Q4 2022 Rani Therapeutics Holdings Inc Earnings Call
Speaker 1: You you.
Operator: Hello and welcome to Roni Therapeutics' fourth quarter and four year 2022 financial results and corporate update conference call. At this time, all participants are on a listen-only mode. Following management's prepared remarks, we will 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 22nd, 2023. I will now like to turn the conference over to Lawrence Watts of the Gil Martin Group. Please go ahead, sir.
Speaker 2: that's on a listen-only mode.
Speaker 2: Following management's prepared remarks, we will hold a Q&A session. To ensure that we have ample time to address everyone's questions during the Q&A session, we will ask for a limit of one question and one follow-up question per person.
Speaker 2: As a reminder, this call is being recorded today, Wednesday, March 22nd, 2023.
Speaker 2: I would now like to turn the conference over to Lawrence Watts of Gilmartin Group. Please go ahead, sir.
Lawrence Watts: Thank you, Operators. Joining us on the call today from Ronnie Therapeutics are Chief Executive Officer Talat Imran, Chief Financial Officer Spice Sanford, and Chief Scientific Officer Mia Hesha. During this conference goal, 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 10K and quarterly reports on Form 10Q, which identify the specific factors that may cause actual events or results to differ materially from those described in these forward-looking statements.
Speaker 3: Thank you, operator.
Speaker 3: Joining us on the call today from Rani Therapeutics are Chief Executive Officer Talaat Imra, Chief Financial Officer, and Chief Scientific Officer, Mir Hashem.
Speaker 3: During this conference call, management will make forward-listen statements that are subject to risks, uncertainties and assumptions, such as, but not limited to, those discussed in the Risks Back to the Section of the company's filings with the Securities and Exchange Commission, including its annual report on Form 10-K and quarter reports on Form 10-Q .
Speaker 3: which identifies the specific factors that may cause actual events or results different materially from those described in these forward-looking statements.
Lawrence Watts: These statements may include, without limitation, statements regarding product development and clinical trials, product potential, device progress and performance, potential impact on patients, regulatory environments, manufacturing progress, certain business strategies, capital resources, or operating performance. However, actual results on 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.
Speaker 3: These statements 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.
Speaker 3: Actual results on the timing of events could differ materially from those projected in such forward-looking statements.
Talat Imran: Good afternoon, everyone, and thank you for joining our fourth quarter and full year 2022 Financial Results Conference. I'm delighted to share the highlights of Ronnie Therapeutics' strong performance in 2022, during which the company achieved numerous milestones in the progression of its pipeline programs and improvements in device performance. I would like to start by reviewing the important milestones that Rani achieved throughout the year.
Speaker 3: With that, I will turn the call over to Talat Imran, Chief Executive Officer of Rani. Talat?
Speaker 3: I will turn the call over to Talat Imran, Chief Executive Officer of Rani. Talat. Thank you, Lawrence.
Speaker 4: Good afternoon, everyone, and thank you for joining our fourth quarter and full year 2022 results conference call.
Speaker 4: I'm delighted to share the highlights of Roni Therapeutics' strong performance in 2022, during which the company achieved numerous milestones in the progression of its pipeline program and improvements in device performance.
Talat Imran: Last year, we made significant enhancements to the RaniPill platform highlighted by the unveiling of our high-capacity RaniPill H-C device and continued improvement in both the manufacture and performance of our RONIPIL Go device. In February of 2022, Ronnie announced the development of the Ronnie Pill HC, capable of administering 500% plus higher payloads than our standard Ronnie Pill Go. While the RonniePil Go is designed to deliver drugs with a daily dose of up to 3 milligrams, the RonniePill HC can potentially deliver up to 20 milligrams per day. We are currently in pre-clinical studies with the RaniPil-A.
Speaker 4: I would like to start by reviewing the important milestones that Ronnie achieved throughout the year. I would like to start by reviewing the important milestones that Ronnie achieved throughout
Speaker 4: Last year, we made significant enhancements to the RonnyPill platform highlighted by the unveiling of our high-capacity RonnyPill 8C device and continued improvement in both the manufacture and performance of our RonnyPill Go device.
Speaker 4: In February of 2022, Ronnie announced the development of the RonnyPill 8C, capable of administering 500% plus higher payloads than our standard RonnyPill Go.
Speaker 4: While the Ronipil Go is designed to deliver drugs with a daily dose of up to 3 mg, the Ronipil 8C can potentially deliver up to 20 mg per pill.
