Thank you for joining us. My name is Edward Nash, senior biotech analyst on the equity research biotech team at Canaccord Genuity. I have the pleasure of having with us today Rani Therapeutics. Joining us from the company is Kate McKinley, the Chief Business Officer, and Spike Sanford, the Chief Financial Officer of the company. Thank you both for joining us this afternoon. Thank you for having us. So I wanted to start off with the general 10,000-foot view question I ask all the companies, just to kind of give general background to the audience is, maybe you could talk a little bit about Rani, and just what the company's mission is, what your, what your program is, your lead program, what your technology... And then just, just 10,000-foot view, your, your therapeutic pipeline, and we can dig in a little bit more after that. Absolutely. Well, thank you so much, Ed. Great to be here. Rani Therapeutics is a clinical stage biotherapeutics company, and we have a very bold mission, and that is to end what continues to plague biologics: delivery via a painful injection. And we do that through our proprietary technology, the RaniPill, which is a pill that actually has the ability to deliver bioavailability of over 90 different drug candidates with the same bioavailability of the SubQ and IV injection. And we've been able to demonstrate that now 15 times in preclinical studies and 3 times in the clinic. We are drug agnostic and therapeutic agnostic, so we can house over 90 drug candidates within the RaniPill. And another core to our strategy is our very strong patent protection. So we have close to 500 filed and pending patent applications. Our lead program, you may have seen the recent announcement, is a partnership with ProGen. The program is called RT-114. It's a program in obesity, and through ProGen's proprietary technology, a molecule called PG-102. It's a GLP-1/GLP-2 dual agonist housed within the RaniPill. So, we are really excited, because this is the first of what we envision multiple programs in obesity with the RaniPill. You may have touched on this, but you also have a high capacity ability as well. It's just, you're not just relegated... As you said, you're agnostic to therapeutic area, but also to size as well. Absolutely. So great question. We have now shifted to what we call the RaniPill HC, RaniPill High Capacity, and in every pill, we now have the ability to hold 200 microliters of aqueous solution, liquid solution. And so not only does it expand our capacity in terms of 90, over 90 drug candidates and countless others that are in development, what's exciting as we look at RT-114 is the ability to deliver a dosing scheme, potentially on a weekly or even less frequent basis, which, as you're aware, in obesity, is a huge competitive advantage, 'cause there are several orals in development, however, all are a daily pill. I wanna talk a little bit, so you just recently, the company just kind of revamped its whole therapeutic pipeline recently, and that's where you debuted the GLP-1, GLP-2 agonist. And I just wanted to talk a little bit about where we've known GLP-1 and GIP, GLP-1, and glucagon, or the triple, but GLP-2 is probably new to most people. Could you talk a little bit about GLP-2 and what that brings to the equation, if you will, with in obesity? Absolutely, and that's a great question. There's several different molecules in development with GLP-1 and GLP-2 that we can speak a little bit about. But the strategic rationale behind this partnership is the potential to bring what we believe is could be a best-in-class GLP-1, GLP-2 within the oral dosing of the RaniPill. So convenience, as we've talked about, flexible dosing schedule. What's interesting about ProGen. And maybe I can step back also and share a little bit about ProGen. They're a company that's based in Korea, been around actually for 20 years. Very strong innovators. They have a proprietary Fc fusion platform called NTIG, and they've utilized this platform to create PG-102, which is the GLP-1, GLP-2 dual agonist that is the molecule that will be part of this RT-114 program. They spent a lot of time looking at the ratio of GLP-1 to GLP-2. So when you look at the molecule, it's significantly biased towards GLP-1. The GLP-1 is 80-fold higher than the GLP-2. So of all the molecules they tested, they found with PG-102, significant more weight loss, better tolerability, and also overall impact to body composition with the PG-102. And so what will be the first clinical steps will be taken on this? And you have all U.S. rights to this program? Correct. Yeah. So to clarify, it's a, it's a 50/50- Mm-hmm ... co-development, co-commercial partnership, and so we'll split costs equally. RANI has the rights to all the major markets, so U.S., all of North America, Europe, and Australia. ProGen has rest of world, and then both companies actually have the right to sublicense without getting approval from the other party. So we intend to move very quickly with the clinical development. We've already begun the tech transfer and the preclinical work. We intend to move into the clinic in early 2025, and then have efficacy data as quickly as possible, likely early 2026. Our phase I proposal is looking at doing a single ascending dose study, where we would test at least two, potentially more doses, bring a couple of those into the multiple ascending dose, and in the multiple ascending dose, the Part 1C, we'll actually