Hi. Good afternoon, everyone. My name is Edward Nash, senior biotech analyst here at Canaccord Genuity. I have the pleasure of having Rani Therapeutics with us this afternoon. From Rani is Talat Imran, who is the company's CEO, and Nick Maestas, 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. Glad to have him here today. Maybe we could start off just a 10,000 foot view of just giving us an overview of Rani, 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. 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.
All right.
Rani 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 commensurately high variability. We're getting equivalent bioavailability in most cases, and equivalent variability to a subcu injection with monoclonal antibodies with 300 kilodalton proteins. It doesn't matter what you put into the RaniPill. This opens up the world of biologics more broadly to be turned into pills. With our current RaniPill, that's what we call our technology, which is essentially a swallowable auto-injector.
Looks like a pill. It goes into the small intestines, and then capsule shell dissolves, and there is 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%-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. Like STELARA as an example, if we have 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 dose as STELARA.
That is great. No, appreciate that overview. 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 are able to generate with this technology. You guys announced last year a $1 billion agreement with Chugai. Maybe you could talk a little bit about that agreement, and what Rani gets out of that, and what the pharma company gets out of that.
I think right off the bat, it is validation. Chugai is part of Roche. They are an incredible innovator. If you do not know, they developed HEMLIBRA, which our lead program with them is in rare disease. They are the market leader in hemophilia. Orforglipron, Lilly's small molecule GLP-1 agonist is theirs. Even Galderma's IL-31 came from them. There is ACTEMRA. They have had a long string of innovation, particularly in antibody engineering. They are looking at making more potent antibodies, making them less frequent in terms of the injection regimen, and it is almost a perfect fit for what we are doing. They spent two years 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. After coming on site and doing additional diligence, they expanded the deal.
Looking at validation, they have included 11 targets, of which we have prenegotiated economic terms for five additional programs, primarily in high value immunology categories.
Is the goal to continue to do these types of deals? We will talk a little bit about you have another collaboration where you are having your own proprietary, with this partner program in obesity. But is the goal to do more of these types of relationships where you are 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%-85% of on market biologics in some dosing regimen with the RaniPill. We cannot, as a company, a small biotech, go after all of those opportunities. We need partners. There is the validation, there is the cash, that helps with our own runway. We will absolutely do more of these deals, I believe, in the months and years to come. Having said that, we also think there is value in not just doing technology licenses but doing product licenses. So on a very selective basis, we will bring assets in, and we have done that, and I think we are going to talk about that a little bit here today.
But we will continue to do that very selectively. Ultimately, we are not going to be running late stage studies or building out commercial operations. We are a platform technology that delivers biologics orally, and that is 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.
Yep.
I think we'll have a mix of these over time.
Got it. I guess then that leads us to RT-114, which you guys have a collaboration with ProGen for this drug, which is GLP-1/GLP-2. You just recently announced phase I-A data on bioavailability, which was really impressive.
Yeah.
Maybe you could share a little bit about that bioavailability data and what the next steps now are.
If we take a step back to frame in the space, if you look at the orally available peptides, the dose typically is 75x to 100x to 150x the subcu dose. 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. 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 subq, and this is with an Fc fusion protein, almost 70 kilodalton molecule, not a small peptide. 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 in Fc and the first time we brought an incretin into the clinic. Being able to replicate what we have done before and show that with an obesity drug speaks to how broad we can go in this space. We do not have to go after just mono agonists. This is a GLP-1, GLP-2, as you mentioned. And I think we will talk about this as a portfolio approach that we are taking, and there are additional targets that we could go after in the future that this helps read onto. 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 subcutaneous studies.