Talat Imran: Importantly, with this new device, we now have the potential to target a much larger market of molecules such as Pemberlizamab, Itanerset, Trasthusamab, and Pekinaemoneum. Concurrent with the development of the Ronnieville A3, we have continued to make improvements in the development of the Ronnieville 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.
Speaker 4: We are currently in preclinical studies with the Roni Pill HC.
Speaker 4: Importantly, with this new device, we now have the potential to target a much larger market of molecules such as pembrolizumab, etanercept, trastuzumab, and secrikinumab.
Speaker 4: Concurrent with the development of the RonnyPill 8C, we have continued to make improvements in the development of the RonnyPill GO, which is being utilized across our current internal development pipeline.
Speaker 4: 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.
Talat Imran: We also plan to support three additional phase one clinical studies of other pipeline programs concurrently in 2020. In addition, subtle but important improvements in our manufacturing processes resulted in our latest iteration of the RONI-Pil-Go, achieving a 92% drug delivery success rate in our recently completed phase one study of RT 102. Beyond the improvement in device performance, the phase one study of RT 102 met all of its objectives; RT102 delivered PTH with 300 to 400% higher bioavailability for 20 micrograms and 80 micrograms of PTH, respectively when compared to 20 micrograms of Porteo delivered via subcutaneous injectors. 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.
Speaker 4: We also plan to support three additional Phase I clinical studies of other pipeline programs concurrently in 2023.
Speaker 4: In addition, subtle but important improvements in our manufacturing processes resulted in our latest iteration of the Ronny Pill Go, achieving a 92% drug delivery success rate in our recently completed Phase 1 study of RT-102.
Speaker 4: Beyond the improvement in device performance, the phase 1 study of RT-102 met all of its endpoints.
Speaker 4: 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 Portao delivered via subcutaneous injection.
Speaker 4: In addition, RT-102 was well tolerated and no serious adverse events were reported in the study.
Speaker 4: Of the few minor adverse events reported, all were deemed mild to moderate and resolved on their own.
Speaker 4: The Phase 1 study results add to our robust and growing body of data supporting the safety and performance of the Rani Code.
Speaker 4: We are very pleased with the favorable safety profile demonstrated by the Ronny Pill capsule to date.
Speaker 4: 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.
Speaker 4: particularly the feedback received during our pre-IND meeting for RT-102.
Speaker 4: Based on guidance from the FDA, we believe that the 505b2 pathway is suitable for RT-102, or PTH analog program.
Talat Imran: The phase one study results add to our robust and growing body of data supporting the safety and performance of the Ronnie Pill. We are very pleased with the favorable safety profile demonstrated by the Ronnie Pill 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 two 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-I&D meeting for RT102.
Speaker 4: 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 program.
Speaker 4: Turning to the development of RT-111, we were pleased to recently announce our partnership with Celtreon.
Speaker 4: Under this partnership, Celtreon will exclusively supply to Rani the oosakinumab biosimilar drug substance CTP43 required for RT-111.
Speaker 4: Ronnie has been granted an exclusive license to use CTP43 in the development and commercialization of RT-111.
Speaker 4: and Celtreon in turn has been granted a right of first negotiation to acquire worldwide rights to RT-111 following a Phase 1 clinical trial.
Speaker 4: We believe our partnership with Celtreon, a leader in biosimilars and biologics manufacturing, validates the strength of our RoniPill oral drug delivery platform.
Talat Imran: Based on guidance from the FDA, we believe that the 505B2 pathway is suitable for RT102, 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 program.
Speaker 4: We are delighted to be working with Celtreon and look forward to potentially broadening our partnership over time.
Speaker 4: 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
Speaker 4: and initiating three additional phase one studies with pipeline molecules. RT-105 containing an adalimumab biosimilar, RT-110 containing PTH for hyperparathyroidism, and RT-111 containing celtreons oostakinumab biosimilar.
Talat Imran: Turning to the development of RT11, we were pleased to recently announce our partnership with Celtrion. Under this partnership, Celtreon will exclusively supply to Rani the Usikinomal Biosimilar drug substance, CTP-43, required for RT111. Ronnie has been granted an exclusive license to use CTP 43 in the development and commercialization of RT11. Enceletion, in turn, has been granted a right of first negotiation to acquire worldwide rights to RT11 following a phase one clinical trial.
Speaker 4: With that, let me now turn the call over to Mir Hashim to discuss our preclinical and clinical updates in more detail. Mir?
Speaker 5: Thank you, Salat, and thank you everyone for joining us.
