Moleculin Biotech, Inc. (MBRX) is a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses. The company’s core focus is on developing Annamycin, a next-generation anthracycline chemotherapeutic agent, which has the potential to revolutionize the treatment of acute myeloid leukemia (AML) and beyond.
Business Overview and History Moleculin was founded in July 2015 as a Delaware corporation and is headquartered in Houston, Texas. The company was established to develop and commercialize novel cancer therapies based substantially on discoveries made at and licensed from the University of Texas MD Anderson Cancer Center. Moleculin’s core technologies consist of Annamycin, the WP1066 portfolio, and the WP1122 portfolio.
Since its inception, Moleculin has made significant progress in advancing its clinical programs. The company’s drugs have completed, are currently in, or have been permitted to proceed in, fourteen clinical trials across its portfolio. To conduct these trials, Moleculin has utilized both internal resources and funds as well as physician-sponsored trials utilizing external funds.
In 2019, Moleculin sublicensed its technologies to Animal Life Sciences, Inc. to enable research and commercialization for non-human use, expanding the potential applications of its drug candidates.
In March 2022, Moleculin received a subpoena from the SEC requesting information and documents related to the development of and statements regarding the company’s COVID-19 drug candidate. The company has been cooperating with the SEC and has received periodic further requests for information. While Moleculin believes in the accuracy and adequacy of its prior public disclosures, the outcome and timeline of this investigation remain uncertain.
Annamycin, the company’s lead drug candidate, is a next-generation anthracycline designed to overcome the key limitations of currently approved anthracyclines – cardiotoxicity and multidrug resistance. Anthracyclines are one of the most widely used classes of chemotherapy, with applications across various cancer types, including AML, breast cancer, lymphomas, and childhood cancers. However, the use of current anthracyclines is limited due to their significant cardiotoxicity risks and susceptibility to multidrug resistance mechanisms.
Annamycin’s unique lipid-based delivery technology, developed in collaboration with MD Anderson, enables improved tissue distribution and dramatically reduced toxicity, including cardiotoxicity. In multiple clinical trials, Annamycin has demonstrated the ability to deliver higher dosages and more treatment cycles than what was previously thought feasible with anthracyclines, without causing the typical cardiotoxicity associated with this class of drugs.
The WP1066 portfolio includes compounds designed to inhibit the activity of certain transcription factors, such as p-STAT3, which are associated with tumor activity. These compounds also aim to stimulate a natural immune response to tumors by inhibiting the errant activity of regulatory T-cells (TRegs). WP1066 has been evaluated in clinical trials for central nervous system tumors, including in pediatric patients, while WP1066 and WP1220 have been tested in clinical trials in topical formulations.
The WP1122 portfolio contains compounds designed to exploit the potential uses of glycolysis inhibitors, such as 2-deoxy-D-glucose (2-DG), to cut off the energy supply of tumors. WP1122 has completed a Phase 1 clinical study in normal volunteers.
Financials and Liquidity Moleculin does not currently generate any revenue, as it is a clinical-stage pharmaceutical company. For the fiscal year 2023, the company reported a net loss of $29,769,000, with operating cash flow (OCF) of -$24,101,000 and free cash flow (FCF) of -$24,225,000. In the most recent quarter, Moleculin reported a net loss of $10,592,000, with OCF and FCF both at -$6,113,000. The decreases in net income, OCF, and FCF from the prior year quarter were primarily due to increased research and development costs and the change in fair value of warrant liabilities.
As of September 30, 2024, the company had $9.4 million in cash and cash equivalents, which it believes is sufficient to fund its planned operations into the first quarter of 2025. The company will need to seek additional funding of approximately $15 million to support the MIRACLE trial and its operations into the third quarter of 2025.
For the nine months ended September 30, 2024, Moleculin reported a net loss of $19.88 million, compared to a net loss of $19.50 million in the same period of the prior year. The company’s research and development expenses were $13.27 million, while general and administrative expenses were $6.63 million during this period.
Moleculin’s cash flow statement shows that the company used $18.78 million in operating activities for the nine months ended September 30, 2024, compared to $18.69 million in the same period of the prior year. The company’s financing activities provided $4.63 million during the nine-month period, primarily from the $5.5 million public offering it completed in August 2024.
In terms of liquidity ratios, Moleculin has a debt-to-equity ratio of 0.052, a current ratio of 2.075, and a quick ratio of 2.075. The company does not appear to have any available credit lines disclosed. Moleculin’s current market capitalization is approximately $15.9 million.
Annamycin’s Potential in Acute Myeloid Leukemia (AML) Moleculin’s primary focus is on the development of Annamycin for the treatment of AML, a highly aggressive form of blood cancer with limited treatment options. The company is currently preparing to initiate the pivotal, adaptive Phase 3 MIRACLE trial, which is designed to evaluate Annamycin in combination with cytarabine (also known as Ara-C) for the treatment of relapsed or refractory AML (R/R AML).