So no new AEs emerged, and then critically, there were no AEs attributed to the RaniPill in this study. So it continues a trend of very clean data on the RaniPill 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. We just put out great data with our RT-114 program. We are very proud of it, and we are very invested in that program. Nothing to read into that. When we did the ProGen RT-114, PG-102, 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 is no one drug that is going to cover all of that. There is going to be elderly women where you really care about lean body mass preservation, muscle loss, bone loss. There is going to be patients who are candidates for gastric bypass or Roux-en-Y, where you need close to 30% weight loss. There are patients that have concomitant illnesses, MASH, hyperlipidemia, and there is 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, platform technology that can deliver any drug orally, but we do not discover our own drugs. It is important for us, with Chugai, they are going to be supplying drugs and running the programs. 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. PegBio is a really great partner from that perspective. They have an approved GLP-1 in China. That is not what we are looking at, but we are looking at the next generation that they are developing. These are multi-agonists. They go after some of the patient populations I just described. They have siRNAs that they are working on. They have ultra-long actings that could be dosed once a month or less frequent than that even.
Those are interesting because I will not point out any companies in particular, but some of these long actings do not 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 is 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. These are the types of things that we will 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 are not restricted to working with them either. If there are other opportunities, we can pursue those.
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 their BD apparatus the opportunity to market making oral versions of their drugs. We can, with the large pharma companies that we are 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. You alluded to it a bit already, but I just wanted to see if you could maybe just give a little more detail as to different. We all are very familiar with the GLP-1s, and then you have the additional incretin with GIP or glucagon that you can add into that mix or all three. You are one of, I think, of only two companies I know that are working on a combination of GLP-1, GLP-2. What does GLP-2 bring to the table that is different than just the GLP-1?
Yeah, great question, and I should have answered it before. GLP-2 is not a weight loss drug, but it is an important incretin. It helps with lean body mass preservation because it improves absorption through the gut, and micronutrient absorption in particular. It is 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 much longer time to Tmax than half-life, means that in ProGen's PG-102 subcu study, they showed virtually no vomiting and little nausea because it took about four times longer to get to Tmax than semaglutide or tirzepatide. When they moved to their titration and their MAD study in obese patients, there was no vomiting at all.
One of our primary thesis in getting into this space was you can not just make incretins that are convenient. They also have to be tolerable, and that has been the trade-off 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 are typically limited to single agonists, with some exceptions. Then we talked about the peptide volume issues for the oral peptides.
Yeah.
I think between the combination of the Fc fusion and then the GLP-2, this is not going to be a 25% weight loss drug. That is not what we are shooting for. But we want to make the most tolerable and convenient oral incretin on the market. That is the goal and why we did this partnership. I guess the very last thing, the cherry on top, and we will 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. That could be another patient population looking at diabetic obese that we could go after.
Nice. 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. Correct me if I'm wrong, but do you agree that the competitive landscape in the obesity space is actually a big plus for Rani? I also just want to get your comments on the orals that are out there now.
Yes.
The oral that's out there now. Your thoughts on that.
Sure. 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 semaglutide 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 subcu. Even with all of those issues, there's clearly a pull towards it. I would say that this goes beyond just obesity. If any of you have followed the Avere deal with Hansoh that just 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. We intrinsically, because we're taking long acting drugs, we can do weekly, monthly, quarterly. That is what we're going to be doing. I think it has been a real tailwind for us in that regard. 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 RaniPill. Some of the questions I remember from a couple of years ago, and you may remember this, Ed, as well, when we got the PG-102 asset was, does the world really need oral incretins, right? 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. I said, "Well, okay, maybe that's true, but they won't do it if they have another option." I think that is proving to be true. 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. 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. One of the companies I covered aging myself way back in the day was Protein Design Labs, where they had their 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 this. 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 huge amount of royalty revenue for them. Is that what we should expect to see Rani be, say another three, five, 10 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, right? 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. I think as the whole world moves, because a lot of these categories we think about, whether it's incretins 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 fair amount companies, Oruka, Spyre, 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.
I ask that question because it leads me now to say, what is it going to take 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 Rani? Why hasn't that happened to date, do you think?
Well, we did a billion-dollar deal with Chugai Pharmaceutical.
