Moleculin Biotech (NASDAQ:MBRX) CEO Walter Klemp said the company has enrolled its 45th patient in the MIRACLE Phase III trial evaluating annamycin in relapsed/refractory acute myeloid leukemia (AML), marking what he described as a notable acceleration in recruitment after early delays tied to the European Union’s new Clinical Trials Information System (CTIS).
Speaking with Roth Capital Partners senior biotechnology analyst Jonathan Aschoff, Klemp said MIRACLE is a “registration-enabling” Phase III study with a two-part design intended to support dose optimization and streamline development. He added that the company expects to unblind data from the first 45 patients within “a few months,” and characterized that interim look as a key catalyst for the program.
MIRACLE trial design and enrollment update
According to Klemp, data from both parts of the trial are planned to be combined for approval purposes, which he said makes the design “very efficient.” He added that recruitment momentum has increased, noting that the company reported blinded data from the first 30 patients roughly a month earlier and has now reached 45 patients.
While emphasizing that the available results are still blinded, Klemp said the data “appear to be supportive” of what the company hopes to see when the 45-patient dataset is unblinded, while cautioning that such interpretations remain speculative until unblinding occurs.
What the company expects to disclose at the 45-patient unblinding
Klemp said Moleculin expects the initial interim look to include approximately 15 patients in the control arm and 30 treated with annamycin, split roughly evenly between 190 mg and 230 mg dose arms, though he noted randomization could lead to some variation.
He said the company expects to report:
- Complete remission (CR) rates for each arm
- Overall median age
- The percentage of patients entering the trial as venetoclax-regimen failures
Klemp highlighted the inclusion of venetoclax-regimen failures as an important differentiator, saying many AML trials exclude those patients due to difficulty in treatment. He said Moleculin is “welcoming” them and cited what he described as surprisingly strong Phase II results in that subgroup.
Ultimately, Klemp said the key value driver for approval is the primary endpoint comparison: the CR rate for patients receiving annamycin versus the CR rate for control.
Annamycin’s positioning as a “next-generation” anthracycline
Klemp described annamycin as a new chemical entity with patent protection through 2040 and “probably extendable into 2045.” While placing it within the anthracycline class, he argued its structure and lipid-based delivery system make it behave differently from traditional anthracyclines.
He contrasted annamycin with what he called the “pleiotropic” nature of existing anthracyclines, which he said can attack cardiomyocytes and drive cardiotoxicity. Klemp cited risks associated with exceeding lifetime dosing limits for current anthracyclines, and said that even within limits, cardiac dysfunction can be a long-term issue for childhood cancer survivors.
Klemp said annamycin has shown “zero cardiotoxicity” in more than 100 patients treated to date, and added that most were treated beyond the FDA’s lifetime limit for existing anthracyclines. He also said the drug has been generally more tolerable, with “almost no alopecia,” and that mucositis “can now be completely avoided.” In discussing the broader anthracycline class, he said mucositis is typically expected in the “20%+ range,” and can be difficult to manage without prophylactic approaches such as cryotherapy.
On efficacy and resistance, Klemp said annamycin is not recognized by typical multidrug resistance mechanisms and avoids cross-resistance with current anthracyclines, venetoclax, and cytarabine. He added that the company’s most recent Phase II trial showed efficacy he characterized as better than any drug approved for relapsed/refractory AML, while also noting later in the discussion that Phase II results can be viewed skeptically due to small sample sizes.
Market landscape, broader indications, and supply constraints
Klemp said the relapsed/refractory AML treatment conversation has been dominated by gene-targeted therapies, which he contended have not met expectations. He stated that six approved drugs collectively help about 18% of relapsed/refractory patients, and said triplet-therapy studies are emerging but face regulatory hurdles. He suggested that a trend toward multi-drug regimens could favor annamycin, particularly because some of the better-performing triplets include an anthracycline, where toxicity can become a major concern.
In terms of opportunity, Klemp said the company sees at least a $500 million global market for annamycin in AML, and “possibly” up to $1 billion.
Klemp also discussed what he called annamycin’s “organotropism,” describing an affinity to hyperaccumulate in certain organs. He cited animal-model data suggesting accumulation in the lungs at more than 30 times the rate of doxorubicin without associated pulmonary toxicity, and said the company also sees organotropism in the liver, pancreas, and spleen. He linked this concept to potential opportunities in soft tissue sarcoma—particularly lung metastases—and said Atlantic Health is sponsoring a clinical trial of annamycin in pancreatic cancer based on the potential to reach therapeutic levels in the pancreas.
However, Klemp said Moleculin is currently constrained by drug supply and has had to decline investigator interest to prioritize completion of the Phase III MIRACLE trial. He said inbound requests have been strongest in sarcomas (soft tissue and osteosarcoma), particularly lung metastases, with additional inquiries in colorectal cancer (including liver and lung metastases), renal cell carcinoma, and other indications via compassionate use requests.
Upcoming milestones and regulatory considerations
Discussing investor focus and valuation, Klemp said he believes the company’s market capitalization reflects a “disconnect,” citing what he characterized as strong Phase II data and mutation-agnostic activity in AML. He acknowledged that some skepticism may stem from the small size of the Phase II dataset and concerns about selection bias, but argued that the multinational Phase III trial—spanning nine countries, as he described it—reduces the ability to “cherry-pick.”
Looking ahead, Klemp said the company may have sufficient data from the first 45 patients to support a request for breakthrough therapy designation. He also said Moleculin expects another unblinding at the 90-patient mark by the end of the year, adding that this would provide more patient data than some targeted therapies have had at the time of approval. He also noted the company’s fast track status, which he said could allow for a rolling NDA submission as the study nears completion.
About Moleculin Biotech (NASDAQ:MBRX)
Moleculin Biotech, Inc is a clinical-stage pharmaceutical company focused on the development of novel therapies for the treatment of highly resistant tumors and viral infections. The company’s research platform centers on the design and synthesis of drug candidates that target key cellular pathways in cancer cells and viral replication processes. By leveraging a proprietary chemistry approach, Moleculin aims to address diseases that have limited therapeutic options and high unmet medical need.
The company’s pipeline includes multiple product candidates at various stages of development.
