Sanjay Shukla
Analyst · Oppenheimer
Thank you, Ashlee. Good afternoon, everyone, and thank you for joining us for our third quarter 2020 results conference call. As we begin with our third quarter 2020 update, I would like to take a moment to acknowledge all the hard work and dedication from the aTyr team, our investigators, partners, collaborators and patients who have risen to the challenge of learning to operate under the unique circumstances that we have all experienced this year due to the COVID-19 global pandemic. With everyone's support and cooperation, we believe we are having an incredibly productive year even amidst the pandemic. Now let's get started with our quarterly review and corporate update. During the third quarter of 2020 and subsequent period, aTyr remained focused on our clinical program for our lead therapeutic candidate, ATYR1923. We now have 3 active clinical trials as part of this program. Most notably, we have completed enrollment in our Phase II trial in COVID-19 patients with severe respiratory complications, and we expect to report top line data from this study around the turn of the calendar year. Our trial in patients with pulmonary sarcoidosis and our partner Kyorin's trial in healthy volunteers in Japan both continue to enroll. In addition, we achieved key milestones in our research and discovery programs, where today, I am proud to announce that we have selected our lead candidate from our NRP2 antibody program in oncology. As we begin, I will summarize additional key highlights from the third quarter and subsequent period. We entered into a research collaboration with the Medical University of South Carolina, or MUSC, and principal investigator, Dr. Robert Gemmill to support our NRP2 antibody program in oncology. We discovered new receptor targets for 2 tRNA synthetases from our pipeline as part of our research collaboration with CSL Behring. The receptor targets may have utility in the development of new therapeutic approaches for cancer and fibrosis. And finally, we published a paper in the peer-reviewed journal mAbs, which highlighted the novel technological advances pioneered by our research team to isolate, characterize and engineer high affinity therapeutic antibodies. We've made significant headway with our clinical and research programs, with steady and consistent progress throughout 2020 amidst the challenges presented by the pandemic. And we fully expect this momentum to continue through the fourth quarter. Today, I will provide an update on our clinical program with our lead therapeutic candidate 1923 for each of our 3 trials. I will also comment on our ongoing preclinical research and development efforts for our programs in NRP2 and tRNA synthetase vitality. Jill will conclude with a review of our financial position. Let's begin with our Phase II trial of 1923 in COVID-19 patients, which recently completed enrollment. Many COVID-19 patients with severe disease experience a form of interstitial pneumonia, caused by an excessive inflammatory response in the lung, which can lead to serious and sometimes fatal respiratory complications. These patients are more likely to be hospitalized, require supplemental oxygen, need mechanical ventilation and spend time in the ICU. They may also experience longer hospital stays and permanent injury to their lungs. While we are encouraged by the progress in the development of vaccines and standard of care has improved, we believe there will continue to be a need for new and effective therapies to treat the symptoms of patients hospitalized with severe cases of COVID-19. 1923 is a potential first-in-class immunomodulator that downregulates cavern immune responses in inflammatory disease states. 1923 has been shown preclinically to downregulate T cell responses, thereby dampening the inflammatory cytokine and chemokine signaling, both of which have been implicated in these severe COVID-19 cases. Further, NRP2 is upregulated on key immune cells known to play a role in inflammation. And as we have learned, this includes lung tissue in patients who have died from COVID-19-related severe respiratory failure. We believe 1923 binds selectively to NRP2 to normalize the immune system, serving to resolve inflammation and prevent progressive fibrosis, thereby stabilizing lung function and alleviating morbidity and mortality. Data from 1923 in animal models of the new mediated acute lung injury demonstrate that 1923 is more effective if given earlier in disease progression. Further, 1923 downregulated T cells, serving to do more than just act on one individual cytokine. We believe that by administering 1923 earlier in the excessive inflammatory response in COVID-19, notably before patients require mechanical ventilation, 1923 may be able to dampen the immune response and improve patient outcomes. Based on the strong scientific rationale with 1923's mechanism of action and overlapping disease pathology, we worked very closely with the FDA to initiate a Phase II randomized, double-blind, placebo-controlled study in hospitalized COVID-19 positive patients with severe respiratory complications, who do not require mechanical ventilation. Patients enrolled in the trial were randomized 1:1:1, to a single intravenous dose of either 1 or 3 milligrams of 1923 or placebo and are followed for 60 days post treatment. The trial is designed to evaluate the safety and preliminary efficacy of 1923 as compared to placebo through the assessment of key clinical outcome measures. An independent data and safety monitoring board, or DSMB, conducted a preplanned blinded interim safety analysis after the first 5 patients were dosed. The study drug, 1923 or placebo, was observed to be generally safe and well tolerated with no drug-related serious adverse effects. And the DSMB recommended the trial continue unmodified. These findings are consistent