Hi, good afternoon, everyone. My name is Edward Nash, Senior Biotech Analyst here at Canaccord Jaduity. I have the pleasure of having Ronnie Therapeutics with us this afternoon. From Ronnie is Talat Imran, who is the company's CEO, and Nick Mestas, who is the company's Chief Financial Officer. Just joined the company, so great. That's our first live face-to-face interaction with him. So glad to have him here today. So maybe we could start off just a 10,000 foot view of just giving us a review of Ronnie, what Ronnie, what the business is and what the focus is, and then we can dive in from there.

Sure. First off, Ed, thank you to you and to Canaccord for allowing us the opportunity here to have this conversation. And as you said, this is Nick's not only first interaction with you, but his first conference altogether, so make sure to ask him some tough questions. So Ronnie Therapeutics is a clinical stage biotech, and we've developed a platform technology for the oral delivery of virtually any biologic with bioavailability that's comparable to a subcutaneous injection. This has been called the holy grail of drug delivery. There have been dozens and dozens of attempts that preceded us. We call those mostly chemistry-based approaches, where you add an excipient to typically small peptides to enhance absorption. The bioavailability of those tends to be sub-1%, and you get commensurally high variability. We're getting equivalent bioavailability in most cases and equivalent variability to a sub-Q injection with monoclonal antibodies, with 300 kilodalton proteins. It doesn't matter what you put into the Rani pill. And so this opens up the world of biologics more broadly to be turned into pills. With our current Rani pill, that's what we call our technology, which is essentially a swallowable auto-injector. It looks like a pill. It goes into the small intestines and then capsule shell dissolves and there's a reaction that expands a balloon and pokes a needle through the gut wall pain-free. The needle dissolves and the remnants are excreted out. Because of that, we can deliver, as I said, 80 to 85% of all on-market biologics in a pill, and we can do it with dosing schedules that you cannot really recreate with most other technologies. So like Stellara, as an example, if we were to, we've brought that into the clinic and shown great bioavailability, if we turn that into a pill regimen on an annualized basis, you would take 12 pills to recreate the same doses still are.

That's great. I appreciate that overview. So, you know, I think one of the important parts of the story is not only what you can do with having your own proprietary pipeline, but also the partnerships that you're able to generate with this technology. And you guys announced in the last year a $1 billion agreement with Shkai. And just maybe you could talk a little bit about that agreement and what Ronnie gets out of that and what the company gets out, what the pharma company gets out of that.

I think right off the bat, it's validation. Chugai is part of Roche. They're an incredible innovator. If you don't know, I mean, they developed Hemlibra, which our lead program with them is in rare disease. And they're the market leader in hemophilia. And Orphoglipron, Lilly's small molecule GLP-1 agonist, is theirs. And even Galderma's IL-31 came from them. There's Actemra. They've had a long string of innovation, particularly in antibody engineering. And so they're looking at making more potent antibodies, making them less frequent in terms of the injection regimen. And it's almost a perfect fit for what we're doing. So they spent two years of doing diligence on RANI. We tested a couple of their molecules. And from there, it turned into a license agreement around the rare disease candidate. And then after coming on site and doing additional diligence, they expanded the deal. So again, looking at validation, they've included 11 targets, of which we have pre-negotiated economic terms for five additional programs, primarily in high-value immunology categories.

So is the goal to kind of continue to do these types of deals? I mean, we'll talk about a little bit about you have another collaboration where you're having your own proprietary with this partner program in obesity. But is the goal to do more of these types of relationships where you're able to use your technology to leverage the protein drugs from other companies?

