Atossa Therapeutics Announces Presentation of Mechanism-Driven (Z)-Endoxifen Data in McCune-Albright Syndrome at AACR Special Conference on Rare Cancers
Rhea-AI Summary
Atossa Therapeutics (NASDAQ: ATOS) reported preclinical findings on (Z)-endoxifen in McCune-Albright syndrome-associated peripheral precocious puberty (MAS-PPP) at the AACR Special Conference on Rare Cancers held July 18-20, 2026, in Vancouver, Canada.
The poster describes a dual mechanism of action in estrogen-driven pathology: blockade of estrogen receptor (ER)-mediated transcription downstream of autonomous estrogen production and suppression of PKC-β/AKT-related proliferative and cell-cycle signaling. Using weighted gene expression signatures in ER-positive MCF7 cells with integrated phosphoproteomic and RNA-seq datasets, (Z)-endoxifen was associated with marked downregulation of cell-cycle programs (including G2M Checkpoint and E2F Targets) and modulation of estrogen-response pathways. According to Atossa, these data support further evaluation of (Z)-endoxifen as a mechanism-driven candidate for MAS-PPP and potentially other estrogen-driven neoplasms.
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Market reaction after MAS preclinical data: ATOS -3.61% in the Jul 21 session
In the Jul 21 session, ATOS declined 3.61%, reflecting a moderate negative market reaction. Argus tracked a trough of -8.5% from its starting point during tracking. Our momentum scanner triggered 4 alerts that day, indicating moderate trading interest and price volatility.
Data tracked by StockTitan Argus on the day of publication.
Key Figures
Historical Context
| Date | Event | Sentiment | 24h Move | Catalyst |
|---|---|---|---|---|
| Jun 12 | Offering closing | Negative | -4.5% | Registered direct offering closed with shares, warrants, and approximately $4.5 million gross proceeds. |
| Jun 11 | Registered offering | Negative | -41.3% | Registered direct offering announced with approximately $4.5 million upfront proceeds and additional warrants. |
| May 27 | Clinical research update | Positive | +3.4% | ASCO abstracts highlighted (Z)-endoxifen activity and the ongoing Phase 2 EVANGELINE trial. |
| May 20 | Research manuscript | Positive | +2.7% | Manuscript described potential utrophin-pathway modulation by (Z)-endoxifen in Duchenne muscular dystrophy. |
| May 14 | KOL event | Neutral | -0.2% | Company announced a virtual KOL event discussing (Z)-endoxifen development in ER-positive breast cancer. |
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
Positive research-related announcements were generally followed by gains, while offering announcements were followed by declines.
Key Terms
pkc-β/akt medical
gnas mutations medical
phosphoproteomic technical
rna-seq technical
g2m checkpoint medical
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Preclinical Data Poster Highlights Dual Estrogen Receptor and PKC-β/AKT Pathway Modulation as a Potential Therapeutic Strategy for Estrogen-Driven Pathology in McCune-Albright syndrome
Presentation Details
Session Type: Poster Session A
Date: Saturday, July 18, 2026, 7:30-9:30 pm PT
Abstract Number: A010
Location: AACR Special Conference in Cancer Research: Breaking Barriers in the Fight Against Rare Cancers,
Poster Title: Dual estrogen receptor and PKC-β signaling modulation by (Z)-Endoxifen: A mechanism-driven therapeutic strategy for estrogen-driven pathology in McCune-Albright Syndrome
Presenter: Sandra Hammer, PhD, Atossa Therapeutics Inc.
Summary: The poster supports a dual mechanism of action for (Z)-endoxifen in estrogen-driven pathology relevant to McCune Albright Syndrome-associated Peripheral Precocious Puberty (MAS-PPP): the blockade of ER-mediated transcription downstream of autonomous estrogen production and suppression of PKC-β/AKT-associated proliferative and cell-cycle signaling. This multi-pathway profile may address a key therapeutic gap in MAS-PPP, where estrogen suppression alone may not fully mitigate downstream proliferative signaling.
These findings support further evaluation of (Z)-endoxifen as a targeted therapeutic strategy for MAS-PPP and illustrate how transcriptomic and kinase-network integration can enable therapeutic repositioning for rare endocrine-driven diseases with limited dedicated drug development. They also highlight the potential relevance of (Z)-endoxifen to estrogen-driven neoplasms.
Key Highlights
- McCune-Albright Syndrome (MAS) is a rare mosaic disorder driven by activating GNAS mutations that can result in autonomous estrogen production and chronic estrogen receptor activation.
- Activating GNAS alterations are recognized oncogenic drivers in multiple neoplasms, positioning MAS a genetically defined model of chronic proliferative signaling that is highly relevant to rare tumor biology.
- The poster evaluates (Z)-endoxifen, the active metabolite of tamoxifen, as a mechanism-driven strategy to modulate both estrogen receptor signaling and non-ER proliferative kinase pathways relevant to estrogen-driven MAS symptomatology, peripheral precocious puberty.
