As biotechnology increasingly looks to extract greater precision and value from established biology, companies that rethink proven mechanisms through smarter molecular engineering and strategic development are gaining attention. Atossa Therapeutics, a Seattle-based clinical-stage biotechnology company, is advancing such a strategy through its differentiated small-molecule platform built around (Z)-endoxifen.

Led by physician-scientist Dr. Steven Quay, Atossa is leveraging the well-understood endocrine foundation of tamoxifen while improving pharmacologic precision, dosing reliability, and therapeutic flexibility.

Drug Development & Delivery spoke with Dr. Quay about how (Z)-endoxifen is being positioned as both an oncology backbone therapy and a potential treatment in rare diseases with substantial unmet need.

Q: How would you describe Atossa Therapeutics’ overarching strategy and platform?

A: Atossa is a clinical-stage biotechnology company advancing a differentiated small-molecule platform built around (Z)-endoxifen. Our strategy is rooted in the belief that well-validated biology can often be meaningfully improved through greater molecular precision and more thoughtful clinical execution.

Tamoxifen has been one of the most widely prescribed endocrine therapies in medicine for decades and has saved countless lives. However, its clinical performance is inherently limited by metabolic variability. Tamoxifen must be converted into active metabolites, particularly (Z)-endoxifen, through CYP2D6 mediated metabolism. That conversion varies widely across patients due to genetic differences and drug interactions, resulting in inconsistent drug exposure and unpredictable therapeutic response.

By administering (Z)-endoxifen directly in oral form, we eliminate that metabolic variability. This allows for consistent pharmacologic exposure, more predictable receptor engagement, and the ability to dose with precision across diverse patient populations. In effect, we are refining and optimizing a well-established endocrine mechanism into a more reliable therapeutic platform. Importantly, our strategy extends beyond improving tamoxifen. We view (Z)-endoxifen as a scalable endocrine backbone with potential applications across oncology and other diseases where estrogen receptor signaling and related molecular pathways are biologically relevant.

Q: What differentiates (Z)-endoxifen biologically from traditional endocrine therapies?

A: (Z)-endoxifen’s differentiation lies both in its pharmacokinetics and its pharmacodynamics.

Pharmacokinetically, direct administration results in consistent systemic exposure that is independent of hepatic metabolism. This reduces interpatient variability and enables clearer dose-response relationships in clinical development.

Pharmacodynamically, (Z)-endoxifen functions as a potent Selective Estrogen Receptor Modulator and Degrader (SERM/SERD). It not only binds to and inhibits estrogen receptors but also promotes receptor degradation, which may provide enhanced suppression of estrogen-driven signaling compared to agents that function purely as receptor antagonists.

In addition, (Z)-endoxifen has been shown to modulate oncogenic signaling pathways, including protein kinase C beta 1 (PKCβ1). This broader biologic activity suggests potential utility beyond classical endocrine modulation and may help explain its versatility across disease models.

Clinically, the molecule has been evaluated in more than 700 subjects, including healthy volunteers and breast cancer patients, and has demonstrated a strong safety and tolerability profile. Notably, no maximum tolerated dose has been identified at doses up to 360 mg per day. That degree of dose flexibility is particularly important when considering combination strategies and expansion into additional therapeutic areas.

Q: How is Atossa positioning (Z)-endoxifen within oncology?

A: We are currently evaluating (Z)-endoxifen in Phase 2 studies in ductal carcinoma in situ and through several ongoing I-SPY 2 trials investigating its neoadjuvant activity in ER-positive, HER2-negative breast cancer. These studies are assessing (Z)-endoxifen as a monotherapy and in combination with abemaciclib (VERZENIO®), a CDK4/6 inhibitor marketed by Eli Lilly, as well as with elagolix (ORILISSA®), marketed by AbbVie. In the monotherapy arm, newly diagnosed ER+/HER2- breast cancer patients received daily 10 mg doses of (Z)-endoxifen for one month prior to surgery, with preliminary data demonstrating favorable tolerability and reductions in Ki-67, functional tumor volume (FTV), and tumor size.

Enrollment in the combination arms is nearing completion, with preliminary data from the elagolix-containing arms expected in the second quarter of 2026 and additional readouts, including from the abemaciclib arms, anticipated in the second half of 2026. This reflects our continuum-of-care mindset, strategically exploring earlier-stage and hormone-modulation settings where improved endocrine precision could meaningfully impact outcomes.

Q: Beyond oncology, where do you see additional utility for (Z)-endoxifen?

A: The broader potential of (Z)-endoxifen emerges from its underlying biology. Estrogen receptor modulation influences a range of cellular processes beyond breast tissue, and the molecule’s ability to impact signaling pathways such as PKCβ1 opens additional therapeutic possibilities.

In January 2026, the FDA Office of Orphan Products Development granted Orphan Drug Designation to (Z)-endoxifen for the treatment of Duchenne muscular dystrophy (DMD), following a previously granted Rare Pediatric Disease designation. Preclinical data suggest that (Z)-endoxifen can upregulate utrophin, a functional analog of dystrophin. Because DMD is characterized by the absence of dystrophin, increasing utrophin expression represents a biologically rational approach to mitigating disease progression.

What makes this particularly compelling is that (Z)-endoxifen represents a small-molecule strategy in a field often dominated by gene-based approaches. Small molecules can offer advantages in scalability, manufacturability, and potential global access.

We are also engaging with the FDA regarding potential clinical strategies in women carriers of DMD and in McCune-Albright Syndrome, both serious conditions with limited treatment options. These initiatives reinforce the concept that (Z)-endoxifen is not confined to a single disease category but may represent a biologically versatile platform.

Q: How does regulatory strategy support the scalability of this platform?

A: Regulatory strategy is central to how we think about scalability. Because (Z)-endoxifen builds on decades of clinical experience with tamoxifen and well-characterized endocrine biology, we are able to engage constructively and proactively with the FDA regarding efficient and appropriately tailored development pathways.

We are leveraging regular FDA interactions, including Type B and Type C meetings, to inform and align on our clinical study designs and overall regulatory strategy before formal IND submissions. These early and ongoing discussions are intended to help ensure that our IND submissions are as complete and efficient as possible, minimize the risk of delays, and ideally facilitate “study may proceed” determinations that allow us to initiate clinical work in close alignment with the agency.

In parallel with clinical trial design and protocol alignment, we are also pursuing applicable FDA designations that may meaningfully enhance our development pathway. These include Rare Pediatric Disease and orphan drug designations, which can provide important benefits such as expedited regulatory review processes, market exclusivity protections, and other regulatory incentives. Rare Pediatric Disease designation carries the potential for priority review voucher eligibility, which can represent a significant non-dilutive source of future capital if monetized.

By combining a well-understood mechanism with disciplined regulatory planning, proactive agency engagement, and strategic pursuit of available designations, we aim to streamline development, protect long-term value, and scale the platform efficiently and responsibly.

Q: What does this platform approach mean for the future of drug development?

A: We believe the future of drug development will increasingly emphasize optimization over reinvention. There is enormous value in revisiting validated mechanisms with improved molecular precision and smarter development strategies.

(Z)-endoxifen embodies that philosophy. It refines a decades-proven endocrine approach into a more precise and adaptable molecule. Its safety profile and dosing flexibility allow us to explore combinations in oncology while also extending into rare diseases where the underlying biology supports rational application.

If successful, this model demonstrates how a single, well-characterized small molecule can address both large oncology markets and rare diseases with substantial unmet need. That kind of scalability, rooted in scientific rigor and regulatory discipline, has the potential to deliver meaningful impact across diverse patient populations.