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

Rhea-AI Summary

Atossa Therapeutics (Nasdaq: ATOS) presented four clinical updates at SABCS 2025 on (Z)-endoxifen, covering DCIS active surveillance, low-dose I-SPY2 pilot data, ESR1-mutant mechanistic results, and the Phase 2 EVANGELINE neoadjuvant trial.

Key facts: daily 10 mg (Z)-endoxifen was well tolerated with 95% of patients completing ≥75% therapy; MRI tumor volume median change was -72%; ctDNA clearance occurred in 70% of initially positive patients; EVANGELINE run-in showed 86% with Week 4 Ki-67 ≤10% supporting a 40 mg Phase 2 dose.

Positive

• 95% of I-SPY2 patients completed ≥75% of 10 mg therapy
• Median MRI tumor volume reduction of -72%
• ctDNA cleared in 70% of initially positive patients
• 86% achieved Week 4 Ki-67 ≤10% in EVANGELINE run-in

Negative

• Clinical impact at 10 mg described as modest with only one mPEPI-0 outcome
• Program requires dose escalation to 40 mg to target broader mechanisms

Key Figures

Clinical trial updates 4 updates SABCS 2025 presentations on (Z)-endoxifen

Low-dose (Z)-endoxifen 10 mg daily I-SPY2 Endocrine Optimization Pilot neoadjuvant dose

Therapy completion rate 95% Patients completing ≥75% of 10 mg (Z)-endoxifen therapy

Tumor volume change -72% median MRI functional tumor volume reduction with low-dose (Z)-endoxifen

ctDNA clearance 70% Initially ctDNA-positive patients clearing ctDNA on treatment

Escalation dose 40 mg/day Next-step dosing, with or without abemaciclib

Ki-67 responder rate 86% EVANGELINE Week 4 Ki-67 ≤10% with (Z)-endoxifen + OFS

Ki-67 response threshold 65% Non-inferiority design target in EVANGELINE Phase 2

Market Reality Check

Volume Volume 1,163,779 is at 1.27x the 20-day average of 916,093, indicating elevated trading interest pre-announcement. normal

Technical Price 0.825 is slightly above the 200-day MA at 0.82, despite a -8.82% move before this news.

Peers on Argus

Peers show mixed moves with no clear sector trend: examples include ANRO up 1.14%, while MGNX, PYXS, and SPRO are down between -1.69% and -2.78%. With ATOS down -8.82% and no peers in the momentum scanner, trading appears stock-specific.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 11	Regulatory designation	Positive	+6.5%	FDA Rare Pediatric Disease designation for (Z)-endoxifen in DMD.
Dec 09	IP / patent grant	Positive	+3.5%	USPTO issuance of broad patent on enteric oral (Z)-endoxifen.
Dec 04	Regulatory strategy	Positive	+2.7%	FDA Type C meeting clarifying accelerated paths for (Z)-endoxifen.
Dec 02	Preclinical / AI study	Positive	-5.7%	AI-driven study identifying (Z)-endoxifen as GBM candidate.
Nov 17	New indication thesis	Positive	-1.9%	Peer-reviewed support for DMD and symptomatic carrier use.

Pattern Detected

Recent (Z)-endoxifen news has often coincided with modest positive reactions, though several scientifically positive items still saw negative price moves.

Recent Company History

Over the past six weeks, ATOS has reported multiple (Z)-endoxifen milestones, including an FDA Rare Pediatric Disease designation for DMD, issuance of a broad U.S. patent with 100 claims, and FDA feedback on expedited strategies across breast cancer settings involving ~800 trial participants. It also highlighted AI-driven GBM research and a DMD opportunity. Today’s SABCS clinical updates extend this trajectory, emphasizing neoadjuvant efficacy, ESR1-mutant activity, and risk-reduction potential within the same therapeutic franchise.

Market Pulse Summary

This announcement consolidates four (Z)-endoxifen clinical updates, highlighting strong tolerability, substantial MRI and Ki-67 changes, and mechanistic support in ESR1-mutant disease, plus a non-inferiority EVANGELINE design targeting a 65% Ki-67 response threshold. Placed alongside prior FDA feedback and trial streamlining, it underscores a focused breast cancer strategy. Investors may watch for longer-term outcomes, invasive recurrence data, and how neoadjuvant and risk-reduction readouts shape future regulatory discussions.