Yeah, I think if you take a step back, as I said, we can deliver 80 to 85 percent of on-market biologics in some dosing regimen with the Rani pill. We cannot, as a company, a small biotech, go after all of those opportunities. So we need partners. There's the validation. There's the cash that helps with our own runway. So we will absolutely do more of these deals, I believe, in the months and years to come. Having said that, we also think there's value in not just doing technology licenses, but doing product licenses. So on a very selective basis, we will bring assets in. And we've done that, and I think we're going to talk about that a little bit here today. But we'll continue to do that very selectively. Ultimately, we're not going to be running late-stage studies or building out commercial operations. We're in platform technology that delivers biologics orally, and that's what we will continue to invest in. But you get a lot more economics out of product licenses than you do out of technology licenses. So I think we'll have a mix of these over time.

Got it. And so, I guess then that leads us to RT114, which you guys have a collaboration with Progen for this drug, which is GLP1, GLP2. You just recently announced phase 1A data on bioavailability, which was really impressive. So maybe you could share a little bit about that bioavailability data and what the next steps now are.

So if we kind of take a step back to frame in this space, if you look at the orally available peptides, the dose typically is 75X to 100X to 150X, the sub-Q dose, right, the equivalent oral dose. That's an incredible amount of API that's required per patient. There's a cost of goods issue in there as the competition grows and the price of these incretins comes down. They'll be less and less competitive. So that's the backdrop, this sub-1% bioavailability. The data that we put out just a few weeks ago, we showed greater than 150% relative bioavailability to the sub-Q. And this is with an FC fusion protein, almost 70 kilodalton molecule, not a small peptide. So it's really, for us, it's par for the course. We did this with Stelara, which is 150 kilodalton. We've done this 20 times preclinically with peptides, proteins, antibodies, bispecifics. But this is the first time we brought an FC and the first time we brought an incretin into the clinic. So being able to replicate what we've done before and show that with an obesity drug speaks to how broad we can go in this space. We don't have to go after just monoagonists. This is a GLP-1, GLP-2, as you mentioned. And I think we'll talk about this as a portfolio approach that we're taking. And there's additional targets that we could go after in the future that this helps read on to. A little bit more color on the data. We showed greater than 150% bioavailability. Variability was very similar. And the AEs were commensurate with the exposure level that we showed relative to what our partner has demonstrated in their prior sub-Q studies. So no new AEs emerged. And then critically, there were no AEs attributed to the Rani pill in this study. So it continues a trend of very, very clean data on the Rani pill itself and excellent bioavailability, which with this program speaks to potentially weekly dosing with this drug.

Yeah. So you recently also announced a collaboration with PegBio where you would actually use your technology with some of their obesity molecules. Can you talk a little bit about the motivation behind that deal?

Yeah. So we just put out great data with our RT114 program. We're very proud of it, and we're very invested in that program. So nothing to read into that. When we did the ProGen RT114, PG102, however you want to describe it, deal, we said we want to build a portfolio. That we think this is a more than $100 billion market, that there's no one drug that's going to cover all of that. There's going to be elderly women where you really care about lean body mass preservation, muscle loss, bone loss. There's going to be patients who are candidates for gastric bypass or Roux-en-Y where you need close to 30% weight loss. There's patients that have concomitant illnesses, MASH, hyperlipidemia, and there's a number of really interesting drugs that are being developed. We can make any and all of those oral. Now, we have this incredible, I believe, sorry, platform technology that can deliver any drug orally, but we don't discover our own drugs. So it's important for us, you know, with Chugai, they're going to be supplying drugs and running the programs. But we also, within the incretin space, wanted to find a partner that is deeply committed and is developing a panoply, if you will, of incretins that cover these different patient populations. So PEGbio is a really great partner from that perspective. They have an approved GLP-1 in China. That's not what we're looking at, but we're looking at the next generation that they're developing. These are multi-agonists. They go after some of the patient populations I just described. They have siRNAs that they're working on. They have ultra-long actings that could be dose once a month or less frequent than that And those are interesting because I won't point out any companies in particular, but some of these long actings don't show as good efficacy as if they were given weekly. You can go back and look at the data on one in particular, and it's pretty clear. We can give a weekly pill of a once-a-month injection, maintain much better serum concentration, and keep it convenient for the patient. So these are the types of things that we'll be exploring with them. The way the partnership is structured, we have access to their whole library of drugs. We can test whatever we want, and then we can potentially do a deal around those at that point in time. We're not restricted to working with them either, so if there's other opportunities, we can pursue those. And then China, I think, is now responsible for north of 30% of all BD transactions globally. They are getting regularly approached by pharma partners, and this gives them their BD apparatus the opportunity to market making oral versions of their drugs. and we can, with the large pharma companies that we're talking to, not just talk about technology, but speak to product profiles that we can create now with real drugs, not just in the theoretical.

