Morning, everyone, and welcome to the 2024 Jefferies Healthcare Conference. It's my pleasure to now introduce Joe Payne, the CEO of Arcturus Therapeutics.
All right, thank you. It's good to be with you, and I appreciate the invitation from Jefferies to participate in today's conference. I had the wonderful opportunity this weekend, prior to the conference, to go around to different areas of London. Three of the four of my grandparents were born and raised in the United Kingdom, so I got to see where the homeland was all about, so it has been a great experience. But today, it's all about business, and so I'm very happy to introduce to you Arcturus. It's a messenger RNA medicines company, a next-generation messenger RNA medicines company based in San Diego. We're a global mRNA medicines company, but we've also initiated a commercialization process with our first approval in Japan, so we're just entering the world of commercialization. If you're ever in San Diego, you're more than welcome to come on by.
We're on Science Center Drive, where there's a lot of biotech companies there. We have mRNA medicine candidates for—we have a rare liver disease pursuing ornithine transcarbamylase deficiency, and also we have an inhaled messenger RNA product going after cystic fibrosis. There's three technologies that help us succeed in this effort. We have mRNA technology capabilities. We have delivery expertise and also manufacturing know-how. And the areas that I would like to emphasize here is, on the mRNA side, we have a leadership position in strong IP and self-amplifying mRNA, and this is a differentiator in the vaccine space. As you look at the LNP, or lipid nanoparticle technology, that we trademark as LUNAR, this is a key differentiator for us in the therapeutic space. And finally, our manufacturing know-how.
We're one of a very short list of companies that know how to make these sophisticated therapeutics on very large scale, but how we differentiate here, again, is we're the only company in the world that's done very large manufacturing efforts in self-amplifying mRNA. This is three times larger than conventional mRNA, so we have a very unique skill set with making, purifying, formulating these very large mRNA molecules that sets us apart there. I touched on that our delivery technology is differentiating, and what do I mean by that? Well, they're highly optimized for specific cell types. There's 200 different cell types in the body, and Arcturus is very good at delivering RNA to three of them. We can do so to myocytes after an intramuscular injection. We can access hepatocytes after an intravenous administration, and then bronchial epithelial cells after inhaled applications, so these are highly optimized programs.
What differentiates us is this is a chemically different lipid nanoparticle and platform. These chemical differences translate into benefits, including biodegradability and non-accumulation. We've showcased this benefit in multiple clinical trials now that after 48 hours, it's no longer detectable, these lipids. That's a very important feature. As you go through the pictures on the slide, no matter what the cell type we're going after, you have to not only access. You have to survive the blood or the sputum or the phlegm in the lungs in certain cases. There's a survivability aspect to the optimization process to access these cells. Then once you're in the cells, you need to break out of that endosome. There's a different biochemical process for each cell type.
We have some really strong know-how and capabilities in how to optimize these lipids for breaking out of that endosome and delivering that mRNA to the cytosol and do it effectively. It's something we do very well. I just want to showcase two of our flagship assets that have meaningful data readouts coming up here shortly. Our flagship liver asset, again, it's OTC deficiency. It's the number one urea cycle disorder. We have phase two readout interim data in the first half of next year. We've already completed the European cohort. We're now recruiting patients in the U.S., but that's a near-term upcoming milestone for us. In the respiratory division, our flagship asset is going after cystic fibrosis, and we have some interim data coming out in the first half of next year. We have several partnered self-amplifying mRNA vaccines.
CSL is a very large Australian company with a vaccine division called CSL Seqirus. We're working with them and funded by them with multiple programs listed on this slide. Starting at the top, you have KOSTAIVE. This is our approved COVID-19 vaccine that's been approved and is now being sold and distributed presently in Japan. We also have an MAA filed in Europe, and we are anticipating a CHMP opinion in December, just next month, for that program. So that's very active. Going down to the bottom of the slide, I'd like to emphasize some recent news with the pandemic flu program. This is funded by the U.S. government, the BARDA, and this has recently been approved to proceed into phase 1. So this is going to be an important program for pandemic preparedness for the U.S. government. We're working closely with them, and that's been in the news recently.
