Crinetics Pharmaceuticals Provides New Data from Paltusotine and ACTH Antagonist Development Programs at European Congress of Endocrinology

SAN DIEGO, Sept. 04, 2020 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. 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 that a presentation on the company's orally administered, small molecule adrenocorticotropic hormone (ACTH) antagonist was selected for a late-breaking session at the virtual European Congress of Endocrinology (eECE) on September 8, 2020. In addition, a poster summarizing results from Phase 1 bioavailability studies of paltusotine (formerly CRN00808), the company's lead candidate for the treatment of acromegaly, will be available to congress attendees from September 5-9, 2020.

Crinetics is developing an ACTH antagonist for the treatment of diseases associated with excess ACTH such as Cushing's disease and congenital adrenal hyperplasia (CAH). In the presentation at eECE, Crinetics will present data that one of a lead series of experimental ACTH antagonists reduced corticosterone levels and had a positive effect on adrenal gland size, morphology and function after seven days of repeat dosing in a rat model of ACTH excess. Based on these favorable preclinical in vivo results, Crinetics plans to advance its lead ACTH antagonist into Phase 1 single-ascending dose (SAD) and multiple-ascending dose (MAD) studies in healthy volunteers in late 2020 or early 2021.

"Our drug candidate is on track to be the first ACTH antagonist to enter clinical development for treatment of diseases driven by ACTH excess, including Cushing's Disease and CAH," explained Alan Krasner M.D., Chief Medical Officer of Crinetics. "An orally available, potent, nonpeptide drug could have a very meaningful impact in these patients for whom there are limited therapeutic options. We look forward to achieving the next milestone in this program by advancing our lead ACTH antagonist candidate into Phase 1."

Separately, in a poster presentation at eECE, Crinetics will report results from a Phase 1 study showing that paltusotine provided a favorable mean oral bioavailability of 70%. In addition, no abundant circulating metabolites of paltusotine were identified. Adverse events associated with paltusotine were generally mild and transient and were consistent with those reported with other somatostatin agonists. The results of this study suggest that paltusotine exhibits excellent properties appropriate for chronic once-daily oral treatment of patients with acromegaly.

In April 2020, Crinetics reported interim results from an exploratory analysis of the first 13 patients who entered the ACROBAT Edge Phase 2 trial on octreotide or lanreotide depot monotherapy, which showed that, as of the cutoff date, switching to once daily oral paltusotine maintained IGF-1 levels at those achieved with prior depot therapy. Paltusotine was well tolerated and the adverse events observed were similar to those of other somatostatin agonists. No discontinuations due to drug-related adverse events occurred, and the most common treatment-emergent adverse events (>10%) were headache, arthralgia, peripheral swelling, back pain and hyperhidrosis.

Scott Struthers, Ph.D., founder and Chief Executive Officer of Crinetics, added, "We look forward to reporting topline results from the full ACROBAT dataset in the fourth quarter of this year. At that time, we anticipate having a more complete picture of paltusotine's pharmacokinetic and clinical profile, including the ability to maintain IGF-1 levels after switching patients from their prior somatostatin receptor ligand depot therapy."

The poster and oral presentations will be made available on www.crinetics.com following the conclusion of the eECE meeting. Within the virtual ECE environment, they are:

In addition to the above eECE presentations, Crinetics will hold a Hub session titled: New Frontiers in Endocrine Research on September 9^th at 08:00 CET during which Dr. Krasner will provide an overview of Crinetics and its pipeline programs. The eECE Hub sessions are open to all healthcare professionals who are registered for eECE 2020. More information may be found on the ECE website: ese-hormones.org/e-ece-2020.

About Paltusotine
Paltusotine (formerly CRN00808) is an orally available nonpeptide biased agonist that is designed to be highly selective for the somatostatin receptor type 2 (sst2). It was designed by the Crinetics discovery team to provide a once daily option for patients with acromegaly and neuroendocrine tumors that are currently treated by injected therapies that sell approximately $3.1 billion annually. Non-clinical chronic toxicology studies are complete and no dose limiting toxicity was identified at the maximum feasible doses in rats and dogs. Crinetics previously completed a Phase 1 trial that showed potent suppression of the growth hormone (GH) axis in healthy volunteers, which provided clinical proof-of-concept. In addition, the molecule's observed plasma half-life of ~2 days suggested the potential for paltusotine for once daily oral administration. A subsequent Phase 1 trial showed that paltusotine is 70% orally bioavailable.

About Acromegaly
Acromegaly is a serious disease generally caused by a benign growth hormone secreting tumor in the pituitary. Excess GH secretion causes excess secretion of insulin-like growth factor-1 (IGF-1) from the liver, which causes bone and cartilage overgrowth, organ enlargement, and changes in glucose and lipid metabolism. The symptoms of acromegaly include abnormal growth of hands and feet and changes in shape of the bone and cartilage that result in alteration of facial features. Overgrowth of bone and cartilage and thickening of tissue leads to arthritis, carpal tunnel syndrome, joint aches, enlarged lips, nose and tongue, deepening of voice due to enlarged vocal cords, sleep apnea due to obstruction of airways, and enlargement of heart, liver, and other organs.

