Welcome to Rani Therapeutics Fourth Quarter and Full Year 2021 Financial Results and Corporate Update Conference Call. At this time, all participants are a in a listen-only mode. Following management's prepared remarks, we'll hold a question-and-answer session.

To ensure that we have ample time to adjust everyone's questions during the Q&A session, we'll ask for a limit of one question and one follow-up question per person. [Operator instructions] As a reminder, this call is being recorded today Tuesday, March 29, 2022.

I'd now like to turn the conference over to Laurence Watts, Managing Director at Gilmartin Group. Please go ahead..

Thank you, operator. Joining us on the call today 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 and uncertainties related to 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 factor section of the company's filings with the Securities and Exchange Commissions 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 breaking 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 all for joining our fourth quarter and full year 2021 financial results conference call. 2021 proved to be a transformative period for Rani Therapeutics.

During the year, the company completed an initial public offering on NASDAQ, expanded its executive leadership, progressed its development pipeline and made further progress optimizing the RaniPill oral delivery platform. Before I turn to recent events, I would like to start today's call by going over the key milestones we achieved in 2021.

Our most notable achievement was the completion of the successful IPO in August, which raised approximately $84 million in gross proceeds. As a result, Rani exited the year in a strong financial position. On a personal note, I was honored to be appointed CEO prior to us going public and to lead Rani Therapeutics through the IPO process.

In 2021 Rani's executive team was further altered by the appointment of Eric Groen to General Counsel. We also expanded our non-executive team, welcoming Lyn Baranowski, Laureen DeBuono, and Jean-Luc Butel to our Board of Directors with Lisa Rometty, joining our Board in January.

Turning to our operations, we have made significant progress in refining and furthering our drug development plans over the past year.

Following our positive Phase I study results for Octreotide using our original RaniPill capsule, which were announced in 2020, and which serve as a proof of concept for our injectable to oral delivery platform, we further refined not only the platform itself, but also our near term clinical development plans for the oral delivery of biologics.

As a reminder, the original RaniPill capsule can deliver doses of up to three milligrams of drug per pill. This capacity enables us to pursue a whole host of disease indications, including neuroendocrine tumors or NETs, acromegaly, psoriatic arthritis, growth hormone deficiency, osteoporosis and hypoparathyroidism.

Parathyroid hormone or PTH is administered by a daily injections for the treatment of osteoporosis and quickly became a key focus for us and led to the development of our drug candidate RT-102. As such in November, we completed a GLP 7-day repeat dose oral administration study that evaluated the safety and tolerability of RT-102 in a canine model.

The study demonstrated successful delivery of a PTH payload via the RaniPill capsule with a pharmacokinetic profile comparable to the published data for once daily PTH, subcutaneous injection. I'm happy to announce that our second clinical program began last week with the initiation of our Phase I study of RT-102 for osteoporosis.

The initiation of this study represents a significant milestone for Rani as our second program to enter the clinic. We intend to initiate another Phase I study with RT-109, our oral human growth hormone program in the second half of the year.

Now let me turn to our other major development initiative, the RaniPill HC, a newly designed high capacity oral biologic delivery device capable of administering 500% plus higher payloads than our current RaniPill capsule.

We believe this is a significant breakthrough in drug delivery with the potential to provide expansive opportunities for the company, such that we could potentially pursue a daily dosing option for over 50 additional biologics for internal development or through partnership.

Importantly, we believe this development will not detract from us making progress with our original RaniPill capsule, which forms the core of our current development pipeline. The current RaniPill capsule is optimized for drugs with a daily dose of up to three milligrams. The RaniPill HC can potentially deliver up to 20 mgs.

To give you an idea, some of the potential drugs that we could now target with the RaniPill HC include pembrolizumab, intercept, etanercept, trastuzumab, and secukinumab. From these alone, you should be able to tell the potential market opportunity for us with this higher capacity device is significant.

As we reported in February of this year, in a preclinical in-vivo study, we successfully delivered an 80 milligram dose of drug in three canine test subjects using the RaniPill HC device placed by a laparotomy in the [indiscernible]. Systemic serum drug concentration was detected and measured over five days.

Lastly, before I turn the call over to Mir to cover our preclinical data in more detail, I want to discuss the market research that we released on patient preference for ingesting an oral therapeutic over receiving an injection.

We commissioned an independent third party survey to investigate US patient and physician preference for oral medications versus injections.