with previous safety assessments of 1923, including a Phase I study in healthy volunteers and blinded DSMB reviews in our ongoing Phase Ib/IIa trial in pulmonary sarcoidosis patients, including reviews of cohorts testing the very same doses being tested in the COVID-19 study. Last month, we announced that we completed enrollment in this study. The trial enrolled a total of 32 patients at hospitals in the U.S. and Puerto Rico, exceeding the target enrollment of 30 patients. We expect to report top line data from this study right around the turn of the calendar year. The top line data will include data on safety, including adverse events and some of the key clinical outcome measures for all patients enrolled in the trial. In particular, we will focus on time to recovery and proportion of patients achieving recovery as well as clinical improvement as assessed by change from baseline in the WHO ordinal scale. These clinical outcome measures are in line with those being prioritized by the FDA and similar to those reported by other trials investigating new therapies for this patient population, including some that have been approved or granted emergency use authorization. We're very pleased to have completed enrollment in this study. We believe 1923 holds great promise as a potential therapy to treat respiratory complications that result from COVID-19. 1923 is not a repurpose therapy. It has been rigorously designed and developed to target aberrant immune responses in the lung. It has an existing and growing safety database and the disease pathology of COVID-19 continues to unfold as one with increasing overlap with 1923's mechanism of action. Our approach to initiating and conducting this trial has been thoroughly evidence-based, and we are now focused on reporting the data in a manner with the highest degree of integrity. By doing so, we aim to provide for the optimal outcome and potential next steps for the program. We're very eager to share the top line results very soon. Now let's discuss our Phase Ib/IIa trial of 1923 in patients with pulmonary sarcoidosis, which is currently enrolling. Pulmonary sarcoidosis is a major form of ILD and is characterized by the formation of granulomas or clumps of immune cells in the lungs. If left untreated, it can lead to irreversible scarring and diminished lung function. Current treatments are limited and often include treating the inflammation with corticosteroids and other immunosuppressive therapies, which have limited efficacy and serious long-term toxicity. Additionally, many patients do not respond to this current standard of care. There remains a need for a novel therapeutic option for patients with progressive disease with a better efficacy and side effect profile. As a reminder, this Phase Ib/IIa trial is a randomized, double-blind, placebo-controlled multiple ascending dose clinical trial in 36 pulmonary sarcoidosis patients. The trial consists of 3 cohorts testing doses of 1, 3 and 5 milligrams per kilogram of 1923 or placebo, dosed intravenously every month for 6 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. Throughout the course of the trial, an independent DSMB conducted 2 safety reviews, both of which had positive outcomes and permitted progression to recruit the third and final cohort of the study, which we are enrolling -- which we were enrolling at the start of the year when the pandemic emerged. At that point, some, but not all, of our investigational sites had to pause enrollment. We've learned a lot throughout the year as it pertains to navigating patient enrollment and conducting clinical trials in this environment, including with this high risk patient population. We've worked with each site and patient to adapt to the challenges that presented in order to ensure patient and provider safety, while maintaining the integrity of the trial. When needed, we allowed for the use of alternate medical safety assessments such as phone contact and the use of local labs, for example, for spirometry testing. These adjustments were within the FDA guidelines on conducting clinical trials during the COVID-19 public health emergency. And we believe they've been instrumental in permitting the trial to proceed. In August, we announced that the majority of our sites that were paused had resumed clinical trial activities. These sites continue to screen and dose patients, including in geographic areas, that have experienced a recent increase in COVID-19. We plan to provide an update on the expected timing of the results once the trial has fully completed enrollment. We'll finish the discussion of our clinical program for 1923 with a few comments on our third trial, a Phase I study currently enrolling by our partner Kyorin in Japan. Earlier this year, we entered into a collaboration and license agreement with Kyorin for the development and commercialization of 1923 for ILDs in Japan. In order to conduct clinical trials with a new therapeutic drug candidate in ILD patients, Kyorin is required by the Japanese regulator, the Pharmaceuticals and Medical Device Agency, to investigate safety and pharmacokinetics in the Japanese population. This requirement remains despite the existing data for 1923 from trials conducted in the U.S. and Australia. In September, Kyorin dosed the first subjects in this trial, which is a Phase I placebo-controlled study to evaluate the safety, pharmacokinetics and immunogenicity of 1923, known as KRP-R120 in Japan, in 32 healthy male Japanese volunteers. This trial is currently enrolling and has not experienced any delay as a result of the pandemic. We look forward to the results, which upon successful completion, will permit Kyorin to initiate patient trials for ILDs in Japan. Now let's turn to our research pipeline, starting with our NRP2 antibody program, which we believe has great potential to produce future value-driving candidates. As a reminder, NRP2 is a compelling therapeutic target in the areas of oncology and inflammation. In cancer, NRP2 is upregulated on a variety of different solid tumors. High NRP2 expression is linked to worsened patient outcomes in many cancers and may contribute to drug resistance with current therapies. Antibodies that can selectively block different NRP2 signaling pathways may have therapeutic potential. So aTyr has developed a panel of fully humanized monoclonal antibodies to selectively target distinct domains of NRP2 for diverse therapeutic applications. Today, we are proud to announce our lead investigational new drug, or IND candidate from this panel, ATYR2810. 