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

Welcome to the Rani Therapeutics RT-102 Phase I Part 2 repeat-dose study conference call. [Operator Instructions]. As a reminder, this call is being recorded today. Tuesday, December 6, 2022. I would now like to turn the conference call over to Laurence Watts, Managing Director at Gilmartin Group.

Thank you, operator. Joining us on the call today from Rani Therapeutics are Chief Executive Officer, Talat Imran; Chief Financial Officer; Svai Sanford, Chief Scientific Officer; Dr. Mir Hashim; and Vice President of Clinical Development, Dr. Arvinder Dhalla. Please turn to Slide 2. During the conference call, management will make forward-looking statements that are subject to risks and uncertainties related to the future events and/or financial performance of the company. These forward-looking statements are subject to a number of 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 results or events to differ materially from those described in these forward-looking statements. These factors may include, without limitation, statements regarding product development and clinical trials, product potential, the regulatory environment, 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 Therapeutics. Talat.

Thank you, Laurence. Please turn to Slide 3. Good afternoon, everyone. We're very excited to share Part 2 data from our RT-102 Phase I study. Recall, this is a 7-day repeat-dose study in healthy volunteers. In addition, this was the first repeat-dose experience in humans, and we collected promising data on the safety, tolerability and and reliability of the RaniPill platform as well as initial data on whether food has any effect on the performance of the device. In short, I'm very pleased with the outcome of the study and the implications not only for the RT-102 program and the Phase II plan for 2023, but also for the potential of the RaniPill platform in general. So with that, I'm going to get into the details of the RT-102 Phase I study. Please turn to Slide 4. This was a Phase I study to evaluate the safety tolerability and pharmacokinetics of RT-102, which is the RaniPill pill capsule containing our proprietary parathyroid hormone 1-34 analog or PTH. In Part 1 of the study, we tested single doses delivered by RaniPill using 2 different dose levels, 20 micrograms and 80 micrograms compared to a control group of 20 micrograms of Forteo or teriparatide delivered subcutaneously. In Part 2 of the study, we tested once daily dosing of 20 micrograms of RT-102 delivered via the RaniPill for 7 consecutive days. Please turn to Slide 5. Just to summarize the previously announced Part 1 top line results, both doses of RT-102 delivered by the RaniPill were well tolerated. There were no SAEs reported in the study and there were no AEs related to the RaniPill. We were able to show improved device performance compared to the octreotide Phase I study we ran in 2019, achieving a 95% success rate in the Part 1 portion of the study. Furthermore, RT-102 delivered PTH with 300% to 400% higher bioavailability for 20 micrograms and 80 micrograms of PTH, respectively, compared to 20 micrograms of Forteo delivered via subcutaneous injection. So with that, I'm going to hand it over to Dr. Arvinder Dhalla, our Vice President of Clinical Development, to walk you through the Part 2 results. Arvinder?

