Rani Therapeutics Holdings, Inc. Q4 FY2022 Earnings Call

Hello, and welcome to Rani Therapeutics' Fourth Quarter and Full Year 2022 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we'll hold a Q&A session. To ensure that we have ample time to address everyone's questions during the Q&A session, we'll ask for a limit of one question and one follow-up question per person. As a reminder, this call is being recorded today, Wednesday, March 22, 2023. I'd 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 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 factor 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 things may include without limitation statements regarding product development and clinical trials, product potential, device progress and performance, potential impact on patients, the regulatory environment, 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'll 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 manufacturing and performance of our RaniPill GO device. In February of 2022, Rani announced the development of the RaniPill HC capable of administering over 500% 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 2 program in the second half of this year with our current manufacturing line. We also plan to support three additional Phase 1 clinical studies of other pipeline programs concurrently in 2023. In addition, several 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 1 study of RT-102. Beyond the improvement in device performance, the Phase 1 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 1 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 2 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 the right of first negotiation to acquire worldwide rights to RT-111 following a Phase 1 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 milestone, which includes initiating a Phase 2 clinical trial with RT-102 in the second half of 2023 and initiating three additional Phase 1 studies with pipeline molecules, RT-105 containing an adalimumab biosimilar, RT-110 containing PTH for hyperparathyroidism, 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 Teriparatide. As you all know, we initiated a Phase 1 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 controlled 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, five of whom were postmenopausal received RT-102 20 micrograms once daily for seven 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. In fact, none of the participants withdrew from the study due to any adverse event 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. 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 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 1 study support the initiation of a Phase 2 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, a RaniPill capsule containing ustekinumab biosimilar for the treatment of inflammatory conditions. We look forward to the initiation of a Phase 1 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 securities 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 securities to sufficiently fund our operations 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 period in 2021 respectively. General and administrative expenses for the three 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 periods 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 non-cash 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 periods 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 have laid out could be transformative for our company. We look forward to the initiation of our Phase 2 clinical trial in RT-102 in the second half of 2023, our first Phase 2 trial, as well as the initiation of three additional Phase 1 studies with pipeline molecules RT-105, RT-110, 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?

Our first question comes from Brandon Folkes with Cantor. Your line is open.

Hi, thanks for taking my questions and 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 database they may require for the RaniPill device in light of the 505(b)(2) pathway? I'll stop there and ask a follow-up.

Sure. 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 eight weeks. It turns out that in this Phase 2, 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, where 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. Thanks. And then maybe just a follow-up to that. How should we think about the size of the Phase 1 trial that you're running in 2023, and then similarly on the RT-102 Phase 2 trial? And then maybe just focusing in on the RT-111, is that just going to be a normal Phase 1 trial or any nuances we should pay attention to there just given the Celltrion option post that? Thank you.

Sure. So they will look very similar to the single-dose portion of the RT-102 Phase 1. 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 1 and then to the option period.

Great. We look forward to seeing that data. And again, congrats on all the progress over the last segments.

Thank you so much.

Thank you. Please stand by for our next question. Our next question comes from the line of Geoff Meacham with Bank of America. Your line is open.

Good afternoon. This is Hao, calling in for Geoff Meacham, and thank you for the question. So I think maybe go back to the RT-102 multiple dose trial. I think you have the sales delivery for most patients happen in day 1 and day 2. So I just wanted to double-check if then any interventions happened once patients miss the sales delivery of joining that spin up?

Hi, Hao. In response to your question, there was no intervention, and we do not anticipate any. While there will be some mixed doses, we manage that by utilizing RT-102, which has significantly higher bioavailability. If you remember from our preclinical study, we observed faster bone growth compared to the subcutaneous method. With monoclonal antibodies at this dose, there will be a wash due to the drug's long half-life. As for the timing of these occurrences, it was completely random. The key takeaway is that the study experienced very few failures, which suggests that although there might have been more at the start, we believe it was merely due to random chance.

Great. And just a quick follow-up. So the Phase 2 expected by the second half, what exactly needs to happen before the Phase 2 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 2 started, as you said, in the second half of 2023.

Okay. Makes sense. Thank you.

Yes, absolutely.

Thank you. Please stand by for our next question. Our next question comes from the line of Wedbush, Andreas. Your line is open.

All right. Hi, guys. Thanks for taking our questions here. So just two 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, is the Celltrion deal indication specific? I mean, could you still partner out RT-111 for a different indication? Thanks.

Sure. I'll take the second one first. It's a short answer. No, it is not indications 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 is 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.

