Glad to be able to host Rani Therapeutics. With me in attendance is Svai Sanford, CFO of Rani, and Arvinder Dhalla, Chief Medical Officer of Rani. I'm sorry, that was your official title. But guys, thanks so.
I've been promoted.
You've been promoted. Thanks so much for making the time to join us here. Pleasure to have you. Very interesting story you guys have. I would love to kind of get into details, but before I do, maybe give us a highlight of the business, your technology, and what we can look forward to next year.
Yeah, thank you for having us. Our CEO, Talat Imran, he's traveling for other commitments, so he apologized for not being here, but we appreciate you hosting us. As you said, our VP of Clinical Development, Arvinder, is here to help me dig into any technical areas that you may have questions on. For those of you who don't know, Rani Therapeutics is a clinical stage biotech company focusing on developing a technology that can deliver biologic drugs orally. It is unlike any other that you would have seen. This is essentially a robotic autoinjector. We have this technology called the RaniPill. That is a platform that can pretty much have drug agnostic in terms of delivery. We've tested 15 different drugs in preclinical, and we've also tested three different drugs in phase one.
The tolerability of the drug, the safety profile of the drug, of the device has been well vetted. The biggest advantage that we have is that we can deliver the same amount of drug to a sub-Q injection. We don't have to put any more API in there, so we can get drug absorption that's very consistent with sub-Q.
Got it. For folks not as familiar with the story, maybe kind of describe mechanically how the RaniPill works. I know, and I'm oversimplifying, so please, I know you ingest it, it releases or works in a pH of 6.5, so it opens in the small intestine. Perhaps kind of just take us through the journey from ingestion to the pill opening and working.
Yeah, the Rani Pill is essentially the same size as a fish oil or a large triple zero vitamin capsule. You swallow it. It has special enteric coating on it that won't dissolve in the stomach. When the pill travels from the stomach to the small intestine, when the pH level, to your point, is higher, at six and above, the pill will start to dissolve and it activates an injection. That injection is powered by a gas as a power source, the same chemical as in Alka-Seltzer. If you have taken Alka-Seltzer, you drop it in water, it activates CO2. That gas is powerful enough to inflate the balloon to create an injection delivering the drug into the small intestinal wall. The drug is quickly absorbed through there. The needle that's in the Rani Pill is dissolvable.
The rest of the device is the balloon, the plastic, it deflates and it's safely passed out.
Got it, and I know you guys are developing kind of two versions of the RaniPill, kind of a generation one and also a high capacity for larger packages of drug. Maybe describe how much drug could the generation one deliver versus the high capacity one.
Yeah, the.
Kind of the milligrams.
Yeah, the GO is what we call it. Generation one has a capacity that can deliver up to three milligrams of drug per capsule. And that particular version is a solid form of drug. The RaniPill HC, which is our latest one and the one that we're most focused on going forward, is a liquid formulation. So we don't have to reformulate the drug. We take drug from manufacturer and we just put it into the RaniPill. There's essentially a syringe. And we can deliver up to 20 milligrams of drug per pill. And depending on concentration, it could be as high as 40 if it's highly concentrated. Anything to add, Arvinder?
Yeah, no, that's correct. So the HC capacity is dependent on the concentration of the drug. So if it's a highly concentrated solution, we can deliver up to 30, 40, 50 milligrams.
Whereas the generation one is strictly for solid state types of.
More like a daily dose type of regimen.
Okay, but in both cases, there's a needle that kind of injects this into the intestine.
Yes.
And so the obvious question is that I've gotten from investors, what's the risk of perforation here? I mean, safety-wise.
So as Svai was saying, we've conducted three phase one studies already, and we've done numerous, numerous injections in the preclinical setting. We've delivered up to 7,000 capsules in the preclinical settings. And we have not seen any safety concerns. We've done histopathology on these animals that have been injected with the Rani Pill, and we have seen no evidence of any injury up to 60 days of repeat dosing. So we have a lot of safety data already. In addition, the clinical study shows we've dosed to 250 Rani Pills in about 150 subjects. And again, no serious adverse events and not even very significant adverse events we've seen. So the needle is actually so small.
It's a microneedle.
It's a microneedle. And it dissolves within minutes after it's injecting the drug. So it basically acts as a conduit to just deliver the drug and carry the drug. And it dissolves rapidly right after the delivery. So we don't see any issues or any safety concerns with it.
I would, yeah, I would add in our 60-day GLP study. So 60-day of repeated dosing in animal models. We couldn't even find where the injection site was in the actual follow-on analysis by an independent.
Pathologist.
