annamycin plus Ara-C a atteint 60% de CR/CRi chez les sujets réfractaires/récidivants aux régimes de Venetoclax, dépassant les taux historiques de plus de 4 fois. L'essai de phase 1B/2 a démontré un taux de rémission complète de 50% et un taux de CRc de 60% pour les sujets de deuxième ligne, avec une survie médiane de 11,6 mois pour ces sujets.
L'essai MIRACLE sera mené à l'échelle mondiale, en utilisant un design adaptatif en deux parties. La Partie A randomisera 75-90 sujets, tandis que la Partie B comprendra environ 244 sujets supplémentaires. La société a engagé Catalyst Clinical Research en tant que CRO pour l'essai.
Moleculin Biotech (MBRX) hat die IRB-Zulassung für seine entscheidende Phase-3-Studie 'MIRACLE' erhalten, die Annamycin in Kombination mit Cytarabin zur Behandlung von R/R AML untersucht. Die vorläufigen Ergebnisse der Studie werden für das zweite Halbjahr 2025 (n=45) und das erste Halbjahr 2026 (n=~75-90) erwartet, mit dem möglichen Beginn eines NDA-Prozesses im Jahr 2027.
Aktuelle vorläufige klinische Ergebnisse zeigen, dass Annamycin plus Ara-C 60% CR/CRi bei Patienten, die auf Venetoclax-Regime rezidiviert/refraktär waren, erreicht hat, was die historischen Raten um mehr als das Vierfache übersteigt. Die Phase 1B/2-Studie zeigte eine vollständige Remissionsrate von 50% und eine CRc-Rate von 60% bei Patienten der zweiten Linie, mit einer mittleren Überlebenszeit von 11,6 Monaten für Patienten der zweiten Linie.
Die MIRACLE-Studie wird weltweit durchgeführt und nutzt ein adaptives Design mit zwei Teilen. Teil A wird 75-90 Probanden randomisieren, während Teil B etwa 244 zusätzliche Probanden umfasst. Das Unternehmen hat Catalyst Clinical Research als CRO für die Studie engagiert.
- 60% CR/CRi achievement in Venetoclax-resistant patients, 4x higher than historical rates
- Phase 1B/2 trial showed 50% Complete Remission rate in 2nd line subjects
- Median survival of 11.6 months for 2nd line subjects
- Fast Track Status and Orphan Drug Designation from FDA and EMA
- Accelerated timeline for Phase 3 trial data readouts
- Full Phase 3 results not expected until 2028
- NDA submission process won't begin until 2027 at earliest
- Complex trial design requiring multiple stages and large patient enrollment
Insights
The Phase 3 MIRACLE trial represents a pivotal moment for Moleculin's Annamycin development. The 60% CR/CRi rate in Venetoclax-resistant patients is particularly noteworthy, as it's 4x higher than historical rates. This demonstrates exceptional efficacy in a difficult-to-treat population.
The adaptive trial design is strategically sound, with early unblinding at 45 subjects allowing for rapid efficacy assessment. The accelerated timeline with potential readouts in H2 2025 could fast-track the path to market. Key differentiators include Annamycin's superior safety profile compared to current anthracyclines and demonstrated efficacy in Venetoclax-resistant cases.
For context, in AML treatment, achieving a CR/CRi rate above 30% is considered clinically meaningful. At 60%, Annamycin's performance suggests potential market leadership.
This development program positions Moleculin strategically in the lucrative AML market. With a market cap of just
The dual development in both AML and soft tissue sarcoma expands market potential. Fast Track Status and multiple Orphan Drug Designations provide regulatory advantages and market exclusivity. The ability to outperform existing treatments in resistant populations suggests potential for premium pricing and rapid market adoption.
Annamycin's efficacy in Venetoclax-resistant cases addresses a critical unmet need in AML treatment. The median survival of 11.6 months in second-line patients and 8-month durability of response are clinically meaningful improvements over current standards. The safety profile advantage over traditional anthracyclines could position it as a preferred treatment option.
The 'pipeline in a product' potential through activity in multiple indications (AML and sarcoma) enhances its therapeutic value. The Phase 3 trial design, incorporating FDA's Project Optimus recommendations, maximizes chances of approval while ensuring optimal dosing strategy.
