PTH

Trial continues as planned to 52 weeks to further characterise the risk-benefit profile LONDON, UK I March 17, 2025 I High-level results from the CALYPSO Phase III trial showed that eneboparatide (AZP-3601), an investigational parathyroid hormone (PTH) receptor 1 agonist, met its primary endpoint with statistical significance in adults with chronic hypoparathyroidism (HypoPT) at 24 weeks, compared to placebo. The primary endpoint is a composite of normalisation of albumin-adjusted serum calcium levels and independence from active vitamin D and oral calcium therapy. HypoPT is a rare endocrine disease caused by a deficiency of PTH and characterised by impaired regulation of calcium and phosphate levels in the blood. This dysregulation of the physiological action of PTH can lead to clinical manifestations, including negative impact on the kidney and bone. 1 HypoPT is one of the largest known rare diseases, affecting over 200,000 people in the United States and the European Union, approximately 80% of whom are women. 2-4 Marc Dunoyer, Chief Executive Officer, Alexion, AstraZeneca Rare Disease, said: “People living with HypoPT, a rare endocrine disease, are often at increased risk of hypercalciuria, osteopenia and osteoporosis, and these results from the CALYPSO trial underscore eneboparatide’s potential to be another option for these patients. We look forward to reviewing clinical results at 52 weeks to fully characterise the risk-benefit profile.” Eneboparatide was well tolerated. After the 24-week randomised treatment period, all patients receive eneboparatide in the ongoing long-term extension period until 52 weeks. Full efficacy and safety data will be analysed at 52 weeks. Alexion plans to share these data with global health authorities and present them at forthcoming medical meetings. Notes Hypoparathyroidism Hypoparathyroidism (HypoPT) is a rare endocrine disease caused by a deficiency of parathyroid hormone (PTH) and characterised by decreased calcium and elevated phosphate levels in the blood, which can lead to a variety of neuromuscular, renal and skeletal manifestations. 1,5,6 The primary cause in approximately 75% of people with HypoPT is injury to or removal of the parathyroid glands during neck surgery. 5,6 There are over 200,000 people in the United States and the European Union living with HypoPT, approximately 80% of whom are women. 2-4 Despite available treatments, people living with HypoPT continue to experience a significant unmet need. 1,8 CALYPSO CALYPSO is a global Phase III, randomised, double-blind, placebo-controlled, multicentre trial designed to evaluate the efficacy and safety of eneboparatide in adults with chronic hypoparathyroidism. A total of 202 patients treated with standard of care (active vitamin D and oral calcium supplementation) were randomised in a 2:1 ratio to receive eneboparatide or placebo. 9 The primary efficacy endpoint is a composite of the proportion of patients that achieve albumin-adjusted serum calcium within the normal range and independence from standard of care after 24 weeks of treatment. The key secondary efficacy endpoints include normalisation of 24-hour urinary calcium in patients with hypercalciuria at baseline and assessment of patient-reported outcomes that reflect physical symptoms and impact on quality of life. 9 After the 24-week randomised main treatment period, all patients receive eneboparatide treatment in the ongoing long-term extension period. 9 Eneboparatide (AZP-3601) Eneboparatide (AZP-3601) is an investigational parathyroid hormone (PTH) receptor 1 agonist for the treatment of chronic hypoparathyroidism (HypoPT). It is designed to bind with high affinity to a specific conformation of the PTH receptor 1 to restore PTH function to manage the symptoms of HypoPT, while preserving kidney function and bone health. 6 Eneboparatide has been granted fast track designation and orphan drug designation by the US Food and Drug Administration and orphan designation by the European Medicines Agency for the treatment of HypoPT. Alexion Alexion, AstraZeneca Rare Disease, is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and delivery of life-changing medicines. A pioneering leader in rare disease for more than three decades, Alexion was the first to translate the complex biology of the complement system into transformative medicines, and today it continues to build a diversified pipeline across disease areas with significant unmet need, using an array of innovative modalities. As part of AstraZeneca, Alexion is continually expanding its global geographic footprint to serve more rare disease patients around the world. It is headquartered in Boston, US. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca . References SOURCE: AstraZeneca