Speaker 5: 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 Ranipil capsule containing PTH-134, also known as teriparatide.
Speaker 5: 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.
Talat Imran: We believe our partnership with Celtrion, a leader in biosimilars and biologics manufacturing, validates the strength of our Ronnie Pill oral drug delivery platform. We are delighted to be working with Seltrion and look forward to potentially broadening our partnership. 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 two clinical trial with RT 102 in the second half of 2023 and initiating three additional phase one studies with pipeline molecules.
Speaker 5: In part one 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.
Speaker 5: In part two of the study, the same parameters were evaluated with repeat dosing of RT-102 at 20 micrograms for up to seven days. In part one, 15 subjects received RT-102 at a dose of 20 micrograms, while 14 subjects received RT-102 at a dose of 80 micrograms.
Speaker 5: A control group of 10 participants received a single 20 microgram subcutaneous injection of Fotao, which is the commercial formulation of teriparatide approved for subcutaneous administration.etic Femoralbus
Talat Imran: RT10, containing an adalamamab biosimilar, RT110, containing PTH for hypoparthyroidism, and RT11, containing Celtrion's Oostokinamab biosim. With that, let me now turn the call over to Mir Hashim to discuss our preclinical and clinical updates in more detail.
Speaker 5: RT-102 was well tolerated in both those groups and delivered PTH with bioavailability estimated to be up to 3-4 fold higher than that of subcutaneous photovoltaic.
Speaker 5: There were no serious adverse events reported in the study at any dose.
Mia Hesha: Thank you, Talat, and thank you everyone for joining us. Let me begin by highlighting some of the updates we have provided for RT1 or 2, which is being developed for the treatment of osteoporosis. RT102 is the Rani pill capsule containing PTH-134, also known as Teriparotide. As you all know, we initiated a phase one clinical study of RT 102 in Australia in March of 2022 and released top line data for part one of the study in August and part two of the study in December.
Speaker 5: Now in part two of the study, 10 healthy female volunteers, five of whom were postmenopausal, received RT-102 training micrograms once daily for seven consecutive days.
Speaker 5: On the seventh day, complete pharmacokinetic profiles of RT-102 were obtained for each subject.
Speaker 5: 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 event related to the radical capsule.
Speaker 5: The bioavailability of RT-102 was high relative to subcutaneous forteo, again confirming the data from part one of the study.
Mia Hesha: In part one of the study, we evaluated the safety, tolerability, reliability, and pharmacokinetics of RT102 in healthy adult female volunteers at a single dose of either 20 micrograms or 80%. In part two of the study, the same parameters were evaluated with repeat dosing of Part E102 at 20 micrograms for up to 7. In part one, 15 subjects received RT1 or 2 at a dose of 20 micrograms, while 14 subjects received R310.2 at a dose of 80 micrograms.
Speaker 5: And importantly, as Talat indicated earlier, the overall reliability or success rate of R2D was 92%.
Speaker 5: Additionally, we were also pleased to have received preliminary feedback and guidance from the FDA on our RT-102 development plans.
Speaker 5: 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. Beyond the RT-102 program, we are excited about the progress we have made so far, and we believe that the safety, reliability, and pharmacokinetic data that we have made so far, and we believe that the safety, reliability, and pharmacokinetic data that we have made
Mia Hesha: A control group of 10 participants received a single 20 microgram subcutaneous injection of Foteo, which is the commercial formulation of Therparatide approved for subcutaneous administration. RT1 or 2 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 forte. There were no serious adverse events reported in the study at any dose.
Speaker 5: has the potential to make a real difference for patients by providing them with an oral alternative to the current injectable standard of care.
Speaker 5: Overall, we are delighted with the ongoing clinical and preclinical development of our pipeline programs. The advancements in our core programs reiterate our commitment to delivering the Rani pill capsule as an effective oral alternative that could change the treatment paradigm for the millions of patients currently taking injections.
Mia Hesha: Now, in part two 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 RT1 or two were obtained for each subject. We again observed that RT1 or 2 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 event related to Rani. The bioavailability of RT1 or 2 was high relative to subcutaneous foetero again, confirming the data from part one of the study.
Speaker 5: for their chronic disease conditions. Now I will turn it over to Swai to go over the financial results of the fourth quarter and year in 2022.
Speaker 6: Bye.
Speaker 3: Bye. Thank you, Hashim. Good afternoon, everyone.
Speaker 3: In addition to the financial results summarized in our press release that was issued earlier today,
Speaker 3: I will briefly share some key financial highlights on this call.