Got it. So you alluded to it a bit already, but I just wanted to see if you could maybe just get a little more detail. We all are very familiar with GLP-1s, and then you have the additional incretins with GIP or glucagon that you can add into that mix, or all three. Can you talk, you're one of, I think, of only two companies I know that are working on a combination of GLP-1 and GLP-2. What does GLP-2 bring to the table that's different than just the GLP-1?

So, yeah, great question, and I should have answered it before. GLP-2 is not a weight loss drug, but it is important in Cretin. It helps with lean body mass preservation because it improves absorption through the gut and micronutrient absorption in particular. it's used for short bowel syndrome. It can also heal the gut and lower inflammation, local inflammation, which is an important thing in obese patients. The combination of that and the fact that this particular drug is an FC fusion protein with a much longer time to Tmax and half-life means that in ProGen's PG-102 sub-Q study, they showed virtually no vomiting and little nausea because it took about four times longer to get to T-max than semaglutide or terzepatide. When they moved to their titration in their MAD study in obese patients, there was no vomiting at all. So one of our primary theses in getting into this space was you can't just make incretins that are convenient. They also have to be tolerable. And that has been the tradeoff if you look at the small molecules that are under development. they tend to have to dose lower, titrate longer, and get lower overall efficacy because of it. And they're typically limited to single agonists, some exceptions. And then we talked about the peptide volume issues for the oral peptides. So I think between the combination of the FC fusion and then the GLP-2, this isn't going to be a 25% weight loss drug. That's not what we're shooting for. But we want to make the most tolerable and convenient oral and cretin on the market. That's the goal and why we did this partnership. And I guess the very last thing, the cherry on top, and we'll see this in later studies, is the combination of GLP-1 and GLP-2, this is in the literature, has a pretty profound glycemic control effect at the same dose as some of these other drugs. So that could be another patient population looking at diabetic obese that we could go after.

Nice. So I think that anytime you hear of a company, especially a smaller biotech, trying to get in the obesity space, which is so fiercely competitive, it's just like, really, why would you want to do that? But you're very unique because of your platform technology. So correct me if I'm wrong, but do you agree that the competitive landscape in the obesity space is actually a big plus for Ronnie? And then also just wanted to get your comments on the orals that are out there now, or the oral that's out there now. Your thoughts on that.

Sure. So one of our advisors said to me that oral therapeutics in general are having a moment right now. And I do believe that's because of the incretins. Oral semiglutide, I think, is the fastest commercial launch ever. And it has all these limitations on it in terms of food effect. you have to fast before and after. You have to give 75. They didn't take the highest dose out of their study. They took one lower, but it's still 75 times the drug that you would need for the sub-Q. So even with all of those issues, there's clearly a pull towards it. And I would say that this goes beyond just obesity. If any of you have followed like the Avere deal with HANSO that just, you know, taped out in the last few weeks, a once a week oral for IL-23 for psoriasis best-in-class convenience I think is how they're putting it and we intrinsically because we're taking long-acting drugs we can do weekly monthly quarterly that's that is what we're going to be doing so I think it has been a real tailwind for us in that regard and the fact that we're not limited to just one drug this is not a reformulation play we take the drug exactly as it is and do a fill-and-finish operation into our pill we can move rapidly with any other incretin or frankly with any other drug that we want to put into the Rani pill. So some of the questions I remember from a couple of years ago, and you may remember this as well, when we got the PG-102 asset was, does the world really need oral incretins? This was the pushback. It was, everyone's taking these injectables. Look how they're growing. People would poke themselves in the eye if they could lose weight. That's what one doctor said to me. And I said, well, okay, maybe that's true, but they won't do it if they have another option. And I think that is proving to be true. And we take this to its logical conclusion. It's not just, hey, we can deliver this GLP-1 with a small molecule agonist that has half the half-life of even semaglutide. We don't have to have trade-offs, potentially, in delivering these incretins or immunology drugs in a pill. And I guess the last thing I would say is, while we are deeply focused on obesity, we are also very excited about immunology.

