Ethos Technologies Inc.

Good afternoon, ladies and gentlemen, and welcome to the 8th Higher Pharma First Quarter 2022 Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will be given at that time. As a reminder, this conference is being recorded for replay purposes. It is now my pleasure to hand the conference call over to Ashley Dunston, ATAR's Director of Investor Relations and Corporate Communications. Ms. Densiton, you may begin.

Thank you, Operator, and good afternoon, everyone. Thank you for joining us today to discuss ATAR's first quarter 2022 operating results and corporate update. We are joined today by Dr. Sanjay Shukla, our President and CEO, and Ms. Jill Broadfoot, our CFO. On the call, Sanjay will provide an update on our corporate strategy and including our clinical program for Exocetamol and our research and discovery programs in Neuropilin 2, including our preclinical program for ATYR 2810. Jill will review the financial results and our current financial position before handing it back to Sanjay to open up the call for any questions. Before we begin, I would like to remind everyone that except for statements of historical facts, the statements made by management and responses to questions on this conference call are forward-looking statements under the safe harbor provision of the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Please see the forward-looking statement disclaimer in the company's press release issued this afternoon, as well as the risk factors in the company's SEC filings, and included in our most recent annual report on Form 10-K, subsequently filed quarterly reports on Form 10-Q, and in other SEC filings. Undue reliance should not be placed on forward-looking statements which speak only as of the date they are made as facts and circumstances underlying these forward-looking statements may change. Except as required by law, a tire farmer disclaims any obligation to update these forward-looking statements to reflect future information, events, or circumstances. I will now turn the call over to Sanjay.

Thank you, Ashley. Good afternoon, everyone, and thank you for joining us for our first quarter 2022 results conference call. We're very pleased with the start of 2022 as we work to develop a new class of medicines from our tRNA synthetase biology platform. Throughout the first quarter, we continue to make important progress with our F-sulfidamide clinical program in pulmonary sarcoidosis, our initial interstitial lung disease, or ILD, indication. With the receipt of FDA orphan drug designation for efsofitamide for sarcoidosis and a positive end of phase two meeting with the FDA, we are on track to initiate a planned registrational study in pulmonary sarcoidosis in the third quarter of this year. As we begin, I will summarize a few highlights since we last spoke in March. We announced that posters for efsofitamide in pulmonary sarcoidosis were accepted for presentation at the American Thoracic Society or ATS International Conference. We received FDA orphan drug designation for efsofetamide for the treatment of systemic sclerosis, or SSC, also known as scleroderma. We presented preclinical data in a poster at the American Association for Cancer Research, or AACR, annual meeting for ATYR2810, or 2810, our lead antineuropilin 2, or NRP2, antibody in cancer. We've had a highly productive first quarter and a good start to the year. The second quarter is shaping up to be a very important period as we prepare to present clinical data from the Phase 1b-2a study of F-sulfenamide in pulmonary sarcoidosis at ATS next week and anticipate the potential publication of a related manuscript. We're focused on operational preparation for upcoming planned registrational study. So the balance of the year may center upon initiating the study in the U.S. and Europe and supporting our partner, Cure and Pharmaceutical, with the anticipated launch of the study in Japan. Let's discuss our clinical program for efsofitamide first. Efsofitamide is a potential first-in-class immunomodulator for fibrotic lung disease. Efsofitamide is a novel FC fusion protein based on naturally occurring splice variant of the lung-enriched tRNA synthetase HARS fragment that downregulates average immune responses in inflammatory disease states. Epsifidamide has been shown preclinically to downregulate inflammatory cytokine and chemokine signaling and reduce inflammation and fibrosis. NRP2 is upregulated on key immune cells, known to play a role in inflammation, and is enriched in inflamed lung tissue. Epsifidamide binds selectively to NRP2 and, therefore, has the potential to normalize the immune system, serving to resolve inflammation and prevent progressive fibrosis. thereby stabilizing lung function and alleviating morbidity and mortality for patients. We're developing F-sulfidamide as a potential treatment for patients with fibrotic lung disease, initially focusing on patients with ILD, a group of rare immune-mediated disorders that can cause progressive fibrosis of the lung. Our initial ILD indication for F-sulfidamide is pulmonary sarcoidosis, which is an inflammatory disease characterized by the