Speaker 3: You can also find additional information on our Form 10-K for the year ended December 31, 2021.
Speaker 3: on our Form 10-K for the year ended December 31, 2022.
Speaker 3: Cash, cash equivalent and marketable security as of December 31, 2022, total of $98.5 million.
Speaker 3: compared to 117.5 million as of December 31.
Speaker 3: 2021. Without additional financing, we expect the current cash, cash equivalent, and marketable security to sufficiently fund our operation to mid-2024.
Speaker 7: Research and development expenses for the fourth quarter and full year 2022 were $10.4 million and $36.6 million respectively.
Speaker 7: compared to 7.4 million and 26.5 million for the same period in 2021, respectively.
Speaker 7: General and administrative expenses for the three months and 12 months ended December 31, 2022.
Speaker 7: were 7.1 million and 26.8 million respectively, compared to 5.9 million and 27.8 million for the same period in 2021.
Speaker 7: respectively. Lastly, our net loss for the fourth quarter and full year 2022 was 17.3 million.
Mia Hesha: And importantly, as TELAT indicated earlier, the overall reliability or success rate of RT102 delivery was 902, Additionally, we were also pleased to have received preliminary feedback and guidance from the FDA on our RT102 development plans. Overall, for RT102, 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 one study support the initiation of a phase two trial of RT 102 in osteoporosis, which we anticipate beginning in the second half.
Speaker 7: and 63.3 million respectively.
Speaker 7: compared to 13.3 million and 53.1 million.
Speaker 7: for the same period in 2021 respectively.
Speaker 7: Excluding non-cash charges, primarily equity-based compensation expense,
Speaker 7: The non-GAAP net loss was $13.3 million for the fourth quarter.
Speaker 7: and $47.8 million for the full year 2022.
Speaker 7: compared to 10 million and 28.8 million for the same period in 2021 respectively.
Speaker 7: This concludes my remark on the financial results.
Speaker 7: And I will now turn the call back over to Talhag for closing comments.
Speaker 7: turn the call back over to Talat for closing comments. Talat?
Speaker 4: Thank you, Subbai.
Speaker 4: In closing, we are very pleased with our progress so far and look forward to maintaining our momentum in 2023.
Speaker 4: 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.
Speaker 4: 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 all of our members for their support.
Mia Hesha: Now, beyond the RT 102 program, we are also pleased with our ongoing progress in the development of RT11, a rani pill capsule containing Ostenemab biosimilar for the treatment of inflammatory conditions, and we look forward to the initiation of a phase one study for RT11 later this year. We believe that RT11 has the potential to make a real difference for patients by providing them with an oral alternative to the current injectable standard of care.
Mia Hesha: Overall, we are delighted with the ongoing clinical and preclinical development of our pipeline program. The advancements in our core programs reiterate our commitment to delivering the Rani pill 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 Sway to go over the financial reserves for the fourth quarter and year in 2020. Bye.
Speaker 8: questions.
Speaker 9: Operator.
Speaker 6: Thank you.
Speaker 2: Ladies and gentlemen, to ask the question, please press star 11 on your telephone.
Speaker 2: You will then hear an automated message advising your hand is raised and then wait for your name to be announced.
Speaker 2: As a reminder, please limit yourself to one question and one follow-up.
Speaker 2: To withdraw your question, please first start 1-1 again.
Speaker 2: Please stand by while we compile the Q&A roster. Our first question comes from the line of Brandon, folks, with cancer. Your line is open.
Spice Sanford: Good afternoon, everyone. In addition to the financial results, which summarize a 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 10K for the year ended December 31, 2020. Cash inequivalent and marketable security as of December 31, 2022 total 98.5 million, compared to 117.5 million as of December 31, 2021. Without additional financing, we expect the current cash, cash equivalence, and marketable security to sufficiently fund our operations to mid-2020.
Speaker 3: All right, 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 Rainpool device in light of the 505d2 pathway?
Speaker 4: I'll stop there 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.
Speaker 4: over eight weeks. It turns out that in this phase two we will reach thereabouts or maybe a little bit higher. So, you know, 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.
Spice Sanford: 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. General and Administrative Expenses for the three months and 12 months ended December 31, 2022, or 7.1 million and 26.8 million respectively compared to 5.9 million and 27.8 million for the same period in 2021, with respect 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.
Speaker 3: 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 that RT-111, is that just going to be a normal Phase 1 trial or any nuances we should pay attention to there, just given that you have to consider?
Speaker 4: 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.