2810 specifically and functionally blocks the interaction between NRP2 and one of its primary ligands, VEGF. The role of NRP2 and VEGF signaling in the tumor microenvironment and it's importance in the progression of certain aggressive cancers is becoming increasingly validated. Earlier this year, we presented preclinical data at the American Association for Cancer Research Virtual Annual Meeting from a collaboration with Dr. Arthur Mercurio, one of our key scientific advisers and his lab at the University of Massachusetts Medical School. This data showed that 2810 demonstrated tumor inhibitory effects and increased sensitivity to chemotherapy in human-derived organoids and other in-vitro models of triple-negative breast cancer, an extremely aggressive cancer where NRP2 has been shown to be highly expressed and many patients are not responsive to currently available treatments. These findings suggest that targeting NRP2 and the VEGF pathway may be an effective therapeutic strategy for breast cancer, and potentially other aggressive solid tumors. Based on this and additional data we have generated, internally, over the past several months in various tumor models, we will be targeting 2810 for therapeutic application in cancer with IND-enabling activities starting immediately. In addition to advancing 2810 in cancer, we continue to explore and optimize the capabilities of our antibody engineering platform by leveraging both our internal expertise and external collaborators. Dr. Robert Gemmill, Professor of Medicine Emeritus in the Division of Hematology/Oncology at MUSC will serve as a principal investigator for the collaboration, which is focused on evaluating antibodies that selectively target specific NRP2 isoforms for potential use in the treatment of lung cancer, where NRP2 is also [indiscernible]. Lung cancer is the most common cancer globally and the leading cause of cancer death. Despite currently available treatments, many tumors become metastatic or develop resistance to targeted therapies. The development of new therapeutic strategies, which may offer alternative mechanisms to existing therapeutic approaches and reduce drug resistance are greatly needed. Dr. Gemmill is a noted expert in the field of NRP2 biology and its role in cancer. His research focuses on the alteration of genes during lung and kidney cancer development. We look forward to collaborating in this area of research with Dr. Gemmill. Our NRP2 antibody program is a product of the state-of-the-art antibody discovery platform that aTyr scientists have developed. This work was recently recognized through the publication of a peer-reviewed article in the journal mAbs. This article highlights novel technological advances pioneered by our research team to isolate, characterize and engineer high affinity therapeutic antibodies. Our team continues to deploy these and other cutting-edge antibody discovery techniques to generate future pipeline opportunities. This research was conducted in collaboration with AbCellera Biologics, a leader in antibody technology and drug discovery platforms. We served as co-author of the publication. Finally, I will finish with an update on our tRNA synthetase discovery program. Through our research collaboration with CSL Behring, a leading global biotherapeutics company, we have discovered new receptor targets for 2 tRNA synthetases from our pipeline. Identifying target receptors for an extracellular tRNA synthetase helps inform our discovery and development activities by providing additional focus towards relevant disease pathways and potential therapeutic applications. These new receptor targets that we identified may have utility in the development of new therapeutics to treat not only cancer, but also fibrosis. We expect to present findings from this research at a scientific conference in the very near future. We continue to analyze the data from these intriguing findings and are in discussion to map out next steps in collaboration with our partner, CSL. Overall, we're very pleased with the progress we've made to date in 2020. We have momentum with our 3 active clinical trials for 1923. We initiated and completed enrollment in our COVID-19 trial, and we expect to report top line data from this trial very soon. We continue to enroll patients in the third and final cohort of our trial in patients with pulmonary sarcoidosis. And our partner, Kyorin, is enrolling its initial study in Japan. Today, we declared the first IND candidate from our NRP2 antibody program, ATYR2810 for oncology. And additionally, we have discovered new receptor targets for 2 tRNA synthetases from our pipeline. When we look at our progress this year compared to where we were a year ago, we're highly encouraged. We now have 3 clinical trials, a preclinical program that's advanced a new IND candidate, and 2 tRNA synthetase discovery initiatives that have advanced. As we make our way through the final quarter of the year, we're excited by our progress and the potential that our clinical programs and pipeline hold. With that, I'd like to turn it over to our Chief Financial Officer, Jill Broadfoot, to review our financial results.