On March 30, 2022 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, reported that financial results for the fourth quarter and year ended December 31, 2021 (Press release, Crinetics Pharmaceuticals, MAR 30, 2022, View Source [SID1234611191]).

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"We are excited to have started 2022 with the momentum that we generated in 2021 across all facets of the company," said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. "Last year was transformative for Crinetics as the company achieved multiple key milestones in our discovery and clinical programs, raised significant additional capital, and continued to add world-class talent to the company from the bench to the board. Since inception, we have had a strategy of investing in innovative drug discovery programs to build a diverse endocrine pipeline. We advance this pipeline by following a uniquely efficient development paradigm that leverages endocrine biomarkers from preclinical experiments through patient studies. I am proud of how this strategy came together over the past year to move us significantly closer to our vision of building the world’s leading endocrine company."

FULL YEAR 2021 AND RECENT HIGHLIGHTS
Reported positive proof-of-concept data from two Phase 1 programs of CRN04777 and CRN04894. In September 2021 and via a separate press release issued today, Crinetics announced positive data from a Phase 1 single- and multiple-ascending dose (MAD) study of CRN04777, a somatostatin receptor type 5 (SST5) agonist being developed as a treatment for congenital and syndromic hyperinsulinisms. The results supported clinical proof-of-concept, showing strong dose-dependent suppression of fasting insulin as well as dose-dependent suppression of glucose- and sulfonylurea-induced insulin secretion. In August 2021, Crinetics announced positive preliminary data from the single ascending dose (SAD) cohorts of an ongoing Phase 1 study of CRN04894, its adrenocorticotropic hormone (ACTH) antagonist being developed for the treatment of conditions of ACTH excess, including Cushing’s disease and congenital adrenal hyperplasia. The data supported clinical proof-of-concept by providing evidence of clinically relevant cortisol suppression as well as showing dose-dependent reductions in basal cortisol levels and suppression of cortisol following ACTH challenge. The data from the Phase 1 studies for CRN04777 and CRN04894 suggested that the molecules are both orally bioavailable and support once daily dosing schedules. Preliminary data from the MAD cohorts of the CRN04894 Phase 1 study
Initiated Phase 3 PATHFNDR program evaluating paltusotine in acromegaly. In the second quarter of 2021, Crinetics initiated its Phase 3 PATHFNDR program, which consists of two Phase 3 trials assessing the safety and efficacy of once-daily oral paltusotine. Together these trials are designed to evaluate paltusotine in a wide cross section of acromegaly patients. If successful, Crinetics believes these trials could support registration of paltusotine for all acromegaly patients who require pharmacotherapy, including untreated patients and those switching from standard of care. Topline data from both of these trials (PATHFNDR-1 and PATHFNDR-2) are expected to be available in 2023.
Entered into strategic licensing agreement with Sanwa Kagaku Kenkyusho Co., Ltd. ("Sanwa") for the development and commercialization of paltusotine in Japan. Per the agreement, Crinetics received $13 million upfront and is eligible to receive development, regulatory, and commercial milestones. In addition, Crinetics will be eligible to receive tiered royalties on net product sales should paltusotine receive marketing approval in Japan. In exchange, Sanwa was granted an exclusive right to develop and commercialize paltusotine in Japan and will assume all costs associated with clinical trials and regulatory applications in the territory. Crinetics retains all rights to develop and commercialize paltusotine outside of Japan.
Co-founded Radionetics Oncology. In October 2021, Crinetics, together with 5AM Ventures and Frazier Healthcare Partners, founded Radionetics Oncology, Inc., an independently operated company that aims to develop a deep pipeline of novel, targeted, nonpeptide radiopharmaceuticals for the treatment of a broad range of oncology indications. In conjunction with formation of the company, Radionetics received an exclusive world-wide license to Crinetics’ radiotherapeutics technology platform and associated intellectual property in exchange for equity, milestones in excess of $1 billion, and single-digit royalties on net sales. Radionetics launched with $30 million from a private financing with 5AM Ventures and Frazier Healthcare Partners as the sole investors.
Announced data from an open-label extension trial of paltusotine in acromegaly. Results showed that oral paltusotine maintained serum IGF-1 at levels previously achieved with injected somatostatin receptor ligands for up to 51 weeks. The results were featured in a poster presentation at the Society for Endocrinology BES congress, which can be found here.
Unveiled a parathyroid hormone receptor antagonist program. In September 2021, Crinetics announced its intent to develop a nonpeptide oral parathyroid hormone (PTH) receptor antagonist for the treatment of hypercalcemia associated with hyperparathyroidism (HPT) and other diseases of PTH receptor type 1 (PTHR1) over-activation. Crinetics is in the late stages of selecting a lead candidate from this family of compounds and anticipates initiation of IND-enabling studies in 2022. If successful, PTHR1 antagonists could represent a viable treatment option to improve the outcomes and experience of patients with primary hyperparathyroidism. Details on the preclinical efforts supporting the program were presented in a late-breaking poster at the annual meeting of the American Society for Bone and Mineral Research (ASBMR). More information on the program and a copy of the poster can be found here.
Strengthened balance sheet with successful common stock offerings. In April 2021, Crinetics completed an underwritten follow-on offering of 4,562,044 shares of its common stock at a price to the public of $16.44 per share, raising gross proceeds of approximately $75.0 million. In July 2021, Crinetics entered into a securities purchase agreement with Frazier Healthcare Partners for the private placement of 851,306 shares at $17.62 per share, raising gross proceeds of $15.0 million. In October 2021, Crinetics completed an underwritten public offering of 8,712,400 shares of its common stock at a price to the public of $19.80 per share, raising gross proceeds of approximately $172.5 million.
Strengthened company leadership with appointments to management team and Board of Directors. Throughout 2021 and in early 2022, Crinetics built upon its strong leadership and scientific expertise by appointing Garlan Adams to the role of general counsel, Jeff Knight to the role of chief operating officer, James Hassard to the role of chief commercial officer, Christopher Robillard to the role of chief business officer, and Dr. Rogério Vivaldi Coelho and Caren Deardorf to the Board of Directors.

