Crinetics Pharmaceuticals, Inc. presented efficacy, safety and patient-reported outcome (PRO) data at ENDO 2023 for paltusotine, an experimental, once-daily, oral, small molecule somatostatin receptor type 2 (SST2) agonist in Phase 3 clinical development for the treatment of acromegaly. The Endocrine Society’s annual meeting, ENDO 2023, was held June 15-18, 2023, in Chicago, Illinois. Dr. Monica R. Gadelha, M.D., Ph.D., professor of endocrinology at the Medical School of the Universidade Federal do Rio de Janeiro and a principal investigator in the Phase 2 ACROBAT program presented results from a planned two-year analysis of the company’s ongoing ACROBAT Advance open-label extension study at a podium presentation at ENDO 2023.

Results demonstrated that patients switching from therapy with injected somatostatin receptor ligands (SRLs) to oral paltusotine maintained stable levels of key measures associated with acromegaly including insulin-like growth factor 1, growth hormone, acromegaly symptom diary (ASD) score, blood pressure, hemoglobin A1c, ring size, and body weight. The ASD score was a composite representing participants’ daily impressions of common acromegaly symptoms including headache, joint pain, sweating, fatigue, weakness, swelling, and numbness/tingling. Approximately 90% of participants said they preferred once-daily, oral paltusotine over current standard of care of injected SRLs when asked after one year of treatment.

Paltusotine was well tolerated, with a safety profile similar to injected SRLs. Two Phase 3 studies for paltusotine in acromegaly are currently ongoing. Crinetics also presented preclinical proof-of-concept data on a parathyroid hormone receptor type 1 (PTH1R) antagonist, which is initially intended for the treatment of primary hyperparathyroidism (PHPT), which leads to hypercalcemia and bone loss if untreated.

PHPT affects approximately 100,000 people annually in the U.S. Additional indications that may be addressed by a PTH1R antagonist include humoral hypercalcemia of malignancy (HHM), which is estimated to occur in as many as 200,000 cancer patients annually. The data presented in a poster at ENDO on June 17th show Crinetics’ PTH1R antagonist suppressing PTH-stimulated increases in ionized calcium, urinary cAMP, and bone resorption biomarkers in rats. In addition, a thyroid-stimulating hormone (TSH) receptor antagonist for the treatment of thyroid eye disease (orbitopathy) associated with Graves’ disease was unveiled in a poster presentation.

Graves’ is an autoimmune disease characterized by chronic overstimulation of the TSH receptor, which results in hyperthyroidism. In approximately 30% of patients, it also results in thyroid eye disease (TED) due to overactivation of the TSH receptor in orbital fibroblasts. Crinetics described preclinical proof-of-concept results from a pharmacologic rat model of Graves’ disease.

These results showed an oral small molecule TSHR antagonist suppressing production of a key thyroid hormone, thyroxine (T4), which is over expressed in Graves’ disease and can lead to the pain, swelling, blurry vision, and proptosis associated with TED.