Hello, everyone. Welcome to the H.C. Wainwright 26th Annual Global Investment Conference. I'm Thomas Yip. I'm part of the H.C. Wainwright research team. For our next presentation, we have Arcturus Therapeutics, and joining us today is President and CEO, Joe Payne.
Yeah.
Great having you with us. Go ahead.
Thanks, Thomas, for the introduction. Arcturus Therapeutics, it is an mRNA vaccines and therapeutics company. We have next-generation technologies that support our pipeline, and we'll be talking about that in these programs, giving an update here shortly. We're out of San Diego, so if you're ever in San Diego, right on Science Center Drive, we have a couple sites there and about 170 employees, and we have therapeutics and vaccines in our pipeline. Our strategic partners are listed at the bottom of the slide: CSL, the CF Foundation, and BARDA. CF Foundation supports our CF program, and BARDA supports our pandemic flu program. CSL is our vaccine partner. The next-generation technologies are summarized here. We've got exceptional capabilities in designing and manufacturing mRNA molecules of different types, including self-amplifying mRNA, the STARR technology.
This is a low-dose vaccine technology that is something that we're spearheading. We've got the first-ever self-amplifying mRNA product approved in Japan, and we're soon to be doing that in Europe as well. The LUNAR delivery technology is one of our central or key capabilities. The ability to safely and effectively deliver these mRNA molecules to where they need to be is, of course, extremely important, something we do very well, to whether it's to hepatocytes in the liver or myocytes in the arm after a vaccine injection, or after inhalation to bronchial epithelial cells. The manufacturing know-how is actually something that we should be emphasizing.
You know, recently, Moncef Slaoui joined our board, and he pointed out that this was what really differentiates our company, is the ability to make, purify, and formulate these very large mRNA molecules, is a unique set of know-how, and our manufacturing know-how is definitely something that sets us apart. Our delivery technology is a proprietary, biodegradable, and optimized for each cell type. And as this LUNAR delivery technologies enters the cell, it also allows. It's engineered to break out of the endosome. And when we say optimized for each cell type, this is important because every cell type is different. The process of the particle entering that cell and breaking out of the endosome, that biochemical process is different depending on what cell you're pursuing, and we've got optimized delivery technologies for different cell types.
The Arcturus-owned mRNA therapeutic pipeline is summarized here. We have a flagship asset for the liver called OTC deficiency or ornithine transcarbamylase deficiency, where this is the number one urea cycle disorder, and it helps control ammonia levels in the blood, and our next milestone there is some interim data next quarter. We've completed our first cohort at 0.3 mg per kg, and we'll have that data available in next quarter. The respiratory franchise is led by our CF program. It's sponsored and supported by the CF Foundation, but our phase II trial has initiated. We've just recently had approval to proceed here in the U.S. with that trial, so we're gonna be recruiting patients and getting some data, you know, as soon as possible next year.
The pipeline of partnered self-amplifying mRNA vaccines is summarized here. We have an approved product called Kostaive in the top left. This is being launched in Japan very shortly. In fact, our team is gonna be traveling there to support the public relations and media and marketing for the launch of this product here just in a few weeks in Tokyo. So we're excited about that. Behind that is the MAA has been filed in Europe as well, so we're looking forward to getting that approved later this year. The bivalent Kostaive is an ongoing trial, which is becoming more meaningful. We've seen some inconsistencies in the mRNA space with respect to multi-antigens or multiple antigens or bivalency, so people are looking forward to seeing this data to see if our platform is consistent in the monovalent or bivalent setting.
We have an XBB trial as well. This trial is being conducted in the Southern Hemisphere in multiple ethnicities, and this is gonna be very important to supporting a US application. The bulk of our data collected to date has been in Southeast Asia, so it'll be helpful to get some Latin American, Caucasian, and African American safety results out of that trial. The LUNAR flu program is ongoing with CSL as well, and the pandemic flu program is going to be starting here in the fourth quarter. So we're excited about that. There's elevated attention on pandemic flu. People don't appreciate this, but if the death rate for pandemic flu is over 50%, so that is dramatically worse than COVID.
So that's why there's elevated attention on this with all the countries, and the U.S. has selected us to provide, and to fund this program, to get it into the clinic, and ultimately, we may be able to help with stockpiling there for pandemic preparedness. CSL is our global partner. They're a big player in the vaccine space. We're very fortunate to be working with them. They're number one or number two in the flu shot, so they understand endemic vaccines, like COVID has become. It's now an endemic virus that's changing on an annual basis, so having their commercial footprint to support us in Europe and U.S. is gonna be very helpful. Just a reminder of our vaccine partnership with up to $4.3 billion in milestone payments.
