Atossa Therapeutics Announces Publication of KARISMA Endoxifen Trial Demonstrating Significant Reduction in Mammographic Breast Density in Healthy Premenopausal Women

• Peer-reviewed data support (Z)-endoxifen's (Endoxifen) potential as a differentiated breast cancer risk prevention candidate by marked reduction of mammographic breast density (MBD)
• Doses of both 1 mg and 2 mg daily Endoxifen significantly reduced MBD versus placebo after six months
• 1 mg dose achieved clinically meaningful density reduction with a tolerability profile similar to placebo, supporting further development in women at elevated breast cancer risk

SEATTLE, May 6, 2026 /PRNewswire/ -- Atossa Therapeutics, Inc. (Atossa or the Company) (Nasdaq: ATOS), a clinical-stage biopharmaceutical company focused on developing novel therapies targeting breast cancer and rare diseases, today announced the publication of results from the KARISMA Endoxifen trial in the Journal of the National Cancer Institute (JNCI). The randomized, double-blind, placebo-controlled Phase 2 study evaluated daily oral Endoxifen and demonstrated that low-dose Endoxifen significantly reduced MBD, a key risk factor for breast cancer.

The article titled "Endoxifen for Mammographic Density Reduction – Results from the KARISMA Endoxifen Trial," highlighted data collected by investigators at Karolinska Institutet (Stockholm, Sweden) and collaborators, from a study funded by Atossa. The study evaluated placebo, 1 mg, and 2 mg Endoxifen administered daily for six months in 240 healthy premenopausal women enrolled through the Swedish national mammography screening program.

Elevated MBD is an established risk factor for breast cancer and a recognized pharmacodynamic marker of response to endocrine risk-reduction therapy. In the KARISMA Endoxifen trial, both the 1 mg and 2 mg Endoxifen dose levels produced statistically significant reductions in MBD compared with placebo. The 1 mg dose reduced MBD by 19.3% versus placebo (p=0.004), while the 2 mg dose reduced MBD by 26.5% (p<0.001) versus placebo. These reductions were comparable to those previously reported with standard-dose tamoxifen, but were achieved using direct administration of Endoxifen, the most therapeutically active metabolite of tamoxifen.

Both levels demonstrated a favorable tolerability profile. However, the similar tolerability profile between the 1 mg dose and placebo with effective MBD reduction is significant for potentially addressing future breast cancer risk reduction. Discontinuations due to adverse events considered related to the study drug were similar between placebo and 1 mg Endoxifen, occurring in 4 placebo participants and 5 participants receiving 1 mg Endoxifen, compared with 11 participants receiving 2 mg Endoxifen. No clinically significant changes in hematologic safety tests, serum chemistry, coagulation, urinalysis, blood pressure, heart rate, or physical examination findings were observed during the trial. Adverse events were generally vasomotor in nature, consistent with those previously reported for tamoxifen.

"These data are an important step toward redefining breast cancer prevention," said Steven Quay, M.D., Ph.D., President and Chief Executive Officer of Atossa Therapeutics. "Tamoxifen is approved by the U.S. Food and Drug Administration (FDA) for breast cancer risk reduction, but its use has been limited by tolerability, variable metabolism, and patient acceptance. Endoxifen is the active metabolite responsible for much of tamoxifen's anti-estrogenic activity. By administering Endoxifen directly, we believe there is an opportunity to preserve the biologic benefit of endocrine prevention while improving predictability and potentially improving tolerability."

The study also provides important dose-selection insight. Investigators observed that meaningful MBD reduction appeared to occur at relatively low Endoxifen plasma concentrations, with the response reaching an approximate 20% decrease at concentrations of roughly 3–4 ng/mL, and with no substantial additional density reduction at higher concentrations. In contrast, vasomotor symptoms appeared more prominent at higher concentrations, supporting the 1 mg dose as the preferred candidate for future prevention studies.

Dr. Quay continued, "Prevention requires a paradigm shift from current cancer treatment. A medicine intended for healthy women at elevated risk must be effective, convenient, and acceptable over time. We believe the KARISMA Endoxifen trial gives us a clear signal that low-dose Endoxifen can produce a biologically meaningful reduction in mammographic breast density with a tolerability profile that may support long-term use. That is the central value proposition for Endoxifen in this setting."

The authors concluded that both 1 mg and 2 mg Endoxifen significantly reduced MBD to a degree comparable to the established 20 mg dose of tamoxifen, and that the 1 mg dose indicated superior tolerability. The authors also noted that future studies are needed to determine whether Endoxifen reduces incidences of breast cancer in women at increased risk. The Karolinska Institutet news release can be found here: New treatment with fewer side effects reduces breast density | Karolinska Institutet.

Atossa believes these results strengthen the rationale for advancing Endoxifen as a potential MBD reduction therapy, particularly for women with elevated MBD or other risk factors who may benefit from endocrine risk reduction but are reluctant to use currently available options.

About the KARISMA Endoxifen Trial

The KARISMA Endoxifen trial was a proof-of-concept, dose-determining, double-blind, randomized, placebo-controlled Phase 2 clinical trial conducted in Sweden. The study enrolled 240 healthy premenopausal women aged 40 to 55 years who were participating in the national mammography screening program in Stockholm, Sweden. Participants were randomized 1:1:1 to receive placebo, 1 mg Endoxifen, or 2 mg Endoxifen daily for six months. The primary objective was to evaluate the effect of Endoxifen on MBD. Safety and tolerability were also assessed. The study is registered at www.ClinicalTrials.gov under identifier NCT05068388.

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 Endoxifen, the potential for 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 for our lead program, 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.

SOURCE Atossa Therapeutics Inc