Preclinical Data Abstract Demonstrates Robust Estrogen Receptor (ER) Inhibition in ESR1-Mutant Breast Cancer Models at Clinically Relevant Concentrations
Trial-in-Progress Abstract Details Ongoing Phase 2 EVANGELINE Study of (Z)-Endoxifen Plus Goserelin as Neoadjuvant Therapy in Premenopausal Women With ER+/HER2- Breast Cancer
SEATTLE, May 27, 2026 /PRNewswire/ -- 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 medical need, today announced that two abstracts featuring (Z)-endoxifen have been accepted for presentation at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, being held May 29 to June 2, 2026 in Chicago, IL.
"Both abstracts highlight the scientific rationale and ongoing clinical development of (Z)-endoxifen in ER-positive breast cancer," said Dr. Steven C. Quay, M.D., Ph.D., President and Chief Executive Officer of Atossa Therapeutics. "Our preclinical data demonstrate that (Z)-endoxifen achieved robust estrogen receptor inhibition across clinically relevant ESR1 mutations associated with endocrine resistance, while the EVANGELINE trial is evaluating its potential in combination with ovarian function suppression in premenopausal women in the neoadjuvant setting. Together, these abstracts underscore our belief that (Z)-endoxifen has the potential to address important unmet needs across multiple treatment settings in ER-positive breast cancer."
Presentation details are as follows:
Session Type: Online Publication
Abstract Title: Effect of (Z)-endoxifen Demonstrates Robust Estrogen Receptor Signaling Inhibition Across Clinically Relevant ESR1 Mutations
Summary: The abstract highlights new preclinical data demonstrating that (Z)-endoxifen delivers robust ER inhibition across clinically relevant estrogen receptor alpha gene (ESR1) mutations. ESR1 mutations are a major mechanism of acquired endocrine resistance in ER-positive breast cancer and remain associated with limited treatment options despite the emergence of next-generation endocrine therapies. These data therefore support the ongoing clinical development of (Z)-endoxifen, as well as its potential as a promising treatment option for breast cancer patients with limited therapeutic alternatives.
Key Data Highlights
- (Z)-endoxifen demonstrated robust dose-dependent and statistically significant inhibition of ER signaling across clinically relevant concentrations.
- In parental MCF-7 breast cancer cells, ER activity was reduced to 16-26% of control (p < 0.001). In ESR1 wild-type models, studied therapies reduced ER signaling to <5% of control (p < 0.001).
- (Z)-endoxifen maintained consistent ER inhibition across key ESR1 mutations (Y537N, Y537S, D538G) (p < 0.01).
- Comparator oral Selective Estrogen Receptor Degraders (SERDs), including elacestrant and imlunestrant, showed reduced efficacy in ESR1-mutant settings, particularly in D538G, as compared to (Z)-endoxifen.
- The D538G mutation demonstrated the highest resistance, while Y537N remained the most sensitive across treatments.
Session Type: Poster Presentation
Date: June 1, 2026, 1:30 PM-4:30 PM CT
Poster Board Number: 133b
Abstract Title: A Phase 2 Clinical Trial in Progress of (Z)-Endoxifen Plus Goserelin as Neoadjuvant Therapy in Premenopausal Women With ER+/HER2- Breast Cancer (EVANGELINE)
Presenters: Dr. Steven C. Quay & Hayley Erickson
Summary: The abstract describes EVANGELINE (NCT05607004), an ongoing, multicenter, open-label Phase 2 study evaluating daily 40 mg (Z)-endoxifen plus goserelin administered every 28 days as neoadjuvant therapy in premenopausal women with ER+/HER2-negative, cT2-3, cN0-1 breast cancer.
Key Highlights
- EVANGELINE is evaluating (Z)-endoxifen plus ovarian function suppression (OFS) as a neoadjuvant therapy in premenopausal women with ER+/HER2-negative, cT2-3, cN0-1 breast cancer.
- The primary objective is to determine the proportion of patients with baseline Ki-67 >10% who achieve Ki-67 of 10% or less after 4 weeks of therapy.
- A Simon two-stage design is being used to study whether, after four weeks, at least 65% of patients treated achieved a Ki-67 of 10% or less, with 20 patients enrolled in the first stage and, if promising, another 25 patients enrolled in the second stage (cohort A).
- A parallel cohort of 20 patients with baseline Ki-67 of 10% or less (cohort B) is enrolled to assess objective response rate at 24 weeks per RECIST v1.1.
- Secondary objectives include safety and tolerability, residual cancer burden, and PEPI score; correlative analyses include examining the effect of treatment on select tumor and plasma biomarkers.
- A pharmacokinetic run-in phase has been completed and informed selection of (Z)-endoxifen 40 mg daily plus OFS for Phase 2 evaluation. Phase 2 enrollment opened in May 2025.
About ESR1-Mutant Breast Cancer
Mutations in ESR1 commonly arise in patients with advanced ER+ breast cancer following endocrine therapy and are associated with resistance to treatment. These mutations drive ligand-independent ER activation, leading to continued tumor growth despite standard therapies. Effective treatment options for ESR1-mutant disease remain limited.
About EVANGELINE
EVANGELINE (NCT05607004) is an ongoing, multicenter, open-label Phase 2 study evaluating (Z)-endoxifen plus goserelin as a neoadjuvant therapy in premenopausal women with ER+/HER2-negative, cT2-3, cN0-1 breast cancer. The study will characterize early antiproliferative activity, clinical response, safety and biologic effects of dual ER and PKCβ1/AKT pathway targeting in this setting.
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, including the potential role of (Z)-endoxifen plus goserelin in neoadjuvant endocrine therapy, 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, including the EVANGELINE study, 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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