Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumours.  They have a lead molecule, paltusotine (also referred to as CRN01941 for NET and more recently as CRN00808 for Acromegaly and NET), that may turn out to be best in class. Phase 2 testing for Acromegaly is on track to be completed in Q4 2020. Phase 3 trial likely in 2021 and if successful, they are hoping for FDA approval in 2023 (although the impact of COVID may move these dates to the right).  But it is already behind as FDA recently approved Chiasma’s Mycapssa product earlier this year.  This article indicated paltusotine may be a superior product. 

The company is also developing oral nonpeptide somatostatin agonists for hyperinsulinism, as well as oral nonpeptide ACTH antagonists for the treatment of Cushing’s disease and an SST5 antagonist for hyperinsulinism.

What is Paltusotine

It’s an oral nonpeptide somatostatin receptor subtype 2 (sst2) biased agonist* designed for the treatment of neuroendocrine tumours (NETs) that originate from neuroendocrine cells commonly found in the gut, lung, or pancreas.  From the detail contained in the clinical trials document (see below), it appears to involve a capsule.  The method of operation appears to be similar in that it wants to bind to somatostatin receptor 2 (SST2).   I will bring more technical detail once I have it.  * chemical that binds to a receptor and activates the receptor to produce a biological response.  In the meantime, see short video and note that the drug for Acromegaly is more advanced in pipeline terms.  

Paltusotine for Neuroendocrine Tumors (NETs)

In terms of the effect on NETs, these tumours typically over express SST2, somatostatin type 2 receptors. Both SST2 and 3 are involved in apoptosis of neuroendocrine tumour cells.” Paltusotine’s high level of selectivity for the SST2 receptor may translate into better efficacy in the treatment of neuroendocrine tumours given the role of the SST2 receptor. In fact, Crinetics describes paltusotine as an “oral selective SST2 agonist” differentiating it from existing molecules lacking this selectivity. Clinical trials scheduled to begin in early 2021 will determine whether this selectivity translates to improved efficacy in the treatment of neuroendocrine tumours.

For more information, please visit http://www.crinetics.com

The Phase 1 Clinical Trial of Paltusotine (formerly CRN01941) for NETs

The trial is initially only based in Perth Western Australia with a target of around 120 participants. It is not yet known if there are any plans to expand locations in subsequent phases or parts of the trial.  It also appears they are trialling the use of a capsule-based drug and another delivery method as yet unknown; the clinical trial only mentions “Oral Solution”, so it isn’t an injection. Read more at ClinicalTrials.gov using the identifier NCT03936166.  This trial is now complete. 

This is not the first somatostatin receptor-based product in the pipeline, please also check out my article about Somatostatin Analogues and Delivery Mechanisms in the pipeline – click here.

Summary of sources:

1.  Press Release – click here.
2. Manufacturers Website – click here.
3. Clinical Trials Document – click here.