Ethos Technologies Inc.

Good afternoon, ladies and gentlemen, and welcome to the A-Tire Pharma second 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. To ask a question during the session, you'll need to press star 1-1 on your telephone. As a reminder, this conference is being recorded for replay purposes. It is now my pleasure to hand the conference over call over to Ashley Dunstan, ATAR's Director of Investor Relations and Corporate Communications. Ms. Dunstan, you may begin.

Thank you, and good afternoon, everyone. Thank you for joining us today to discuss ATAR's second quarter 2022 operating results and corporate updates. We are joined today by Dr. Sanjay Shukla, our President and CEO, Ms. Jill Broadfoot, our CFO, and Dr. Leslie Nangle, our VP of Research. On the call, Sanjay will provide an update on our corporate strategy, including our clinical program for Epsos Vitamot, and Leslie will go over our research and discovery programs in NeuroPillin 2 and our TRNA Synthetase platform. Jill will review the financial results on 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 on our 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, ATAR-Pharma 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 second quarter 2022 results conference call. We're pleased with the progress we've made in the second quarter as we advance our phase three study of F-sulfenamide in patients with pulmonary sarcoidosis. This global pivotal study is a major milestone for Atire and the sarcoidosis community, as it is projected to be the largest interventional study for patients with sarcoidosis to date. I'm happy to report that the study is underway with several centers initiated in the US. And importantly, we remain on track to enroll a patient this quarter. As we begin, I'll summarize a few highlights since we last spoke in May. We announced plans to initiate FSOFIT, a global pivotal Phase III study to evaluate the efficacy and safety of FSOFITAMOD in patients with pulmonary sarcoidosis. We announced Fibroblast Growth Factor Receptor 4, or FGFR4, as the target receptor for a fragment of the allonyl tRNA synthetase, which is also known as ARS. And we were recently very pleased to receive FDA fast track designation for esophitamide for the treatment of pulmonary sarcoidosis. Since the announcement of the esophit study in May 2022, we've rapidly executed a number of operational milestones to advance the study start. Multiple interactions with regulatory authorities in the US, EU, and Japan have occurred. Along with the submission of the study protocol and clinical trial applications to regulatory authorities, ethics committees, and institutional review boards. Site selection, qualification, and initiations for several sites have occurred, as well as an investigator meeting for U.S. sites. It's been a highly productive period for ATAR from the point of receiving our FDA green light on the design of the FSOFIT study just last quarter to now, and we eagerly anticipate enrolling a patient soon. I'd like to acknowledge our fantastic clinical operations team that has moved at light speed to get our pivotal trial launched so expeditiously. With that said, let's discuss our clinical program for efsofitamide in a bit more detail. As a reminder, efsofitamide is a first-in-class immunomodulator for fibrotic lung disease. Efsofitamide is a novel FC fusion protein based on the naturally occurring splice variant of the lung-enriched tRNA synthetase HARs fragment that down-regulates aberrant immune responses in inflammatory disease states. Efsofitamod has been shown pre-clinically to down-regulate inflammatory cytokine and chemokine signaling and reduce inflammation and fibrosis. The Neuropilin 2, or NRP2 receptor, is up-regulated on key immune cells during active inflammation and is enriched in inflamed lung tissue. Efsofitamod 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. We're developing F-sulfidamide as a potential treatment for patients with interstitial lung disease, or ILD, a group of rare immune-mediated fibrotic lung disorders. Our initial ILD indication for F-sulfidamide is pulmonary sarcoidosis. Sarcoidosis is the most prevalent ILD and is 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 called pulmonary sarcoidosis and occurs in more than 90% of cases. If left untreated, persistent granulomatous inflammation can lead to irreversible scarring or fibrosis, which may lead to respiratory failure and death. We estimate that there are close to 200,000 patients with pulmonary sarcoidosis in the U.S., around 150,000 in major European markets, and another 20,000 in Japan. Up to 75% of patients require treatment for their disease. Approximately half of these will progressively progress disease despite treatment, and around one in five of all patients will undergo, will go on to develop lung fibrosis. Indication for treatment of sarcoidosis is twofold, to avoid danger to an organ or to improve quality of life. First-line treatment is typically corticosteroids, which may effectively control symptoms but are associated with severe debilitating side effects, particularly with chronic treatment. Second and third-line treatments are anti-metabolite immunosuppressants such as methotrexate and biologic immunomodulators such as infliximab. These drugs are also known to cause serious side effects. Outside of prednisone and other glucocorticoids approved in the 1950s, none of these therapies are approved for the treatment of sarcoidosis and all are used based on limited clinical evidence. We believe the initial target population for epazofenamide will be patients whose disease is progressing despite steroid treatment. However, even patients who are able to control their symptoms with steroids often experience such debilitating side effects, that they are forced to