Greetings, and welcome to the 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. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Neda 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. Pad Chivukula, our CSO and COO, will join in for the Q&A session as well. 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 statements. 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. Arcturus specifically disclaims any obligation to update such statements to reflect future information, events or circumstances. And with that, I'll now turn the call over to Joe.

Hey. Thank you, Neda, 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 Seqirus 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 ARCT-154 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 3 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. Juergen Froehlich as our Chief Medical Officer, overseeing mRNA therapeutics and Dr. Igor Smolenov, 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 are 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’ mRNA manufacturing expertise and the 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 on 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 3 booster study in Japan designed to compare ARCT-154 to Comirnaty, targeting 780 adult participants based on non-inferiority immunogenicity. Meiji moved quickly with the enrollment process, very impressed and appreciative of 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 one-month blood draws have also been completed. This timely execution allows us to immediately collect the pre-requisite 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 ARCT-810. 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 to 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 ARCT-810 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 mg 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 ARCT-032 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 variant. 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 ARCT-032 has demonstrated robust expression of CFTR protein and restoration of chloride current. Supported by these encouraging data, we are now evaluating ARCT-032 at four different dose levels in a Phase 1 study being conducted in New Zealand. We have successfully completed the enrollment 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 27 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' LUNAR delivery of systemically administered mRNA or gene editing applications. In this past quarter, we have strengthened our management team. We have brought on Dr. Juergen Froehlich, to be our Chief Medical Officer to provide seasoned leadership over our mRNA therapeutics pipeline and also have brought on board Dr. Igor Smolenov to be our Chief Development Officer, who will lead our Arcturus' clinical development efforts for our promising COVID and seasonal flu self-amplifying mRNA vaccines. Now, Dr. Froehlich 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 Genevant. Juergen completed medical school at the University of Wartburg 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 U.S., 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 1, 2 and 3 trials with inhaled therapeutics in patients with CF to treat chronic lung infection. We are fortunate to have Dr. Juergen Froehlich, join our management team as our Chief Medical Officer. Now moving on to introduce our Chief Development Officer of Vaccines, Dr. Igor Smolenov 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. Smolenov 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. Smolenov 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. Smolenov 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. Smolenov 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 Smolenov join our team here at Arcturus as our Chief Development Officer overseeing our vaccine franchise. I will now pass the call on to Andy Sassine, our CFO, to provide financial updates.

Thank you, Joe, and good afternoon, everyone. The press release issued earlier today includes financial statements for the fourth quarter and fiscal year 2022 and provides a summary and analysis of year-over-year and sequential financial performance. Please also reference our Form 10-K for more details on the financial performance. I'll begin with the CSL agreement. Arcturus received a $200 million upfront payment that was received in the fourth quarter of 2022. Additionally, in March 2023, our first achieved development milestones primarily associated with nominating next-generation candidate for COVID-19 and seasonal flu programs, resulting in $90 million invoiced to CSL. We are excited to continue working on these programs under the guidance and leadership of our partner CSL. Our CSL collaboration is a 40-60 profit sharing agreement related to the COVID-19 vaccine product. With respect to program costs related to the bivalent COVID-19 vaccine, we expect that future anticipated milestones will cover all related expenses going forward. Additionally, the program cost for the seasonal flu candidate will be reimbursed in full on an ongoing basis. CSL can apply a $37.5 million R&D credit to be used within the next five years against costs incurred on the flu and three other respiratory disease vaccines. As you heard earlier, we are excited that Meiji completed enrollment during the first quarter of 2023 for the Phase 3 COVID-19 booster trial of ARCT-154 in Japan. Meiji is responsible for all related clinical, regulatory, development, and manufacturing expenses for the ARCT-154 booster vaccine. Our manufacturing loan with the Singapore government, which had a principal and interest balance of $50.4 million as of December 31, 2022, was renegotiated in March 2023, which resulted in Arcturus paying back $17.1 million and the remaining $33.3 million being forgiven. As a result, Arcturus has no further loan obligation payable to Singapore. On the treasury side, in March 2023, we paid off the remaining loan with Western Alliance Bank, which had a balance of $10 million as of December 31, 2022, and we entered into a new banking relationship with Wells Fargo. Based on the substantial funding provided by the CSL collaboration, we expect Arcturus to be in a very strong financial position in the next few years. Our cash runway now extends to the beginning of 2026 based on our current pipeline and assuming no milestones or revenues from any commercial product sales. I will now provide a quick summary of our financial results for the fourth quarter of 2022. We reported revenues of $160.3 million for the fourth quarter compared to revenues of $5.8 million in the fourth quarter of 2021. The increase in revenue was predominantly driven by the license portion of the upfront payment from the CSL transaction. We reported total operating expenses of $38.8 million during the fourth quarter of 2022 compared to operating expenses of $43.4 million in the fourth quarter of '21. The decline in operating expenses was primarily due to lower COVID-19-related manufacturing and clinical-related expenses. Finally, we reported a net income of approximately $117.3 million, or $4.43 per diluted share during the fourth quarter of 2022 compared to a net loss of $38.7 million, or $1.47 per diluted share during the fourth quarter of 2021. I am happy to report for the first time in the history of the company, we reported a net income of $9.3 million for the fiscal year ended 2022. In summary, we believe that the company is in a strong financial position and has the resources needed to achieve multiple near-term value-creating milestones for the vaccine and therapeutic programs over the next 12 months. I will now pass the call back to Joe.