Okay, great. Thanks. Congrats on all progress. Thanks.

Thank you.

Thank you. Please stand by for our next question. Our next question comes from the line of Annabel Samimy with Stifel. Your line is open.

Hi. Thanks for taking my questions. Thanks. 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 1 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 the first negotiation? And then secondly, any further discussion with FDA regarding the design of the Phase 2 trial for 102, I think you're contemplating three different doses. Do you have a sense of the dosing range, the timeframe, how large it could be, etc., or was this primarily about the 505(b)(2) pathway? Thanks.

We don't expect to need to conduct repeat dosing to complete the Phase 1 study. It's designed to be a single-dose trial, likely using doses of 0.5 mg and 0.75 mg for the RT-111 program. Our goal is to demonstrate bioavailability comparable to a subcutaneous injection of the CT-P43 ustekinumab biosimilar, which has been a key focus for us and others in the industry. This would mark a significant achievement as it would be the first instance of demonstrating systemic bioavailability for an orally administered monoclonal antibody. We believe this milestone will attract interest from Celltrion during the option period. Regarding the Phase 2 design for RT-102, we consulted with the FDA about the expected endpoints and will focus on biomarkers such as P1NP and CTX, with a likely duration of eight weeks. We anticipate seeing separation in those biomarkers fairly quickly, and based on those results, we would then plan for a Phase 3 study with bone mineral density as the endpoint.

Okay. Great. Thank you so much.

Thank you, Annabel.

Thank you. Please stand by for our next question. Our next question comes from the line of Ash Verma with UBS. Your line is open.

Hi. Thanks for taking my questions. Congrats on the progress so far. I have two. So one was just, on the Phase 1 study that you're planning right in 2023. So single-dose study, these should be relatively quick, I would imagine like what kind of timeline 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 2 for RT-102 in the second half year, how would OpEx compare in '23 versus 2022? Thanks.

Thank you, Ash. Appreciate the questions. You are correct. The timeline for these Phase 1s 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. I hope everyone can hear me. Ash, I appreciate your question. As noted in our filing, we concluded 2022 with the cash portion of operating expenses just under $50 million. I anticipate that our operating expenses will rise for 2023 in the range of 20% to 30% compared to last year.

Great. Thanks, guys.

Thank you, Ash.

Thank you. Please stand by for our next question. Our next question comes from the line of Bert Hazlett with BTIG. Your line is open.

Yes, thank you. Thank you for taking the question and 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. Thank you.

Sure. So it's a great question, Bert. First off, thank you for the questions. In terms of our 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 can't provide guidance around that at this moment in time, but we have time. The Phase 1 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 the 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, if daily administration and increasing serum C trough levels, if you will, improves the efficacy of 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 standalone or as maintenance to one of the popular oncology drugs like pembro or an evo. 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.

Thanks for the color. Appreciate it.

Yes, absolutely. Thank you.

Thank you. Please stand by for our next question. Our last question comes from the line of Mitchell Kapoor with H.C. Wainwright. Your line is open.

Hi, team. I hope everyone is doing well, and thank you for taking the questions. I wanted to start with RT-102 and understand more about the pharmacokinetic profile. Do you believe you have established a margin of safety at this stage for moving forward? If efficacy follows pharmacokinetics, as we anticipate, could the pharmacokinetics appear slightly different in the upcoming trials and still be deemed positive?

Thank you for the question, Mitchell. I realize that I didn't answer one of Annabel's questions, so I'll address both now. We're considering doses between 10 and 40 micrograms, specifically 10, 20, and 40. To respond to your inquiry about whether we're achieving improved bone growth, I want to mention that we observed a lower incidence of adverse events with our single dose and, although we didn't compare multi-dose data, even with the 80-microgram Rani oral versus the 20-microgram Forteo in the single dose, it appeared to have a cleaner adverse event profile. We need to conduct a study in Phase 2 to evaluate the adverse event rates. However, through dose selection, I believe we can identify an optimal range that delivers the necessary efficacy for non-inferiority while maintaining a safety profile comparable to what is currently seen with Forteo.

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 development from that program or what the plan could be going forward?

Sure. As I mentioned previously, we are developing a sustained release formulation for our RT-110 PTH program aimed at hypoparathyroidism. We have made significant progress, which is why it is included in our roadmap for Phase 1. We will also be applying the same approach this year to reformulate our RT-101 into a long-acting version to make it more competitive, similar to Sandostatin LAR. There are no updates to share at this moment, but we expect to revisit this later in the year.

Okay, great. Thank you very much.

Thank you.

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.