Okay, thanks. Thanks, everyone, for being here. My name is Yan and Zhu, and I'm one of the biotech analysts here. It is my great pleasure to be joined by Joe Payne, CEO of Arcturus Therapeutics, for this session. Thanks, Joe, for being with us. Yeah, thank you, Yenon. For the invitation, it's always good to see investors in this great hotel. Great. Thanks for the kind words. So it's an interesting time for mRNA therapeutics and especially also mRNA vaccines. Can you kick off with your thoughts on recent dynamics in the mRNA vaccines space, both infectious disease and cancer? And maybe segue into the company's mRNA platform and the pipeline initiatives. Yeah, I think it's been a good quarter for mRNA. The perception around the space and vaccines and therapeutics has grown and become more positive. It was good to see additional infectious disease vaccines and the flu space get traction and approval. And then the recent cancer data, of course, I think was exciting for the field of oncology. It's, you know, messenger RNA is here to stay in oncology. And I think there's a lot of opportunity there to pursue. It's a, I think we're just scratching the surface of the opportunity. There's been elevated interest in Arcturus because of these processes. We do have a self-amplifying mRNA vaccine platform that is exciting in the infectious disease and potentially cancer area. Great. And let's talk about costing. Sure. Your COVID-19 vaccine self-amplifying mRNA platform. Now that you have gained the full control of this asset, what does future hold for costing? Yeah, so costing is an approved COVID vaccine in 32 countries approximately. And we have the complete rights and control over that asset. In terms of, there's three premier markets. There's the US market, there's Europe, and then there's Japan. With the United States, under the present administration, I think the strategic approach is for us to potentially identify a partner that can help us in the United States. With respect to, you know, commercialization efforts there. In Europe, we're already approved and, you know, we're looking at opportunities there that may have been neglected under the previous partnership. In terms of sales, and then in Japan, we're strengthening our relationship with Meiji. We already have a partner in Japan. That is distributing costing there, and we anticipate that that will continue going forward. So overall, there's two things. Is how can we capture sales and monetize this platform? Give us non-dilutive monies to fund our value-creating therapeutic franchise. Is it sales or is it through re-partnering efforts? And I think it's a combination of both. And strengthening our relationship with Meiji in Japan, looking at unique and traditional opportunities in the United Kingdom and Europe, of course. And then also look to re-partner the costing franchise in the US. There's four large vaccine companies that do not have self-amplifying mRNA technology, and they do not have a COVID vaccine. And I think it's helpful just to touch on this. The RSV opportunity is multi-billion, frankly. And then you look at shingles, that's three times larger. Many people say it's a $6 billion annual opportunity. You look at pneumonia, that's over $9 billion, and flu as well. But the COVID opportunity is as large, if not larger than all of these segments. And it's dominated by a, you know, a lead vaccine company. And I think there's an opportunity to compete there. I really do, with the right partner, with what we believe to be a superior platform, self-amplifying mRNA expresses much more protein. It clearly lasts a longer time, and it has higher immune immunogenicity. And all the implications there of a more protection, longer lasting vaccine and is going to have value, especially with the right partner in the US. Got it, got it. Very helpful. Let's talk about personalized cancer vaccine. Yeah. How is self-amplifying mRNA positioned for potential development in personalized cancer vaccines? Yeah, Arcturus always knew that self-amplifying mRNA would find success in oncology. But recently, there has been some fuel put on that strategy because of the success of conventional mRNA in the space. But if you look at self-amplifying mRNA, it expresses 30 times more protein. That's 30 times more antigen. That's not a small number. Arcturus' wheelhouse technology is delivery. We believe we do that as good or better than anyone in the world. That's a significant statement. But that's what we brag about. We know delivery. And delivering that antigen is a big deal. And self-amplifying mRNA is also well understood in the academic and academia and our own internal data, that self-amplifying mRNA does a great job engaging T cell. T cells and T cell biology. And we think it's significantly better. So if you add all that up, whether it's expressing the antigen, delivering, or on T cell engagement, that's a lot of multiples of potential improvement. And I think this is a next generation technology that can be applied to the right areas. So even though we're excited about self-amplifying mRNA for oncology, we are not an oncology company. That's not who Arcturus is. But we do like to monetize our self-amplifying mRNA platform, whether it's the infectious disease vaccine space and seals or sales or deals there. And likewise in business development opportunities for cancer. So I think that's how it fits into a strategic role for Arcturus. Is we'll look at opportunities to partner this technology with the right players that will be able to not just approach these challenging oncology indications, but do it with the right combinations. And remember, it's not just personalized cancer vaccines; they're shared antigen vaccines, and then there's other unique approaches that are being evaluated with mRNA and self-amplifying mRNA in oncology. So it's a space that's unfolding. We're excited about it. We're clearly looking to monetize in some manner. In the coming quarters and years. But that's how it fits into our strategy, is self-amplifying mRNA is the fuel, and our therapeutic pipeline is the value. It's the rocket ship, and the self-amplifying mRNA activities is the non-dilutive monies to fuel that growth. Great, great. Yep, yeah. Let's do talk about those pipeline programs that you hope to take to the market and patients, right? Yeah, absolutely. So let's