test this dosing scheme. We definitely believe weekly is a strong potential for this program, but we also wanna test looking at even less frequent. You know, does it become a couple times a month, even potentially a monthly dose? Okay, I was gonna ask that because I believe you said weekly or monthly, Red. Yeah. Just was curious as to what the probability of a monthly dose really happening is? Yeah. Is that really a real possibility? Well, we have, and that's a really great question. We have the benefit at RANI to watch ProGen's development. So PG-102 continues to be in development in the subcu in Korea, but ProGen is carrying that forward. So we're gonna watch their data, we're doing that right now, to design the phase one, and see how their data progresses to really make that decision. Because we have the capacity to hold any of those versions, we'll definitely move forward with the weekly, and we'll see how their data progresses with the subQ to test potentially less frequent dosing. Will ProGen's development in Korea always tend to lead so that you're always able to learn from what they're doing? Or at some point, will you be starting a trial here that they probably potentially have not started as of yet? As of right now, it'll potentially lead. Okay. I think ProGen is clear this is becoming their lead program as well. So if, you know, eventually they end up phasing out the SubQ development, we'll see. But as of right now, they're continuing to progress and, and are ahead. Okay, and this program falls within the high capacity? Yes, correct. Rani high capacity. Yeah. The RaniPill HC. Great. Great. And then how do you picture RT-114 fitting in with the rest of the competitive landscape? So we already have the GLP-1 and then obviously the glucagon but also GIP. So how is this— Is this gonna be competitive as in this could be a first line, or is this something that would potentially be something that if a patient is intolerant to some of the other drugs, that they would then start to use the RT-114? How is it gonna fit? We spend a lot of time looking at the competitive landscape of obesity, and you're right, there's a lot of products in development. When ProGen first approached Rani, we immediately saw the strategic fit. So the majority of the products that are in development or even on market, obviously, are injectables. There are some orals in development, but when we look at the oral landscape, we see several issues. The first is they're all single agonists, so there's no orals in development that are multi-agonist. And of course, with RT-114, this is a dual agonist. The next challenge is, particularly with the small molecule, there's a lot of tolerability issues. So Pfizer's program with danoglipron is a good one to look at. In their phase 2, they reported over 50% discontinuation rates, so they're actually terminating that version of the molecule and going back to study that. We already have the benefit of seeing ProGen's phase 1 data. We saw that in diligence, and they actually launched it at the ADA, and essentially have no, none, zero AEs until you get to the highest dose, and even that was less than half the patients that experienced diarrhea and nausea. So it appears, and this GLP-2 appears to be leading to some of those tolerability benefits of the PG-102. Another challenge we're seeing, and this is more with the peptides in the orals, is significant API is being utilized. So 100-300 times the amount of API in the oral matched up to the injectable. With the RaniPill, and again, we've demonstrated it now 15 times in preclinical, 3 times in the clinic, we take the exact same dose or maybe a slightly modified dosing scheme, right from the injectable. So we will not be utilizing additional API. And then the final piece, which we've talked about, is the dosing frequency of a daily versus now a potential weekly or less. So I know one of the issues associated with the GLP-1 class is the effect on lean body mass and losing that. Do we have any evidence whatsoever, even in the animal studies, that the GLP-2 addition, in any way, has a benefit in reducing the lean body mass loss? This was our dream, and we didn't think we'd get it with the first program. However, there appears to be a significant benefit on total body composition. It's kind of a hallmark of this PG-102. So in the DIO mouse model, which you know is highly translatable into humans, PG-102 outperformed Zecan, the molecule we spoke about, in terms of total weight loss. So their GLP-1, GLP-2, ProGen beat in terms of weight loss. With tirzepatide, it actually matched the weight loss in the DIO mouse model. However, when you look at the ratio of fat loss to lean muscle mass preservation, ProGen's at the highest dose, had a 6.4%, 6.4-fold ratio, compared to 2.9 in the tirzepatide. And what's interesting is we've watched tirzepatide's development in their SURMOUNT-Phase 3 trial, they actually also had a 2.9 fat loss to muscle preservation. So speaking again to the high translatability of the DIO mouse model. So this appears to be this product that can get the quality weight loss, and continue to preserve that lean muscle mass. So you're running 114 as your own proprietary program, partnered with ProGen in the other territories. Do you have... Do you still- are you still open to partners coming in and accessing the technology for their own GLP-1 or GLP-1 plus programs? ... That's a great question, because