Fireside Chat: Beyond the Needle: Oral, Intranasal & AI-Driven Drug Delivery Platforms - RANI THERAPEUTICS HOLDINGS INC

All right, great. I know we're all coming off lunch in the panel here, so I hope everyone can get settled down now. I'm excited to welcome the team from Ronnie. We have Talat Imran, CEO, here joining us. Kate McKinley. Kate McKindley, and then Nick. Myosis. MyosIS, okay. Our special guest, in a way. I didn't expect them to come, so thank you guys for making the trip and joining us here. So let's get into it, actually. Why don't we do this? For anyone new to the story, what actually happens after a patient swallows a Ronnie pill? Well, first of all, let's just do this. Maybe give us a quick overview of what Ronnie does, how it's differentiated from a lot of the companies out here, what I guess would be the, call it the holy grail of what everyone's trying to do in terms of taking a biologic and putting it into a pill. This is why we're excited about what you guys are working on. So just give us a quick intro, and then we'll jump into some of the questions. Absolutely. First, Andreas, thank you for giving us the opportunity to be here and have this conversation. So Ryan Therapeutics is a clinical stage biotech, and I promise you, at a minimum, you will not hear this story again today or any other day. what we've developed is a platform technology for the oral administration of virtually any biologic with bioavailability that is equivalent to a subcutaneous injection doesn't matter if you deliver a monoclonal antibody a protein a peptide an oligo we've done all of those and they're all equivalent and as andrea said that's been called the holy grail of drug delivery the state of the art before us was uh permeation enhancers that really are only geared towards delivering small peptides. And even there, you get sub 1% bioavailability, incredibly high variability, and a food effect. The reason we've been able to make it work is we're working with the anatomy and physiology of the gut as opposed to against it. What we've developed is essentially a swallowable autoinjector. It looks like a pill. Patient swallows it. And when it gets to the small intestines, there's a reaction, an Alka-Seltzer reaction that occurs that inflates and aligns a balloon there's a micro syringe inside of the balloon that delivers the drug through an injection pain-free because there's no sharp pain receptors in the gut and the needle itself that does this dissolves so we don't even leave a sharp in the body the balloon deflates and is excreted out and i can see people's faces it sounds like science fiction uh it is very real We've been through four clinical studies, a repeat dose study, 250 pills, over 250 pills orally administered, showing incredibly high bioavailability, whether it's a peptide or an antibody. Any? Any. Any. We've delivered Stelara in a pill in humans. We've done Factor VIII, which is a 300 kilodalton molecule. Yeah, and literally anything. there's no limitation yeah we'll take questions so there's a balloon that inflates and aligns and it provides apposition so we don't have a picture of it but it has a hump at the back that provides sort of back force and then the needle comes out very quickly and the drug is delivered into the intestinal wall pain free comes out in less than a second and thenthe needle dissolves about 30 seconds later Very intuitive and very cool if you guys want to watch the video on the website. And the story is even cooler, right? Because you said Alka-Seltzer, right, I think that, you know, the founder or the creator or the inventor saw the Alka Seltzer dissolving, right. And he figured out how you can configure it. Well, he had spicy Indian food one night and he had an upset stomach. And he'd been working on this for about a year and a half, but it had springs and levers and it was really a complicated mechanical device. And when he dropped the Alka-Seltzer in water to calm his stomach, he said, okay, this is going to be it. Yeah. Yeah. It's cool. It's why we're excited about it. So, I mean, I guess we've been talking about it, so what actually happens after a patient swallows the Ronnie pill, and why does that solve the problem that has defeated biologics for decades, oral biologrics for decades? Well, I'll just take the last part of that, because I think I answered most of it. The permeation enhancers are trying to fight evolution. The gut evolved to break down biologic material. so you don't absorb a virus through your gut and it's to absorb nutrition so it'll destroy any biologic you put in we are bypassing that completely with an injection whereas the permeation enhancers are trying to get infinitesimally small amounts of small peptides across the wall of the gut it doesn't work very well as i said we have solved this problem at this point well okay you're answering my next question so we're going to sorry let's get into uh 114 and obesity. In July, you reported that RT-114, the Ronnie pill-delivering progens GLP-1, GLP2 dual agonist PG-102 achieved bioavailability