Acth-Independent Macronodular Adrenal Hyperplasia

MENLO PARK, Calif., April 01, 2024 (GLOBE NEWSWIRE) -- Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrinologic, oncologic, metabolic and neurologic disorders by modulating the effects of the hormone cortisol, today announced completion of enrollment in GRADIENT, a Phase 3 trial of its proprietary selective cortisol modulator relacorilant in patients with Cushing’s syndrome (hypercortisolism) caused by an adrenal adenoma or adrenal hyperplasia. “Hypercortisolism with adrenal etiology affects many patients and is associated with serious cardiometabolic comorbidities, including hypertension and hyperglycemia, and increased risk of premature death,” said Bill Guyer, PharmD, Corcept’s Chief Development Officer. “GRADIENT is the first prospective placebo-controlled study to be conducted exclusively in these patients with Cushing’s syndrome. We expect data from GRADIENT in the fourth quarter of this year.” GRADIENT is a randomized, double-blind, placebo-controlled trial conducted at sites in the United States, Europe and Israel. One-hundred thirty-seven patients were randomized 1:1 to receive relacorilant or placebo for 22 weeks. Primary endpoints are improvement in glucose metabolism and hypertension. About Cushing’s Syndrome (Hypercortisolism)Cushing’s syndrome is caused by excessive activity of the hormone cortisol. Endogenous Cushing’s syndrome is an orphan disease that most often affects adults aged 20-50. Symptoms vary, but most patients experience one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper-body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Cushing’s syndrome can affect every organ system and can be lethal if not treated effectively. About RelacorilantRelacorilant is a selective cortisol modulator that binds to the glucocorticoid receptor (GR), but does not bind to the body's other hormone receptors. Corcept is studying relacorilant in a variety of serious disorders, including ovarian, adrenal and prostate cancer and Cushing’s syndrome. Relacorilant is proprietary to Corcept and is protected by composition of matter, method of use and other patents. Relacorilant has orphan drug designation in the United States and the European Union for the treatment of Cushing’s syndrome. About Corcept TherapeuticsFor over 25 years, Corcept’s focus on cortisol modulation and its potential to treat patients across a wide variety of serious disorders has led to the discovery of more than 1,000 proprietary selective cortisol modulators. Corcept’s advanced clinical trials are being conducted in patients with hypercortisolism, solid tumors, amyotrophic lateral sclerosis (ALS) and liver disease (NASH). In February 2012, the company introduced Korlym, the first medication approved by the U.S. Food and Drug Administration for the treatment of patients with Cushing’s syndrome. Corcept is headquartered in Menlo Park, California. For more information, visit Corcept.com. Forward-Looking StatementsStatements in this press release, other than statements of historical fact, are forward-looking statements based on our current plans and expectations that are subject to risks and uncertainties that might cause our actual results to differ materially from those such statements express or imply. These risks and uncertainties include, but are not limited to, our ability to operate our business; risks related to the study and development of Korlym as well as relacorilant, miricorilant, dazucorilant and our other product candidates, including their clinical attributes, regulatory approvals, mandates, oversight and other requirements; and the scope and protective power of our intellectual property. These and other risks are set forth in our SEC filings, which are available at our website and the SEC’s website. In this press release, forward-looking statements include those concerning the development of relacorilant as a treatment for Cushing’s syndrome, and design, timing and expectations regarding our GRADIENT trial. We disclaim any intention or duty to update forward-looking statements made in this press release. CONTACTInvestor inquiries:ir@corcept.comMedia inquiries:communications@corcept.com www.corcept.com