The survey involves 611 patients aged 18 years or older, and presently using an injectable biologic to treat a condition and 201 physicians, mostly endocrinologists and rheumatologists, presently prescribing injectable biologics to their patients.

Across all patient groups, genders, ages, conditions treated and severity of condition, there was a consistently strong preference for switching from injection to pills, even for infrequent injection regimens of up to six months.

For example, for Prolia, which is administered as a subcutaneous injection, once every six months, 76% of patients surveyed indicated a preference for a daily pill versus a current regimen. For Humira, which is dosed by biweekly, the percentage of patients who prefer daily pills was 88%.

All groups surveyed indicated a preference for oral over injectable drugs at or exceeding 64%. This demonstrates that there is a tremendous latent demand among patients for an oral alternative to many blockbuster biologic drugs.

Together with the RaniPill HC, this presents a number of potential opportunities for expansion of Rani's pipeline in the future. In addition to the commission surveys, we conducted our own preference and tolerability study involving a mock RaniPill capsule containing potato starch to evaluate the ease with which a RaniPill capsule could be swallowed.

Of the 150 individuals that participated, all were able to swallow the mock RaniPill capsule with no reported difficulty. Remember the RaniPill is a OOO sized pill similar in size to that of official old pill. Once again, we found that people overwhelmingly favor taking a pill in place of an injection.

Thus, the market research confirmed what we believe to be true. People hate needles and patients prefer pills. With that, let me now turn the call over to Mir Hashim to discuss our preclinical and clinical updates in more detail..

Thank you, Talat and thank you everyone for joining us. Let me provide some updates on two major developments. One focused on our pipeline program, RT-102 and the other on the development of a higher capacity RaniPill device, which we call RaniPill HC. Let me begin with an update on the RT-102 project.

RT-102 is a RaniPill capsule containing a formulation of the human Parathyroid Hormone analog PTH 1-34, which is being developed by Rani as an oral osteoanabolic therapy for osteoporosis. With the goal of launching a Phase I human clinical study in early 2022, we initiated a seven-day repeat dose nonclinical GLP study in November of 2021.

This study was conducted in awake canines to evaluate the safety and tolerability of RT-102, which was administered daily to these subjects for seven days. The RaniPill capsules were well tolerated in all animals with no clinically adverse observations noted.

Specifically, there were no significant gastrointestinal abnormalities associated with the oral administration and dozing of RT-102. Based on these findings, we were able to feed the requirements for initiating a Phase I clinical of RT-102.

This Phase I study is designed as a single center open label trial, evaluating the pharmacokinetic, safety and tolerability of RT-102 in healthy adult women volunteers. Each subject will be administered a single dose of RT-102 over a range of 20 micrograms to 80 micrograms.

I'm happy to report that this study was initiated or planned in the third week of March and we have already successfully dosed the first human subjects. We expect to announce the top line results of the RT-102 Phase I study in the second half of the year.

Now turning to the second major update, Rani has been working on the development of a high capacity RaniPill over RaniPill HC with the potential to deliver drug payloads of up to 20 milligrams. We are pleased to announce the successful completion of our first preclinical study in the canine model with the RaniPill HC.

This preclinical study utilized a RaniPill HC device without an enter coating or chemical reactance and was inserted directly into the duodenum via laparotomy. The device was actuated by an external pressure source to deliver approximately 18 milligrams of adalimumab to the canines.

We achieved successful delivery in each of the three test subject, which was then followed by the monitoring of systemic serum drug concentrations over a five-day period to get a PK curve.

We compared the PK levels of the 18 milligrams of adalimumab deliver by the RaniPill HC to PK levels of 2.5 milligrams and 5 milligrams approximately of adalimumab that were delivered previously using the original RaniPill capsules.

The data when normalized for dose and weight unit of PK curve, which was proportional to the historical PK curves generated with the lower doses. While we are in the early stages of development of the RaniPill HC, we are excited to expand its reach to additional drug candidates that are currently delivered parentally at higher doses.

And by the way, the RaniPill HC shares many similarities with our existing RaniPill capsule. Now I will turn it over Svai to go the financial results for the fourth quarter and year end 2020.

Svai?.

Thank you, Hashim and good afternoon, everyone. The press release we issued earlier today provide our financial results in detail. So I will only provide highlights on this call.