greater than 150% of a matched 12-meg subcutaneous dose in 30 healthy volunteers with a similar half-life and no device-related adverse events. Why would oral delivery beat subcutaneus, and how variable was exposure from patient to patient? So Kate McKinley is our chief business officer. She led that deal. I'm going to have her talk through it. Great. Thanks, Andreas, and thank you for having us today. So first we'll step back and talk a little bit about the partnership that Ronnie has with Progen, which is a company based in South Korea. Ronnie and Progen have a strategic partnership for the oral delivery of Progen's PG-102 via the Ronnie pill. And the strategic imperative behind this partnership is to take the potential best-in-class GLP-1, GLP2 in obesity and put in the best-In-class oral delivery. And there's some properties that are really unique to PG-102 and got our team very excited to enter into this partnership. The first is it appears that they've demonstrated preservation of lean body mass, which we know is really significant in this obesity space. There's also potential benefits around nutrient absorption and a much more tolerable AE profile. So to your point, Andreas, we reported out data from our phase one study. And in that study, we were able to demonstrate a PK of greater than 150% PG-102 delivered via the RONI pill compared to the sub-Q. Notably, this was at the exact same dose, which we know is very unique with oral delivery in obesity. And there were no AEs related to the Roni pill. So Rani and Progen were obviously very pleased at these results because what we've seen at these other attempts at oral delivery of biotherapeutics is they tend to deliver less than 1% bioavailability. So what we're seeing here is a really efficient route of delivery via the Rani pill. And notably, we didn't see the impact to AEs. We did not see the AE differentiation between the two arms. They were very consistent with what we've seen in this class, mild to moderate and transient GIs. And we saw no variability between the two arms or from patient to patient. So we're really excited to continue to advance this first program that we have in obesity with the Ronnie pill. All right, Kate, do you want to go ahead? I was just going to say real quick, that was an FC fusion protein, 70 kilodaltons. So it wasn't even a small peptide that we showed that with. Awesome. And maybe a follow-up for you, Kate, the expansion cohort adds 15 volunteers. So what are you specifically trying to learn before Phase 1B? So great question. So we did announce that we intend to expand our 1A to better characterize this oral to sub-Q PK relationship. So these 15 healthy volunteers will now take two doses, Each of the 12-mig PG-102 delivered via the Ronnie pill for a total of 24-migs. And depending on what we see with these PK results, we may be able to actually achieve higher serum concentrations at lower-than-expected dosing. So ultimately, the goal is to inform the dosing for the 1B. Okay, great. And we're going to segue. There's a question. What are you calling that? so we may do that yeah completely we agree okay all right I love it. Literally, it's the best drug. It's going to be the best product ever. FYI, everyone's going crazy. That's the title. Best drug ever. Okay. I love the enthusiasm from the audience. We don't get that, as opposed to the silence that we get, so we appreciate you. No, this is awesome. Let us continue, at least. You heard it here first. Okay. Your name? Kevin. Oh, okay. What were we going to give preference to now? We've got to give credit to you. all right um well i'll remember your face and i'll remember the moment um the phase the phase 1b repeat dose study in obesity is slated to start by the end of the year with data in 2027 in a market where Lilly's oral or a fog licupon, whatever, an oral semaglutide oral already offer a pill. What is the case for an orally delivered injectable class peptide, and what does PG-102's GLP-2 component add? So great question, and we've been particularly excited as we've seen these oral launches because it demonstrates what we know, what the thought leaders say, And that is that despite a challenging side effect profile, which we are seeing with these orals on the market, as well as the other orals in development, patients will still select an oral every time it's offered. And so our goal is obviously to move forward, generate weight loss data. But this is not necessarily a retractor tide. That's a different program. we think we'll have really competitive weight loss, but have a much more tolerable AE profile consistent with what Progen has demonstrated in their sub-Q, a drug that patients can actually stay on, but in a weekly pill. And we know the challenges with the small molecules are these really significant AE profiles. They're much more frequent dosing scheme than what we're proposing with RT-114. And of course, with the oral peptides in development, they're putting significant amount of API from dose to dose, 100 to 300 times the patients are ingesting