Rani Therapeutics Holdings, Inc. (RANI) Earnings Call Transcript & Summary

Hello, and welcome to Rani Therapeutics Fourth Quarter and Full Year 2022 Financial Results and Corporate Update Conference Call. [Operator Instructions] As a reminder, this call is being recorded today, Wednesday, March 22, 2023. I would now like to turn the conference over to Laurence Watts of Gilmartin Group. Please go ahead, sir.

Thank you, operator. Joining us on the call today from Rani Therapeutics are Chief Executive Officer, Talat Imran; Chief Financial Officer, Svai Sanford; and Chief Scientific Officer, Mir Hashim. During this conference call, management will make forward-looking statements that are subject to risks, uncertainties and assumptions, such as, but not limited to, those discussed in the Risk Factors section of the company's filings with the Securities and Exchange Commission including its annual report on Form 10-K and quarterly reports on Form 10-Q, which identify the specific factors that may cause actual events or results to differ materially from those described in these forward-looking statements. These statements may include, without limitation, statements regarding product development and clinical trials, product potential, device progress and performance, potential impacts on patients, the regulatory environments, manufacturing progress, certain business strategies, capital resources or operating performance. Actual results and the timing of events could differ materially from those projected in such forward-looking statements. With that, I will turn the call over to Talat Imran, Chief Executive Officer of Rani. Talat?

Thank you, Laurence. Good afternoon, everyone, and thank you for joining our fourth quarter and full year 2022 financial results conference call. I'm delighted to share the highlights of Rani Therapeutics' strong performance in 2022, during which the company achieved numerous milestones in the progression of its pipeline program and improvements in device performance. I would like to start by reviewing the important milestones that Rani achieved throughout the year. Last year, we made significant enhancements to the RaniPill platform, highlighted by the unveiling of our high-capacity RaniPill HC device and continued improvement in both the manufacturer and performance of our RaniPill GO device. In February of 2022, Rani announced the development of the RaniPill HC capable of administering 500%-plus higher payloads than our standard RaniPill GO. While the RaniPill GO is designed to deliver drugs with a daily dose of up to 3 milligrams, the RaniPill HC can potentially deliver up to 20 milligrams per pill. We are currently in preclinical studies with the RaniPill HC. Importantly, with this new device, we now have the potential to target a much larger market of molecules such as pembrolizumab, etanercept, trastuzumab and secukinumab. Concurrent with the development of the RaniPill HC, we have continued to make improvements in the development of the RaniPill GO, which is being utilized across our current internal development pipeline. We have progressed our manufacturing scale-up and automation efforts, and I'm happy to report that we are now capable of supporting a Phase II program in the second half of this year with our current manufacturing line. We also plan to support 3 additional Phase I clinical studies of other pipeline programs concurrently in 2023. In addition, subtle but important improvements in our manufacturing processes resulted in our latest iteration of the RaniPill GO, achieving a 92% drug delivery success rate in our recently completed Phase I study of RT-102. Beyond the improvement in device performance, the Phase I study of RT-102 met all of its endpoints. RT-102 delivered PTH with 300% to 400% higher bioavailability for 20 micrograms and 80 micrograms of PTH, respectively, when compared to 20 micrograms of Forteo delivered via subcutaneous injection. In addition, RT-102 was well tolerated, and no serious adverse events were reported in the study. Of the few minor adverse events reported, all were deemed mild to moderate and resolved on their own. The Phase I study results add to our robust and growing body of data supporting the safety and performance of the RaniPill. We are very pleased with the favorable safety profile demonstrated by the RaniPill capsule to date. We have now dosed nearly 100 human subjects in clinical studies with no serious adverse events to report. As we plan for the initiation of our first Phase II clinical trial in the second half of 2023, I would like to remind everyone about our recent interactions with the FDA, particularly the feedback received during our pre-IND meeting for RT-102. Based on guidance from the FDA, we believe that the 505(b)(2) pathway is suitable for RT-102, our PTH analog program. We appreciate the interactions we have had to date with regulators and will continue to take their input into account as we progress our development programs. Turning to the development of RT-111. We were pleased to recently announce our partnership with Celltrion. Under this partnership, Celltrion will exclusively supply to Rani the ustekinumab biosimilar drug substance, CT-P43, required for RT-111. Rani has been granted an exclusive license to use CT-P43 in the development and commercialization of RT-111, and Celltrion in turn has been granted a right of first negotiation to acquire worldwide rights to RT-111 following a Phase I clinical trial. We believe our partnership with Celltrion, a leader in biosimilars and biologics manufacturing, validates the strength of our RaniPill oral drug-delivery platform. We are delighted to be working with Celltrion and look forward to potentially broadening our partnership over time. Lastly, before I turn it over to Mir Hashim to cover our preclinical and clinical data in more detail, I would like to remind you of our anticipated near-term milestones, which include initiating a Phase II clinical trial with RT-102 in the second half of 2023 and initiating 3 additional Phase I studies with pipeline molecules: RT-105 containing an adalimumab biosimilar, RT-110 containing PTH for hypoparathyroidism and RT-111 containing Celltrion's ustekinumab biosimilar. With that, let me now turn the call over to Mir Hashim to discuss our preclinical and clinical updates in more detail. Mir?