Thank you, Talat. Good afternoon, everyone. Please turn to Slide 7. The Part 2 of the Phase I RT-102 study was designed to evaluate the safety and tolerability of repeat doses of PTH delivered via the RaniPill capsule. The study population consisted of healthy women and postmenopausal women who received 20-microgram dose of RT-102 daily for 7 days. Further to safety, the other important end point of this study was to determine the reliability of RaniPill capsule delivering PTH to participants in the study. Please turn to Slide 8. I would like to begin by briefly going over the study procedures, which are outlined on this slide to help convey how the data was collected throughout the study. For days 1-6 of the study, all participants were fasted overnight and had a blood sample taken and then the participant was dosed with RT-102. Subsequently, there were 3 additional blood samples taken at 3-hour interval. Following the first 3-hour interval, participants were given food. Between hour 6 and 9, a fluoroscopic image was taken of the participant to determine the status of RaniPill. We were essentially looking to see if RaniPill capsule had deployed and where it was in the GR system. On the seventh and final day, participants were dosed after an overnight fast and serial fluoro imaging was conducted to determine the exact time of RaniPill deployment. This time point was considered to be time 0 and serial PK sampling was started after that. Please turn to Slide 10. Shown here are the demographics of the 10 participants who completed the 7-day repeat-dose study. As you can see, we had an equal number of participants in the 2 groups of 5 healthy women as well as 5 postmenopausal women. As you would expect, the age of the postmenopausal group was higher than the healthy women group. However, the weight and BMI were similar between the 2 subgroups. Please turn to Slide 11. There were 17 subjects enrolled in the study, 10 of which completed the 7-day repeat-dose protocol. Listed on this slide are the exclusion criteria for those who did not complete the 7-day repeat-dose protocol. Please note that these exclusions were due to predefined protocol exclusion criteria and not due to any adverse events related to RT-102, and none of the participants stopped dosing due to any adverse events related to the RaniPill capsule. Please turn to Slide 12. In fact, we are delighted with the overall safety and tolerability of RT-102 seen through our repeat-dose study. There were no serious adverse events reported in the study. As you can see, there were just a few adverse events, which were deemed mild to moderate and resolved on their own. With these data, we have now dosed 98 subjects with RaniPill across 2 clinical studies, and we have not observed any serious safety concerns related to the platform technology. Please turn to Slide 13. Another endpoint for the study was device performance or reliability with repeat doses of RT-102. Here, we are showing the data on drug delivery by the RaniPill through the 7-day study. A green color box and a checkmark indicate that there was a successful drug delivery for that particular subject on that specific day. A red color box and an X indicates that the drug was not detected on that date. In the 10 participants who completed the 7-day study, there were 69 confirmed device deployments within the observation window. Out of the 69 deployment, 63 successfully delivered drugs, resulting in a 91% successful success rate of drug delivery. And this corroborates the device performance data obtained in Part 1 of the Phase I study of RT-102 that was announced in August of this year. Please turn to Slide 14. While we did not design the study to evaluate the effect of food on the performance of RaniPill in this study, we were able to obtain additional insight into the effect of food or [indiscernible] because the participants are fed at the 3-hour mark following dosing. In approximately half of the cases, RaniPill has already deployed and delivered the drug to the participants prior to their fluid intake. On days 1-6, there were a total of 72 successful deployments and 35 of those deployments were seen under fasting conditions while the other 37 were observed after the intake of food. As a note, we were able to track these through detecting PTH levels in the blood samples obtained before and after providing food. Data from day 7 is not included here because participants were kept fasted on that day to obtain complete PK profile. Ultimately, these data suggest that presence of food does not affect performance of RaniPill. And this result is expected and corroborates Rani's very first clinical study that was conducted without a drug which also showed that the device performance was not altered by the presence of food. Please turn to Slide 15. Here, you will find the complete PK profile for RT-102 on the seventh day of repeat dose study following serial imaging. We're pleased to report that drug levels were detected in all 10 subjects, resulting in a 100% success rate of drug delivery by RT-102 on day 7. Plotted here are the main drug concentrations of PTH delivered via RT-102 through the 16-hour window. Also shown for comparison is the PK profile for subcutaneous injection of Forteo that was obtained in Part 1 of the study, which is presented in August. RT-102 yielded a Cmax that is similar to Forteo but demonstrated a much higher bioavailability as was the case in Part 1 of the study. Please turn to Slide 16. To summarize, what we have shown is that repeat doses of RT-102 are well tolerated with no serious adverse events observed during the study. All subjects were able to pass device remnants without any issues. RaniPill continues to perform well with a greater than 90% reliability of drug delivery which is seen with RT-102. Finally, we observed the high bioavailability with RT-102 compared to the subcu injection of Forteo, similar to what was seen in Part 1. Now I will turn the call back over to Talat for next steps and closing comments. Talat?

Thank you, Arvinder. Please turn to Slide 18. We are very pleased by the results of the RT-102 Phase I study. As we look ahead, we have already requested a pre-IND meeting with the FDA regarding RT-102, which will further inform our development of the program. Based on prior interaction, we anticipate conducting a 28-day GLP study and has begun preparing for such in early 2023. The data from the GLP study are to support the initiation of a Phase II study in the second half of 2023. Additionally, we plan to publish and present these exciting data from the RT-102 Phase I study in upcoming conferences in the near future. Regarding our other programs, let me remind you that we have multiple additional prospective miles films in 2023, including initiating a Phase I study of RT-111 containing an ustekinumab biosimilar, initiating Phase I study of RT-105 containing an adalimumab biosimilar and initiating a Phase I study of RT-110 containing a sustained release formulation of PTH for hypoparathyroidism. With that, I will now open up the call for questions. Operator?

[Operator Instructions] And today's first question of Hao Shen with Bank of America.

This is Hao calling in for Geoff Meacham from Bank of America. Congratulations on the data. So I think my first question would be really if you can provide maybe any additional color on that abdominal pain patient looks like this. Two, if you consider all your patients -- participants and maybe one, if you consider those 10 who completed the 7 days dose. So any color you can provide on that?

