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AACR 2025: Liposomal Annamycin May Enhance Chemotherapy Efficacy Across Hematologic and Solid Tumors
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Key Takeaways
- Annamycin (ANN) is a non-cardiotoxic anthracycline with potential to enhance efficacy of existing anticancer agents in hematologic and solid tumors.
- ANN's liposomal formulation improves delivery and activity, avoiding dose-limiting cardiotoxicity seen with traditional anthracyclines.
Liposomal annamycin demonstrates broad synergistic activity with multiple FDA-approved chemotherapies across hematologic and solid tumors in preclinical models, offering a promising and safer combination strategy for resistant and high-risk cancers.
Annamycin (ANN, Moleculin Biotech), a non-cardiotoxic, liposome-formulated anthracycline and potent topoisomerase II inhibitor, has the potential to synergize with a wide range of FDA-approved anticancer agents across both hematologic and solid tumors, according to findings from Zielinski et al. In a poster presented at the American Association for Cancer Research (AACR) Annual Meeting 2025 in Chicago, Illinois, Zielinski et al discuss the potential for ANN to enhance the efficacy of currently approved agents in both hematologic and solid malignancies, including leukemia, sarcomas, and pancreatic cancer.
ANN is a promising chemotherapeutic agent due to its unique pharmacokinetic and safety profile. Unlike doxorubicin, ANN avoids dose-limiting cardiotoxicity and exhibits improved delivery and activity through liposomal formulation (L-ANN). The agent has shown strong efficacy in drug-resistant cancer cell lines and enhanced tissue penetration and, due to ANN’s non-cardiotoxic nature, is a viable candidate for combination therapies.
An artificial intelligence depiction of a cancerous cell. Image Credit: © Johannes - stock.adobe.com
“Anthracycline-induced cardiotoxicity remains a source of cardiovascular morbidity and mortality for patients, and the development of non-cardiotoxic topoisomerase II inhibitors may have significant impact across oncology treatments,” said Matthew Lei, PharmD, BCOP, clinical pharmacy specialist – lymphoma at Massachusetts General Hospital in Boston and editorial advisory board member for Pharmacy Practice in Focus: Oncology, to Pharmacy Times. “While one strategy is to deliver the compound by itself, another strategy of interest may be to conjugate non-cardiotoxic topo II inhibitors with antibody drug conjugates to further add a layer of tumor specificity.”
The objective of the study by Zielinski et al was to determine how ANN performs in combination with agents with established roles in cancer therapy, and to identify promising synergistic interactions that might warrant further clinical exploration. The researchers tested L-ANN with several FDA-approved agents including cytarabine (ARA-C), vincristine (VCR), gemcitabine (GEM), ifosfamide (IFO, Ifex; Fresenius Kabi USA and Aarti Pharmalabs), azacitidine (AZA), and trabectedin (TRB, Yondelis; Janssen Biotech). These combinations were evaluated in vitro and in vivo across multiple cancer models, including acute myeloid leukemia (AML), pancreatic ductal adenocarcinoma, fibrosarcoma, osteosarcoma, and various sarcoma cell lines.
In an AML mouse model (AML-mr1γ32), L-ANN combined with ARA-C significantly increased survival and reduced minimal residual disease compared to monotherapy. Zielinski et al show that the combination group demonstrated better leukemia clearance in bone marrow as evidenced by immunofluorescent staining and quantification. Furthermore, survival analysis showed a marked improvement in the combination group, suggesting a synergistic effect.
The researchers also tested L-ANN in a murine model of acute myeloid leukemia in combination with vincristine. The combination treatment led to a significant survival advantage compared to controls or monotherapy arms. The synergy index calculations supported the hypothesis of enhanced efficacy when L-ANN is used in tandem with VCR.
In pancreatic cancer, L-ANN was evaluated in combination with GEM using the MDA PATC53 xenograft model. Zielinski et al observed there was tumor volume reduction and extended time to progression in the combination group, along with improved survival. The confidence interval (CI) values again confirmed synergy between L-ANN and GEM, reinforcing the drug’s utility in combination regimens even in difficult-to-treat solid tumors, such as pancreatic ductal adenocarcinoma.
Lung metastasis models using the MCA205 fibrosarcoma line revealed that combining L-ANN with IFO significantly reduced tumor burden in the lung. This was supported by histologic examination and tumor weight analysis. In a separate osteosarcoma model, the combination of L-ANN and IFO yielded similar results, with dramatic reductions in tumor size and viable cell percentage, and without any additive toxicity. Importantly, histograms showed less weight loss and toxicity in mice receiving the combination therapy, underlining L-ANN's favorable safety profile.
Additional in vitro synergy assays examined the effects of combining L-ANN with TRB in pancreatic and sarcoma cell lines. Heat maps and dose-response 3D plots confirmed synergistic cytotoxicity, particularly in MPanc96 and MS1PaCo2.5 pancreatic lines, as well as sarcoma lines. These results suggest a broad potential application of L-ANN across solid tumors, where traditional anthracyclines are limited by toxicity.
Zielinski et al present in vitro results of ANN combined with AZA in MOLM-13 cells, a human AML line. The combination led to increased apoptosis and decreased proliferation relative to either agent alone. Quantitative analysis again demonstrated CI values less than 1, indicating synergy. Given AZA’s use in myelodysplastic syndromes and AML, its pairing with ANN may offer a new avenue for overcoming resistance or improving outcomes in refractory disease.
Zielinski et al conclude that ANN is not only active across a range of tumor types but also exhibits strong synergistic potential with a diverse set of chemotherapy agents. These effects are consistently observed across in vitro assays and in vivo models. More importantly for oncology pharmacists and clinicians, the lack of cardiotoxicity makes ANN an especially attractive to use in anthracycline-based regimens. This could allow for more aggressive treatment strategies without compromising cardiac safety—particularly important in pediatric oncology, relapsed/refractory settings, or patients with pre-existing cardiac conditions.
From a clinical development perspective, the authors highlight the need to translate these preclinical findings into early-phase trials. Identifying the optimal ANN combinations for specific tumor types, understanding pharmacodynamic interactions, and refining dosing schedules will be crucial next steps.