Pathologist, yeah.
The gut is very, very self-repairing and very fast healing tissue. So it gets repaired very quickly. So there is no injury that you see with the small needle.
So it wouldn't be a case where, like, a microneedle kind of punches a major artery in the small intestine and causes major bleeding. That's out of the realm of possibilities.
Yeah, that's correct.
Got it.
The questions we have remaining is no more about whether or not we can deliver it. Safety, obviously, will have to be further validated. But the remaining question we most often get are more about scale-up and growth from here on.
Got it. Just thinking about the COGS involved, assuming that your pills will come to market, I mean, it seems like a pretty involved pill. Is this going to be like a large molecule type of COGS involved? Maybe kind of get into that a little bit.
No, in fact, I think because from a drug payload standpoint, we don't have to put multiple folds of API in the pill. So we can deliver the same amount of what is required in a sub-Q today. The cost of the RaniPill device itself is pretty inexpensive. We're talking about plastic bags, balloon, the Alka-Seltzer chemical reactant. Those are all very cheap. And it was done on purpose. We didn't put any electronic on this to do any delivery signal or anything like that. So the majority of the COGS is going to be the amortizations of the equipment and the facilities and the labor that goes into the manufacturing. At the higher commercial scale, we expect that this would be the COGS of it on a per pill basis would be consistent with the current autoinjector today.
Okay. Last question on the platform before I delve into specific assets. Recently, or fairly recently, I think MIT announced that they had a collaboration with Novo Nordisk for a needle-free jet injection system for gastrointestinal drug delivery. So the big question is, how does this compare to your technology?
Yeah, we're aware of that publication that just came out in Nature. And as I said, we are, first of all, way ahead of that other technology. We have human data, clinical data showing high bioavailability, safety, efficacy, all of those things. We've done repeat dosing with the RaniPill up to seven days in humans and showed no adverse events of that and successful drug delivery. Their technology, we believe, is at an early phase. So both the safety as well as the efficacy of that technology needs to be still evaluated. In fact, we're paving the way for others who are working on similar technologies as to how to clinically develop this oral delivery platform.
Got it. Moving on to RT-102 and RT-111. I think both are phase two ready. Is that correct?
Yes.
Okay. When will the phase two trial start? Obviously, next year sometime?
So on RT-111, and then you can speak to 102. RT-111, we did the first phase one using the GO.
Again, remind folks what medicine that is.
It's biosimilar to ustekinumab for psoriasis as our first indication. It's essentially biosimilar to Stelara.
Stelara.
So we did the first phase one using the GO version of the RaniPill. And it was very successful. 84% drug bioavailability, which is unheard of for an antibody in an oral capsule. What we have to do before we go into phase 2 is repeat the phase one study using the liquid version of the RaniPill. But the liquid and the solid is essentially 80% of it is essentially the same. All the mechanism is essentially the same. The only difference is that it's liquid needle as opposed to a solid needle. So what we plan to do with RT-111 is to repeat that study, which we've done three times now in Australia. We know exactly what to do. The cash runway and resources have been a gating factor for us. Right now, we're focused on RT-114, which is our obesity program.
And then 111 is the next priority. And we plan to put that back into the clinic later part of next year.
Okay. Maybe just segueing into your obesity program. At least earlier this year, you had a collaboration with ProGen. You licensed on a collaboration for the GLP-1, GLP-2. What's the current status of that program? And tell us more about it.
Yeah, we're gearing up to initiate a phase one study with that in the early, maybe second quarter of next year. So yeah, it's going pretty well. ProGen itself is doing a sub-Q version of the program or the drug. So they are also conducting a phase one study, and they're ahead of us. So I think that program is moving along pretty well.
We can learn a lot from their sub-Q program, so they're running that on their own, but in the combination of PG-102 is the name of the drug that came from ProGen. We're collaborating with them on a 50-50 basis, so we have the key driver or the ownership of the major market, the U.S., Europe, including Australia and the U.K. They have the rest of the world, but regardless of where the study is held or what market it is for, we're sharing the cost 50-50 in terms of development, and then we'll share the economics 50-50 as well.
Rani is responsible or has the mandate to develop it as far as phase one, correct?
We'll be the lead developer.
That phase 1 study is going to proceed next year?
It'll be early part of next year.
Early part of next year.
All of the preclinical study and all that is ongoing right now.
Got it. Got it. Just taking a step back, you're going to embark on a phase 1 for this obesity drug, this GLP-1, GLP-2. You've done phase 1 studies for RT-111 and RT-102. Just given the technology, I mean, can you speak to the PK variability? I can imagine it's wide. Or is it not? I mean, I would imagine that there's a lot of intrapatient variability here. How do you tackle that?