Hey. Thanks, Andy. It's been a productive quarter. We hit the ground running with CSL, as indicated by meaningful early milestones being achieved in the partnership. We made measurable progress in each of our clinical programs, which has put us in a position to potentially file our first NDA in Japan and collect meaningful clinical data in 2023 for each one of our pipeline programs. This will showcase the intramuscular, intravenous, and inhaled applications of our proprietary mRNA and delivery technologies. And we've also strengthened our management team and look forward to many of you meeting them over the remainder of the year. So with that, we would like to turn the time over to the operator for questions.

Thank you. Ladies and gentlemen, at this time, we will be conducting a question-and-answer session. First question comes from the line of Seamus Fernandez with Guggenheim. Please proceed with your question.

Thanks for the question. So, my first question is actually on the Meiji trial. It sounds like the team there has made a lot of progress enrolling patients and we're almost on the cusp of actually getting the clinical data. I was just hoping that the team could comment on what your hope or expectations are for those data relative to Comirnaty? And if there will be follow-up data because I believe there has been in the past some suggestion of greater durability with the self-amplifying RNA as a potential advantage over just a standard modified mRNA. And then the second question, just really wanted to get a better sense if you are willing to share the dosing regimen in a little bit more detail and the number of patients that have been dosed so far in the OTC study? Thanks so much.

Thank you, Seamus. Regarding your first question, the main goal of that trial is to demonstrate non-inferiority in terms of the immunogenicity data. A crucial component of the immunogenicity data is the one-month blood data that has already been collected. You are right in noting that we are currently gathering data that is highly relevant to the potential new drug application in Japan. We aim to ensure that this immunogenicity data is part of that application. As for your question about durability in CSL, we will be monitoring that simultaneously. However, this durability data is not required for obtaining approval from the PMDA in Japan. It will serve as supplementary information that could enhance our commercial case if we succeed in commercialization this year. Regarding your second question, we have indicated for the first time that we have enrolled multiple patients in the OTC study, but we cannot provide further specifics at this time. Additionally, we want to clarify that we are still on track to share Phase 2 data later this year.

Joe, if you don't mind, can I just clarify enrolled patients? Or have you started dosing patients officially?

Yes, enrolled means that I define as dosing, correct. So whenever I mentioned the word enrollment in this context, it's past screening, they have been dosed, correct.

Okay. Great. Thank you.

Hey, Seamus. Just one other point is that even in the early, the first dosing, we are expecting some pharmacological activity because it is a dose level where we’ve seen pharmacological effect in preclinical models.

Our next question comes from the line of Yanan Zhu with Wells Fargo. Please proceed with your question.

Thank you for addressing the questions, and congratulations on the progress. Regarding the Japan COVID study, could you discuss what the non-inferiority margin might be for the primary analysis? Additionally, have you mentioned the potential economic aspects of obtaining regulatory approval in Japan? Thank you.

