Arcturus Therapeutics Holdings Inc.

Greetings and welcome to Arcturus Therapeutics' fourth quarter 2022 financial update and pipeline progress 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, Netta Safarzadeh. Vice President, Head of Investor Relations, Public Relations, and Marketing. Thank you. You may begin.

Thank you, Operator. Good afternoon and welcome to Arcturus Therapeutics' fourth quarter 2022 financial update and pipeline progress call. Today's call will be led by Joseph Payne, our President and CEO, and Andy Sassine, our CFO. Dr. Pat Chipakula, our CSO and COO, will join in for the Q&A session as well. Before we begin, I would like to remind everyone that the 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 guaranteed 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 factor section in our Form 10-K file with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made. Our service specifically disclaims any obligation to update such a statement to reflect future information, events, or circumstances. And with that, I will now turn the call over to Joe.

Thank you, Netta, and good afternoon to all. Thank you for joining us for today's call. The recent period has been characterized by substantial operational and pipeline progress here at Arcturus. We will be highlighting four areas on today's update call. First, we closed our strategic vaccine collaboration agreement with CSL Securus at the end of last year. We have received the $200 million upfront payment and invoiced $90 million in additional milestones, demonstrating the positive progress that the companies have made on our partnered COVID and seasonal flu vaccine programs. Second, we've entered into an agreement with Meiji Pharma to evaluate ARCT154 as a booster vaccine for SARS-CoV-2, also known as COVID-19. And we're very happy to report significant operational progress in the ongoing phase three study in Japan, and we'll be providing an update there. Third, we have continued to advance our RNA platform technology and our earlier stage clinical programs, and we will provide an update on recent progress there. Fourth, we have strengthened our management team by the addition of Dr. Jurgen Frohlich, as our Chief Medical Officer overseeing mRNA therapeutics and Dr. Igor Smolinov as our Chief Development Officer overseeing clinical development of our vaccine franchise. I'll begin with our recently announced strategic collaboration with CSL. We are in the initial phase of our now four month old collaboration and very pleased with how the teams are working together. Arcturus has achieved substantial milestones this month associated with nominating next generation candidates for COVID and seasonal flu programs. Mutual respect is evident between the working groups of both companies. There is a clear passion and solid work ethic behind the competent execution that has led to these important and early milestones being achieved. We remain eligible for additional development and commercial milestones as covered pipeline programs advance. Our collaboration with CSL is focused on the development and commercialization of next generation mRNA vaccines targeting COVID, influenza, three additional pathogens, as well as pandemic preparedness. Our collaboration combines CSL's well-established global vaccine, commercial, and manufacturing infrastructure with Arcturus's mRNA manufacturing expertise and innovative Star mRNA vaccine and lunar delivery platform technologies. We expect this collaboration to drive the development, manufacture and global commercialization of next-generation self-amplifying mRNA vaccines over the coming years. The impact of this collaboration to our balance sheet and runway continues to be meaningful and Andy will be speaking to that shortly. Now on to our agreement with Meiji Pharma to advance ARCT 154 development in Japan. Our contracted relationship with Meiji is focused on developing ARCT 154. This is our next generation self-amplifying mRNA booster vaccine for COVID-19. You may already appreciate that Japan has one of the world's highest rates of COVID booster vaccination. Given the Japanese government's focus on public health, and infectious disease prevention, we fully expect high levels of COVID booster utilization for many years to come. In addition, the Japanese government has been clear about their interest in establishing independence in mRNA vaccines, and we're very pleased to be part of this effort with Meiji. Meiji Group received a significant subsidy from the Japanese government in the fourth quarter of 2022 to support this effort. and Meiji is responsible for all development costs related to ARCT 154 in Japan. In December 2022, we announced that Meiji had initiated a phase three booster study in Japan designed to compare ARCT 154 to Comirnaty in targeting 780 adult participants based on non-inferiority immunogenicity. Meiji moved quickly with the enrollment process. very impressed and appreciative with the productivity and progress we've seen there. I'm very pleased to report today that the study is now fully enrolled with over 800 participants exceeding our target enrollment and ahead of schedule. In addition, the one month follow up visits and the one month blood draws have also been completed. This timely execution allows us to immediately collect the prerequisite immunogenicity data and be in a position to potentially file our first NDA in Japan. Now moving to our earlier stage programs, and I'll begin with ARCT810. This is our therapeutic candidate for ornithine transcarbamylase deficiency or OTC deficiency. This investigational therapeutic aims to address the deficient OTC enzyme in the livers of individuals with this disease. ARCT 810 has the potential to restore urea cycle activity and prevent metabolic crises that cause neurological damage and potentially liberalize strict dietary protein restrictions and improve the quality of life for people living with this condition. The program utilizes our proprietary lunar delivery technology and one important attribute of this technology is that the lipids administered are rapidly degraded which we expect will contribute to a favorable safety