Thank you, Talat, and thank you, everyone, for joining us. Let me begin by highlighting some of the updates we have provided for RT-102, which is being developed for the treatment of osteoporosis. RT-102 is the RaniPill capsule containing PTH(1-34) also known as a teriparatide. As you all know, we initiated a Phase I clinical study of RT-102 in Australia in March of 2022 and released top line data for Part 1 of the study in August and Part 2 of the study in December of 2022. In Part 1 of the study, we evaluated the safety, tolerability, reliability and pharmacokinetics of RT-102 in healthy adult female volunteers at a single dose of either 20 micrograms or 80 micrograms. In Part 2 of the study, the same parameters were evaluated with repeat dosing of RT-102 at 20 micrograms for up to 7 days. In Part 1, 15 subjects received RT-102 at a dose of 20 micrograms, while 14 subjects received RT-102 at a dose of 80 micrograms. A control group of 10 participants received a single 20-microgram subcutaneous injection of Forteo, which is the commercial formulation of teriparatide approved for subcutaneous administration. RT-102 was well tolerated in both those groups and delivered PTH with bioavailability estimated to be up to three- to four-fold higher than that of subcutaneous Forteo. There were no serious adverse events reported in the study at any dose. Now in Part 2 of the study, 10 healthy female volunteers, 5 of whom were postmenopausal, received RT-102 20 micrograms once daily for 7 consecutive days. On the seventh day, complete pharmacokinetic profiles of RT-102 were obtained for each subject. We again observed that RT-102 was generally well tolerated with no serious adverse events noted during the study. And in fact, none of the participants withdrew from the study due to any adverse events related to the RaniPill capsule. The bioavailability of RT-102 was high relative to subcutaneous Forteo, again confirming the data from Part 1 of the study. And importantly, as Talat indicated earlier, the overall reliability or success rate of RT-102 delivery was 92%. Additionally, we were also pleased to have received preliminary feedback and guidance from the FDA on our RT-102 development plans. Overall, for RT-102, we are enthusiastic about the progress we have made so far, and we believe that the safety, reliability and pharmacokinetic data that we collected through both parts of the Phase I study support the initiation of a Phase II trial of RT-102 in osteoporosis, which we anticipate beginning in the second half of 2023. Now beyond the RT-102 program, we are also pleased with our ongoing progress in the development of RT-111, RaniPill capsule containing ustekinumab biosimilar with the treatment of inflammatory conditions. And we look forward to the initiation of a Phase I study for RT-111 later this year. We believe that RT-111 has the potential to make a real difference for patients by providing them with an oral alternative to the current injectable standard of care. Overall, we are delighted with the ongoing clinical and preclinical development of our pipeline programs. Advancements in our core programs reiterate our commitment to delivering the RaniPill capsule as an effective oral alternative that could change the treatment paradigm for the millions of patients currently taking injections for their chronic disease conditions. Now I will turn it over to Svai to go over the financial results for the fourth quarter and year-end 2022. Svai?

