PTH1R

Trial Initiation Marks Septerna’s Transition to a Clinical-Stage Company Developing a Portfolio of Oral Small Molecule GPCR-Targeted Medicines Phase 1 Clinical Trial Designed to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SEP-786 in Healthy Volunteers SOUTH SAN FRANCISCO, CA, USA I September 27, 2024 I Septerna , a clinical-stage biotechnology company pioneering a new era of GPCR-targeted drug discovery, today announced the dosing of the first participants in its Phase 1 clinical trial of SEP-786, its novel, potent and selective, oral small molecule parathyroid hormone 1 receptor (PTH1R) agonist being developed for the treatment of patients with hypoparathyroidism. The Phase 1 clinical trial is a single-ascending dose (SAD) and multiple-ascending dose (MAD) clinical trial to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SEP-786 in healthy adult volunteers. Hypoparathyroidism is a debilitating endocrine disease caused by a deficiency of the parathyroid hormone (PTH) that results in a range of symptoms, including muscle cramps, fatigue, cognitive dysfunction, and life-threatening complications, such as cardiac arrhythmias, seizures, and renal failure. Conventional therapy requires patients take high doses of calcium and Vitamin D supplements orally several times daily or life-long daily injections of PTH replacement therapy. “GPCR-targeted drugs have been the most productive target class in drug discovery history, with about one-third of all FDA-approved drugs targeting these receptors. Our proprietary Native Complex Platform™ fuels the discovery of oral small molecule compounds for a wide range of GPCRs, such as PTH1R, a validated receptor target for hypoparathyroidism,” said Jeffrey Finer, M.D., Ph.D., Chief Executive Officer and Co-founder of Septerna. “An oral small molecule PTH1R agonist has transformative potential as a convenient, disease-modifying treatment option that could provide patients with full-day calcium control, while resolving the serious effects of low blood calcium levels due to PTH deficiency. We look forward to assessing the safety of SEP-786 and its potential to normalize serum calcium levels, as we have seen in preclinical models, in this Phase 1 clinical trial. I am very proud of the rapid execution by our R&D team in achieving this milestone, which underscores the power of our Native Complex Platform™ to take on GPCR targets which have been historically challenging for small molecule drug discovery.” The randomized, placebo-controlled, SAD and MAD Phase 1 clinical trial is expected to enroll up to 180 healthy adult participants. Dosing is underway in the SAD portion of the clinical trial, which will evaluate the safety and tolerability of SEP-786 at escalating oral doses. The MAD portion of the clinical trial is designed to evaluate the safety and tolerability of once-daily and twice-daily oral dosing of SEP-786 over multiple days of treatment with secondary endpoints including PK, changes in serum calcium and urinary calcium, and other biomarkers. About SEP-786 and Hypoparathyroidism Septerna is developing SEP-786, a novel, potent and selective oral small molecule parathyroid hormone 1 receptor (PTH1R) agonist for the treatment of patients with hypoparathyroidism, a rare endocrine disease characterized by a deficiency of the parathyroid hormone (PTH). Hypoparathyroidism results in a wide range of debilitating symptoms, including muscle cramps, fatigue, cognitive dysfunction and life-threatening complications, such as cardiac arrhythmias, seizures, and renal failure. Currently available treatments include supplements that only partially address PTH deficiency, or PTH peptide replacements, which require daily injections. Preclinical safety studies support that SEP-786 has demonstrated the ability to normalize serum calcium and was generally well-tolerated in 28-day Good Laboratory Practice toxicology studies. SEP-786 has the potential to be a differentiated treatment for hypoparathyroidism. About Septerna Septerna, Inc. is a clinical-stage biotechnology company pioneering a new era of G protein-coupled receptor (GPCR) oral small molecule drug discovery powered by its proprietary Native Complex Platform TM . Its industrial-scale platform aims to unlock the full potential of GPCR therapies and has led to the discovery and development of its deep pipeline of product candidates focused initially on treating patients in three therapeutic areas: endocrinology, immunology and inflammation, and metabolic diseases. Septerna was launched in 2022 by preeminent drug discovery company builders and scientific leaders in the biochemistry, structural biology, and pharmacology of GPCRs. For more information, please visit www.septerna.com . SOURCE: Septerna

