All right, hey, good morning, everyone. I think it's still morning. Just on the cusp. Good morning, everyone. Welcome to day two of our Cantor Global Healthcare Conference. My name is Olivia Brayer. I'm one of the senior biotech analysts here at Cantor, and we're really excited to have with us the Rani Therapeutics team. We've got Kate McKinley, who's Chief Business Officer, and then we have Svai Sanford, who's CFO. Guys, thanks so much for taking the time to join us today.
Thanks for having us.
Thank you.
A lot has changed since we had the team up here this time last year at the company. A lot of progress. Maybe just give us a sense for where the company's at today, the direction that you guys are heading, and maybe just areas of priority as we get into 2025.
Yeah, perfect. Well, great to see you again, Olivia. We're looking forward to the discussion. So Rani Therapeutics is a clinical stage biotherapeutics company, and our mission is to end the issue that continues to plague biologics, and that is delivery via painful injections. And we do that via our proprietary technology, the RaniPill, and we've been able to demonstrate bioavailability comparable to subQ and IV injections now in 15 preclinical studies and three studies in the clinic. So, our areas of focus, we have entered into obesity. Our lead program is RT-114, and this is the RaniPill delivering a dual agonist, GLP-1, GLP-2. And then our follow-on program is RT-111, which is the RaniPill delivering the biosimilar ustekinumab, Stelara, and this is the first time that a monoclonal antibody has ever been delivered orally.
Yeah, I mean, it's a really interesting and unique approach, right? So maybe just talk a little bit about the technology. You know, I mean, obviously, you guys are differentiated in your own ways, but talk to us a little bit about the technology, why you have high conviction in it, and, you know, maybe as a follow-up to that, how you decided on obesity, right, as sort of the forefront to take the company in that direction.
Yeah, perfect, so we do have a lot of conviction about our technology, and really are trailblazers in this robotic oral delivery space, so as I said, the data speaks for itself. Everything that we have studied works, 15 in preclinical, three in the clinic, and so the way that our technology works, the RaniPill actually has a proprietary enteric coating, so when the patient swallows the pill, it's very easy because of this coating, but it also allows the RaniPill to pass through the acidic environment of the stomach. As you're aware, previous attempts at delivering biologics orally have struggled to pass through the acidic environment of the stomach, so that gives us a lot of conviction because it's clearly differentiated.
Once the RaniPill reaches the small intestine, the pH levels cause the enteric coating to break down, causing reactants to mix, creating carbon dioxide to allow a balloon that's actually within the RaniPill to inflate. It's a very small balloon. It's longer than it is wide, so it orients perfectly into the small intestine. The pressure from the balloon causes a microsyringe containing liquid drug to inject the drug directly into the intestine. It's well established actually, that the small intestine has no sharp pain receptors, so the patient doesn't feel the drug delivery happening. Because it's so highly vascular, the drug is rapidly absorbed.
Mm-hmm.
And then the balloon deflates and is safely passed out. It happens in a matter of seconds. Takes a lot longer to explain our technology. And then specific to obesity, obviously, there’s over 90 drug candidates that we can have, so we really do have to focus our efforts. So we look for those high-value markets: immunology, endocrinology, obesity, that also really have limited to no oral delivery, where we know we can have a differentiation. Obesity, I think the debate is, is it a $100 billion or a $125 billion dollar market? Obviously, was a natural fit, and we’ve had a lot of companies approach us in obesity-
Mm-hmm
... and obviously seized upon what we believe is a potential best-in-class with our new program that we have.
Yeah, clearly, no, no lack of interest around obesity these days.
I would, yeah, I would also add that the RaniPill has been thoroughly tested. In preclinical testing, we've tested 7,000 pills. 4,000 of those were in live animal testing. So the model that we use is mainly in canine. So dog would swallow the pill without chewing it, without damaging it, and it has 4,000 of those in live animal testing. And in human testing, we've done three phase I studies, and 140 human subjects have taken the RaniPill in clinical studies. Over 230 capsules had been taken by the RaniPill, and from a safety and tolerability perspective-
Mm-hmm
... no, no issue has been reported.
Well, and how are you guys exactly comparing, right, the bioavailability of your drugs versus subQ or IV drugs? 'Cause that's obviously a big part of the discussion.
It's not even comparable. When you try to compare it to the traditional, what we call chemistry-based approach, they get, you know, anywhere from 0.5%-1% at the very best.
Mm-hmm.
That's dosing 50 to 100 times more API than you would normally take in a subQ. In a RaniPill, we get bioavailability that go from 80 to 140% of a subQ.
