Ethos Technologies Inc.

Good afternoon, ladies and gentlemen, and welcome to the Atire Pharma Second Quarter 2021 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 will need to press star 1 on your telephone. If you require any further assistance, please press star 0. As a reminder, this conference is being recorded for replay purposes. It is now my pleasure to hand the conference call over to Ashley Dunstan, ATAR's Director of Investor Relations and Corporate Communications. Ms. Dunstan, you may begin.

Thank you, Operator, and good afternoon, everyone. Thank you for joining us today to discuss ATAR's second quarter 2021 operating results and corporate updates. 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, including our clinical program for APYR 1923 and our research and discovery program in Neuropilin 2, including our preclinical program for APYR 2810. Jill will review the financial results and our current financial positioning 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 and quarterly reports on Form 10-Q. 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 second quarter 2021 results conference call. As we make our way through 2021, we continue to make significant progress in our mission to translate novel biological pathways into innovative therapeutics for improved outcomes for patients. Notably, we recently completed the last subject visit in our phase 1B, 2A proof of concept study of our lead therapeutic candidate, ATYR1923 or 1923 in pulmonary sarcoidosis, our lead interstitial lung disease or ILB indication. We expect to report results from this important study in mid-September of this year. This is a significant milestone for ATYR and the upcoming readout represents a key inflection point for our 1923 clinical program and tRNA synthetase biology platform. The clinical proof of mechanism for 1923, established from our Phase II study in COVID-19 patients and the favorable safety profile demonstrated today, along with the preclinical efficacy observed in multiple translational ILD models, support the potential for 1923 as a new therapeutic approach for pulmonary sarcoidosis and possibly other forms of ILD. We believe 1923 could potentially offer an alternate to current treatments such as steroids with improved efficacy and fewer side effects. In addition to finishing up the important work for our 1923 clinical program, we've continued to generate new data and publish research related to our preclinical program, further strengthening our pipeline. As we begin today, I'll summarize a few additional highlights since we last spoke in May. We hosted a key opinion leader or KOL event on current treatment options for pulmonary sarcoidosis featuring Dr. Daniel Culver, Chair of Pulmonary Medicine and Director of Diffuse Parenchymal Lung Disease at the Cleveland Clinic. Cura and Pharmaceutical Company, our partner for the development and commercialization of 1923 for ILD in Japan, completed a phase one study in healthy Japanese volunteers. We had two abstracts for 1923 accepted for presentation at the upcoming European Respiratory Society, or ERS, International Congress. We expanded our research collaboration with the Ohio State University, or OSU, to deepen the understanding of the immune mechanisms of sarcoid granuloma formation and identify potential biomarkers of efficacy for 1923 for pulmonary sarcoidosis. Dr. Elliot Krauser, Professor of Pulmonology, Critical Care, and Sleep Medicine at OSU, will serve as principal investigator. We received a patent grant from the US Patent and Trademark Office covering methods for the use of histidyl tRNA synthetase, or HARs, FC fusion proteins, which includes the use of 1923 for reducing inflammatory response in the lung. We appointed Dr. Sarah Zachnoin, a highly accomplished drug development and clinical research executive, to our board of directors. Dr. Zachnoin is a hematologist oncologist who has previously held chief medical officer positions at several biotech companies. We presented a poster at the Keystone Symposia Cancer Stem Cells, Advances in Biology and Clinical Translation meeting related to preclinical research highlighting mechanistic insights into the tumor inhibitory effects of ATYR2810 or 2810, our lead anti-neuropilin 2 or NRP2 VEGF antibody candidate in preclinical development for cancer. And finally, we presented a poster at the Antibody Engineering and Therapeutics Europe virtual conference related to a second anti-NRP2 antibody, which demonstrated the selective blocking of that antibody to semaphore and 3F signaling. We've made significant progress during the first half of this year, and we see the second half of this year shaping up to be as equally productive. Let's begin with our clinical program for 1923. We're developing 1923 as a potential treatment for patients with ILD, a group of rare immune mediated disorders that can cause progressive fibrosis of the lung. There are more than 200 types of ILD, but roughly 80% of these patients fall into four main disease categories, pulmonary sarcoidosis, chronic hypersensitivity pneumonitis, connective tissue disease, ILD, and idiopathic pulmonary fibrosis. All of these diseases have limited standard of care with substantial morbidity and mortality. 