YORVIPATH® (palopegteriparatide) is now registered by the Therapeutic Goods Administration (TGA) for the treatment of chronic hypoparathyroidism in adults1 First-in-class novel PTH replacement therapy Australia becomes the first country to obtain Marketing Authorisation for YORVIPATH since FDA approval SINGAPORE, Feb. 20, 2025 /PRNewswire/ -- Independent biopharmaceutical company Specialised Therapeutics (ST) welcomes the registration of YORVIPATH® (palopegteriparatide) by the Therapeutic Goods Administration (TGA), "for the treatment of chronic hypoparathyroidism in adults".1,2 YORVIPATH was granted an Orphan Drug Designation and assessed through the TGA's Priority Review pathway.3,4 It is the first and only medicine to be listed on the Australian Register of Therapeutic Goods (ARTG) for the treatment of chronic hypoparathyroidism. Hypoparathyroidism is a rare, complex endocrine disease, affecting an estimated 6.4-37 per 100,000 people globally.5,6 It is an endocrine disorder in which the production of parathyroid hormone (PTH) by the parathyroid glands is abnormally low or absent, causing low levels of calcium (hypocalcaemia) and high levels of phosphorous (hyperphosphataemia) in the blood.7,8 This impacts proper functioning of nerves and muscles, leading to weakness, muscle spasms or cramps, headaches, hair loss, numbness or tingling, and memory problems.8,9 Individuals with hypoparathyroidism may experience a range of severe and potentially life-threatening short-term and long-term complications, including neuromuscular irritability, renal complications, extraskeletal calcifications, and cognitive impairment.10 Leading Australian Endocrinologist and Head of the School of Clinical Sciences at Monash Health, Professor Peter Ebeling AO, applauded the TGA approval of YORVIPATH in addressing an unmet medical need for Australian adults diagnosed with chronic hypoparathyroidism. "Until now, the only treatment option for adults with chronic hypoparathyroidism has been conventional therapy with calcium and active vitamin D supplementation to keep blood calcium levels normal," said Professor Ebeling. "While these treatments help to manage the symptoms of hypoparathyroidism, they do not address the underlying deficiency of PTH and contribute to the significant pill burden for patients." "The lack of effective therapeutic options has been an urgent medical need in this area, and the local approval of YORVIPATH represents an important advance in the treatment of chronic hypoparathyroidism in Australia," said Professor Ebeling. YORVIPATH is a first-in-class PTH replacement therapy. A prodrug of parathyroid hormone (PTH [1-34]), YORVIPATH is administered subcutaneously once daily, with sustained release of active PTH designed to provide PTH levels in the physiological range for 24 hours/day.11 YORVIPATH's approval in Australia was supported by the results of Ascendis Pharma's Phase 3 PaTHway trial, a 26-week randomised, double-blind, placebo-controlled study with a 156-week open-label extension, published in the Journal of Bone and Mineral Research.12 Involving 84 adults with chronic hypoparathyroidism, the clinical trial demonstrated the efficacy, safety and tolerability of YORVIPATH as a once-daily PTH replacement therapy. Data from the pivotal trial showed 93% (57/61) of YORVIPATH-treated patients achieved independence from both active vitamin D and therapeutic doses of elemental calcium, which was associated with a clinically meaningful reduction in their daily pill burden.12 The safety analysis demonstrated YORVIPATH was generally well-tolerated, with the most frequently reported adverse reactions being injection site reactions (21.6%), headache (18.7%), and paraesthesia (13.7%).2 In addition to the significant short-term and long-term medical complications of chronic hypoparathyroidism, individuals diagnosed with the condition also experience reduced health-related quality of life, including