Regulus Therapeutics - Q3 2022

Transcript

Speaker 0

Hello, and welcome to the Regulus Therapeutics Inc. Q3 2022 Earnings Conference Call. All participants will be in listen only mode. After today's presentation, there will be an opportunity to ask questions. Please note this event is being recorded.

I would now like to turn the conference over to Chief Financial Officer, Chris Calzada. Please go ahead.

Speaker 1

Thank you, and good afternoon. Thank you for joining us to discuss Regulus Therapeutics' 3rd quarter 2022 financial results and corporate highlights. Joining me on today's call is Jay Hagen, President and Chief Executive Officer and Doctor. Dennis Dreygen, Chief Scientific Officer. Jay will provide opening remarks and share progress on our APKD program, and I will review the financial results before we open the line for questions.

Before we begin, I'd like to remind you that this call will contain forward looking statements concerning Regulus Therapeutics' future expectations, Plans, prospects, corporate strategy and performance, which constitute forward looking statements for the purposes 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 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.

Speaker 2

Thanks, Chris, and welcome everyone to our Q3 earnings call and business update. I'll begin with a general update on our ADPKD program. We continue to make progress in the clinic with RGLS-eight thousand four hundred and twenty nine. In September, we announced positive top line safety and PK data from Phase 1 single ascending dose or SAD clinical trial of RGLS-eight thousand four hundred and twenty nine. RGLS A129 was well tolerated with no serious adverse events reported.

Among the 32 subjects treated with RGLS A429 or placebo, there were only 9 adverse events, all of which were mild, except 1, a sinus infection, which was graded moderate In addition, importantly, preliminary results suggest that plasma exposure It's approximately linear across the 4 dose levels tested and is similar to the PK data from the 1st generation compound RGLS Last week, we announced the dosing of our first patient in our Phase 1b multiple ascending dose or MAD study of RGLS-eight Since then, we've enrolled the 2nd patient and have several more in screening at the 6 sites that are now currently active. The study is a double blind, placebo controlled, multiple ascending dose study to assess safety, tolerability and pharmacokinetics of RGLS-eight thousand four hundred and twenty nine in adult patients with ADPKD. The study will evaluate the safety and efficacy of treatment with 4,329, excuse me, 8,429 across 3 different dose levels, including measuring changes in polycystins, cystic kidney volume or height adjusted total kidney volume and overall kidney function. The first cohort is being dosed at 1 milligram per kilogram of RGLS A129 or placebo every other week for 3 months. Top line data 3 months ended September 30, 2022, we sold and settled approximately 2,200,000 shares for net proceeds of $4,500,000 under our ATM facility.

Almost all the shares were sold to a new institutional investor. With the completion of this transaction, we believe our cash, cash equivalents and short term investments will now fund current planned activities through 2023. Last week, we presented data at the American Society of Nephrology Kidney Week meeting In Orlando, the poster presentation was titled Discovery of Next Generation AntiMIR-seventeen Oligonucleotide RGLS-eight for the treatment of autosomal dominant polycystic kidney disease. And it highlighted data supporting the potential of A129 in this important disease. We are excited about our progress as well as the attention ARGELISH A129 receives in the marketplace, which helps validate the effort our team is putting forth each day to advance this therapy and its potential to improve the current standard of care.

With that, I will turn the call back over to Chris for an update on our financials. Chris?

Speaker 1

Thanks, Jay. Turning to our financial results. As of September 30, 2022, our cash, cash equivalents and short term investments totaled Approximately $45,300,000 We expect our cash runway to extend through 2023. Research and development expenses for the Q3 of 2022 totaled $5,300,000 compared to $5,900,000 in the same period in 2021. These amounts reflect the internal and external costs associated with advancing our ADPKD program and other research efforts within our pipeline.

General and administrative expenses for the Q3 of 2022 totaled 2 $300,000 compared to $2,500,000 for the same period in 2021. These amounts reflect Personnel related and ongoing general business operating costs. Net loss for the Q3 of 2022 was 7.6 Basic and diluted net loss per share for the Q3 of 2022 was $0.50 per share compared to basic and diluted net loss of $0.99 per share for the same period in 2021. With that, I will turn the call back over to Jay.

Speaker 2

Thanks, Chris. At this time, we'd be happy to take any questions. Operator, please open the line.

