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

Rhea-AI Summary

Atossa Therapeutics (Nasdaq: ATOS) announced publication of the KARISMA Endoxifen Phase 2 trial in JNCI showing that daily low-dose Endoxifen significantly reduced mammographic breast density (MBD) in healthy premenopausal women.

Both 1 mg and 2 mg doses reduced MBD versus placebo (1 mg: −19.3%, p=0.004; 2 mg: −26.5%, p<0.001) after six months, with a tolerability profile similar to placebo for 1 mg and no clinically significant lab or vital-sign changes reported.

Positive

• MBD reduction of 19.3% with 1 mg Endoxifen versus placebo
• MBD reduction of 26.5% with 2 mg Endoxifen versus placebo
• 1 mg tolerability similar to placebo with comparable discontinuations (5 vs 4)
• No clinically significant hematologic, chemistry, coagulation, or vital-sign changes reported

Negative

• Breast cancer incidence impact unproven: additional studies required to show reduced cancer events
• Higher discontinuations at 2 mg (11 participants) versus 1 mg (5) and placebo (4)
• Long-term safety and effectiveness beyond six months not established

News Market Reaction – ATOS

+3.94%

+3.94% Session close to close

In the May 6 session, ATOS gained 3.94%, reflecting a moderate positive market reaction.

Data tracked by StockTitan Argus on the day of publication.

Market Context

This announcement reports peer-reviewed Phase 2 data showing that low-dose Endoxifen (1 mg and 2 mg)...

Analysis

This announcement reports peer-reviewed Phase 2 data showing that low-dose Endoxifen (1 mg and 2 mg) achieved significant mammographic breast density reductions over 6 months in 240 healthy premenopausal women, with the 1 mg dose offering a tolerability profile close to placebo. The results build on Atossa’s broader Endoxifen strategy highlighted in recent regulatory and corporate filings. Investors may watch for future prevention trials, long-term safety data, and how the company funds development given rising R&D expenses and its existing at-the-market equity facility.

Key Figures

Participants: 240 healthy premenopausal women Treatment duration: 6 months MBD reduction (1 mg): 19.3% vs placebo (p=0.004) +5 more

8 metrics

Participants 240 healthy premenopausal women KARISMA Endoxifen Phase 2 trial enrollment

Treatment duration 6 months Daily Endoxifen or placebo administration period

MBD reduction (1 mg) 19.3% vs placebo (p=0.004) Reduction in mammographic breast density at 1 mg dose

MBD reduction (2 mg) 26.5% vs placebo (p<0.001) Reduction in mammographic breast density at 2 mg dose

Discontinuations placebo 4 participants Adverse events considered related to study drug in placebo arm

Discontinuations 1 mg 5 participants Adverse events considered related to 1 mg Endoxifen

Discontinuations 2 mg 11 participants Adverse events considered related to 2 mg Endoxifen

Effective plasma level 3–4 ng/mL, ~20% MBD decrease Concentration where meaningful density reduction observed

Historical Context

5 past events · Latest: May 04 (Positive)

Pattern 5 events

Date	Event	Sentiment	24h Move	Catalyst
May 04	FDA RPD designation	Positive	+9.9%	Rare Pediatric Disease designation for Endoxifen in McCune-Albright Syndrome.
Mar 25	Earnings and update	Negative	-13.1%	Higher 2025 operating expenses and year-end financial update with development focus.
Mar 19	Leadership additions	Positive	+0.4%	Hires of two medical directors to support breast oncology and rare disease programs.
Mar 12	Clinical data update	Positive	+5.7%	Preclinical Endoxifen data in Duchenne models presented at MDA conference.
Feb 11	Shareholder letter	Neutral	-16.0%	Review of 2025 progress, reverse split, cash position, and 2026 priorities.

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

Pattern Detected

Recent Endoxifen-related and regulatory milestones have often coincided with sizable price moves, with a mix of positive reactions to clinical/designation news and negative reactions around broader corporate or financial communications.

Recent Company History

Over the last few months, Atossa has concentrated on advancing its oral (Z)-endoxifen program across oncology and rare diseases. Key milestones include FDA Rare Pediatric Disease designation for McCune-Albright Syndrome on May 4, 2026 and earlier regulatory designations for Duchenne muscular dystrophy. The company also expanded clinical leadership and presented supportive preclinical data in Duchenne models. Shareholder letters and earnings updates highlighted higher operating expenses and strategic repositioning, which previously coincided with notable drawdowns. Today’s published Phase 2 MBD data fits the pattern of news deepening the Endoxifen story.