daily, sometimes twice a day. So it brings in questions around cost of goods, supply chain. With RT-114, this is the only proposed oral in development that matches the sub-Q dosing at a weekly pill, competitive weight loss, and a very tolerable AE profile. So if I give just a couple of bullet points on this, we're talking about titration within a month. That's what Progen has been able to show, as opposed to four months. An AE profile where even at the top dose, you're getting half the rates of nausea and vomiting of any of the other incretins. And then now the cherry on top, which we don't have data for, and Progen doesn't yet, but they will in their phase two and beyond, a lean body mass preservation that looks twice as good as trisepatide. So this is, it's not ritatratide. You're not going to get 28% weight loss. But this is a drug that, you know, if half of patients are dropping off within the first 20 weeks, which is what the data shows, this is for those patients. Do you want to put a bar for the weight loss number? No, we're not gonna hold you back. Not yet. Not yet, okay. Maybe quickly, and I guess maybe for Nick, because we're not going to forget you, I guess, but who owns the what in the pro-gen collaboration? How is the economic split? Oh, that's a Kate question? Okay, sorry. So it is a 50-50 cost share. So it's a co-co deal. We jointly own IP, and the markets are split. Pro-gen owns generally Asia and U.S. are ronnie owns the major markets u.s europe uk australia canada 50 50 cost share and future revenue split okay great um i apologize nick maybe i have a question of a finance question for you right now um shugai licensed the ronny pill for a rare disease antibody development for hemophilia 10 million up front up to 18 million in tech transfer and 57 development milestones 100 million in sales milestones and single digital royalties with options on up to five more targets for a headline of one point i'm rounding up one billion what is the next milestone and what would trigger shugai to exercise more options any questions it's okay i'm not a my cog you just happen to be picking the kate question so we are really pleased so thank you for bringing this up because both Chugai and Ronnie are very pleased at how our partnership has begun this past year. And Chugui has been very validating for the Ronnie Pill platform, obviously generated a lot of interest from investors. We had a concurrent financing as part of that deal announcement. And they did a significant amount of diligence over a two-year period, digging into our manufacturing processes, all our quality controls, a lot of work testing two of their molecules in the Ronnie pill and then got so comfortable that the deal expanded to now these additional targets so while we can't guide to the exact timing of the additional targets because it is Chugai's option what I will tell you is a couple of those early milestones are tied to Ronnie advancing our platform and our manufacturing processes we're moving along very well and do anticipate to be able to report out on at least one in 2027 and then along with the program going very well Chugai has been quite vocal around their confidence in Ronnie in a very long-term partnership and do intend to option off those option on those future partnerships. Okay great a quick I'm going to do a quick follow on. In July, you added the PEG-Bio collaboration on obesity and metabolic molecules. Is the strategy to own obesity assets or to be the delivery partner for many? That's a great question. So Ronnie's strategy in obesity is to have numerous programs in our pipeline with diverse drugs. So the gentleman brought up ritatratide. There's nothing about our current obesity program that says we couldn't also have a retatratide program. Ronnie doesn't develop drugs. We don't design drugs. What we do is deliver drugs very efficiently across modalities. So this PEG Bio partnership is a perfect fit. They're based in China. They have an on-market GLP in China and numerous different molecules in development. They've a couple pentagonists that are really interesting, some triagonist, ameritide-like drug, siRNAs. So Ronnie will have the opportunity to test lots of different drugs, then generate the data to go out and find partners or potentially reinvest and further those programs ourselves. Okay. I'm going to have one for Talat and then one for you, Nick, I think. I whiffed twice on that. So skeptics raise three issues, whether bioavailability above subcutaneous will hold up in larger repeat dose studies the cost of goods for an ingestible device versus a peptide pen or a small molecule pill and that earlier ronnie programs never advanced past early clinical studies all right so in terms of whether we're at 150 160 or 100 bioavialability honestly who cares we're talking about delivering a monoclonal antibody with equivalent bioavailability or superior. I'd be happy with any of those. It'll just get modeled into the dosing. So I don't think that's a really big deal. Number two is cost of goods. We are, the input