profile. We are evaluating ARCT810 in two ongoing clinical studies, a Phase 1b study in adults and a multi-dose Phase 2 study in adolescents and adults with OTC deficiency. These studies build upon a completed Phase 1 study that demonstrated a favorable safety profile when dosed up to 0.4 mgs per kilogram, the highest dose evaluated in that study. We continue to advance ARCT 810 in the Phase 2 study. The study will enroll up to 24 adolescents and adults living with OTC deficiency distributed across two dose cohorts. The study has enrolled multiple subjects. We remain on track to report ARCT 810 Phase 2 interim clinical data later this year. Now, moving on to ARCT 032, This is our inhaled messenger RNA therapeutic candidate for cystic fibrosis. With this drug, we are aiming to express fully functional CFTR protein in the lungs of individuals with cystic fibrosis. Our approach is agnostic to the underlying mutations associated with the disease, and we believe that ARCTO32 could provide benefit across a very wide range of those living with CF, especially type 1 CF and for individuals who are not well served by CFTR modulator therapies. We're grateful to have obtained support from the CF Foundation for the advancement of this promising investigational medicine. We also benefit from invaluable scientific collaboration with the experts at the CF Foundation. Previously, we reported encouraging preclinical data demonstrating successful delivery to the lung in four different animal species, mice, rats, ferrets, and primates. Notably, our data have shown the ability to deliver mRNA to airway epithelium in the CF ferret. This is a disease model that produces significant mucus in the airways, similar to patients with CF. Finally, in vitro treatment, of bronchial epithelial cells from CF donors with ARCTO32 has demonstrated robust expression of CFTR protein and restoration of chloride current. Supported by these encouraging data, we are now evaluating ARCTO32 at four different dose levels in a phase one study being conducted in New Zealand. We have successfully completed the enrolment of the first two cohorts with expectation to complete enrollment of the entire 32-subject study in the second quarter of this year and plan to report study results later this year. Arcturus is excited to share our lunar HBV data next month. We have been optimizing our in vivo intravenously dosed gene editing platform for years. Our preclinical gene editing mRNA platform data for hepatitis B virus will be presented on April 27th at the 18th annual Global Hepatitis Summit Conference in Paris, France. This will be the first opportunity for the scientific community to evaluate the benefits of Arcturus's lunar delivery of systemically administered mRNA for gene editing applications. In this past quarter, we have strengthened our management team. We have brought on Dr. Jurgen Frohlich to be our CMO, our Chief Medical Officer, to provide seasoned leadership over our mRNA therapeutics pipeline. And also have brought on board Dr. Igor Smolinov to be our Chief Development Officer, who will lead Arcturus' clinical development efforts for our promising COVID and seasonal flu self-amplifying mRNA vaccines. Now, Dr. Froelich has broad and successful experience in the field of rare diseases, including OTC deficiency and cystic fibrosis. He will assuredly increase our likelihood of success as Arcturus initiates and navigates through late stage clinical trials for our rare disease therapeutic programs. He has three decades of broad and late stage therapeutic clinical development experience at Genentech, Quintiles, BMS, Ipsen, Vertex, and Genovont. Jurgen completed medical school at the University of Würzburg in Germany. He is a diplomat of the American Board of Clinical Pharmacology and holds a dual executive MBA from Zurich, Switzerland, and the State University of New York at Albany. Jurgen has been directly involved in successful global marketing authorizations of drugs in the US, Canada, the European Union, Switzerland, and Australia. Since 2011, he's been involved in early and late stage development of CF therapeutics, including the approval of Kalydeco and clinical development planning for other CFTR modulators. He has seasoned experience in phase one, two, and three trials with inhaled therapeutics in patients with CF to treat chronic lung infection. We are fortunate to have Dr. Jurgen Frohlich join our management team as our chief medical officer. Now, moving on to introduce our Chief Development Officer of Vaccines, Dr. Igor Smolinov has a strong record of successfully developing vaccines all the way through approval. He will help our vaccine team and our partnership with CSL get our COVID and flu programs to this next level. And we're excited about that. Dr. Smolinov is a recognized leader in clinical development with a proven record of accomplishment in biotech and large pharmaceutical companies, he contributed to the successful development and licensure of several innovative vaccines. Before joining Arcturus, Dr. Smolanoff was the executive vice president at Clover Pharmaceuticals. That's where he built a strong team that was able to rapidly generate pivotal clinical data, leading to a COVID-19 vaccine authorization and product launch there. Before that, Dr. Smolanoff served as a therapeutic area head leading the development of several seasonal flu vaccines at CSL Seqirus. Igor was the head of clinical development at Moderna, managing the initiation of the first clinical trials of messenger RNA vaccines in humans. At Novartis vaccines, Dr. Smolinov contributed to the development and global licensure of multiple vaccines there as well. Igor graduated from Volgograd State Medical University in Russia, where he holds an MD, a PhD, and a doctor of science degrees from this university. He's the author of more than 50 publications in peer-reviewed journals in clinical pharmacology, infectious disease, and vaccine development. We are indeed fortunate to have Dr. Igor Smolinov join our team here at Arcturus as our CDO overseeing our vaccine franchise. I will now pass the call on to Andy Sassine, our CFO, to provide financial updates.