Hyperparathyroidism, Primary

AstraZeneca is splashing out $800 million upfront to bolster its rare disease pipeline with the purchase of Amolyt Pharma and its Phase III asset for chronic hypoparathyroidism.Marc Dunoyer, chief executive of AstraZeneca’s rare-disease unit Alexion, noted that patients with chronic hypoparathyroidism “face a significant need for an alternative to current supportive therapies,” with Amolyt’s eneboparatide holding “the potential to lessen the often debilitating impact of low parathyroid hormone and avoid the risks of high-dose calcium supplementation.”Eneboparatide – also known as AZP-3601 – is a PTH receptor 1 agonist that in Phase II studies has shown the ability to achieve normalisation of serum calcium levels, as well as the potential to eliminate dependence on daily calcium and vitamin D supplementation. AstraZeneca noted that in adults with chronic hypoparathyroidism and hypercalciuria, eneboparatide normalised calcium in urine, while it also preserved bone mineral density.According to Amolyt’s website, its pipeline also includes AZP-3813 for acromegaly - with initial Phase I results expected later this year - and the preclinical candidate AZP-40XX for primary hyperparathyroidism and humoral hypercalcemia of malignancy.Along with the upfront payment, Amolyt shareholders are eligible to receive an additional $250 million payable upon achievement of a specified regulatory milestone. The acquisition is expected to close by the end of the third quarter.

Pictured: AstraZeneca's headquarters in Silicon Valley/iStock, Sundry Photography AstraZeneca on Thursday announced that it is acquiring rare disease specialist Amolyt Pharma in a deal that could reach $1.05 billion in value. Under the terms of the agreement, AstraZeneca will buy Amolyt’s outstanding shares for a total of $800 million, due on the deal’s closing. Amolyt will also be entitled to a contingent payment of $250 million upon meeting a yet-undisclosed regulatory milestone. The partners expect to complete the transaction in the third quarter of 2024, pending regulatory clearances and other customary closing conditions. After the acquisition is closed, Amolyt and its employees will join AstraZeneca’s rare disease unit Alexion. At the center of the acquisition is Amolyt’s late-stage candidate for the rare disease hypoparathyroidism, which is characterized by low levels of the parathyroid hormones in the blood. Patients with hypoparathyroidism also have abnormal levels of calcium and phosphorous, which can lead to complications such as kidney problems and heart failure. “Chronic hypoparathyroid patients face a significant need for an alternative to current supportive therapies, which do not address the underlying hormone deficiency,” Alexion CEO Marc Dunoyer said in a statement, adding that eneboparatide could “lessen the often-debilitating impact of low parathyroid hormone” while also avoiding the “risks of high-dose calcium supplementation.” Dubbed eneboparatide, Amolyt’s candidate for hypoparathyroidism activates the parathyroid hormone receptor 1, leading to stable and sustained calcium levels in the blood and normal calcium excretion through the urine. According to the biotech’s website, this mechanism of action allows eneboparatide to treat the symptoms of hypoparathyroidism and avoid kidney disease, while also slowly removing the need for calcium and vitamin D supplementation. Eneboparatide also helps preserve bone integrity by normalizing bone turnover levels and lowering bone resorption. In a Phase IIa study, 93% of patients who were treated with eneboparatide were able to stop standard of care treatment using calcium and vitamin D supplementation. Urinary calcium excretion also dropped to normal levels, while serum calcium levels remained within target range. Patients also showed stable bone mineral density, including those who had osteopenia. In May 2023, Amolyt announced that it had competed an end-of-Phase II meeting with the FDA and that it would launch a Phase III study of eneboparatide in hypoparathyroidism. The biotech at the time envisioned the study, dubbed Calypso, to be the largest Phase III trial to date in this indication. Top-line data are expected by the end of 2024. In addition to eneboparatide, AstraZeneca will also gain ownership of AZP-3813, which is being assessed for acromegaly with topline Phase I data expected in the first half of this year. Amolyt is also developing AZP-40XX, which is still in the very early stages of development for primary hyperparathyroidism and humoral hypercalcemia of malignancy. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Phase 3 PATHFNDR-2 Study Topline Results Expected in March 2024; Pending Results, NDA Submission in Acromegaly Anticipated 2H 2024 Phase 2 Study of Paltusotine in Carcinoid Syndrome Full Topline Results Expected 1H 2024 Announced a $350 Million Private Placement Equity Financing Management Hosting Conference Call and Webcast at 4:30 p.m. ET Today SAN DIEGO, Feb. 28, 2024 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today reported financial results for the fourth quarter and full year ended December 31, 2023. “As we reflect on our achievements in 2023, this was a truly significant year for Crinetics, laying the foundation for our next phase of growth,” said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “Our lead investigational compound, paltusotine, continues to demonstrate highly promising results, underscored by the success of the Phase 3 PATHFNDR-1 study in acromegaly and encouraging initial findings in the ongoing Phase 2 study in carcinoid syndrome. Pending results from our second Phase 3 PATHFNDR-2 study this quarter, we are on track to submit a New Drug Application (NDA) for paltusotine in acromegaly in the second half of 2024. We also expect full results from our Phase 2 study in carcinoid syndrome in the first half of this year. Looking ahead, 2024 