the negative impact of symptoms on their daily life and work productivity.12 Chief Executive Officer of the Australian Thyroid Foundation (ATF), Beverley Garside, acknowledged the significance of the TGA approval in offering adults living with chronic hypoparathyroidism the opportunity to improve their health and wellbeing. However, she reinforced that this is not the time for complacency, as it is just the first step towards securing subsidised access to an important new treatment option for this community. "As the leading national voice for good thyroid health in Australia, the ATF recognises the importance of the TGA registration of YORVIPATH as a new treatment option for the hypoparathyroid community. While this is positive news, it is only the first step," said Ms Garside. "For adults diagnosed with chronic hypoparathyroidism to truly benefit from this new treatment, it is essential they have the option of subsidised and affordable access to YORVIPATH through the Pharmaceutical Benefits Scheme as quickly as possible." YORVIPATH is being made available in Australia by Specialised Therapeutics (ST), under an exclusive distribution agreement with global biopharmaceutical company Ascendis Pharma A/S that covers Australia, New Zealand, Singapore, Malaysia, Brunei, Thailand, and Vietnam. The Australian registration of YORVIPATH follows approvals issued to Ascendis Pharma by the United States Food and Drug Administration (US FDA)13 in August 2024 and the European Medicines Agency (EMA)14 in November 2023. "The Australian approval of YORVIPATH reflects our values and dedication to applying science to help address the significant unmet medical needs expressed by the hypoparathyroidism community," said Roy Khoury, Vice President, Head of International Markets at Ascendis Pharma. "We are pleased to partner with Specialised Therapeutics to broaden access to this innovative therapy, based on our TransCon technology, which offers a new approach to the treatment of this often-debilitating rare disease." ST Chief Executive Officer, Mr Carlo Montagner, said the approval of YORVIPATH was a meaningful milestone, but the company would not stop until it achieved reimbursement for eligible Australians with hypoparathyroidism through the Pharmaceutical Benefits Scheme (PBS). "We are proud to have brought the first and only TGA-registered treatment for chronic hypoparathyroidism to Australians living with the condition so rapidly following the recent FDA and EMA approvals," said Mr Montagner. "Chronic hypoparathyroidism has considerable and life-long wide-ranging impacts on these individuals and we are committed to working with the local hypoparathyroidism community and the Australian Government to ensure YORVIPATH is accessible to eligible patients through the PBS at the earliest opportunity." YORVIPATH will be reviewed by the Pharmaceutical Benefits Advisory Committee (PBAC) at its first meeting of the year, to be held from 12-14 March 2025. YORVIPATH will be made available for prescribing in Australia once it has been listed on the PBS. About Specialised Therapeutics Founded in 2007, Specialised Therapeutics is the region's largest independent specialty pharmaceutical company, providing new therapies and technologies to patients in Australia, New Zealand and across Southeast Asia. Headquartered in Singapore, ST partners with global pharmaceutical, biotech and diagnostic companies to bring novel healthcare opportunities to patients who are impacted by a range of diseases. ST has built a strong track record of success, navigating complex regulatory, reimbursement and commercialisation environments in its diverse regions. The ST mission is to provide specialty therapies where there is an unmet need. The company's broad therapeutic portfolio currently includes novel agents in oncology, haematology, CNS, neurology, endocrinology, ophthalmology and supportive care, although it is not confined to these areas. ST is a member of the World Orphan Drug Alliance (WODA). Additional information can be found at About Ascendis Pharma Ascendis Pharma is applying its innovative TransCon technology platform to build a leading, fully integrated biopharma company focused on making a meaningful difference in patients' lives. Guided by its core values of patients, science and passion, the company uses its TransCon technologies