Atossa Therapeutics Proposes Potentially Groundbreaking Study Aimed at Reducing Interval Breast Cancer in High-Risk Women at AACR 2025
Atossa Therapeutics has proposed a groundbreaking Phase 3 clinical study called SMART 2.0 at the AACR 2025 Annual Meeting. The study aims to investigate (Z)-endoxifen, a Selective Estrogen Receptor Modulator (SERM), for reducing interval breast cancer in high-risk women.
Key highlights:
- The study targets interval breast cancers, which occur between regular mammography screenings and are typically more aggressive
- Low-dose (1mg) Z-endoxifen reduced mammographic density by nearly 20% at six months in Phase 2 KARISMA trial
- Side effects were not statistically different from placebo
- The proposed trial will use AI Risk modeling to identify and randomize participants
- Primary endpoint: measuring reduction in interval breast cancer incidence over two years
This research represents a potential advancement in breast cancer prevention, offering a safer alternative to existing treatments like tamoxifen.
Atossa Therapeutics ha presentato uno studio clinico di Fase 3 innovativo chiamato SMART 2.0 durante l'AACR 2025 Annual Meeting. Lo studio mira a valutare (Z)-endoxifen, un modulatore selettivo del recettore degli estrogeni (SERM), per ridurre il rischio di cancro al seno ad intervallo nelle donne ad alto rischio.
Punti chiave:
- Lo studio si concentra sui tumori al seno ad intervallo, che si sviluppano tra le mammografie di controllo e sono generalmente più aggressivi
- La somministrazione a basso dosaggio (1mg) di Z-endoxifen ha ridotto la densità mammografica di quasi il 20% dopo sei mesi nella fase 2 dello studio KARISMA
- Gli effetti collaterali non sono risultati significativamente diversi rispetto al placebo
- Il trial proposto utilizzerà modelli di rischio basati sull'intelligenza artificiale per selezionare e randomizzare i partecipanti
- Obiettivo primario: misurare la riduzione dell'incidenza del cancro al seno ad intervallo nell'arco di due anni
Questa ricerca rappresenta un possibile progresso nella prevenzione del cancro al seno, offrendo un'alternativa più sicura ai trattamenti attuali come il tamoxifene.
Atossa Therapeutics ha propuesto un estudio clínico innovador de Fase 3 llamado SMART 2.0 en la Reunión Anual AACR 2025. El estudio tiene como objetivo investigar (Z)-endoxifen, un modulador selectivo del receptor de estrógeno (SERM), para reducir el cáncer de mama intervalo en mujeres de alto riesgo.
Puntos clave:
- El estudio se enfoca en los cánceres de mama intervalo, que ocurren entre las mamografías regulares y suelen ser más agresivos
- La dosis baja (1 mg) de Z-endoxifen redujo la densidad mamográfica en casi un 20% a los seis meses en el ensayo de Fase 2 KARISMA
- Los efectos secundarios no fueron estadísticamente diferentes al placebo
- El ensayo propuesto utilizará modelos de riesgo basados en IA para identificar y asignar aleatoriamente a los participantes
- Objetivo principal: medir la reducción en la incidencia de cáncer de mama intervalo durante dos años
Esta investigación representa un posible avance en la prevención del cáncer de mama, ofreciendo una alternativa más segura a tratamientos existentes como el tamoxifeno.
Atossa Therapeutics는 AACR 2025 연례 회의에서 SMART 2.0이라는 혁신적인 3상 임상 연구를 제안했습니다. 이 연구는 고위험 여성에서 간격 유방암을 줄이기 위해 선택적 에스트로겐 수용체 조절제(SERM)인 (Z)-endoxifen을 조사하는 것을 목표로 합니다.
주요 내용:
- 이 연구는 정기 유방촬영 검사 사이에 발생하며 보통 더 공격적인 간격 유방암을 대상으로 합니다
- 저용량(1mg) Z-endoxifen은 2상 KARISMA 시험에서 6개월 만에 유방 밀도를 거의 20% 감소시켰습니다
- 부작용은 위약과 통계적으로 유의미한 차이가 없었습니다
- 제안된 시험은 AI 위험 모델링을 사용하여 참가자를 선정하고 무작위 배정할 예정입니다
- 주요 평가 지표: 2년 동안 간격 유방암 발생률 감소 측정
이 연구는 기존 타목시펜과 같은 치료법보다 안전한 대안을 제공하며 유방암 예방에 있어 중요한 진전을 의미합니다.