Efforts to further increase commercial readiness ongoing as Phase 3 PATHFNDR trials of paltusotine in acromegaly approach topline data readouts which are expected in 2H 2023 Phase 2 trial of paltusotine in carcinoid syndrome on track for topline data in 2H 2023 Clinical trials of CRN04894 in ACTH-dependent Cushing’s Syndrome and Congenital Adrenal Hyperplasia expected to begin in 1Q 2023 SAN DIEGO, Jan. 09, 2023 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced that Scott Struthers, Ph.D., founder and chief executive officer of Crinetics, will provide a company update at the 41st Annual J.P. Morgan Healthcare Conference, which is taking place in San Francisco, CA from January 9-12, 2023. Dr. Struthers’ presentation will take place on Wednesday, January 11th at 3:00 p.m. Pacific Time. A live webcast of the presentation may be accessed on the Events page of the company’s website. A replay of the webcast will be accessible at the same location. The presentation will feature an overview of Crinetics’ key priorities and anticipated milestones for 2023. These include: The continued advancement of the Phase 3 PATHFNDR-1 and PATHFNDR-2 trials of once-daily oral paltusotine in acromegaly. The trials remain on track for topline data readouts in the third and fourth quarters of 2023, respectively. If successful, Crinetics plans to submit data from the two studies to regulatory authorities in support of applications seeking approval for the use of paltusotine for all acromegaly patients who require pharmacotherapy, including untreated patients and those switching from other therapies. Efforts to further increase commercial readiness so that the company can rapidly provide acromegaly patients with access to once-daily oral paltusotine, if approved. The continued advancement of the Phase 2 trial of paltusotine in carcinoid syndrome, which remains on track for topline data in the second half of 2023. Following proof-of-concept Phase 1 results for CRN04894, an investigational adrenocorticotropic hormone (ACTH) antagonist, initiating clinical trials in ACTH-dependent Cushing’s syndrome and congenital adrenal hyperplasia. Both studies are expected to begin in the first quarter of 2023. Building off proof-of-concept Phase 1 results for CRN04777, an investigational, oral somatostatin receptor type 5 (SST5) agonist being developed as a treatment for congenital hyperinsulinism. The continued preclinical evaluation of investigational, oral small molecule parathyroid hormone receptor antagonists to identify a candidate for advancement into clinical trials. Initial target indications for this program may include primary hyperparathyroidism and hypercalcemia of malignancy, with potential opportunities in chronic kidney disease also being evaluated.Leveraging the company’s leading G-protein-coupled receptor (GPCR) drug discovery platform to generate and develop additional small molecule drug candidates with the potential to address unmet needs in indications such as polycystic kidney disease, Graves’ Disease (including thyroid eye disease) and metabolic diseases (including diabetes and obesity). “Crinetics is entering 2023 with strong momentum and potentially transformative milestones expected over the next year,” said Dr. Struthers. “If successful, upcoming readouts from our Phase 3 PATHFNDR trials will support regulatory filings seeking paltusotine’s approval in acromegaly, while significantly de-risking its development in carcinoid syndrome. As in acromegaly, many patients with carcinoid syndrome are not well served by burdensome SST2 agonist injections and therefore may benefit from oral paltusotine. We are currently evaluating this hypothesis in a Phase 2 trial that we expect to provide proof-of-concept data later this year.” “Looking broadly, we believe successful readouts from our acromegaly and carcinoid syndrome trials could validate our endocrine driven strategy that is also being applied to CRN04894, CRN04777, and each of our other programs,” continued Dr. Struthers. “Paltusotine is only the first of what we hope will be many future products that will come from the remarkable discovery and development engine that we have built. We are now beginning to lay the foundations for a commercial capability serving the same global community of endocrinologists that are helping us evaluate our drug candidates in their clinics. This coming year will be a critical step towards our long-term goal of building the premier fully integrated endocrine company that can sustainably innovate pioneering therapies for our patients around the world.” 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. Paltusotine, an investigational, 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 Phase 1 clinical studies for CRN04777, an investigational, oral somatostatin receptor type 5 (SST5) agonist in development for congenital hyperinsulinism, and for CRN04894, an investigational, oral ACTH antagonist in development for the treatment of Cushing’s disease, congenital adrenal hyperplasia, and other diseases of excess ACTH. All of the company’s drug candidates are orally delivered, small molecule new chemical entities resulting from in-house drug discovery efforts. 