to create new and potentially best-in-class therapies. Ascendis is headquartered in Copenhagen, Denmark and has additional facilities in Europe and the United States. Please visit: ascendispharma.com to learn more. About Hypoparathyroidism10 Hypoparathyroidism is an endocrine disease caused by insufficient levels of parathyroid hormone (PTH), the primary regulator of calcium and phosphate balance in the body, acting directly on bone and kidneys and indirectly on the intestines. Individuals with hypoparathyroidism may experience a range of severe and potentially life-threatening short-term and long-term complications, including neuromuscular irritability, renal complications, extra-skeletal calcifications, and cognitive impairment. Post-surgical hypoparathyroidism accounts for the majority of cases (70-80%), while other etiologies include autoimmune and idiopathic causes. About PaTHway12 The PaTHway trial was a double-blind, placebo-controlled, 26-week, Phase 3 study that assessed the efficacy and safety of PTH replacement therapy with palopegteriparatide for individuals with hypoparathyroidism. Participants (n=84) were randomised 3:1 to once-daily palopegteriparatide (initially 18 μg/d) or placebo, both co-administered with conventional therapy. The study drug and conventional therapy were titrated according to a dosing algorithm guided by serum calcium. The composite primary efficacy endpoint was the proportion of participants at week 26 who achieved normal albumin-adjusted serum calcium levels (8.3–10.6 mg/dL), independence from conventional therapy (requiring no active vitamin D and ≤600 mg/d of calcium), and no increase in study drug over 4 weeks before week 26. At week 26, 79% (48/61) of participants treated with palopegteriparatide versus 5% (1/21) with placebo met the composite primary efficacy endpoint (p < 0.0001). Additionally, 93% (57/61) of participants treated with palopegteriparatide achieved independence from conventional therapy. Palopegteriparatide treatment normalised mean 24-hour urine calcium. Overall, 82% (50/61) treated with palopegteriparatide and 100% (21/21) with placebo experienced adverse events; most were mild (46%) or moderate (46%). No study drug-related withdrawals occurred. About YORVIPATH® (palopegteriparatide) YORVIPATH® (palopegteriparatide, developed as TransCon™ PTH) is a once-daily prodrug providing sustained release of active PTH. It was approved by the European Union as a parathyroid hormone (PTH) replacement therapy for the treatment of adults with chronic hypoparathyroidism15 and the United States for the treatment of hypoparathyroidism in adults13. Treatment should be initiated and monitored by physicians or qualified healthcare professionals experienced in the diagnosis and management of patients with hypoparathyroidism. Yorvipath® is a registered trademark of Ascendis Pharma A/S (NASDAQ: ASND). References: Therapeutic Goods Administration. Australian Register of Therapeutic Goods (ARTG). Available at: . [Accessed Dec 2024]. YORVIPATH (palopegteriparatide) AU Product Information. Therapeutic Goods Administration. Prescription medicine determinations and designations: Notice for palopegteriparatide (Specialised Therapeutics Pharma Pty Ltd) – Orphan drug designation. Available at: . [Accessed Dec 2024]. Therapeutic Goods Administration. Prescription medicine determinations and designations: Notice for palopegteriparatide (Specialised Therapeutics Pharma Pty Ltd) – Priority review. Available at: . [Accessed Dec 2024]. Siggelkow H, Pacaud D, et al. Clin Endocrinol (Oxf). 2020;92(2). Bjornsdottir S, Sikjaer T, et al. J Bone Miner Res. 2022;37(12). Australian Thyroid Foundation. Thyroid Facts: Parathyroid Glands – Hypoparathyroidism. Available at: [Accessed Dec 2024]. National Organization for Rare Disorders. Disease Overview: Hypoparathyroidism - Symptoms, Causes, Treatment, 14 August 2024. Available at: [Accessed Dec 2024]. Endocrine Society. Endocrine Library: Patient Resources; Hypoparathyroidism, 24 January 2022. Available at: [Accessed Dec 2024]. Bilezikian JP. J Clin Endocrinol Metab. 