Atossa Therapeutics Announces Full Results from I‑SPY 2 Endocrine‑Optimization Sub‑Study Evaluating Low‑Dose (Z)‑Endoxifen

Feasibility endpoint achieved; rapid Ki‑67 suppression and substantial MRI‑confirmed tumor shrinkage observed with favorable safety profile

SEATTLE, May 14, 2025 /PRNewswire/ -- Atossa Therapeutics, Inc. (Nasdaq: ATOS) ("Atossa" or the "Company"), a clinical-stage biopharmaceutical company developing innovative medicines for breast cancer, today reported full results from the Phase 2 Endocrine Optimization Pilot (EOP) sub‑study within the I‑SPY 2 TRIAL evaluating low‑dose oral (Z)‑endoxifen (10 mg daily) as a neoadjuvant treatment in 20 women with stage II/III estrogen‑receptor–positive (ER+), HER2‑negative breast cancer.

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 U.S. patents and numerous pending applications worldwide.

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.

SOURCE Atossa Therapeutics Inc