Arcturus Therapeutics Holdings Inc.

Greetings and welcome to Arcturus Therapeutics' third quarter 2021 earnings call. At this time, all participants are in a listen-only mode. A 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, Deepak Naroy, Senior Director of Investor Relations. Thank you. You may begin.

Thank you, Doug. Good afternoon and welcome to Arcturus Therapeutics' third quarter 2021 financial results and corporate update call. Thank you all for joining us. Today's call will be led by Joseph Payne, President and CEO, Andy Sassine, CFO, Dr. Pat Shivakula, CSO and COO, and Dr. Steve Hughes, our Chief Medical Officer. Before we begin, I would like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed or implied by the statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the risk factors section in our forms 10-Q and 10-K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, November 8, 2021. And Arcturus specifically disclaims any obligation to update such statements to reflect future information, events, or circumstances. With that, I'll now turn the call over to Joe. Joe?

Hey, thank you, Dipankar. Good afternoon to all. Thank you for joining Arcturus' third quarter quarterly call today. We are, we are looking forward to telling you more about our recent progress highlighted by the advancement of our ARCT 154 COVID vaccine program. At Arcturus, we are developing differentiated mRNA based vaccines and novel therapeutics. Since the inception of the company, we've been working to develop a differentiated platform technology, and we've also more recently advanced a number of highly promising pipeline candidates into clinical development. We believe that our approach developing mRNA vaccines and therapeutics has the potential to directly address the underlying molecular basis of many serious diseases and in doing so we hope to provide transformative new medicines to patients living with many types of life-threatening conditions. We've made excellent progress advancing our mRNA-based vaccines and I'll begin with a discussion of our vaccine programs targeting COVID-19. So let's begin with ARCT154. This is our vaccine candidate that targets the SARS-CoV-2 variants of concern including those that are currently widespread across the globe. ARCT154 utilizes our self-transcribing and replicating RNA or the STAR technology. This vaccine includes an optimized mRNA sequence along with multiple proprietary modifications to improve its stability and increase its translation. These modifications, as well as the key rational optimizations performed, may improve the immunogenic profile of the expressed antigen, which in this case is the spike protein. I'll take a moment to identify some of the key differentiators for ARCT154. Firstly, it was designed to require a low dose level, so only 5 micrograms per dose. Secondly, it's been updated to target the currently widespread variants of concern. Third, it includes rational modifications to the antigen intended to improve immunogenicity, such as inactivating the furin cleavage site. Also, it utilizes our proprietary lunar delivery technology, our lipid nanoparticle platform. And finally, ARCT154 utilizes a self-amplifying mechanism that's designed to extend the duration of antigen expression, and this platform has shown robust T-cell responses in multiple preclinical models. Well, we've previously disclosed ARCT154 preclinical data demonstrating strong neutralizing immunogenicity in non-human primates to SARS-CoV-2 alpha, beta, gamma, and delta variants. The preclinical NHP data demonstrate that ARCT154 elicits approximately 14 to 26-fold greater neutralizing antibody titers than ARCT021, our first-generation COVID vaccine candidate. In addition, we've observed robust T-cell responses to these various strains following administration of ARCT154 in non-human primates. But shifting on to human clinical trials, we've been working closely with our collaborators in biotech to operationalize a phase one slash two slash three study designed to efficiently and rapidly apply for an EUA or an emergency use authorization application in Vietnam and also provide for a path to full approval in Vietnam. This study has the potential to lead to an EUA in Vietnam as early as the first quarter of 2022. All phases of this trial are sponsored and funded by Vinbiotech. And the randomized observer-blind study with both placebo-controlled and active-controlled cohorts that will assess the safety, immunogenicity, and efficacy of ARCT154 against COVID-19. Well, I want to pause now and emphasize that we have had an efficient quarter progressing ARCT154. It was just last August, August 2021, when we first announced the 100-participant Phase 1 cohort and had commenced enrollment. Then the 300 participant phase two and the 600 participant phase three cohorts initiated enrollment shortly thereafter. Then last month in October, we announced that the phase three B cohort had begun enrolling. The Vietnam Ministry of Health gave approval to advance into this large phase three B trial based upon its assessment of early safety data from the first 1,000 individuals dosed in the Phase 1 and 2 and 3A cohorts. Well, I'm very pleased with the extraordinary effort of our team, and I'm excited to report today that enrollment of the ARCT154 Phase 3B study is completed. And a Phase 3C sub-study is expected to meet target enrollment this week. This will bring us to a total of over 19,000 participants in the combined study. The Phase 1-2-3A cohorts have now completed two doses of ARCT154 given 28 days apart. The Phase 3 trial has been amended. The size of the Phase 3B is now about 16,000 participants, and it also includes an immunogenicity non-inferiority sub-study of approximately 2,000 participants, which we call the Phase 3C cohort. The total size of Phase 3B and Phase 3C is anticipated to be around 18,500 participants. This sub-study will evaluate immunogenicity non-inferiority of ARCT154 against AstraZeneca's COVID vaccine. The Phase 3B cohort has completed enrollment with over 16,000 participants, and the Phase 3C sub-study is expected to meet target enrollment this week. The safety and immunogenicity data from the Phase I, II, and III-A cohorts has the potential to form the basis for filing an EUA or Emergency Use Authorization application in Vietnam in December. The immunogenicity non-inferiority data from Phase III-C, together with the safety and efficacy data from the other phases of the trial, are designed to form the basis of filing for potential full approval in Vietnam in the second half of 2022. Dr. Steve Hughes, our CMO, our Chief Medical Officer, he's going to provide more details later in today's call regarding the ARCT-154. I'll now move on to ARCT-021. ARCT-021 is a differentiated COVID mRNA vaccine candidate, and this was our first vaccine to enter the clinic. And we'd previously discussed that a single administration of ARCT We shared this data that a single administration of ARCTO21 resulted in what we expect to be a meaningful humoral and T cell response. We have an ongoing fully enrolled ARCTO21 phase 2 study, and we have previously discussed the encouraging preliminary tolerability and immunogenicity data from this study. Specifically, immunogenicity data from the study shows greater than 90% seroconversion for IgG antibodies binding to the full length spike protein at day 28, following a single shot dose of ARCTO21. As previously reported, ARCTO21 has been selected by a global entity for inclusion in the phase three vaccine trial against COVID-19 and is sponsored and funded by the entity. At this time, per our agreement, we're unable to discuss further specifics. However, we are understandably very grateful for this group's support, which has been so valuable in the global fight against COVID-19. I'll now turn the time over to Dr. Steve Hughes.