On July 28, 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 the publication of a peer-reviewed preclinical study in npj Breast Cancer evaluating five novel chemical entities structurally related to (Z)-endoxifen. The study titled, "Novel (Z)-endoxifen-related new chemical entities exhibit potent anti-cancer activity in ERα+ breast cancer," reported anti-estrogenic and anti-cancer activity across multiple estrogen receptor-positive breast cancer models, including models harboring clinically relevant activating mutations in ESR1.
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Publication Details
Journal: npj Breast Cancer
Publication Date: July 20, 2026
Article Title and Link: Novel (Z)-endoxifen-related new chemical entities exhibit potent anti-cancer activity in ERα+ breast cancer
Research Collaboration: Mayo Clinic and Atossa Therapeutics, Inc.
Summary
The investigators evaluated five previously uncharacterized compounds generated during the synthesis of (Z)-endoxifen – AT416E, AT416Z, AT402E, AT402Z and AT300 – alongside (Z)-endoxifen in a broad panel of laboratory assays. The studies assessed two- and three-dimensional tumor-cell growth, apoptosis, cell-cycle progression, migration, invasion, estrogen receptor transcriptional activity, gene-expression changes and activity in combination with the CDK4/6 inhibitor abemaciclib.
Several compounds demonstrated potent anti-estrogenic effects, and affected multiple anti-cancer processes including apoptosis, cell-cycle progression, migration, invasion and estrogen receptor-driven transcription.
In certain experimental settings and models, selected compounds combined with abemaciclib demonstrated additive to synergistic activity that was comparable to or greater than the activity observed with abemaciclib plus (Z)-endoxifen.
The compounds also showed activity in models containing activating ESR1 mutations, which are associated with endocrine resistance and recurrent or metastatic estrogen receptor-positive breast cancer.
RNA-sequencing analyses identified shared anti-estrogenic effects as well as distinct compound-specific transcriptional programs that may help differentiate the candidates.
The authors concluded that select compounds warrant further in vivo safety evaluation, as well as efficacy studies, including as potential second- or third-line approaches for recurrent disease. These findings are preclinical and do not establish safety or efficacy in patients.
"This publication expands the scientific foundation of our endoxifen platform and identifies additional compounds with compelling activity across difficult-to-treat estrogen receptor-positive breast cancer models," said Dr. Steven C. Quay, M.D., Ph.D., President and Chief Executive Officer of Atossa Therapeutics. "Of particular interest is the activity observed in ESR1-mutant models and in combination with a CDK4/6 inhibitor. While these results are early and preclinical, we believe they provide a strong rationale for further evaluation of selected candidates as we continue to explore opportunities to address endocrine resistance and recurrent disease."
About Estrogen Receptor-Positive Breast Cancer
Estrogen receptor-positive breast cancer is the most common molecular subtype of breast cancer. Although endocrine therapies are effective for many patients, recurrence and late relapse remain important clinical challenges. Activating mutations in ESR1 can allow estrogen receptor signaling to continue despite estrogen deprivation and are a recognized mechanism of acquired resistance in advanced disease. New therapies capable of inhibiting estrogen receptor signaling in ESR1-mutant tumors, alone or in rational combinations, may help address this unmet need.
(Press release, Atossa Therapeutics, JUL 28, 2026, View Source [SID1234669469])