Good morning, everyone. Thanks for joining us for another session at the 41st JPMorgan Healthcare Conference. I'm Brian Cheng. I'm the senior biotech analyst here at the firm. Presenting next is Arcturus Therapeutics. We have their CEO, Joe Payne, and also CFO, Andy. I'm gonna turn the floor to the Arcturus team. The presentation will be followed by a Q&A session. Joe, the floor is yours.
Great. Okay, thanks, Brian. It's good to be with you. It feels good to come out of a great year and to be able to present and provide an update on what we're doing at Arcturus. Arcturus is a messenger RNA medicines and therapeutics company. We are based in San Diego, headquartered there. We have over 170 employees now, and we're approaching our 10-year anniversary. You know, 10 years ago, Pat and I started the company with $15,000, so it's an entrepreneurial story. It's just, it's been fantastic to see the progress of the company, and it's good to be with you today. We now have a pipeline of messenger RNA medicines. We've got great strategic partners.
Some are here in support in attendance today as with CSL and Ultragenyx. The CF Foundation supports our CF program, and we're assisting the government in pandemic flu preparation. Hopefully, God forbid, we have to do that again. Proprietary mRNA technologies drive our therapeutic programs. Arcturus excels at designing these mRNA molecules, but also self-amplifying mRNA technology is something we're known for. This is a lower dose vaccine technology. We have a delivery system, a lipid nanoparticle delivery system called LUNAR, and this allows us to deliver to hepatocytes and myocytes and bronchial epithelial cells through different routes of administration, intravenous, intramuscular, and inhaled applications of messenger RNA. We'll speak to that later in the presentation.
We've also built a significant amount of manufacturing know-how for these complex therapeutics, not only on the mRNA drug substance, but also in the purification of these messenger RNA molecules. Purification of mRNA is becoming more and more important, especially as we're now administering these molecules systemically and through inhalation. Also formulating these into drug products and lyophilizing these sorts of therapeutics is also an area of expertise. Our pipeline of Arcturus-owned mRNA therapeutics is summarized here. We have a liver program, rare liver disease. We're pursuing ornithine transcarbamylase deficiency with a prevalence of over 10,000 people worldwide, and the upcoming milestone for that is some interim data of our phase 2 dataset out of Europe expected this year.
Our CF program, which I mentioned, is primarily funded by the CF Foundation, has a much higher prevalence, and we're initiating a phase 1 trial this quarter. With respect to our pipeline, our of partnered mRNA therapeutics and vaccines, we have a GSD 3 program, glycogen storage disease type 3, partnered program with Ultragenyx that's in early clinical trials. We've recently partnered our COVID vaccine and our flu vaccine to CSL, that's in phase 3 and preclinical respectively. Our BARDA collaboration is focused on pandemic influenza. This is not seasonal flu, but pandemic flu, that's in the preclinical stage. I wanna take some time to summarize our recent partnership that came out last quarter. We're very happy to announce that we've partnered our vaccine enterprise with CSL. This is a global vaccine company.
They're very good at what they do. They have exceptional capabilities in manufacturing and distribution and commercialization of vaccines worldwide. Arcturus had an accelerated dataset for self-amplifying mRNA because of the pandemic. From South America and Singapore and U.S. and Vietnam, we collected almost 20,000 subjects of data in an accelerated window. We had this fantastic dataset, and we needed to find an appropriate partner that can help us maximize and capitalize on it. We found that in CSL. We're very happy to be working with them. On my right, your right, you can see the terms of the partnership. It's a $4.5 billion deal.
$200 million upfront, which is well timed given that we're entering a recession, we are, it extends our runway to at least three years, we're very happy with that. There's also $1.3 billion in potential milestones spread across five programs that are listed on the bullet point on the left, including COVID, influenza, and three other respiratory infectious disease vaccines. The most near term or more significant portion of that development milestones will be on the COVID program, as that's the most advanced. We also have $3 billion in potential commercial milestones. A 40% profit sharing on the COVID vaccine enterprise and then also double-digit royalties or up to double-digit royalties for influenza and three additional respiratory infectious disease vaccines.
CSL will be taking care of all guidance pertaining to the US and Europe progress of the bivalent vaccine or any sort of progress of the vaccine in US and Europe. We also entered into a contracted relationship recently with Meiji. This was kind of in stealth. We were fairly quiet about it, but we're happy to provide an update today. As a background, Japan, just so people are aware, they have a very high COVID vaccination and booster vaccination rate. Almost 3 doses per person have been vaccinated and/or boosted with COVID vaccines. It's an attractive market in the vaccine area. Meiji Pharma received the rights to conduct a 154 clinical study in Japan. The Meiji group received a significant subsidy from the Japanese government.
