Regulus Therapeutics Inc.

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.

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.

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?