Atossa Therapeutics Streamlines EVANGELINE Breast Cancer Clinical Trial to Prioritize for 2026 NDA-Enabling Activities

Rhea-AI Summary

Atossa Therapeutics (NASDAQ: ATOS) amended its Phase 2 EVANGELINE study of (Z)-endoxifen in premenopausal ER+/HER2– early breast cancer to a single-arm, open-label, non-registrational design. The amendment reduces planned enrollment from 214 to 40–65 patients, implements a Cohort A two-stage futility rule using Week-4 Ki-67 ≤10% for earlier go/no-go decisions, and retains unchanged patient-safety data collection and DSMC oversight. Run-in data showed a Week-4 Ki-67 ≤10% rate of 86%. The company says the change aims to cut future study costs, accelerate objective readouts, and prioritize NDA-enabling activities in 2026.

Positive

• Planned enrollment cut from 214 to 40–65 patients
• Run-in Week-4 Ki-67 ≤10% rate of 86%
• Two-stage futility rule enables earlier go/no-go decisions
• Focus on NDA-enabling activities in 2026

Negative

• Study changed to non-registrational Phase 2 design
• Smaller 40–65 patient size reduces statistical power versus 214

Insights

Clinical Development Strategist

Streamlining EVANGELINE shrinks sample size, speeds early biological readouts, and redirects resources to NDA work in 2026.

The company shifts EVANGELINE to a smaller, single-arm Phase 2 (now 40–65 patients versus the original 214) and adopts a two-stage futility rule in Cohort A using Week-4 Ki-67 ≤ 10% as an objective early stop criterion. This design reduces trial duration and costs and concentrates data collection on endpoints deemed most relevant for an NDA-enabling package while keeping safety monitoring and DSMC oversight unchanged.

Key dependencies and risks include reliance on short-interval biological signals rather than larger randomized comparisons, and the non-registrational design limits definitive efficacy claims. The prior run-in Ki-67 signal of 86 supports signal detection but does not prove clinical benefit; regulators typically expect more comprehensive evidence for approval. Operationally, smaller sample size raises statistical fragility and increases the impact of outliers on readouts.

Concrete items to monitor: the formal two-stage futility thresholds and outcomes at Week-4 for Cohort A, Week-24 RECIST results for Cohort B, and whether planned NDA-enabling activities proceed during 2026. Expect near-term cost and timeline clarity from early futility decisions and watch enrollment pace given the reduced target of 40–65 patients.

Changes are expected to reduce future study costs, accelerate objective readouts, and extend operating runway under current plans

SEATTLE, Oct. 6, 2025 /PRNewswire/ -- Atossa Therapeutics, Inc. (Nasdaq: ATOS; "Atossa" or the "Company), a clinical-stage biopharmaceutical company developing new approaches in breast cancer treatment and prevention, announces an amendment to its Phase 2 EVANGELINE study of (Z)-endoxifen in premenopausal women with newly diagnosed early-stage ER+/HER2- breast cancer. The amended, non-registrational design is expected to accelerate objective readouts while reducing projected future study costs, consistent with Atossa's focus on extending operating runway and deploying capital where it is most impactful. In 2026, Atossa is concentrating its resources on near-term, NDA-enabling activities for investigational (Z)-endoxifen.

"This amendment is about efficiency, focus, and financial discipline," said Steven Quay, M.D., Ph.D., Atossa's Chairman and Chief Executive Officer. "By streamlining EVANGELINE, we are rationalizing study spending and concentrating our strong balance sheet on the NDA-enabling package we plan to advance in 2026, without changing our safety oversight or commitment to rigorous data."

Capital Allocation Highlights

• Prioritizing runway and catalysts: The amended design is expected to reduce future EVANGELINE study costs and further focus on NDA-enabling work under Atossa's 2025-2026 operating plan
• Faster, objective decision points: Cohort A patients with an initial Ki-67 of > 10% employ a pre-specified two-stage futility rule using short-interval, objective endpoints (e.g., Week-4 Ki-67 ≤10%) to enable earlier go/no-go decisions. Cohort B will be for patients with initial Ki-67 of < 10%
• Safety unchanged: There is no change to patient-safety data collection or Data Safety Monitoring Committee (DSMC) oversight with this amendment
• Operational focus: A single-arm, open-label structure concentrates efforts on one regimen and the data elements most relevant to a future NDA

EVANGELINE Design Snapshot (As Amended)