We did receive a $200 million upfront payment from when we initiated the collaboration, but we're just in the process of entering the commercial milestones phase with our first commercial milestones coming up here in Japan and Europe later this year. So, 40% profit sharing on the COVID franchise, and also up to double-digit royalties on flu and the other respiratory infectious disease vaccines. Meiji is our partner in Japan, so while CSL is gonna be supporting us in Europe and U.K. and U.S., Meiji is a key distributor for us in Japan. They're the number one flu shot company in that part of the world, in Japan. So, whether it's the private sector or the government relationships, we're fortunate to be working with them.
We've provided them with four million doses of our vaccine, and we'll be anxiously following how well they distribute this vaccine throughout this upcoming season. We have a joint venture manufacturing facility in Japan that's been funded primarily by the Japanese government. We've received close to $200 million from the Japanese government to help us build this facility. We're in the process of finalizing our GMP certification. Once this is GMP-certified, then the PMDA, the government of Japan, can then start to initiate dose orders from this facility, and that's very important for Meiji. It's important for Arcalis, our joint venture, but also for the government of Japan.
It's essential for them to establish independence for pandemic preparedness, not only just because of the last recent experience, but looking forward, having a fully integrated mRNA manufacturing facility in Japan is central to the Japanese government's thesis. The Kostaive phase III clinical studies are summarized here. The monovalent Kostaive activities are on the top, and the bivalent activities are on the bottom of this slide. But we, you know, we saw some exceptional efficacy against Delta, the Delta variant, which is far more challenging than Alpha, Beta, and Gamma. So the Delta variant was a difficult version of the virus, and we had just extraordinary success against that in Southeast Asia. And then, in addition, we've established really nice safety and tolerability data, and this phase III studies are published in The Lancet.
So I, I've spent a lot of my time as a CEO selling this technology and the potential of the technology, and I don't need to do that anymore. I just start to point to a lot of publications showing that we have higher antibodies and extended durability and we do this at much, much lower dose levels. And everybody wants more protection, right? We want more antibodies. We want a longer durability, more persistent vaccine, and less stuff being injected. So as we commercialize this, first in Japan and moving to Europe and U.S., this data is gonna support, help our sales force with our partners, get the message out. We are gonna be sharing even more information on durability. We've guided that later this month.
Just in a couple weeks, we're gonna be presenting at the Options conference, and there's gonna be more data on how durable are we talking about, and so we're gonna have some twelve-month durability data that's gonna be presented or published, so we look forward to that in a couple weeks. We remind people that this is a historic approval. This, again, was the first ever self-amplifying mRNA product to be approved, and we consider this a big deal because this is a next-generation technology, and usually it takes over a decade to advance another generation. But because of the pandemic, we got thirty-eight thousand subjects of recipients to accelerate this data set forward and allow us to get this approved in an efficient manner. So this is the six-month data.
I did allude to the twelve-month data coming out in just a couple weeks, so this is your last look at the six-month data. But clearly, the five microgram Kostaive outperformed the thirty microgram competitor. There's no doubt about this in every aspect. So we're very proud of this data that continues to mature, and this is just for one of our three phase III trials that are ongoing. So we look forward to the bivalent data set coming out and the subsequent XBB monovalent data set to come out, just to keep showcasing the value of this platform relative to the conventional mRNA peers. Now, moving on to therapeutics, our flagship lung program is targeting cystic fibrosis. This is an exciting opportunity for mRNA. The ability to make a brand-new transporter in these lungs is a big deal.
The entire business, the pharmaceutical industry and CF is in the business of fixing what's broken. They modulate a broken transporter. That's not what we do. We're in the business of giving folks a brand-new transporter, not fixing or modulating a broken one. This is a new era, very disruptive technology that people are tracking. The ability to inhale messenger RNA and make proteins of interest is frankly disruptive. Our phase I study was completed in New Zealand successfully, 32 subjects, four dose levels. We continued on to a phase Ib study in seven patients, CF patients, and each of them received two administrations. Now that's 39 subjects of data, not one serious adverse event. At the higher doses in healthy volunteers, we saw some minor febrile reactions.
