Ethos Technologies Inc.

Good afternoon, ladies and gentlemen, and welcome to ATAR Pharma, fourth quarter and full year 2021 conference call. At this time, all participants are in listen-only mode. Later, we will conduct a question-and-answer session, and instructions will be given at that time. If anyone should require assistance during the conference, please press the star, then zero on your touchtone telephone. 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. Dunston, you may begin.

Thank you, and good afternoon, everyone. Thank you for joining us today to discuss ATAR's fourth quarter and full year 2021 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, including our clinical program for Epsom Phenomone and our research and discovery programs in Neuropillin 2, including our preclinical program for ATYR 2810. Jill will review the financial results in 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, quarterly reports on Form 10-Q, and in 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, ATI or PHRMA 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 fourth quarter and full year 2021 results conference call. 2021 was a milestone year for ATYR, which culminated in clinical proof of concept for our lead therapeutic candidate, efsofitimod, which was formerly known as ATYR1923, and validation for our tRNA synthetase biology platform. The positive results reported from our Phase 1b-2a study of afsofitamide in pulmonary sarcoidosis suggest that this novel immunomodulator has the potential to be a transformative disease-modifying therapy for patients with this and other fibrotic lung diseases with high unmet need. We've carried this momentum into the start of 2022. The receipt of the U.S. Food and Drug Administration, or FDA, orphan drug designation for esophetamide for sarcoidosis underscores the significant unmet need for new treatments for these patients. And our positive end of phase two meeting with the FDA has provided a path forward to initiate a planned registrational study of esophetamide that will incorporate their feedback. Preparations for this study are underway and we are on track to initiate this study in the third quarter of this year. We also remain on track with the IND enabling work for ATYR2810 or 2810, our lead anti-neuropilin 2 or NRP2 antibody. And we expect to initiate a phase one study in cancer patients in the second half of this year. Importantly, the strength of the proof of concept data for sulfidamide provided the opportunity to generate the necessary capital to carry out the planned registrational trial, which we expect to be the highest value driving catalyst for ATAR yet. We ended 2021 with approximately $108 million in cash, and our strong balance sheet positions us well to advance our clinical programs and progress our pipeline in the year ahead. As we begin, I will summarize a few highlights since we last spoke in November. We will be proceeding with the advancement of F-sulfidamide and pulmonary sarcoidosis following a positive end of Phase II meeting with the FDA. We received orphan drug designation from the FDA for efsofitamide for the treatment of sarcoidosis. We announced an agreement with Fujifilm DioSynth Biotechnologies, a leading contract development and manufacturing organization for biologics, viral vaccines, and viral vectors for the manufacture of efsofitamide. And we had a poster accepted for presentation at the upcoming American Association for Cancer Research, or AACR, annual meeting that details additional preclinical data generated for 2810 in cancer. We're very proud with all that we accomplished in 2021, and we're off to a strong start thus far in 2022. That provides a solid foundation to execute on what we expect to be another highly productive year for ATAR. Let's begin talking about our clinical program for efsofitamide. Efsofitamide is a potential first-in-class immunomodulator for fibrotic lung disease. F-sulfidamide 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. F-sulfidamide has been shown preclinically to downregulate inflammatory cytokines 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. F-sulfidamide binds selectively to NRP2 and therefore has the potential to normalize the immune system, serving to resolve inflammation, prevent progressive fibrosis, and 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 interstitial lung disease, or ILD, a group of rare immune-mediated disorders that can cause progressive fibrosis. Our initial ILD indication for epistophetamide is pulmonary sarcoidosis. Sarcoidosis 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 called pulmonary sarcoidosis, and the lungs are affected in more than 90% of sarcoidosis cases. The formation of these granulomas is driven by persistent aberrant inflammation. And if left untreated, it can lead to irreversible scarring or fibrosis, diminished lung function, which may lead to respiratory failure or the need for a lung transplant. We estimate there are close to 200,000 patients in the U.S. with pulmonary sarcoidosis, 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 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 substantial need for a safer, more effective treatment that could reduce or replace the requirement for chronic corticosteroid or other immunosuppressive therapy and prevent disease