Operating expenses for the fourth quarter and full year 2021 were $13.4 million and $54.3 million compared to $5.1 million and $17 million for the same period in 2020 respectively.

Excluding stock-based compensation, depreciation and amortization, non-GAAP operating expenses were $10.1 million for the fourth quarter and $31.2 million for the full year 2021.

Turning to our balance sheet; cash, cash equivalent and short term investments were $117.5 million as of December 31, 2021, which we believe is sufficient to fund our plan operation, at least until the end of 2023. With that, I will 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 2022. We look forward to sharing the top line results from our Phase I clinical trial of RT-102 in the second half of the year, and to initiating our third clinical program RT-109.

We also plan to make further progress with the RaniPill HC and are exploring a number of opportunities involving this higher payload system. 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 subsequently.

I'd also like to thank all of our stakeholders for your continued support of Rani and helping us move closer to our vision of making oral biologics a reality. With that. I will now open the call up for questions.

Operator?.

[Operator instructions] Our first question comes from the line of Geoff Meacham with Bank of America. Your line is open. Please. Go ahead..

Hey guys. Thanks so much for the question. Just had a few. When you look at the health -- the high capacity pill, are there any additional modifications beyond just the ability to scale up those? I wasn't sure if the device within the pill was changed at all to accommodate.

I was just thinking whether you guys would have to go back and maybe repeat any prior safety or tolerability studies. And the second question is, is it fair to say that the HC strategically could be the preferred product going forward? Just given that, a lot of approved agents are likely to be a higher dose product. Thank you very much..

Thank you, Jeff. And it's good to hear your voice. Appreciate the questions. I'll try and take them in order. The RaniPill HC shares a number of commonalities with our current generation RaniPill platform. There are obviously some modifications to increase the dose by 500%. Ultimately, it'll be packaged into the same capsule.

The balloon is similar or the same, I should say and from the perspective of the patient, the size of the capsule itself doesn't change at all.

Having said that, given that there is a different mechanism in this device, we expect that we will be doing some --at least some safety and tolerability work, where there may be some ability to use what we've done already would be in the biocompatibility space in areas like that.

In terms of where this goes relative to the current RaniPill platform, you're absolutely correct that this opens up a number of new opportunities and where a lot of the growth is in the biopharma -- pharmaceutical space.

So looking at therapeutic monoclonal antibodies in the immunology space or oncology in the like, those are likely because of their dosing to go into a RaniPill HC. Having said that, the current RaniPill generation is really ideally suited for lower dose drugs, the ones that are in our pipeline currently like a PTA for osteoporosis.

So there's no plan to move that over to the HC and we're fully committed to moving that forward and turning it into a commercial product once we get through the clinical cases..

Okay, great. Thank you very much..

Appreciate it. Thank you..

Thank you. And our next question comes from the line of Annabel Samimy with Stiefel. Your line is open. Please go ahead..

Hi, thanks for taking my question.

So you kind of touched on this before, but I was curious with the HC, are there any programs of your current programs that you think would be better suited to the high capacity? I guess what you call, to formulation or mechanism, like for example maybe human growth hormone, where it would be administered to kids and maybe they could deal with like a smaller pill size or something like that.

And are there any therapies that you have access to now, which obviously you do that would take priority over some of the current programs that you had listed initially with the RaniPill? And then as a follow-up there's, I guess you kind of also touched on this, but for the master file that you're going to have for the RaniPill, do you have to start a whole new master file for the high capacity? Thanks..

Yeah, sure. Thank you, Annabel. So I think you touched on an important point here around HC or for any pediatric application of the RaniPill getting to a smaller size would let you get to patients who are under 10 years of age.

So that is potentially an application where you could move to the RaniPill HC but that would require further development because the current version of the RaniPill HC is the same size as the current RaniPill.

In terms of new programs well, just continuing on that before I move on to new programs, our adalimumab biosimilar would fit in our current RaniPill, but there are, could be certain applications, higher dose applications where it makes sense to put that into the HT. But primarily we're looking at new programs.

So that's a good segue to your second question.

We don't have any to announce right now, and we're not making any changes to our pipeline as of yet, but I think what you're intimating is that yes, because of the RaniPill HC, we're going to be adding some additional programs and perhaps later in the year, we'll give some guidance on how we'll strategically prioritize those.

