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spk03: Ladies and gentlemen, thank you for standing by and welcome to the Regulus Therapeutics Q4 2021 conference call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you need to press star 1 on your telephone. If you require any further assistance, please press star 0. I will now turn the caller over to your host, Chris Calzatti. You may begin.
spk01: Thank you, Operator. Good afternoon, and thank you for joining us to discuss Regulus Therapeutics fourth quarter and full year 2021 financial results and corporate highlights. With me on today's call is Jay Hagan, President and Chief Executive Officer, and Dr. Dennis Drygen, Chief Scientific Officer. Jay will provide opening remarks and share progress on our 80 PKD program, and I will review the financial results before we open the line for questions. Before we begin, I would like to remind that this call will contain forward-looking statements concerning Regulus Therapeutic's future expectations, plans, prospects, corporate strategy and performance, which constitute forward-looking statements for the purpose of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors including those discussed in our filings with the SEC. In addition, any forward-looking statements represent our views only as of the date of this webcast and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligations to update such statements. I will now turn the call over to Jay.
spk02: Thank you, Chris. Welcome, everyone, to our fourth quarter and full year 2021 earnings call and business update. 2021 was a transformational year for Regulus with the accomplishments in our ADPKD program and steady progress in our Alport Syndrome program made by our partner, Sanofi. I'll begin first by mentioning the financing last November in which we successfully closed a $34.6 million private placement on favorable terms That included several new institutional investors and support from several of our existing institutional investors. Given the challenging recent market conditions in the biotechnology sector and more broadly, our ability to secure this financing speaks to the promise and viability of our pipeline, which continues to move steadily forward. In December, we announced the appointment of Dr. Mohamed Amedian as Vice President, Chemistry and Pharmaceutical Development. Mo's deep experience leading operations for life science companies and background managing various projects, including the development and manufacture of therapeutic oligonucleotides, make him a natural fit for helping to guide our programs forward. His hiring came at a particularly opportune time as we entered into discussions with the FDA regarding the IND for our RGLS 8429 ADPKD program. In January, we announced the successful completion of the pre-IND meeting for RGLS 8429 which included minutes detailing FDA's overall agreement with the sufficiency of the non-clinical package, the overall trial design, and the length of our planned phase one study. With this feedback, we remain on track with our plan to submit an IND application in the second quarter of this year. As a reminder, our phase one study plan involves a single dose escalation study in healthy volunteers, followed by a multiple dose escalation study in patients with ADPKD. with the goal to establish a dose response around the dose level where robust clinical biomarker effects were demonstrated with RGLS4326, the first generation compound. Top line biomarker data in the first cohort of RGLS8429 treated patients with ADPKD is anticipated in the first half of next year, and we look forward to providing updates on progress. Importantly, we are leveraging the clinical pharmacology data from the first generation molecule to better understand the relationship between dose and exposure, which we intend to use in fine-tuning the dose selection in the SAD and MADS portions of the Phase 1b program. We plan to extrapolate the dose for the fourth and final cohort based on the PK data from the first two cohorts of the SAD in healthy volunteers and the exposure at the NOA ELs in the IND enabling tox studies. This will allow us to demonstrate safety and tolerability in humans at the exposure levels from the NOAELs. We will also use these data, along with learnings from the first-generation PK results, to ensure that the dose levels chosen in the MAD portion of the study in patients will provide the exposure that was achieved at the one milligram per kilogram level and that produced the robust increases in polycystin levels noted last year. Importantly, we believe our completed IND-enabling tox studies for RGLS8-429 will allow us to dose significantly higher than the 1 mg per kg, where we saw the impressive increases in polycystins in the first-generation compound. And one other bit about the upcoming study. We also look at changes in GFR, total kidney volume, and cystic architecture over the three-month dosing period. Since this is a short-term dosing study, We're not likely to see meaningful improvements in these parameters. However, we may be able to correlate polycystin changes with cystic improvements, a potentially significant advancement in understanding the impact of targeting MIR-17 in this disease. Turning briefly to the lenomericin or RG012 program for the treatment of Alport syndrome. Last month we announced Sanofi's completion of enrollment in the phase two global HERA clinical study evaluating lenomericin for the treatment of adult patients with Alport syndrome under our collaboration and license agreement with Sanofi. Alport syndrome represents a significant unmet need with no approved therapies. Final data from this phase two study is expected in the first half of 2023. Under the terms of the agreement, the company is eligible to receive $25 million upon successful completion of the ongoing HERA study, or initiation of the next phase of development for Lenomersen. And more importantly, potentially provide further validation of our platform technology designed to address genetic kidney diseases. This potential additional cash infusion would further our cash runway into 2024. We have an ambitious but achievable year ahead of us, and I look forward to continuing our work to further understand the role of microRNA in disease, where we can leverage our technology to ultimately improve the lives of patients. I'll now turn the call back over to Chris for a discussion of our financial results. Chris?