Thank you, Hashim, and good afternoon, everyone. In addition to the financial results summarized in our press release that was issued earlier today, I will briefly share some key financial highlights on this call. You can also find additional information on our Form 10-K for the year ended December 31, 2022. Cash, cash equivalents and marketable security as of December 31, 2022, totaled $98.5 million compared to $117.5 million as of December 31, 2021. Without additional financing, we expect the current cash, cash equivalents and marketable security to sufficiently fund our operation to mid-2024. Research and development expenses for the fourth quarter and full year 2022 were $10.4 million and $36.6 million, respectively, compared to $7.4 million and $26.5 million for the same periods in 2021, respectively. General and administrative expenses for the 3 months and 12 months ended December 31, 2022, were $7.1 million and $26.8 million, respectively, compared to $5.9 million and $27.8 million for the same period in 2021, respectively. Lastly, our net loss for the fourth quarter and full year 2022 was $17.3 million and $63.3 million, respectively, compared to $13.3 million and $53.1 million for the same periods in 2021, respectively. Excluding noncash charges, primarily equity-based compensation expense, the non-GAAP net loss was $13.3 million for the fourth quarter and $47.8 million for the full year 2022 compared to $10 million and $28.8 million for the same period in 2021, respectively. This concludes my remarks on the financial results, and I will now turn the call back over to Talat for closing comments. Talat?

Thank you, Svai. In closing, we are very pleased with our progress so far and look forward to maintaining our momentum in 2023. From a clinical perspective, 2023 is really going to be a year of execution for Rani. And we believe that the potential milestones I've laid out could be transformative for our company. We look forward to the initiation of our Phase II clinical trial in RT-102 in the second half of 2023, our first Phase II trial as well as the initiation of 3 additional Phase I studies with pipeline molecules RT-105,-RT110 and RT-111. We have built a world-class leadership team at Rani, and I would like to thank everyone at the company for their efforts this past year and so far in 2023. I'd also like to thank all of our stakeholders for your continued support of Rani and for helping us move closer to our vision of making oral biologics a reality. With that, I will now open the call up for questions. Operator?

[Operator Instructions] Our first question comes from the line of Brandon Folkes with Cantor.

Congratulations on all the progress in 2022. Maybe just firstly from me, when you sat down with the FDA, did they provide any color in terms of the safety base -- safety database that may require for the RaniPill device in light of the 505(b)(2) pathway? I'll stop here and then ask a follow-up.

Sure. And Brandon, good to hear from you. Thank you for your question. They did not in the context of the RT-102 program, but we have had prior interactions with the FDA, where the database size was about 2,000 deployments, 40 subjects over 8 weeks. It turns out that in this Phase II, we will reach thereabouts or maybe a little bit higher. So I think we're hopefully going to be answering that question for them as well. But we've decided to do it essentially concurrent with the data that we're generating around the efficacy and biomarkers with the RT-102 program.

Great. And then maybe just a follow-up to that. How should we think about the size of the Phase I trials that you're running in 2023 and then similarly on RT-102 Phase II trial? And then maybe just focusing in on the RT-111, is that just going to be a normal Phase I trial? Or any nuances we should pay attention to there, just given the Celltrion option post that?

Sure. So they will look very similar to the single-dose portion of the RT-102 Phase I. So it will be on the order of 15 to 20, maybe a little bit more in terms of the number of subjects. These are healthy volunteers, single dose. We may test with RT-111 a couple of different doses just to see what the dose response curves look like similar to what we did with RT-102. But I think you framed it well. It's going to look very, very similar. It's become -- I don't want to say cookie-cutter whenever you go into the clinic, it's work, and you have to take it very seriously. But I think we've gotten relatively good at putting these together and conducting them. And I guess one last point around the Celltrion relationship, I think the expectation is similar data to what we generated with RT-102 should be sufficient to get us completed with the Phase I and into the option period.

Our next question comes from the line of Geoff Meacham with Bank of America.

This is Hao calling in for Geoff Meacham. So I think maybe go back to the RT-102 multiple-dose trial. I think you have the sales delivery for most of the patients happened in day 1 and day 2. So I just wanted to double check if there any intervention happened once patients miss the -- ahead of sales delivery during that setup?