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, CRN04777 and CRN04894, including the therapeutic potential and clinical benefits thereof; the expected timing of topline data from the ongoing Phase 3 clinical trials of paltusotine in acromegaly and Phase 2 trial of paltusotine in carcinoid syndrome; plans to submit data from the ongoing Phase 3 clinical trials of paltusotine in acromegaly to regulators in support of applications seeking approval for the use of paltusotine in acromegaly patients; the expected timing of the initiation of studies of CRN04894 in ACTH-dependent Cushing’s syndrome and congenital adrenal hyperplasia; plans to continue evaluation of investigational, oral small molecule parathyroid hormone receptor antagonists to identify a candidate for advancement into clinical trials; and plans to generate and develop additional small molecule new chemical entities with the potential to address nonfunctional pituitary adenomas, polycystic kidney disease, metabolic diseases and Graves’ Disease. 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 trials and such data may not accurately reflect the complete results of a clinical trial, 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; 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; 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 trials and nonclinical studies; regulatory developments in the United States and foreign countries; clinical trials 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, 2021. 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. Contact: Investor Relations 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

Sept. 28, 2022 12:00 UTC Sparrow has also been granted SME status by the European Medicine Agency PORTLAND, Ore.--(BUSINESS WIRE)-- Sparrow Pharmaceuticals, a clinical-stage biopharmaceutical company developing novel, targeted therapies to address unmet needs in both endocrinology and rheumatology, today announced that the first patient has been dosed in the RESCUE trial, a phase 2 clinical trial of SPI-62, a potent and selective HSD-1 inhibitor, for the treatment of ACTH-dependent Cushing’s syndrome. This study is one of three phase 2 trials planned to investigate SPI-62 as a treatment for disorders of glucocorticoid excess. “Dosing our first patient in this phase 2 trial is an important milestone in our clinical development process of SPI-62,” said Frank Czerwiec, MD, PhD, Chief Medical Officer of Sparrow. “Cushing’s is a devastating rare disease with debilitating morbidities such as depression, bone loss, and diabetes, and if left untreated, high levels of mortality. Current treatments have limited efficacy or serious side effects, so there is a pressing need for new treatments that help these patients mitigate the effects of hypercortisolism.” The international, multicenter, randomized, double- and single-blind, placebo-controlled study is evaluating the pharmacologic effect, efficacy, and safety of SPI-62. The primary endpoint is to determine the pharmacologic effects of SPI-62 in patients with adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome. This includes measurement of the body’s activation of cortisol in important target tissues such as the liver, which is expected to be inhibited by SPI-62. The study will also explore SPI-62’s safety and effect on and Cushing’s features that include hyperglycemia, dyslipidemia, adiposity, hepatic steatosis, hypertension, glaucoma, mood, sleep, pain, osteopenia, and muscle strength. Sparrow is actively enrolling up to 26 patients for the trial, which is being conducted at 16 sites in the U.S., Bulgaria, and Romania. Criteria for participation include male and female subjects, ages 18 years or older, with active and consistent cortisol excess and documented diagnosis of ACTH-dependent Cushing’s syndrome. The company has also been granted SME (small- and medium-sized enterprise) status by the European Medicines Agency (EMA), which allows Sparrow greater access to finance and EU support programs. To learn more about the RESCUE trial (NCT05307328), please visit . About Cushing’s Syndrome and SPI-62 Patients develop Cushing’s syndrome due to an excess of glucocorticoids. In Cushing’s disease, this is due to a pituitary tumor that leads to high levels of adrenocorticotropic hormone, which stimulates excess cortisol secretion. ACTH, or its releasing hormone CRH, may also be produced by non-pituitary tumors. By targeting the intracellular activation of cortisol in key organs, SPI-62 can potentially mitigate multiple signs and symptoms of cortisol excess. HSD-1 inhibition would be the first new mechanism of action in decades to treat Cushing’s. In phase 1 studies, SPI-62 demonstrated the ability to reduce intracellular cortisol in the liver and to inhibit HSD-1 in both the brain and adipose tissue, which are three key tissues in which corticosteroid toxicity leads to morbidity. About Sparrow Pharmaceuticals Sparrow Pharmaceuticals was founded to spare patients the ravages of steroids. Leveraging underappreciated scientific insights into steroid biology, the company is working to provide better treatment options for serious disorders of hypercortisolism, and to revolutionize the treatment of autoimmune and inflammatory conditions. SPI-62, is an oral, small molecule, novel therapeutic treatment designed to target the source of active intracellular glucocorticoids in key tissues.