Steven Quay
Analyst · H.C. Wainwright. Your line is now open
Thank you, Michael, and good day to everyone joining us. We appreciate your time and continued support of Atossa during today's call, I'll provide an overview of our recent corporate developments and strategic priorities, as well as clinical progress updates on our lead program (Z)-endoxifen. Then Heather will discuss our full year 2024 financial results, and we will conclude with a Q&A session. However, before we provide those updates I just want to take a moment to talk about the critical challenges practitioners face with endocrine therapy and breast cancer and the significant unmet needs that remain in this treatment landscape. First, we all know that endocrine therapy has been a cornerstone of treatment for hormone receptor-positive breast cancer. However, despite being a [mean-state](ph) therapy, there are still major gaps and areas for improvement. One of the biggest issues we see is patient adherence. 30% to 50% of patients stop taking their adjuvant endocrine therapy before they're supposed to. This could be caused by side effects, daily pill fatigue or other quality-of-life factors, all of which underscore the need for more tolerable and patient-friendly options. Another point to consider is efficacy, while endocrine therapy can be highly effective for many women not all patients get the long-term benefits they need. We're looking to develop a treatment that not only prevents recurrence, but also improves overall outcomes, especially for those with tougher disease profiles. Resistance to endocrine therapy remains a serious hurdle, ultimately leading to disease progression in many cases. There is a pressing need for therapies that can circumvent or delay the onset of resistance to extend the window of effective treatment. We also need strategies that can effectively induce apoptosis or programmed cell death in the tumor cells, a therapy that reliably triggers tumor-specific cell death could significantly enhance treatment results and patient survival. Finally, beyond these points, the broader breast cancer community is calling our treatments with fewer side effects, better tolerability and higher patient adherence. Meeting these needs could greatly improve both patient's quality of life and the clinical efficacy of endocrine therapy. Now that we've identified the high unmet needs in endocrine therapy for breast cancer, ranging from early patient discontinuation to drug resistance. Let's turn our focus to what we believe is a very promising solution (Z)-endoxifen. This is an innovative next-generation anti-estrogen therapy that we believe could address many of the gaps we just discussed. [(Z)-endoxifen] (ph) stands apart from current endocrine therapies due to its potent anti-estrogenic activity. It not only targets estrogen receptors very effectively but may also help overcome issues related to patient metabolism and drug resistance, challenges clinicians often face with existing treatments like tamoxifen, the pro-drug form from which (Z)-endoxifen drives. Several factors set (Z)-endoxifen apart. First, there's enhanced potency compared to older agents, the (Z)-endoxifen is able to achieve higher, more consistent blood levels, resistant mitigation. Its unique mode of action may help delay or reduce development of resistance. And finally, tumor cell apoptosis. Laboratory research suggests (Z)-endoxifen can induce robust apoptosis in breast cancer cells, a key goal in stopping disease progression. One of the most exciting aspects of (Z)-endoxifen is its flexibility. We believe it could play a role across the spectrum of breast cancer care from early prevention treatment to more advanced metastatic disease. This versatility may also offer a valuable backbone for combination therapies particularly in settings where common mutations like PIK3CA, AKT1, and PTEN are factors in driving tumor growth. With a more tolerable safety profile and a dosing strategy designed to minimize side effects, we believe that (Z)-endoxifen could also improve patient adherence. By addressing some of the quality of life challenges that often lead to early discontinuation of endocrine therapy, we hope this agent will help more patients complete their full course. So in summary (Z)-endoxifen aims to tackle the exact issues we discussed on the third slide enhancing efficacy, reducing resistance, inducing meaningful tumor cell apoptosis and improving overall adherence and tolerability. This is precisely why we view it as a next-generation anti-estrogen with the potential to set a new benchmark in breast cancer treatment. Our goal is simple but ambitious to deliver a best-in-class therapy that significantly improves patient outcomes. So the question is, how