And to answer your question, no, there was no intervention, and we don't expect there to be any. There will be some missed doses, but we manage that through -- in the case of RT-102 having significantly higher bioavailability. And if you recall from our PD preclinical study showing faster bone growth than we saw with the subcutaneous. And when you get to monoclonal antibodies, a missed dose here or there will be a wash because of the long half-life of the drug. And in terms of when they happened, it was completely random. There was -- I think the point is there were so few failures in that study that you can kind of look at it and say that maybe they were more at the beginning, but we don't think it was anything more than just random chance.

Great. Just got a quick follow-up. So for the Phase II expected by second half, what exactly needs to happen before the Phase II can be initiated?

Sure. So the guidance we got from the FDA was to run a repeat-dose GLP study of 28 days. We're going to be doing that here in the first half of the year and completing it and then submitting and hopefully getting that Phase II started, as you said, in the second half of '23.

Our next question comes from the line of Wedbush, Andreas.

So just 2 for us here. So how does the Celltrion deal in the right of first negotiation indicate what the strategy would be for the company and the pipeline of biosimilars going forward? And then secondly, the Celltrion deal indication specific, could you still partner out RT-111 for a different indication?

Sure. I'll take the second one first. It's a short answer. No, it is not indication specific. It's for ustekinumab biosimilar or ustekinumab in general. So it's that entire drug, if you will and any indications you could pursue with it. So CD -- ulcerative colitis or psoriasis. In terms of what the relationship with Celltrion implies, I think from our perspective, implies that what we're doing is valuable, and there's an interest in supporting us both in the clinical and commercial development from Celltrion, but also potentially taking over commercial rights as well. I think as we look ahead to additional deals, this could be the flavor of how things are done. And as we generate more data, I think there is a potential that pharma companies will be less inclined to enable us to compete against them as opposed to working with us.

Our next question comes from the line of Annabel Samimy with Stifel.

Good progress. So on the Celltrion partnership again, are there any key requirements or metrics that Celltrion is looking for as far as the Phase I is concerned? Like they're seeing bioavailability or delivery success and do you need repeat dosing for that trial before you offer it up for an option or right of first negotiation? And then secondly, any further discussion with FDA regarding the design of the Phase II trial for 102? I think you're contemplating 3 different doses. Do you have a sense of the dosing range, the time frame, how large it could be, et cetera? Or was this primarily about a 505(b)(2) pathway?

Sure. So we should not need to do repeat dosing to complete the Phase I. It's a single dose study with probably 0.5 mg and 3/4 of the mg as the doses that we use for the RT-111 program for the Phase I. There's nothing in particular beyond showing the bioavailability is similar to a subcutaneous injection of their CT-P43 ustekinumab biosimilar. I think that's what everyone has been looking for, what we would like to demonstrate as well. And just to remind everyone, this would be the first time, us or really anyone has been able to demonstrate systemic bioavailability of an orally administered monoclonal antibody. So this is a big milestone for the company. And I think, hopefully, that's sufficient to garner interest from Celltrion as we get into the option period. As far as the RT-102 Phase II design is concerned, we did ask the FDA what they would want to see in terms of end points and we're going to be looking at biomarkers, so P1NP and CTX and the duration is likely going to be 8 weeks. You can see separation on those biomarkers fairly rapidly. And then from there, we would start planning for a Phase III where we would likely be looking at BMD as the endpoint.

Our next question comes from the line of Ash Verma with UBS.

Congrats on the progress so far. I have 2. So one on just one of these Phase I studies that you are planning, right, in 2023. So single dose study, we should be relatively quick, I would imagine, like what kind of time line do you think we can expect for the completion of these studies? And then second, anything that you can comment on kind of the cadence of OpEx given that you plan to initiate the Phase II for RT-102 in the second half year, how would OpEx compare in '23 versus 2022?

Thank you, Ash. I appreciate the questions. You are correct. The time line for these Phase I is relatively short. It's a matter of months to get them done. I will say the RT-111 will take a bit longer than RT-102 single dose, just because the half-life of that drug is significantly longer. So in order to get the full curve, you have to track the patients for a bit longer. But -- we're also hoping and hope is not a plan. But with COVID not being as much of an issue as it was early last year that if recruitment is fairly straightforward, this is a healthy volunteer study that we should be able to enroll fairly quickly, and that will help with getting it done quickly as well. And we all are incentivized to do so. With your second question, I'm going to turn that over to Svai Sanford, our CFO, to answer.