1923 has the potential to address this unmet need by targeting the aberrant immune responses central to ILD pathology and preventing progression of fibrosis, the key driver of poor outcomes in these patients. We estimate there are over 500,000 ILD patients in the U.S. alone and over 3 million patients globally. While our initial focus for 1923 is pulmonary sarcoidosis, the mechanism of action or MOA, data from preclinical models, and demonstrated effects on key inflammatory biomarkers in patients with COVID-19 pneumonia suggest that 1923 could have potential in other ILD indications as well. Our initial ILD indication for 1923 is pulmonary sarcoidosis. A hallmark disease characteristic of pulmonary sarcoidosis is the formation of granulomas, or clumps of immune cells in the lungs. The formation of these granulomas is driven by persistent aberrant inflammation. If left untreated, it 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 the patient population for pulmonary sarcoidosis to be approximately 200,000 patients in the U.S., although estimates do vary. About half of all patients will require some form of systemic therapy, and unfortunately 30% of all patients will have chronic progressive disease despite available treatments. The current standard of care for pulmonary sarcoidosis typically includes treating the inflammation with corticosteroids and other immunosuppressive therapies. While these treatments can help manage inflammation and alleviate symptoms, such as cough and shortness of breath, 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. So there is a substantial need for a safer, more effective treatment that could reduce or replace the requirement for chronic corticosteroid or other immunosuppressive therapy. This need was recently reinforced by one of the leading experts in the field, Dr. Daniel Culver at the Cleveland Clinic. In June, we hosted a KOL event with Dr. Culver, who discussed limitations with the current standard of care and unmet medical need for treating patients with pulmonary sarcoidosis, including the toxicity burden of chronic steroid use and the need for better steroid-sparing agents. Through this event, we heard firsthand from Dr. Culver about some of the side effects related to steroid use in sarcoidosis, including some staggering statistics related to metabolic complications, quality of life, economic burden, and risk of mortality, leading him to believe that there is no safe maintenance dose of corticosteroids in patients with sarcoidosis. If you are unable to attend the event, I encourage you to listen to the replay, which can be found on our website. Now let's talk a bit more about 1923 and why we believe It is a potential first-in-class immunomodulator for some of the inflammatory lung diseases we've been discussing, including pulmonary sarcoidosis. 1923 is a novel FC fusion protein based on the naturally occurring splice variant of the lung-enriched tRNA synthetase HARS fragment that downregulates aberrant immune responses in inflammatory disease states. 1923 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. 1923 selectively binds 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. As a reminder, our ongoing trial in pulmonary sarcoidosis is a phase 1b2a randomized, double-blind, placebo-controlled, multiple ascending dose clinical trial in 37 pulmonary sarcoidosis patients. The trial consists of three cohorts testing doses of one, three, and five milligrams per kilogram of 1923, or placebo, dosed intravenously every month for six months. The primary objective of the study is to evaluate the safety and tolerability of multiple ascending doses of 1923. Secondary objectives include assessment of the potential steroid sparing effects of 1923, in addition to other exploratory assessments of efficacy, such as lung imaging, lung function assessed by pulmonary function tests, and relevant serum biomarkers. Based on our trial design, which includes a forced steroid taper, an integral element of the study is to assess steroid burden in the 1923 treatment groups compared to placebo. As we have discussed here a bit today and reinforced by Dr. Culver, there is a crucial need for alternatives to existing treatment options, including steroids. We look forward to the results of this study, which we expect to report in mid-September of this year. While we have advanced our clinical program for 1923, we continue to conduct research to deepen our understanding of 1923's MOA and advance our understanding of sarcoidosis disease pathology. We are pleased to have announced that we have two abstracts for 1923 that have been accepted for presentation at ERS in September. One of these abstracts will present the biomarker data from our Phase II study in patients with COVID-19 pneumonia. Earlier this year, we released some findings from this data, which showed substantial anti-inflammatory effects in patients, consistent with findings from our animal models. This data provides the first inpatient mechanistic proof of concept for 1923. and we look forward to sharing more details about the data at ERS. A second abstract will present data from a pilot proof of concept study conducted in collaboration with Dr. Elliot Krauser, a leader in sarcoidosis research and treatment at OSU, which demonstrated the ability of a splice variant of HARS, the active component and portion of 1923, to disrupt sarcoid granuloma formation in vitro. Based on these successful pilot study findings, we announced just earlier today