I want to ensure I understand your question. Regarding the Phase 3 trial in Japan, I am confident that it has been properly designed to achieve statistical significance for a non-inferior endpoint, so there are no concerns about the required margins. We will certainly see numerical superiority, but we need to collect the data to determine statistical superiority. As for your second question, I can pass that along to Andy.

Yeah. No, thank you for the question. Unfortunately, we don't provide guidance with respect to economics. And when we do have that available, we will share with the market what the economics are for CSL, and Meiji and ourselves going forward. So, thanks for the question.

Got it. And then a couple of questions on OTC deficiency. In terms of data later this year, you mentioned a subset of patients. Would we see one or both cohorts of data and also what would define success for that readout?

Sure. So, the success is biological proof-of-concept, and that's being defined by biomarker changes being observed in this patient population. So the biomarkers include ammonia and orotic acid in urea, ammonia in the blood, orotic acid in the urine. Urea genesis will be measured. Other amino acids will also be measured for, and the OTC enzyme itself will be measured in the blood through an unvalidated assay. So, our several biomarkers will be measured. And so, when we indicate biological proof-of-concept, we mean being able to measure or determine changes in those biomarkers because of the therapeutic. With respect, what was the other question?

Would we see one or both cohorts of patients?

That depends on the rate of enrollment. We're recruiting up to 24 subjects in this trial and 12 of them are at one particular dose and 12 were at another dose. And this is placebo controlled. So it's a 9:3, 3:1 ratio at each of those cohorts. So, if the rate of enrollment exceeds 12, then yes, we'll be able to provide those observations.

Great. Lastly, regarding the cystic fibrosis program with upcoming data later this year, what would be the most significant readout for the healthy volunteer study that we should pay attention to? Also, how do you decide on the dosage to be used for cystic fibrosis patients afterwards? Thank you.

This is the most significant exercise involving these four doses being tested in early Phase 1 subjects. Our main goal is to determine the safety and tolerability of the dosing regimen itself. Since this is an inhaled therapeutic, we will quickly assess the maximum tolerated dose. We'll also evaluate how long a person can utilize this therapeutic, which will yield the most interesting data.

This is Pad. Based on our Phase 1 data, we will definitely be examining both the lowest and highest doses. When we move into Phase 2, we may remove some of the lower doses and select a dosage that we believe is safe and has a good margin for safety to begin with.

Great. Very helpful. Thank you.

Thanks, Yanan.

Our next question comes from the line of Yigal Nochomovitz with Citi. Please proceed with your question.

Hi, team. This is Ashiq Mubarack on for Yigal. Thanks for taking my questions. On the OTC program, you had some earlier comments on enrollment and how that's going. Can you comment at all on the rate of enrollment, in particular, site activation and if there are still outstanding challenges there or if was more or less an solved? And in terms of the OTC data itself, you're planning on sharing. Can you comment at all on your expectations for kinetics of response, meaning as in how long do you need to dose and follow these patients before accumulating enough response data that would be meaningful enough to share? Thanks.

Sure. So, I can update the market that we have now onboarded nine active sites for OTC deficiency. The bulk of that effort was last year. This is the year where we've initiated enrollment officially. So, with respect to the pace of enrollment, it's nothing that is out of the ordinary for a rare liver disease in Europe. So that's the only comment I can provide there. All we've disclosed is multiple patients being enrolled so far. With respect to the kinetics, it's helpful to understand that this is a six-administration trial. So these doses are separated by two weeks. So there's six administrations. And what we've seen preclinically is that OTC is additive in our preclinical animal studies. So we may see this in humans as well. So that with respect to kinetics, we are collecting blood draws after each administration over these half a dozen doses.

Yes, this is Pad. I want to highlight that we are the first protein replacement therapy targeting this indication specifically through mRNA. We are exploring a largely uncharted area. We expect to observe results from the initial doses, and to facilitate this, we are monitoring several biomarkers. We are hopeful to see progress soon and will provide updates on our findings.