- The analysis used weighted gene expression signatures in ER-positive MCF7 cells and integrated published phosphoproteomic and RNA-seq datasets to assess modulation of PKC-β and AKT signaling pathways.
- The analysis identified a shared estrogen-responsive gene network and showed that (Z)-endoxifen markedly downregulated cell-cycle progression programs, including G2M Checkpoint and E2F Targets, while concurrently modulating estrogen-response pathways.
- Integration of published mechanistic data further demonstrated that (Z)-endoxifen targets PKC-β1, promotes its dephosphorylation and degradation, and inhibits PMA-induced PKC-β1 and AKT phosphorylation.
"MAS related PPP remains a rare and underserved condition where current approaches focus primarily on reducing estrogen production but may not fully address downstream ER-dependent and proliferative signaling," said Dr. Steven C. Quay, M.D., Ph.D., President and Chief Executive Officer of Atossa Therapeutics. "These data support the potential of (Z)-endoxifen as a differentiated, mechanism-driven candidate that may simultaneously modulate estrogen receptor biology and PKC-β/AKT-associated cell-cycle signaling. This finding has direct relevance to several tumor types."
About McCune-Albright Syndrome
MAS is an extremely rare genetic disorder caused by activating mutations in the GNAS gene, leading to mosaic endocrine dysregulation. Because it is so rare and has a broad spectrum of symptoms, diagnosis can be challenging. The disease is characterized by a triad of symptoms: Polyostotic Fibrous Dysplasia: replacement of normal bone with weak, fibrous tissue, leading to fractures, deformities, and pain; Café-au-lait Spots: hyperpigmented skin patches with irregular, "jagged" borders that typically respect the body's midline; and Hyperfunctioning Endocrinopathies: commonly known as precocious puberty, where children (especially girls) may begin puberty as early as age two. In pediatric patients, MAS commonly presents with gonadotropin-independent precocious puberty, particularly in females, which can result in accelerated growth, premature epiphyseal closure, and reduced adult height. Additional complications may include thyroid dysfunction, growth hormone excess, and other endocrine abnormalities. There are currently limited effective treatment options, highlighting the need for new therapeutic approaches.
About Atossa Therapeutics
Atossa Therapeutics, Inc. (Nasdaq: ATOS) is a clinical-stage biopharmaceutical company developing innovative medicines in oncology and other areas of significant unmet need. The Company's lead product candidate, (Z)-endoxifen, is currently in development across several clinical settings.
(Z)-endoxifen is a potent Selective Estrogen Receptor Modulator/Degrader (SERM/D) with demonstrated activity across multiple mechanisms of interest. Atossa is evaluating its potential applications in oncology and rare diseases. The Company's proprietary oral formulation has shown a favorable safety profile and pharmacology distinct from tamoxifen, including ER-targeted effects and PKC inhibition. Atossa's (Z)-endoxifen is not approved for any indication.
Atossa's (Z)-endoxifen program is supported by a growing global intellectual property portfolio, including multiple recently issued U.S. patents and numerous pending applications worldwide.
More information is available at https://atossatherapeutics.com.
Forward-Looking Statements
This press release contains certain "forward-looking statements" within the meaning of applicable securities laws, including, but not limited to, our expectations regarding the Company's development and regulatory strategy and related milestones, including the potential indications that the Company may pursue for (Z)-endoxifen, the potential role of (Z)-endoxifen in endocrine therapies, the potential for (Z)-endoxifen to receive regulatory approval and the timing thereof, expectations regarding the design, enrollment, data, timing, results and outcomes of the Company's clinical studies, the potential clinical significance of preclinical data, and the potential market and growth opportunities for the Company. Words such as "expect," "potential," "continue," "may," "will," "should," "could," "would," "seek," "intend," "plan," "estimate," "anticipate," "believe," "design," "predict," "future," or other similar expressions or statements regarding intent, belief or current expectations, are forward-looking statements.
Forward-looking statements in this press release are subject to risks and uncertainties that may cause actual results, outcomes, or the timing of actual results or outcomes to differ materially from those projected or anticipated, including, without limitation, risks and uncertainties associated with: our ability to successfully execute our strategy to shorten our clinical development timelines for our lead program, (Z)-endoxifen; expected timing, completion and results of our preclinical studies, clinical trials, and research and development programs; the unpredictable relationship between preclinical study results and clinical study results; the timing or likelihood of regulatory filings and approvals; the outcome or timing of necessary regulatory approvals; our ability to maintain compliance with Nasdaq listing requirements; our ability to establish and maintain intellectual property rights covering our products; the impact of general macroeconomic conditions on our business; our ability to raise capital; and other risks and uncertainties detailed from time to time in Atossa's filings with the SEC, including, without limitation, its Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q.
Forward-looking statements are presented as of the date of this press release. Except as required by law, we do not intend to update any forward-looking statements.
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SOURCE Atossa Therapeutics Inc