Last quarter, the Japanese government is maintaining their message that they want to establish independence in mRNA vaccines. We're very pleased to be a part of the team that's helping Meiji Seika Pharma do that for the country of Japan. The study design here, the phase 3 study that's fully funded by Meiji Seika Pharma, is a non-inferiority immunogenicity trial. It's all conducted in Japan. The trial is expected to support PMDA approval. You'll see that half the participants will be receiving ARCT-154. The other half will be receiving an approved comparator messenger RNA vaccine Comirnaty. The study was approved to proceed last quarter, and we initiated that on December 13th, and already 2 sites have vaccinated 65 subjects with no, you know, serious adverse events or cardiac related events reported.
I'm happy to report that we've already opened up 11 sites, we've expanded that to 11 sites presently, and we've scheduled over 700 additional vaccinations. This trial is well on track, and I just wanna commend all those involved with boots on the ground in Japan and our friends at Meiji that have done an exceptional job with executing on this trial. This is gonna provide an opportunity, everybody, to compare directly self-amplifying mRNA with conventional mRNA. It'll put to bed all questions and concerns on how does this technology fit into this space. We look forward to collecting that data. I want to highlight that we have a successful working contractor relationship with a manufacturer in Japan called ARCALIS.
Axcelead and folks here are present in support of that effort. ARCALIS is a subsidiary of Hitachi. Arcturus has a presence with respect to manufacturing and a pharma presence with that have excellent relationships with the Japanese government, and we just have excellent support of CSL as a partner in this process. Now on to ARCT-810. This is a systemically administered messenger RNA for ornithine transcarbamylase deficiency. One of the unique advantages to the LUNAR delivery technology is that it's biodegradable. It is non-accumulating. If you're injecting larger amounts of messenger RNA intravenously, it's very important that these lipids not only do their job, but they degrade and they clear the body.
We have shown that these lipids are no longer measurable in human beings after 48 hours, and this is a significant advantage or differentiator of this type of technology. It can be applied to intravenous therapeutics and the applications therein. These particles, after they enter the bloodstream, there's a protein in the blood called ApoE that sticks to the surface, and that facilitates receptor-mediated uptake in these hepatocytes. After they enter the cell, we've designed this nanoparticle technology. We've engineered it to break out of the endosome. The endosome ages, becomes more acidic, and that activates the particle, releases the payload, the messenger RNA, into the cytosol, and that messenger RNA expresses, you know, very important therapeutic and pharmaceutically relevant proteins. This technology is being utilized for OTC deficiency.
This is an excellent market opportunity. It's the number 1 or most common urea cycle disorder. When the urea cycle takes place in the periportal portion of the liver, and this is how we control ammonia levels in our blood. If the urea cycle is dysfunctional, ammonia levels rise, and the ammonia crosses the blood-brain barrier, and that is very bad. We need to control ammonia, and you and I have normal urea cycles. If you have a dysfunctional ornithine transcarbamylase enzyme, then elevated ammonia is of significant concern. The present standard of care is to sequester that ammonia with ammonia scavengers, and you drink lots of water to try to urinate out the ammonia.
It presents challenges because if you eat the wrong food, there's a spike of ammonia, and the spikes of ammonia is where you have hospitalization events. Extraordinary pain is associated with this. You have to be rushed to the hospital. Sometimes they have to induce coma, and they have to clear the blood of the ammonia, it's just a, you know, it's a very challenging disease. Rather than sequester the ammonia, we think the ideal approach here is a messenger RNA molecule that expresses the ornithine transcarbamylase right into the cell and restoring normal activity. There's a significant diet associated with this disease too. This patient population, it has a very strict no-non-protein diet. If you're heavy on carbohydrates, you can imagine how taxing that is on you.
There's a significant desire to just remove this need for ammonia scavengers and remove this need of this aggressive diet, and not have any of these scary hyperammonemic episodes. How much OTC do you need? This used to be speculated and one of opinion. It's now been clarified this past year with the publications at the bottom. The field now understands that with just 5% functional OTC, we may be able to save lives. This is an X-linked disorder. A lot of the young males die at a very young age, and we may be able to prevent that with this technology at some point with just 5% restoration. We've looked at the periportal expression of OTC after administration of our therapeutic and models of this preclinically in genetically engineered OTC deficient mice.