Yes, absolutely. Thank you,. I'm going to turn this over to Arvinder Dhalla to answer. Arvinder, please take it away.

Yes. Thank you for the question. The abdominal pain that we observed was mild and transient and happened intermittently in that subject and resolved on its own. So there were no serious consequences of that.

Yes, the pain scores are all between 1 and 3.

Yes, 1 and...

Yes. Pardon me, Arvinder go ahead.

No, please continue.

No. So I think this is the first indications we've had of anyone having any sensation but we're now almost 100 subjects and only 2 subjects expressing any issues. I think one thing of note, when we conduct our Phase II study, we'll have a controlled placebo group that take potato starch pills, mark RaniPills because there's a potential when you're dosing for 12 weeks or more that any individual is going to have some GI distress at some point or another, constipation, diarrhea, abdominal cramps and the like. So to be able to weed this out, we'll have a control arm going forward.

Okay. Great. And just a quick follow-up. So regarding to the success rate, is 90% the bar or based on your conversational feedback from FDA, what is really sort of maybe the bar for the success rate?

Yes. Great question. So the FDA has not set any bar for us. In our initial conversations around the platform technology, there was a dialogue around tracking the reliability rate, which you've seen that we've done. But I think the context I can provide is, for those who are familiar with Novo Nordisk oral semaglutide sold under the brand name Rybelsus. In their Phase I study, their best-performing cohort, I believe, had a 67% success rate. That's a commercial product. It's an FDA-approved product. So you don't have to take my word for it, so to speak. The regulators care about efficacy ultimately. So are we meeting the clinical endpoints in the subsequent studies is the thing that's going to matter not a specific reliability rate. Having said that, we are absolutely thrilled with this data. This is an incredibly reliable device it seems from the single dose and now the repeat-dose data that we've generated. It's consistent, it seems to work. We had no subjects where they received no drug over that period of time. So it seems consistent across the group and consistent even within a patient. So this bodes well not only for this program, but as we look ahead into 2023, and we have monoclonal antibodies that are currently infrequently dosed by injection turning those into a daily oral could potentially make those products, I don't want to say better, but more consistent in the serum concentration even with a failure rate of 5% or 10%.

One moment for our next question, that will come from the line of Brandon Folkes with Cantor Fitzgerald.

Congratulations on the data. The two from me, maybe just staying on the device deployment, the Slide 13, there. Any color on subject 8, who had the 2 non-deployment, I guess, just any characteristics of that patient worth noting at this stage? And then secondly, just some of the deployment failures, I guess we're early on day 1 or 2 versus the rest of the day. Granted it's a small sample size. So -- but is there any biological reason for that or just sort of coincidence at this stage?

So Brandon, great to hear from you, and thank you for the 2 questions. The short answer is no to both questions. It is coincidental. We don't see anything in the data to support that the 2 -- the ends were small here in terms of the number of days. So the difference between 1 and 2 failures is not that material. And the fact that they happened earlier or later, again, we can't draw any conclusions from that. It seems like it's more likely just a manufacturing defect. We've brought those down dramatically from our 2019 Phase I. You can see how well the device works now, but there's always going to be a few edge cases where maybe a device doesn't deploy or doesn't get to sufficient pressure or whatever.

One moment for our next question, and that will come from Andreas Argyrides with Wedbush Securities.

Congrats on the progress. On Slide 14, just a little bit of clarity. So you had 35 successful deployments that occurred before 3 hours and then 37 deployments occurred after 3 hours. Can you just clarify if it took the food to be delivered for the 37 deployments after 3 hours?

Could you repeat that last part, Andreas, Sorry.

Yes. Could you just clarify if it took the food to be delivered for the 37 deployment after the 3 hours.

So what this slide is saying is that at 3 hours, the subjects were given food, and we tracked 37 successes thereafter. So we know that there was food in their system. We can't come to any other conclusions than that, right, where the food was, where the capsule was, because the fluoro wasn't done for several more hours thereafter. But what you can take away from it is there were as many successes before the administration of food as they were afterward. This is our first foray into a food effect study, but this is incredibly promising to see that it seems to have no effect on the success rate.

Okay. And another way of just asking it is it didn't take up to 9 hours for some of the pills to be delivered, right?

