Arcturus Therapeutics Holdings Inc.

Greetings and welcome to the Arcturus Therapeutics fourth quarter and full year 2020 earnings call. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Nita Savardzada, Head of Investor Relations, Public Relations, and Marketing. Thank you, Nita. You may begin.

Thank you, Operator, and good afternoon, everyone. We are joined today by Joseph Payne, President and CEO, Andy Sassin, CFO, Dr. Pat Chivikula, CSO and COO, Dr. Steve Hughes, our Chief Medical Officer, and Professor Wing-Ying Yang, Deputy Director of Emerging Infectious Diseases Program from Duke-NUS Medical School, who is also in Arcturus' Vaccine Platform Scientific Advisory Board. Before we begin, I would like to remind everyone that except for statements of historical facts, the statements made by management and any responses to questions on this conference call constitute forward-looking statements that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. Any statements other than the statements of historical facts included in this communication including those regarding the company's supply agreements and potential supply agreements, the potential future manufacturing and other operations, the status and results of clinical development programs, the planned initiation, design or completion of clinical trials, the likelihood of success of the company's coronavirus COVID-19 vaccine candidate or other product candidates and the company's current and future cash and financial position are forward-looking statements. Actual results and performance could differ materially from those projected in any forward-looking statements as a result of many factors including without limitation, an inability to develop and market product candidates, unexpected clinical results, and general market conditions that may prevent such achievements or performance. Such statements are based on management's current expectations and involve risks and uncertainties, including those discussed under the heading risk factor in ArcTrace's most recent annual report on Form 10-K with the SEC and in other filings that ArcTrace makes with the SEC. Except as otherwise required by law, we disclaim any intention or obligation to update or revise any forward-looking statements which speak only as of the date they were made, whether as a result of new information, future events, or circumstances, or otherwise. Now it is my pleasure to pass the call to Joe Payne, President and CEO of Arcturus. Joe, please go ahead.