we don't envision only one program in obesity, and in fact, we worked really hard to carve out the rights with ProGen to be able to pursue any other molecule in obesity. We just can't, nor would we want, to do another GLP-1, GLP-2 program. So that's the first thing. The second is certainly RT-114 was a real catalyst, you know, to other companies coming our way. We're in a number of confidential discussions with some of the preeminent obesity companies, as well as several smaller emerging companies. But going back to those 15 preclinical studies, 2 were actually in obesity. So we've already tested a single agonist in exenatide, where we were able to deliver similar bioavailability in the RaniPill compared to the SubQ program. And then we also released data with a triagonist, which is really exciting. And this is a confidential research agreement with one of the major pharma obesity companies, and we actually generated PD efficacy data, and we were able to match the weight loss and the lipid reduction with the subQ compared to the RaniPill delivery, and it was at the exact same dose. So I think really all three of those are starting to put Rani into the discussion around obesity and generating a lot of interest from companies. Speaking of triagonist, is there anything that can be added to the GLP-1, GLP-2 that could potentially see even additive effects, or is that something you would look at in the future? I think that's something we would wanna look at in the future, because obviously, the goal here, as we said, you know, getting into the clinic, will be speed, and we're really watching the other companies and how they're progressing their development. We're seeing companies, you know, arguing to FDA to be able to move a little bit quicker. So we'll get it to market as quickly as possible. But then beyond that, absolutely looking at what else could there be, with this potentially best-in-class molecule. So to that point of being expeditious, what is the next steps now? With now that you've—we've got this, you've announced this program, what are the next steps you're taking? Yeah. So, you know, we're standing up the agreement, doing the tech transfer, all of the preclinical work to ready for the clinic, getting into Phase 1 quickly. Yeah. And then concurrently, putting together our package for the pre-IND meeting and standing up the IND. We'll move into... So we'll do our phase 1 in Australia, and then move into the US with our phase 2. Great. And then maybe switching gears to some of your other programs, with the higher dose study for ustekinumab in psoriasis, will that be conducted as a Phase 2? Hey, let me take that question, give Kate a little break from speaking. As you know, we successfully finished the first Phase 1 for RT-111, ustekinumab. This is a biosimilar Stelara. That was done using the RaniPill GO. GO stands for Generation 1. That was a solid tablet injection using the RaniPill. While that was very successful, you know, well-tolerated by the subject in study, the PK or drug absorption was 84% compared to SubQ. So it's relatively the same as a SubQ injection in terms of getting the drug on board. However, in order to deliver at this higher dose, we have to repeat the Phase 1 study, and we'll plan to do so using the RaniPill HC, the high capacity. Okay. And then I know, I mean, there's a reason why we've been in the phase 1 for so long, and I keep saying this, phase 1s are important for- Yeah for especially for drug delivery, when you're using drugs already approved. But so we run the phase 1 with a higher dose, we would then expect to run it, go right into a phase 2, correct? So, it's very likely we'll move into the phase 2 using the HC. Okay. We wouldn't, we wouldn't be using the GO, especially for this program. Okay. Because the target dosing program is 7-12 milligrams per capsule. Mm-hmm. What that does is that we expect that to get a really good therapeutic window in terms of getting the drug. You know, the reason why the current treatment is 1 injection per month is 'cause, you know, injection is painful and is inconvenient. So if you can take a pill that. We expect that in the dosing loading phases, the patient will have to take 30 days of the 7-12 milligrams per capsule, and then after the first month, you only have to take 3 pills a month. So imagine the convenience and the ease of, for patient and for the doctors of, you know, having to take the, you know, less pills. Also from a cost perspective for us, it doesn't have to be a daily pill, so it lessens the burden of having to make the many RaniPill to make the drug work. Yep, yep. Now, I know we've, you know, we've done this many times before, and then this is something that you have to do because this is what your business is, is drug delivery. So I've did this before, where I talk about the therapeutic programs because that's the most important part, but then it couldn't happen if it weren't for actually the technology itself. So it's important, maybe if we could just spend a couple of minutes just talking about the technology and what exactly it is, and some of the, I guess, typical misnomers that people have about it, that is, that has already been overcome or proved by the company. Yep. If you could. Do you want me to take that? Yeah, please. So, as I said, the RaniPill aims to deliver at comparable bioavailability to the subQ or the injection. So how do we do that? It's the RaniPill is a triple zero capsule, about the size of a fish oil or calcium pill. It has a proprietary enteric coating around the pill, and that serves several purposes. The first is it makes it very easy to swallow. In fact, we've done a swallowability study with the actual RaniPill, 150 patients, aged 25 to 75. 