Yeah, and then the other thing I wanted to ask you is, you know, you had your, your sort of first generation, right, RaniP ill, and I know you guys have started to transition to the high-capacity pill. So maybe just talk to us about how did you decide to transition, right? Your level of conviction in the high capacity, just given that, you know, you, you sort of studied the, I don't wanna call it smaller capacity, but the, the initial pill, right? I mean, talk to us about the transition. Again, how do you get comfortable with having this higher capacity in patients? Does it change the user experience at all? You know, just help us get more comfortable, right, with that higher capacity program.
Yeah, that's a really great question. So the RaniPill HC high capacity now has the ability for us to carry over 90 drug candidates. Each RaniPill has a payload capacity of 200 microliters of aqueous liquid drug. And so not only has it expanded our ability to carry more drugs, it also enables a much more flexible dosing scheme. So previously, when we've talked about the RaniPill, we've always considered it as a daily pill.
Mm-hmm.
Now, we've shifted virtually all of our programs to the HC, and we're talking about weekly dosing, potentially monthly, or even just a handful of pills at the beginning of the month. And those, those therapeutic areas of focus, like obesity and immunology, really have nothing available for oral delivery, and what's in development is the daily, sometimes twice a day, dosing. So it's really a complete disruption of this historically injectable market. The, the beauty of the HC is that there is very limited changes to the RaniPill. It's the exact same size, and virtually all of the components are the same. The only difference is a microsyringe that carries liquid drug, as opposed to the previous version, which was solid dose.
In terms of our manufacturing processes, the automation scale that we've created, it also is almost virtually the same, except for the manufacturing of the microsyringe.
Okay, so size is exactly the same.
Size, exactly.
Does it react any differently once it's in the patient's stomach or small intestine?
It does not, except for that it's injecting liquid drug, whereas the previous version inserted a solid dose drug delivery.
From a safety consideration standpoint, I mean, any worries, right, of sort of that change in going from liquid or solid to liquid, for patients-
No difference-
Of adverse events.
... in terms of, right, the adverse events, the safety profile. In fact, it's a cost reduction as well as a time. Because with the micro dosing that we did previously, micro tablet, we actually had to go through several formulations that took additional time. Now, we can literally get the drug right from an IV bag or even a subcutaneous injection and load it right into the RaniPill.
Yeah, very interesting. And then maybe let's talk a little bit about the actual obesity program, right? A lot of interest in that program. I think it was the right decision to move into obesity. You know, you did partner with ProGen. Maybe talk to us about how that partnership came about, how you decided on them as partners, and then is the door still open to potential other partnerships, right? Because, like I said, there is a lot of interest in obesity. There is a lot of R&D spend in obesity. I don't think that's going away anytime soon.
We think it was the right decision as well, so thank you for that feedback. The team is really energized and excited. It's now our lead program. We had multiple companies approach Rani and continue to still have that happen in the obesity space, but when ProGen came to us, we immediately saw the fit with their PG-102 program. ProGen is a biotech company based in South Korea. They have a really innovative technology, an Fc fusion platform, that they've utilized to innovate PG-102. PG-102 is a GLP-1, GLP-2 dual agonist, and we'll put it in the RaniPill in a weekly, potentially monthly, dosing scheme. The strategic rationale is a potential best-in-class GLP-1, GLP-2 agonist with the convenience and flexible dosing scheme of the RaniPill.
What's interesting about this agonist platform that ProGen has is they've really spent a lot of time perfecting the combination of GLP-1, GLP-2, and the combination that they landed on with PG-102 actually has an eighty-fold higher bias towards GLP-1. And what we're seeing in the preclinical, as well as some of the early clinical data, is really strong weight management, great tolerability, and even body composition improvements over what's data that's already been presented.
Mm-hmm. In terms of that mechanism, I mean, GLP-1, GLP-2, I think is probably less familiar to a lot of folks that have been doing work on the obesity space. You know, why that mechanism? Why did you guys decide to go forward with that mechanism over, you know, others or maybe more tried and true, right? The GLP, for example.
... And the door is still open, and we're still in discussions-
Mm-hmm.
-with other combinations. So we see this as the first of what will ultimately be multiple programs in the obesity space for Rani. For this program being, the first program, we saw it as a great fit. The GLP-2 actually appears to really be what's leading towards, PG-102 ProGen's really early strong data. So they released, phase one data, the SAD portion of their phase one at ADA this year. Great tolerability data. Essentially, no AEs in the first three doses that they tested, and less than 30%, GI-related adverse events in their highest dose. So we're seeing significant tolerability, benefits with PG-102 in the clinic, and then when we look at their preclinical data in the DIO mouse model, they compared to, Zealand's, recently announced data in the, dapiglutide, as well as tirzepatide.