2020;105(6):1722-1736. doi:10.1210/clinem/dgaa113. YORVIPATH (palopegteriparatide) US Prescribing Information. Khan AA, Bilezikian JP, Cusano NE, et al. J Bone Miner Res. 2023;38(1). US Food and Drug Administration. FDA approves new drug for hypoparathyroidism, a rare disorder, 9 August 2024. Available at: [Accessed Dec 2024]. European Medicines Agency. Yorvipath: Palopegteriparatide, 17 November 2023. Available at: [Accessed Dec 2024]. YORVIPATH (palopegteriparatide).EU Summary of Product Characteristics. SOURCE Specialised Therapeutics Asia WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Peer-reviewed publication features positive results from multiple ascending dose (MAD) portion of Phase 1 MBX 2109 study in healthy participantsCARMEL, Ind., Dec. 02, 2024 (GLOBE NEWSWIRE) -- MBX Biosciences, Inc. (Nasdaq: MBX), a clinical-stage biopharmaceutical company focused on the discovery and development of novel precision peptide therapies for the treatment of endocrine and metabolic disorders, today announced the publication of a peer-reviewed article highlighting results from the Phase 1 study of MBX 2109, the Company’s parathyroid hormone (PTH) peptide prodrug in development for the treatment of hypoparathyroidism (HP). The publication, titled “MBX 2109, a Once-Weekly Parathyroid Hormone Replacement Therapy Prodrug: Phase 1, First-in-Human, Randomized Trial”, was published in The Journal of Clinical Endocrinology and Metabolism (JCEM) and can be accessed here. “We are pleased to have published results from our Phase 1 MAD study of MBX 2109 in JCEM, a leading peer-reviewed journal of endocrine and metabolic research,” said Kent Hawryluk, President and Chief Executive Officer of MBX Biosciences. “MBX 2109’s long half-life and flat exposure profile demonstrated in the Phase 1 study may lead to a more consistent therapeutic effect and minimize symptoms from large fluctuations in calcium compared to PTH agonists with a shorter half-life. These results, combined with its safety profile to date and pharmacodynamic activity, support the continued development of MBX 2109 as a potential once-weekly PTH prodrug for the treatment of HP. We look forward to completing enrollment in our Phase 2 Avail™ trial of MBX 2109 in patients with HP in the first quarter of 2025 and reporting topline results in the third quarter of 2025.” The publication features results from the multiple ascending dose portion of the Phase 1 study of MBX 2109, a peptide prodrug yielding a biologically active PTH agonist. The Phase 1 study was a randomized, double-blind, placebo-controlled trial designed to evaluate safety, pharmacokinetics (PK), and pharmacodynamics (PD) of MBX 2109 in healthy adults. Forty participants were randomized 4:1 to receive four once-weekly subcutaneous doses of either placebo or MBX 2109 at 200, 400, 600, or 900 µg. Key highlights from the publication: The observed half-lives of the prodrug (79-95 hours) and the active drug (184-213 hours) reflected the prodrug design and were supportive of once-weekly administration.Peak-to-trough exposures to the active drug with weekly dosing were relatively flat, with ratios ranging from 1.47 and 1.79 across dose levels.With weekly injections, dose-proportional increases in albumin-adjusted serum calcium and concomitant suppression of endogenous PTH(1-84) were observed, consistent with the expected PTH pharmacology in healthy participants.Repeat doses of MBX 2109 were generally well-tolerated at all doses tested.Most treatment emergent adverse events (TEAEs) were mild in severity. Injection-site reaction was the most common TEAE.No MBX 2109 dose-related serious or severe adverse events or deaths were reported. About HypoparathyroidismHP is a rare endocrine disease caused by a deficiency of PTH released by the parathyroid glands that results in decreased calcium levels in the blood leading to hypocalcemia. Hypocalcemia can result in a variety of acute symptoms, such as muscle cramping or spasm, tingling, and neurological symptoms such as depression, confusion and cognitive impairment. More serious complications can occur, including seizures and cardiac arrhythmias. As a result, HP can interfere with daily activities, negatively impacting the quality of life for patients and we estimate that HP affects approximately 120,000 people in the United States and more than 250,000 in the United States and Europe. The most common cause for HP, in approximately 75% of cases, is the inadvertent removal or damage to the parathyroid glands during neck surgery. It can also be caused by certain autoimmune processes and genetic conditions. The