Atossa Therapeutics Presents Four Clinical Trial Updates Highlighting (Z)-Endoxifen Research at the 2025 San Antonio Breast Cancer Symposium

Studies highlight findings regarding the potential use of (Z)-endoxifen to advance breast cancer treatment and risk reduction

SEATTLE, Dec. 15, 2025 /PRNewswire/ -- Atossa Therapeutics, Inc. (Nasdaq: ATOS) ("Atossa" or the "Company"), a clinical-stage biopharmaceutical company developing innovative medicines in oncology and other areas of high unmet need, presented four clinical trial updates on (Z)-endoxifen at the San Antonio Breast Cancer Symposium (SABCS), held December 9-12, 2025, in San Antonio, TX.

"Clinical trial updates and data presented at SABCS 2025 reinforce our focus on the therapeutic value of (Z)-endoxifen across the breast care continuum," said Steven Quay, M.D., Ph.D., Atossa Therapeutics' President and Chief Executive Officer. "With support from our growing body of clinical evidence, we continue to advance our high value clinical programs. Following our more streamlined pathway for our Phase 2 EVANGELINE study, we expect continued enrollment and data generation for neoadjuvant ER+/HER2- breast cancer. Finally, we are committed to advancing a low-dose treatment strategy designed to reduce mammographic breast density. High mammographic breast density has been associated with a higher risk of developing future breast cancer."

Presentation Highlights:

Initial results from RECAST DCIS: Multicenter platform trial testing active surveillance and novel endocrine therapy agents for DCIS management

Clinical significance

Early RECAST findings suggest that short-term endocrine therapy combined with MRI response assessment may identify patients with low-risk DCIS who can avoid surgery and pursue active surveillance, offering a potential pathway to reduce overtreatment while personalizing care

Key takeaways

• RECAST is testing whether short-term endocrine therapy plus MRI response can identify appropriate DCIS patients for long-term active surveillance while avoiding surgery
• Early results show excellent tolerability and steady enrollment, with many patients electing to continue active surveillance, suggesting feasibility of this patient-centered "window of opportunity" approach
• Future work focuses on integrating imaging and molecular biomarkers to refine prediction of progression risk, guide personalized care pathways, improve patient experience and quality of life, and assess long-term outcomes including durability of active surveillance and invasive recurrence

Low dose (Z)-endoxifen in the I-SPY2 Endocrine Optimization Pilot

Clinical significance

The excellent tolerability and biologic activity of low-dose (Z)-endoxifen, demonstrated by reductions in Ki-67, MRI tumor volume, and ctDNA, support its potential as an effective neoadjuvant endocrine therapy for HR+/HER2- early breast cancer and justifies dose escalation and combination strategies to further improve patient outcomes

Key takeaways

• The daily 10 mg (Z)-endoxifen dose was well tolerated, with 95% of patients completing ≥75% of therapy and low-grade side effects, demonstrating strong feasibility in an endocrine-naïve HR+/HER2- population
• Biologic activity was evident, with meaningful reductions in Ki-67, MRI functional tumor volume (–72% median), and ctDNA clearance observed in 70% of patients who were initially ctDNA-positive, indicating endocrine responsiveness
• Clinical impact was modest but supportive, with one mPEPI-0 outcome; the program is now escalating to 40 mg/day (targeting both ERα and PKCβ1) with or without abemaciclib to further optimize neoadjuvant endocrine therapy

(Z)-Endoxifen Maintains ERα Antagonist Function Against ESR1 Mutants via Inactive Conformation Stabilization and Reversal of Mutant ESR1-Associated Transcriptional Signatures

Clinical significance

Findings demonstrate (Z)-endoxifen as a promising therapeutic option for patients with ER+/ESR1 mutant breast cancer, a population with limited effective endocrine treatments and high unmet need

Key Takeaways

• (Z)-Endoxifen shown to maintain potent ERα antagonist activity across key ESR1 mutations (Y537S, D538G) by stabilizing inactive receptor conformations, with computational, energetic, and metadynamics analyses showing ESR1 mutants still retain antagonist-compatible states
• Functional assays confirmed strong suppression of ER signaling in both wild-type and mutant ESR1 backgrounds, demonstrating robust inhibitory activity even under estrogen-rich conditions and validating the mechanistic modeling findings
• Transcriptomic analyses showed that (Z)-endoxifen reverses multiple mutant ESR1–associated oncogenic pathways (e.g., estrogen response, E2F, Myc) while restoring beneficial programs (oxidative phosphorylation, p53), highlighting its therapeutic potential for ER+ / ESR1 mutant breast cancer

A Randomized Phase 2 Non-Inferiority Trial of (Z)-Endoxifen + Goserelin vs Exemestane + Goserelin as a Neoadjuvant Treatment for Premenopausal Women with ER+/HER2- Breast Cancer (EVANGELINE)

Clinical Significance

(Z)-endoxifen with Ovarian Function Suppression (OFS) may offer a more tolerable and biologically potent alternative to aromatase-inhibitor (AI)-based regimens for premenopausal ER+/HER2– patients, potentially expanding endocrine therapy options and improving adherence while maintaining robust neoadjuvant efficacy

Key Takeaways

• EVANGELINE is the first trial to evaluate (Z)-endoxifen with OFS as a neoadjuvant therapy for patients with premenopausal ER+/HER2– breast cancer, addressing a major unmet need for patients who cannot tolerate AI with OFS therapy
• Pharmacodynamic run-in data showed strong early biologic activity, with 86% of patients achieving a Week 4 Ki-67 ≤10%, supporting the selection of 40 mg (Z)-endoxifen with OFS for Phase II, and demonstrating promising antiproliferative efficacy
• The study design incorporates a Simon two-stage approach to test whether (Z)-endoxifen with OFS can meet or exceed a 65% Ki-67 response threshold, with secondary endpoints including safety, RCB, PEPI score, and MRI-based tumor response

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. Atossa's strategy emphasizes disciplined capital allocation, focusing resources on programs and data packages that can enable future regulatory submissions and potential commercialization. For more information, visit www.atossatherapeutics.com and refer to Atossa's filings with the U.S. Securities and Exchange Commission (SEC).

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, the potential indications that the Company may pursue for (Z)-Endoxifen, 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, 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 and pursue a metastatic breast cancer indication, DMD indication or other indications 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 regain and 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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