Spice Sanford: Excluding non-cash chargers, primarily equity-based compensation expense, the non-gap 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. This concludes my remarks on the financial results, and I will now turn the call back over to Talad for closing comments. Talat?
Speaker 4: But I think we've gotten relatively good at putting these together and conducting them. And I guess one last point around the celtreon 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 one and into the option period.
Speaker 3: Great, I look forward to seeing that data and again congrats on all the progress over the last 12-13 months. Thank you so much.
Speaker 2: Thank you. Please stand by for our next question. Our next question comes from the line of Jeff Meacham with Bank of America. Your line is open.
Speaker 3: Good afternoon. This is how calling info just mentioned and thank you for the question. So I think maybe go back to the R2-R2 multiple dose trial. I think you have the cell delivery for most patients happen in day one and day two.
Talat Imran: In closing, we are very pleased with our progress so far and look forward to maintaining our momentum in 2020. From a clinical perspective, 2023 is really going to be a year of execution for Ronnie, and we believe that the potential milestones I've laid out could be transformative for our company. We look forward to initiating our Phase 2 clinical trial in RT 102 in the second half of 2023, our first Phase 2 trial, as well as initiating three additional Phase 1 studies with Pipeline molecules, RT10, and RT11.
Speaker 4: 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.
Talat Imran: We have built a world-class leadership team at Ronnie, and I would like to thank everyone at the company for their efforts this past year and so far in 2020. 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 a call for questions. Operator. Thank you.
Speaker 4: 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. 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 there were more at the beginning.
Operator: Ladies and gentlemen, to ask the question, please press Star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. And then wait for your name to be called now.
Speaker 4: But we don't think it was anything more than just random chance.
Operator: As a reminder, please limit yourself to one question and one follow-up. To withdraw your question, please first start it again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Brendan, folks with cancer. 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 met with the FDA, did they provide any color in terms of the safety database that may be required for the Renneport device in light of the 505 pathway? I'll stop by name and ask the colonel. Sure.
Speaker 3: Great. Just a quick follow up. So, the Phase 2 expected by second and a half, what exactly needs to happen before the Phase 2 can be initiated?
Speaker 4: 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 two started, as you said, in the second half of 23.
Speaker 3: Okay, makes sense. Thank you. Yeah, absolutely.
Speaker 2: Thank you. Please stand by for our next question.
Speaker 2: Our next question comes from the line of Wedbush. Andrea, your line is open.
Talat Imran: 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 eight weeks. It turns out that in phase two, we will reach thereabouts or maybe a little bit higher. So, you know, I think we're hopefully going to be answering that question for them as well, but we've decided to do it essentially concurrently with the data that we're generating around the efficacy and biomarkers with the RT102 program.
Speaker 3: Thanks for taking our questions here. So just two for us here. So how does the Celtreon deal in the right of first negotiation indicate what the strategy would be for the company in the pipeline of biosimilars going forward? And then secondly, is the Celtreon deal indication specific?
Speaker 4: 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 indication specific. It's for oostakinumab, biosimilar or oostakinumab in general. So it's that entire drug, if you will.
Speaker 4: and any indications you could pursue with it. So CD, ulcerative colitis, or psoriasis.
Speaker 4: In terms of what the relationship with Celtreon implies, I think from our perspective, it implies that what we're doing is valuable and there's an interest in supporting us both in the clinical and commercial development from Celtreon, but also potentially
Talat Imran: Great, thanks. And then maybe just a follow-up to that. How should we think about the size of the phase one trial that you're running in 2023, and then similarly on the RT1 or two phase two trials? And then maybe just focusing on that RT-1-1. Is that just going to be a normal phase one trial, or are there any nuances we should pay attention to there, just given the sole TRI-on option post that? Thank you. Sure.
Speaker 4: 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.
Talat Imran: Thank you. Sure.
Talat Imran: So they will look very similar to the single dose portion of the RT1 or phase one. So it'll 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 RT11 at 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.
Speaker 4: enable us to compete against them as opposed to working with us. Great, thanks and that's all progress. Thanks. Thank you.
Speaker 3: them as opposed to working with us. Okay, great. Thanks and congrats on all the progress. Thanks. Thank you. Thank you.
Speaker 2: Please stand by for our next question.
Speaker 2: Our next question comes from the line of Annabelle Samimi with CIFIL. Your line is open. Your line is open.