Hey, thank you, Netta, and good afternoon to all. Thank you for joining the Arcturus' quarterly call today. I'd like to begin by congratulating J&J on their recent approval of their one-shot COVID vaccine. I'm sure their team has been working very hard and it's great to see their efforts being rewarded with success. No doubt the world wants access to one-shot vaccines this year in 2021. And it appears that COVID is here to stay for years to come. It's now a global pathogen, very contagious, airborne, and new challenging variants are arising. The endemic market will very likely be addressed through periodic single administrations. Therefore, a vaccine that is redosable is also important. A vaccine with an immunological profile that could potentially provide broader variant coverage is important. A vaccine technology that is rapidly updatable as needed is also important. Arcturus is developing differentiated next generation class of mRNA-based medicines. and we're very excited about the prospects for our company and our rapidly maturing pipeline. We believe that mRNA therapeutics have now come of age as a therapeutic modality to provide enormous benefit to human health, not just in vaccines, but also for a wide range of transformative medicines for serious diseases. During the last several months, there has been an increasing appreciation for the promise of mRNA approaches with the clinical successes and widespread use in tens of millions of individuals of the first wave of mRNA vaccines. We believe that this is only the beginning and that our platform has the potential to generate vaccines with a differentiated profile compared to those in use today, as well as to create medicines for numerous other diseases. Arcturus has made substantial progress during 2020 and during the beginning of this year with our lead clinical pipeline candidates, our promising preclinical candidates, and in advancing Arcturus' core capabilities and underlying science. We have continued to move our leading chemistry forward, expanded our intellectual property estate, and rapidly advanced our CMC, our manufacturing capabilities. I'll begin with an overview for ARCTO21. That's our differentiated COVID-19 vaccine candidate based on a self-transcribing and replicating mRNA, also known as self-amplifying mRNA technology. When we consider the COVID-19 pandemic at a macro level, our expectation is that it will be a prolonged global issue that will require the vaccination of billions of individuals for years to come. RNA coronaviruses are well known to mutate rapidly, and while we're not surprised with the emergence of viral variants during this global pandemic, We are carefully monitoring the situation. We're carefully evaluating these variants as they arise. We believe that because of the specific type of cellular immunogenicity that ARCTO21 promotes, that our vaccine candidate may provide broad protection to many of the SARS-CoV-2 variants in circulation. It is also possible that these variants may require periodic adaptation of vaccines administered. as is already done with vaccines for influenza. One of the benefits of an mRNA approach is that our vaccines are easily and rapidly able to be modified as needed. Furthermore, we believe that ARCTO21 could have a differentiated and highly attractive profile, a vaccine product that is not a frozen liquid, one that is lyophilized and requiring only a single administration. ARCTO21 has the potential over time to become a favoured vaccine option for many countries. We continue to rapidly advance our clinical development program for ARCTO21, and based on the highly promising clinical and preclinical data that we've obtained to date, we have recently made the decision to move forward with a single administration regimen and phase three development. Our decision to advance the single administration regimen is based on our phase one slash two study data that show favorable tolerability and both substantial humoral and cellular immunity observed after a single injection. In addition to our clinical data, we have supportive data from both primate and human ACE2 transgenic mouse challenge models that demonstrate robust protection with a single dose regimen. We are particularly encouraged by the robust cellular immune response seen in phase one slash two study subjects that were administered our vaccine. A growing body of clinical data provides support for the important role of CD8 cells in providing protection against COVID-19, and our data gives us additional confidence in the potential efficacy of our vaccine. We are currently conducting final analysis on the results of the Phase 1-2 study, and we plan to submit the results for publication in the second quarter. I also want to mention new data that has been submitted for publication based on work from Dr. Uy and his colleagues. We have been seeing several reports emerging that conventional mRNA vaccines may be highly effective after the first shot. So it begs the question, how does ARCT021, a self-amplifying mRNA vaccine, compare to the single shot of an approved conventional mRNA vaccine? Directly comparing vaccines has been challenging for investors and scientific community. because everyone uses different methods and assays to measure immunogenicity. But to help us all, to help all of us with this challenge, the Duke NUS Medical School and their colleagues have recently collected immunogenicity data from participants receiving a single injection of an approved conventional mRNA vaccine. And the data collected utilized the same assays and methods that we used for determining the immunological profile of ARCTO21. The research examined the adaptive immune responses following administration of the approved conventional mRNA vaccine based on a cohort of 20 healthcare workers. The key results from the study are included in our press release issued just recently this afternoon. The data suggest that following a single administration of an mRNA vaccine, Binding antibodies and cellular immunity, or T cells, are associated with protection against COVID-19 at early time points. Interestingly, at these same time points where clinical protection is observed, neutralizing antibodies or antibody levels have been found to be negligible, suggesting that these are not necessarily required for clinical efficacy. The findings from our ARCTO21 single-shot immunogenicity based on our phase one slash two study results compares favorably with the findings from Dr. Uwe's study examining the correlates of protection based on conventional mRNA vaccines. We believe these data provide additional support for the potential efficacy of the ARCTO21 vaccine. Following our phase one slash two study, we have now dosed over 500 subjects in our ongoing phase two study. This is a multicenter, randomized, observer-blind study, which is designed to evaluate the safety and immunogenicity of the study vaccine in younger and older adult participants. The study is being conducted in both the United States and Singapore. It is evaluating two dose levels, 5 micrograms and 7.5 micrograms. We are also evaluating prime boost regimens. By evaluating a prime boost regimen, we'll be studying the redosability of our approach. We believe that a redosable vaccine that utilizes the novel lunar non-viral vector delivery system is important, and that a single-shot mRNA vaccine that is more easily distributable, like lyophilized or non-frozen liquid, would be a valuable option for many countries. We plan to finalize the specific ARCT021 dose for our Phase III study, to be confirmed by the pending interim analysis data from this ongoing phase two study, which we expect to get during the second quarter. Our clinical team in parallel is already preparing to advance a five microgram single dose regimen for phase three development. And we continue to track towards Q2 study start. We believe that we have the potential to obtain data in the second half of the year and could obtain ARCTO21 EUA or Emergency Use Authorization in at least one jurisdiction in the second half of this year or H2 2021. Well, we are fortunate to have Dr. Uy, the Professor of Emerging Infectious Diseases at Duke NUS Medical School. He's here on the call today to present the recent data. Dr. Uy, the time is now yours. And we here in San Diego will advance the slides per your direction.