Arcturus Therapeutics Holdings Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Rather than a fireside presentation today, we decided to go through a more formal slide deck. This is a corporate deck that is available on our website, but as we go through it, I will provide some context, maybe some information that is not necessarily detailed on the slides, and then we will have a Q&A session afterwards, and we can follow up. Arcturus is a messenger RNA medicines company. It differentiates itself from the other mRNA companies with our next-generation technologies. We have a different delivery technology and capabilities in purifying mRNA and manufacturing a customized nebulizer for the inhaled treatments. As we go through, we hope that you see that we are a next generation mRNA medicines company with an extraordinary near-term and long-term opportunity for investors to pay attention to. We are based in San Diego. We have about 100 employees, so we are right on Science Center Drive there.

If you're ever in San Diego and want to stop by, it's a well-known area for biotechnology. San Diego has about 450 companies, and 100 of them have walls and mortar, and that includes us, and about 40 to 50 of those are publicly traded, and we sit in around the 15th in terms of a rank order with publicly traded biotech companies in San Diego. On the left, you see that we have an approved product, and we've recently regained control, strategic control, 100% control, of the KOSTAIVE asset. This is a COVID vaccine that's approved in 32 countries, including Japan, the U.K., and the European Union. We've also partnered with BARDA and will be able to speak. That data's going to be published. BARDA went out and looked at the bird flu aggressively, and they explored different technologies and different vaccines, including ours.

We'll have the opportunity to publish on that relatively soon, and we have a good relationship with them. On the right side, you see that we have a therapeutic franchise for ornithine transcarbamylase deficiency and CF. These are two rare disease assets that lead two platforms in the therapeutics arm of our company. Whether you're inhaling messenger RNA for cystic fibrosis as a flagship asset there, or injecting messenger RNA intravenously, our flagship program is ornithine transcarbamylase deficiency. We're partnered with the Cystic Fibrosis Foundation for our CF program, and we also engaged, signed a deal with Thermo Fisher. We've strengthened our manufacturing relationship in exchange for commercial manufacturing rights. They're helping us and supporting our CF program, and it could be significant if we make the decision to proceed further there into phase III. We have proprietary technologies. Just want to emphasize that what differentiates us in the vaccine side is self-amplifying mRNA, and what differentiates us on the therapeutics arm of the company is our delivery technology.

That is what is uniquely different. It's chemically different, it's biodegradable, it's non-accumulating, and these differentiations are helping to set us apart from a data and a commercial strategy going forward. Manufacturing know-how is a big deal. There's very few companies that have scaled, especially on commercial products, on mRNA. We're one of them, and if you go to self-amplifying mRNA, we are the only one, even though we're a relatively small company. We have a proprietary process that we use in GMP facilities to make self-amplifying mRNA products on scale, and that's very differentiating. Self-amplifying mRNA is large. It's difficult to make, purify, formulate, and ship, and the logistics of shipping, but we've managed that successfully, and we're the first to do so with that process.

I just want to emphasize the differentiation know-how there. A simple therapeutics pipeline. I know that we have a product in vaccines that provides stability to the organization. It provides a source of non-dilutive monies, which is great as a CEO, but the value, the true value being created at Arcturus is in the therapeutics branch, and we have a respiratory product and a hepatic or liver product. You can see that even though there's more than 100,000 global prevalence of CF, our initial focus is on Class 1 cystic fibrosis. About 10%-15% of the population doesn't respond effectively to modulators or other standards of care.

We're first movers in this field of Class 1 CF, which is an exciting opportunity for us commercially. On the ornithine transcarbamylase side, happy to report that we have a phase II data readout that we're going to be sharing later this month, so it's a very near-term milestone for us. It's not just a phase II data readout, but we've had a pair of Type C meetings for our OTC deficiency program this year. We've already indicated that it's been positive and productive, those meetings. But additional details, granularity on the regulatory path forward, we'll be able to share that later this month. In addition to a data readout and regulatory clarity, we're also providing a platform update. It's the cake, the icing, the cherry. It's a fulsome update, and we encourage investors to participate and pay attention to that communication later this month.