Key Terms

mammographic breast density, premenopausal, (z)-endoxifen, phase 2, +4 more

8 terms

mammographic breast density medical

"marked reduction of mammographic breast density (MBD)"

Mammographic breast density describes how much of the breast shows up as dense (firm tissue) versus fatty tissue on a mammogram; denser tissue appears whiter and can hide abnormalities much like fog on a window can hide shapes behind the glass. It matters to investors because higher density affects screening accuracy, drives demand for more advanced imaging and supplemental tests, influences regulatory and reimbursement decisions, and therefore impacts market size, product adoption, and potential liability for companies in diagnostics and women’s health.

premenopausal medical

"in 240 healthy premenopausal women enrolled through the Swedish"

Premenopausal describes the phase in a person's life before menopause, when natural menstrual cycles and reproductive hormones are still active. For investors, it signals a distinct patient or consumer group with specific healthcare needs—such as contraception, fertility care, hormone treatments and related testing—similar to how a particular customer segment shapes demand for certain products; understanding its size and characteristics helps forecast markets and regulatory or clinical trial impacts.

(z)-endoxifen medical

"Atossa Therapeutics Receives FDA Rare Pediatric Disease Designation for (Z)-Endoxifen"

(Z)-endoxifen is an active drug molecule formed when the body breaks down certain breast cancer medicines; it directly blocks estrogen signals that can fuel some tumors. Investors care because its safety, trial results, regulatory approvals, patent status and manufacturing plans determine commercial potential—similar to how a new engine design can make a car model more valuable if it proves safer, cheaper or more effective than rivals.

phase 2 medical

"The randomized, double-blind, placebo-controlled Phase 2 study evaluated"

Phase 2 is the mid-stage clinical trial where a new drug or treatment is tested in a larger group of patients to see if it works and to keep checking safety after initial human testing. Think of it as a field test that proves whether a product actually delivers its promised benefit. Investors watch Phase 2 closely because its results strongly influence a medicine’s chances of reaching the market, the size of its potential sales, and the company’s valuation.

randomized, double-blind, placebo-controlled medical

"The randomized, double-blind, placebo-controlled Phase 2 study evaluated"

A "randomized, double-blind, placebo-controlled" process is a method used to test the effectiveness of a new treatment or intervention. Participants are randomly assigned to different groups, with one receiving the real treatment and the other a fake version, called a placebo. Neither the participants nor the researchers know who is receiving which, which helps ensure unbiased results. For investors, this rigorous approach increases confidence that the findings are accurate and not influenced by guesswork or bias.

pharmacodynamic medical

"a recognized pharmacodynamic marker of response to endocrine"

Pharmacodynamic describes how a drug acts on the body — the biological effects it produces, how strong those effects are, and how long they last. For investors, pharmacodynamic data show whether a treatment actually works and at what dose, shaping expectations about a drug’s safety, effectiveness, regulatory success and market potential; think of it like testing how well a key turns a lock and whether it reliably opens the door.

vasomotor medical

"Adverse events were generally vasomotor in nature, consistent with"

Relating to the body’s control of blood vessel widening and narrowing, vasomotor describes the processes that change blood flow and body temperature—think of it like a thermostat that opens or closes pipes to adjust heat. Investors care because drugs or devices that affect vasomotor function can be key clinical targets or safety concerns, influence regulatory outcomes, and shape market demand for treatments addressing symptoms such as flushing, blood pressure changes, or circulation disorders.

metabolite medical

"Endoxifen, the most therapeutically active metabolite of tamoxifen."

A metabolite is a chemical produced when the body or a drug is broken down or used by cells — think of it as the crumbs left after digesting a meal. For investors, metabolites matter because they can be harmless, active (helping or changing a drug’s effect), or harmful, and their behavior drives safety tests, regulatory decisions, patent scope and a drug’s commercial prospects.

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• 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.

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SOURCE Atossa Therapeutics Inc

FAQ

What were the KARISMA trial results for Endoxifen (ATOS) on mammographic breast density?

Both 1 mg and 2 mg Endoxifen significantly reduced MBD versus placebo after six months. According to the company, 1 mg reduced MBD by 19.3% (p=0.004) and 2 mg by 26.5% (p<0.001).

Is the 1 mg Endoxifen dose tolerable for women at elevated breast cancer risk (ATOS)?

Yes, the 1 mg dose showed a tolerability profile similar to placebo in the six-month trial. According to the company, discontinuations related to study drug were similar between 1 mg (5) and placebo (4).

How does Endoxifen’s MBD reduction compare with tamoxifen for breast cancer prevention (ATOS)?

Endoxifen produced density reductions comparable to standard-dose tamoxifen at much lower doses. According to the company, both Endoxifen doses achieved reductions similar to reported tamoxifen effects.

Does the KARISMA trial show Endoxifen reduces actual breast cancer cases (ATOS)?

No, the trial showed MBD reduction but did not measure cancer incidence. According to the company, future studies are needed to determine whether Endoxifen reduces breast cancer events.

Were there safety or lab concerns reported in the KARISMA Endoxifen trial (ATOS)?

No clinically significant changes in labs, coagulation, urinalysis, blood pressure, heart rate, or physical exams were reported. According to the company, adverse events were generally vasomotor and consistent with expectations.

Which Endoxifen dose does Atossa plan to advance for prevention studies (ATOS)?

Atossa favors the 1 mg dose for future prevention work due to effective MBD reduction and better tolerability. According to the company, meaningful density reduction occurred at plasma concentrations linked to the 1 mg dose.