The Science
(Z)-endoxifen is a next-generation selective estrogen receptor modulator (SERM) engineered to deliver almost 100-fold greater potency than existing SERMs, while offering a more favorable tolerability profile.
Redefining Breast Cancer Care—From Prevention to Metastasis… and Beyond
Atossa is on a mission to transform the breast cancer journey at every stage. Our lead candidate, (Z)-endoxifen, combines breakthrough potency—nearly 100-fold that of legacy SERMs—with an encouraging tolerability profile, empowering physicians and patients with a versatile tool against ER-positive disease.
Metastatic Breast Cancer
In late-stage settings, (Z)-endoxifen has demonstrated meaningful clinical benefit. Prior studies showed extended progression-free survival and measurable tumor shrinkage versus tamoxifen, even in patients who have exhausted multiple lines of therapy—offering renewed hope and extended quality of life for those facing advanced disease.
Beyond Metastatic
We envision a future where breast cancer is halted long before it reaches Stage IV. Guided by predictive biomarkers and personalized risk assessment, our long-term vision encompasses:
Prevention: Prophylactic oral regimens to reduce breast cancer incidence in high-risk women, making annual risk reduction as commonplace as routine screenings.
Neoadjuvant Therapy: Targeted use of (Z)-endoxifen to shrink tumors pre-surgery, improving surgical outcomes and long-term remission rates.
Adjuvant Settings: Sustained, low-dose maintenance therapy post-surgery to minimize recurrence, extend disease-free intervals, and support lasting survivorship.
By advancing (Z)-endoxifen across this continuum—from intercepting disease before it takes hold to reclaiming lives in metastatic settings—we are redefining what’s possible in breast cancer care.
Mission:
To transform the lives of patients battling advanced breast cancer by delivering breakthrough therapies that extend survival, preserve quality of life, and redefine standards of care in the metastatic setting.
Long-Term Vision:
We envision a future where breast cancer prevention is as routine and accessible as annual health screenings—where early intervention, personalized risk assessment, and novel oral therapeutics like (Z)-endoxifen intercept disease before it ever takes hold. By advancing our pipeline and forging strategic partnerships, we aim to shift the paradigm from lifelong management of Stage IV disease to durable, proactive prevention that dramatically reduces both incidence and mortality.
Building on Tamoxifen’s Legacy
Tamoxifen remains one of the most prescribed breast cancer therapies of all time, with decades of proven benefit in reducing recurrence and extending survival. (Z)-Endoxifen takes this legacy even further: by delivering the active molecule directly, it bypasses the need for liver metabolism, ensuring predictable, uniform drug levels in every patient. As a truly next-generation SERM, (Z)-endoxifen combines tamoxifen’s trusted mechanism with optimized pharmacology for enhanced consistency and efficacy.
Dual Mechanism
(Z)-endoxifen’s dual mechanism of action not only blocks estrogen receptor (ER) signaling but also promotes degradation of the receptor itself. In addition, (Z)-endoxifen targets protein kinase C beta 1 (PKCβ1) and ESR1 mutations—two key drivers of endocrine resistance—giving it a differentiated profile compared to aromatase inhibitors and other SERMs that currently available.
Evidence from Clinical Trials
In clinical trials, (Z)-endoxifen has demonstrated meaningful anti-tumor activity and a favorable safety profile.
Metastatic Breast Cancer
(Z)-endoxifen’s potent anti‐estrogen activity has been validated in both Phase 1 and Phase 2 settings, demonstrating clear advantages over tamoxifen in patients with advanced, ER-positive disease:
Superior Progression-Free Survival in Front-Line Patients
In CDK4/6 inhibitor–naïve metastatic patients, (Z)-endoxifen more than doubled progression free survival (PFS) compared to tamoxifen (7.2 vs. 2.4 months), underscoring its enhanced efficacy in an endocrine-sensitive population.
Meaningful Benefit After Tamoxifen Failure
Patients who progressed on tamoxifen and then crossed over to (Z)-endoxifen achieved notable clinical benefit—ranging from partial tumor responses to prolonged stable disease. A subset of these heavily pretreated individuals maintained disease control for more than 2–3 years, highlighting (Z)-endoxifen’s ability to overcome resistance.
These data from early‐stage trials reinforce (Z)-endoxifen as a next-generation SERM with the potential to redefine standards of care in metastatic breast cancer.
In the neoadjuvant setting – The EVANGELINE trial
85% achieved Ki-67
The EVANGELINE trial showed that more than 85% of patients (with or without ovarian function suppression (OFS)) achieved suppression of Ki-67, a marker of tumor proliferation, after just four weeks of treatment.
The I-SPY2 trial
Monotherapy and combination therapy with abemaciclib
(In collaboration with Quantum Leap Healthcare Collaborative)
Readout:
- (Z)-endoxifen at 10 mg once daily met the primary endpoint with 95% of patients receiving greater than 75 % of planned treatment with promising rapid activity in reducing 3-wk Ki-67 and functional tumor volume (FTV) at 69% and 30%, respectively.
- (Z)-endoxifen combination data expected 2026.
Breast Cancer Prevention – Reducing mammographic breast density (MBD)
And in breast cancer prevention, low doses of (Z)-endoxifen significantly reduced mammographic breast density (MBD)—a known risk factor for the disease—with better tolerability than tamoxifen.
17.3% reduced MBD compared to placebo
In the KARISMA Trial, (Z)-endoxifen has demonstrated 1 mg dose of (Z)-endoxifen reduced MBD by 17.3 percentage points (p<0.01), compared to a minimal change in the placebo group of 0.27 percentage points.
Moving forward, prioritizing metastatic breast cancer
Atossa is now prioritizing the development of (Z)-endoxifen as a treatment for metastatic breast cancer, where current options often lack durability and carry burdensome side effects. This indication represents a high unmet need and may offer a more streamlined regulatory path. At the same time, Atossa continues to explore parallel development in prevention, neoadjuvant, and adjuvant settings, leveraging the compound’s broad therapeutic potential.
With a proprietary oral formulation, strong intellectual property protection, and multiple Phase 2 trials underway, (Z)-endoxifen is positioned to become a best-in-class endocrine therapy that meets patients’ needs across the full spectrum of breast cancer care.