– Received US Institutional Review Board (IRB) approval for pivotal, adaptive Phase 3 clinical trial (the "MIRACLE" trial) and engaged leading contract research organization (CRO); On track to begin dosing of Annamycin in combination with cytarabine for the treatment of R/R AML in Q1 2025
– Expected timelines for recruitment updates and preliminary readouts of MIRACLE trial accelerated to 2H 2025 (n=45); 1H 2026 (n=~75-90) with potential for accelerated NDA process beginning as early as 2027
– Continued growing body of data with recently announced new preliminary clinical results demonstrating Annamycin plus Ara-C achieved
"We have positioned Moleculin to achieve value-driving milestones through the next several years, starting with the imminent beginning of enrollment for MIRACLE and the first interim read-out from that study later this year. Having a readout in the first year of a Phase 3 approval trial is, we believe, exceptional. Prior data support our belief that Annamycin is a potential game-changing asset for the treatment of AML, and we believe it can lead to significant value creation for Moleculin as we aggressively move forward with our clinical development plan. Not only has Annamycin appeared to be safer and more effective than currently prescribed anthracyclines, but we believe the recently announced preclinical data demonstrating significant activity of Annamycin in a Venetoclax-resistant AML model underscores the potential that Annamycin has 'pipeline in a product' potential and represents a much-needed treatment option for other patients who otherwise have very poor outcomes. Annamycin's performance in Phase 2 has outperformed the response rates seen in billion-dollar assets in the AML space and AML remains among the highest unmet needs in healthcare. Simply stated, the bar for approval is low, and the potential reward for shareholders is substantial and we have never been more excited about the prospects for Annamycin," commented Walter Klemp, Chairman and CEO of Moleculin.
Clinical Development Update
Relapsed or Refractory Acute Myeloid Leukemia (AML)
The Company is currently advancing the development 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") to a Phase 3 pivotal trial 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) will be global, including sites in the US,
The MIRACLE study, 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 amended protocol allows for the unblinding of preliminary primary efficacy data (CR) and safety/tolerability of the three arms at 45 subjects, in addition to the conclusion of Part A (at 75 to 90 subjects). This early unblinding will yield 30 subjects with Annamycin (190mg/m2 and 230/m2) and HiDAC and 15 subjects 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 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 244 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. This increase from 240 to 244 subjects represents the statistical "cost" of the additional interim unblinding.
Important Development Program Highlights
- Phase 3 MIRACLE trial builds off of positive results of Phase 1B/2 clinical trial evaluating AnnAraC for the treatment of subjects with AML as both first line therapy and for subjects who are refractory to or relapsed after induction therapy (MB-106):
- Complete Remission (CR) rate was
50% and CRc (CR plus CRi (CR with incomplete recovery of blood counts)) rate was60% for 2nd line subjects (n=10); - Median durability: ~8 months and increasing;
- Median overall survival in MB-106 was 9.1 months for 0-6 prior lines of therapies (n=22) and 11.6 months for 2nd line subjects (n=10); and
- Strong efficacy signal even where a prior venetoclax combination therapy has failed.
- Complete Remission (CR) rate was
- Received US Institutional Review Board (IRB) approval;
- Leveraging expertise of Catalyst Clinical Research, a leading contract research organization (CRO), with our recent engagement with them to help conduct the MIRACLE trial; and
- Accelerated planned unblinded data readout to H2 2025.
Expected Milestones for Annamycin AML Development Program
- 1Q – 3Q 2025 – Update on MIRACLE trial site selection/approvals by countries
- 1Q 2025 – First subject enrolled and treated in MIRACLE trial
- 2025 – Recruitment update for MIRACLE trial
- 2H 2025 – Data readout (n=45) unblinded efficacy/safety review
- 2H 2025 – 2026 – Impact of data readout (n=45) on regulatory pathway; Recruitment update
- 1H 2026 – Interim efficacy and safety data (n=~75-90) unblinded and Optimum Dose set for MIRACLE trial
- 2027 – Begin enrollment of 3rd line subjects in MIRACLE2
- 2027 – Enrollment ends in 2nd line subjects
- 2028 – Primary efficacy data for 2nd line subjects in MIRACLE
- 2028 – Begin submission of a Rolling New Drug Application (NDA) for the treatment of R/R AML for accelerated approval on primary endpoint of CR from MIRACLE
Soft Tissue Sarcoma (STS) Lung Metastases
As previously announced, the Company completed enrollment in the Phase 2 portion of its
Expected Milestones for Annamycin STS Lung Mets Development Program
- 2025 – Final MB-107 data readout
- 2025 – Identify next phase of development / pivotal IIT (investigator-initiated-trial) program
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
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SOURCE Moleculin Biotech, Inc.
FAQ
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