We are seeing better weight loss than Zealand's GLP-1, GLP-2 combination in the DIO mouse model, comparable weight loss to tirzepatide. What appears to be a really strong differentiation with PG-102 is the body composition benefits. The fat loss to muscle preservation ratio for tirzepatide is two point nine, and at the highest dose of PG-102, which is again very tolerable, is six point four ratio. What's interesting when we look at the translation of the DIO mouse model with tirzepatide in their phase three, they had the exact same fat to muscle ratio. We really have a lot of promise of what this could do for overall body composition, which is still the untapped potential in the obesity space.
I mean, I think it'll be really interesting once you guys start to produce some data there, right? So in terms of... Do you wanna-
I would just, I would just add that we didn't just jump into the obesity space because of how hot it is, and it is hot, but it's, it's-
You timed it right, though.
Time is right, but we've been looking at this for a few years. If you recall, we released a triagonist data last year. It's the drug came from a partner that we can't disclose, but we did a feasibility study and were able to show the same PK curve that we would expect, like anything else we've tested. And beyond that, we were testing a single agonist before that years ago. So this space has been, you know, evolving, but we started a long time ago.
Am I still on? Yeah. Well, in terms of next steps, right, moving into the clinic, phase one trial design, I mean, anything that you guys can tell us today, I know a lot of that isn't necessarily, you know, hasn't been publicly disclosed, but whatever tidbits that you can tell us that, you know, we should be mindful of.
We are moving rapidly with this program, being our lead program. We'll be in the clinic next year, and then aim to have efficacy data in humans in twenty twenty-six. We also have the benefit of watching ProGen's subQ program for PG-102, so they're a little bit ahead, and that will really inform our dosing strategy.
Mm-hmm.
But in the phase 1a portion, we intend to study two or more doses and then bring several of those into the MAD portion, again, focused on a weekly dosing scheme, potentially monthly or even biweekly.
And then in terms of... I mean, we'll have to see how things play out, right, over the next twelve, eighteen months. But in terms of potentially having MAD data, any sense for when we could see that?
So we'll aim to have that data, you know, towards the end of next year, early twenty-six, so that we can really press forward then on the phase two.
Yeah, and then speaking of the phase two, again, I know it's a premature question, but given that there is so much competition in the space, that there are so many agents that you know are ahead, so to speak, in development, you know, is there anything that you can do to accelerate timelines there, right? Whether it's building in a potential interim readout, you know, anything that can help you accelerate, you know, to get on the market and be commercialized sooner rather than later.
Yeah. So we're really watching, obviously, PG-102's advancement, as I said, but also the advancement of other companies that are a little bit ahead. Novo and Lilly have done a fabulous job really paving the way, and it appears that, you know, less, particularly in the phase three, trials-
Mm-hmm
... will be needed. But for our phase two, as of right now, intend to be a 12- to 16-week efficacy study, and should be able to move very quickly from the phase one into that phase two.
So the phase 2, you think, will be a 12- to 16-week or the phase-
Yeah.
Okay.
Based on watching what we've seen other companies be able to do with their phase twos.
Okay. Interesting. And then, you know, I understand the interest, right, in having an oral, and you did mention, Kate, earlier, that there are other oral agents on the market, or excuse me, in development, working their way towards commercialization. Obviously, most of those are once daily, right? So when you guys think about the broader competitive landscape, you'll have subQ, you'll have IV, you'll have, you know, potentially other orals on the market before you all come to market. You know, where do you think that you can fit into the treatment landscape? Are there certain patient subgroups? You know, is it really competing on the dosing schedule convenience? I mean, where do you feel like you can compete in such a lucrative but competitive market?
Great question. We've done a lot of work on really assessing the obesity landscape. There's a lot of injectables in development, less or so, but obviously some orals, as you mentioned. When we look at the orals in development, we see actually a lot of limitations. We've already talked about dosing, but the other challenges that we see are really significant discontinuation rates. Pfizer's data came out at over 50% discontinuation. Last week, Novo announced their oral amycretin, and over 80% of those patients had pretty significant GI side effects. So the tolerability is a challenge. We've spoken at length about the potential tolerability benefits of this program, but they're also using significant amount of API, which is probably leading to some of these tolerability challenges, but is also a really big hit to the supply chain.
We've seen that with the on-market products, 100-300 times the API in one dose. So that's another significant challenge. The other piece is, to our knowledge, we haven't seen any orals in development beyond a single agonist, and with the RaniPill, we're now pursuing a dual agonist, and to Svai's point, we've already released data with a triagonist. So it, it is so much more than the convenience of an oral or a-
Mm-hmm
... once-weekly program. We really see significant benefit to the Rani delivery in the obesity space.