• Study type: Single-arm, open-label, non-registrational Phase 2 in premenopausal women with ER+/HER2– breast cancer in the pre-surgical setting
• Cohort A (signal-seeking): Two-stage futility design assessing the Week-4 Ki-67 ≤10% rate to allow early stop if not promising
• Cohort B (estimation): Week-24 objective response (RECIST 1.1, central review)
• Rationale: Focus on objective, short-interval endpoints to inform development decisions efficiently while preserving patient safeguards
• Study size change: The original EVANGELINE study design included 214 patients. This amendment reduces the patient total to 40-65 patients

Clinical context

EVANGELINE run-in data previously presented at the 2024 San Antonio Breast Cancer Symposium showed a Week-4 Ki-67 ≤10% rate of 86% across evaluated (Z)-endoxifen dose levels with/without Ovarian Function Suppression (OFS). In 2021, Atossa reported an 86% response rate of Ki-67 < 10% for women on low dose (4 mg/day) endoxifen in the same pre-surgery neoadjuvant setting. Published comparators in similar settings report a 41% response rate with tamoxifen and a 78% response rate with an aromatase inhibitor and OFS (Nitz UA, et al., J Clin Oncol. 2022 Aug 10;40(23):2557-2567). However, no efficacy conclusions can be drawn from the ongoing study at this point. There is no change to patient safety data collection or Data Safety Monitoring Committee oversight by this amendment.

ABOUT EVANGELINE

EVANGELINE is a single-arm, open-label, non-registrational Phase 2 study evaluating investigational (Z)-endoxifen in premenopausal women with ER+/HER2– breast cancer in the pre-surgical setting. The trial uses short-interval, objective endpoints with a pre-specified two-stage futility rule to enable faster, data-driven decisions.

Participating U.S. centers include: Mayo Clinic Rochester; Mayo Clinic Arizona; Mayo Clinic Florida; Washington University School of Medicine; St. Elizabeth Healthcare; Bon Secours Cancer Institute; Vanderbilt-Ingram Cancer Center; Henry Ford Cancer Institute; Fred Hutch; Dana-Farber Cancer Institute; Baylor University; University of Arizona; Northwestern University; Avera Cancer Institute; and California Research Institute. For current site activation status and updates, see ClinicalTrials.gov (NCT05607004).

ABOUT (Z)-ENDOXIFEN

(Z)-endoxifen is an investigational, active metabolite of tamoxifen being developed by Atossa for hormone receptor–positive breast-cancer settings. Its safety and efficacy have not been established.

ABOUT ATOSSA THERAPEUTICS

Atossa Therapeutics, Inc. (Nasdaq: ATOS) is a clinical-stage biopharmaceutical company developing innovative therapies for significant unmet needs in breast cancer. Atossa's strategy emphasizes disciplined capital allocation, focusing resources on programs and data packages that can enable future regulatory submissions and potential commercialization. For more information, visit the Company's website at www.atossatherapeutics.com and refer to Atossa's filings with the U.S. Securities and Exchange Commission (SEC).

FORWARD-LOOKING STATEMENTS

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the anticipated impact of the EVANGELINE amendment; expected reductions in future study costs; expected timelines, operating runway, and capital allocation; and plans for NDA-enabling activities in 2026. Forward-looking statements are based on current expectations and are subject to risks and uncertainties that could cause actual results to differ materially. These risks include, without limitation, clinical, regulatory, operational, financial, and market risks; the possibility that study timelines or costs differ from current expectations; that clinical results may not support further development or regulatory submissions; and other risks described in Atossa's most recent periodic reports filed with the SEC, including the "Risk Factors" sections therein. Atossa undertakes no obligation to update forward-looking statements except as required by law.

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SOURCE Atossa Therapeutics Inc

FAQ

What change did Atossa announce for EVANGELINE (NASDAQ: ATOS) on October 6, 2025?

Atossa amended EVANGELINE to a single-arm, non-registrational Phase 2 with enrollment reduced to 40–65 patients.

How does the amended EVANGELINE design speed decisions for ATOS?

Cohort A uses a pre-specified two-stage futility rule and Week-4 Ki-67 ≤10% endpoints for earlier go/no-go reads.

Will patient safety monitoring change after the EVANGELINE amendment for ATOS?

No. Patient-safety data collection and DSMC oversight remain unchanged.

What clinical signal did EVANGELINE run-in data report for (Z)-endoxifen?

Run-in data showed a Week-4 Ki-67 ≤10% rate of 86% across evaluated dose levels.

How will the EVANGELINE amendment affect Atossa’s 2026 plans (NASDAQ: ATOS)?

The amendment is intended to reduce study costs and concentrate resources on NDA-enabling activities in 2026.