and 2025 are poised to be transformational years as we advance our late-stage product candidate and prepare for a potential commercial launch, while also leveraging our world class in-house R&D expertise to enrich our pipeline with additional promising candidates in high-prevalence endocrine and metabolic indications. To support these growth activities, we announced a $350 million private placement that is expected to extend our cash runway into 2028.” Full Year 2023 and Recent Highlights: Phase 3 PATHFNDR-1 study achieved primary and all secondary endpoints. In September 2023, Crinetics reported positive topline results from its placebo-controlled Phase 3 clinical study of paltusotine in participants with acromegaly switching from standard-of-care injected depot somatostatin analogs, which is designed to support an indication for the maintenance of acromegaly treatment. Reported positive initial data from Phase 2 study of paltusotine in carcinoid syndrome. In December 2023, Crinetics reported an initial analysis of data from a subset of 27 patients. The study has completed enrollment. Completed enrollment in Phase 3 PATHFNDR-2 study of paltusotine. PATHFNDR-2 is a placebo-controlled Phase 3 study of oral paltusotine in participants with acromegaly who are treatment-naïve or not currently receiving medical therapy, which is designed to support an indication for the treatment of acromegaly. Presented clinical and preclinical data at the ENDO 2023 Annual Conference. Presentations at the June 2023 conference featured results from in vivo studies of the company’s preclinical parathyroid hormone receptor type 1 (PTH1R) antagonist being developed for the treatment of primary hyperparathyroidism (PHPT), and the company’s preclinical thyroid-stimulating hormone (TSH) receptor antagonist for the treatment of thyroid eye disease (orbitopathy) associated with Graves’ disease. In addition, Scott Struthers, Ph.D., Crinetics’ founder and CEO was awarded the John D. Baxter Prize for extraordinary achievement in endocrinology entrepreneurship at ENDO 2023. Strengthened balance sheet with $350 million private placement financing. Earlier today, February 28, 2024, Crinetics announced a private placement equity financing for gross proceeds of approximately $350 million. Additional details regarding the financing are available in the press release (click here). Key Upcoming Milestones Topline results from the Phase 3 PATHFNDR-2 study of paltusotine are expected in March 2024. Topline results from the Phase 2 study of paltusotine in carcinoid syndrome are expected in the first half of 2024. Paltusotine NDA submission is anticipated in the second half of 2024. Pending successful data from the PATHFNDR-2 study, Crinetics plans to submit an NDA to the U.S. Food and Drug Administration (FDA) seeking regulatory approval for both the treatment of and maintenance of treatment of acromegaly indications. Initial results from ongoing Phase 2 study of oral CRN04894 in congenital adrenal hyperplasia (CAH) are expected in the second quarter of 2024. The Phase 2 study is an open-label, study evaluating the safety, efficacy and pharamacokinetics of different doses of CRN04894 in participants with CAH after 12 weeks of treatment. Fourth Quarter and Full Year 2023 Financial Results Research and development expenses were $45.6 million and $168.5 million for the three months and full year ended December 31, 2023, compared to $37.0 million and $130.2 million for the same period in 2022. The increases were primarily attributable to an increase in personnel costs of $7.1 million for the quarter ended December 31, 2023 and $29.3 million for the year ended December 31, 2023, and increased outside services of $5.6 million for the year ended December 31, 2023. General and administrative expenses were $17.1 million and $58.1 million for the three months and full year ended December 31, 2023, compared to $11.3 million and $42.4 million for the same period in 2022. The increases were primarily attributable to an increase in personnel costs of $4.2 million for the quarter ended December 31, 2023 and $12.8 million for the year ended December 31, 2023. Net loss for the three months ended December 31, 2023, was $60.1 million, compared to a net loss of $45.0 million for the same period in 2022. For the year ended December 31, 2023, the company’s net loss was $214.5 million compared to a net loss of $163.9 million for the year ended December 31, 2022. In addition to the financial results above, the company’s net loss also included a loss on equity method investment of $4.2 million and $5.2 million for the three months and full year ended December 31, 2023, compared to no loss on equity method investment for the three months ended December 31, 2022 and $1.0 million for the year ended December 31, 2022. This loss was derived from the company’s investment in Radionetics Oncology, Inc. Revenues were $4.0 million for the full year ended December 31, 2023, compared to $4.7 million for the same period in 2022. There were no revenues for the three months ended December 31, 2023, compared to $0.7 million for the three months ended December 31, 2022. Revenues were derived from licensing arrangements for our paltusotine and CRN01941 product candidates. Unrestricted cash, cash equivalents, and investments totaled $558.6 million as of December 31, 2023, compared to $334.4 million as of December 31, 2022. On February 28, 2024, the company announced a private placement equity financing for gross proceeds of approximately $350 million. Based on its current projections, the company now expects that its cash, cash equivalents and short-term investments will be sufficient to fund its current operating plan into 2028. Conference Call and Webcast Details Management will hold a live conference call and webcast today, Wednesday, February 28, 2024 at 4:30 p.m. ET. To participate, please dial 1-888-886-7786 (domestic) or 