Atossa Therapeutics Announces Full Results from I‑SPY 2 Endocrine‑Optimization Sub‑Study Evaluating Low‑Dose (Z)‑Endoxifen
Atossa Therapeutics (NASDAQ: ATOS) has reported full results from its Phase 2 Endocrine Optimization Pilot sub-study within the I-SPY 2 TRIAL, evaluating low-dose oral (Z)-endoxifen for treating stage II/III ER+, HER2-negative breast cancer. The study achieved its primary feasibility goal with 95% of participants completing at least 75% of planned dosing. Key findings showed median Ki-67 reduction from 10.5% to 5% by Week 3, and median functional tumor volume decreased 77.7%. The treatment demonstrated a favorable safety profile with mostly Grade 1 adverse events.
However, no participants achieved pathologic complete response (pCR), with residual cancer burden classes showing moderate to extensive residual disease. This was expected due to the intentionally low 10mg dose. Atossa is now enrolling participants for additional I-SPY 2 cohorts testing higher doses (40mg) of (Z)-endoxifen, both alone and combined with abemaciclib, with top-line data expected in 2026.
Atossa Therapeutics (NASDAQ: ATOS) ha riportato i risultati completi del suo sottostudio pilota di ottimizzazione endocrina di Fase 2 all'interno della sperimentazione I-SPY 2, valutando il (Z)-endoxifen orale a basso dosaggio per il trattamento del carcinoma mammario ER+, HER2-negativo in stadio II/III. Lo studio ha raggiunto il suo obiettivo primario di fattibilità con il 95% dei partecipanti che ha completato almeno il 75% della dose pianificata. I risultati principali hanno mostrato una riduzione mediana del Ki-67 dal 10,5% al 5% entro la terza settimana, e un calo mediano del volume tumorale funzionale del 77,7%. Il trattamento ha dimostrato un profilo di sicurezza favorevole, con eventi avversi per lo più di grado 1.
Tuttavia, nessun partecipante ha raggiunto una risposta patologica completa (pCR), con classi di residuo tumorale che indicano una malattia residua da moderata a estesa. Ciò era previsto a causa della dose volutamente bassa di 10 mg. Atossa sta ora reclutando partecipanti per ulteriori coorti I-SPY 2 che testeranno dosi più elevate (40 mg) di (Z)-endoxifen, sia da solo che in combinazione con abemaciclib, con dati principali attesi nel 2026.
Atossa Therapeutics (NASDAQ: ATOS) ha informado los resultados completos de su subestudio piloto de optimización endocrina de Fase 2 dentro del ensayo I-SPY 2, evaluando el (Z)-endoxifen oral en dosis bajas para el tratamiento del cáncer de mama ER+, HER2-negativo en estadio II/III. El estudio alcanzó su objetivo principal de factibilidad con el 95% de los participantes completando al menos el 75% de la dosis planificada. Los hallazgos clave mostraron una reducción mediana del Ki-67 del 10,5% al 5% para la semana 3, y un volumen tumoral funcional mediano disminuyó un 77,7%. El tratamiento mostró un perfil de seguridad favorable con eventos adversos mayormente de grado 1.
Sin embargo, ningún participante logró una respuesta patológica completa (pCR), con clases de carga residual de cáncer que mostraron enfermedad residual de moderada a extensa. Esto era esperado debido a la dosis intencionalmente baja de 10 mg. Atossa ahora está inscribiendo participantes para cohortes adicionales del I-SPY 2 que prueban dosis más altas (40 mg) de (Z)-endoxifen, tanto solo como combinado con abemaciclib, con datos principales esperados en 2026.
Atossa Therapeutics (NASDAQ: ATOS)는 I-SPY 2 임상시험 내 2상 내분비 최적화 파일럿 하위 연구의 전체 결과를 발표했습니다. 이 연구는 2기/3기 ER+, HER2 음성 유방암 치료를 위해 저용량 경구 (Z)-엔독시펜을 평가했습니다. 연구는 참가자의 95%가 계획된 투여량의 최소 75%를 완료함으로써 주요 실행 가능성 목표를 달성했습니다. 주요 결과로는 3주차에 Ki-67 중간값이 10.5%에서 5%로 감소했고, 기능적 종양 부피는 77.7% 감소했습니다. 치료는 대부분 1등급 부작용으로 안전성 프로필이 양호했습니다.
하지만, 참가자 중 병리학적 완전 반응(pCR)은 없었으며, 잔존 암 부담 등급은 중등도에서 광범위한 잔존 질환을 나타냈습니다. 이는 의도적으로 낮은 10mg 용량 때문으로 예상되었습니다. Atossa는 현재 (Z)-엔독시펜의 더 높은 용량(40mg)을 단독 및 아베마시클립과 병용하여 테스트하는 추가 I-SPY 2 코호트의 참가자를 모집 중이며, 주요 데이터는 2026년에 발표될 예정입니다.
