Preclinical Data Show Annamycin Makes Pancreatic Cancer Responsive to Checkpoint Inhibitors, Opening a Combination Path with Immunotherapies

Moleculin plans to sponsor a pancreatic cancer trial in 2027 while keeping its immediate focus on the MIRACLE leukemia trial.

Rhea-AI Summary

Moleculin Biotech (Nasdaq: MBRX) announced preclinical findings showing Annamycin combined with PD-1 immune checkpoint blockade extended survival in pancreatic cancer mice. The combination significantly increased survival versus either treatment alone in an immune-intact mouse model, with confirmation in a second independent experiment.

Annamycin achieved higher and more sustained pancreatic tissue exposure than doxorubicin at the same dose. Treated tumors showed DNA damage and increased infiltration of CD8+ and CD4+ T cells, types of immune cells. Blocking CD8+ cells shortened survival in treated animals. Moleculin plans to sponsor an investigator-initiated pancreatic cancer trial in 2027; the animal findings may not predict clinical outcomes. Its immediate priority remains the MIRACLE trial in acute myeloid leukemia, with a Q1 2027 data readout.

Positive

• Minor pointAnnamycin plus PD-1 blockade significantly increased mouse survival versus either agent alone, confirmed in an independent experiment.
• Minor pointPancreatic tissue exposure was higher and more sustained with Annamycin than doxorubicin at the same dose.
• Minor pointTreated tumors showed DNA damage consistent with topoisomerase II targeting and significantly increased CD8+ and CD4+ immune-cell infiltration.
• Minor pointCD8+ cell inhibition shortened survival in treated mice, supporting these immune cells' contribution to Annamycin activity.
• Minor point. Forward-looking: it has not happened yet and may not happen.Pancreatic cancer clinical trial sponsorship is planned for 2027 as an investigator-initiated study.
• Minor point. Forward-looking: it has not happened yet and may not happen.MIRACLE leukemia trial remains the company's immediate priority, with a Q1 2027 data readout.

Negative

• None.

Key Figures

Independent confirmation: Second independent experiment Planned investigator-initiated trial: 2027

Independent confirmation

Second independent experiment

Preclinical Annamycin and PD-1 checkpoint blockade combination result

Planned investigator-initiated trial

2027

Annamycin for pancreatic cancer

Key Terms

pd-1 immune checkpoint blockade, syngeneic, pharmacokinetic, topoisomerase ii alpha, +1 more

5 terms

pd-1 immune checkpoint blockade medical

"combined with PD-1 immune checkpoint blockade, extended survival"

A class of cancer immunotherapy that blocks the programmed cell death protein 1 (PD-1) pathway on immune T cells so those T cells can attack cancer cells more effectively. Drugs that achieve PD‑1 immune checkpoint blockade are typically antibodies that bind PD‑1 (or its ligand interactions) and remove an inhibitory signal that normally limits T‑cell activity; as a result, the immune response against tumors can increase but may also produce immune‑related inflammatory side effects in normal tissues.

syngeneic medical

"In a syngeneic, immunocompetent KPC mouse model"

Syngeneic describes cells, tissues, or whole animals that are genetically identical or from the same strain so they do not trigger immune rejection when transferred between individuals. Investors should care because syngeneic models are used in preclinical research to test therapies in an immune-compatible setting, which can make early results more predictable or limited in how well they will translate to genetically diverse human patients—like testing a product only on one exact phone model.

pharmacokinetic medical

"Pharmacokinetic studies show that Annamycin achieves"

Pharmacokinetic describes how a drug moves through and leaves the body — how it is absorbed, spread to tissues, broken down and excreted — like tracking a package from pickup to delivery and disposal. For investors, these properties determine effective dose, safety risks, how often a medicine must be taken, and how reliably it works, which in turn influence clinical trial success, regulatory approval chances, production complexity and a drug’s commercial value.

topoisomerase ii alpha medical

"Topoisomerase II alpha (TOP2A) is elevated in pancreatic cancer"

A cellular enzyme (commonly abbreviated TOP2A) that relieves twists and tangles in DNA by cutting both strands, passing another segment of the double helix through the break, and resealing the DNA; this action lets cells replicate and divide without the genome becoming entangled. It is one of two human type II topoisomerases, is most active during cell replication, and is a frequent target in oncology because drugs that interfere with its cutting-and-resealing cycle can block rapidly dividing cells. The name refers to the specific isoform (alpha) and does not include other topoisomerase types or isoforms.

cardiotoxicity medical

"has been shown to avoid cardiotoxicity in preclinical and clinical studies"

Cardiotoxicity is damage to the heart caused by a drug, chemical or medical treatment that can weaken heart function, disrupt heartbeat or cause inflammation. It matters to investors because evidence of cardiotoxicity can halt or delay product approvals, trigger costly additional testing, recalls or legal risk, and reduce future revenue potential—similar to how rust in an engine can undermine a machine’s reliability and resale value.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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Inhibition of CD8+ T cells shortens survival in Annamycin-treated mice, demonstrating the immune system is a functional contributor to Annamycin’s antitumor activity, not a bystander

Annamycin achieves substantially higher pancreatic tissue exposure than doxorubicin, offering a potential explanation for why topoisomerase II, a validated target in pancreatic cancer, has never been successfully drugged there

HOUSTON, Nov. 10, 2026 (GLOBE NEWSWIRE) -- Moleculin Biotech, Inc. (Nasdaq: MBRX) (“Moleculin” or the “Company”) today announced new preclinical data showing that its lead drug candidate, Annamycin (naxtarubicin), combined with PD-1 immune checkpoint blockade, extended survival in pancreatic cancer models beyond that achieved with either agent alone. The findings will be presented today by Waldemar Priebe, PhD, of The University of Texas MD Anderson Cancer Center, in an oral presentation at the 6th Annual Marie Skłodowska-Curie Symposium on Cancer Research and Care organized by Moffitt Cancer Center, being held November 8–11, 2026 in Tampa, Florida.

