Arcturus Therapeutics Holdings Inc.

Greetings. Welcome to the Arcturus Therapeutics fourth quarter and full year 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. Please note this conference is being recorded. I will now turn the conference over to your host, Dipankar Roy, Senior Director of Investor Relations. You may begin.

thank you kyle good afternoon and welcome to our tourist therapeutic sport quarter and full year 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 uh andy sassine our cfo and dr pat chivikula our cso and ceo 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, and they involve known and unknown risks, uncertainties, and assumptions that may cause actual results to vary. So performance and achievements 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 Form 10-K, filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, February 28, 2022. And our tour specifically disclaims any obligation to update such statements to reflect future information, events, or circumstances. With that, I will now turn over the call to Joe. Joe?

Hey. Thank you, Dipankar. Good afternoon to all. Thank you for joining Arcturus' quarterly call today. Before we begin, I would just like to acknowledge that today is National Rare Disease Day, February 28th, and given that two of our pipeline programs are rare diseases, you know, that is OTC deficiency, a rare liver disease, and cystic fibrosis, a rare lung-centric disease, I wanted to publicly express my gratitude to all those working diligently on these programs here at Arcturus, and to the clinicians and patients and families on this National Day of Recognition. Now on to our update about our recent progress. We have continued to make excellent progress advancing our mRNA-based vaccines and therapeutic candidates. I'll begin with a discussion of our vaccine programs targeting COVID-19. So let's begin with ARCT154, our most advanced program and a vaccine that is designed to protect against the SARS-CoV-2 variants of concern. This program is supported by encouraging clinical data including the recent booster data we reported showing that a low dose of only 5 micrograms of ARCT154 boosted or increased neutralizing antibody activity against the SARS-CoV-2 ancestral D614G and Omicron strains by 28 and 54 folds respectively. We are excited to announce today that our collaborator VinBiocare has completed an emergency use authorization filing with the Vietnam Ministry of Health for ARCT 154. This represents a very important milestone for our company as we mature and strive toward becoming an integrated commercial stage global biopharmaceutical company. ARCT 154 is a product of our self-amplifying mRNA technology or the trademarked STAR platform. In addition, this vaccine includes an optimized mRNA sequence with multiple proprietary modifications to improve its stability, half-life and increase its translation. We believe that these modifications and others incorporated into ARCT154 improve the immunogenicity profile of this vaccine candidate and may enable high levels of clinical efficacy, especially as a booster. ARCT154 is designed to extend the duration of antigen expression, and this platform has shown robust T cell responses and high levels of humoral immunity in multiple preclinical models. We've also been efficient in progressing 154 in clinical studies. We designed and developed this vaccine very rapidly based on our understanding of mutations in the clinically relevant variants circulating across the world. And we expeditiously moved this program into the clinic in a combined phase one, two, three study. Earlier in this quarter, we announced highly encouraging immunogenicity phase one slash two booster data from our ARCT 154 program, as well as our alternative ARCT 165 vaccine candidate. These data showed that when administered at low five microgram doses, at least five months following initial vaccination with Comirnaty, we observed robust increases of 54 and 47-fold respectively in neutralizing antibody responses against the Omicron variant for these two booster vaccine candidates in an exploratory microneutralization assay. This is in addition to the data that showed broad coverage and encouraging neutralizing antibody activity of these candidates against the D614G ancestral, beta, delta, and several other variants of concern and variants of interest using validated and exploratory neutralization assays. These results provide us with confidence in the potential for ARCT154 to provide substantial clinical efficacy against a wide range of circulating variants. So, supported by these strong data, our goal is to develop ARCT154 as a broadly immunogenic vaccine that can be used for primary and booster vaccination. We aim to explore its potential use in populations currently seeking vaccination for initiation of or continuation of protection against severe COVID-19 disease. We are working closely with our collaborator, VinBioCare, to operationalize the Phase I, II, III study of ARCT154 in Vietnam. The study objectives include the evaluation of safety, immunogenicity, and efficacy of ARCT154 against SARS-CoV-2 infection. All of the cohorts in this study, meaning Phase I, II, IIIa, IIIb, and IIIc, have all completed two doses of ARCT154 or comparator given 28 days apart. The safety and immunogenicity data from the first 1,000 participants of the phase 1, 2, 3A cohorts are included in the EUA application that was submitted today. Efficacy data from the pivotal trial will be subsequently submitted to the Ministry of Health in application for a potential full approval. In addition, our global manufacturing footprint continues to mature. and our technology transfer to VinBioCare's manufacturing facility in Hanoi, Vietnam, continues to progress toward anticipated production capacity of 200 million doses per year. We remind everyone that this trial and the development of the Hanoi manufacturing facility is fully sponsored and funded by VinBioCare, and we are indeed grateful for their support. I will now turn to ARCT 810, our therapeutic candidate for ornithine transcarbamylase deficiency, or OTC deficiency. OTC is a rare and serious disease with no approved treatments that address the root cause of the disease. Our therapeutic candidate aims to restore expression of the normal ornithine transcarbamylase enzyme in the liver of patients with OTC deficiency. ARCT 810 has the potential to restore urea cycle activity, prevent neurological damage, and prevent the need for liver transplantation. We previously completed a phase one healthy volunteer dose escalation study with ARCT810 and demonstrated that ARCT810 administration was associated with favorable tolerability and an attractive pharmacokinetic profile. Lipid excipients were no longer observed in the plasma after 48 hours. The doses we are now clinically evaluating are within the anticipated therapeutic range that we have estimated based upon our preclinical studies. I'm happy to report that the Phase 1B trial for adults with OTC deficiency is now identifying additional patients for screening after COVID-related delays, and we expect to complete dosing in the first cohort in the second quarter. We have obtained approval from the United Kingdom Health Research Authority, as well as from Belgium and Spain, to initiate a phase two multiple dose clinical trial for ARC-TA10. And we continue to conduct site startup activities while seeking authorization in additional European countries. This is a randomized placebo-controlled double-blind study with a nested single and multiple ascending dose design that would enroll 24 adolescents and adults with OTC deficiency. We anticipate that phase two screening will commence in the second quarter, and we expect to obtain interim data in the second half of 2022 in a subset of participants. Moving now to our cystic fibrosis program. We have continued to progress the necessary preclinical studies to enable ARCT 032, this is our mRNA therapeutic candidate for cystic fibrosis, to move into clinical studies. we anticipate the submission of a clinical trial application for ARCTO32 in the third quarter of 2022. Our flu vaccine program, termed Lunar Flu, also continues to progress toward candidate selection and clinical development. We believe that self-amplifying mRNA vaccines have tremendous promise to address the gaps with the current flu vaccines, which often suffer from suboptimal efficacy and require lengthy manufacturing and release. In addition, mRNA-based vaccines potentially have the advantage of being able to be adapted through much more rapid mRNA manufacturing processes to target currently circulating flu strains. We expect to make a final selection of our lunar flu development candidate this year with a self-amplifying star platform candidate and advanced toward a clinical trial application in 2023. In addition to these internally developed programs, Arcturus has also partnered several of our lunar therapeutic programs with some of the leading biopharmaceutical companies, including Ultragenyx and J&J and Takeda. The most advanced of these programs is a very promising therapeutic candidate for glycogen storage disease, which is currently being evaluated by Ultragenyx in a Phase I-II study. I will now pass the call on to Andy, our CFO.