Atossa Therapeutics (NASDAQ : ATOS) a publié les résultats complets de son sous-étude pilote d'optimisation endocrinienne de phase 2 dans le cadre de l'essai I-SPY 2, évaluant le (Z)-endoxifène oral à faible dose pour le traitement du cancer du sein ER+, HER2 négatif de stade II/III. L'étude a atteint son objectif principal de faisabilité avec 95 % des participants ayant complété au moins 75 % de la dose prévue. Les résultats clés ont montré une réduction médiane du Ki-67 de 10,5 % à 5 % à la semaine 3, et un volume tumoral fonctionnel médian en baisse de 77,7 %. Le traitement a démontré un profil de sécurité favorable, avec principalement des événements indésirables de grade 1.
Cependant, aucun participant n'a atteint une réponse pathologique complète (pCR), avec des classes de charge résiduelle tumorale indiquant une maladie résiduelle modérée à étendue. Cela était attendu en raison de la dose intentionnellement faible de 10 mg. Atossa recrute désormais des participants pour des cohortes supplémentaires de l'I-SPY 2 testant des doses plus élevées (40 mg) de (Z)-endoxifène, seul et en combinaison avec l'abémaciclib, avec des données principales attendues en 2026.
Atossa Therapeutics (NASDAQ: ATOS) hat die vollständigen Ergebnisse seiner Phase-2-Endokrin-Optimierungs-Pilotstudie innerhalb der I-SPY 2-Studie veröffentlicht, in der niedrig dosiertes orales (Z)-Endoxifen zur Behandlung von Brustkrebs im Stadium II/III ER+, HER2-negativ untersucht wurde. Die Studie erreichte ihr primäres Durchführbarkeitsziel mit 95 % der Teilnehmer, die mindestens 75 % der geplanten Dosierung einnahmen. Wichtige Ergebnisse zeigten eine mittlere Ki-67-Reduktion von 10,5 % auf 5 % bis Woche 3 sowie eine Abnahme des medianen funktionellen Tumorvolumens um 77,7 %. Die Behandlung zeigte ein günstiges Sicherheitsprofil mit überwiegend Grad-1-Nebenwirkungen.
Es erreichte jedoch kein Teilnehmer eine pathologische Komplettremission (pCR), wobei die Klassen der verbliebenen Krebsbelastung auf eine mäßige bis ausgedehnte Restkrankheit hinwiesen. Dies war aufgrund der absichtlich niedrigen Dosis von 10 mg erwartet worden. Atossa rekrutiert nun Teilnehmer für weitere I-SPY 2-Kohorten, die höhere Dosen (40 mg) von (Z)-Endoxifen sowohl allein als auch in Kombination mit Abemaciclib testen, wobei die wichtigsten Daten für 2026 erwartet werden.
- 95% of participants completed at least 75% of planned dosing, exceeding the 75% threshold
- Significant tumor shrinkage with 77.7% decrease in median functional tumor volume
- Well-tolerated safety profile with predominantly Grade 1 adverse events
- Demonstrated early anti-proliferative activity with Ki-67 reduction from 10.5% to 5%
- No participants achieved pathologic complete response (pCR)
- Residual cancer burden showed moderate to extensive residual disease
- Low 10mg dose insufficient for significant pathologic clearance
- Top-line data from higher dose trials not expected until 2026
Insights
Atossa's low-dose (Z)-endoxifen showed bioactivity but limited pathological response, setting stage for higher-dose trials targeting better outcomes.
The Phase 2 Endocrine Optimization Pilot sub-study results for Atossa's (Z)-endoxifen demonstrate a mixed clinical profile at the 10mg daily dose. While the trial successfully met its primary feasibility endpoint with 95% of participants completing at least 75% of planned dosing (exceeding the 75% threshold), the pathological responses were limited.
From a biomarker perspective, the results show promising early signals. The Ki-67 proliferation marker decreased from a median of 10.5% at baseline to 5% by Week 3, with 65% of patients achieving the target Ki-67 ≤ 10%. Tumor shrinkage was also observed with a 77.7% median reduction in functional tumor volume and a 36.8% reduction in longest tumor diameter from baseline to surgery.
However, the critical pathologic findings reveal no patients achieved pathologic complete response (pCR), with residual cancer burden (RCB) classes skewing toward RCB-II/III, indicating moderate to extensive residual disease. This wasn't unexpected, as the company acknowledges that significant pathologic clearance typically requires higher systemic exposures to (Z)-endoxifen (>500 ng/mL) to enable inhibition of both PKCβ1 and ERα. The 10mg dose was intentionally selected as a preliminary dose to establish tolerability.
