Crinetics Ends Development of Experimental Therapeutic for Congenital Hyperinsulinism

Rare Daily Staff

Crinetics Pharmaceuticals, a company developing treatments for rare endocrine disorders, said in its second financial report that it is stopping development of an experimental therapy for congenital hyperinsulinism.

Congenital hyperinsulinism (CHI) is a rare disease that affects newborns and children and results in persistent hypoglycemia that can lead to serious neurological complications including seizures and brain damage. It is caused by a defect in the pancreas that results in the over production of insulin. Approximately one in every 50,000 new births are diagnosed with CHI each year. Existing pharmaceutical treatments are less than satisfactory, often necessitating the surgical intervention of partial or full pancreatectomies, the latter resulting in the patient developing type 1 diabetes.

“Unfortunately, we also suffered a setback with our CRN04777 program and made the difficult decision to wind down its development. said Scott Struthers, founder and CEO of Crinetics. “However, our recently evolved understanding of the nonclinical profile of CRN04777 suggests that it no longer meets the high standards to which we hold all drug candidates in our pipeline.”

In 2022, Crinetics reported topline data from a German phase 1 trial of CRN0477, a somatostatin receptor type 5 (SST5) agonist, and filed to start a phase 2 study in the United States. The U.S. Food and Drug Administration placed a clinical hold on the proposed study and Crinetics began collecting additional data to address the FDA’s concerns.

“While developing our response to the clinical hold issued by the FDA, results from additional nonclinical studies became available. These studies uncovered findings at exposure levels that eroded anticipated therapeutic margins for CRN04777,” the company wrote in its Q2 results.

Crinetics says these new findings are not related to those originally cited by the FDA for the clinical hold and are not present in nonclinical studies that have been conducted with other Crinetics candidates under development.

“We believe them to be specific to CRN04777 and not associated with its SST5 mechanism of action,” the company said. “In light of these findings, the company has decided to suspend further significant investment into the molecule at this time.”

Photo: Scott Struthers, founder and CEO of Crinetics