formation of granulomas or clumps of immune cells in one or more organs of the body. Sarcoidosis that affects the lungs is commonly called pulmonary sarcoidosis, and the lungs are affected in more than 90% of SARC patients. The formation of these granulomas is driven by persistent aberrant inflammation, which, if left untreated, can lead to irreversible scarring or fibrosis and diminish lung function, which may lead to respiratory failure or the need for a lung transplant. We estimate there are close to 200,000 patients with pulmonary sarcoidosis in the U.S., although estimates do vary. About half of these patients will require some form of systemic therapy, and 30% of all patients will have chronic progressive disease despite available treatments. The current standard of care typically includes treating the inflammation with corticosteroids and other immunosuppressive therapies, which can help manage inflammation and alleviate symptoms such as cough and shortness of breath. However, they have no demonstrated efficacy on disease progression and can result in serious long-term toxicity. Additionally, many patients do not respond to currently available treatments. There's a substantial need for safer, more effective treatments that could reduce or replace the requirement for chronic corticosteroid or other immunosuppressive therapy and prevent disease progression. Because this is an orphan disease and treatment options are limited, We applied for and received FDA orphan drug designation for efsofitamide for the treatment of sarcoidosis. We recently generated a clinical proof of concept for efsofitamide based on the positive results from a Phase 1b-2a study in pulmonary sarcoidosis that we reported in September 2021. The study, which included a forced steroid taper, demonstrated safety, tolerability, and consistent dose response for efsofitamide on key efficacy endpoints. and improvements compared to placebo, including measures of steroid reduction, lung function, sarcoidosis symptom measures, and inflammatory biomarkers. According to medical experts, this is the first randomized placebo-controlled trial of any therapy for pulmonary sarcoidosis that demonstrates effects on physiologic and quality-of-life measures concurrent with steroid reductions. These findings confirm the potential of esophidamide to be a tremendously impactful therapy. We're excited to present additional data from this study in two posters at ATS next week. Some of the clinical findings that we will present for the first time include greater details regarding steroid reduction and improvements in lung function. Notably, we will also present details of the biomarker data for the first time. The hallmark lung granulomas in patients with pulmonary sarcoidosis are comprised of immune cells that secrete pro-inflammatory chemokines and cytokines, and if left untreated, can promote aberrant inflammation both systemically and locally that lead to fibrosis. Standard of care agents such as oral corticosteroids can suppress inflammation, but may come with toxicity, and in some cases can oversuppress the immune system, leading to increased risks. The ability of F-sulfidamide to effectively control inflammatory and sarcoidosis disease biomarkers in a dose-dependent manner over 24 weeks in the context of a corticosteroid taper are very important findings, as they are the first demonstration of F-sulfidamide's anti-inflammatory mechanism in pulmonary sarcoidosis patients. We encourage you to review the posters, which will be available on our website once they are presented. During ATS, we also plan to host a company reception. The event will bring together sarcoidosis medical experts, principal investigators, advocacy organizations, analysts, investors, and members from ATAR's management team, providing an opportunity to learn more about our F-sulfenamide clinical program and the ways in which we can all work together to deliver a potential new treatment to patients in need. A presentation featuring leading sarcoidosis experts, Dr. Daniel Culver, Director of Diffuse Parenchymal Lung Disease at the Cleveland Clinic, and Dr. Robert Boffman, Emeritus Professor of Medicine at the University of Cincinnati, will review results from the Phase 1b-2a study and discuss the outlook for the planned registrational study. In addition to the posters at ATS, we also anticipate the potential publication of a related manuscript with the full results of the study in a major medical journal in the very near future. An additional abstract further exploring the molecular and cellular mechanisms of action of F-sulfidamide in sarcoidosis that was previously accepted for presentation at ATS will instead be submitted for inclusion at another medical conference later this year. As we mentioned, we've been busy preparing for the next stage of F-sulfidamide's clinical development in pulmonary sarcoidosis. We had a positive end of phase two meeting with the FDA that provided productive feedback regarding trial duration, dose evaluation to assess the optimal dose for chronic use, and endpoint prioritization, including discussion around outcome measures that would best