On July 21, 2026 Atossa Therapeutics, Inc. (NASDAQ: ATOS) ("Atossa" or the "Company"), a clinical-stage biopharmaceutical company developing novel therapies in oncology and other areas of significant unmet clinical need, reported that a poster presentation titled "Dual estrogen receptor and PKC-β signaling modulation by (Z)-Endoxifen: A mechanism-driven therapeutic strategy for estrogen-driven pathology in McCune-Albright Syndrome" was presented at the AACR (Free AACR Whitepaper) Special Conference in Cancer Research: Breaking Barriers in the Fight Against Rare Cancers, which took place July 18-20, 2026, in Vancouver, BC, Canada.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Presentation Details
Session Type: Poster Session A
Date: Saturday, July 18, 2026, 7:30-9:30 pm PT
Abstract Number: A010
Location: AACR (Free AACR Whitepaper) Special Conference in Cancer Research: Breaking Barriers in the Fight Against Rare Cancers, Vancouver, BC, Canada
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.
(Press release, Atossa Therapeutics, JUL 21, 2026, View Source [SID1234669343])