Got it. That's very helpful. And if I could ask one more on the cystic fibrosis program. Do you think it's possible we could get some initial healthy volunteer data this calendar year or is that you think that's more likely to be a 2024 event? Maybe once you have that data in hand, how do you think you can pivot into treating actual cystic fibrosis patients? Thanks.

Yeah. The study is being conducted in New Zealand, the Phase 1 study for CF because we've already dosed a pair of cohorts, there may be some initial feedback from, and we haven't had any serious or severe adverse events, right? We have to report on that. So after the first survey after the first couple of cohorts, it does present the potential opportunity to end Phase 1 to add CF patients. But whether we add CF patients to the Phase 1 trial itself or quickly pivot to a more traditional Phase 2 regulatory process is yet to be determined and communicated.

Very helpful. Thanks very much.

Thanks.

Our next question comes from the line of Pete Stavropoulos with Cantor Fitzgerald. Please proceed with your question.

Hello, Joe, Andy, and team. Thank you for taking my questions. So I have one on 810, the OTC deficiency program. What type of patients are you enrolling? Can you speak to their baseline characteristics? Are you kind of enrolled patients stable on stable background meds? And are they controlled or uncontrolled? And can you speculate in which type of patients you may be able to see the most pronounced effects in?

Yeah. These are stable adult and adolescent subjects. That will be the initial focus. So, both adults and adolescents in the European Phase 2 multiple ascending dose trial. So I can comment on that. With respect to the other, and what was the other aspect of your question?

Can you lay on which type of patients you may actually see the most pronounced effect?

Okay. Well, I think this therapeutic has the opportunity to have a biological impact on every patient injected. However, if they are already on ammonia scavengers, for example, the other biomarkers will be more meaningful, like, urea genesis and OTC itself. But if they are not on ammonia scavengers then, of course, ammonia will be looked at erotic acid and other amino acids are going to be investigated on, so the collective body of data should be sufficient to negotiate the regulatory path efficiently with regulatory agencies.

Okay. Sorry go ahead.

No. That’s it.

Yeah. I have a couple of questions. So if you can give a sense of how many subjects have gone through the full dosing cycle in the Phase 2 MAD study? And is there like a safety look built in by, let's say, the SMD?

Yeah. There's always safety checkpoints, but we've already got approval to proceed in a multiple ascending dose for six administrations, right? Always communicated as multiple subjects. But if every two weeks, there's another administration. So, you can make your assumptions based on that, that there's enrolled subjects that if they continued on in the study, of course, they would have multiple administrations so far.

Okay. Moving on to 032, congratulations on that. The enrollment seems to be going well. I know you briefly mentioned preclinical data in your prepared remarks, but could you provide more detail? Pad, what aspects of the preclinical data strengthen our belief in advancing to human studies? Additionally, can you discuss the predictive value of the model and how phenotypically similar it is to see patients replicate human disease in the lungs? Has it been validated with other therapeutic agents?

The CF ferret model is a relatively new and exciting development recommended by the CF Foundation and others for companies to use, as it likely represents the human condition more accurately due to the mucus produced in the lungs. While it is challenging to confirm that this model is a validated predictive tool, it seems reasonable to assume it is more representative because of the additional mucus. Our approach differs from previous methods as we properly modify and purify our messenger RNA molecule using the Arcturus proprietary technology. This is the first time an inhaled messenger RNA therapy for CF has been tested in a clinical setting utilizing the LUNAR technology, which is highly optimized for delivering to bronchial epithelial cells and for functioning in the mucus environment, as well as for inhalation and aerosolization. Additionally, the CFTR construct has been specifically optimized to enhance its functional activity. This therapeutic differs significantly from previous attempts, and we consider the CF ferret model to be very meaningful since not many companies or therapies have been demonstrated in this specific model. Thus, it could have significant implications.

All right. Thank you for taking my questions.

Yes. Thank you, Pete.

That is all the time we have for questions, at this time. I'd like to hand the call back to Joseph Payne for closing remarks.

Thank you all for joining the call. If you have any further questions, please contact the team, and we will respond promptly. Goodbye for now.

Ladies and gentlemen, this does conclude today's teleconference. Thank you for your participation. You may disconnect your lines at this time and have a wonderful day.