On August 20, 2025 Atossa Therapeutics, Inc. (Nasdaq: ATOS) ("Atossa" or the "Company"), a clinical-stage biopharmaceutical company developing innovative medicines for breast cancer, reported it has selected PSI, a leading global contract research organization (CRO), to operationalize and manage its planned (Z)-endoxifen monotherapy dose-ranging study in women with metastatic breast cancer (mBC) (Press release, Atossa Therapeutics, AUG 20, 2025, View Source [SID1234655412]). The study was designed following guidance from the U.S. Food and Drug Administration (FDA) and is intended to directly inform a subsequent Phase 3 trial.
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The global Phase 2, multi-center dose-ranging study is designed to evaluate (Z)-endoxifen monotherapy for safety, pharmacokinetics/pharmacodynamics, and preliminary anti-tumor activity. Patient enrollment is expected to follow the Investigational New Drug (IND) filing in Q4 2025, with topline data anticipated in 2026.
"This is a defining milestone for Atossa," said Dr. Steven Quay, Chairman and Chief Executive Officer of Atossa. "With PSI as our partner, we are advancing (Z)-endoxifen into its final steps before Phase 3. Unlike existing endocrine therapies, (Z)-endoxifen has demonstrated clinical activity even in tumors resistant to aromatase inhibitors and fulvestrant. If successful, this program could reshape the standard of care in breast cancer treatment, including in the metastatic setting, and deliver hope to patients who currently face limited options."
PSI is widely recognized for excellence in global oncology trial execution with the ability to move swiftly from Phase 2 into Phase 3 trials. In 2024, 93 percent of PSI-managed studies enrolled on time or ahead of schedule, leveraging its proprietary machine-learning feasibility platform, VISIONAL. Atossa selected PSI, following a highly competitive process, for its proven ability to:
Deliver regulatory-grade data through rigorous quality and compliance systems.
Consistently achieve on-time enrollment across diverse geographies.
Seamlessly scale programs into Phase 3 and pivotal studies, often reducing operational risk and accelerating timelines.
"We are excited to partner with Atossa on this pivotal study of (Z)-endoxifen. Based on our assessment, the program is designed to transition seamlessly into Phase 3, and we are allocating significant global resources to accelerate its execution. We believe this is a high-priority program with the potential to reshape the standard of care in metastatic breast cancer." — said Nick Sinackevich, PSI’s President.
Market Opportunity
Each year, approximately 5.6 percent of newly diagnosed invasive breast cancers in women in the U.S., or about 13,000 women annually, are diagnosed at the metastatic stage. In total, there are an estimated 170,000 women living with metastatic breast cancer in the United States. Current therapies often fail due to resistance to existing therapies, leaving patients with limited options. Atossa believes (Z)-endoxifen has the potential to become a first-in-class therapy in this multi-billion-dollar market.
Pipeline Momentum
In addition to the upcoming metastatic dose-ranging trial, Atossa is advancing additional Phase 2 studies in the ER+/HER2- neoadjuvant breast cancer setting (i.e., before definitive surgery), including studies of monotherapy of (Z)-endoxifen in early stage breast cancer; combination therapy with abemaciclib in women with early stage breast cancer at high risk of recurrence; and monotherapy in women with a biopsy-proven diagnosis of ductal carcinoma in situ (DCIS). Multiple clinical readouts are anticipated in the coming months.
About (Z)-Endoxifen
(Z)-endoxifen is a highly potent Selective Estrogen Receptor Modulator/ Degrader (SERM/D) with dual mechanisms of action:
Estrogen receptor inhibition and degradation, including in tumors resistant to other endocrine therapies.
Direct inhibition of protein kinase C beta 1 (PKCβ1), an oncogenic signaling protein, at clinically achievable blood levels.
Preclinical and clinical studies suggest (Z)-endoxifen may deliver superior bone-protective effects relative to tamoxifen, while maintaining a favorable safety profile. Across more than 700 subjects dosed up to 360 mg/day, no maximum tolerated dose (MTD) has been identified, underscoring its potential for broad dose exploration. Clinical studies with tamoxifen demonstrate an inverse correlation between endoxifen blood concentration and hot flash severity score following adjustment for age, BMI, and menopausal status, suggesting it may deliver a better tolerance profile.
Atossa’s proprietary oral, enteric-coated formulation is designed to preserve the active (Z)-isomer and promote optimal bioavailability, overcoming limitations of prior formulations.