On July 29, 2025 Atossa Therapeutics, Inc. (NASDAQ: ATOS), a clinical-stage biopharmaceutical company developing innovative medicines in oncology, reported positive written feedback from the U.S. Food and Drug Administration (FDA) regarding the company’s proposed dose optimization trial of (Z)-endoxifen for the treatment of estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (Press release, Atossa Therapeutics, JUL 29, 2025, View Source;metastatic-breast-cancer-302516013.html [SID1234654614]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The FDA has provided highly constructive responses ahead of the scheduled pre-Investigational New Drug (IND) meeting, affirming key elements of Atossa’s clinical development plan, negating the need for a virtual meeting, and paving the way for a potential IND submission targeted for the fourth quarter of 2025.
"These FDA responses mark a significant milestone for the Company and are supportive of our comprehensive approach to developing (Z)-endoxifen for metastatic breast cancer," stated Dr. Steven Quay, Atossa’s Chief Executive Officer and Chairman of the Board. "The detailed feedback received significantly advances our goal of submitting an IND by year-end. Importantly, the FDA’s support of our dose optimization strategy and general agreement with our nonclinical data package leave us confident in our scientific rationale and overall regulatory approach."
Key Highlights:
Dose Optimization Strategy Affirmed: FDA agreed that existing clinical and nonclinical data are sufficient to initiate Part A (monotherapy) of the proposed dose optimization study and provided clear guidance on randomization cohort sizes and study design enhancements.
Combination Study Support: The Agency agreed with the scientific rationale for combining (Z)-endoxifen with approved breast cancer standard-of-care therapies, such as some CDK4/6 inhibitors, PI3K inhibitors, mTOR inhibitors, and capecitabine. While not all combinations will be investigated in this study, FDA guidance on the matter is helpful in narrowing the strategic approach for the potential IND.
Nonclinical Data Package Deemed Adequate: FDA indicated the existing nonclinical safety data package is adequate to proceed without additional general toxicity or neurotoxicity studies.
Agreement on Cardiac Safety Assessments for Monotherapy: FDA confirmed Atossa’s cardiac safety assessment plan, including serial electrocardiograms (ECGs) and QT interval monitoring, is sufficient for the monotherapy portion of the trial.
Next steps: In the coming weeks, Atossa will announce plans for the target patient population, combination backbone, and overall trial design for the upcoming dose-ranging study. The Agency acknowledged the Company’s plan to file an IND in 2025 and encouraged Atossa to incorporate specific safety and eligibility refinements in the final protocol, which the Company has accepted.
Dr. Quay continued, "With the FDA’s feedback now in hand, Atossa is energized and moving quickly. We believe the company is well positioned to maintain strategic momentum and meet regulatory milestones, bringing us closer to delivering (Z)-endoxifen to patients in need and driving shareholder value. Further updates will be provided as the trial design is finalized, and next steps are implemented."
Atossa’s progress reflects the strong strategic momentum promised in the March 11, 2025 announcement of a metastatic focus; momentum that aligns well with FDA expectations and regulatory standards, including fulfilling Project Optimus requirements, a crucial next step in advancing (Z)-endoxifen toward potential approval.
The FDA’s Project Optimus initiative emphasizes data-driven dose exploration to maximize benefit and minimize toxicity. In line with this guidance, Atossa will explore multiple dose levels in its upcoming clinical study to define the optimal dose for combination therapy, while seeking to maintain a balance between efficacy and patient safety.
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.
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. In over 700 subjects (healthy volunteers and breast cancer patients), doses up to 360 mg/day have been administered with no maximum tolerated dose (MTD) identified, supporting continued dose-ranging exploration.
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. 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.