FOURTH QUARTER AND FULL YEAR 2021 FINANCIAL RESULTS
Research and development expenses were $24.6 million and $84.3 million for the three months and full year ended December 31, 2021, respectively, compared to $16.8 million and $57.0 million for the same periods in 2020. The increases were primarily attributable to increased spending on manufacturing and development activities associated with our clinical and nonclinical activities for paltusotine, CRN04777, CRN04894, and our other preclinical research programs.
General and administrative expenses were $7.4 million and $24.5 million for the three months and full year ended December 31, 2021, respectively, compared to $5.0 million and $18.0 million for the same periods in 2020. The increases were primarily due to personnel-related costs.
Net loss for the three months ended December 31, 2021, was $30.8 million, compared to a net loss of $21.6 million for the same period in 2020. For the year ended December 31, 2021, the company’s net loss was $107.6 million compared to a net loss of $73.8 million for the year ended December 31, 2020.
Unrestricted cash, cash equivalents and investments totaled $333.7 million as of December 31, 2021, compared to $193.3 million as of September 30, 2021, and $170.9 million as of December 31, 2020.
Revenues were $1.1 million for the three months and full year ended December 31, 2021, consisting of non-cash upfront consideration recognized upon the transfer of intellectual property from Crinetics to Radionetics Oncology.
The company had 47,784,611 common shares outstanding as of March 25, 2022.

WEBCAST AND CONFERENCE CALL ON CRN04777 MULTIPLE-ASCENDING DOSE DATA
Crinetics will hold a conference call and live audio webcast today, March 30, 2022, at 4:30 p.m. Eastern Time to discuss results from the multiple-ascending dose cohorts of the Phase 1 trial of CRN04777. These results were announced in a separate press release issued earlier today, which is available on the company’s website. To participate, please dial 1-877-407-0789 (domestic) or 1-201-689-8562 (international) and refer to conference ID 13727857. To access the webcast, click here. Following the live event, a replay will be available on the Events page of the Company’s website.