That's near term. Ornithine transcarbamylase is greater than 10,000 people, if you can Google that. Says the prevalence, and that prevalence is U.S. and Europe. So, there's potentially thousands of early adopters for this product if we're successful. This could be an extraordinary product for us. We're excited about its potential commercially. Beginning with our CF product, we have a key decision for the CF product in Q4. The reason we're guiding the go/no-go decision to proceed into phase III, that decision, if positive, if we proceed into phase III, that triggers a significant increase in contributions from the Thermo Fisher deal that we signed in July. So that's why we're providing guidance towards the decision. It's an open label study that's presently ongoing for our CF program.

You can see that as we provide a background, this is an inhaled messenger RNA therapeutic that makes or produces CFTR protein in the lungs. So we're not in the same business as other competitors in the CF space. Most CF companies are in the business of modulating a broken transporter. That is not what we do. We make a brand new one. So we're expressing a new CFTR protein in the lung that's very different from the field. It's been generally safe and well-tolerated in all studies, in phase I, phase I-B and phase II, even up to 28 daily days at 15 milligrams daily. So that's a significant accomplishment for inhaled RNA therapeutics. If you have been tracking this field, human beings do not like to inhale lipids and RNA. There's been extreme challenges in doing this with safety and tolerability over decades.

It doesn't matter what type of RNA, whether small, medium or large RNAs for different applications. There's been a lot of challenges for the field. There's been a lot of efforts because the lung is considered a trillion dollar organ. It is a very important part of our bodies, and so you can understand why these copious amounts of companies have been trying to accomplish this. But what is significant is that going up to the second bullet point is we've established safety and tolerability at 15 milligrams daily, and we did it without steroids before, during or after. We administered this drug in the home, self-administration, not in a clinic under the oversight of nurses and doctors. The FDA is allowing us to do this, so this is a very significantly differentiated platform.

And why am I emphasizing safety and tolerability is because Class 1 CF, guys, is a tough disease. It's a nested, messy disease in the lung, and you have to hit it daily. That's our view. You have to hit it daily, every day, inhale it, and chip away at this disease and resolve those mucus plugs, resolve the undesired inflammation, swelling, cirrhotic disease, right? Just heal the lung to allow other treatments or other things to work better. But we believe that this is the ideal approach for Class 1 CF. The Cystic Fibrosis Foundation has already committed $25 million. The reason we're emphasizing our relationship with the Cystic Fibrosis Foundation is because they've been very helpful in enrollment, in trials, in sites, and also, not just the cash, but the support of the foundation has been very important and meaningful to us.

And they know where all the Class 1 subject patients are. They have a nice database in the U.S. and Europe especially, so it's very helpful. We've received all the Rare Pediatric Disease Designations in Europe and U.S. That's also a good indication of potential regulatory progress. I mentioned earlier, but Thermo Fisher, if we make the decision to proceed into phase III, the financial contributions associated with that contract increase significantly, up to $40 million. I've already mentioned that the CF is a significant market opportunity, and if we can simply make new CFTR in their lungs, this would be functionally curing that local area of the lungs. It's not just modulating anything. It's functionally curing the local lung environment. So this could be a very meaningful drug, not only for Class 1 CF. If it works, it'll be applicable to everybody, potentially, in the field.

It's very franchisable, a very attractive commercial opportunity. In Class 1 CF, we mentioned there's approximately 10,000 or more Class 1 CF subjects globally. So there'd be thousands of early adopters to this technology if it became available. The summary, we've been in phase I, successfully phase I-B. We've already summarized at phase II on a previous slide. I want to focus on the bottom point of this slide, that we're presently in a 12-week open label study, enrolling up to 20 people in Class 1, including in Israel and Turkey. Israel and Turkey have high prevalence of Class I CF. It's like 30%-40%. So there's access to a considerable number of Class I subjects.