Speaker 0

Thank you, Jay. We will I'll now begin the question and answer session. Our first question today comes from Whitney Ajam with Canaccord. Please go ahead.

Speaker 3

Hey, guys. The question I have, I guess, is around expectations headed into the data mid next year. Can you remind us what you saw in animal studies with slightly extended dosing? I know there's 3 months of dosing here versus a slightly shorter course in the 1st gen compound. So curious what you saw with longer dosing in animal studies and if you think there's read through there to what we should be expecting from the clinical data readout

Speaker 2

Yes. Maybe I'll touch on the clinical part and ask Dennis to comment on dosing duration in a variety of animal models, Which depending on the animal model, some are more rapid than others offering less opportunity to dose for extended periods. But just to remind folks that at the 1 milligram per kilogram dose level that we're testing currently With our next gen compound, we saw a statistically significant increase in both polycystin 1 and polycystin 2 From baseline of approximately 60% 40% increases in those at that And as I mentioned earlier, the PK between the molecules is very similar. We anticipate types of effects. And if you recall, the trajectory of the change from baseline would suggest that with continued dosing, higher levels of polycystic It could be achieved prior to it plateauing once we reach steady state in the kidney.

So that's what we'll be looking for in the clinic. And Dennis, I don't know if you want to comment on duration of dosing in animals.

Speaker 4

Thank you, Jay. Indeed, as Jay mentioned earlier, the majority of the models for ADPKD are quite aggressive and do not allow extended period of treatment. We did test 1st generation molecule in longer monophologous model where the treatment Was for 7 weeks. And with the longer treatment, there was more and more evidence of the inhibition of systole expansion and growth.

Speaker 0

The next question comes from Yanan Xu with Wells Fargo Securities. Please go ahead.

Speaker 5

Hi, thanks for taking the question. I mainly have a question about enrollment and Time line for the data from different cohorts. So I think the Previously, the data expectation for the first dose cohort might have been first half twenty twenty three. Please correct me if I'm wrong. And this time we hear mid year.

Could you elaborate on this might be a small change First half versus mid year, but any changes in your expectations for enrollment, speed or any other factors? And also For the additional cohorts, do you have any suggestion on potential timeline for the data from those cohorts? Thank you.

Speaker 2

Sure, Yanna. So the guidance that we provided for data from the first cohort In the first half of twenty twenty three dates back to when we did our financing in October, November last year, Outlining at that time our expectation for both initiation of the SAD and then initiation of the MAD. And as often the case, as you work through these processes, sometimes things take a little bit longer to get up and going. So We chose to update our guidance in terms of when we would have data now that the MAD is actually initiated. We're a year after that initial guidance was provided.

We're taking a look at how quickly we think we're going to enroll the study and think guidance of mid-twenty 3 is more accurate than the first half of twenty twenty three, which includes the Q1. So effectively, we're saying the Q1 is likely out. We'd To be done enrollment this month probably to hit the Q1. And enrollment is obviously a forward looking statement and actual results We're pleased with the progress the team is making thus far in getting now 6 sites up and a good pipeline of patients in screening and 2 now in the study of the total 12 that we're targeting for the 1st cohort. And so guidance for mid-twenty 23 feels more appropriate and accurate with how we project Enrollment is going to go.

When the last patient is initiated, we know quite clearly The time it will take then to complete that, they're going to have 3 months of dosing and 1 month of follow-up after which we've got the analytical work that's needed. So that is forms the basis of the overall timeline for the first cohort. As far as the subsequent cohorts, I mentioned earlier that we have 6 sites up. We're targeting up to 25 total sites currently. And so as more sites come up, Then obviously more potential patients will come into the queue geographically and otherwise.

And so while it's premature to estimate the time of enrollment of subsequent cohorts, one can anticipate that it could go more quickly Than the first cohort, just given more sites up and active. So what we've guided to for data from the second cohort is the second half of twenty twenty three.

Speaker 5

Got it. Thank you. Thank you for the answer and congrats on the progress. Thank

Speaker 0

you. Seeing no further questions, I would like to turn the conference back over to Jay Hagen for any closing remarks. Great.

Speaker 2

Thank you, operator, and thanks everyone

Speaker 0

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.