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Atossa Therapeutics Reports Significant Progress in I-SPY 2 Trial

Atossa Therapeutics, Inc. (Nasdaq: ATOS), a clinical-stage biopharmaceutical firm focusing on innovative treatments for breast cancer, recently announced crucial findings from the Phase 2 Endocrine Optimization Pilot (EOP) trial that forms part of the I-SPY 2 initiative. This sub-study evaluated the effects of low-dose oral (Z)-endoxifen at 10 mg daily on women diagnosed with stage II/III estrogen-receptor-positive (ER+), HER2-negative breast cancer.

Key Discoveries from the Trial

The trial's primary objectives were met successfully, with an impressive 95% of participants (19 out of 20) completing at least 75% of the planned dosage, far exceeding the pre-defined benchmark of 75%. One of the standout outcomes was the marked reduction of Ki-67, from 10.5% at the commencement of the treatment to just 5% by the third week, demonstrating early anti-proliferative activity. At this point, 65% of patients managed a Ki-67 level of 10% or lower, which was sustained through the time of surgery.

Moreover, imaging results indicated a significant reduction in median functional tumor volume (FTV). Measurements taken at baseline, week 3, week 12, and at the surgical stage showed a remarkable 77.7% reduction in FTV, dropping from an average of 9.0 cc to 1.2 cc. Furthermore, the longest diameter of the tumors also shrank by 36.8% before surgery, underscoring the treatment's robust imaging response.

Safety Profile and Patient Experience

The safety profile for (Z)-endoxifen was highly favorable, with adverse events predominantly classified as Grade 1. The most reported side effects were mild, including hot flushes and fatigue. Notably, only three instances of Grade 3 events—two skin infections and one post-procedural infection—were recorded in a single patient, which the researchers deemed unrelated to the drug under study. No Grade 4 or 5 events were reported, further emphasizing the tolerability of the treatment.

Understanding the Pathological Findings

While the study did not achieve a pathologic complete response (pCR), overall results fell within expected parameters given previous studies. The classification of the residual cancer burden (RCB) tended toward RCB-II/III, suggesting moderate to extensive residual disease. This outcome aligns with earlier findings which indicated that a higher systemic exposure to (Z)-endoxifen is typically essential for reaching significant pathologic clearance. The 10 mg dose was intentionally selected to prioritize tolerability and establish proofs of early biological activity in patients not previously treated with endocrine therapy, making the limited pCR rates predictable.

Dr. Steven Quay, the President and CEO of Atossa, commented on these findings, stating, “These results demonstrate that even at a low dosage, (Z)-endoxifen showcases bioactivity. The rapid suppression of Ki-67 and meaningful tumor shrinkage—and with an excellent safety profile—reinforces our hypothesis that targeting both ERα and PKCβ1 is critical for initiating a pathological cancer response.”

Looking ahead, Atossa is progressing towards additional cohorts within the I-SPY 2 trial, assessing higher doses of (Z)-endoxifen, both alone and in tandem with the CDK4/6 inhibitor abemaciclib. This research aims to translate these early biomarkers into more substantial pathologic responses, with results from these explorations expected to surface in 2026.

The Future of (Z)-Endoxifen

(Z)-endoxifen is recognized for its strong efficacy as a Selective Estrogen Receptor Modulator (SERM). This compound represents a potential breakthrough, particularly for tumors that have become resistant to other hormone therapies. Key to its action, it targets protein kinase C beta 1 (PKCβ1), a protein implicated in oncogenic signaling.

Atossa is also innovating a proprietary oral formula of (Z)-endoxifen, designed to avoid stomach acid, which can convert the active (Z)-isomer into its inactive (E)-form. This advancement aims to ensure that patients receive the optimal therapeutic dose.

With a profound commitment to tackling breast cancer, Atossa Therapeutics is dedicated to enhancing treatment efficacy while delivering sustainable value to stakeholders. Their ongoing research and development initiatives highlight a deep-seated priority on improving patient outcomes in a field where innovative, effective treatments are crucial.