Arcturus Therapeutics Holdings Inc.

Jim, welcome to the Arcturus Therapeutics first quarter 2022 earnings call. Today's conference is being recorded. At this time, I'd like to turn the conference over to Dipankar Roy, Senior Director of Investor Relations. Please go ahead, sir.

Thank you, James. Good afternoon and welcome to Arcturus Therapeutics first quarter 2022 financial results and corporate update call. Thank you all for joining us. Today's call will be led by Joseph Pate, our President and CEO, and Andy Sassine, our CFO. Dr. Pat Chivukula, our CSO and COO, will join in for the Q&A session. 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, May 9th, 2022. AFTURA 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 Jill.

Hey thank you Dipankar. Good afternoon to all. Thank you for joining Arcturus' Q1 quarterly call. My comments today initially capture a list of summary points for the for the quarter and I'll follow that up with additional detail per program before I turn the time over to Andy for financial updates. This quarter has been highlighted by several key achievements. Indeed we've made significant progress advancing our pipeline of mRNA based vaccines and therapeutics. So let's begin with ARCT 154. This is our most advanced COVID vaccine candidate that has shown impressive activity against SARS-CoV-2, both as a primary vaccine and as a booster. We're pleased with the promising results coming from a Phase 1-2 study evaluating ARCT 154 and its potential as a booster in individuals primed with Comirnaty. The boost with ARCT 154 generated high booster numbers, these are the geometric mean fold rises or GMFRs in neutralizing antibody titers and we'll share more of those results in a moment. Importantly, this quarter we learned from VinBiocare that the phase one slash two slash three study has met its primary endpoint objective of vaccine efficacy. And that ARCT 154 demonstrated very strong protection against severe and fatal COVID disease, even when up against the most challenging variants that have escaped other vaccines like Delta and Omicron. We believe this is a significant milestone for the company and for the field of RNA vaccines. This represents the first time ever that phase three vaccine efficacy endpoint has been achieved. with a low-dose self-amplifying mRNA vaccine, showing that we can prevent COVID-19 symptomatic disease, severe disease, and death. With over 19,000 participants involved in this study and a comparable safety profile in the ARCT154 vaccinated arm and placebo arms, respectively, we view this as important validation of our self-amplifying mRNA technology platform and its applicability towards developing vaccines. The vaccine efficacy data, along with the available safety and immunogenicity data, has been shared with the Vietnam Ministry of Health, and we anticipate a decision around the EUA in the near future. The application for full market authorization is expected to be filed later this year. We're also pleased to share that Arcturus has provided an expression of interest letter to the World Health Organization to potentially include ARCT154 in its emergency use listing process. We're sincerely thankful to the WHO and to the Vietnam Ministry of Health for their support and encouragement in this process. Coming back to our booster trial, last week we released additional data from our Phase 1-2 booster clinical trial here in the United States and Singapore, showing the durability of neutralizing antibody response extending to at least three months after a five-microgram ARCT154 booster dosing following primary vaccination with Comirnaty. We announced new data today that our low-dose self-amplifying mRNA vaccine shows a 46-fold rise in neutralizing antibody levels for Omicron BA.2, and that's a month or 29 days post-boost. All of these data, including those from the current Omicron variants, provide important clinical validations and highlight ARCT154's potential as an effective booster candidate against a broad range of variants of SARS-CoV-2. As the world transitions now into an endemic period of COVID, the booster market represents the most significant commercial opportunity. These data are a step towards ARCT154 realizing that potential. We have begun our startup activities toward a global registrational booster trial and look forward to starting dosing soon. Now let's get into the details now about the ARCT154 clinical results. I'll begin with a recap of the ARCT154 phase three efficacy data that we reported a few weeks ago. The ongoing phase 1, 2, 3 registrational study sponsored by Arcturus' collaborator in BioCare enrolled over 19,000 adult participants in Vietnam, including a large percentage of individuals at higher risk of severe complications of COVID disease. The phase 3 placebo-controlled vaccine efficacy portion of the study enrolled over 16,000 participants. Evaluation of vaccine efficacy demonstrated that the study met its primary endpoint of prevention of virologically confirmed COVID-19 disease. Data show that in an analysis of COVID-19 cases accrued between seven days and 56 days after completion of a two-dose vaccination series, two five-microgram doses of ARCT154 demonstrated 55% vaccine efficacy for preventing symptomatic COVID-19. Key secondary endpoint evaluating severe COVID-19 disease including COVID-19 related deaths was analyzed and demonstrated over 95% efficacy for prevention of severe COVID including deaths. Notably, this study was conducted during a period characterized by the dominance of the Delta and Omicron variants. We are currently conducting additional analyses of the swabs taken from the COVID cases in this study to characterize which SARS-CoV strains led to infections in this study, and particularly to confirm if there's further evidence of protection against these two very challenging variants of concern that have escaped protection from many other vaccines. The data from the study are also reassuring from the safety and tolerability perspective. The incidence of unsolicited adverse events in the ARCT154 and placebo group are comparable in the safety data collected from over 17,000 participants enrolled in the Phase 1, 2, and 3 through one month post-fold vaccination. In addition, the frequency and severity of those events was generally consistent upon the second administration. No cases of myocarditis or pericarditis have been reported. Although the study size was not large enough to detect large numbers of these rare events, the absence of such events in a study of this size is still comforting. We and our partners at VinBioCare will continue to carefully monitor the safety of participants in this ongoing study. The study