materials are plastic, sugar, and Alka-Seltzer. There's de minimis costs, right? And that was by design. We didn't put electronics. We Didn't put any of those things in there. So the cost of goods is really just a factor of amortizing the scale of our manufacturing over the number of pills you make. And so let's take our Stelara program that we've shown 84% relative bioavailability for. We've modeled that it's 12 pills per year to recreate the Stelora PK curve, 12 pills every year, three pills every quarter. So whether it's 10 bucks a pill, 15 bucks a bill, or five bucks a fill, who cares, right? Again, it falls into that category. And when you talk about obesity volumes, that's going to come down to low single digits per pill, and we're talking about weekly administration in most cases. So $100, $200 of COGS, it's not going to make a difference, right? Why did we discontinue our early programs? We do get this question a lot, and I'm going to be candid here. We put out great data to crickets from investors for a while, and it's because what we're doing, and you guys got to hear this, sounds like science fiction. And so people look at it and say, this is great. Why isn't anybody coming and licensing your platform? I'm not trying to say it in a negative sense, because we just did a $1.1 billion deal a year ago. But that took time. It took time, and it was two years of diligence from Chugai. The partnership expanded over that period of time. But after that, we raised the pipe with really great institutional investors, brought in a sovereign fund this year. Raising capital has not been as difficult, and I think that'll be able to support the programs that we Yeah, that's for sure. You've been pushing through for a long time. So kudos to get to where you guys are today. Truly. I think this is for you, Nick. Okay. It's on me. I'm like missing whiffing here. All right, so you ended June with $53 million in cash and securities after the $20 million registered direct led by Sovereign Wealth Fund, as you just alluded to. And you guided runway at least through $27 million. Last October, after the$60 million pipe and issue guide deal, the guide was into $28 million. What changed, and how do you fund phase one and beyond without repeated dilution, I guess? Yeah, so this is my question. So you're right. In October, when we did the deal in October of 25, we guided runway into into 28. We did update guidance in in March to getting into Q4 of 2027. So what changed there, just investment in the platform, and we'd also retired some debt after, you know, doing that $60 million raise. so now you know fast forward to where we do the 20 million dollar raise in May and our update our updated guidance now is through 2027 so what changed from there is one we extended the runway now we're getting into 2027 the other piece that changed is when I came on board I'm three months now on the CFO role looked at you know what we were including in our runway and decided to be a bit more conservative so in the prior guidance we had one of the milestones from chew guy that that kate had mentioned nothing changed there we're you know fully you know um confident in those milestones but me being a little more conservative decided to use cash on hand to guide our runway so if and when you know we do get a shoe guy milestone that'll be upside and hopefully extend our runway from there okay and maybe i'll just add one thing real quick to this our our actual clinical studies are incredibly efficient because these are drugs that are known so they're not really single ascending dose in most cases they're single dose right because we know what the target is 114 notwithstanding where we got significantly higher bioavailability and we're doing one more dose and even in that case uh half of the the cost is borne by our partner and for the chew guy programs they cover 100 of the costs so we can do a number of programs and as these options get exercised there'll be a stream of upfronts and milestones that'll help support the company fantastic so the next milestone that we can look for is some data from the phase 1b in 27. yes you're welcome to we got one more minute so go ahead and see you i'm done with my questions Thank you. We are going to be testing that this year. We'll have a little bit of data, I think. There is a possibility of that. I don't want to guide to it until we have the data. Oh, so if you're talking about ISRs, we get none. We've never seen one at all. So this is something that large pharma companies actually are pretty interested in talking to us with their MABs that have ISR. We're a public company. Ticker Rani, R-A-N-I. It's our fourth phase. The fourth phase one. We've shown 400% relative bioavailability. You get the same look I had when I covered this company years ago. Yep. Everybody turn them away. I'm a stupid Albert Einstein. Thank you, everybody. All right. Anyway, everybody, thank you. Thank you for the questions from the audience. Guys, appreciate it. We're going to start our next panel in a second. That was awesome.