Speaker 10: Hi, thanks for taking my question. Thanks for the progress. So on the Celtreon partnership again, are there any key requirements or metrics that Celtreon is looking for as far as the Celtreon is concerned like they're saying bioavailability or delivery success and do
Talat Imran: 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 in And I guess one last point, yeah, around the Seltreon relationship, I think the expectation is that similar data to what we generated with R2 should be sufficient to get us completed with phase one and then to the option.
Speaker 10: to repeat dosing for that trial before you offer it up for an option or right of first negotiation.
Speaker 10: And then secondly, any further discussion with FDA regarding the design of the phase two trial for 102? I think you're contemplating three different doses. Do you have a sense of what the
Speaker 4: the dosing range, the time frame, how large it could be, etc., or was this primarily about a 505b2 pathway? Sure. So we should not need to do repeat dosing to complete the phase one. It's a single dose study with probably half a meg and three quarters of a meg.
Talat Imran: Great, I look forward to seeing that data. And again, congratulations on all the progress over the last 12 to 18 months. Thank you so much. Thank you. Our next question comes from the line of Jeff Meacham with Bank of America. Your line is open.
Operator: Good afternoon, and this is Jeff Mitchin calling in on behalf of Jeff Mitchin, and thank you for the question. So I think maybe we should go back to the R2, multiple dose trial. I think you have the self-delivery for most of the patients happen on day one and day two. So I just want to double check if then any interventions happen once a patient missed or had a failed delivery. I'm joining that setup.
Speaker 4: that's what everyone's 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 Celtreon as we get into the...
Talat Imran: Hi How, and to answer your question, no, there was no intervention, and we don't expect there to be any. There will be some misdoses, but we manage that through, in the case of RT1 or two, 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 monocole antibodies, misdiscope. There will be a wash because of the long half-life of the drug.
Speaker 4: into the option period. As far as the RT-102 phase 2 design is concerned, we did ask the FDA
Speaker 4: what they would want to see in terms of endpoints. And we're going to be looking at biomarkers. So P1NP and CTX.
Speaker 4: and the duration is likely going to be eight weeks. You can see separation on those biomarkers fairly rapidly and then from there we would start planning for a phase three where we would likely be looking at BMD at the end point.
Talat Imran: And in terms of when they happened, it was completely random. I think the point is that there were so few failures in that study that you can kind of look at it and say that maybe there were more at the beginning, but we don't think it was anything more than just random chance.
Speaker 10: Okay, great. Thank you so much.
Speaker 11: Thank you so much. Thank you, Annabel. Thank you.
Speaker 2: Thank you. Please stand by for our next question. Our next question comes from the line of Ash Burrema with UBS. Your line is open.
Talat Imran: Great. Just for a quick follow-up. So the phase two expected by a second and a half, what exactly needs to happen before phase two can be initiated? Sure.
Speaker 12: Hi, thanks for taking our questions. Congrats on the progress so far. I have to so what was this just on these phase 1 studies that you're planning right in point 23. So single single dose study, we should be relatively quick. I would imagine like what kind of timeline do you think we can.
Talat Imran: 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 two started, as you said, in the second half of 23.
Operator: Okay, that makes sense. Thank you. Yeah, absolutely. Thank you.
Operator: Please stand by for our next question. Our next question comes from the line of Wedbush and Dres. Your line is open. All right, hey guys, thanks for taking our questions here. So just two for us here.
Speaker 12: in 2023 versus 2022.
Speaker 13: is 2022. Thanks.
Speaker 4: Thank you, Ash. Appreciate the questions. You are correct. The timeline for these phase ones is relatively short. It's a matter of months to get them done. I will say the RT-111 one will take a bit longer than RT-102 single dose just because the half-life of that drug is significantly longer.
Operator: So how does the Seltrean deal in the right of first negotiation indicate what the strategy would be for the company in the pipeline of biosimilers going forward? And then, secondly, is the Seltriand deal indication specific, and could you still partner out RT11 for a different indication? Sure. I'll take the
Speaker 4: 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. So we're hoping and hope is not a plan, but with COVID not being as much of an issue as early last year, that if recruitment is fairly straightforward, this is a healthy volunteer study.
Talat Imran: Sure, I'll take the second one first. It's a short answer. No, it is not indication specific. It's for usokinomab biosimilar or usokinamad in general. So it's that entire drug, if you will, and any indications you could pursue with it. So CD, you also, have a condition called alterative colitis or psorias.
Speaker 4: that we should be able to enroll fairly quickly and that'll help with getting it done quickly as well. And we all are incentivized to do so.