Yeah, and you bring up a great point, right, just around supply constraints, manufacturing, that we are seeing play out real time. You know, what is the process for you all for the high-capacity pill? Is manufacturing capacity... You know, is that something that you feel like you have a very good handle on moving forward?
We do. We have built all of our own manufacturing and automation processes. We are phase II ready with our manufacturing and now working on phase III readiness. And we also are embarking upon several discussions with all the very well-known CDMOs. So we intend to, you know, do the development work for manufacturing and then ultimately pass on the manufacturing to a third party. So we've had several site visits this summer from some of the major manufacturing. So that'll be another piece that to be really commercial ready for manufacturing.
Great. It sounds like you guys are ahead of the game there. The other thing I did wanna ask, and I know we touched on safety earlier, but given that you are now, you know, moving into obese patients, right? Is there any potential risk of this mechanism in obese patients that maybe you guys have not seen, right, in some of the other patients that you have run a lot of these safety, you know, safety trials in and safety tests in? Just given that, you know, again, I mean, it does go through the stomach and the small intestine, right? And obese patients do have a different, let's call it, body composition, so to speak.
We don't, and it's a great question, and we don't anticipate any additional safety risks in this population. To Svai's point, the robust safety database that we have amassed really gives us, you know, a lot of confidence, and the way that the mechanism does work, we do not anticipate, you know, that there will be anything different in the label with an incretin in the RaniPill than a typical incretin label.
Mm-hmm. Okay, understood. And then, kind of jumping back a little bit, but we did talk about the potential for other partnerships going forward. So maybe just to clarify, I mean, it sounds like there is interest and willingness on your end to potentially partner with another partner or maybe look at another dual mechanism. Is that... Do you have the option available, right? Like, does your current partnership and collaboration, is the door still open to potentially do more collaborative partnerships and deals?
I can speak to that. So the only restriction we have with the ProGen arrangement is that we cannot do another GLP-1, GLP-2. Everything else is wide open. We are in discussion with a number of different companies to just not just the combination, but potentially we can put, like, a, well, semaglutide on a RaniPill-
Mm
... low dose maintenance type of therapy, and that's potentially one of the best way to go.
Okay.
This is a huge opportunity there.
Yeah. And just again, given sort of the timelines, right, and how fast this competitive space is moving, you know, is it... I don't wanna put words in your mouth, but is it safe to say that another partnership could come about, you know, sooner than later?
I think predicting a partnership, you know, it's hard to do. It's not within our control, but we are in a number of discussions at different stages.
Okay.
You know, some that are just getting started, but there's some where we had some, you know, pens on paper and some number being thrown around.
Mm-hmm. Well, and how important is it to really choose the right partner, right? I mean, in a way, you have a choice of a lot of different companies that are involved in the obesity space right now.
I think it's really important because I think from how well-established the RaniPill delivery is, if there's a failure, it's likely tied to the drug product.
Mm-hmm.
So I think being able to partner with as best-in-class in the various segments will be critical, as well as looking at the segmentation of this patient population. I think there's definitely a maintenance opportunity that could be pursued with a single agonist, certainly your kind of typical obese, and then, you know, looking at a more aggressive therapy, like a triagonist, for the morbidly obese-
Mm-hmm
... patients. So we're also looking at making sure that we don't enter into a product that would directly compete, but a different segment within the obesity space.
What about outside of obesity? You know, where is sort of the biggest area of interest for you all? You know, is it, you know, going after sort of the most successful intravenous drugs in terms of revenue potential, right, where you feel like you could have a the right fit? Is it maybe, you know, trying to be more of a patent expiration play for certain drugs that are very successful, but maybe are going off patent cycle sooner rather than later? You know, where do you all feel like you can really, you know, take this program to the next level?
I mean, I recognize obesity will be a very high priority and probably the priority area for the company going forward, but outside of obesity, you know, how do you think about areas where you can, you know, add the most value?
Our partner discussions do range everything from NCEs that are in earlier stages in the clinic, biosimilars, obviously we have several programs, and then, certainly companies with the big, dominant, well-established brands that are looking at LOE strategies. That is obviously very significantly tied to timing and making sure you can match up the launch of the RaniPill program prior to loss of exclusivity. In terms of therapeutic areas of focus, immunology, endocrinology, rare disease, oncology, and obesity are our areas of focus. We get approached all across the spectrum and have to make those strategic decisions in terms of, you know, where we're gonna place our best value. But really untapped potential, where there's limitations with the current standard of care-
Mm-hmm
... where the RaniPill can really come through and offer this disruptive technology.
Okay, great. We are looking forward to all the progress, and I'm sure this time next year we'll have a lot more to talk about. Kate, Svai, thank you so much for joining us. Really appreciate having you guys here.