spk01: Thank you, Jay. Turning to our financial results, as of December 31st, 2021, our cash and cash equivalents totaled approximately $60.4 million. We expect that our existing cash will fund planned activities through 2023. This guidance does not include the potential Sanofi milestones. Research and development expenses for the fourth quarter of 2021 totaled $4.4 million compared to $4 million in the same period for 2020. For the full year 2021, R&D expenses were $17.8 million compared to $15.3 million for the prior year. These amounts reflect the internal and external costs associated with advancing our ADPKD program and our other research efforts in our pipeline. General and administrative expenses for the fourth quarter of 2021 total $2.6 million compared to $2.1 million for the same period in 2020. General and administrative expenses for the full year 2021 were $10 million compared to $8.8 million for the prior year. These amounts reflect personnel-related and ongoing general business operating costs. Net loss for the fourth quarter of 2021 was $7.1 million compared to a net loss of $1.3 million for the same period in 2020, which included an interim enrollment milestone of $5 million from our ongoing collaboration with Sanofi for Latimereson. Basic and diluted net loss per share for the fourth quarter of 2021 was 7 cents per share compared to basic and diluted net loss per share of 3 cents per share for the same period in 2020. Net loss for 2021 was $27.8 million compared to $15.7 million for the previous year. Basic and diluted net loss per share for 2021 was 32 cents per share compared to 45 cents per share for the prior year. With that, I will turn the call back over to Jane.
spk02: Thanks, Chris. We're happy to take any questions now. Operator, please open the lines.
spk03: Ladies and gentlemen, if you have a question or a comment at this time, please press the star, then the one key on your touch-tone telephone. If your question has been answered, or you wish to move yourself from the queue, please press the pound key. Our first question comes from Brian Cheng with Cantor.
spk00: Hey, guys. Thanks for taking my questions. So first question is on your Phase I study. I'm just curious how you view COVID as a factor in meeting the timeline that you have laid out for data from the Phase I SAD portion and also Phase IB inpatient portion as well. And I have one follow-up.
spk02: Sure. Thanks, Brian. Yeah, with respect to the SAD, we're planning to conduct a The study at the same site we used before where, you know, a couple years ago, COVID was a much more significant impact. It happened to be in a state that tended to be a little more liberal with respect to COVID restrictions and didn't really encounter any significant issues in terms of recruiting healthy volunteers at a single phase one unit. So we don't anticipate any impact on that. Of course, these are forward-looking statements, you know, and things could change with respect to the pandemic. And then with respect to the, you know, the Phase 1B inpatients, we're targeting about double the number of sites we had in the first, in the study with the first-generation molecule, which, you know, should alleviate concerns about hitting timelines with respect to the time beginning data here.
spk00: Okay. And to follow up on your comments about some of the efficacy measures for the second gen molecule, you know, in the phase 1B, you'll be looking at GFR and total kidney volume. Based on what you've seen in preclinical data, what's your thoughts about how long we'll need to, you know, for the patients to be on the study, to be on treatments, to see a meaningful response on GFR or total kidney volume?
spk02: Yeah. So, you know, we obviously, in patients with the disease, we've only studied treatment for six weeks thus far. So, I'm basing our commentary, you know, primarily based on what has been required for other compounds in development. And, of course, though our mechanism is quite unique, I think the impact on cystic architecture we've seen with targeting MIR-17, to our knowledge, we haven't seen that with any other mechanism. So we're hopeful that we can see something in a short period of time, but that's why we guided that we're cautiously optimistic with respect to seeing something in short of three months. In terms of where we think it would take, ultimately in the trial design we've discussed before in a phase two study, of one year in duration to see an impact on TKV. We may see something in GFR in that timeframe, but it may take a bit longer. And that's, again, based on historical precedent. But importantly, there are advancements in MRI imaging that enable one to look at what we're describing as cystic architecture, cyst count and cyst volume. And that's where we're particularly intrigued to see if we can't correlate a change in polycystin levels from baseline with changes in that architecture, which would be quite interesting. And that's where we might be able to see something in this shorter-term duration study.
spk03: Got it. Thank you, Jay. Sure. Our next question comes from Yi Chen with H.C. Wainwright.
spk04: Thank you for taking my question. My first question is, could you clarify what exactly needs to happen for the company to receive the additional 25 million milestone payments from Sanofi?
spk02: Yeah, so some of this is obviously confidential with respect to negotiated agreement. We tried to describe it here, Yi, and that is success in the phase two, meaning hitting the primary endpoints. or their decision to advance further into clinical development. Because often, you know, when you prospectively design a study, you're not quite sure of the treatment effect. And so you might see trends that don't quite reach statistical significance, and you still may decide to move forward into clinical development. So in our view, there's sort of two ways to win here.
spk04: Got it. Got it. So my next question is, so recently we had to receive a complete response letter for rhodoxalome. So how do you see that affects the field for Alper syndrome and for ADPKD as well? Thank you.
spk02: Yeah, I don't know any more than what's been disclosed by Rihanna, but obviously they've indicated they plan to work with FDA to find what additional information they can provide to address the complete response letter with respect to the CRL for Alport syndrome. So I do know that, you know, in discussions with our partner that we still have the potential here to be potentially, you know, first approved therapy, which is a very significant unmet need, you know, as was discussed at the ADCOM and is what we know with our work with the Alport community And, you know, given the pharmacology that was described in that advisory committee, I don't expect there to be much of a difference in the ADPKD setting where you do have an improved therapy and it is an older patient population who might be at greater risk for potential cardiovascular events. So we shall see. They have made a number of adjustments to the trial design, including the amount of follow-up. I think they extend it from four weeks to eight weeks, and they increase the sample size. So that's ongoing, and we'll see.
spk04: Okay. Got it. Thank you.
spk03: Again, ladies and gentlemen, if you have a question or a comp time, please press the star, then the one key on your touchtone telephone. And I'm not showing any further questions at this time. I'd like to turn the call back to Jay for any closing remarks.
spk02: Great. Thanks, everyone, for joining us today. We appreciate your interest and support of Regulus and look forward to providing updates as we move forward with our programs. Thank you.
spk03: Ladies and gentlemen, this does conclude today's presentation. You may now disconnect and have a wonderful day.
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