Atossa Highlights (Z)-Endoxifen's Multi-Pathway Potential In Duchenne Muscular Dystrophy And Carrier-Associated Pathologies

Author: Benzinga Newsdesk | November 17, 2025 09:11am

Published article outlines rationale for multi-pathway efficacy for (Z)-endoxifen in Duchenne Muscular Dystrophy (DMD); November scientific presentation to spotlight potential in Duchenne carrier–associated pathologies

SEATTLE, Nov. 17, 2025 /PRNewswire/ -- Atossa Therapeutics, Inc. (NASDAQ:ATOS) ("Atossa" or the "Company"), a clinical-stage biopharmaceutical company developing innovative medicines in oncology, announces a growing body of scientific work supporting the potential role of its investigational therapy (Z)-endoxifen in DMD, a severe, progressive, and ultimately fatal neuromuscular disease, in addition to Duchenne carrier–associated pathologies (D-CAPs) that affect a subset of female carriers. The momentum is anchored by a newly published, peer-reviewed hypothesis article and an upcoming invited scientific presentation.

Newly published hypothesis article outlines why (Z)-endoxifen may matter in DMD

The article about (Z)-Endoxifen in Duchenne Muscular Dystrophy (DMD), surveys the DMD treatment landscape and details how (Z)-endoxifen's pharmacology could address multiple downstream drivers of disease, including inflammation, fibrosis, calcium dysregulation, mitochondrial dysfunction, and lipid abnormalities. A video abstract of the paper can be found here.

The paper emphasizes (Z)-endoxifen's direct estrogen-receptor (ER) modulation, allosteric inhibition of PKC (notably PKC-β1), and effects along AKT/mTOR and NF-κB axes, mechanisms that together may help slow disease progression when used as an adjunct to standard care. Notably, the authors underscore (Z)-endoxifen's potential to deliver more consistent therapeutic exposures than tamoxifen by bypassing CYP2D6 metabolic variability, an important limitation of the pro-drug approach. As illustrated in the mechanistic diagram, page 7 of the publication, the paper maps (Z)-endoxifen's ER-dependent and ER-independent signaling effects relevant to dystrophic muscle.

• Clinical context: Prior tamoxifen studies in DMD showed safety and encouraging trends but were underpowered due to premature termination during the pandemic, supporting continued exploration of more potent, exposure-reliable metabolites like (Z)-endoxifen.
  
  
  
   
• Tissue exposure: (Z)-endoxifen tissue concentrations may substantially exceed plasma levels in certain settings, supporting a rationale for sustained pharmacodynamic activity at the muscle level.
  
  
  
   
• Cardio-skeletal relevance: The paper reviews pathways tied to cardiomyopathy, now a leading cause of death in DMD, and discusses how ER/PKC-linked modulation could complement existing standards of care, including glucocorticoids and recently approved agents.
  
  
  
   
• Pragmatic access: As a small-molecule candidate, (Z)-endoxifen could, if proven safe and effective, offer a potentially more scalable and accessible option alongside high-cost genetic approaches, while remaining mechanistically complementary.

As a follow-up to our initial publication, Atossa recently submitted a second manuscript investigating the potential mechanism of action of (Z)-endoxifen in Duchenne muscular dystrophy (DMD). This study focuses specifically on the role of (Z)-endoxifen in modulating utrophin expression and signaling pathways. The manuscript, entitled "(Z)-Endoxifen as a Modulator of Utrophin Pathways in Duchenne Muscular Dystrophy," is currently under review with the Journal of Degenerative Neurological and Neuromuscular Disease. Utrophin is a structural and functional analog of dystrophin that can compensate for the loss of dystrophin in DMD, stabilizing the sarcolemma and mitigating muscle fiber damage. Pharmacological upregulation of utrophin represents a promising therapeutic strategy that is independent of the underlying dystrophin mutation. Our work explores how (Z)-endoxifen influences utrophin-related pathways, potentially offering a novel, mutation-agnostic therapeutic approach for DMD.

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