No, no, no. This was just looking at before that time point because we were taking a blood sample at the hour 3. So we're just looking at what happened before or after. So we didn't take a lot of blood samples here. It's at 3 hours, 6 hours, 9 hours. So if we saw a success at 6 or if we saw a signal, I should say, at 6 or 9 hours, then it was scored as a success, obviously, and then not attributed but put into the category of post administration of food.

Congrats on the results.

One moment for our next question, that will come from the line of Bert Hazlett with BTIG.

Thanks and add my congratulations to the rest of the group as well. Just a couple of questions, I guess, on Slide 15. First, the -- is it fair to say -- maybe you said it in the remarks. But is it fair to say that the PK on days 1-6 matched day 7 that shows on the slide for RT-102.

So great question and hi Bert. We did not take full PK on days 1-6 because if you recall from even our Phase I Part 1 experience, we have to do a considerable amount of fluoro to find time 0 and then take blood samples thereafter. That's not really feasible when you're doing -- when you're dosing over multiple days. So we just took 6 samples at 0, 3, 6 and 9 hours. So we can't really compare it to that. There was no PK -- full PK curve. There was the only 1 that's on day 7.

Okay. That's helpful. It's certainly a nice one. But just kind of a follow-up question. How does this make you think about dosing as you move into Phase II? I think at some point, you've talked about higher doses. Now you're talking about potential lower doses. I'd love to hear you elaborate on your thinking with regard to dose as you move forward?

Yes. So we've -- thank you for that question. as well. We tested obviously in the Part 1 an 80-microgram dose, and it was well tolerated. It actually had a lower adverse event rate than the 20 micrograms subcu. But as we look ahead, we'll likely go with -- we'll definitely go with a 20-microgram dose and perhaps even a lower dose as well, given the high bioavailability, it may not be necessary to go much higher to get as good or better bone growth as subcu Forteo at 20 micrograms.

Congrats, again.

One moment for our next question, that will come from the line of Mitchell Kapoor with H.C. Wainwright.

Congrats on the data. It's so impressive. So I just wanted to ask a question about -- I know we talked in the past about potential to be able to tailor dosing to a patient potentially. Is there anything in this data that kind of like suggests or adds that potential for a physician to be able to kind of do that with the RaniPill?

Yes. I think that, that's something that is probably more relevant for a monoclonal antibody that's infrequently dosed where you have a very high peak-to-trough variability, taking ustekinumab biosimilar, it's a good case study, RT-111, the next one we're going to bring forward. We'll likely try -- we'll try obviously, at least 1 dose, but we'll likely try to approximate different portions of that curve because you can maybe target the upper third, middle third or lower third of serums concentration, relative to the subcu. And that could lead to different AE or efficacy profiles potentially. For PTH, 1-34, we are going to try multiple doses in our Phase II, this is more to tease out what is necessary from an efficacy perspective. I think longer term, whether we take more than one into a Phase III remains to be seen. There's perhaps some commercial advantages or implications to that, but we have not made a determination at this point.

Great and congrats, everyone.

One moment for our next question, that will come from the line of Annabel Samimy with Stifel.

This is Jack calling in for Annabel. Congratulations on the data. Just a quick clarification on the 91% deployment success rate. So in the fixed instances where a drug signal wasn't detected for a given day, did the RaniPill just never deploy in these patients at all and the entire pill ended up passing? Or did the pills ultimately end up deploying but just after the 9-hour time point?

Yes. Jack, I'm glad it's you, not Annabel, because when I heard your voice, I was a little afraid. I thought she had COVID or the flu or something. But to answer your question, the way we frame this is at least 91%, because as you heard me say, we took time -- serum samples, blood samples, at 0, 3, 6 and 9 hours. And we used seeing the markers that we put -- the radiopaque markers we put inside of the capsule between 6 and 9 hours when we did the fluoro to say yes or no whether the capsule had -- whether those are separated and we know that the coding had dissolved. All we can say with certainty are the successes of our successes. The ones that we count as failures, they may have deployed later, they may have been successful overnight. There's just no way for us to know. So this is really the floor of the reliability rate, not the ceiling.

Thank you. And speakers, I'm showing no further questions in the queue at this time. I would now like to turn the call back over to Talat Imran for any closing remarks.

Thank you, operator. This concludes our RT-102 Phase I Part 2 repeat-dose study conference call. Thank you again, everyone, for joining us this afternoon.

Thank you all for participating. This concludes today's conference call. You may now disconnect.