Yep, understood. So one of the companies I used to cover, AJ and myself, way back in the day was Protein Design Labs, where they had their humanization patents on the humanization technology for people who were developing monoclonal antibodies back when chimericans were starting to get a little bit questionable in researching those. But they had the strategy of they had some of their own proprietary products, never really worked for them, but they had all these licenses coming in, right, where it was a huge amount of royalty revenue for them. Is that what we should expect to see a Ronnie be, say, another, you know, three, five, ten years from now, is building more and more of these relationships and kind of being the go-to company for the delivery of larger molecules?

I think so and hope so. I think that if you want to deliver a monoclonal antibody or a bispecific in a pill, it's us or I don't know what else. And as this becomes more of a reality, because there are oral peptides that are being developed, small molecule mimetics, you don't have to have the safety tolerability risks that sometimes come with those drugs, or the efficacy loss that is very often an attribute of not having the specificity of the biologic. So we can do this without those trade-offs. And I think as the whole world moves, because a lot of these categories we think about, whether it's in cretins or in immunology, psoriasis, atopic derm, there's some great therapies, right? The question now isn't so much about differentiation around therapy. It's around convenience and patient experience. You look at all the Fairmount companies, Ruka, Spire, Apogee, Apogee just sold. that was about, hey, you're injecting once every two months or once every three months, go out to once every six months or once every 12 months. We could do the same thing, but put them in pills. We think that's fundamentally valuable.

So I ask that question because it leads me now to say, what is it going to take for, or what's going to have to be the key to turn to where you start to see all these companies lining up and wanting to do a deal with Ronnie? Why hasn't that happened today, do you think?

Well, we did a billion dollar deal.

True, that's true. What have you done for me lately?

We're not even at a year, but we're having a number of conversations going on. These are the things we can't obviously speak to the market about until they're done. But there's no shortage of interest. And this goes across rare disease, immunology, obesity, and even oncology now.

Got it. So maybe we could switch a little bit over now over to the financial side of things and just trying to better understand, you know, you kind of do these two-guy deals, you know, and you start to do more of those. That really helps, right? You get non-dilutive money coming in to help you kind of continue to keep growing the engine. But the funding you have now, what can that get us? Because all eyes are kind of on 114 at this point. And so, you know, where does what you have now, what kind of major inflection point will that get us to?

So I'll take the first part of that, and then Nick, maybe you can take the second. And in terms of catalyst events that are coming up, after getting this greater than 150% bioavailability data out of our RT114 phase 1A, we decided to expand the 1A and add an additional cohort to confirm that that is the relationship between oral and sub-q. So we'll get that back into the clinic quickly and have data before the end of the year. We're going to start the 1B thereafter. And I think at some point in the first half of 27, we should expect to see data out of that. And that's an eight-week study. And we're in obese patients there looking at weight loss and safety and tolerability. So this is PD data. We've done that five times pre-clinically. This will be the first time we look to translate that into humans. So I think those are two really important value inflection points for the company. Then there's all the things around our ChewGuy partnership that we can't speak to. they'll have to do that. And then any other deals that we do in the intervening time potentially.

Got it.

And then in terms of runway, I'll leave that to Nick.