choose between living with the burden of disease or the toxic effects of steroid treatment. Therefore, we also see an upside opportunity for efsofitamide as a steroid sparing agent in patients who are responsive but unable to tolerate their steroid treatment. Combined, these populations represent an addressable market of roughly 150,000 to 200,000 patients in major markets. Even with conservative market penetration and pricing assumptions, this represents a significant peak sales opportunity in sarcoidosis alone. Because this is an orphan disease and treatment options are limited, the FDA granted orphan drug designation for F-sulfidamide for the treatment of sarcoidosis. Additionally, we recently announced that FDA has also granted fast-track designation for F-sulfidamide for the treatment of pulmonary sarcoidosis. The FDA's FAST-TRACK designation helps facilitate development and expedite the review of drugs that treat serious or life-threatening diseases with unmet medical needs. FAST-TRACK designation provides certain benefits, including more frequent interactions with the FDA throughout the development program, as well as eligibility for accelerated approval, priority review, and rolling review. This fast-track designation underscores the significant need for a new therapy that provides clinically meaningful outcomes for patients living with pulmonary sarcoidosis and reinforces the potential of efsofitamide to be a transformative disease-modifying therapy and address a major unmet medical need. We see further upside potential for efsofitamide in other forms of ILD, where immunomodulatory treatment is the current standard of care. This includes indications such as scleroderma-related ILD, other connective tissue disease-related ILDs, and chronic hypersensitivity pneumonitis, among others. These diseases share overlapping immune pathology with sarcoidosis and are currently treated with similar drugs. Additionally, F-sulfidamide has been shown to be effective in animal models of these diseases. Taken collectively, the opportunity for efsofitamide in sarcoidosis and other ILDs represent $2 to $3 billion in peak sales. Let's take a moment to go over the data we generated for efsofitamide and some of the details around the current efsofit study. As a reminder, last September we reported clinical proof of concept for efsofitamide based on positive results from my Phase 1b, 2a study in pulmonary sarcoidosis. The study, which included a forced steroid taper, demonstrated safety, tolerability, and a consistent dose response for F-sulfatamide 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 reduction. Based on findings from the Phase 1b2a study and feedback from the FDA, in May of this year, we announced plans to initiate the FSOFIT study. This is a global pivotal Phase 3 randomized double-blind, placebo-controlled study to evaluate the efficacy and safety of FSOFITimod in patients with pulmonary sarcoidosis. This is a 52-week study consisting of three parallel cohorts, randomized equally to either three milligrams per kilogram or five milligrams per kilogram of efzopidamide or placebo, dosed intravenously once a month for a total of 12 doses. The study intends to enroll 264 patients with pulmonary sarcoidosis at multiple centers in North America, Europe, and Japan. The trial design incorporates a forced steroid taper design with the primary endpoint of the study being steroid reduction. Secondary endpoints include measures of lung function and sarcoidosis symptoms. The trial design for FSOFIT is based on key learnings from the Phase 1b2a trial that we believe sets up this study for clinical and regulatory success. This includes takeaways from the forced steroid taper and results for steroid reduction in the post-taper period. In the 1b2a study, which was a six-month trial, patients underwent a forced steroid steroid taper to five milligrams, with the option to be titrated to zero at week 16 based on symptoms. We learned that patients could generally handle the forced taper, and even though an eight-week taper was aggressive, we found that those patients on efsofitamide were able to taper more successfully. To be able to best evaluate the efficacy of efsofitamide compared to placebo, in efsofit, patients will be forced to fully taper their steroid to zero milligrams. though over 12 weeks instead of eight. We believe that by providing more time for the taper and tapering steroids completely, and finally by following patients for an additional 24 weeks compared to the prior study, we expect more patients receiving placebo to experience worsening symptoms requiring increased steroids compared to patients receiving efsofitamide. We also have adjusted the entry criteria for background steroids from a minimum of 10 milligrams in the 1b2a study to a minimum of 7.5 milligrams of prednisone per day in the phase three. This aligns with feedback from physicians, but there are many patients who require a bit less than 10 milligrams of daily steroids to maintain their symptoms and could really benefit from a reduction. Even a reduction of two or 2.5 milligrams of daily steroids for these patients over the course of time could be very impactful. On the whole, we believe these adjustments will enrich the study and build upon the positive findings from the Phase 1b-2a trial. Again, efsofit is the largest interventional study for patients with sarcoidosis to date. With this study, efsofitamod is positioned to be the first disease-modifying therapy to market for patients with this debilitating disease. And based on data to date, we believe one that could reduce steroid burden, maintain lung function, and improve symptoms. I'll now turn the call over to Leslie Nangle, our VP of Research, to discuss our preclinical and discovery programs and our PR&A Synthetase platform.