On September 8, 2025 Atossa Therapeutics, Inc. (Nasdaq: ATOS; "Atossa" or the "Company") reported it has requested a Type C meeting with the U.S. Food and Drug Administration (FDA) to discuss a regulatory strategy aimed at accelerating development of low-dose (Z)-endoxifen for breast cancer risk reduction (Press release, Atossa Therapeutics, SEP 8, 2025, View Source [SID1234655844]). Atossa is a clinical-stage biopharmaceutical company developing new approaches in breast cancer treatment and risk-reduction, commonly termed prevention of breast cancer.

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Beginning in June 2025, Atossa engaged an internationally recognized FDA law firm and senior regulatory affairs experts to review the Company’s extensive (Z)-endoxifen data and the considerable published scientific literature on (Z)-endoxifen. They evaluated whether existing evidence could support a faster regulatory path in breast cancer risk-reduction, specifically, in the adjuvant setting, in ductal carcinoma in situ (DCIS), and in high-risk women without cancer.

The experts recommended Atossa rapidly schedule a Type C meeting with the FDA to align on the requirements needed to complete a New Drug Application (NDA). Atossa has now filed this meeting request and expects to update shareholders on the outcome of the meeting before year end 2025, based on standard agency timelines. While there can be no assurance of success, a favorable meeting outcome could shorten approval timelines by years and avoid tens of millions of dollars in clinical trial costs. Atossa had approximately $57.9 million in cash and no debt as of June 30, 2025.

Market opportunity for low-dose (Z)-endoxifen

An estimated 1.6 to 2.1 million tamoxifen prescriptions are filled annually in the United States, including in three breast cancer risk-reduction settings:

Adjuvant therapy (post-surgery recurrence risk-reduction): According to the American Cancer Society, approximately 4.3 million U.S. women are living with a history of breast cancer, as of January 1, 2025. About 79 percent of U.S. breast cancers are hormone-receptor positive. Professional guidelines recommend ≥5 years of adjuvant endocrine therapy, for these patients, with extension to 7–10 years in selected, higher-risk cases. Approximately 1 million women are currently taking adjuvant endocrine therapy in the U.S. based on initiation and real-world persistence data.

Risk reduction following DCIS surgery: It is estimated that a few hundred thousand women are taking SERMs or aromatase inhibitors for breast-cancer risk-reduction, including post-DCIS and other high-risk settings in the U.S. DCIS alone likely accounts for up to 80,000 women on therapy at any given time.

Risk reduction in high-risk women without prior cancer: 2010 NHIS data estimated that roughly 120,000 U.S. women are using preventive SERM therapy for primary risk-reduction.
In addition, approximately 600,000–800,000 women are currently taking an aromatase inhibitor as adjuvant endocrine therapy in the U.S. About one-third to one-half experience musculoskeletal symptoms on AIs (pooled prevalence about 46 percent) and more than 30 percent discontinue treatment early due to those symptoms (e.g., about 32 percent within two years in a large prospective cohort).

(Z)-Endoxifen has demonstrated equivalent anti-estrogen pharmaceutical activity to tamoxifen, but with important differences. It avoids the CYP2D6 metabolism variability of tamoxifen, in which up to 20 percent of women do not achieve a therapeutic level of (Z)-endoxifen following tamoxifen administration. This exposure variability is well-documented and contributes to inconsistent endoxifen levels on tamoxifen; recurrence rates of 30 percent despite adjuvant therapy highlight the residual unmet need.

In Atossa clinical trials, direct oral (Z)-endoxifen achieved high systemic (Z)-endoxifen concentrations independent of CYP2D6 metabolism, whereas during tamoxifen therapy (Z)-endoxifen constitutes approximately six percent of the total tamoxifen-related metabolites at steady state.

In addition, tamoxifen takes four weeks to reach plasma steady state and its primary intermediate (N-desmethyl-tamoxifen) takes eight weeks. Direct (Z)-endoxifen can achieve target endoxifen concentrations within hours and typically reaches steady state within about one week in clinical studies.

Complementary Role of Project Optimus

Atossa continues to advance its FDA-aligned Phase 2 Project Optimus trial to identify the optimal (Z)-endoxifen dose in metastatic breast cancer. We believe this program not only supports the development of endoxifen in the metastatic setting but also strengthens the scientific and regulatory bridge for development in the low dose risk-reduction setting.

Dr. Steven Quay, Chairman and CEO of Atossa, commented, "This new regulatory strategy could dramatically accelerate the timeline for the development and potential approval of low-dose (Z)-endoxifen in the reduction of the incidence of breast cancer. We see a potential multi-billion-dollar market opportunity given the number of women currently on tamoxifen in the risk-reduction settings, and of women on aromatase inhibitors, half of whom experience painful arthritic symptoms. Importantly, this strategy could bring (Z)-endoxifen to patients, years sooner, at lower cost, and with a more predictable and faster-acting therapy than tamoxifen."

About (Z)-Endoxifen

(Z)-endoxifen is a highly potent Selective Estrogen Receptor Modulator/Degrader (SERM/D) with demonstrated ability to inhibit and 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 the oncogenic signaling pathway, protein kinase C beta 1 (PKCβ1), at clinically achievable blood and tumor levels. (Z)-Endoxifen also seems to deliver comparable or superior bone-protective effects relative to tamoxifen.

Atossa is developing a proprietary enteric oral formulation of (Z)-endoxifen that bypasses stomach acid, which would otherwise partially convert the active (Z)-isomer to its inactive (E)-form. We believe this innovation allows for 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) receiving doses up to 360 mg/day, no maximum tolerated dose (MTD) has been identified, supporting continued dose-range exploration.

Atossa is prioritizing development in metastatic breast cancer. In parallel, (Z)-endoxifen is being evaluated in three Phase 2 studies, one in DCIS and two in ER+/HER2- breast cancer. Monotherapy in DCIS and low risk cancer, and combination therapy in high-risk cancer, with Lilly’s CDK4/6 inhibitor, Verzenio (abemaciclib), are being investigated. 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.