that we are expanding our research collaboration with OSU and Dr. Krauser to continue this important work. The collaboration is intended to deepen our understanding of the immune mechanisms of sarcoid granuloma formation and identify potential biomarkers of efficacy for 1923. The study will assess the effect of 1923 on sarcoid granuloma formation in vitro using blood samples taken from sarcoidosis patients. We'll also focus on identifying the relevant immune mechanisms triggered in granuloma formation and analyze promising biomarkers predictive of strong granuloma formation in order to assess whether they could be used as a predictive biomarker for treatment selection or treatment response to 1923. We're very excited to continue our work with Dr. Krauser and his lab at OSU. The research generated from this collaboration may help direct us to biomarkers indicative of a population that may be sensitive to treatment with 1923, which could present the opportunity to take a much needed step forward in managing this disease and lead to improved patient outcomes. To wrap up our discussion on 1923, we're pleased to inform you that Cure and Pharmaceutical, our partner for the development and commercialization of 1923 for ILD in Japan, has completed its phase one study which investigated the safety, pharmacokinetics, or PK, and immunogenicity of 1923, known as KRP-R120 in Japan, in 32 healthy Japanese volunteers. In this study, 1923 was observed to be generally safe and well tolerated, with no drug-related serious adverse events, and PK findings were consistent with previous studies of 1923. Before we turn to our preclinical program, I want to take a minute to highlight an important business update that occurred in the second quarter. In May, we announced the appointment of Dr. Sarah Zachnoin to ATAR's Board of Directors. Dr. Zachnoin, a hematology oncologist by training, is an experienced pharmaceutical drug development and clinical research executive, who has previously held chief medical officer positions at several biotech companies. She also has a wealth of experience working at large pharmaceutical companies, including Novartis and sharing plow, now Merck, where she was involved in supporting the development of a number of important marketed therapies, including Gleevec, Tasenia, Xshade, and Temadar. We believe Dr. Zachnone's experience in advancing programs at both biotech and large pharma companies is ideally situated to support and guide ATAR as we prepare for the next clinical stage program to emerge, from our tRNA synthetase biology platform. Now I'd like to take a few minutes to discuss our preclinical program, which includes the development of anti-NRP2 antibodies for cancer and inflammation. NRP2 is a compelling therapeutic target in a number of disease areas, including oncology and inflammation. When it comes to cancer, NRP2 is upregulated on a variety of solid tumors and is particularly enriched in highly aggressive tumors, with expression linked to worsened patient outcomes in several cancers, which may include drug resistance to current therapies, such as chemotherapy or targeted agents. NRP2 is also highly expressed on key immune cells, implicating in regulating cancer progression, including tumor-associated macrophages and myeloid-derived suppressor cells, among others. Antibodies that can selectively block different aspects of NRP2 signaling pathways may have the therapeutic potential in these aggressive cancers where NRP2 is implicated. Our lead anti-NRP2 antibody in IND candidate is 2810, a fully humanized monoclonal antibody that specifically and functionally blocks the interaction between NRP2 and VEGF. The role of NRP2 and VEGF signaling in the tumor microenvironment and its potential importance in the progression of certain aggressive cancers is becoming increasingly validated. We have generated a body of compelling preclinical data in both human derived and animal models demonstrating 2810's blocking ability and tumor inhibitory effects. Notably, we have continued to strengthen our mechanistic understanding of the link between NRP2 and the critical process of epithelial mesenchymal transition, or EMT, which is of great importance in regulating tumor growth, progression, and metastatic cascade. as well as being implicated in tumor evasion of the immune system. At a recent Keystone Symposium of Cancer Stem Cells, Advances in Biology and Clinical Translation, we presented a poster demonstrating that in preclinical studies, 2810 sensitized certain patient-derived xenograft models of triple negative breast cancer to chemotherapy. And we are actively working to understand the underlying gene signatures that confer responsiveness. These findings build upon our mechanistic understanding of 2810. and demonstrate the molecular basis for selectivity by directly obstructing the VEGF binding site of NRP2. 2810's ability to affect EMT and cancer stem cell properties may be one mechanism by which it mediates the anti-tumor effects we have observed. This work moves us closer to identifying the underlying characteristics within a tumor that may confer responsiveness to treatment with 2810. IND enabling activities for 2810 to support advancement to clinical trials in cancer in the future are ongoing. I will now turn it over to our Chief Financial Officer, Jill Broadfoot, to review our financial results.