current standard of care for HP does not address the PTH deficiency, which is the underlying cause of the disease. To avoid hypocalcemia and its symptoms due to PTH deficiency, the current standard of care consists primarily of high doses of oral calcium supplements and active vitamin D. About MBX 2109MBX 2109 is a parathyroid hormone peptide prodrug that is designed as a potential long-acting hormone replacement therapy for the treatment of HP. Leveraging the company’s proprietary Precision Endocrine Peptide™ (PEP™) platform technology, MBX 2109 was designed to provide convenient, once-weekly administration and a continuous, infusion-like PTH exposure with lower daily peak-to-trough ratios than observed with daily PTH dosing regimens. MBX 2109 received orphan drug designation from the U.S. Food and Drug Administration for the treatment of HP. About MBX BiosciencesMBX Biosciences is a biopharmaceutical company focused on the discovery and development of novel precision peptide therapies based on its proprietary PEP™ platform, for the treatment of endocrine and metabolic disorders. The Company is advancing a pipeline of novel candidates for endocrine and metabolic disorders with clinically validated targets, established endpoints for regulatory approval, significant unmet medical needs and large potential market opportunities. The Company’s pipeline includes its lead product candidate MBX 2109, in Phase 2 development for the treatment of chronic hypoparathyroidism (HP); MBX 1416, in Phase 1 development for the treatment of post-bariatric hypoglycemia (PBH); and an obesity portfolio that includes MBX 4291, as well as multiple discovery and pre-clinical candidates in development for the treatment of obesity. The Company is based in Carmel, Indiana. To learn more, please visit the Company website at www.mbxbio.com and follow it on LinkedIn. About MBX’s Proprietary Precision Endocrine Peptide (PEP™) PlatformMBX was founded by global leaders with a transformative approach to peptide drug design and development. Leveraging this expertise, the Company designed its proprietary Precision Endocrine Peptide™ (PEP™) platform to overcome the key limitations of unmodified and modified peptide therapies and to improve clinical outcomes and simplify disease management for patients. PEPs are selectively engineered to have optimized pharmaceutical properties, including extended time-action profiles and consistent drug concentrations with low peak-to-trough concentration ratios, consistent exposure to target tissues, and less frequent dosing. Forward-Looking StatementsThis press release contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, but are not limited to, express or implied statements regarding: MBX Biosciences’ expectations regarding the Phase 2 Avail™ trial of MBX 2109, including the timing of enrollment of patients and topline results; and statements relating to MBX 2109’s clinical profile, including the potential to be a once-weekly PTH prodrug for the treatment of HP. Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect MBX Biosciences’ business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to the Company’s research and development activities; uncertainties relating to preclinical and clinical development activities; the risk that preliminary results may not be indicative of later results; the Company’s dependence on third parties to conduct clinical trials; MBX Biosciences’ ability to attract, integrate and retain key personnel; risks related to regulatory developments and approval processes of the U.S. Food and Drug Administration and comparable foreign regulatory authorities; as well as other risks described in “Risk Factors,” in MBX Biosciences’ Registration Statement on Form S-1 filed with the Securities and Exchange Commission (SEC), most recent Quarterly Report on Form 10-Q, as well as subsequent filings with the SEC. MBX Biosciences expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. MBX uses and intends to continue to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company’s Investor Relations website, in addition to following the Company’s press releases, SEC filings, public conference calls, presentations, and webcasts. Media Contact:Kate BurdickInizio Evoke Commskate.burdick@inizioevoke.com 860-462-1569 Investor Contact:Jim DeNikeMBX Biosciencesjdenike@mbxbio.com