Atossa Therapeutics (NASDAQ: ATOS) expands (Z)-endoxifen to DMD: Will investors buy the thesis?

Atossa Therapeutics Inc. (NASDAQ: ATOS), a clinical-stage biopharmaceutical company focused on developing novel therapies for unmet needs in oncology and rare diseases, is now drawing industry attention for its emerging strategy in Duchenne Muscular Dystrophy, or DMD. The company is spotlighting its investigational compound (Z)-endoxifen, a small-molecule estrogen receptor modulator, as a potentially differentiated therapy not only for DMD but also for Duchenne carrier–associated pathologies that affect a subset of female carriers. This development follows the publication of a new peer-reviewed hypothesis article as well as an upcoming scientific presentation in Rome, which together lay the groundwork for possible expansion of Atossa Therapeutics’ development portfolio into neuromuscular diseases.

How could (Z)-endoxifen address both skeletal and cardiac pathways in Duchenne Muscular Dystrophy?

The published article, authored in collaboration with academic researchers, outlines how (Z)-endoxifen could act on multiple biological pathways implicated in DMD, including chronic inflammation, fibrosis, calcium dysregulation, mitochondrial dysfunction, and lipid abnormalities. These mechanisms represent the downstream effects of dystrophin deficiency, which is the primary cause of muscle degeneration in DMD. Atossa Therapeutics believes this multi-pathway activity, when deployed alongside existing standards of care such as glucocorticoids or exon-skipping agents, could offer synergistic benefit in slowing disease progression.

What sets (Z)-endoxifen apart, according to the article, is its pharmacological precision and ability to bypass metabolic variability that limits other estrogen receptor modulators such as tamoxifen. Specifically, (Z)-endoxifen avoids the reliance on CYP2D6 metabolism, which can result in inconsistent systemic exposure and reduced efficacy in patients with certain genetic polymorphisms. By contrast, (Z)-endoxifen delivers active drug directly, offering more consistent therapeutic levels that may translate to sustained muscle-level activity.

In addition to estrogen receptor modulation, the compound is noted for its inhibition of protein kinase C beta 1 (PKC-β1), a signaling molecule linked to muscle fibrosis and cardiomyopathy. The article further explores the interaction of (Z)-endoxifen with AKT/mTOR and NF-kappa B pathways, both of which play a central role in regulating muscle inflammation and cell survival. These combined effects point to the possibility of (Z)-endoxifen functioning as a pathway-agnostic adjunct therapy that could be layered onto other modalities including gene therapy or anti-sense oligonucleotide treatments.

Why is Atossa Therapeutics targeting cardiomyopathy and tissue exposure in DMD treatment design?

Cardiac relevance has also emerged as a focal point. In DMD, cardiomyopathy has become one of the leading causes of death, with the heart muscle deteriorating due to similar dystrophin-related processes as those affecting skeletal muscle. The article suggests that (Z)-endoxifen’s dual action on estrogen receptors and PKC pathways could help stabilize both skeletal and cardiac muscle by reducing pro-fibrotic and inflammatory signaling. In this context, Atossa Therapeutics sees (Z)-endoxifen not only as a potential add-on to existing therapeutic regimens but also as a unique candidate for addressing cardiac involvement in DMD, which remains poorly treated.

The pharmacokinetic rationale is also gaining attention. Researchers believe that (Z)-endoxifen accumulates in target muscle tissues at concentrations higher than what is reflected in plasma levels, suggesting a potential for durable pharmacodynamic activity without requiring complex delivery systems. This tissue-level exposure further strengthens the argument for (Z)-endoxifen as a scalable therapeutic candidate with functional impact across multiple muscle groups.

What makes symptomatic female carriers a strategic expansion opportunity for Atossa Therapeutics?

Atossa Therapeutics is also turning its attention to a patient group often overlooked in DMD research: symptomatic female carriers. These are women who carry one faulty copy of the dystrophin gene and who may develop clinical symptoms ranging from muscle weakness to dilated cardiomyopathy. Estimates suggest that between 2.5 and 19 percent of female carriers experience skeletal muscle symptoms, while 7.3 to 16.7 percent may develop heart-related complications. Given that most current DMD drug development has focused exclusively on male patients with confirmed mutations, this represents an important expansion opportunity both medically and commercially.

The company’s strategy to address this population will be highlighted in a presentation at the 2nd International Conference on Women’s Health, Reproduction and Obstetrics in Rome. H. Lawrence Remmel, Director at Atossa Therapeutics, will deliver a talk titled “Endoxifen: A Potential Novel Therapy for Duchenne Carrier-Associated Pathologies,” which aims to translate the mechanistic hypothesis into a clinical framework. The company sees this subset of patients as not only underserved but biologically well-matched to the proposed mechanism of action of (Z)-endoxifen, which targets estrogen receptor and protein kinase pathways known to influence muscle health.

How is Atossa Therapeutics exploring utrophin upregulation as a mutation-agnostic strategy in DMD?

In parallel, Atossa Therapeutics has submitted a second scientific manuscript for peer review that focuses specifically on (Z)-endoxifen’s potential to modulate utrophin expression. Utrophin is a naturally occurring structural and functional analog of dystrophin and is capable of partially compensating for the loss of dystrophin in muscle cells. By stabilizing the sarcolemma and reducing membrane fragility, utrophin upregulation has been identified as a promising mutation-independent therapeutic strategy. The manuscript, entitled “(Z)-Endoxifen as a Modulator of Utrophin Pathways in Duchenne Muscular Dystrophy,” explores how (Z)-endoxifen may stimulate these pathways, potentially broadening its therapeutic utility even further.