The presentation, titled “Targeting pancreatic cancer with Annamycin and turning immune cold tumor into hot tumor,” is scheduled for November 10th at 2:45 p.m. ET during the symposium’s gastrointestinal and urologic malignancies session.

In a syngeneic, immunocompetent KPC mouse model of advanced pancreatic ductal adenocarcinoma, treatment with liposomal Annamycin (L-ANN) in combination with PD-1 checkpoint blockade significantly increased survival compared with cohorts treated with either agent alone. The result has been reconfirmed in a second, independent experiment. Pancreatic cancer is among the tumor types least responsive to immune checkpoint inhibitors such as pembrolizumab and nivolumab, in large part because its tumor microenvironment is immunologically “cold,” with few infiltrating T cells. The Company believes these data support the evaluation of Annamycin in combination with approved PD-1 inhibitors in pancreatic cancer and, potentially, in other tumors where efficacy of checkpoint inhibitors is limited by an immunologically cold microenvironment.

The combination result builds on a series of findings from Dr. Priebe’s laboratory. Topoisomerase II alpha (TOP2A) is elevated in pancreatic cancer, and its expression correlates with shorter overall survival and higher rates of metastasis; yet approved topoisomerase II -targeting agents such as doxorubicin have not proven effective in the disease. Pharmacokinetic studies show that Annamycin achieves substantially higher and more sustained exposure in pancreatic tissue than doxorubicin at the same dose, offering a potential explanation. In treated tumors, Annamycin was measured at high concentrations, accompanied by evidence of DNA damage consistent with topoisomerase II targeting and by significantly increased infiltration of both CD8+ cytotoxic T cells and CD4+ helper T cells. Inhibiting CD8+ T cells in treated animals shortened survival, demonstrating that these cells are functional contributors to Annamycin’s antitumor activity rather than bystanders. These data extend results presented at the AACR Annual Meeting in April 2026 and at the AACR Conference on Pancreatic Cancer in September 2026, which demonstrated Annamycin’s activity across human orthotopic and syngeneic pancreatic cancer models, including liver metastasis models, and first identified the contribution of CD8+ T cells to its antitumor effect.

“In April we showed Annamycin reaches pancreatic tumors in animal models and shrinks them. In September we showed the immune system is part of why. These data close the loop: when you pair Annamycin with a checkpoint inhibitor the animals live longer than with either drug alone,” said Walter Klemp, Chairman, President and Chief Executive Officer of Moleculin. “This combination logic presents an exciting opportunity for potentially enabling immuno-oncology approaches in pancreatic cancer, and it comes with an additional benefit as Annamycin, in contrast to doxorubicin, has been shown to avoid cardiotoxicity in preclinical and clinical studies. While our immediate priority remains the MIRACLE trial in AML and its Q1 2027 data readout, this body of work continues to expand the strategic value of Annamycin well beyond AML.”

“Topoisomerase II is a validated but effectively undrugged target in pancreatic cancer, not because the target is wrong but because doxorubicin does not appear to reach the pancreas and consequently pancreatic cancer in sufficient concentration. We have successfully demonstrated in preclinical models that Annamycin does,” said Dr. Priebe. “What we did not anticipate is that once it is there, its action increases tumor infiltration of functional CD8+ and CD4+ T lymphocytes, and that is what makes the combination with checkpoint blockade work.”

The pancreatic cancer research described in this release is preclinical, which may not be predictive of clinical outcomes. The Company is currently planning to sponsor an investigator initiated clinical trial of Annamycin for the treatment of pancreatic cancer in 2027.

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 (also known as naxtarubicin), has shown to be an efficacious and well tolerated anthracycline designed to avoid multidrug resistance mechanisms and to lack 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 conducting the MIRACLE (Moleculin R/R AML AnnAraC Clinical Evaluation) Trial (MB-108), a pivotal, adaptive design, multi-center, randomized, double-blind, placebo-controlled Phase 2/3 trial evaluating Annamycin in combination with cytarabine (also referred to as “Ara-C”), 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 toward a potential approval for Annamycin for the treatment of AML. This study remains 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 also has in its pipeline 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 potential efficacy and safety of Annamycin, the potential for Annamycin to be used in combination with immune checkpoint inhibitors or in indications other than AML, the timing and results of the second interim analysis of the MB-108 trial, the potential for the MB-108 trial to support a New Drug Application submission, the Company’s plans to sponsor an investigator-initiated clinical trial of Annamycin in pancreatic cancer, and the Company’s ability to secure additional financing to conduct its clinical trials. 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 completion of the clinical trials described in this press release assumes 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. The Company relies on the reports of its expert with regard to the absence of cardiotoxicity. The dataset referenced in this press release is subject to the review of the data from future subjects in its current and future clinical trials and long-term follow-up with subjects in its current trials. 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

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Moleculin's Annamycin combination show in pancreatic cancer research?

Annamycin combined with PD-1 immune checkpoint blockade significantly increased survival compared with either agent alone in an immune-intact mouse model of advanced pancreatic cancer. A second independent experiment reconfirmed the result. These are preclinical findings and may not predict clinical outcomes.

When does Moleculin plan a pancreatic cancer clinical trial for Annamycin?

Moleculin plans to sponsor an investigator-initiated clinical trial in 2027 evaluating Annamycin for pancreatic cancer. This is a planned study, not a trial reported as underway.