July 15, 2024 -- Amolyt Pharma, a global, clinical-stage biopharmaceutical company specializing in developing therapeutic peptides for rare endocrine and related diseases, today announced that its previously announced acquisition by the global pharmaceutical company, AstraZeneca, has closed. The acquisition bolsters the Alexion, AstraZeneca Rare Disease late-stage pipeline and expands on its bone metabolism franchise with the notable addition of eneboparatide (AZP-3601), a Phase III investigational therapeutic peptide with a novel mechanism of action designed to meet key therapeutic goals for hypoparathyroidism. In patients with hypoparathyroidism, a deficiency in parathyroid hormone (PTH) production results in significant dysregulation of calcium and phosphate, which can lead to life-altering symptoms and complications, including chronic kidney disease. This programme, together with Amolyt’s talented team, expertise, and earlier pipeline, will enable Alexion’s expansion into rare endocrinology. Under the terms of the definitive agreement, AstraZeneca has acquired all of Amolyt Pharma’s outstanding shares for a total consideration of up to $1.05 billion, on a cash and debt free basis. This includes $800 million upfront at deal closing, plus the right for Amolyt Pharma’s shareholders to receive an additional contingent payment of $250 million payable upon achievement of a specified regulatory milestone. Amolyt Pharma, a clinical stage biotechnology company, is building on its team’s established expertise to deliver life-changing treatments to patients suffering from rare endocrine and related diseases. Its development portfolio includes eneboparatide (AZP-3601), a long-acting PTH1 receptor agonist as a potential treatment for hypoparathyroidism, and AZP-3813, a peptide growth hormone receptor antagonist for the potential treatment of acromegaly. To learn more, visit https://amolytpharma.com/ or follow us on Twitter and LinkedIn. The content above comes from the network. if any infringement, please contact us to modify.

Eneboparatide therapeutic peptide binds to the parathyroid hormone receptor. Credit: Prostock-studio/Shutterstock. AstraZeneca has closed the acquisition of Amolyt Pharma, a company specialising in treatments for rare endocrine diseases. The deal between the parties was announced in March 2024. AstraZeneca made a $1.05bn payment for all outstanding shares of Amolyt Pharma, free of cash and debt. The transaction includes an upfront payment of $800m and an additional $250m contingent upon reaching a particular regulatory milestone. The strategic move strengthens AstraZeneca’s late-stage pipeline within its Alexion rare disease division and adds the investigational therapeutic peptide eneboparatide (AZP-3601) to its bone metabolism portfolio. See Also: Sumitomo Pharma’s DSP-5336 gains FDA fast track for AML AstraZeneca completes Amolyt Pharma acquisition Eneboparatide is in Phase III development for hypoparathyroidism and binds to the parathyroid hormone (PTH) receptor with high affinity. Hypoparathyroidism is a rare condition defined by PTH deficiency that results in low calcium and elevated levels of phosphorus in the blood. Clinical manifestations of this condition impact tissues and organ systems, specifically kidneys and bone. Eneboparatide is a subcutaneous parathyroid hormone receptor 1 agonist for the treatment of hypoparathyroidism. Its therapeutic goals are to regulate serum calcium levels, manage hypoparathyroidism symptoms, reduce urine calcium excretion and potentially prevent kidney function decline and chronic kidney disease. Its short plasma half-life may help normalise bone turnover and maintain bone health. Another candidate in Amolyt’s pipeline is AZP-3813, a peptide growth hormone receptor antagonist being developed as a potential add-on to somatostatin analogues for the treatment of acromegaly, a condition associated with abnormally high secretion of growth hormone. AstraZeneca’s rare disease portfolio generated $7.76bn in global sales in 2023, as reported in the company’s fourth-quarter financial reports.