So I just wanted to emphasize that. Get to knowing our partners a little bit more. I mentioned CSL is a very large company based in Australia, but their CSL Seqirus division is a world leader in flu vaccines, more than billions of dollars of annual revenue out of that division. So they're an ideal partner to help us in the U.S. and in Europe. We entered into the vaccine partnership now two years ago. It's been a whirlwind relationship for those two years. We're big fans of CSL. We'd like to think they're big fans of Arcturus. We had a substantial upfront payment back then, but since then, we've had hundreds of millions of dollars of development milestones paid out. And you also see that we are slated for $3 billion of commercial milestones, and we received our first commercial milestone recently.
So I want to emphasize that: $25 million for having our first commercial sale in Japan. And so we look forward with anticipation to getting more of these commercial milestones. And that's a key thing to emphasize: 40% profit sharing in the COVID-19 vaccine or the KOSTAIVE franchise in the U.S. and Europe, and also double-digit royalties for the other programs. We're pursuing flu and other respiratory infectious disease vaccines in this collaboration. I mentioned that we have an approval in Japan. We don't have a commercial presence in Japan, but we brought in Meiji to help CSL and Arcturus with distribution and sales. A fantastic company. They're a very well-known brand in Japan. If you ever have the experience to go there, the brand Meiji is absolutely everywhere. It's a well-trusted brand, a great company.
They're also the number one flu shot company in Japan, approximately 40% of the market share. So they understand endemic vaccines and distribution there. So we have a great partner to help us with our KOSTAIVE product, this next-generation COVID vaccine in Japan. I also want to emphasize the recent news that Meiji has invested in our joint venture mRNA manufacturing, Arcalis. Arcalis is our JV mRNA manufacturing partner. You see on the left side there that the major equity owners now include Meiji. And so this is a recent development. We're happy to bring them on. This, I believe, is a positive development. It shows that they're committed not only to a near-term distribution process, but to building the relationship further and making more products in this plant, in this factory.
You see that it's 78,000 sq ft, has been completed, and it's very near PMDA approval as a commercial manufacturer, which is exciting. And there's also an expansion phase that's already planned that's summarized on the bottom. There's a lot on this slide, so I'm just going to summarize it. But KOSTAIVE has had many multiple phase 3 studies to showcase the benefits of this next-generation technology. Self-amplifying mRNA extends the duration of expression of the antigen, and this has significant benefits. If you want elevated antibodies, this is a great technology. If you want a broader spectrum of antibodies relative to conventional mRNA, this is an ideal technology. If you want extended durability, a longer lasting immunogenicity, and the implied protection that that provides, then this is an outstanding technology. And then we do it at multifold lower dose.
We check a lot of boxes with this next-gen tech, and we've now proven it in multiple phase three trials and in multiple publications in the Lancet Infectious Diseases. So we've completed a non-inferiority safety and immunogenicity trial, achieved a primary endpoint, achieved a secondary endpoint in that trial. It's generally safe and well tolerated. We've repeated this with additional versions of the vaccine, including a bivalent version. So there's a lot there to read and access on our website, but it's an excellent technology. And it's the first. It's the first self-amplifying mRNA product in the world. Very proud of this accomplishment. Last November, we approved the updated version of that of KOSTAIVE that's being presently distributed as well. And we're working closely not only with the government of Japan, who's been a collaborator in this process, but of course, CSL and Meiji.
The data here, I could have had many, many slides of data. I just want to summarize what do I mean by elevated antibodies and extended durability? I could show multiple graphs here where it extends out to 12 months. There's clear advantages to this next-generation mRNA technology in the clinic directly compared with approved conventional mRNA vaccines. So now on to therapeutics. Cystic fibrosis is our flagship asset for inhaled messenger RNA. This is just at the cusp. This is a new technology. Everyone knows about mRNA. Everyone here has been probably injected with it in the arm. But what other applications? People are really looking closely at this, and they should. Because if you can successfully, safely, and effectively inhale messenger RNA and access the bronchial epithelial cell, that is a big deal. This is a very important cell type in the pharmaceutical industry.