Thank you, Talat. Hopefully, everyone can hear me. Ash, thank you for the question. We ended as you can see in our filing, we ended the 2022 with the non -- with the cash portion of the OpEx, just under $50 million. I expect that our operating expenses will increase for 2023 in the range of 20% to 30% from last year.

Our next question comes from the line of Bert Hazlett with BTIG.

Congratulations on all the progress. Two topics in general. One is Celltrion. And as you think about the development of RT-111/CT-P43, is there a prioritization with regard to indication with the development of that program? Or how are you thinking about kind of steps beyond Phase 1? And then second question is kind of a similar question with regard to prioritization of the monoclonals that you mentioned, whether that's pembrolizumab, trastuzumab or others, how are you thinking about maybe prioritization of those types of molecules? Just general thoughts there would be helpful.

Sure. So it's a great question, Bert. First off, thank you for the questions. In terms of RT-111/CT-P43, we are in discussions with Celltrion right now to figure out how to prioritize. It would either be psoriasis or Crohn's disease, I would imagine. And part of it will be determining the cost, the time to proof of concept and also the regulatory plan and if there's PK read on from what we're doing to whichever trial we decide to run to other indications, so I can't provide guidance around that at this moment in time, but we have time. The Phase I is a healthy volunteer study. So we'll take this year to kind of coalesce around the plan, and we'll share that early next year. In terms of what we're planning to do with the RaniPill HC, immunology, I think as a general area is right in sweet spot for what we're doing, chronic diseases, crowded categories, where differentiation to oral with a monoclonal antibody could be tremendous. After that, we are looking at the delivery of antisense oligonucleotides and siRNA. We're exploring that in discovery this year. And I would like to look in the future, I think, Bert, we've talked about this in the past at if daily administration and increasing serum C trough levels, if you will, improves the efficacy of a monoclonal antibody. There's some evidence of that with certain drugs in the past. So we would want to look at that with oncology, whether it's as a stand-alone or as a maintenance to one of the popular oncology drugs like pembro or nivo. So that's for maybe next year. We have plenty on our plate as it is now, but that's kind of how we're thinking about utilizing the RaniPill HC.

Our last question comes from the line of Mitchell Kapoor with H.C. Wainwright.

I wanted to start out with RT-102, and I wanted to understand more about the PK profile in terms of have you -- do you think you've established a margin of safety at this point for moving forward in a way that if efficacy follows PK, which we would expect that it probably should, could PK look slightly different in the next trials and still be considered positive?

Sure. So thank you for the question, Mitchell, and I realize in you asking that, that I failed to answer one of Annabel's questions, I'll do both in the same shot. We're looking at doses between 10 and 40 micrograms, so 10, 20 and 40, specifically to address the question you just had, which is if we're getting better or significantly better bone growth, I would caution that we had a lower AE incidents in our single dose and even in our multidose. Well, we didn't compare in the multidose, but compared to the -- even the 80-microgram Rani oral versus the 20-microgram Forteo in the single dose, it looked cleaner from an AE perspective. We need to conduct that study in the Phase II or look at the AE rates, I should say. But through the dose selection, I think we can find a sweet spot where we have the efficacy we need for non-inferiority and a safety profile that is commensurate with what you see with Forteo currently.

Okay. That's very helpful. And then on the RT-101 program, could you just provide an update there and when we might be able to see more developments from that program? Or what the plan could be going forward?

Sure. So as I mentioned in the past, we're working on a sustained release formulation. This is the technology that's going into our RT-110 PTH for hypoparathyroidism program. We have made considerable progress, which is why it's in our road map for Phase I. And that same approach is what we're going to be working on this year with our RT-101 formulation, to reformulate it into a long-acting, so that it's more competitive with like a Sandostatin LAR. So nothing to report at this moment in time, but I think that's something that we'll revisit later this year.

Thank you. I'm showing no further questions in the queue. I would now like to turn the call back to Talat for closing remarks.

Thank you, operator. This concludes our fourth quarter and full year 2022 financial results and corporate update conference call. Thank you again, everyone, for joining us this afternoon.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.