The MIRACLE trial is expected to begin enrollment in the first quarter of 2025, with the first subject treated during that time. The trial will initially utilize an adaptive design, with the first 90 subjects randomized to receive high-dose cytarabine (HiDAC) combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin. This will allow the independent Data Monitoring Committee to select the optimum dose of Annamycin based on the overall balance of efficacy, safety, and pharmacokinetics.
Moleculin’s previous Phase 1b/2 clinical trial (MB-106) has demonstrated Annamycin’s potential to significantly outperform the current standard of care for R/R AML patients. The trial has reported a complete remission (CR) rate of 50% and a complete remission composite (CRc) rate of 60% in second-line AML subjects, which is more than double the expected performance of the current standard of care, high-dose cytarabine (HiDAC). Additionally, the median durability of response for these subjects has now exceeded 8 months and is still climbing. Out of the 9 patients who responded, 4 have gone on to receive a bone marrow transplant, which is remarkable for second-line patients as bone marrow transplant is key for long-term durability.
Importantly, Annamycin has shown no signal of cardiotoxicity in subjects who have received greater than the lifetime cumulative anthracycline dose associated with increased risk of cardiomyopathy. This is a significant advantage over currently approved anthracyclines, which are limited in their use due to their cardiotoxicity risks.
The FDA has agreed to allow AML patients in the US to be treated above the current lifetime maximum allowable anthracycline dose, indicating their confidence in Annamycin’s safety profile. This represents a key regulatory milestone and further de-risks the path to approval for Annamycin in the AML indication.
For the Phase 3 MIRACLE trial, Moleculin plans to enroll 330 patients total. The company expects to see an update on the overall CR rate and recruitment progress in the second half of 2025. The key interim data readout on the first 75-90 patients is expected in mid-2026, providing data on primary efficacy and safety. Moleculin then plans to complete enrollment of Part B of the MIRACLE trial and start enrollment of a second trial, MIRACLE2, for third-line AML patients. The primary efficacy data for the second-line AML patients in the MIRACLE trial is expected in 2028, which will allow for submission of a rolling NDA for accelerated approval.
Expanding Horizons Beyond AML While Annamycin’s potential in AML is the primary focus, the drug candidate also has significant opportunities beyond this initial indication. Anthracyclines are widely used in the treatment of various cancer types, including breast cancer, lymphomas, and childhood cancers. Moleculin believes Annamycin’s unique characteristics, such as its lack of cardiotoxicity and ability to overcome multidrug resistance, could make it a valuable treatment option in these broader oncology indications as well.
The company’s other drug portfolios, WP1066 and WP1122, also hold promise in addressing hard-to-treat cancers and viruses. The WP1066 portfolio is being explored for the treatment of central nervous system (CNS) tumors, while the WP1122 portfolio is investigating the potential use of glycolysis inhibitors in targeting the energy supply of tumors and viruses.
Risks and Challenges As a clinical-stage pharmaceutical company, Moleculin faces several risks and challenges common to the industry. These include the inherent uncertainty of clinical trial outcomes, the need for regulatory approvals, the ability to secure sufficient funding for ongoing operations and future development, and the competitive landscape in the oncology and viral disease treatment markets.
The company’s reliance on its key drug candidate, Annamycin, also represents a concentration risk. While Annamycin has shown promising results in clinical trials, there is no guarantee that the MIRACLE trial will meet its endpoints or that the drug will ultimately receive regulatory approval and market acceptance.
Additionally, Moleculin’s limited financial resources and the significant costs associated with drug development and clinical trials pose ongoing funding challenges. The company’s ability to raise additional capital on favorable terms will be crucial to its continued operations and the advancement of its pipeline.
Conclusion Moleculin Biotech, Inc. is a late-stage pharmaceutical company with a compelling opportunity to disrupt the treatment landscape for AML and potentially other cancer types. The company’s lead drug candidate, Annamycin, has demonstrated the potential to overcome the key limitations of currently approved anthracyclines, including cardiotoxicity and multidrug resistance.
The upcoming MIRACLE trial, designed to evaluate Annamycin in combination with cytarabine for the treatment of R/R AML, represents a significant milestone for the company. Moleculin’s previous clinical data, regulatory milestones, and the significant unmet need in the AML space suggest that Annamycin could be a transformative therapy for patients if the MIRACLE trial is successful.
While Moleculin faces the typical risks and challenges associated with a clinical-stage pharmaceutical company, the company’s innovative approach, experienced management team, and robust pipeline of drug candidates position it as a compelling investment opportunity for those seeking exposure to the oncology and infectious disease treatment markets.
Disclaimer: This article is for informational purposes only. It does not constitute financial, legal, or other types of advice. While every effort has been made to ensure the accuracy of the information presented here, the author and the publisher do not make any guarantees about the completeness, reliability, and accuracy of this information.