progression. Considering that pulmonary sarcoidosis is a rare disease with limited treatment options, we filed a request with the FDA to obtain orphan drug designation for efsofitamide. Orphan drug designation is granted to support the development of medicines for patients with unmet needs for disorders affecting fewer than 200,000 people in the U.S. This designation provides certain benefits, including the potential for seven years of market exclusivity following regulatory approval, exemption from FDA application fees, and tax credits for qualified clinical trials. We are pleased to announce earlier this year that the FDA granted orphan drug designation for efsofitamide for sargodosis. This designation emphasizes the need for new treatment options for these patients and will help support our advancing clinical program and future commercial strategy. The orphan drug designation followed the positive results from our proof-of-concept study for efsofitamide and pulmonary sarcoidosis that we reported in September 2021. Let's briefly recap some of the key findings from that important study. Regarding safety and tolerability, monthly dosing of F-sulfenamide was safe and well-tolerated at all doses. There were no drug-related serious adverse events and no signals of immunogenicity. Regarding steroid reduction and some of the other exploratory assessments of efficacy, the study demonstrated a consistent dose response and improvements compared to placebo across all key efficacy endpoints. These included steroid reduction of 58% overall from baseline compared to placebo, in steroid usage post-taper in the five milligram per kilogram treatment group, and a 49% overall baseline reduction compared to placebo in the three milligram per kilogram treatment group. Complete steroid taper to zero milligram was achieved and maintained for 33% of patients in the five milligram per kilogram treatment group, compared to no patients in any other group. Clinically meaningful improvement in forced vital capacity, or FBC, which is a measure of lung function. At week 24 of 3.3% in the five milligram cohort and 2.8% in the three milligram cohort, both compared to placebo. Clinically meaningful improvement over placebo observed for symptoms and sarcoidosis specific quality of life indices in the five milligram and three milligram treatment groups. Finally, dose dependent trends of improvement in key inflammatory biomarkers compared to placebo with control seen in all efsofitamide treated groups. To the best of our knowledge, 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. And these findings confirm the potential of efsofitamide to be a tremendously impactful therapy. We plan to present some of these findings in more detail in several posters that have been accepted for presentation at the upcoming American Thoracic Society, or ATS, international conference, which is scheduled to take place May 13th through 18th in San Francisco this year. We've also submitted a manuscript with full results to a major medical journal to be considered for publication in the near future. Following the proof of concept results, we met with the FDA in a Type B end of phase two meeting to discuss these data and subsequent clinical development and path to registration for efsofitamide for pulmonary sarcoidosis. We're very pleased with the productive feedback we received, and as a result, we intend to initiate a planned registrational study of efsofitamide in the third quarter of this year. Following the FDA's review of the data package, including data from the non-clinical program, early clinical trials, and the recently completed Phase 1b2a study, we are proceeding with the advancement of efsofitamide. The FDA discussed endpoints that we detailed in our proposed registrational study and prioritization of outcome measurements that would best support the evaluation of efsofitamide's efficacy, including a combination of both objective and subjective clinically meaningful outcomes, as the assessment of these outcomes is what is most meaningful to providers and patients. The FDA advised the continued evaluation of multiple doses of efsofitamide in a longer duration study to establish a controlled safety database that supports the determination of the optimal dose for chronic use. While we saw the strongest efficacy effects in the five milligram per kilogram treatment group in the phase 1b2a study, signals of efficacy demonstrated in the three milligram per kilogram treatment group also warrant further exploration in order to assess the safest, most effective dose, rather than only a maximum effective dose. In addition, the FDA determined that the completed, ongoing, and planned non-clinical studies were considered supportive of clinical development, and a waiver of carcinogenicity studies requirement was granted, a waiver of that was granted. Based on the weight of evidence from the non-clinical studies, no additional animal safety studies are required for this novel biologic. We were fortunate to be joined in this meeting by some very strong supporters. This includes Dr. Robert Boffman, professor of medicine and pulmonologist at the University of Cincinnati Medical Center. Dr. Boffman is a world leading authority on sarcoidosis, and he came away from the meeting impressed that the FDA appreciated the need for a therapeutic that