True. That's true. What have you done for me lately?
Yeah. 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.
Yeah.
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 do these Chugai deals, when you start to do more of those, that really helps, right?
Yeah.
You get non-dilutive money coming in to help you continue to keep growing the engine. But the funding you have now, what can that get us? Because all eyes are on RT-114 at this point. So what you have now, what kind of major inflection point will that get us to?
I'll take the first part of that, and then Nick, maybe you can take the second. In terms of catalyst events that are coming up, after getting this greater than 150% bioavailability data out of our RT-114 phase I-A, we decided to expand the I-A and add an additional cohort to confirm that that is the relationship between oral and subcu. 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 I-B thereafter, and I think at some point in the first half of 2027, we should expect to see data out of that. And that's an eight-weeks 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. I think those are two really important value inflection points for the company. There is all the things around our Chugai partnership that we cannot speak to. They will have to do that. Then any other deals that we do in the intervening time, potentially.
Got it.
Then in terms of runway, I will leave that to Nick.
Yeah. We reported, our last report 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. You have talked now about wanting to 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, I do not want to put words in your mouth. I will let you.
No, no.
Tell me where you think that is going.
I think it is not either/or.
Okay.
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 Chugai deal alone with the five predefined options that they have a number of those are in really high value immunology categories. Even if we do not do anything, we will probably end up in that space.
Okay. With RT-114, you just reported the phase I-A. Has anything changed in your minds from what you have seen there on dosing frequency or anything that could change going into a phase II?
Yeah, this is part of why we wanted to do a second dose. The dosing frequency may not change, but the dose that we select will. Because we gave 12 mg in this study versus the subcu. 12 mg is a subtherapeutic dose subcu. It looked like it was threshold therapeutic given how much higher the bioavailability was in the RaniPill, and the absorption kinetics. And we did not 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.
We need to know what those are, model it out, and then we will make the pills and run our phase I-B study. But it is going to be less drug. I can tell you that with certainty given the bioavailability.
Got it.
Which is, just taking it aside, that is kind of a staggering thing if you think about it, compared to every other oral biotherapeutic technology where you are going 10x, 50x-
Yeah.
-100x-
Yeah.
-150x. It is not an exaggeration. We are going to have to lower the dose.
Yep. From an immunology standpoint, now we got obesity, are we going to start to see immunology play a much bigger role in the overall-
Yes.
-scheme of things for the company?
Yes, absolutely. We have two immunology programs. We have supply agreements with Celltrion for an adalimumab biosimilar HUMIRA, and a STELARA biosimilar. We have brought the STELARA biosimilar into the clinic already.
Yeah.
We have generated data. This is not just aspirational.
No.
We are mindful this is not 2020 or 2021 anymore, so we are being mindful with our spend and how we sequence things. 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.
Got it.
Sorry, I was just going to say-
That's all right.
-with HUMIRA,
Yeah.
You're talking about a once a week pill for HUMIRA, and that would be really interesting. The data in that space is if you go to from biweekly to weekly, the efficacy and the onset of efficacy goes up. There are 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. There's a lot of data on that. The Oruka 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 SKYRIZI. 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. With the remaining seconds we have left-
Seconds.
-I just wanted to. Important thing, we keep talking about this RaniPill form technology, but can you just talk a little bit about are there any manufacturing capacity strong limits that you have with the device?
Well, 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. Then we need to scale it up to 50k, which will come later, and that'll support obesity.
Got it.
This is a core part of our spend, and our focus is on scaling the manufacturing now.
Got it. Well, I think it's extremely, obviously we like it. We cover you guys with a buy rating, but I think that the story is one of the more interesting ones that I've ever seen in the drug delivery space.
Thank you.
I think given, you're right, things like Apogee that have happened, I think we see that that's still a huge potential for the company. We look forward to seeing more additional deals next year at this time.
So do we.
Okay.
So do we.
Thank you very much for joining us.