The lungs are an important organ. We like to breathe. So you can imagine the importance of this. CF is our flagship program. It's a large, well-known, even though it's a rare disease, it's a well-known rare disease. Very lucrative opportunity for us. There's a lot of unmet medical need. Approximately 18% of the CF community does not benefit or qualify for modulators that are very successful for the other portion of the population. But there's a significant unmet medical need in about 18% of the CF community. And what we aim to do with this product is, after inhalation, the mRNA molecule replaces and builds a new CFTR protein in the lungs. So there's leaders in the CF space that are in the business of fixing or modulating a broken transporter. That is not what we are doing. We're in the business of making a new transporter.
We're not fixing or modulating a broken one, so this is going to be an exciting opportunity for us if we can prove this out, and where are we? Well, we had a very successful phase 1 study in 32 healthy volunteers, and then we transitioned successfully to a phase 1b in seven CF subjects that received two administrations. And the safety and tolerability data of that study supported advancing it into a phase 2 study, and this phase 2 study in CF subjects, again, that do not qualify for or benefit from modulators is the focus of this phase 2 study. We're presently recruiting for this. It's a multiple ascending dose open-label study, so it's not a placebo-controlled study. We're evaluating the safety, tolerability, and efficacy, and by efficacy, I mean FEV improvements in lung function.
This is a simple test to evaluate, can we improve their lung function? These folks that do not have where there's considerable unmet medical need have deteriorating lung function over time. And if we can correct that and actually inflect it upwards, this is going to be transformational for this group of people. And we'd be excited to get this data. We've already seen snippets, okay, early data in our phase 1b study that showcase the potential of this. And there was one Cass I subject in our phase 1b study, for example, that improved 4% FEV after just two administrations. So this is encouraging, and we're going to be looking closely at this phase 2 study. Some points summarized on the bottom. We have to recognize the funding and support from the CF Foundation for this program. $25 million has been committed.
And also, we've received rare pediatric disease designation and orphan designations in both the U.S. and Europe that showcases where we are within the competitive community and how to protect our IP for this product. And at the bottom, you see that our phase 2 interim data is expected just around the corner. We're going to blink, and this data is going to come here soon so you can understand why we're excited. Now, earlier in the presentation, I mentioned that our LUNAR delivery technology, that beautiful cartoon in the middle, differentiates us from our competitors. It's chemically different. These differences translate into differentiated preclinical data sets. We've showed that this technology works very well in mice, rats, ferrets, and primates. And the ferret data is especially interesting because ferrets are an excellent model of the human condition.
Humans that get CF develop a lot of phlegm and subsequent fibrotic disease, cirrhotic disease, and challenges there. Ferrets are the same. They have a lot of phlegm in their lungs, so looking closely at the ferret data, we believe this is the most meaningful data set. We got a spontaneous applause at a national CF conference when we first presented this. It was a very proud moment for our scientific team, as you can imagine, but in the upper and lower respiratory tract showing functional proteins being expressed in the ferret model, and when you look at a functional readout, mucociliary clearance, you can see that after a single administration, the green line outperformed the positive control, the blue line, after a single administration in this model. If you look at some, you complement this with some cellular human data.
So these are human cells from actual CF patients that have donated these cells. We saw high expressions of CFTR in human cells, and we restored chloride ion activity in these cells. You take all of this together, and the 39 subjects of humans that have already received this, including seven patients that have received two administrations and some early positive signals, even though it was a safety study, we enjoy these early positive signals. The breakthrough proof of concept data is anticipated and hoped for in the first half of next year. Now on to ARCT-810. This is our flagship liver program asset that's pursuing ornithine transcarbamylase deficiency, or OTC deficiency. This is the number one urea cycle disorder. If this urea cycle is dysfunctional, ammonia levels rise. For the non-scientists, that's Windex. All right?
You don't want ammonia crossing the blood-brain barrier and having negative neurological impacts, as you can imagine, so having tight control of the ammonia levels in the body is very, very important, and if you have a dysfunctional OTC enzyme, then ammonia levels are very high. The present standard of care is ammonia scavengers. You take a lot of pills, you drink a lot of water, and you urinate a lot, 10 times a day and throughout the evening and the night, so it would be much more preferred to just simply fix what's broken, replace the dysfunctional or missing OTC enzyme, and restore the urea cycle, and that's what this product aims to do with mRNA, gets into the hepatocytes with our proprietary delivery technology that's differentiated from everybody else, and break out of the endosome and express that enzyme and correct this disorder.