We do want to show clinical validation of the RaniPill HC, as soon as we put we can, right? There's the development that'll go on this year, but if we can move into the clinic, I think it's good for us and good for everybody. As far as the master file is concerned, you're right. I did kind of speak to this.

I think that realistically, we will have to do some repeat dose safety and tolerability with the RaniPill HC, where they will share commonality is it's many of the components are identical and so biocompatibility and many of the other things that are going to go into verification and validation of these platforms they'll be able to share..

Okay, great.

But is it going to be a whole new file though?.

No. So there'll be one master file. You can have chapters in it to cover different embodiments and also for those will have to be there for specific drugs potentially as well..

Okay, great. Thank you. .

So just one file. Yeah..

Thank you. And our next question comes from the line of Michelle Gilson with Canaccord Genuity. Your line is open. Please. Go ahead..

Hi, thanks for taking my question. I have one on RT-102 and then one on the high capacity pill program too. Yes, for RT-102, you recently initiated the Phase I study in healthy volunteers.

Can you maybe walk us through the trial design in a bit more detail, and are there other parameters that you're planning to evaluate in that study? I guess, anything else other than the different doses that is, I guess, experimental within the pill. And then, maybe you can help us understand what a good result is for that study.

What can we learn from the PK profile? And, it's been very difficult translating PK data for some other PTH programs. I guess they use alternative dosing routes that aren't subq in terms of the read through to biomarker or BMD results.

So, maybe you can address why, you can get -- why we should be comfortable with the PK profile, I guess, that you guys show for RT-102?.

Sure. should I answer that and then we'll go to the HC question..

Yeah, that sounds good..

Okay. Fair enough. So hi Michelle, by the way. Thank you for the question. Happy to go into some details on our RT-102 Phase I. It is a single dose study in healthy volunteers. As you mentioned, we're doing a 20 microgram dose, which is the commercial forteo dose. We're also doing an 80 microgram, which is where a [indiscernible] is clinically dosed.

And we're going to do an intermediate dose as well. You are correct that you need to look at biomarkers ultimately, and this area has had a number of failures both in oral formulations and with the patch most recently. The difference in what Rani is doing to what everyone else has attempted is this is an injection.

It's an jejunum injection to be sure, but it's ultimately an injection. So the peak and the trough as we've shown preclinically is very similar to what you'd expect to see subcutaneously.

You are correct though, that the PD part of this is an important part of that story and nothing to report yet, but hopefully we'll have some additional details to share later this year when we share the read out on the Phase I that will give some comfort that this is going to produce similar results to what you'd expect from subcutaneous delivery of Teriparatide..

Okay, thank you. And in terms of, I guess for the RaniPill HC, the first initial proof of concept was done with the placement of the RaniPill via laparotomy into the jejunum.

Should we expect, I guess the next steps to be very similar to, what you did for the original RaniPill or what, I guess, what are the next steps for evaluating the HC pill? And, at what point do you get comfortable bringing to the clinic? I know you're looking forward to bring this into people..

Well, thank you for that question. And I'm glad that folks are excited enough that two months or a month after announcing it, everyone's asking me when are we getting it into the clinic? I think it is an important development for the company. You're, correct.

We did a placement vial laparotomy, and it was externally powered that was in order to visualize the delivery. We did this with the first RaniPill platform as well.

And the next step is to have -- take a fully packaged product and put it in via laparotomy again, watch it unfold, watch it deliver, and hopefully get good reliable results in terms of PK and from there, the final step is in oral administration in canines. We'll get through those knock on wood, hopefully this year, that's the plan.

And then in parallel, we're doing candidate selection both, for our pipeline and then talking to some potential partners and with the goal of getting that into the clinic, as soon as reasonably possible.

I think development is always hard to predict down to the day, right, or even perhaps the month, but a lot of the heavy lifting has been completed, which is why we were comfortable announcing it. Getting a mechanism that could deliver 500% plus or more. That was the really hard part and we've been able to show that already..

Right. Well, thank you for taking my question and congrats on your, your first earnings call as a public company..

Thank you so much, Michelle..

Thank you. And our next question comes from the line of Brandon Folkes with Cantor Fitzgerald. Your line is open, please. Go ahead..

Hi, thanks for taking my questions and congratulations on all the success.

So maybe just following along a similar line, as we look at longer term, is there RaniPill HC, something you expect to pursue in parallel with the original RaniPill? And I mean that, from the aspect of understanding what you have communicated today that you still committed to the second Phase I study getting RT-102 to market.

