Atossa Therapeutics Announces Publication of Novel (Z)-Endoxifen-Related Compounds Demonstrating Potent Anti-Cancer Activity in ER-Positive Breast Cancer

Rhea-AI Summary

Atossa Therapeutics (NASDAQ: ATOS) announced a peer-reviewed preclinical study in npj Breast Cancer describing five novel (Z)-endoxifen-related compounds (AT416E, AT416Z, AT402E, AT402Z and AT300) evaluated alongside (Z)-endoxifen in multiple estrogen receptor-positive (ERα+) breast cancer models, including ESR1-mutant models.

The compounds showed anti-estrogenic and anti-cancer activity across assays of tumor growth, apoptosis, cell cycle, migration, invasion, and estrogen receptor-driven transcription. In certain models, combinations with the CDK4/6 inhibitor abemaciclib produced additive to synergistic activity comparable to or greater than abemaciclib plus (Z)-endoxifen. Investigators concluded select candidates warrant further in vivo safety and efficacy evaluation; Atossa emphasized the findings are preclinical and do not establish safety or efficacy in patients.

Positive

• Five new (Z)-endoxifen-related compounds characterized with anti-cancer activity in ERα+ breast cancer models
• Activity observed in ESR1-mutant models, which are linked to endocrine resistance and recurrent or metastatic ER-positive disease
• Additive to synergistic effects with abemaciclib in some models, sometimes comparable to or greater than abemaciclib plus (Z)-endoxifen
• Peer-reviewed publication in npj Breast Cancer supports scientific validation of Atossa’s endoxifen-related platform

Negative

• Data are preclinical only and do not establish safety or efficacy in human patients
• Further in vivo safety and efficacy studies are required before any clinical development decisions

News Market Reaction – ATOS

+2.33%

2 alerts

+2.33% Session close to close

-7.3% Trough Tracked

$24.06M Market Cap

0.2x Rel. Volume

In the Jul 28 session, ATOS gained 2.33%, reflecting a moderate positive market reaction. Argus tracked a trough of -7.3% from its starting point during tracking. Our momentum scanner triggered 2 alerts that day, indicating moderate trading interest and price volatility.

Data tracked by StockTitan Argus on the day of publication.

Market Context

ATOS’s 9.02% short interest was categorized as low in the platform data. The publication adds labora...

Analysis

ATOS’s 9.02% short interest was categorized as low in the platform data. The publication adds laboratory evidence, but no patient safety or efficacy was established; further in vivo work is the key watchpoint.

Key Figures

Compounds evaluated: Five compounds Publication date: July 20, 2026 Tumor-growth models: Two- and three-dimensional +1 more

4 metrics

Compounds evaluated Five compounds Preclinical study of entities related to (Z)-endoxifen

Publication date July 20, 2026 npj Breast Cancer publication

Tumor-growth models Two- and three-dimensional Laboratory tumor-cell growth assays

Potential treatment lines Second- or third-line Potential approaches for recurrent disease

Historical Context

5 past events · Latest: Jul 21 (Positive)

Pattern 5 events

Date	Event	Sentiment	24h Move	Catalyst
Jul 21	Preclinical data	Positive	-3.6%	Preclinical (Z)-endoxifen findings presented at an AACR rare-cancers conference.
Jun 12	Registered offering	Negative	-4.5%	Registered direct offering closed with shares, warrants, and gross proceeds.
Jun 11	Registered offering	Negative	-41.3%	Company announced a registered direct share and warrant offering.
May 27	Clinical-trial update	Positive	+3.4%	ASCO abstracts highlighted endoxifen activity and an ongoing Phase 2 trial.
May 20	Manuscript acceptance	Positive	+2.7%	Review manuscript described endoxifen’s potential utrophin-modulation role in Duchenne muscular dystrophy.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Pattern Detected

Prior reactions mostly aligned with the direction of the announced news, although the July 21 preclinical update diverged.

Key Terms

ESR1 mutations, CDK4/6 inhibitor, RNA-sequencing, apoptosis, +1 more

5 terms

ESR1 mutations medical

"models containing activating ESR1 mutations"

ESR1 mutations are changes in the DNA of the ESR1 gene, which makes the estrogen receptor that many breast cancers rely on to grow. These changes can make standard hormone-blocking treatments less effective, like changing a lock so the usual key no longer fits; for investors, that alters the prospects for related drugs, diagnostic tests and clinical trial outcomes, and therefore can materially affect companies developing therapies or tests.