met its primary objectives in both the demonstration of acceptable immunogenicity and safety in the Phase 1-2-3a readout and in meeting the protocol-specified vaccine efficacy endpoint in Phase 3b. These results have been submitted by VinBiocare to the Vietnam Ministry of Health for the express purpose of seeking emergency use authorization. We also continue to work with VinBiocare to support filing for full marketing authorization to be completed later this year. We are very encouraged by the data from this Phase 1-2-3 study. With two low-dose administrations of the ARCT154 vaccine, effective prevention of COVID disease and particularly severe and fatal disease has been shown. The safety profile was well-tolerated, and we view these findings as an important illustration of the potential of our self-amplifying mRNA platform, which includes the STAR technology, and STAR is the trademark for self-transcribing and replicating RNA technology, and the Lunar Delivery Platform, our trade secret know-how and proprietary manufacturing processes, including purification formulation and lyophilization methods toward the mRNA drug substance and the vaccine drug product. Given the continued circulation of SARS-CoV-2 and the discussion of its movement into an endemic phase, we are moving forward with development of ARCT154 as a booster vaccine. In an ongoing Phase 1-2 study evaluating ARCT154 given as a 5-microgram booster dose approximately five months after primary vaccination with Comirnaty, the ARCT154 vaccine responses are promising. The acceptable reactogenicity accompanied by robust immune responses continue to build our enthusiasm toward next steps. We've observed noteworthy neutralizing antibody responses soon after vaccination with ARCT154 and now have shown the high GMFRs to be sustained through three months after vaccination. In addition, the neutralizing antibody responses to the parent strain of the vaccine, also known as D614G, and antibody responses against a panel of SARS-CoV-2 variant strains have demonstrated antibody responses that have remained 13 to 30 fold elevated over three months, after three months, 91 days to be exact, over day one baselines for all SARS-CoV-2 strains tested on the panel. We're even further encouraged by additional data from this study demonstrating strong neutralizing antibody activity against the Omicron BA.2 variant upon boosting with ARCT154 with a 46-fold increase seen in NAB activity at day 29 over day 1 baseline. This data, paired with the 54-fold increase in neutralizing antibodies against BA1 over the 29-day window that we reported earlier this year, generates an appealing profile for ARCT154 as a broadly immunogenic and next-generation low-dose booster. Given these collective data, we have been in discussions with major regulatory agencies, including the FDA, the MHRA and EMA, regarding the path to pivotal trial and future approval as a booster. These conversations have informed the design elements of our pivotal booster trial intended to support global registration. In parallel with our development activities, our global manufacturing footprint continues to advance. with ongoing technology transfer activities to VinBiocare's manufacturing facility, and we expect it to become operational this year with a capacity to manufacture 200 million doses annually. The development of the Hanoi manufacturing facility is fully sponsored and funded by VinBiocare, and we are looking forward to the next steps in our collaboration to potentially add Hanoi as an international hub for manufacturing self-amplifying mRNA medicines. Our self-amplifying mRNA influenza vaccine program has continued its preclinical work, and we expect to make a final decision of our lunar flu development candidate this year. Given the comparative speed of mRNA vaccine production and precise antigenic matching against circulating influenza strains, this is expected to offer an important improvement over currently marketed influenza vaccines. With its comparatively lower dose, than other mRNA vaccines in development. We hope to understand if there are other meaningful ways to differentiate in the influenza vaccine space. Well, now I'd like to shift from our vaccine franchise over to our therapeutic mRNA pipeline programs. Indeed, we also continue to make progress in our mRNA therapeutic programs. I'll begin with an update on ARCT 810. our therapeutic candidate for Ornithine Transcarbamylase Deficiency or OTC deficiency. OTC is the number one urea cycle disorder. It's a rare and serious disease with no approved treatments that address the root cause of the disease. Our approach aims to augment the deficient or absent OTC enzyme in the liver of patients living with this disease. ARCT 810 has the potential to restore urea cycle activity preventing or slowing the progression of neurological damage and potentially expanding dietary options and improving on quality of life for people living with this condition. Well, we've obtained approval from the United Kingdom's HRA or Health Research Authority and other European authorities to initiate a phase two multiple dose clinical trial for ARCT810 designed to enroll 24 adolescents and adults. Patient screening and enrollment is underway at multiple sites in the United Kingdom, Spain, and Belgium, with other countries soon to follow. We anticipate that phase two enrollment will commence before the end of the second quarter, and we expect to obtain interim proof of concept data in the second half of 2022 from a subset of participants. We've also completed dosing of the first cohort of our ascending dose phase 1B study here in the U.S., wherein the participants received a dose of 0.2 milligrams per kilogram of ARCT A10. We're pleased also to report that the Data Safety Review Committee has recommended continuation of this study without modification. Therefore, the dosing of the screened second cohort will begin imminently. Moving briefly now to our Cystic Fibrosis Program. We've continued to progress the necessary preclinical studies to enable ARCT 032 This is our inhaled messenger RNA therapeutic candidate for cystic fibrosis to move into clinical studies, and we anticipate the submission of a clinical trial application, or CTA, for ARCT 032 in the third quarter of 2022. In addition to our internally developed pipeline programs, Arcturus continues to support our partnered or licensed therapeutic programs. The most advanced of these is a very promising therapeutic candidate for glycogen storage disease, which continues to be evaluated by Ultragenyx in a Phase 1-2 study. Well, with that, I will now pass the call on to Andy Sassine, our CFO, to provide the financial updates.