100% could swallow the pill, and over 90% called it easy to swallow. So the patient swallows the pill. The enteric coating allows it to get through the acidic environment of the stomach, which, as you know, has been a challenge for many years as they've tried to turn biologics into oral therapy. Once it reaches the small intestine, the pH levels in the small intestine break down the enteric coating, and they're causing reactants inside the RaniPill to mix. The reactants actually inflate a balloon, so there's a very small balloon housed within the RaniPill. The balloon is longer than it is wide, so it perfectly orients itself into the small intestine. There is a micro syringe that pops out and is perfectly perpendicular to inject a microneedle, which is about the size of the tip of your pen. It is so tiny to inject the liquid drug directly into the intestine. The microneedle dissolves, and the balloon deflates, and the balloon, and the very small micro syringe pass out safely in the patient's next bowel movement. So all of this took me much longer to explain than when it actually happens. We have lots of different videos depicting this process. It's a matter of several seconds. So I think that, you know, obviously, we get a lot of questions about this process. Everyone's fascinated by it, but, you know, how does it work? I think the piece that's important is we've tested now. Though we've done a lot this summer, we always say 7,000 in vivo and in vitro is getting ready for the clinic. We're probably way beyond that. We've obviously done the 15 preclinical. Within the clinic, we've actually delivered 233 RaniPill capsules to close to 150 patients. We've never had a blockage. We've never had any sort of, you know, safety risk. We've actually conducted a 60-day GLP repeat administration in our preclinical. We actually use a canine model. We've perfected, tried every animal, perfected the canine model in beagle dogs for multiple reasons, and 60-day repeat administration came back clean. All the histopathology, no impact to food effect. Even the dogs that were terminated at the end of the trial, several hours later in investigating, were not able to locate where the injection had taken place in the intestine. We've done a 60-day repeat dose study in humans, again, no serious adverse events, no serious adverse events in any of our clinical trials, no impact to food intake. So, lots of good, you know, safety data that we're generating. We'll obviously continue to do more, but probably the biggest questions are, does it actually work? And, you know, is it safe? Yeah. And thus far, we've demonstrated that. No, you don't feel the injection when it injects. Yeah. You don't. But for those who may not be familiar with this. Yeah ... the GI tract has no sharp pain receptor. Yeah. When you do get the injection, you don't feel a thing, you know, similar to any injection you would have on the outer body. Right. So, pretty, pretty fascinating. And then what about manufacturing of this? Is this something that you have already feel or have already started working on the ability to scale up since you're now moving into multiple programs and something like a metabolic indication like GLP-1, 2 itself is very- So yeah. Yeah. I can take that. So we are fully integrated, vertically integrated operations. We have the... You know, from the time we get the drug from a partner, we can load it into the RaniPill. We manufacture everything in-house. There's a few components that we do buy from external party, but the making of the RaniPill, the material itself, it's very low cost. So we expect the cost of the RaniPill will be consistent with the cost of a SubQ in terms of the COGS itself. But in terms of scaling up, you know, at the moment, it's semi-automated. We have some machines that do certain steps, but we also have a lot of assemblers making the RaniPill. So our headcount is a little bit higher, but they are a lower cost, you know, headcount. We have, we have capacity now to support multiple trials in phase 1, phase 2, and can easily scale up to support multiple phase 3. We'll move towards full automation next year. Obviously, depending on the program, would then be ready with that full automation to do tech transfer to a third-party manufacturer. Got it. And then maybe the last thing we could end with is that, you know, it sounds like the one fourteen really is the lead program now that you're really focused on. What is the next thing we're gonna hear from you on with regards to that program? Yeah. So, the initiation of the phase 1. Phase 1. And there will be data released from ProGen also. So obviously, paying attention to that, and we'll have coordinated efforts to communicate the PG-102 SubQ progress. But the initiation of phase 1 will be a real, real catalyst to look forward to in 2025. Fantastic. Well, we're really excited with the story, we have been, and I think especially now, with even more so with the GLP-1, GLP-2, this is clearly the time to be in obesity. But nice to see you're bringing something completely new with regards to the combination of the actual agents, but then also the device.