Regulus Therapeutics Inc.

Ladies and gentlemen, thank you for standing by and welcome to the Regulus Therapeutics 2021 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After this feature's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require further assistance, please press star 0. I would like to hand the conference over to Chris Calzada. Thank you. Please go ahead.

Good afternoon, everyone, and thank you for joining us to discuss Regulus Therapeutics' first quarter 2021 financial results and corporate highlights. Joining me on today's call is Jay Hagan, President and Chief Executive Officer, and Dennis Drygen, Chief Scientific Officer. Jay will provide opening remarks and share progress on our 80PKD program and I will review the financial results before we open the line for questions. Before we begin, I would like to remind you that this call will contain forward-looking statements concerning regular therapeutics, 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 the 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'll now turn the call over to Jay.

Thanks, Chris, and welcome, everyone, to our Q1 earnings call and business update. Last week, we were very pleased to announce top-line data from the first cohort of patients who completed dosing and follow-up in our ongoing Phase 1B mechanism of action study of RGLS4326 in patients with ADPKD. We were successful in showing that measured levels of polycystin 1 and 2 increased greater than 50% and 20%, respectively, by the end of study compared to baseline levels in this short treatment duration study. We shared those preliminary results from the available data set because we believe these initial data demonstrate human proof of mechanism that the drug hits the target MIR-17 in the kidney as designed. You may recall that we indicated in the press release that eight of the nine patients had completed the study follow-up with the remaining ninth patient anticipated in the next couple of weeks. That ninth patient's trends through day 44, or end of dosing, were very encouraging. And as we complete the overall data analysis and have any material updates, we'll be sure to share them with you. We are also planning an earlier scientific presentation at PKD Connect in late June of this year with more detailed top line data, as well as what we believe are new compelling preclinical data validating the impact of RJLS4326 treatment in animal models of the disease. Recall that the design of the molecule is to bind the MIR17 in the kidney. This then leads to increased expression of the PKD1 and PKD2 genes and the resultant proteins these genes encode for, polycystin 1 and 2. Measured levels of PC1 and PC2 have been shown to inversely correlate with disease severity and are believed to be directly linked to the underlying genetic drivers of the disease. The overall trend that we saw in polycystin showed increasing levels of both PC1 and 2 over time, with a sustained effect one month after completion of dosing, suggesting that less frequent dosing could be utilized. Understanding patient mutational status may further contribute to understanding impacts on response rates. Approximately 85% of patients with ADPKD are reported to have a mutation in the PKD1 gene, with the remaining 15% having a mutation in the PKD2 gene. Additionally, the PKD1 gene has one predicted binding site for MIR17, while the PKD2 gene has two predicted binding sites, potentially contributing to differential response rates between the biomarkers. On the safety front, RGLS4326 was well tolerated by all nine patients with no serious adverse events reported. All reported AEs were mild and generally transient in nature. Overall, the PK profile of RGLS4326 in patients was similar to that observed in a prior healthy volunteer study. Concentrations of the drug in plasma were greater in patients with a Cmax of approximately 3 micrograms per milliliter relative to healthy volunteers where the Cmax was approximately 2 micrograms per milliliter, which suggests that lower doses may be effective in achieving the desired exposure in the kidney, the target organ of interest. In this disease, there are approximately 160,000 diagnosed in the U.S. alone, and it is the fourth leading cause of end-stage renal disease. As I mentioned earlier, ADPKD is caused by a mutation in either the PKD1 or PKD2 gene. A mutation in either of these genes disrupts the normal functions of their encoded proteins, polycystin 1 and 2, and reduces their levels, and leads to excessive proliferation of the kidney epithelium formation of multiple cysts, which eventually leads to kidney failure. 50% of ADPKD patients eventually develop end-stage renal disease requiring dialysis or transplant by the age of 60. There is only one recently approved therapy in the U.S. pointing to the need for new treatment options. Regulus has evolved the strong foundational technology from its inception from Ionis and Onilam to develop a specific proprietary kidney targeting technology. In preclinical models, we have demonstrated that RGLS4326 preferentially distributes to the kidney and collecting duct-derived kidney cysts. Treatment with RGLS4326 inhibits MIR17 function, increasing the expression of the PKD1 and 2 genes, as well as their encoded proteins, polycystin 1 and 2, and most importantly, slows down cyst growth in primary human ADPKD cyst cultures and multiple ADPKD mouse models of the disease. Additionally, both kidney weight to body weight and kidney injury markers are reduced compared to untreated mice, both signs of improved kidney health through treatment with this drug in these disease models. Our ADPKD program consists of two compounds, Our GLS4326, the lead molecule, which is being tested in the ongoing Phase 1B study reported last week, as well as our next-generation molecule, which is moving towards the clinic and should be IND-ready around year-end or early Q1 of next year. These molecules are designed to do the same thing, and that is inhibit the function of the MIR17 family of microRNAs, which is upregulated in both humans with the disease as well as in mouse models with the disease. So in summary, we are very pleased with these data and look forward to the results from the second cohort later this summer, as well as engaging FDA on the remaining hold requirements that would permit us to move 4326 into phase two and beyond. The research team at Regulus also continues to advance our platform technology with some exciting earlier stage programs in the laboratory. And finally, before I turn the call back over to Chris, I wanted to welcome our recent addition to our board of directors, Dr. Alice Wong, Dr. Wong brings an extensive scientific background to the board to help direct the company's drug discovery and development efforts. Dr. Wong is currently Senior Faculty Associate of Biology and Biologic Engineering at the California Institute of Technology. We are pleased to add someone of her caliber to the Regulus Board. Chris?