Crinetics Pharmaceuticals, Inc.

Greetings and welcome to Krenetics Pharmaceuticals conference call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn this conference over to your host, Mr. Thomas Galassi with LifeSite Advisors. Thank you, sir. You may begin.

Thank you, Operator, and thank you all for participating in today's conference call. Before we start, I would like to point out that there is a slide deck that will accompany today's presentation. This slide deck can be viewed using the webcast link provided on the Investors page of the Kinetics Pharmaceuticals website. Also posted on this webpage is a news release issued earlier today announcing top-line data from the multiple ascending dose portion of the Phase 1 study evaluating CRN 04777, which is the topic of today's call. However, before we get to discussion of the Phase I results, I'd like to remind all listening that some of the information contained in the news release and on this conference call is covered under the safe harbor provisions of the Private Securities Litigation Reform Act and contains forward-looking statements based on current expectations, including statements about the initiation of planned clinical trials. Such forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those stated or implied in such statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's news release, the company's other news releases, and Crenatix's SEC filings, including its annual report on Form 10-K. I'd also like to point out that the content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, March 30, 2022. Crenatix takes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. With that, I'd like to turn the call over to Dr. Scott Struthers, founder and CEO of Krenetics. Please go ahead, Scott.

Thank you, Tom. It's my pleasure to be speaking with you and all of those listening this afternoon. I'll be giving today's presentation with our Chief Medical Officer, Dr. Alan Krasner, and I'm also joined by our Chief Financial Officer, Mark Wilson, who will be available to answer questions following the prepared remarks. The primary purpose of today's call is to discuss new data from the Phase I Multiple Ascending Dose Cohort studying CRN4777, or I'll just call it 777, the investigational oral nonpeptide SST5 agonist that we are developing as a treatment for congenital and syndromic hyperinsulinism. Though we also reported our 2021 fourth quarter and year-end financial results today, we won't be talking about these during the prepared remarks. Those interested in our financials can find the relevant details in our earnings press release issued earlier today. Allow me to start with the key takeaways. I'm extremely pleased to announce the top line results from our multiple ascending dose study build on the pharmacologic proof of concept data previously reported for our single ascending dose study and its support advancement into clinical trials in patients later this year. Specifically, safety results show that 777 was well tolerated when administered daily for 10 days. We observed no serious adverse events in the trial, and all adverse events were considered mild or moderate. Pharmacologic data showed dose-dependent decreases in fasting insulin, corresponding increases in fasting plasma glucose after the first dose of 777, which was sustained with repeated daily dosing for 10 days. Additionally, we saw clinically meaningful suppression of sulfonylurea-induced insulin secretion at day 10. This pharmacologically mimics the most common form of congenital hyperinsulinism or congenital HI. These results were dose-dependent with the highest dose of 777, leading to elimination of the need for supplemental glucose support in most subjects. These findings mirror what we saw in our SAD study, which is precisely the results we were expecting. Finally, pharmacokinetic analysis from the multiple ascending dose trial were also consistent with expectations based on our single ascending dose trial, as 4777 was orally available with a half-life of approximately 40 hours. These favorable PK results support a once-daily oral dosing regimen, which we view as a potential major advantage considering congenital HI's patient population is made up primarily of neonates, infants, and children. Taken together, we believe the top line data from our phase one program provide pharmacologic proof of concept for 777, not only in congenital HI, but potentially any disease driven by excess insulin secretion. The next step for 777 is to meet with regulators so that we can discuss our data and the specifics of our planned clinical program in patients. We also believe we are now positioned to head into our clinical studies in patients with 4777. We were able to achieve proof of concept in these early developments thanks to one of the most favorable features of endocrinology and the chronetics drug development strategy that assesses the molecule's pharmacologic activity with evolutionarily conserved biomarkers that have the potential to translate all the way from our animal models to healthy volunteer studies to patients. We pioneered this strategy with paltucetine, which is now in Phase III registrational programs. Primary endpoint for phase three there is based on normalization of IGF levels, the same hormone we measured in preclinical animal models, phase one healthy volunteer study, and our phase two acromeg leak patient studies. We're also applying this strategy to our 4894 ACTH antagonist program and plan to take a similar strategy or similar approach with our recently unveiled PTH antagonist program. This efficient approach to endocrine drug development is a central component of our corporate strategy for bringing an entire next generation of therapeutic options to patients with endocrine-related diseases. With that intro, I'll hand it over to our CMO, Dr. Alan Krasner, to discuss how we are working to address unmet needs in congenital HI and other forms of hyperinsulinism with our 777 program. Alan?