talk about ARCT810 for OTC deficiency. I think you completed dosing in the ongoing phase two study. And you expect to provide an update on study data as well as regulatory strategy this month, right? Yes. So let's please first remind us of any data that you have disclosed so far from the study, and then we can go from there. Sure. Yeah, yeah. We've shared a successful phase one and phase one B data and we've provided an interim update on phase two and US and Europe. Phase two studies with respect to our OTC deficiency program. That's ornithine, transcarbamylase deficiency. It's the number one urea cycle disorder. And the data we've collected is, first of all, safety is very important. There's been a lot of programs that have gone through challenges with accumulation of lipids and inflammatory particles. But our technology is differentiated. It's different there. We don't have any of those challenges so far. And so I think that's what we've shown that it's safe and well tolerated to date. And then with respect to efficacy, there's multiple biomarkers in this disease. This is a urea cycle disorder. And when that urea cycle is dysfunctional, ammonia levels rise, and ammonia crosses the blood-brain barrier. And it creates neurological deficits and challenges. So it's a very serious disease. And you got to control that ammonia. But there's a pair of biomarkers. There's ammonia itself and that is a very important biomarker, as we advance this through clinical trials. And it's a surrogate biomarker. Ammonia itself is bad for you. It's Windex, right? You don't have to be a rocket scientist to understand it's bad for the human body. But there's another biomarker called glutamine, and it's a significant challenge. So there's what we've learned as we've developed this program is that there are many people that are addressing or treating this disease with ammonia scavengers. They take all these pills, they drink a lot of water, they urinate 10 times a day, and they're just trying to get rid of the ammonia. These pills will grab the ammonia, sequestering ammonia, sequestering agents, and you drink a lot of water and you excrete it. So however, there's still going to the doctor and they're not feeling great. So why is that? They're managing their ammonia levels, but they don't feel well. And that's because of glutamine. So what people don't understand is the ammonia, the excess ammonia, when you eat protein, you generate excess ammonia. That excess ammonia gets converted to glutamine, and before it's scavenged by the ammonia scavenger, so even though these patients are doing all the right things, they're following their doctor, their diet, their nutritionist, they still don't feel well because glutamine crosses the blood-brain barrier and then creates ammonia in the brain. And so it's not just about ammonia, it's about glutamine as well. Especially in the stable adult population. But you'll notice that as we've had regulatory interactions with the agency, that there's an increased emphasis on ammonia in severe disease in children. And there's an increased interest in glutamine with stable adults because of this problem I just highlighted. That even though they're on ammonia scavengers, they want that glutamine reduced. So there'll be an opportunity later this month to provide. We've had two type C meetings with the regulatory agency. We've already indicated that they were positive and productive meetings, but we will be sharing more details of those meetings at the data readout that's later this month. And so we'll have some data that builds on the interim data sets we've shared previously and also provides some more granularity on the path forward with respect to the regulatory trials or path, especially to the pediatrics. And to the kids. Got it, got it. Great. Presumably those positive productive meetings suggest a more expedited pathway for the pediatric indication. I know you can't really give the details, but. Well, we can't give the details, but you can imagine that there's a lot of interest in our program and more so than last year because there's been a lot of programs and technologies and platforms that have dropped out. And we're finding this is a recurring theme, but our platform seems to be safe and well tolerated and was working at the interim readout. We look forward to sharing the more complete data set here shortly. But yeah, there's increased interest in this platform for the liver, because there's just straight up challenges with other programs. Lipids can be toxic. They can accumulate. And this is a presents a challenge for other platforms. And so we're now the only one treating this disease with mRNA and so I feel the increased urgency, especially in the pediatrics where children are dying, frankly. And they need this therapeutic as soon as possible. Got it, got it, got it. Now with the focus on data, I was wondering how much new data will we see compared with previously? Can you give us a sense about number of patients, kind of population, dosing, additional sounds like glutamine will be an important data point, but any other? Yeah, there's multiple biomarkers. In the type C meetings, we were given some just really good advice from the agency. They're trying to help us. They want to get this approved as well. So they gave us just some advice on how the data should be presented and what additional data that we can dig up and present that will be helpful. And so without saying too much, there's going to be more data than just ammonia and glutamine. But it was requested by the FDA or suggested that we start to share this. So we've gone through and retroactively dug up that data set as well. And so we'll be able to share some additional data. We've completed our studies in the United States, so that's most of the new data will be from the US participants. But we look forward to sharing it in a couple of weeks. And it's not just the data, it's the regulatory path forward and also we'll be providing an update on our platform. In general, because we remind people this is a flagship asset. And people need to be reminded of the value of the platform. And so we'll it's an op presents an opportunity to provide an update with the general platform for intravenous dosing to the liver. Got it, got it. Would you mind to give us a sense of the bar for success for, for example, glutamine? How