Crinetics Pharmaceuticals Announces Dosing of First Patient in Phase 3 PATHFNDR-1 Study Evaluating Oral Paltusotine for the Treatment of Acromegaly

Rhea-AI Summary

Crinetics Pharmaceuticals (CRNX) announced the randomization of its first acromegaly patient in the Phase 3 clinical trial of paltusotine, known as PATHFNDR-1. This trial aims to evaluate the safety and efficacy of this once-daily oral treatment compared to placebo in patients already controlled by injectable therapies. Successful results could support paltusotine's market registration in the U.S. and Europe. Topline data is anticipated in 2023, marking a significant step toward offering an innovative treatment option for acromegaly patients.

Positive

• First patient randomized in Phase 3 trial of paltusotine, marking progress in clinical development.
• Potential to offer a once-daily oral treatment option for acromegaly patients, differing from painful injections.
• Successful Phase 3 outcomes could support registration in the U.S. and Europe.

Negative

• Regulatory hurdles may necessitate additional trials before approval.
• The trial is dependent on external factors such as FDA feedback and COVID-19 impacts.

- If successful, paltusotine would offer acromegaly patients a once-daily oral treatment option -

SAN DIEGO, June 28, 2021 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: 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 the randomization of the first acromegaly patient in its Phase 3 clinical trial of paltusotine, PATHFNDR-1. This trial will be one of two planned Phase 3 studies assessing the safety and efficacy of once-daily oral paltusotine in acromegaly patients that together will evaluate paltusotine in a wide cross section of acromegaly patients. If successful, Crinetics believes its Phase 3 program could support registration of paltusotine in the United States and Europe for all acromegaly patients who require pharmacotherapy.

“The dosing of the first patient in the PATHFNDR program represents a key step in paltusotine’s clinical development. We believe that, if successful, these trials would support paltusotine’s approval as the first nonpeptide, oral alternative to the injected standard of care for the treatment of acromegaly,” said Alan Krasner, M.D., Crinetics’ chief medical officer. “Our goal for paltusotine is to provide a once daily oral option for acromegaly patients that can help control excess hormone levels while at the same time relieving the burden and pain of currently available therapies.”

“This is the first product candidate in our emerging endocrine pipeline to reach Phase 3 clinical trials. I am very proud of the team that created paltusotine and facilitated its development to this stage,” added Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “We are now focused on completing these trials and, if approved, making paltusotine available to acromegaly patients around the world. At the same time, we remain committed to advancing our pipeline of nonpeptide product candidates for endocrine patients and investing in our small molecule discovery approach to continue to grow that pipeline.”

About the PATHFNDR-1 Study
PATHFNDR-1 (NCT04837040) is planned to enroll 52 patients with acromegaly who are biochemically controlled, meaning insulin-like growth factor-1 (IGF-1) ≤ 1.0x upper limit of normal (ULN), on octreotide or lanreotide depot monotherapy. Following a screening period, during which baseline values for IGF-1, growth hormone (GH) and total Acromegaly Symptom Diary Score will be determined, participants will be randomized 1-to-1 to receive once-daily oral paltusotine or placebo for nine months. The primary endpoint in PATHFNDR-1 will be the proportion of patients who are biochemically controlled during weeks 32-36. For statistical success on the trial’s primary endpoint, paltusotine needs to demonstrate superiority to placebo in this responder analysis. All eligible patients will have the option to participate in an open-label extension study following conclusion of the PATHFNDR-1 treatment period. Topline data from the PATHFNDR-1 trial is expected to be available in 2023.

About Acromegaly
Acromegaly is a serious disease generally caused by a pituitary adenoma, a benign tumor in the pituitary that secretes growth hormone. Excess GH secretion causes excess secretion of IGF-1 from the liver. Together, excess of these hormones leads to the symptoms and physician manifestations of acromegaly, including abnormal growth of hands and feet, alteration of facial features, arthritis, carpal tunnel syndrome, joint aches, deepening of voice due to enlarged vocal cords, fatigue, sleep apnea, enlargement of heart, liver and other organs, and changes in glucose and lipid metabolism.

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 (SRLs) are the most common initial pharmacologic treatment, however these drugs require monthly depot injections with large gauge needles that are commonly associated with pain, injection site reactions, and increased burden of therapy on the lives of patients.

About Paltusotine
Paltusotine is an investigational, orally available nonpeptide 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. A previously completed Phase 1 trial of paltusotine showed clinical proof of concept by providing evidence of potent suppression of the growth hormone axis in healthy volunteers. In Phase 2 trials, paltusotine maintained IGF-1 levels in acromegaly patients who switched from injectable depot medications to once-daily oral paltusotine. IGF-1 is the primary biomarker endocrinologists use to manage their acromegaly patients.

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, is an investigational, oral, selective nonpeptide somatostatin receptor type 2 agonist for the treatment of acromegaly, an orphan disease affecting more than 26,000 people in the United States. A Phase 3 program to evaluate safety and efficacy of paltusotine for the treatment of acromegaly is underway. Crinetics also plans to advance paltusotine into a Phase 2 trial for the treatment of carcinoid syndrome associated with neuroendocrine tumors. The company is also developing CRN04777, an investigational, oral, nonpeptide somatostatin receptor type 5 (SST5) agonist for congenital hyperinsulinism, as well as CRN04894, an investigational, 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.

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 for the PATHFNDR program to support registration of paltusotine in the United States and Europe for all acromegaly patients who require pharmacotherapy; the expected timing of topline data from the PATHFNDR-1 trial; plans to advance paltusotine into a Phase 2 trial for the treatment of carcinoid syndrome associated with neuroendocrine tumors; and plans to advance other pipeline product candidates and to invest in the small molecule discovery approach. 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 FDA or other regulatory agencies may require one or more additional clinical trials of paltusotine or suggest changes to Crinetics’ planned Phase 3 clinical trials prior to and in support of the approval of a New Drug Application or applicable foreign regulatory approval; advancement of paltusotine into a Phase 2 trial for carcinoid syndrome is 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, CRN04894, CRN04777, 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.

Contacts:
Marc Wilson
Chief Financial Officer
IR@crinetics.com
(858) 450-6464

Investors / Media:
Corey Davis
LifeSci Advisors, LLC
cdavis@lifesciadvisors.com
(212) 915-2577

Aline Sherwood
Scienta Communications
asherwood@scientapr.com
(312) 238-8957

FAQ

What is the purpose of the PATHFNDR-1 trial for CRNX?

The PATHFNDR-1 trial evaluates the safety and efficacy of paltusotine as a treatment for acromegaly patients.

When can we expect topline data from the PATHFNDR-1 trial?

Topline data from the PATHFNDR-1 trial is expected to be available in 2023.

What are the potential market implications if paltusotine is approved?

If approved, paltusotine could become the first nonpeptide oral option for acromegaly patients, potentially expanding treatment options and market reach.

What are the eligibility criteria for patients in the PATHFNDR-1 trial?

Patients eligible for the trial are those with acromegaly, biochemically controlled on octreotide or lanreotide depot monotherapy.

What is paltusotine designed to do?

Paltusotine is designed to be a selective oral treatment for managing excess hormone levels associated with acromegaly.