When we think about new indications going forward, should we think about those coming through in both the RaniPill and the RaniPill HC, or just given the potential multi contemplate maybe relocating resources to the RaniPill HC. And then I'll just ask my second question, because it probably is answered in the same. I have a good….

I have a good memory. You can go for it for sure..

Can you just talk about the study contemplated in the statement of the cash runway through the end of 2023? Just given that's a pretty solid cash runway, any potential to pull programs forward there, especially in the HC programs or is sort of development, you know, still progressing there where that's really the limiting factor versus cash.

Thank you. Sure..

Sure. So in short, I think you will see developments with both platforms in parallel. We still get considerable inbound from pharma companies that want to use our current RaniPill generation for some really interesting next generation applications within the biotech space.

So there are places I won't speak to right now that we could go that are really ideally suited. The other thing that we're doing with the current generation RaniPill platform is a sustained release version and that would take certain peptides and make them deliver over several days instead of an immediate release.

That opens up our RT-110 PTH for hyperparathyroidism for other indications as well. There are very interesting applications that can be used there.

Having said that, of course the RaniPill HC opens up virtually all many, I'll say of the monoclonal antibodies that are currently on the market virtually all in the inflammatory space and many in areas like oncology or rare disease. So clearly there are a number of opportunities for pickup.

Now, where does that fit in terms of our budget? Our budget contemplated running two Phase I, a repeat dose IDE and two Phase I in 2023. So two this year, the repeat dose study into next year. If we're going to add to that, we will obviously need to look at bringing on additional resources or doing that in partnership. But nothing to report right now.

I think we'll figure out where that program is going to -- the RaniPill HC platform I should say is going over the course of this year. And when we're ready to make some additions or alterations or move things up, we'll definitely let you know..

Great. Thank you very much..

[Operator instructions] Our next question comes from the line of Bret [ph] was BTIG. Your line is open, please. Go ahead..

Yeah, it's [indiscernible]. Thank you for taking the question. Congrats on the progress in the past, months and years and just strategic one. You've touched on a lot of the specifics, but strategic one with regard to the portfolio, let's call it both with HC and with their RaniPill, the regular RaniPill, let's call it.

Just how are you're thinking about how much you can actually take yourself versus partnerships and is there a sense of how the strategics are being contemplated internally? Can you give us any sense for the potential for partnerships as you contemplate again, both programs with HC as well as RaniPill regular?.

Sure.

So as far as what we're thinking about doing with our current pipeline and the expansion of it, I think that realistically there may be some small additions, one or two programs on the regular, I call it the OG, the current generation RaniPill platform, RaniPill platform, but then the -- as far as the HC is concerned, we will absolutely add an additional program as we get through our oral preclinical testing.

I think that this is -- there's potential in either case for those to be partnered programs. As I mentioned before, we are getting interest in using the platform to deliver both lifecycle management kinds of products and novel compounds. I think this just remains to be seen. We can't do everything.

I think when we talk about the potential opportunities for expansion, they're very large given the capabilities of the RaniPill platforms. But we, as you said, perfectly, we have to be very strategic in what we go after.

So we'll take into account the clinical trial burden, the cost of running those trials, the revenue potential of those particular products and the burden for patients of the injectable regimen as a currently is, and the opportunity potentially for expansion of access that comes with an oral formulation.

So those are the things that are going into our thinking. And like I said, I think we'll have more color later in the year..

Okay, great.

And just one other quick follow up, maybe you mentioned maybe I missed it, in terms of timing with the master file, a progress or let's call a result from the master file, is there any, any particular timing that you've indicated there?.

No, we haven't, we're on track with our plan. So we have to run a pretty significant GLP or I should say IDE enabling GLP study and we're gearing up for that. That takes a lot of work to get that ready to go.

And it's a two month study and then from there, we'll submit the IDE and get into actually running the study itself and having that data go into a master file. We may have an update sooner rather than later, we'll share that when happens..

Terrific. Thanks. Congrats again..

Thank you so much..

Thank you. And I'm showing no further questions at this time, and I would like to turn the conference back over to Talat for any further remarks..

Well, thank you operator. This concludes our fourth quarter and full year 2021 conference call. Thank you again, everyone for joining us this afternoon..

This concludes today's conference call. Thank you for participating. You may now disconnect everyone. Have a great day..