You can see, in the periportal region of the liver that we've established well over this threshold, and we hope that we can replicate, obviously, this in human beings. Where are we in humans, in human clinical trials? Our phase 1 study was completed in New Zealand. We dosed it up to 0.4 mgs per kilogram, and that's relative to the messenger RNA molecule in 24 subjects. It was generally safe and well-tolerated. There was no steroid co-treatment or pre-treatment or post-treatment associated with this therapeutic. This is a differentiator to have no steroids associated with this therapeutic. The phase 1B trial in the U.S. was a single ascending dose study in adults. We completed enrollment of these cohorts up to 0.4 mgs per kilo, again. We completed that in November of last year.
There's no serious or severe adverse events. We have now initiated a 4th cohort, so this is new information, at 0.5 mgs per kilogram, an additional 4 subjects, 3 on drug, 1 on placebo. Total number of subjects is therefore expanded to 16 in that Phase 1B trial here in the U.S. With respect to Phase 2, this is now a single and multiple ascending dose now that we've established that the lipid's clear and that this appears to be a non-accumulating delivery technology. The regulatory agencies have allowed us to proceed into a multiple ascending dose and expand the patient population to include adolescents, not just adults. We're enrolling 24 subjects across 2 cohorts, we've been approved to proceed in 5 countries in Europe.
That's continue to get good progress with our regulatory discussions. 8 of our 14 planned sites are onboarded, and we have very motivated PIs that are excited to recruit some patients for us. We have interim data that we're expecting this year. When I mean data, what type of data is being collected, you may have already read ahead, but the primary endpoints are safety and tolerability, but the secondary endpoints are PK or pharmacokinetic and pharmacodynamic measures. Ureagenesis can be readily measured in a validated assay. It's a carbon-thirteen acetate assay. 24-hour ammonia profile can be easily measured in the blood. These are very relevant biomarkers. In the past, ammonia has been known to be a surrogate biomarker.
If we show regulatory agencies that we can control ammonia, this could be very meaningful in accelerating our discussions there. We have exploratory endpoints. There's other amino acids that are impacted by the urea cycle, so we can measure those. OTC enzyme itself, we can measure that. It's not a validated assay yet, but we're working on that internally. We can measure orotic acid in the urine too. There's no shortage of biomarkers with this disease, which makes it. It helps us with respect to, you know, understanding the biological proof of concept. We'll be having some of that interim data this year, and we're excited about that. Moving on to ARCT-032. This is inhaled messenger RNA.
It's a different LUNAR technology that's been optimized for bronchial epithelial cell delivery after inhalation. Our first flagship asset in the lung franchise is going after cystic fibrosis. This is a well-understood disease where, in this case, the dysfunctional or missing protein is a transporter called CFTR. When this transporter is missing, chloride ion transport is dysfunctional. That leads to fluid and undesired inflammation and cirrhotic and fibrotic disease, and the patients can no longer breathe properly and becomes very serious and fatal. So we're, in this case, we're inhaling a messenger RNA, getting that messenger RNA to where it needs to be so that it can express and make a healthy, new, functional CFTR transporter and be very impactful to this patient population. We have shown functional delivery of messenger RNA in four different species.
These are all healthy animals in mice, rats, ferrets, and primates. These imaging studies are very conclusive that we can successfully deliver to the epithelium. We've got recent data that we're very excited about. We shared this data on the slide right here at the NACFC, the most significant CF conference of the year, in the plenary session, and there was an applause associated with this data. That's how meaningful it is. If you genetically engineer animals with cystic fibrosis, there's one problem. Several of them do not develop sputum or phlegm or mucus in the lungs. With ferrets, it's different. They do. This is the most challenging model to establish proof of concept in.
What we show here in the green, in the green coloration is bronchial epithelial cells that, you know, successful transduction into these cells, even in the presence of CF mucus, in the trachea and the bronchus, so in different areas of the lung. Very nice, you know, proof of concept of the technology, the ability to functionally deliver even in the presence of a CF in the presence of mucus. The final data slide here is we've also showed that we can restore CFTR expression and function. On the left, you can see in the control arm what would be a normal response. Then with the treated arm, you see a larger response. Clearly we're restoring CFTR expression.