Talat Imran: In terms of what the relationship with Celtrion implies, I think from our perspective, it implies that what we're doing is valuable, and there's an interest in supporting us both in the clinical and commercial development of Celtrion's product, 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.
Speaker 4: So with your second question, I'm going to turn that over to Savaih Sanford, our CFO , to answer.
Speaker 7: Thank you, Talat. Hopefully everyone can hear me. Ash, thank you for the question.
Speaker 7: We ended, as you can see in our filing, we ended the 2022 with the non-
Speaker 7: 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.
Operator: Okay, great. Thank you. That's all progress. Thank you. Thank you. Please stand by for our next question. Our next question comes from the line of Annabelle Samimi with Cefil. Your line is open.
Speaker 14: Thanks guys.
Speaker 2: Thank you. Thank you. Please stand by for our next question.
Speaker 2: Our next question comes from the line of Burt Hazelet with BTIG. Your line is open. Your line is open.
Operator: Hi, thanks for taking my question, thanks for giving me the progress. So on the Celtrane partnership again, are there any key requirements or metrics that Celtrane is looking for as far as phase one is concerned, like dosing bioavailability or delivery success? dosing for that trial before you offered up for an option or right of And then secondly, any further discussion with FDA regarding the design, trial for 102. I think you're contemplating three 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 505B2 path? Sure. So we should not need to
Speaker 15: Yes, thank you. Thank you for taking the question and congratulations on all the progress. Two topics in general. One is Celsius and as you think about the development of RT-111 CTP-43, is there a prioritization with regard to indication with the development of that program or how are you thinking about steps beyond phase one?
Speaker 15: Then second question is kind of a similar question with regard to prioritization of the monoclonals that you've mentioned, whether that's timbrelizumab, trastuzumab, or others. How are you thinking about maybe prioritization of those types of molecules? Just general thoughts there would be helpful. Thank you.
Talat Imran: Sure. So we should not need to do repeat dosing to complete phase one. It's a single dose study and with, you know, probably half a meg and three quarters of the meg as the doses that we use for the RT11 program for phase one. There's nothing in particular beyond showing that the bioavailability is similar to a subcutaneous injection of their CTP-43 or sykinomab biosimilar. I think that's what everyone's been looking for, and what we would like to demonstrate as well.
Speaker 4: 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.
Talat Imran: 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 monocole antibody. So this is a big milestone for the company, and I think hopefully that's sufficient to garner interest from Seltriand as we get into the option. As far as the RT 102 phase two design is concerned, we did ask the FDA what they would want to see in terms of endpoints.
Speaker 4: So can't provide guidance around that at this moment in time, but we have time. The phase one 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 RoniPill 8C, immunology I think as a general area is right in the middle of the year.
Talat Imran: And we're going to be looking at biomarkers, so P1NP and CTX, and the duration is likely going to be eight weeks. You can see separation on those biomarkers fairly rapidly. And then from there, we would start planning for phase three, where we would likely be looking at BMD at the end.
Speaker 4: 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.
Operator: Thank you. Please stand by for our next question. Our next question comes from the line of Ash Burma with UBS. Your line is open.
Operator: Hi, thanks for taking our questions. Congratulations on the progress so far. I have two.
Operator: So one was just on these phase one studies that you're planning right in 2023. So single dose studies, 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 OPEC, given that you can, you plan to initiate phase two for RT102 in the second half here. How would OPEX compare in 23 versus 2022?
Speaker 4: So we would want to look at that with oncology, whether it's as a standalone or as a maintenance to one of the popular oncology drugs like Pembro or Nebo.
Speaker 4: 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 Ronny recruited
Speaker 4: 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 RonipilĀ® AC. Thanks for the color, appreciate it. Yeah, absolutely. Thank you.
Speaker 2: Thank you. Please stand by for our next question. Our last question comes from the line of Mitchell Kapoor with HC Wainwright. Your line is open. Hi, team. Hope everyone is well and thanks for taking the questions.
Talat Imran: That is. Thank you, Ash. I appreciate the questions.
Speaker 15: I wanted to start out with RT-102, and I wanted to understand more about the PK profile in terms of, 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 the PK look slightly different.
Talat Imran: You are correct. The timeline for these phase ones is relatively short. It's a matter of months to get them done. I will say the RT11 one will take a bit longer than the 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 this isn't on 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, we should be able to enroll fairly quickly, and that will help with getting it done quickly as well. And we all are incentivized. With your second question, I'm going to turn that over to survive Sanford or CFO.
Speaker 4: 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 Annabelle's questions. So 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.