This focus on utrophin allows Atossa Therapeutics to position its development program independently of any particular DMD genotype, potentially opening the door to a wider patient base while complementing mutation-specific gene-editing approaches already in use.

What are the next steps in Atossa’s development roadmap for (Z)-endoxifen in neuromuscular disease?

With these foundational steps in place, Atossa Therapeutics is beginning to shape a translational roadmap for (Z)-endoxifen in DMD and carrier-associated conditions. The company is designing a stepwise preclinical and clinical strategy that will prioritize exposure-guided dosing, pharmacokinetics, pharmacodynamics, and functional endpoints relevant to upper limb mobility, diaphragmatic strength, and cardiac output. While the compound is still in investigational stages for this indication, the presence of established safety and exposure data from oncology studies may help accelerate initial clinical validation.

Janet Rea, Senior Vice President of Research and Development at Atossa Therapeutics, stated that (Z)-endoxifen’s small-molecule profile combined with phase-appropriate good manufacturing practices and an exposure-guided development framework could enable a rigorous but capital-efficient advancement path. Rea also noted that early engagement with regulators will be essential in determining whether the drug can qualify for accelerated development pathways under rare disease frameworks.

Founder and Chief Executive Officer Steven Quay reinforced the scientific rationale, emphasizing that DMD remains one of the most high-need areas in pediatric neurology. He pointed to the mechanistic differentiation of (Z)-endoxifen as a core advantage, particularly its direct action on signaling cascades distinct from the gene-editing or exon-skipping technologies that currently dominate the DMD landscape. Atossa Therapeutics intends to engage in biomarker-enriched clinical designs and explore potential combination regimens with existing approved treatments if preclinical data continue to support the hypothesis.

How are institutional investors viewing Atossa’s platform expansion into rare neuromuscular disease?

Investor attention around Atossa Therapeutics has historically centered on its breast cancer programs, but this expansion into DMD could represent a meaningful pipeline diversification opportunity. For equity holders and institutional investors, the attraction lies in the possibility of multiple shots on goal using a single compound platform. (Z)-endoxifen, if proven effective, could generate distinct value streams in oncology, central nervous system disorders, and neuromuscular diseases without requiring a fully new molecular entity for each indication.

As of mid-November 2025, shares of Atossa Therapeutics have shown limited immediate price response to the DMD announcement. However, analysts tracking the stock believe upcoming preclinical milestones, particularly any data related to utrophin modulation or functional restoration in animal models, could act as catalysts. The market will also be watching for updates on potential regulatory submissions, orphan drug designation efforts, and early-stage clinical trial planning.

The broader biopharmaceutical industry has increasingly focused on rare diseases, where regulatory incentives, reduced competition, and defined patient populations offer compelling risk-reward profiles. If Atossa Therapeutics can successfully position (Z)-endoxifen as a scalable, complementary therapy within this space, it could find itself well aligned with payer expectations and clinical adoption trends that favor cost-effective, combination-ready interventions.

Looking ahead, Atossa Therapeutics expects to continue building on the current hypothesis with mechanistic validation studies, tissue-specific exposure data, and early biomarker work. Regulatory feedback, manufacturing readiness, and potential academic collaborations will likely influence the pace and design of formal investigational new drug filings. While significant development remains, the foundation being laid positions (Z)-endoxifen as a candidate worth watching within the evolving DMD treatment landscape.

What are the key takeaways from Atossa Therapeutics’ push into Duchenne with (Z)-endoxifen?

• Atossa Therapeutics Inc. (NASDAQ: ATOS) is expanding its investigational candidate (Z)-endoxifen into Duchenne Muscular Dystrophy (DMD) and symptomatic female carriers, beyond its original oncology focus.
• A peer-reviewed hypothesis article outlines a multi-pathway mechanism of action including estrogen receptor modulation, PKC-β1 inhibition, and downstream effects on AKT/mTOR and NF-κB pathways.
• Atossa highlights (Z)-endoxifen’s potential to bypass metabolic variability seen with tamoxifen by delivering consistent exposure levels at target muscle tissues.
• The therapy could have relevance in addressing both skeletal muscle degeneration and cardiomyopathy, a leading cause of death in DMD patients.
• A second manuscript under review explores (Z)-endoxifen’s role in upregulating utrophin, a mutation-agnostic strategy with potential across all DMD genotypes.
• The company is presenting new data on Duchenne carrier–associated pathologies at a women’s health conference in Rome, targeting an underserved but clinically relevant female subpopulation.
• Preclinical development plans include biomarker-driven, exposure-guided studies focused on safety, pharmacokinetics, and functional endpoints such as upper-limb and cardiac performance.
• Leadership emphasized the need for capital-efficient rare-disease development pathways, including early regulatory engagement and combination strategies with existing standards of care.
• Investor sentiment may shift as (Z)-endoxifen gains traction as a multi-indication platform; analysts are watching for data milestones and potential rare disease designation.
• Atossa’s expansion into rare neuromuscular disease aligns with growing biopharma interest in scalable, small-molecule options that complement expensive gene therapies.