The safety profile appears favorable, with predominantly Grade 1 adverse events (mainly hot flushes and fatigue), and only three Grade 3 events in a single patient deemed unrelated to the study drug.
The results validate Atossa's dual-targeting hypothesis (ERα and PKCβ1) but highlight the need for higher dosing. The company is now enrolling patients in additional I-SPY 2 cohorts testing a higher 40mg daily dose, both alone and in combination with the CDK4/6 inhibitor abemaciclib, with data expected in 2026.
Feasibility endpoint achieved; rapid Ki‑67 suppression and substantial MRI‑confirmed tumor shrinkage observed with favorable safety profile
Key Findings:
- Primary feasibility goal surpassed – 95 percent of participants (19/20) completed at least 75 percent of planned dosing, far exceeding the predefined 75 percent threshold.
- Early anti‑proliferative activity – Median Ki‑67 fell from 10.5 percent at baseline to 5 percent by Week 3 (prior to ovarian suppression); 65 percent of patients achieved Ki‑67 ≤ 10 percent at that time point, and suppression was maintained at surgery.
- Robust imaging response – Median functional tumor volume (FTV) measurement (performed at baseline, week 3, week 12, and at surgery) decreased 77.7 percent (range 9.0 cc → 1.2 cc) from baseline to surgery, and the longest tumor diameter from baseline to preoperative MRI was reduced by 36.8 percent.
- Well‑tolerated safety profile – Adverse events were predominantly Grade 1; vasomotor symptoms (hot flushes) and fatigue were most common. Only three Grade 3 events (two skin infections, one post‑procedural infection) occurred in a single patient and were deemed unrelated to study drug; no Grade 4 or Grade 5 events were reported.
Pathologic Findings:
No participants achieved a pathologic complete response (pCR), and residual cancer burden (RCB) classes skewed toward RCB‑II/III, indicating moderate to extensive residual disease. This result was anticipated based on earlier window‑of‑opportunity (neoadjuvant) studies that showed significant pathologic clearance typically requires higher systemic exposures to (Z)-endoxifen (> 500 ng/mL) to enable inhibition of PKCβ1 in addition to ERα. The 10 mg dose in this pilot was intentionally selected to establish tolerability and early biologic activity in the endocrine‑naïve setting; therefore, limited pCR rates at this dose are consistent with prior dose–response observations.
"These results show that even at a low capsule strength (Z)‑endoxifen is bioactive, producing rapid Ki‑67 suppression and meaningful tumor shrinkage, while remaining highly tolerable. The study strengthens our scientific hypothesis that dual targeting of ERα and PKCβ1 is key to inducing a pathological response," said Steven Quay, M.D., Ph.D., President and Chief Executive Officer of Atossa. "Importantly, it paves the way for our ongoing I‑SPY 2 cohorts evaluating higher, potentially PKCβ1‑engaging doses of (Z)‑endoxifen alone and in combination with the CDK4/6 inhibitor abemaciclib, where we aim to translate early biomarker gains into deeper pathologic responses."
Atossa is actively enrolling participants into an additional I‑SPY 2 cohort testing (Z)‑endoxifen at a 40 mg daily dose and in combination with abemaciclib, with and without ovarian function suppression. Top‑line data from these arms are expected beginning in 2026.
About (Z)-Endoxifen
(Z)-endoxifen is a highly potent Selective Estrogen Receptor Modulator (SERM) with demonstrated ability to inhibit—and potentially degrade—estrogen receptors. It has shown activity even in tumors that have developed resistance to other endocrine therapies. Beyond its anti-estrogenic properties, (Z)-endoxifen also targets protein kinase C beta 1 (PKCβ1), an oncogenic signaling protein, at clinically achievable blood levels. Importantly, (Z)-endoxifen seems to deliver comparable or superior bone-protective effects relative to tamoxifen, while exhibiting minimal or no endometrial proliferative activity—addressing key limitations of current standard-of-care therapies.
Atossa is developing a proprietary oral formulation of (Z)-endoxifen that is enteric-coated to bypass stomach acid, which would otherwise convert the active (Z)-isomer to its inactive (E)-form. This innovation ensures optimal bioavailability and therapeutic integrity. Clinical studies have shown Atossa's (Z)-endoxifen to be well tolerated in both healthy women and those with breast cancer.
Atossa is prioritizing the development of (Z)-endoxifen for the treatment of metastatic breast cancer, where novel therapeutic options are urgently needed. The compound is currently being evaluated in three Phase 2 trials: one in women with ductal carcinoma in situ (DCIS) and two in women with ER+/HER2- breast cancer, including the EVANGELINE trial and the combination I-SPY study. Atossa's (Z)-endoxifen program is supported by a growing global intellectual property portfolio, including three recently issued
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.
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SOURCE Atossa Therapeutics Inc
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