support the evaluation of esophitamide's efficacy, including a combination of both objective and subjective clinically meaningful outcomes. Preparations for the study are underway, and we are on track to initiate this study in the third quarter of this year. While our primary focus for efsofitimod is on our planned registrational study in pulmonary sarcoidosis, efsofitimod's mechanism of action, compelling translational and clinical data, and the shared immune pathology in ILD strongly suggest that efsofitimod could have potential to treat other ILD indications as well. One such ILD that carries a high unmet need is an ILD that results from underlying systemic sclerosis, also known as scleroderma. Scleroderma is a chronic progressive autoimmune disease characterized by inflammation and fibrosis of connective tissues throughout the body. More than half of all patients with underlying scleroderma may develop ILD, which is the primary cause of death in these patients. Like sarcoidosis, SSC-ILD results from an uncontrolled persistent immune response, which if left untreated can result in scarring that permanently causes loss of lung function. Also like sarcoidosis, current treatment options are limited. The pathology of SSC-ILD is driven by the same immune cells that are central to sarcoidosis pathology. An NRP2-F-sulfidamide binding partner is upregulated on these cells, particularly on macrophages. Furthermore, efsofetamide has been shown to reduce lung and skin fibrosis in animal models of fibrotic disease, such as scleroderma and IPF, where it matched or outperformed approved known antifibrotic agents, including nintenatib and profenadone. Nintenatib was recently approved for slowing the rate of lung function decline in scleroderma ILD patients. but did not display any effects on the underlying disease or patient quality of life in those clinical trials. We believe our differentiated mechanism of action targeting NRP2 on immune cells has the potential to translate into benefit not only on lung function, but on the underlying disease as well. It's estimated that approximately 100,000 people in the U.S. are affected with scleroderma. We recently obtained FDA orphan drug designation for F-sulfidamide. for the treatment of scleroderma, which validates the antifibrotic effects of eslifidamide observed in those previously mentioned preclinical models of ILD. Now let's take a few minutes to discuss our preclinical programs, including 2810, an anti-NRP2 antibody in development for cancer. NRP2 is a cell surface receptor that plays a key role in lymphatic development and in regulating inflammatory responses. In cancer, NRP2 is upregulated on a variety of solid tumors and is particularly expressed in many aggressive cancers. Increased NRP2 expression is linked to worsened patient outcomes in several cancers, which may include the promotion of drug resistance to certain current therapies, such as chemotherapy or targeted agents, metastasis, tumor recurrence, and overall survival. 2810 is a fully humanized monoclonal antibody that selectively and functionally blocks the interaction between NRP2 and VEGF, one of its primary ligands. VEGF is a validated mediator of tumor survival and growth and correlates with tumor invasiveness and metastasis. Current therapies that directly target classic VEGF-VEGFR signaling do not block Neuropilin 2. Preclinical data suggests that blocking VEGF interaction through NRP2 that ATYR2810 may be an effective novel therapeutic antibody with a differentiated approach that can target aggressive cancers through the inhibition of metastasis and enhanced chemosensitivity. Last month, we presented some important findings at AACR that characterized the effects of 2810 in highly aggressive tumor subtypes. Research showed that highly aggressive cancers and those associated with metastasis including triple negative breast cancer, or TNBC, were responsive to treatment with 2810 in combination with chemotherapy. Importantly, treatment with 2810 alone is able to inhibit metastasis in models of TNBC, consistent with an emerging understanding of NRP2 slash VEGF signaling as a driver of metastasis and therapy resistance. Additional findings provided key insights regarding 2810's ability to impact the lineage plasticity of cancer cells, which contributes to their ability to differentiate into states that are known to play a role in metastasis. Notably, 2810 has been shown to downregulate ZEB1, a central regulator of these processes, in different model systems, including patient-derived organoids and patient-derived xenografts. The poster highlighted work that characterized the gene expression signatures of breast cancer cells that respond to 2810 treatment in combination with chemotherapy, paving the way for bioinformatic analysis that may help with clinical development design. We're in the process of completing the required work for 2810 to support its planned clinical development in oncology, and we expect to initiate a phase one study of 2810 in cancer patients in the second half of this year. I'll now turn it over to our Chief Financial Officer, Jill Broadfoot, to review our financial results.