Surgical removal of pituitary adenomas, if possible, is the preferred initial treatment for most acromegaly patients. Pharmacological treatments are used for patients that are not candidates for surgery, or when surgery is unsuccessful in achieving treatment goals. Approximately 50% of patients with acromegaly prove to be candidates for pharmacological treatment. Long-acting somatostatin receptor ligands (SRL) are usually the initial pharmacologic treatment, however these drugs require monthly injections and are commonly associated with pain, injection site reactions, and increased burden in the lives of patients. Although over 90% of patients have demonstrable responses to SRLs (Annals of Internal Medicine. 1992; 117:711-718) only 20-40% of patients achieve normalization of IGF-1 (J Clin Endocrinol Metab 99: 791–799, 2014). Additional pharmacological treatment options include dopamine agonists or GH receptor antagonists which may be used in combination with SRLs.

About Cushing's Disease and Congenital Adrenal Hyperplasia
Cushing's Disease is an orphan indication with a prevalence of approximately 12,000 patients in the United States. It presents much more commonly in women, and usually between 30 and 50 years of age. Cushing's disease often takes many years to diagnose and may well be under-diagnosed in the general population as many of its symptoms such as lethargy, depression, obesity, hypertension, hirsutism and menstrual irregularity can be incorrectly attributed to other more common disorders.

CAH encompasses a set of disorders that are caused by genetic mutations that result in impaired cortisol synthesis. This lack of cortisol leads to a breakdown of feedback mechanisms and results in persistently high levels of ACTH, which in turn causes overstimulation of the adrenal cortex. The resulting adrenal hyperplasia and over-secretion of other steroids (particularly androgens) and steroid precursors can lead to a variety of adverse effects including atypical genital development, early puberty, abnormal growth, and infertility. CAH occurs in 1 in 13,000 to 1 in 15,000 live births.

About Crinetics Pharmaceuticals
Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors. The company's lead product candidate, paltusotine (formerly CRN00808), is an oral selective nonpeptide somatostatin receptor type 2 biased agonist undergoing two Phase 2 clinical trials for the treatment of acromegaly, an orphan disease affecting more than 25,000 people in the United States. Crinetics plans to advance paltusotine into a Phase 3 trial in acromegaly and a Phase 2 trial for the treatment of carcinoid syndrome associated with NETs in 2021. The company is also developing an oral nonpeptide somatostatin receptor type 5 (sst5) agonist for hyperinsulinism, as well as an oral nonpeptide ACTH antagonist for the treatment of Cushing's disease, congenital adrenal hyperplasia and other diseases of excess ACTH. All of the company's drug candidates are new chemical entities resulting from in-house drug discovery efforts and are wholly owned by the company. For more information, please visit www.crinetics.com.

Forward-Looking Statements
Crinetics cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the company's current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding: the potential of Crinetics' ACTH antagonist to have a meaningful impact on patient care; the potential to initiate Phase 1 trials of Crinetics' lead ACTH antagonist and the timing thereof; the potential of paltusotine to be an effective treatment option for acromegaly patients; the potential for interim data results to be consistent with final results, once available; the potential for any of our ongoing clinical trials to show safety or efficacy; the potential to initiate a pivotal Phase 3 trial of paltusotine in acromegaly and the timing thereof; and the anticipated timing of topline data for the ACROBAT Phase 2 trials. The inclusion of forward-looking statements should not be regarded as a representation by Crinetics that any of its plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Crinetics' business, including, without limitation: the risk that interim results of a clinical trial do not necessarily predict final results and that one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, and as more patient data become available; potential delays in the commencement, enrollment and completion of clinical trials and the reporting of data therefrom; advancement of paltusotine into a Phase 3 trial and Crinetics' lead ACTH antagonist into Phase 1 trials are dependent on and subject to the receipt of further feedback from the FDA; the COVID-19 pandemic may disrupt Crinetics' business and that of the third parties on which it depends, including delaying or otherwise disrupting its clinical trials and preclinical studies, manufacturing and supply chain, or impairing employee productivity; the company's dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; the success of Crinetics' clinical trials and nonclinical studies for paltusotine, its ACTH antagonist and its other product candidates; regulatory developments in the United States and foreign countries; unexpected adverse side effects or inadequate efficacy of the company's product candidates that may limit their development, regulatory approval and/or commercialization; Crinetics may use its capital resources sooner than it expects; and other risks described under the heading "Risk Factors" in documents the company files from time to time with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Crinetics undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.