Spice Sanford: Thank you, Talad. Hopefully, everyone can hear me. Ash, thank you for the question. We ended, as you can see in our filing, we ended 2022 with the non-cash portion of the OPX just under 50 million. I expect that our operating expenses will increase for 2023 in the range of 20 to 30% from last year.
Speaker 4: or significantly better bone growth. I would caution that we had a lower AE incidence in our single dose and even in our multi-dose. Well, we didn't compare in the multi-dose, but compared to even the 80 microgram Ronnie oral versus the 20 microgram Porteo in the single dose.
Speaker 4: it looked cleaner from an AE perspective. We need to conduct that study in the phase two 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.
Spice Sanford: Great. Thanks, guys. Thank you.
Operator: Thank you. Please stand by for our next question. Our next question comes from the line of Bert Hazlitt 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 Celts, John.
Speaker 4: 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?
Operator: And as you think about the development of
Operator: of RT-11-CTP-43, 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 one? Then, second, is kind of a similar question with regard to prioritization of the monoconals that you've mentioned, whether that's Pembralizumab, Tresutuzumab, or others. How are you thinking about maybe prioritizing those types of molecules? Just general thoughts there would be helpful.
Speaker 4: 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 roadmap for phase one. And that same approach is what we're going to be working on this year with our RT-110.
Operator: Thank you.
Talat Imran: Sure. So it's a great question, Burke.
Talat Imran: First off, thank you for the questions. In terms of our RT11 and CTP 43, we are in discussions with Celtrion right now to figure out how to prioritize. It would either be psoriasis or Crohn's disease, I would imagine.
Speaker 16: Thank you.
Speaker 6: Thank you.
Speaker 2: I'm sure no further questions in the queue. I would now like to turn the call back to Tlaas for closing remarks.
Talat Imran: 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 So I can't provide guidance around that at this moment in time, but we have time. The phase one study is a healthy volunteer study. So we'll take this year to kind of coalesce around the plan, and we'll share that early. In terms of what we're planning to do with the Ronnie Pill 8C, immunology, I think, as a general area, is right in the sweet spot for what we're doing.
Speaker 4: Thank you, operator. This concludes our fourth quarter and full year 2022 financial results and corporate update conference call.
Speaker 2: 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.
Talat Imran: Chronic diseases, crowded categories where differentiation to oral with a monocolon antibody could be tremendous. After that, we are looking at the delivery of antisense oligonucleotides and SIRN.A; 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 about whether daily administration and increasing serum C trough levels, if you will, improves the efficacy of a monocole antibody. There's some evidence of that with certain drugs in the past.
Talat Imran: So we would want to look at that with oncology, whether it's as a standalone or as maintenance therapy to one of the popular oncology drugs like Pembro or 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 Ronnie Pilly. Thanks for the color. I appreciate it.
Operator: Thanks for the color. I appreciate it. Yeah, absolutely.
Operator: Thank you. Please stand by for our next question. Our last question comes from the line of Mitchell Kapoor, which is H.C. Wayne Wright. Hi, team. I hope everyone's well, and thanks for taking the questions. I wanted to start out with RT 102, and I wanted to understand more about the PK profile in terms
Operator: Do you think you've established a margin?
Operator: 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
Operator: PK looks slightly different in the next trials but will still be
Operator: and still be considered positive.
Talat Imran: Sure. So thank you for the question, Mitchell, and I realize in asking that you that I failed to answer one of Annabel's questions. So I'll do both in the same shot.
Talat Imran: 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 incidence in our single dose and even in our multiple. dose, well, we didn't compare it in the multidose, but compared to even the 80-micogram rani oral versus the 20 microgram forte in the single dose, it looked cleaner from an AE perspective.
Talat Imran: We need to conduct that study in phase two or look at the AE rates, I should say. But through 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 Fortale currently.
Talat Imran: 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 on that program or what the plan could be going forward? Sure.
Talat Imran: Sure. As I mentioned in the past, we're working on a sustained release formulation. This is the technology that's going into our RT110 PTH for hypoparthiroidism program. We have made considerable progress, which is why it's on our roadmap for phase one. 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 something like sandostatin LAR. So nothing to report at this moment in time, but I think that's something that we'll revisit later this year.
Talat Imran: 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 Tula for closing remarks.
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 Zem, this concludes today's conference call.
Operator: Ladies and Zem, this concludes today's conference call. Thank you for your participation. You may now disconnect.
Speaker 1: I have.
Operator: and and Thank you The, Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you and Theeus.