With, we collected donor samples from healthy individuals and from cystic fibrosis patients or individuals. The red bar on the right denotes the control. When you treat them or when you treat these cells with a messenger RNA that encodes for CFTR, you see a nice response and restoration of chloride ion activity. In the same range as the non-CF or the normal samples. Restoring CFTR expression and function is also. You combine that with the data that we saw in the ferrets, we're now getting very excited about this therapeutic. This has the potential to be very impactful, and we're excited to watch it. Just an.
Usually you don't see a board of directors slide in a, in a conference like this. I wanted to highlight that John Markels joined our board last month. He was previously the President of Merck Vaccines. We're happy to have him on board. He's gonna definitely provide some strategic oversight to our CSL relationship. We take that very seriously. We look forward to executing on that. Glad to strengthen the presence, you know, the talent and capability of our board. Also, just a quick thanks to the incredible team that we have at Arcturus. Very proud of the group of competent and likable scientists and employees at Arcturus. That is within 30 seconds, Brian. Pretty good, right?
Yeah. You did really well.
And, uh-
It's just 30 seconds.
Now go ahead.
We're gonna switch over to Q&A session. For those of you who are in the audience, we have floor runners to take your questions. You know, for those who are participating online, we also have the question portal on the conference site. Thanks for joining us, Joe and Dee. Maybe just one question that I have is, you know, I think a lot of us in the audience have gone the mRNA vaccine, and mRNA had, you know, been such a topic in the last couple of years since the pandemic started. How do you think about just your technology compared to
Yeah
... you know, what BioNTech or Moderna had? You have COVID vaccine data.
Yeah
What do you see in terms of differentiation compared to other technologies? I think, you know, your technology is slightly different in terms of, it's a self-amplifying mRNA. How does that differ? You know, does that translate to efficacy or safety that you've seen so far?
Sure, sure. I can speak to, first of all, the differentiation of the platform. Arcturus has historically been focused on intravenous and inhaled delivery of messenger RNA, so there's been an increased emphasis on purification. We have a purification IP that we've combined, built internally and licensed in that gives us a really strong position with respect to the purification of messenger RNA. You know, high levels of purity for intravenous grade applications and inhaled grade applications. That's a differentiator on the platform. The delivery technology is different. No one has access or something similar to or identical to the LUNAR technology. This is the lipids included in our delivery technology are different. They're not glycerol-based. We have thiocarboxylate-based lipids. That means we have sulfur and oxygen and nitrogen that's easily and readily hydrolyzable.
Therefore it's biodegradable and non-accumulating, and that's different, and that differentiates us. With respect to our manufacturing know-how, we have experience with not only conventional mRNA, but self-amplifying mRNA, which is 3 times larger. Very large mRNA, gone through that learning curve on how to not only make, but purify on scale the messenger RNA. Also the lyophilization element. Our vaccine is the only lyophilized vaccine. All the other approved vaccines are liquids. They're frozen, you've read about the challenges to keep these stable on the shelf and for supply chain issues associated with that. Having a lyophilization know-how, that's another differentiation on the platform. Pivoting to your second question, how does self-amplifying mRNA differentiate from conventional mRNA?
Well, I've highlighted that it's a larger molecule because it's expressing not only an antigen, but it's expressing an RNA-dependent RNA polymerase, a replicase that helps to extend the duration of expression of the antigen. That's a big difference. It means that our dose is considerably lower, like 6-10 fold lower dose, and all the benefits that that brings. The most expensive component in a messenger RNA drug product is the messenger RNA molecule. If you can reduce that by 600% or 1,000%, that's gonna have some benefits associated with cost of goods. In the vaccine space, speed is everything, clock speed. If each manufacturing run makes 10 times the amount of doses, you can cut off timelines to getting your vaccine distributed.
That could be important just from a time perspective. With respect to tolerability, most people in here have already been injected with vaccines. It's nice to be injected with 6 to 10-fold less lipids and lipid excipients in mRNA. Any sort of dose-related toxicology. You can imagine there's considerable potential benefits there by reducing the dose. That's just on the dose-related aspects. With respect to efficacy, the self-amplifying mRNA molecules are more immunogenic. That's why the dose is much lower. They zing the immune system a little bit more. That is a differentiator.
With respect to the business case for self-amplifying mRNA, besides the efficacy and the tolerability, if you could dose people less often with this technology, that has potential benefits as well with respect to time in between dosing.
Great. Maybe just focusing on the lead indication, because, for OTC, you have a couple competitors also in this space.
Yeah.
I think everyone seems to have a, have a bit of a tweak in terms of how they think about the indication, how they approach it. As we move into your, you know, update later this year, where do you think you would fit, you know? How, how do you kind of stand out from the crowd?