Atossa Therapeutics a proposé une étude clinique de phase 3 révolutionnaire appelée SMART 2.0 lors de la réunion annuelle AACR 2025. L'étude vise à examiner (Z)-endoxifène, un modulateur sélectif des récepteurs aux œstrogènes (SERM), pour réduire le cancer du sein d'intervalle chez les femmes à haut risque.
Points clés :
- L'étude cible les cancers du sein d'intervalle, qui surviennent entre les mammographies régulières et sont généralement plus agressifs
- Une faible dose (1 mg) de Z-endoxifène a réduit la densité mammographique d'environ 20 % à six mois lors de l'essai de phase 2 KARISMA
- Les effets secondaires n'étaient pas statistiquement différents du placebo
- L'essai proposé utilisera la modélisation des risques par IA pour identifier et randomiser les participantes
- Critère principal : mesurer la réduction de l'incidence du cancer du sein d'intervalle sur deux ans
Cette recherche représente une avancée potentielle dans la prévention du cancer du sein, offrant une alternative plus sûre aux traitements existants comme le tamoxifène.
Atossa Therapeutics hat auf dem AACR 2025 Jahreskongress eine bahnbrechende Phase-3-Studie namens SMART 2.0 vorgestellt. Die Studie zielt darauf ab, (Z)-Endoxifen, einen selektiven Estrogenrezeptormodulator (SERM), zur Verringerung von Intervall-Brustkrebs bei Hochrisikopatientinnen zu untersuchen.
Wichtige Punkte:
- Die Studie richtet sich auf Intervall-Brustkrebs, der zwischen regulären Mammographie-Screenings auftritt und typischerweise aggressiver ist
- Niedrigdosiertes (1 mg) Z-Endoxifen reduzierte die mammographische Dichte in der Phase-2-KARISMA-Studie nach sechs Monaten um fast 20 %
- Nebenwirkungen unterschieden sich statistisch nicht vom Placebo
- Die vorgeschlagene Studie wird KI-Risikomodellierung zur Identifikation und Randomisierung der Teilnehmer verwenden
- Primärer Endpunkt: Messung der Reduktion der Intervall-Brustkrebs-Inzidenz über zwei Jahre
Diese Forschung stellt einen potenziellen Fortschritt in der Brustkrebsprävention dar und bietet eine sicherere Alternative zu bestehenden Behandlungen wie Tamoxifen.
- Phase 2 KARISMA trial showed ~20% reduction in mammographic density at 6 months
- Low-dose (1mg) Z-endoxifen showed side effects statistically similar to placebo
- Potential expansion into preventative breast cancer treatment market through SMART 2.0 study
- Advanced AI Risk model integration for patient screening, showing technological advancement
- Phase 3 SMART 2.0 study is only proposed/planned, not yet initiated
- Future study requires potential partnerships to advance
- No immediate revenue generation potential as still in clinical stage
- Regulatory approval timeline remains uncertain
Insights
Atossa's Phase 3 framework for (Z)-endoxifen shows promise for preventing aggressive interval breast cancers with better tolerability than existing options.
Atossa's outlined framework for the Phase 3 SMART 2.0 study represents a strategic approach to breast cancer prevention that targets a significant unmet need. The trial would evaluate oral (Z)-endoxifen in reducing interval breast cancers - those diagnosed between regular mammography screenings that are typically more aggressive and difficult to treat.
What makes this approach scientifically notable is its focus on mammographic density, a well-established modifiable risk factor that also complicates early detection. The company's Phase 2 KARISMA trial demonstrated their low-dose (1mg) formulation reduced mammographic density by
The proposed two-year randomized study would leverage AI risk modeling for patient selection, with a primary endpoint measuring reduction in interval breast cancer incidence. While still in planning stages requiring partnerships to advance, this approach could potentially transform the breast cancer prevention landscape by offering an intervention with an improved safety profile targeting high-risk women most likely to benefit.