Yeah. So we reported, our last reported was Q1, Q2 upcoming, but 43 million in cash and marketable securities. At the time, that was runway into Q4 of 2027, which is enough to get us past these catalysts with Buffer on the other side. Got it.

So you've talked now about wanting to kind of branch over into the immunology space. Can you talk a little bit, is that something where you would do kind of a deal similar to what you do with Progen or is that more of a, yeah, I mean, I'll put words in your mouth. I'll let you know where you think that's going.

I think it's not either or. I think there are some really great assets that we could potentially bring in and generate that early proof of principle, proof of concept data, and then have a potential to license them out. Having said that, just in the true guy deal alone with the five predefined options that they have, a number of those are in really high-value immunology categories. So even if we don't do anything, we'll probably end up in that space.

Okay. And then with 114, you just reported the 1A. So has anything changed in your minds from what you've seen there on dosing frequency or anything that could change going into a phase two?

Yeah. I mean, this is part of why we wanted to do a second dose. It's the dosing frequency may not change, but the dose that we select will. Because we gave 12 milligrams in this study versus the sub-Q. 12 milligrams is a sub-therapeutic dose sub-Q. It looked like it was threshold therapeutic given how much higher the bioavailability was in the Rani pill and the absorption kinetics. And we didn't see new AEs emerge because of that, which was a great sign. but we need to test one more before we decide on the because we have to prefabricate the doses this is not a syringe right right so we need to know what those are model it out and then we'll make the pills and run our 1b study but it's going to be less drug i can tell you that with certainty given given the the bioavailability got it which is you know just taking it aside that's kind of a staggering thing if you think about it compared to every other oral biotherapeutic technology, where you're going 10x, 50x, 100x, 150x, it's not an exaggeration and we're going to have to lower the dose.

So from an immunology standpoint, now we've got obesity, are we going to start to see immunology play a much bigger role in the overall scheme of things for the company?

Yes, absolutely. We have two immunology programs, we have supply agreements with Celtrion for an adalimumab biosimilar Humira and a Stelara biosimilar. And we've brought the Stelara biosimilar into the clinic already. So we have generated data. This is not just aspirational. We are mindful. This is not 2020 or 2021 anymore. So we are being mindful with our spend and how we sequence things. But we think with not a lot of time on a study like that, it would take 12 weeks and you would get MAD efficacy data in psoriasis patients with Stelara as an example. And sorry, I was just going to say with Humira, you're talking about a once-a-week pill for Humira, and that would be really interesting. And the data in that space is if you go from biweekly to weekly, the efficacy and the onset of efficacy goes up. So there's some other interesting things here that we talk about sometimes, but just by changing the dose schedule, you can optimize the drug for the patient and for the outcomes as opposed to make it as infrequent as possible. And there's a lot of data on that. The Uruka data, they just jacked up the dose and they're getting much better PASI scores that from a potency perspective, it's very similar to SkyRizzy. So I think there are things we can do like that where there's no additional burden to the patient because it's a pill.

Yeah, yeah. So with the rating seconds we have left, I just wanted to, importantly, we keep talking about this pallet form technology, but can you just talk a little bit about the, are there any manufacturing capacity strong limits that you have with the device?

Well, I mean, we are scaling our manufacturing to meet the demands. We're rolling out over the next year a 1,500 pill per day line that would support commercial scale for rare disease. We are in the process of building a 10,000 pill per day line, which would support commercial for virtually any immunology category. And then we need to scale it up to 50K, which will come later, and that'll support obesity. So this is a core part of our spend, and our focus is on scaling the manufacturing now.

Well, I think it's extremely, obviously, we like it. We cover you guys with the Y rating, but I think that the story is really one of the more interesting ones that I've ever seen in the drug delivery space. And I think given, you're right, things like Apogee that have happened, I think we see that that's still a huge, huge potential for the company. So we look forward to seeing more additional deals next year at this time, right? Thank you very much for joining us.