Intrapatient, not interpatient variability. Each drug has its own unique PK profile, right? Initial PK study gives us insights into how we develop the subsequent clinical program and the clinical studies. We have not seen high variability, intrapatient variability that you speak of with RaniPill. In fact, it's similar to the sub-Q injection. We believe that with the HC, it's going to be even tighter data we will be obtaining compared to the GO. Differences in Cmax versus Tmax compared to the sub-Q injection that we see, it actually helps us to design the study accordingly, right? We can lower the dose if the Cmax is higher. Earlier Tmax that we see compared to the sub-Q injection, which we have seen with RT-111, for example, that just results in early onset of the efficacy of the drug. It's helpful again.
And so I think we can just look at the PK and do a dose adjustment or dosing regimen adjustment. So it's very helpful, I think, the early PK studies that we do.
So you raise a good point. You don't have to necessarily give the entire dose at once. You can kind of space it out, right? And kind of take advantage of the PK properties in a spaced-out fashion.
As an example for the RT-111 going forward, using the HC, we can dose in the range of 7-12 milligrams per pill. And we can make a better drug than the current Stelara today. Stelara is being injected 45 milligrams every four weeks. Or by the tail end.
Every three months.
Every three months. So at the tail end of that time frame, the data would show that the patient is actually out of therapy. To dose more frequently at a smaller fraction, you actually maintain a therapeutic window. And for that, we think we can make a better drug.
Got it. Got it. Very good. In the last couple of minutes we have left, guys, what's your current cash position? What's your cash runway look like? And what's the, I guess, cadence of clinical data catalysts that we can look forward to next year?
So, our cash position at the end of Q—what quarter are we in? Q3?—we had $30 million in the bank. Then, subsequently, in October, we raised another $10 million. So we have $40 million of cash that affords us a runway into Q3 of 2025. In terms of cadence, we talked about already in terms of 114. We will initiate that phase one early part of next year and then should have data available towards the end of the year. So the focus in terms of additional financing and all that is, as you can imagine, the early part of Rani was more about validating the platform. We took drugs like octreotide, PTH 1-34. Those were available for us to test and validate the platform. The platform is quite validated now. And you can see the data we have. It's pretty amazing.
As we move forward, we are in discussion with a number of potential partners, emerging pharma companies, large-sized pharma companies. The discussions are all in different stages, some of whom have already also done due diligence, visited our facility, and vetting our capacity. So in terms of the catalyst that would drive this company, it's more about putting multiple drugs on the RaniPill platform of the partner drugs.
Gaining new partnerships that would kind of just push back your need for additional financing.
Exactly. And the funding that would come along with that would be a typical licensing model. And the development costs for each of the partner programs will be mostly paid by the partner, if not all.
Got it. Got it. You bring up an interesting point because I cover Halozyme. I'm another drug delivery company. I mean, so for, let's say, a Rani Pill, there's Stelara biosimilar pill comes on the market. Could we think of the company of that product getting a co-formulation patent that's unique that would kind of extend that IP runway? Or how should we think about IP is what I'm trying to get at?
We have over 250 patents that have already been granted. And we have 250 more that are in pending application. I'm not the right person to get into the technical part of this. But there are a number of combination patents between the Rani Pill and a specific drug that have been protected or granted. And any new drug that we put in will also have an extension of the patent.
Got it. Got it. So even though they're biosimilars and kind of technically off-patent, co-formulating in the RaniPill would definitely provide some nice protection.
Exactly. And Rani is the first, the pioneer of doing what we do. There's nothing out there that's comparable to what we can do in terms of delivery.
I'm just thinking kind of ahead and how the IRA may govern this. Since it sounds like you have multiple active ingredients inherent in the Rani Pill, whatever does come to market would not be linked to the original product and would be considered its own. It would have its own IRA clock, is what I'm trying to get.
Can you speak to that?
Yeah, that would be correct. Like adding the unique drug into it that makes it a unique new product.
Right. Right. Got it. Very good. Anything that nuanced things I didn't ask that you would like to highlight?
No, I think the last comment I would make, given the 30 seconds that we have left here, is that the potential partnership discussion is not just about extending life cycle management. There are a number of conversations where new chemical entities that are coming to the market that want the differentiations of an oral as opposed to another sub-Q. We are having a lot of conversation around that.
Great. Great. Now, definitely something to look forward to. Guys, thanks so much for making time. Very informative discussion. I'll look forward to keeping tabs on those stories.
Thank you for having us.