Atossa's Phase 3 framework signals pipeline advancement but remains a future aspiration requiring partnerships, not an imminent revenue driver.
This announcement represents strategic positioning rather than a material clinical milestone for Atossa. The company is leveraging positive Phase 2 KARISMA data showing mammographic density reduction with favorable tolerability to build a case for advancing to Phase 3. The explicit characterization as a "future research program and potential partnership opportunity" signals that Atossa is seeking collaborators to fund and execute this large-scale study.
From a pipeline development perspective, this framework demonstrates continued progress for (Z)-endoxifen and potential expansion into prevention markets beyond treatment indications. The company's approach targets a differentiated position against tamoxifen with potentially better tolerability, which could support commercial success if eventually approved.
However, investors should recognize this represents long-term strategic planning rather than near-term catalysts. The pathway from framework presentation to actual Phase 3 initiation would require securing partnerships, regulatory alignment, and significant funding. No timeline is provided for trial initiation, and the aspirational language indicates this remains a conceptual program rather than an imminent development that would impact Atossa's valuation in the short term.
SEATTLE, April 29, 2025 (GLOBE NEWSWIRE) -- Atossa Therapeutics, Inc. (Nasdaq: ATOS) (“Atossa” or the “Company”), a clinical-stage biopharmaceutical company developing innovative medicines for breast cancer, today outlined a framework for a pioneering Phase 3 clinical study titled SMART 2.0. The proposed trial would investigate the potential of oral (Z)-endoxifen, a potent Selective Estrogen Receptor Modulator (SERM) for estrogen receptor inhibition, to significantly reduce interval breast cancer in women identified as high-risk through advanced mammographic screening techniques. The proposed SMART 2.0 study was presented at the American Association for Cancer Research (AACR) Annual Meeting and represents a future research program and potential partnership opportunity to advance this critical initiative for women at high risk of breast cancer.
Interval breast cancers, diagnosed between regular mammography screenings, are typically more aggressive and challenging to treat than screen-detected cancers. Mammographic density has been recognized as a critical, modifiable risk factor for breast cancer and can complicate early detection. Previous research indicates (Z)-endoxifen, like tamoxifen, effectively reduces breast density and potentially enhances mammogram sensitivity. However, the adverse effects associated with tamoxifen limit its widespread use.
Atossa’s innovative approach utilizes low-dose (1mg) Z-endoxifen, which reduced mammographic density by nearly 20 percent at six months and systemic side effects that were not statistically different than placebo in the Phase 2 KARISMA trial - an important step toward lowering the risk of interval breast cancer. The proposed SMART 2.0 trial would randomize participants identified by leveraging an AI Risk model into treatment and placebo groups to evaluate the effectiveness of (Z)-endoxifen over two years. The primary endpoint would measure the relative reduction in interval breast cancer incidence and tolerability compared to placebo over a two-year period of time.
"The SMART 2.0 study proposal represents a significant step forward for the advancement of breast cancer prevention," said Steven C. Quay, CEO of Atossa Therapeutics. "By targeting mammographic density with Z-endoxifen, we hope to establish a safer, more effective preventive therapy for women at high risk."
The company aspires to conduct a trial such as this in the future in an effort to provide the pivotal data required for regulatory approval of Z-endoxifen as a preventative treatment option.
About (Z)-Endoxifen
(Z)-endoxifen is one of the most potent Selective Estrogen Receptor Modulator (SERM) for estrogen receptor inhibition and may cause estrogen receptor degradation. It has also been shown to have efficacy in the setting of patients with tumor resistance to other hormonal treatments. In addition to its potent anti-estrogen effects, (Z)-endoxifen has been shown to target PKCβ1, a known oncogenic protein, at clinically attainable blood concentrations. Finally, (Z)-endoxifen appears to deliver similar or even greater bone agonistic effects while resulting in little or no endometrial proliferative effects compared with standard treatments, like tamoxifen.