We've shown really strong preclinical data. The threshold is that you see the 5% threshold, that's already been clinically established. If you have 5% normal ornithine transcarbamylase, you don't even know you have the disease. And we've done a great job in preclinical models. These OTC deficient mice, if you give them protein, they all die. And if you administer the drug and give them protein, they're all happy spinning in a wheel. And there's only one way to explain that and that this drug is working as it's intended to do. So we hope to see this in human beings. So where are we? In human studies, phase one was completed in healthy volunteers, 24 subjects there, safe and well tolerated, generally speaking. And phase 1b was also successful.
16 patients here in the U.S. were recruited at four different dose levels, all the way up to 0.5 mg/kg with no SAEs or serious adverse events, and right now, we're in phase 2. We've completed our U.K. cohort and our European cohort at 0.3 mg/kg, and then at the bottom, you can see that we are expanding the study to include multiple dose levels and enrolling patients with more severe disease in the U.S., and that's presently ongoing, so we're going to pool these data together, and we intend to have that data available in the first half of next year, and at the bottom of the slide, you see that, again, we've received orphan drug designation and fast track designation and rare pediatric disease designation from the FDA and also orphan status with the European Commission.
The bullet point on the bottom needs to be reemphasized. I've said it twice. I'll say it a third time just to make sure it's clear that interim phase two data is anticipated in the first half of next year. And this is intravenously dosed mRNA to the liver, another flagship asset, huge commercial opportunity. Liver is, again, a very important organ. Hepatocytes and building proteins in these cells is very interesting. I also added the Arcturus Board of Directors slide because we've recently added Moncef Slaoui, who's Dr. Slaoui is with us in the audience today. He led Operation Warp Speed. He evaluated our technology independently of us. And thankfully, he ranked us first and best. And so we were very fortunate to have him come join our board.
And he's been very helpful in the first few months as he's helped us understand our strategic decisions and where we should direct this self-amplifying mRNA vaccine technology and also leverage his GSK experience on the therapeutic side to really point this technology to the more exciting commercial opportunities under the assumption that we're successful in CF and OTC. We've also brought on John Markels recently, who was previously the president of Merck Vaccines. But just wanted to highlight that. This is my last slide. In the next few quarters, just really punchy here, we have a CF readout in the first half of next year. We have a liver ornithine transcarbamylase OTC deficiency readout in the first half of 2025. And then KOSTAIVE Japanese sales. We're cheering on our partner, Meiji, there as we go through this season into the first half of 2025.
The CHMP opinion for KOSTAIVE is coming up next month and a BLA filing in the first half of next year. We continue to advance our partnered programs. I could go on and on. BARDA, for example, we just announced our phase one trial, and we'll have data for that next year as well. A lot going on. I turn the time over to the audience for questions. If there's no questions, there's only a minute and a half left. Okay. Go ahead.
I can restate it, but go ahead.
How do you guys think about epidemiology and real-world evidence as it informs the development of your various sort of assets in the pipeline on the vaccine side?
Oh, great, great question. There are certain things you can conclude with 1,000 patients, 100 patients, 20,000 subjects of data.
But there are other elements that you can conclude with millions of subjects of data, especially with respect to serious adverse events, for example. There are well-documented and published rates of serious adverse events with conventional mRNA vaccines that you can refer to and Google. Our dose level is dramatically lower. And so it will be very interesting to see if there are dose-related toxicology benefits that can be teased out of larger data sets. So I think that's going to be something that can be easily tracked over time as we get into, hopefully, millions of people and understand on a much larger scale, is there any safety-related benefits that are meaningful by lowering the dose dramatically with self-amplifying mRNA? There's a lot more I could go into there. I know people are looking at these vaccines for their implication in things like cancer as well.
MD Anderson is tracking COVID vaccinations with mRNA vaccines to see how it complements with checkpoint inhibitors, for example. So the academic space, academia will be probably continuing to look at that. We may participate in things like that in the future. Any other questions? Okay. I think we're out of time. I appreciate your time, everyone.