Paltusotine (formerly CRN00808)


Paltusotine, our lead product candidate, establishes a new class of oral, selective, nonpeptide, somatostatin receptor type 2 (SST2) agonists designed for the treatment of acromegaly. Somatostatin is a neuropeptide hormone that broadly inhibits the secretion of other hormones, including growth hormone, or GH, from the pituitary gland. Acromegaly arises from a benign pituitary tumor that secretes excess GH that in turn causes excess secretion of insulin-like growth factor-1, or IGF-1, by the liver. This loss of homeostasis in the GH axis results in excess tissue growth and other adverse effects throughout the body.

For the Treatment of Acromegaly


Somatostatin peptide analogs are the primary pharmacotherapy for those acromegaly patients who are candidates for chronic pharmacological intervention. Currently marketed peptide drugs require painful monthly or daily injections, or a strict twice-a-day oral dosing regimen. In the case of somatostatin peptide drugs, therapies often fail to fully control the disease in many acromegaly patients.

FOR THE TREATMENT OF NEUROENDOCRINE TUMORS (NETs)


Neuroendocrine tumors, or NETs, originate from the neuroendocrine cells commonly found in the gut, lung, or pancreas. NETs are heterogeneic in their behavior, comprising a spectrum of insidious, growing tumors to aggressive, quick-growing tumors. Most NETs express SST2 receptors and injected depots of peptide somatostatin analogs have become the first-line standard of care for many NETs patients, as detailed in National Comprehensive Cancer Network guidelines.

First Half 2021


We will begin Phase 3 trials in acromegaly and anticipate beginning a Phase 2 trial in NETs.

Late 2020


We expect to report data from the Phase 2 trials.

Late 2018


Initiated two global Phase 2 clinical trials of paltusotine in acromegaly patients: ACROBAT EVOLVE and ACROBAT EDGE. Both completed their recruitment phase and were conducted at the same centers in the U.S. and globally. Patients who completed either study were eligible to participate in an open-label extension study (ACROBAT ADVANCE).

EVOLVE: Double-blind, placebo-controlled, randomized withdrawal study to evaluate the safety, efficacy, and pharmacokinetics of paltusotine compared to placebo in subjects with acromegaly who respond to octreotide LAR or lanreotide depot monotherapy.

EDGE: Open-label exploratory study to evaluate the safety, efficacy, and pharmacokinetics of paltusotine in subjects with acromegaly treated with somatostatin analog-based treatment regimens but who do not respond completely to monotherapy.

August 2018


Submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA).

March 2018


Initial results reported from a Phase 1, double-blind, randomized, placebo-controlled, single- and multiple-ascending dose trial to evaluate the safety, pharmacokinetics, and pharmacodynamics of paltusotine in 99 healthy volunteers.

Paltusotine demonstrated POC by potently suppressing stimulated GH and baseline IGF-1 in these subjects. Plasma exposure of paltusotine indicated the drug was well-absorbed with a half-life of 42 to 50 hours, supporting once-daily administration in patients. The safety and tolerability of paltusotine observed in this trial was generally consistent with that of approved peptide somatostatin analogs.

Absolute Oral Bioavailability and Absorption, Metabolism, Excretion of [14C]-Labeled Paltusotine (CRN00808), an Orally Bioavailable, Nonpeptide, Selective, Somatostatin Receptor 2 (sst2) Biased Agonist for the Treatment of Acromegaly

Ajay Madan, Rosa Luo, Christine Ferrara-Cook, R. Scott Struthers, Sjoerd van Marle, and Alan Krasner Crinetics Pharmaceuticals, San Diego, CA, USA. PRA Health Sciences, Groningen, The Netherlands.

Final Results From the First in Man Phase 1 Clinical Trial of CRN00808, an Orally Bioavailable sst2-Selective, Nonpeptide Somatostatin Biased Agonist for the Treatment of Acromegaly: Safety, Pharmacokinetics, Pharmacodynamics, and Midazolam Drug Interaction in Healthy Volunteers

Ajay Madan, Yun Fei Zhu, Stacy Markison, Stephen F. Betz, Alan Krasner, Rosa Luo, Tilman Oltersdorf, Theresa Jochelson, Jason Lickliter, R. Scott Struthers. ENDO 2019. March 23-26, 2019; New Orleans.