MBX Biosciences Announces MBX 2109 Phase 1 Study Results Published in The Journal of Clinical Endocrinology and Metabolism
MBX Biosciences published Phase 1 study results of MBX 2109, their parathyroid hormone peptide prodrug for hypoparathyroidism treatment, in The Journal of Clinical Endocrinology and Metabolism. The multiple ascending dose study involved 40 participants receiving four once-weekly subcutaneous doses. Key findings showed long half-lives (79-95 hours for prodrug, 184-213 hours for active drug), flat exposure profiles, and dose-proportional increases in serum calcium. The treatment was generally well-tolerated with mostly mild adverse events. The company expects to complete Phase 2 Avail™ trial enrollment in Q1 2025 with topline results in Q3 2025.
MBX Biosciences ha pubblicato i risultati dello studio di Fase 1 di MBX 2109, il loro prodrug a base di peptide dell'ormone paratiroideo per il trattamento dell'ipoparatiroidismo, sulla rivista The Journal of Clinical Endocrinology and Metabolism. Lo studio con dosi ascendenti multiple ha coinvolto 40 partecipanti che hanno ricevuto quattro dosi sottocutanee una volta a settimana. I principali risultati hanno mostrato emivite lunghe (79-95 ore per il prodrug, 184-213 ore per il farmaco attivo), profili di esposizione costanti e aumenti proporzionali delle dosi nel calcio sierico. Il trattamento è stato generalmente ben tollerato, con eventi avversi per lo più lievi. L'azienda prevede di completare l'arruolamento della Fase 2 dello studio Avail™ nel primo trimestre del 2025, con risultati preliminari attesi nel terzo trimestre del 2025.
MBX Biosciences publicó los resultados del estudio de Fase 1 de MBX 2109, su prodrug de péptido de la hormona paratiroidea para el tratamiento de la hipoparatiroidismo, en The Journal of Clinical Endocrinology and Metabolism. El estudio de dosis múltiples ascendentes involucró a 40 participantes que recibieron cuatro dosis subcutáneas una vez a la semana. Los hallazgos clave mostraron vidas medias largas (79-95 horas para el prodrug, 184-213 horas para el medicamento activo), perfiles de exposición planos y aumentos proporcionales a las dosis en el calcio sérico. El tratamiento fue generalmente bien tolerado con en su mayoría eventos adversos leves. La empresa espera completar la inscripción del estudio de Fase 2 Avail™ en el primer trimestre de 2025, con resultados preliminares en el tercer trimestre de 2025.
MBX 바이오사이언스는 MBX 2109의 1상 연구 결과를 발표했습니다. 이는 저하 갑상선 기능 저하증 치료를 위한 파라타이로이드 호르몬 펩타이드 프로드러그입니다. 이 다중 용량 상승 연구는 주 1회 4회로 피하 주사를 받은 40명의 참여자가 포함되었습니다. 주요 발견은 길어진 반감기(프로드러그의 경우 79-95시간, 활성 약물의 경우 184-213시간), 평탄한 노출 프로필, 그리고 혈청 칼슘의 용량 비례 증가를 보여주었습니다. 치료는 일반적으로 잘 견뎌졌고, 대부분 경미한 부작용이 있었습니다. 회사는 2025년 1분기까지 2상 Avail™ 시험 등록을 완료할 것으로 예상하며, 2025년 3분기에 주요 결과가 나올 것으로 보입니다.
MBX Biosciences a publié les résultats de l'étude de Phase 1 de MBX 2109, leur prodrug de peptide de l'hormone parathyroïdienne pour le traitement de l'hypoparathyroïdie, dans The Journal of Clinical Endocrinology and Metabolism. L'étude à doses multiples en montée a impliqué 40 participants recevant quatre doses sous-cutanées une fois par semaine. Les principales conclusions ont montré de longues demi-vies (79-95 heures pour le prodrug, 184-213 heures pour le médicament actif), des profils d'exposition plats, et des augmentations proportionnelles de calcium sérique en fonction de la dose. Le traitement a généralement été bien toléré, avec principalement des événements indésirables légers. L'entreprise s'attend à finaliser l'inscription à l'essai de Phase 2 Avail™ au premier trimestre 2025, avec des résultats préliminaires attendus au troisième trimestre 2025.
MBX Biosciences veröffentlichte die Ergebnisse der Phase-1-Studie zu MBX 2109, ihrem Prodrug aus dem Parathormon-Peptid zur Behandlung von Hypoparathyreoidismus, in The Journal of Clinical Endocrinology and Metabolism. Die Studie mit mehrfach ansteigenden Dosen umfasste 40 Teilnehmer, die viermal wöchentlich subkutane Dosen erhielten. Die wichtigen Ergebnisse zeigten lange Halbwertszeiten (79-95 Stunden für das Prodrug, 184-213 Stunden für das aktive Medikament), flache Expositionsprofile und dosisproportionale Anstiege des Serumkalziums. Die Behandlung wurde allgemein gut vertragen, mit überwiegend milden unerwünschten Wirkungen. Das Unternehmen erwartet, die Rekrutierung für die Phase-2-Studie Avail™ im ersten Quartal 2025 abzuschließen, mit vorläufigen Ergebnissen im dritten Quartal 2025.
- Long half-life demonstrated (79-95 hours for prodrug, 184-213 hours for active drug)
- Dose-proportional increases in serum calcium observed
- Generally well-tolerated with mostly mild adverse events
- No serious or severe adverse events reported
- Results support once-weekly administration potential
- Injection-site reaction reported as most common adverse event
Insights
The Phase 1 study results for MBX 2109 demonstrate promising potential in hypoparathyroidism treatment. The key pharmacokinetic findings show impressively long half-lives of 79-95 hours for the prodrug and 184-213 hours for the active drug, supporting weekly dosing - a significant improvement over current daily treatments. The flat exposure profile with peak-to-trough ratios of 1.47-1.79 suggests more stable calcium control compared to existing therapies.
The dose-proportional increases in serum calcium and PTH suppression confirm the drug's mechanism of action is working as intended. The safety profile appears favorable, with mostly mild adverse events and no serious complications. These results position MBX 2109 as a potentially transformative treatment for hypoparathyroidism patients who currently face challenging daily management regimens.
Peer-reviewed publication features positive results from multiple ascending dose (MAD) portion of Phase 1 MBX 2109 study in healthy participants
CARMEL, 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 Hypoparathyroidism
HP 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
About MBX 2109
MBX 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 Biosciences
MBX 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™) Platform
MBX 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 Statements
This 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 Burdick
Inizio Evoke Comms
kate.burdick@inizioevoke.com
860-462-1569
Investor Contact:
Jim DeNike
MBX Biosciences
jdenike@mbxbio.com
FAQ
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