Atossa is developing a proprietary oral formulation of (Z)-endoxifen that is encapsulated to bypass the stomach, as acidic conditions in the stomach convert a significant proportion of (Z)-endoxifen to the inactive (E)-endoxifen. Atossa’s (Z)-endoxifen has been shown to be well tolerated in clinical studies of women with and without breast cancer. (Z)-endoxifen is currently being studied both for the treatment and prevention of breast cancer, including a program in metastatic breast cancer that was announced earlier this year.
About Atossa Therapeutics
Atossa Therapeutics, Inc. (Nasdaq: ATOS) is a clinical-stage biopharmaceutical company dedicated to transforming breast cancer treatment through innovative science and patient-focused solutions. The company’s lead product candidate, (Z)-endoxifen, is a highly potent SERM designed for use across the breast cancer spectrum, including prevention, neoadjuvant, adjuvant, and metastatic settings. Atossa is committed to advancing its robust clinical research programs to improve patient outcomes while creating sustainable value for shareholders. For more information, visit atossatherapeutics.com.
FORWARD LOOKING STATEMENTS
This press release contains certain information that may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. We may identify these forward-looking statements by the use of words such as “expect,” “potential,” “continue,” “may,” “will,” “should,” “could,” “would,” “seek,” “intend,” “plan,” “estimate,” “anticipate,” “believe,” “design,” “predict,” “future,” or other comparable words. All statements made in this press release that are not statements of historical fact, including statements regarding data related to the (Z)-endoxifen program, the safety, tolerability and efficacy of (Z)-endoxifen, the potential of (Z)-endoxifen as a breast cancer prevention and treatment agent, the potential indications that the Company may pursue for (Z)-endoxifen, the potential for (Z)-endoxifen to receive regulatory approval, benefits of the Company’s strategy of pursuing a metastatic indication for (Z)-endoxifen, the expected design and enrollment of trials and timing of data and related publications, and the potential market and growth opportunities for the Company, 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 risks and uncertainties associated with: our ability to obtain patent coverage for our product candidates; macroeconomic conditions and increasing geopolitical instability; the expected timing of releasing data; any variation between interim or preliminary and final clinical results or analysis; actions and inactions by the FDA and foreign regulatory bodies; the outcome or timing of regulatory approvals needed by Atossa, including those needed to continue our planned (Z)-endoxifen trials; our ability to satisfy regulatory requirements; our ability to regain compliance or maintain compliance with the continued listing requirements of the Nasdaq Stock Market; our ability to successfully develop and commercialize new therapeutics; the success, costs and timing of our development activities, including our ability to successfully initiate or complete our clinical trials, including our (Z)-endoxifen trials; our anticipated rate of patient enrollment; our ability to contract with third-parties and their ability to perform adequately; our estimates on the size and characteristics of our potential markets; our ability to successfully defend litigation and other similar complaints and to establish and maintain intellectual property rights covering our products; whether we can successfully complete our clinical trial of oral (Z)-endoxifen in women with mammographic breast density and our trials of (Z)-endoxifen in women with breast cancer, and whether the studies will meet their objectives; our expectations as to future financial performance, expense levels and capital sources, including our ability to raise capital; our ability to attract and retain key personnel; our anticipated working capital needs and expectations around the sufficiency of our cash reserves; and other risks and uncertainties detailed from time to time in Atossa’s filings with the Securities and Exchange Commission, including without limitation its Annual Reports on Form 10-K and Quarterly Reports on 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, whether as a result of new information, future events or circumstances or otherwise.
Contact:
Michael Parks
VP, Investor and Public Relations
484-356-7105
michael.parks@atossainc.com
FAQ
What is the SMART 2.0 Phase 3 trial proposed by Atossa (ATOS) for breast cancer prevention?
How effective is Atossa's (Z)-endoxifen in reducing mammographic density based on Phase 2 results?
What advantages does Atossa's Z-endoxifen have over tamoxifen for breast cancer prevention?
When will Atossa (ATOS) present the SMART 2.0 study framework at AACR?
What is interval breast cancer and why is Atossa targeting it with Z-endoxifen?