demonstrates a steroid sparing effect in these patients. We were also joined by Mary McGowan, CEO of the Foundation for Sarcoidosis Research, or FSR, who is our partner for the Phase 1b-2a study. The FSR is a strong advocate regarding the need for safer, effective treatments, including those that focus on patient-centered outcomes and serve as a critical and much-needed voice on the behalf of the sarcoidosis community. This positive end-of-Phase 2 meeting is an important milestone for ATAR. And we now have a path forward to initiate a planned registrational study of esophitamide that will incorporate the feedback we receive from the FDA. As the most advanced clinical development program for pulmonary sarcoidosis, we have an opportunity to establish efficacy endpoints that demonstrate clinically meaningful treatment effects, which will serve as the basis for future FDA review of other therapies in this significantly underserved disease. Preparations for the study are underway, and we are on track to initiate this study in the third quarter of this year. We're working to finalize a protocol incorporating feedback from the FDA for an IND submission. We're planning for this study to be a large worldwide trial spanning multiple centers throughout the U.S. and other countries. In response to our proof of concept data, we've received excellent interest from physicians who may want to serve as investigators. and we intend to implement a robust clinical operations plan that will permit us to open numerous clinical trial sites to support timely completion of this next study. Cure and Pharmaceuticals, our partner for efsofitamide for ILD in Japan, will be an important part of this study, having successfully completed a required Phase I safety study of efsofitamide in healthy Japanese volunteers, which permits Cure to join this late-stage study in pulmonary sarcoidosis patients. CURIN will manage all operations and enrollment in Japan and may intend to use this data to support their own filing of efsofitimod in Japan. As we've mentioned before, we plan to be active at the upcoming ATS conference in mid-May and anticipate being able to provide additional updates on this program at that time. Now let's take a few minutes to discuss our preclinical programs. Through a broad receptor screen for efsofitimod, which is derived from the tRNA synthetase, HARs, we discovered its binding partner, NRP2, as a target. NRP2 is a cell surface receptor that plays a key role in lymphatic development and in regulating inflammatory responses. NRP2 binds to multiple ligands and co-receptors to influence various cellular functions, and we believe it's a compelling therapeutic target, not only in inflammation and fibrosis, but also cancer. To approach this target in a manner distinct from efsofitamide, We developed a panel of blocking antibodies to selectively target distinct domains of this untapped target, including those interacting with semaphorins, VEGF, and certain chemokines such as CCL21. One of the blocking antibodies we developed, 2810, is a fully humanized monoclonal antibody that selectively and functionally blocks the interaction between NRP2 and VEGF. This novel antibody is our lead candidate to advance the clinical development for cancer, including aggressive solid tumors with increased NRP2 expression, which is linked to worsened patient outcomes and promotion of resistance to certain current therapies in cancer. We've generated a body of compelling preclinical data in multiple aggressive solid tumor models, including triple negative breast and non-small cell lung cancers, demonstrating significant effects on tumor growth with the treatment of 2810. One administers in combination with widely used anti-cancer therapeutics including chemotherapeutic agents such as cisplatin or targeted VEGF antibody bevacuzumab. We've gained key mechanistic insights regarding the ways in which 2810 may mediate its anti-tumor effects. And as we continue to generate valuable data for 2810 to determine tumor types, and exact treatment settings in which this novel antibody may demonstrate the most beneficial treatment effects. We plan to present some of these new findings in a poster at the upcoming AACR Annual Meeting on Monday, April 11th in New Orleans. The presentation will further characterize the shared elements that render certain solid tumor types responsive to 2810 treatment. We're in the process of completing the required work for 2810 to support its planned clinical development in oncology. We're currently finishing up some remaining IND enabling activities and honing in on selection of an indication. Manufacturing activities with our partner Lonza remain on track and we expect to initiate a phase one study of 2810 in cancer patients in the second half of this year. Finally, we continue to mine our tRNA-sensitized biology platform, which is the foundation for ATAR's science and approach to drug development, to discover new targets and signaling pathways affected by these extracellular fragments in order to yield new pipeline candidates. There are 20 tRNA-sensitized gene families, and our intellectual property portfolio covers protein derivatives from all of these, with over 300 protein compositions patented. I'll now turn it over to our Chief Financial Officer, Jill Broadfoot, to review our financial results.