Key Terms

dcis medical

"trial testing active surveillance and novel endocrine therapy agents for DCIS management"

DCIS (ductal carcinoma in situ) is a non-invasive form of abnormal cell growth confined to the milk ducts of the breast that has not yet spread to surrounding tissue. Think of it like a stain on a carpet that hasn’t soaked through—visible and treatable before invasion. For investors, DCIS matters because its diagnosis rates, treatment approaches, and regulatory decisions can affect demand for diagnostics, drugs, surgical procedures and related medical technologies, influencing healthcare company revenues and clinical trial risk.

ctdna medical

"reductions in Ki-67, MRI tumor volume, and ctDNA, support its potential"

Circulating tumor DNA (ctDNA) is tiny fragments of genetic material shed by cancer cells into the bloodstream, like breadcrumbs that can reveal a tumor’s presence and genetic makeup without needing a biopsy. For investors, ctDNA matters because tests and technologies that detect and analyze these fragments can speed diagnosis, track treatment response, and signal relapse, creating commercial opportunities in diagnostics, personalized therapies, and monitoring services.

esr1 medical

"patients with ER+/ESR1 mutant breast cancer, a population with limited"

ESR1 is a gene that makes the estrogen receptor alpha protein, a cellular “lock” that the hormone estrogen (the “key”) fits into to tell cells how to grow, divide and behave. Mutations or changes in ESR1 can change how cancers—especially breast and other hormone-driven tumors—respond to hormone-blocking drugs, so investors track ESR1-linked tests, drugs and trial results because they directly affect treatment choices, market size and regulatory chances in oncology and women’s health.

erα medical

"targeting both ERα and PKCβ1) with or without abemaciclib"

erα is a protein inside certain cells that detects and responds to the hormone estrogen, acting like a lock that the estrogen key fits to change how a cell grows or behaves. For investors, erα matters because many drugs, tests and regulatory decisions focus on whether a disease is driven by this receptor; that affects a therapy’s market size, trial outcomes and the commercial value of related treatments or diagnostics.

ki-67 medical

"reductions in Ki-67, MRI functional tumor volume (–72% median)"

Ki-67 is a protein found in cells that marks how quickly they are dividing; doctors measure it in tumor samples to estimate how fast a cancer is growing, similar to checking a car’s speed to judge how urgently it needs attention. For investors, Ki-67 levels matter because they can influence clinical trial results, help predict a treatment’s effectiveness or approval prospects, and affect the size of the potential market for therapies and diagnostics tied to cancer growth.

p53 medical

"restoring beneficial programs (oxidative phosphorylation, p53), highlighting its"

p53 is a protein produced from the TP53 gene that acts like a cellular quality-control inspector, sensing DNA damage and either pausing cell growth so repairs can happen or triggering damaged cells to self-destruct. Because many cancers arise when p53 stops working, measuring or restoring its activity is a key goal for diagnostics and treatments, so advances involving p53 can affect clinical outcomes and the commercial value of oncology drugs and tests.

ovarian function suppression medical

"(Z)-endoxifen with Ovarian Function Suppression (OFS) may offer a more tolerable"

Ovarian function suppression is a medical approach that temporarily or permanently stops the ovaries from producing hormones such as estrogen, using drugs, implants, or surgery. It matters to investors because the use, effectiveness, and approval of these therapies affect demand for related drugs and devices, clinical trial outcomes, treatment guidelines, and healthcare costs—similar to how changing fuel rules would reshape demand across an auto supply chain.

non-inferiority trial technical

"A Randomized Phase 2 Non-Inferiority Trial of (Z)-Endoxifen + Goserelin vs"

A non-inferiority trial is a clinical study designed to show that a new treatment or drug is not meaningfully worse than an existing standard therapy by a pre-set amount. For investors, these trials matter because they can enable regulatory approval and market entry when a new product offers similar benefit with other advantages (lower cost, easier use, fewer side effects); think of it like proving a new smartphone’s battery lasts nearly as long as the market leader so buyers will consider it.

AI-generated analysis. Not financial advice.

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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SOURCE Atossa Therapeutics Inc

FAQ

What (Z)-endoxifen results did Atossa (ATOS) present at SABCS 2025?

Atossa reported tolerability and activity across four studies: I-SPY2 low-dose biological activity, RECAST DCIS surveillance feasibility, ESR1-mutant antagonist activity, and EVANGELINE run-in supporting 40 mg dosing.

How well tolerated was 10 mg (Z)-endoxifen in the I-SPY2 pilot for ATOS?

The 10 mg daily dose was well tolerated with 95% of patients completing ≥75% of therapy and mostly low-grade side effects.

What efficacy signals did ATOS report for (Z)-endoxifen in early breast cancer?

Reported signals include a median -72% MRI tumor volume reduction and ctDNA clearance in 70% of initially positive patients.

What did EVANGELINE run-in data show for Atossa's ATOS study in premenopausal patients?

EVANGELINE pharmacodynamic run-in showed 86% of patients reached Week 4 Ki-67 ≤10%, supporting selection of 40 mg (Z)-endoxifen with OFS for Phase 2.

Does (Z)-endoxifen appear active against ESR1-mutant breast cancer according to ATOS data?

Yes; (Z)-endoxifen maintained ERα antagonist activity against key ESR1 mutants and reversed mutant-associated transcriptional signatures in presented analyses.