1-416-764-8658 (international). To access the webcast, click here. For instant telephone access, click the Call me™ link here. Following the live event, a replay will be available on the Investors section of the Company’s website. About Crinetics Pharmaceuticals Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors. Paltusotine, an investigational, first-in-class, oral somatostatin receptor type 2 (SST2) agonist, is in Phase 3 clinical development for acromegaly and Phase 2 clinical development for carcinoid syndrome associated with neuroendocrine tumors. Crinetics has demonstrated pharmacologic proof-of-concept in a Phase 1 clinical study for CRN04894 a first-in-class, investigational, oral ACTH antagonist, that is currently in Phase 2 clinical studies for the treatment of congenital adrenal hyperplasia and Cushing’s disease. All of the Company’s drug candidates are orally delivered, small molecule new chemical entities resulting from in-house drug discovery efforts, including additional discovery programs addressing a variety of endocrine conditions such as hyperparathyroidism, polycystic kidney disease, Graves’ disease, thyroid eye disease, diabetes and obesity. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the plans and timelines for the clinical development of paltusotine and CRN04894, including the therapeutic potential and clinical benefits or safety pro the expected timing of topline data from the ongoing Phase 3 clinical studies of paltusotine in acromegaly and Phase 2 study of paltusotine in carcinoid syndrome; plans to submit data from the ongoing Phase 3 clinical studies of paltusotine in acromegaly to regulators in support of applications seeking approval for the use of paltusotine in acromegaly patients and the expected timing of an NDA submission for paltusotine for the treatment or maintenance of treatment of acromegaly in the United States; the expected timing of data from studies of CRN04894 in congenital adrenal hyperplasia and Cushing’s disease; our expected plans and timing for commercialization of paltusotine and other product candidates pending regulatory approval, including efforts to expand our commercial capabilities; and the expected timing through which our cash, cash equivalents, and short-term investments will fund our operating plans. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including, without limitation, topline data that we report may change following a more comprehensive review of the data related to the clinical studies and such data may not accurately reflect the complete results of a clinical study, and the FDA and other regulatory authorities may not agree with our interpretation of such results; we may not be able to obtain, maintain and enforce our patents and other intellectual property rights, and it may be prohibitively difficult or costly to protect such rights; geopolitical events may disrupt Crinetics’ business and that of the third parties on which it depends, including delaying or otherwise disrupting its clinical studies and preclinical studies, manufacturing and supply chain, or impairing employee productivity; unexpected adverse side effects or inadequate efficacy of the company’s product candidates that may limit their development, regulatory approval and/or commercialization; the company’s dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; the success of Crinetics’ clinical studies and nonclinical studies; regulatory developments in the United States and foreign countries; clinical studies and preclinical studies may not proceed at the time or in the manner expected, or at all; the timing and outcome of research, development and regulatory review is uncertain, and Crinetics’ drug candidates may not advance in development or be approved for marketing; Crinetics may use its capital resources sooner than expected; any future impacts to our business resulting from geopolitical developments outside our control; and the other risks and uncertainties described in the company’s periodic filings with the SEC. The events and circumstances reflected in the company’s forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Additional information on risks facing Crinetics can be found under the heading “Risk Factors” in Crinetics’ periodic reports, including its annual report on Form 10-K for the year ended December 31, 2023. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by applicable law, Crinetics does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. CRINETICS PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED FINANCIAL STATEMENT DATA (in thousands, except per share data) (unaudited) Three months ended December 31, Twelve months ended December 31, STATEMENTS OF OPERATIONS DATA: 2023 2022 2023 2022 Revenues $ — $ 709 $ 4,013 $ 4,737 Operating expenses: Research and development 45,580 36,991 168,527 130,225 General and administrative 17,078 11,274 58,094 42,394 Total operating expenses 62,658 48,265 226,621 172,619 Loss from operations (62,658 ) (47,556 ) (222,608 ) (167,882 ) Total other income, net 6,762 2,565 13,277 4,974 Loss before equity method investment (55,896 ) (44,991 ) (209,331 ) (162,908 ) Loss on equity method investment (4,201 ) — (5,198 ) (1,010 ) Net loss $ (60,097 ) $ (44,991 ) $ (214,529 ) $ (163,918 ) Net loss per share - basic and diluted $ (0.90 ) $ (0.84 ) $ (3.69 ) $ (3.15 ) Weighted-average shares - basic and diluted 67,146 53,839 58,071 51,982 BALANCE SHEET DATA: December 31, 2023 December 31, 2022 Cash, cash equivalents and investments $ 558,555 $ 334,425 Working capital $ 530,211 $ 317,461 Total assets $ 635,353 $ 352,176 Total liabilities $ 96,247 $ 35,848 Accumulated deficit $ (653,702 ) $ (439,173 ) Total stockholders’ equity $ 539,106 $ 316,328 Investors: Corey Davis LifeSci Advisors, LLC cdavis@lifesciadvisors.com (212) 915-2577 Media: Natalie Badillo Head of Corporate Communications nbadillo@crinetics.com (858) 450-6464