Sure. Sure. Well, our approach to OTC deficiency is one where it's a transient messenger RNA protein replacement concept. It's not a gene therapy. We have an attenuatable adjustable dosing technology, and it's applicable to, you know, potentially for neonates, children, adolescents under 18. Because OTC deficiency is a pediatric disease where usually it's diagnosed in a younger age, having a technology that's applicable to the younger population is a key differentiator versus the gene therapy or DNA. Clearly there's differences between a biodegradable delivery technology versus a viral vector and potential benefits of that. In terms of others in the space that are looking at messenger RNA approaches to OTC, none of them have access to our LUNAR delivery technology. That's proprietary. It's ours.
And our purification technology is where we have strong IP as well. We also have Orphan Drug Designation in the U.S. and Europe that has some exclusion provisions in there that makes it more challenging for competitors. If you take that all together, I think we're in really good shape.
Earlier today, you talked about how the bar for OTC, you know, you said 5% enzymatic.
Yeah
OTC activity on the slide. How should we think about just what you would want to see at the next interim read? What we deem as a success and, you know, let's say you hit that bar, what could be the next step forward?
Well, if we establish biological proof of concept for protein replacement, that's enormous. That'll trigger the addition of new programs for Arcturus and encourage the field to add more programs in the space. Biological proof of concept for me and for our team means that if we can see ureagenesis impacted and ammonia reduction in human beings, that's a big deal. There's other biomarkers that we're looking at too, like orotic acid in the urine. I think that's what we define as something meaningful and measurable.
If the regulatory agencies are not accepting ammonia as a surrogate biomarker to accelerate approval, then we can start to look at other meaningful endpoints, like transitioning these patients off of their aggressive diet, transitioning them off of the ammonia scavengers, reducing hospitalization events. They also have challenges in exercising for extended periods of time that elevates ammonia and causes problems. We can look at the ability to extend exercise times. I wanna go back to. You know, at first we wanna do our best to negotiate with regulatory agencies on the benefits of approving based on a surrogate biomarker. There are children dying of this disease. The majority of males, under 2 are just dying. We can't get too cute in this process. This is serious.
We need to get there as soon as possible. We'll try our best to negotiate a surrogate biomarker. There's other approaches to do if we're unsuccessful in those negotiations.
Got it. maybe switching gear.
Yeah
... your vaccine partnerships that you have. You got the key one CSL now.
Yeah.
As your keystone partnership for COVID vaccine. What are the key near-term catalysts that, you know, we should look out for? How does the Japanese study also fits in as well?
The Japanese study is something I can definitely speak to today. That's gonna be very important since that's a direct comparison trial. People just wanna see how the self-amplifying mRNA technology compares to the conventional mRNA constructs. That's gonna be very important, and that's a near-term catalyst. With respect to guidance in the U.S. and Europe and the bivalent vaccine and the flu shot and the flu progress, we're respectfully leaving that to CSL to provide that guidance. We're definitely excited about those endpoints and I mean, those milestones this year as well. We'll allow CSL to provide that.
Mm-hmm. I think the primary endpoint is focused on non-inferiority against Comirnaty, right?
Yeah.
Who is gonna take in charge of applying for to the Japanese approval?
Meiji is the primary driver of those efforts. They've done an exceptional job with getting the sites onboarded and with the regulatory application process. Their relationship with the government's strong and they, you know, they received a very large sort of subsidy, the Meiji group did, from the Japanese government. We're glad that we're aligned with them on this. 'Cause they're gonna be driving it. They have the relationships in place.
Okay. Maybe just off topic, you know, you're not working on cancer vaccines yet, but recently we saw the data from the Moderna Merck trial.
Yeah.
Any thoughts on, you know, Your potential to tap into the cancer market? What could be a path for you know, since now You're focused on OTC and CF. Is that something that you would like to do?
We were very excited to see that. Arcturus is not known to be an oncology company. We're, of course, excited to see Moderna and Merck's data. We believe that that was very meaningful, very exciting and to get that sort of data in a very tough advanced melanoma trial. It also opens the door to the question, is self-amplifying mRNA as good, or is it potentially better than conventional mRNA, and why? Self-amplifying mRNA is known preclinically to with respect to T-cell immunogenicity, and that's very important for cancer vaccines. Very important. We could perhaps have a technology that's better, more efficacious. With respect to tolerability, our platform is 10 times lower dose than conventional mRNA, and there might be benefits associated with that, perhaps.
