Crinetics Pharmaceuticals' Oral SST5 Agonist CRN04777 Demonstrated Pharmacologic Proof-of-Concept with Strong Dose-dependent Suppression of Insulin Secretion in Phase 1 Single Ascending Dose Study
CRN04777 Phase 1 Program Progressing to Multiple Ascending Dose Cohorts to Advance Development as a Treatment for Congenital Hyperinsulinisms
Demonstrated Dose-dependent Reductions in Glucose-stimulated and Sulfonylurea-induced Insulin Secretion
Management Hosting Webcast to Discuss Findings Today at 4:30 p.m. Eastern Time
SAN DIEGO, Sept. 15, 2021 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors, today announced positive preliminary findings from the single ascending dose (SAD) cohorts of a first-in-human Phase 1 clinical study with CRN04777 demonstrating pharmacologic proof-of-concept for this investigational oral, nonpeptide somatostatin receptor type 5 (SST5) agonist being developed as a treatment for congenital hyperinsulinism (HI).
“Congenital HI patients and their families live in constant fear of hypoglycemia. It is an ever-present danger that significantly impacts all aspects of daily life for these vulnerable patients and their families. Current treatment options are very limited and not universally effective, resulting in a high burden of care,” explained Chris Ferrara-Cook M.D, Ph.D., a pediatric endocrinologist and senior medical director at Crinetics who has specialized in the treatment of children with hyperinsulinism throughout her medical career.
Alan Krasner, M.D., chief medical officer at Crinetics, added, “We are very encouraged by these single ascending dose data that clearly demonstrate proof-of-SST5 agonism and resultant inhibition of insulin secretion with CRN04777 exposure in healthy volunteers. We are excited by the possibility that CRN04777 may serve as an oral treatment to normalize glucose levels in any child born with congenital HI regardless of their specific genetic mutation and eagerly look forward to better understanding its full potential with additional clinical studies.”
The 80 healthy volunteers who enrolled in the SAD cohorts were administered oral doses of CRN04777 (0.5 mg to 120 mg) or placebo. The pharmacologic effects of CRN04777 were evaluated using two distinct methods. First, oral administration of CRN04777 showed rapid dose-dependent suppression of insulin secretion in response to an intravenous bolus of glucose in an Intravenous Glucose Tolerance Test, or IVGTT. In a second method, oral administration of CRN04777 rapidly eliminated the need for IV glucose support in individuals who were administered a sulfonylurea, a class of drugs that induces insulin secretion analogous to the most common genetic defect in congenital HI patients. The reductions in insulin secretion and resulting changes in plasma glucose in these pharmacologic evaluations suggest that CRN04777 binds and activates pancreatic ß-cell SST5 to inhibit insulin secretion, as designed. CRN04777 was well tolerated in the healthy volunteers who enrolled in these SAD cohorts and all adverse events were considered mild or moderate.
These newly announced findings will be presented during the 2021 Congenital Hyperinsulinism International Virtual Research Conference. The presentation, titled: “Single Dose Results from a Phase 1 Clinical Trial of CRN04777, an Orally Bioavailable SST5-Selective, Nonpeptide Somatostatin Agonist for the Treatment of Congenital Hyperinsulinism: Pharmacokinetics and Pharmacodynamics in Healthy Volunteers,” will be made available to conference attendees in the Clinical Trials and Industry Engagement track from 1:00 PM – 2:05 PM Eastern Time on September 18th. Congenital Hyperinsulinism International is a nonprofit organization dedicated to providing information, resources and support to the global congenital HI community.
Julie Raskin, executive director of Congenital Hyperinsulinism International (CHI), added, “For many congenital HI families, life revolves around trying to maintain normal blood sugar levels in a loved one to avoid brain damage. New treatments are necessary so children and adults with congenital HI can lead a normal life. We applaud the work being done at Crinetics to address this rare disease and are looking forward to the discussion of this compelling Phase 1 data with the broader congenital HI community at our upcoming conference.”<>“Congenital HI patients and their families are a source of inspiration for our company and it is tremendously rewarding to see that we may be able to bring our drug discovery and development talents to their aid,” said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “The pharmacologic proof-of-concept data presented today represent yet another major step forward for Crinetics and are a testament to the abilities and hard work of all our staff and collaborators. Taking a broader view, these data have allowed us to achieve the important goal of expanding our clinical pipeline to three new chemical entities: paltusotine, CRN04894 and CRN04777, each with clinically demonstrated pharmacologic proof-of-concept. We look forward to continuing to advance these compounds and others in our growing pipeline.”
In addition to the ongoing Phase 1 trial of CRN04777, Crinetics also continues to advance its Phase 3 PATHFNDR program evaluating paltusotine in acromegaly and the multiple ascending dose (MAD) portion of its Phase 1 trial evaluating CRN04894, an investigational, oral, nonpeptide adrenocorticotropic hormone (ACTH) antagonist. Data from the MAD portions of the Phase 1 CRN04777 and CRN04894 trials are now expected in Q1 2022.
Data Review Conference Call
In September 2020, it was announced that the U.S. Food and Drug Administration granted rare pediatric disease designation for CRN04777 for congenital hyperinsulinism. A rare pediatric disease is defined to include a serious or life-threatening disease, which primarily affects individuals aged from birth to 18 years and affects fewer than 200,000 people in the United States.
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