do we get from where we are today to delivering a treatment that tens or hundreds of thousands of women they benefit from tomorrow. Let me begin by elaborating on our recent decision to advance our lead program, (Z)-endoxifen in metastatic breast cancer. We are incredibly excited to advance this indication and confident in our impact that we can have for patients at this stage. It is a clinical setting of high unmet need marked by limited durability of response and significant side effects from existing treatment options. We believe there is a compelling rationale to prioritize this area first, potentially leading to a more streamlined path to regulatory approval and faster time to market, not only in metastatic, but for earlier disease as well. Importantly, our confidence in (Z)-endoxifen for metastatic breast cancer is supported by compelling clinical investigations. First, in a Phase I study by Dr. Matthew Goetz, the lead investigator of the Evangeline trial, (Z)-endoxifen demonstrated robust plasma concentration, unaffected by cytochrome genotypes and showed clinically meaningful activity in women, endocrine refractory ER-positive HER2-negative metastatic breast cancer is a remarkable ability for a drug. Next, notably the study observed a clinical benefit rate of approximately 26% in patients who had already progressed on multiple prior therapies, underscoring the agent's potential in difficult-to-treat settings. And additionally, a related Phase II study further suggested that (Z)-endoxifen can prolong progression-free survival relative tamoxifen in certain subgroups such as those who have not been treated previously with CDK4/6 inhibitors with nearly a five-month greater progression-free survival. These data are very encouraging and by pursuing a metastatic indication first, we believe we can expedite patient access to (Z)-endoxifen, especially for those who urgently need new therapeutic approaches. More information on our registrational path will be forthcoming, including our target subpopulation trial design and the potential for a combination therapy. We are excited about this path and look forward to keeping you updated. We also announced our commitment to continue an active dialogue with the FDA regarding the potential for (Z)-endoxifen in earlier disease settings like breast cancer prevention and neoadjuvant therapy, which generally require larger and longer clinical trials. Importantly, we believe the metastatic indication first approach will help us with this goal. Late last year, we presented five abstracts, three of which were EVANGELINE focused at the San Antonio Breast Cancer Symposium. These presentations outlined strong pharmacokinetic and tolerability data for our Phase II Evangeline trial in premenopausal women with ER-positive HER2-negative breast cancer. Substantial tumor suppression was observed with (Z)-endoxifen at multiple dose levels and the four-week Ki-67 was less than 10%, generally above 85% of the women. Moreover, (Z)-endoxifen was very well tolerated with no significant grade 3 or 4 toxicities. The previously disclosed gynecological events at the 80-milligram dose we plan to continue under an amended protocol that compares a 40-milligram per day regimen of (Z)-endoxifen plus ovarian function suppression to exemestane plus OFS. Using the four-week Ki67 reduction as the primary endpoint will also include a single-arm cohort of (Z)-endoxifen monotherapy at 40 milligrams per day over 24 weeks to gather additional safety and efficacy data. Additionally, the San Antonio data from our Phase II KARISMA-Endoxifen study showed that low doses of (Z)-endoxifen significantly reduced mammographic breast density, a key marker in breast cancer. A 1-milligram dose lowered MBD by 17.3 percentage points while a 2-milligram dose achieved a 23.5% reduction, both highly significant when compared to the placebo group. Importantly, the 1-milligram dose exhibited no meaningful difference in adverse events relative to placebo, suggesting (Z)-endoxifen favorable safety and tolerability profile. Our focus on metastatic breast cancer first is driven by both clinical urgency for patients and a potential pathway to expedited approval. We believe this approach can enable a quicker route to market and paved the way for future label expansions into prevention and neoadjuvant settings, which as I said, are larger and longer trials in any case. We remain steadfast in executing our research and regulatory strategies confident that (Z)-endoxifen can transform how we treat and ultimately prevent various stages of breast cancer. I'll now hand the call over to our Chief Financial Officer, Heather Rees, to walk us through our financial results for the full year 2024. Please go ahead, Heather Rees.
