Arcturus Therapeutics Holdings Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Hey. Oh, thanks. Yeah, it's good to be with you, Pete. Thanks for the time, and Arcturus Therapeutics, it's a messenger RNA medicines company. We utilize next-generation technology, so our technologies are differentiated and often in a compelling way. We utilize different technologies. We're building a therapeutics pipeline. We have a pair of programs that are deep in phase II clinical trials. We have a flagship liver program called ornithine transcarbamylase deficiency that's an intravenously dosed messenger RNA therapeutic that has a readout later this month. We'll have a concurrent. We'll be providing clarity on the regulatory path as well, and providing an update on the platform in general, so we have a meaningful update there later this month. With respect to our lung franchise, we also have an inhaled messenger RNA platform, and the flagship indication there is for cystic fibrosis.

We have a key decision that's coming forward in Q4 pertaining to that program that will trigger some good things to help fund that program, too. On the vaccine side, we also have self-amplifying mRNA technology. We have an approved product utilizing this technology in 32 countries in the vaccine space. We have a COVID vaccine called KOSTAIVE that's, like I mentioned, approved in Europe, in the U.K., and Japan. We have a partner called Meiji that's helping us distribute that product in Japan. The application of self-amplifying mRNA has come under additional interest because of recent data in the messenger RNA community outside of infectious disease and into oncology. So there's some interesting applications of that technology there.

We view the self-amplifying mRNA platform as a mechanism to capture non-dilutive monies and cash, basically to fund the value-creating therapeutic programs for the liver and the lung. That summarizes the company, and look forward to today's discussion.

Okay. Ornithine transcarbamylase deficiency, or OTC deficiency, is the number 1 urea cycle disorder. It's when the urea cycle is dysfunctional, ammonia levels rise in the blood, and ammonia crosses the blood-brain barrier and causes neurological challenges, problems. This is a very severe, serious disease, and we need to be able to control that ammonia. The body's natural way to do it is the urea cycle. This urea cycle, this biochemistry happens in the periportal portion of the liver, and Arcturus has an exceptional technology that can safely and effectively deliver mRNA to the periportal portion of the liver and to these hepatocytes to address this disease. The present standard of care for ammonia diseases is ammonia scavengers. People take all these pills, drink a lot of water, and urinate 10 times a day and throughout the night to expel the ammonia.

Unfortunately, the body, whenever it sees excess ammonia, it converts that to glutamine prior to the ammonia being scavenged. This is an important point, in that this glutamine crosses the blood-brain barrier and then releases the ammonia biochemically that way. It's just a really challenging disease. Instead of scavenging the ammonia, we're in the business of replacing what's missing or broken. In this example, you have a dysfunctional ornithine transcarbamylase enzyme. We're in the business of building a brand-new one in those hepatocytes, and this could be, therefore, functionally curing the disease and controlling ammonia, and then people can eat whatever they want. These elevations of ammonia are caused by ingesting or eating proteins. You can imagine the folks suffering with this disease have a very strict diet as well, and that can be, of course, very problematic.

We're in the business of functionally curing the disease, replacing what's missing, allowing these people to eat whatever they want, frankly, and alleviate their requirement or need to be on ammonia scavengers. And controlling that glutamine level, that's also problematic. That's also important for us, too.

Correct. The messenger RNA goes inside these cells and expresses, makes a brand-new ornithine transcarbamylase enzyme. We've successfully navigated our way through phase I and phase I-B. We've done some dose range finding in early phase II studies, and we've now completed enrollment in both in Europe and U.K. and now in the U.S., and we're collecting this data, compiling it, and we're going to be sharing that data. That data readout is later this month. We've also had a pair of Type C meetings this year for this program, so we're regularly communicating updates to the FDA and the regulatory agency. We've received some positive and productive feedback in these meetings. We intend to provide some more granularity there.

In addition to the data, we want to provide a regulatory path and explain a little bit more detail what those Type C meetings provided and provide clarity to Wall Street there.

Among the, yeah, that's a great question. What's published is there's approximately 10,000 people with OTC deficiency in the United States and Europe and U.K. That's a significant opportunity if you look at the pricing for this space. The present standard of care I mentioned is ammonia scavengers. They can be hundreds of thousands of dollars, even exceeding $1 million in treatment. So, it's an expensive disease to treat presently. There's also a recently approved gene therapy that is going to be potentially treating a portion of the stable adults in the population. Our therapy is ideally suited for the unmet need, which is children and those that are in pediatrics. It's much more severe at those stages. It's an X-linked disorder, so young males tend to have severe disease and can pass before they reach school age.

Our intent here is to address the highest unmet need, the largest commercial opportunity in the space. There's also some gene editing data that's been shared for urea cycle disorders. Unfortunately, they've had some challenges with hyperammonemic attacks and lack of response. It's just us, is what I'm trying to get at. It really is. There's a lot of pressure on the organization and the urea cycle disorder community for us to succeed here. We used to have a lot of competitors, but we don't. This data readout that's coming later this month, hopefully it'll provide some hope and optimism for the community as well.