much reduction is considered meaningful? Well, any what we found so far is and in the data we shared is that glutamine is not just elevated, but can be very high in folks. And that there is a correlation between them having fog or headaches or just feeling like crap, frankly. When glutamine is high. So but it's quite variable. But it would be nice to see that reduced significantly or even normalize. Within the normal range is the objective. But if we see significant reductions there, then that will be viewed positively. By the community, especially the stable adult population. I touched on this earlier, but I think in the if you have a child that's dying from this disease, you care more about ammonia and understandably. Normalizing and keeping those levels in check. But as they age and become stable, they care more so about glutamine and so we'll be sharing data from both those biomarkers and additional data that I touched on. Right. I thought previously you also talked about N15. You were a genesis? Is that still something of a focus? Yeah, yeah. We're always looking to there's a lot of different data sets that we're collecting, including the N15 urea genesis. That's a urea itself is another biomarker for a urea cycle disorder disease, right? So there's different creative and new ways to measure urea. And one of them is an N15 urea genesis assay. And what we're collecting that data as well. That's correct. Got it, got it. And dosing frequency is every other week, right? Is that right? Yeah, dosing is every is presently every other week. That's correct. Okay. So whether this will ultimately be once a month or less frequent than that, there's reasons to believe that. But we're dosing every other week so we can get an answer quickly and advance this into a pivotal trial. Got it. Great. So we're looking for this September update. Then what's the next step? You just mentioned the pivotal trial. So can you talk about next steps? And next steps for OTC deficiency? Well, we'll outline that in detail at the next it's in a couple of weeks, so I don't want to steal any thunder away from that presentation. But the objective is that we hope that everyone will understand what our strategy is with respect to OTC deficiency. Later this month. Yeah. Definitely looking forward to that. Okay, so let's pivot to ARCT032 for cystic fibrosis. So this program, you reported data and you kind of refined your approach dosing and everything along the way. And culminating at cohort four currently, right? Yes. You're this is open label, phase two study, 10 mic per cubic, daily inhalation. And for 12 weeks, so that's quite a duration of treatment. Yes. So can you talk about what's the milestone for that program? How is that study going? Well, the first milestone for a 12-week study is safety and tolerability. Just even today when I'm talking to investors, remind them of the 20, 30-year history of inhaled RNA therapeutics. Like all types of RNA, whether it's circular RNA, messenger RNA, gene editing RNA, siRNA, antisense oligotherapeutics. And the list goes on and on. People have been trying to inhale RNA into the lungs. In humans, don't like it. It's like 20 years of evidence. And then but we've solved that problem. And that's a massive, massive, massive problem. It is the number one problem. Is safety and tolerability. So I personally got excited when we started achieving 5 milligrams, 10 milligrams, then 15 milligrams daily for 28 days. And where we are now is doing a study for 12 weeks. And if we maintain safety and tolerability, then that is it brings a lot of hope and optimism and excitement to this program. Looking beyond that, and I think what Wall Street is also looking if not more so is does it work? And we've shown some exciting data preclinically, but they want to see some clinical data. And all we've shown so far is in the 28-day study. In our second cohort, we provided an interim readout. And we saw mucus plug reduction. It had never been shown before. And so this is very interesting. Wall Street's waiting for a an assay that can be used as a regulatory improvement and approval endpoint. And these high-res CT scans aren't there yet, but still very encouraging. To see mucus plugs being reduced. But I think the objective of this 12-week study is first, safety and tolerability to keep people excited that we have a medicine that can be dosed on a frequent basis without any significant adverse events. And then next, we got to we're collecting a copious amount of efficacy data. There's lung function data. We have FEV that we're collecting that people are familiar with in the lung space. All the lung drugs, it's FEV, by the way, has been around since the 1800s. You have a straw and you blow into a box and it tells you how well your lung function is doing. We're doing that as well. And that's an approval endpoint. So that's very important part of our process. But we're also collecting lung clearance index, LCI. And this is a passive maneuver. People being evaluated for LCI, barely even know they're being tested. They're just breathing in and out. And it's how many cycle times does it take to expel a certain gas? And that can be easily measured. And this is also a potential endpoint for us that's exciting. Another lung function measure. And we also have a quality of life measures that are validated. These are surveys. They take this huge long questionnaire. And they track before, during, and after treatment. But these are validated questionnaires. They're respected by the regulatory agency that we're collecting. And then on top of that, we're taking beautiful pictures, AI-assisted this beautiful technology, high-resolution CT scans before and after treatment to look at the changes in mucus volume and mucus plugs and the numbers of these and looking at the walls and of the lungs itself and just gauge how much is healing in the process. And this is all fantastic. And in addition, we have a reach study. There's a normative study, a natural history-like study that's being collected by the CF Foundation. Multiple years, hundreds of subjects looking at lung function measures like FEV and LCI. We're doing the same thing. And we can compare our data to that normative of study. Now, I've just listed a whole bunch of things that we're doing, but I think it's helpful for people to be— remember history.