CDK4/6 inhibitor medical

"combination with the CDK4/6 inhibitor abemaciclib"

A CDK4/6 inhibitor is a type of cancer drug that blocks two proteins (CDK4 and CDK6) that tell cells to divide, effectively slowing or stopping the growth of tumors. Think of it as cutting power to a photocopier that keeps making cancer cells; that control can shrink tumors or delay progression. For investors, these drugs matter because clinical trial results, regulatory approvals, patent life, safety issues and competition directly affect sales potential and company value.

RNA-sequencing technical

"RNA-sequencing analyses identified shared anti-estrogenic effects"

RNA sequencing is a laboratory method that reads which genes are active in cells by measuring their RNA messages, like listening to the passages a cell is reading from its instruction manual. For investors, it matters because the technique helps companies discover drug targets, develop diagnostics, select patients for trials, and show biological proof that a therapy is working — all factors that can speed development, reduce risk, and affect a biotech company's value.

apoptosis medical

"assessed two- and three-dimensional tumor-cell growth, apoptosis"

Apoptosis is a controlled, built‑in process where cells deliberately shut down and are safely removed, like a person retiring and clearing out their belongings so the house stays orderly. Investors care because many drugs and diagnostics target or measure this process: how well a therapy triggers or avoids apoptosis can determine clinical trial success, safety profiles, regulatory approval, and ultimately a company’s valuation.

anti-estrogenic medical

"Several compounds demonstrated potent anti-estrogenic effects"

A substance or treatment that blocks or reduces the action of estrogen, a natural hormone, by preventing it from binding to its receptors or by lowering its production. It matters to investors because anti-estrogenic drugs are used in hormone-sensitive conditions (for example certain cancers and endocrine disorders), so their effectiveness, side effects, and regulatory status can influence clinical trial outcomes, market demand, pricing, and company valuations.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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Peer-reviewed preclinical study published in npj Breast Cancer identifies new chemical entities with activity in ESR1-mutant models

Findings suggest potential for combination with abemaciclib

SEATTLE, July 28, 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 clinical need, today announced 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.

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.

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 and (Z)-endoxifen-related compounds in endocrine therapies, 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, 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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SOURCE Atossa Therapeutics Inc

FAQ

What did Atossa Therapeutics (NASDAQ: ATOS) announce on July 28, 2026 about (Z)-endoxifen-related compounds?

Atossa Therapeutics announced peer-reviewed preclinical results for five novel (Z)-endoxifen-related compounds with anti-cancer activity in ER-positive breast cancer models. According to Atossa, the study showed anti-estrogenic effects across multiple assays and included activity in ESR1-mutant models associated with endocrine-resistant disease.

How do Atossa Therapeutics’ new (Z)-endoxifen-related compounds perform in ESR1-mutant breast cancer models?

The new compounds demonstrated activity in models containing activating ESR1 mutations, which are linked to endocrine resistance and recurrent or metastatic ER-positive breast cancer. According to Atossa, this suggests potential relevance for difficult-to-treat disease settings, pending further in vivo safety and efficacy studies.

What did the Atossa Therapeutics (ATOS) study show about combining the new compounds with abemaciclib?

In certain experimental models, selected compounds combined with abemaciclib showed additive to synergistic activity comparable to or greater than abemaciclib plus (Z)-endoxifen. According to Atossa, these preclinical findings support further evaluation of combinations with the CDK4/6 inhibitor abemaciclib in future studies.

Are Atossa Therapeutics’ new (Z)-endoxifen-related compounds proven safe or effective in patients?

No, the compounds are not yet proven safe or effective in patients. According to Atossa, the published results are preclinical and the authors specifically note that in vivo safety and efficacy studies are still required before any conclusions for patient treatment.

What are the key compounds evaluated in Atossa Therapeutics’ July 2026 npj Breast Cancer publication?

The study evaluated five previously uncharacterized compounds, AT416E, AT416Z, AT402E, AT402Z and AT300, alongside (Z)-endoxifen. According to Atossa, these new chemical entities showed anti-estrogenic and anti-cancer activity in a broad panel of estrogen receptor-positive breast cancer assays.

What are the next steps for Atossa Therapeutics’ new (Z)-endoxifen-related candidates after this preclinical study?

Investigators concluded that select compounds warrant further in vivo safety evaluation and efficacy studies, including in recurrent disease settings. According to Atossa, these early findings provide a rationale to explore the candidates as potential second- or third-line approaches for endocrine-resistant ER-positive breast cancer.