In terms of the business case, you know, conventional mRNA looks like it's 9 shots, 9 visits to the hospital for a treatment course for a cancer vaccine. Self-amplifying mRNA may be considerably less visits to the hospital, and that could have a commercial or. This is all potential. It's definitely interesting. We had a collaboration in the personalized cancer vaccine space historically, you know, several years ago. We no longer have a collaboration in place for that, so we do have some historical relevance and experience there. We're telling the community that this platform's available, of course. If we can help people in cancer with this platform and partner it with a well-known player in oncology, of course, we'd be excited to do so.
I think we talk a lot about self-amplifying mRNA.
Mm-hmm.
I think compared to BioNTech, Moderna, they don't have that technology. What is the self-amplifying part of it? What's driving it?
Sure. A self-amplifying mRNA molecule is 3 times larger than conventional mRNA. It expresses an antigen, but it also expresses this enzyme that extends the expression timeline of the antigen. That's well understood in the vaccine space. We've got a lot of data on that, which shows very encouraged there, and we've partnered it, and we're getting more excited about that. There's a lot of applications where you need to extend the duration of expression of a protein. Self-amplifying mRNA could have meaning in a variety of infectious disease vaccines and cancer vaccines, therapeutic vaccines, and maybe even therapeutics at some point. I don't know if I addressed your question, but did that-
Yeah. Yeah.
Okay.
Yeah. Taking a step back, you have CSL partnership for vaccine. You're working on two rare disease indications.
Correct.
There is potential for you to tap into cancers. How do you think about, you know, how to prioritize, how to allocate resources? Just broadly, how should we think about your portfolio evolve in the next, let's say, 12 to 24 months?
Well, we view our CSL relationship and our internal therapeutic pipeline equivalently. It's very important that we execute on the CSL partnership, that can produce extraordinary amounts of revenues if we're successful, that could fuel and fund a growing and exciting therapeutics platform. We are focused internally on those, the OTC program and CF program. You notice we don't have a huge pipeline. It's very short, very focused by intent and by strategic design. No doubt, if we establish biological proof of concept in OTC, we will highly likely add some programs.
Maybe, Andy, you can.
Yeah.
-also elaborate on how big is the CSL partnership, you know, in terms of contributing to, you know, your capital needs and how you think about, you know, what to focus on next? 'Cause you do have milestone coming up and royalty stream coming up from this partnership.
Yeah. No, thanks, Brian, for that question. I think in our last conference call, we tried to elaborate on the financial impact of this relationship, you know, at the time. What we communicated is that, you know, hypothetically at the time, we didn't have the deal closed due to HSR, but obviously, we had, you know, achieved that opportunity and gotten the $200 million in the bank. You know, if you do it on a pro forma basis, we should have around $400 million in cash roughly. If the guidance that we gave is about 3 years, and you do a simple math linearly of dividing that by, you know, 3, you're looking at about $125 million-$130 million a year, right? That is substantially less than what we have been burning.
That we've been burning, if you go back and look at our history, around $200 million a year. That's a pretty dramatic drop. Of course, our programs are gonna continue, and CSL is gonna be supporting a majority of that, you know, program with relation to the vaccine, you know, franchise. Already that's a substantial impact, and hopefully, that helps crystallize, you know, the impact of the milestone without getting too specific with the granularity of the detail.
Maybe just to wrap up, Joe, what are the key focus for 2023? What should investors be focusing on?
Well, we're fortunate to have 6 key milestones this year. We spoke about the Japanese trial, getting that phase 3 data. That comparison data is gonna be meaningful. PMDA approval in Japan this year is something that is a meaningful update. Without disclosing too many details on the CSL side, we're looking forward to advancing a bivalent program and a flu program, and learning more about Europe and U.S. progress there. With respect to OTC, biological proof of concept is gonna be a significant impact for us. It'll allow us to add new programs to that if we establish that proof of concept. That's this year. Finally, phase 1 data for CF.
Normally, we don't get excited about phase I data, but when it's, you know, first in the field or first in class for mRNA therapeutics, establishing some sort of maximum tolerated dose through inhalation is gonna be meaningful. Even the phase I data I think would be meaningful.
Great.
A lot of milestones this year.
Well, really look forward to it. Thanks, Joe and Andy. This concludes the end of our Q&A session today for Arcturus Therapeutics. Thanks for joining us today.
Thanks, Brian. Good to be with you.