That's exactly what you want to see in a phase I study, and so we've dialed down the dose level for our phase II, and the target doses that we're pursuing in phase II should, you know, are expected to be safe and well-tolerated. We have to prove that out, but this could be exciting proof of concept. You combine that safety data in humans with our preclinical efficacy data, and especially the CF ferret, this is an exciting shot on goal for us with just an extraordinary market opportunity. The phase II study is gonna be primarily focused on those that are not responsive to modulators, so our, you know, most of the drugs in the CF community are modulating the broken transporter.
There are about one in six, about 18% of the CF population does not respond to modulators. They, they don't qualify for them, they don't benefit from them, they don't like them, whatever the reason, and so we're gonna be targeting those folks in this phase II study. We remind people that it's funded in large part by the CF Foundation. And our phase II trial is being conducted in the U.S., where that's the home, that's the backyard of the CF Foundation. So they'll be able to help us and support us with recruitment. And we've received all the designations that you'd like to see with the U.S. FDA and the European Commission to support this trial from a regulatory perspective.
I mentioned some of the efficacy data that you've seen in preclinical animal models, not just mice, and rats, and primates, but ferrets. That bottom left, that's very important because these CF ferrets develop a lot of phlegm in their lungs. They're very representative of the human condition. The other animals, you can give them cystic fibrosis, but they don't get sick and die like the humans do. So the CF ferrets is more representative. You engineer, genetically engineer CF into a ferret, they'll get sick. They'll get copious amounts of phlegm that cover their lungs. It's a very stringent, difficult model to show efficacy, and yet we've shown that.
Even in looking closer in the trachea and the bronchus, the upper and the lower, having the ability of these nanoparticles to biodistribute, survive that sputum, and transfect those cells, and express the desired protein is a big deal. We've also shown functional activity after a single administration. You see that green line? You don't have to be much of a scientist to see the green line. The green line's much higher than the positive blue control. So after a single administration, we saw mucociliary clearance improve in these CF ferrets. So clearly, this is something that we're excited to watch, and hopefully, we'll see the same sort of data in humans.
We have looked at in vitro in human cells, and we've seen that the CFTR has expressed the actual protein of interest, and that translates into restored chloride activity as well. So we have all the pieces of the puzzle in place. We just gotta wait for that data. It's gonna be a big win for us, so cross your fingers for us. We really wanna help a lot of people with that drug. Now, moving on to ARCT-810. This is our flagship asset for the liver. OTC deficiency is the number one urea cycle disorder. If the urea cycle in your liver is dysfunctional, then ammonia levels rise. Ammonia is a bad actor. It crosses the blood-brain barrier and does bad stuff, and we do not want that to occur. It's a very serious disease.
Again, we're in the business of not dealing with the symptoms. We want to functionally replace what's missing or dysfunctional. We want to replace and provide these people a brand-new enzyme called ornithine transcarbamylase. We've done this in animals. The target is 5%. We've learned in human beings that if you have 5% functional OTC, you're normal. They don't even know they have OTC deficiency. And we've shown up to super physiological amounts of the enzyme in our animal models. And in fact, this is a lethal animal study, so all the animals if they are not treated, they all die. But if all the ones that are treated are happy and spinning in a wheel, and so our preclinical data is very strong.
Our clinical data has shown strong safety in phase I, 24 volunteers there, up to 0.4 mg per kg. We had the opportunity to expand into a phase Ib, here in the US, into all the way up to 0.5. We've had even extra patients that we could even elevate the dose further, and so we now have positive data up to 0.5 mg per kg. Our phase II study in Europe is completed. We've completed one cohort at 0.3 mg per kg, and that's the data set that we're gonna be sharing, or have the ability to share it in the fourth quarter. That's a cohort of eight. There's six subjects on drug and two subjects on placebo.
And then we've expanded this phase II study into the U.S. in a non-placebo-controlled study, and we're gaining access to younger, sicker patients, patients that are more advanced, have more advanced disease. And this will allow us to showcase the platform even more so, if we're fortunate that it works. And so we've made that expansion, and that's ongoing in parallel, recruiting patients in the U.S. ARCT-810 has also received all the necessary designations, and whether it's rare pediatric disease designation, orphan drug designation in the U.S. and Europe. Final comment on our board is that we recently added Moncef Slaoui. He ran Operation Warp Speed. He's just a fantastic addition to our company. We're very fortunate to have him. He really, really understands the vaccine space, but also therapeutics.
He worked with GSK, had an extraordinary career there, and just wanted to make people aware that we're working closely with him, and he's excited about the self-amplifying mRNA platform for vaccines, infectious disease vaccines, and other areas, but also the therapeutic side of the business. Just wanted you to be aware that he's joined our board. I'll close there for any questions.