Arcturus Therapeutics Holdings Inc.

Greetings and welcome to the Octurus Therapeutics Third Quarter 2023 Earnings Conference Call. At this time, our participants are in 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, Netta Saravade, Vice President, Head of Investor Relations, Public Relations, and Marketing. Thank you. You may proceed.

Thank you, operator. Good afternoon and welcome to Arcturus Therapeutics' third quarter 2023 financial update and pipeline progress call. Today's call will be led by Joe Payne, our president and CEO, and Andy Sassine, our CFO. Dr. Pat Chivakula, our CSO and COO, will join them for the Q&A session. 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 Secretary's 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 most recent form 10-K and in subsequent filings with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made. Arcturus specifically disclaims any obligation to update such a statement. And with that, I will now turn the call over to Joe.

Thank you, Netta. It's good to be with you again, everybody. I'm going to begin my remarks with an update on progress regarding our monovalent COVID-19 vaccine, ARCT154. Following favorable clinical results from the Phase III pivotal studies, the new drug application is currently under review by Japan's Pharmaceuticals and Medical Devices Agency, or the PMDA. The ARCT154 Japan NDA submission is supported by an active controlled Phase III booster vaccine study, which was conducted in Japan, and a placebo-controlled Phase III primary vaccination series efficacy and safety study, which was conducted in Vietnam. The ARCT154 Phase III booster vaccine study achieved its pre-specified primary endpoint, demonstrating the non-inferiority of an immune response against the SARS-CoV-2 ancestral strain as compared to Comirnaty. In addition, the superiority of ARCT154 in neutralizing antibody response against the SARS-CoV-2 Omicron BA4-5 variant was also demonstrated as a key secondary endpoint. Updated preliminary Phase III booster data was recently presented at the 11th International mRNA Health Conference in Berlin. In a heads-up comparison to an FDA-approved monovalent mRNA vaccine, monovalent ARCT154 showed multifold improvement in durability and multifold superior titers of neutralizing antibodies against Omicron BA4 and 5. And this was at the six months post-boost mark. These phase three booster results were consistent with the phase one slash two booster clinical trial durability data that were collected previously and presented at the ninth ESWI influenza conference in Valencia. All of these observed clinical benefits were achieved with the STAR next generation mRNA technology, which is administered at five micrograms. This is an 83 to 92% lower dose level compared to approved mRNA vaccines. This lower dose level highlights the potential safety and tolerability benefits of this next generation mRNA vaccine platform technology. Based on all the clinical data collected to date, we believe that the next generation STAR mRNA platform is an effective and differentiated vaccine technology that may offer a longer lasting immune response relative to the older conventional mRNA platform technologies. Supported by the ARCT154 clinical data, Meiji Seika Pharma, the partner of CSL Securus, submitted a Japan NDA to support ARCT154 as a primary series and booster vaccine for COVID-19. The review of this application remains underway and is on track for approval in December. We filed a marketing authorization application in Europe, and we are seeking approvals for ARCT 154 and other major markets. We continue to mature the value and scope of the Star Next Generation mRNA vaccine platform by collecting meaningful bivalent vaccine clinical data as well. We're pleased to report today that the planned enrollment target of 850 participants has been reached in the ongoing Phase 3 bivalent COVID vaccine trial, comparing immunogenicity to bivalent Comirnaty. The initial top line results of the study are expected in Q1 of 2024, followed by an anticipated PMDA approval in Q3 2024. In summary, we are delighted with the rapid progress we have achieved this year with our Star Next Generation mRNA vaccine platform. We believe ARCT 154 provides clear validation of the broader opportunity for Arcturus' mRNA vaccine and therapeutic programs. Our strategic collaboration with CSL, which is Arcturus' exclusive global licensee, is focused on developing and commercializing next-generation mRNA vaccines and continues to make substantial progress. Our partnered Lunar Flu program which is also now known as ARCT2138 continues to progress with funding and operational support from CSL. Lunar Flu utilizes Arcturus' next-generation mRNA platform and we are intending to initiate a phase one clinical trial which is expected to begin soon. I'll now move on to ARCT810. This is our messenger RNA therapeutic candidate for Ornithine Transcarbamylase or OTC deficiency. This investigational medicine is designed to functionally replace the deficient OTC enzyme in the liver, restoring urea cycle activity and preventing metabolic crises that cause neurological damage. ARCT 810 could reduce the need for ammonia scavengers and ease the rigid dietary protein restrictions that OTC patients face today, thus improving the quality of life for those with the disease. ARCT 810 has received orphan drug designation and rare pediatric disease designation from the FDA. ARC-TA10 is currently being evaluated in two ongoing clinical studies in patients, a Phase 1B study in adults and a multi-dose Phase 2 study in adolescents and adults with OTC deficiencies. A Phase 1B single ascending dose study is being conducted in the United States and has completed dosing of all planned four cohorts in a total of 16 subjects. We expect the final database lock to occur later in this fourth quarter of 2023. The ARCT 810 Phase 2 study is being conducted in the United Kingdom and Europe and plans to enroll up to 24 adolescents and adults with OTC deficiency. The ongoing study evaluates two dose levels and includes up to six biweekly administrations for each participant. We remain committed to the development of ARCT 810 and we are taking various actions to address the continued challenging enrollment rate in Europe by adding study sites and patient services to improve screening participation. Updated guidance of interim phase two data is expected in H1 or the first half of 2024. Moving now to our ARCT 032 program. ARCT032 is an inhaled messenger RNA therapeutic candidate for cystic fibrosis, formulated with Arcturus' lunar delivery technology, which has been optimized for bronchial epithelial cell delivery. We completed enrollment and dosing in a Phase I study in New Zealand of 32 healthy subjects across four ascending single-dose cohorts. We look forward to presenting safety and tolerability study results of this Phase 1 study at an appropriate conference in the first half of 2024. We're pleased to report that we have initiated enrollment and scheduled dosing of the first patient in a Phase 1B clinical study in New Zealand, which is designed to enroll up to eight adults with cystic fibrosis, with each participant receiving two administrations of ARCTO32. We are presently guiding interim data in H1 2024. Arcturus is sincerely grateful for the continued support of the CF Foundation. In September, the organization agreed to increase its financial commitment to $25 million to advance ARCT 032. In October 2023, ARCT 032 received rare pediatric disease designation from the FDA. As such, if ARCTO32 achieves FDA approval for a pediatric indication, our person is eligible to receive a priority review voucher of a subsequent marketing application for a different product. New data was presented at the North American Cystic Fibrosis Conference, or the NACFC, in November. This new proof of activity in vivo data was collected with a CF ferret model, also known as G551D. The ferrets in the study require continuous treatment with the CFTR modulator Kalydeco to prevent disease progression. A single administration of ARCTO32 showed successful transfection of airway epithelial cells and restoration of mucociliary clearance above the level maintained with Kalydeco.