MBX Biosciences Announces Positive Phase 1 Topline Results for MBX 1416 for the Treatment of Post-bariatric Hypoglycemia
MBX Biosciences (Nasdaq: MBX) announced positive Phase 1 results for MBX 1416, their investigational long-acting GLP-1 receptor antagonist for post-bariatric hypoglycemia (PBH) treatment. The trial, involving 69 healthy volunteers, demonstrated that MBX 1416 was generally well-tolerated with a favorable safety profile.
Key findings include:
- No dose-related serious adverse events observed
- 90-hour median half-life supporting once-weekly dosing
- Dose-proportional concentration increases in both single and multiple ascending dose cohorts
- Increased GLP-1 levels within 60 minutes of meal tests
The company plans to initiate Phase 2 studies in PBH patients in the second half of 2025, pending FDA alignment at a mid-2025 End-of-Phase 1 meeting.
MBX Biosciences (Nasdaq: MBX) ha annunciato risultati positivi della Fase 1 per MBX 1416, il loro antagonista del recettore GLP-1 a lungo termine in fase di sperimentazione per il trattamento dell'ipoglicemia post-bariatrica (PBH). Lo studio, che ha coinvolto 69 volontari sani, ha dimostrato che MBX 1416 è stato generalmente ben tollerato con un profilo di sicurezza favorevole.
I risultati chiave includono:
- Nessun evento avverso grave correlato alla dose osservato
- Emivita mediana di 90 ore che supporta una somministrazione settimanale
- Aumenti delle concentrazioni proporzionali alla dose sia in coorti a dose singola che in quelle a dose ascendente multipla
- Aumento dei livelli di GLP-1 entro 60 minuti dai test di pasto
L'azienda prevede di avviare studi di Fase 2 in pazienti con PBH nella seconda metà del 2025, in attesa dell'allineamento della FDA a una riunione di fine fase 1 a metà 2025.
MBX Biosciences (Nasdaq: MBX) anunció resultados positivos de la Fase 1 para MBX 1416, su antagonista del receptor GLP-1 de acción prolongada en investigación para el tratamiento de la hipoglucemia post-bariátrica (PBH). El ensayo, que incluyó a 69 voluntarios sanos, demostró que MBX 1416 fue generalmente bien tolerado y tuvo un perfil de seguridad favorable.
Los hallazgos clave incluyen:
- No se observaron eventos adversos graves relacionados con la dosis
- Una vida media mediana de 90 horas que respalda la dosificación semanal
- Aumentos de concentración proporcionales a la dosis en cohortes de dosis ascendente simple y múltiple
- Aumento de los niveles de GLP-1 dentro de los 60 minutos de las pruebas de comidas
La empresa planea iniciar estudios de Fase 2 en pacientes con PBH en la segunda mitad de 2025, a la espera de la alineación de la FDA en una reunión de fin de Fase 1 a mediados de 2025.
MBX 바이오사이언스 (Nasdaq: MBX)는 MBX 1416에 대한 긍정적인 1상 결과를 발표했습니다. 이는 비만 수술 후 저혈당증(PBH) 치료를 위한 장기 작용 GLP-1 수용체 길항제입니다. 69명의 건강한 자원자가 참여한 이 시험에서 MBX 1416은 일반적으로 잘 견디며 안전성 프로필이 우수한 것으로 나타났습니다.
주요 발견 사항은 다음과 같습니다:
- 용량 관련 심각한 부작용 없음
- 주 1회 투여를 지원하는 90시간의 중앙 반감기
- 단일 및 다단계 용량 증가군에서 용량 비례 농도 증가
- 식사 테스트 후 60분 이내에 GLP-1 수치 증가
회사는 2025년 하반기에 PBH 환자를 대상으로 2상 연구를 시작할 계획이며, 2025년 중반에 예정된 FDA의 1상 종료 회의에서의 합의에 따를 것입니다.
MBX Biosciences (Nasdaq: MBX) a annoncé des résultats positifs de la Phase 1 pour MBX 1416, leur antagoniste du récepteur GLP-1 à action prolongée en cours d'étude pour le traitement de l'hypoglycémie post-bariatrique (PBH). L'essai, impliquant 69 volontaires en bonne santé, a démontré que MBX 1416 était généralement bien toléré avec un profil de sécurité favorable.
Les résultats clés comprennent :
- Aucun événement indésirable grave lié à la dose observé
- Une demi-vie médiane de 90 heures soutenant une posologie hebdomadaire
- Augmentations de concentration proportionnelles à la dose dans les cohortes de dose unique et de dose ascendante multiple
- Augmentation des niveaux de GLP-1 dans les 60 minutes suivant les tests de repas
L'entreprise prévoit de commencer des études de Phase 2 chez des patients atteints de PBH dans la seconde moitié de 2025, en attendant l'accord de la FDA lors d'une réunion de fin de phase 1 à la mi-2025.
MBX Biosciences (Nasdaq: MBX) hat positive Ergebnisse der Phase 1 für MBX 1416 bekannt gegeben, ihren investigativen langwirksamen GLP-1-Rezeptorantagonisten zur Behandlung von postbariatrischer Hypoglykämie (PBH). Die Studie umfasste 69 gesunde Freiwillige und zeigte, dass MBX 1416 im Allgemeinen gut vertragen wurde und ein günstiges Sicherheitsprofil aufwies.
Wichtige Ergebnisse umfassen:
- Keine dosisabhängigen schwerwiegenden Nebenwirkungen beobachtet
- Medianhalbwertszeit von 90 Stunden, die die wöchentliche Dosierung unterstützt
- Dosisproportionale Konzentrationsanstiege sowohl in einzelnen als auch in mehrfach ansteigenden Dosisgruppen
- Erhöhte GLP-1-Spiegel innerhalb von 60 Minuten nach den Mahlzeittests
Das Unternehmen plant, in der zweiten Hälfte des Jahres 2025 Phase-2-Studien bei PBH-Patienten zu starten, abhängig von der Abstimmung mit der FDA in einem Zwischenbericht zur Phase-1-Sitzung Mitte 2025.
- Phase 1 trial met safety and tolerability endpoints
- 90-hour half-life supports convenient once-weekly dosing
- Demonstrated dose-proportional pharmacokinetics
- No drug interaction observed with rosuvastatin
- Clear timeline for Phase 2 initiation in 2H 2025
- 88% of subjects experienced injection site reactions
- Phase 2 start dependent on FDA alignment
- Commercial launch timeline extends several years into future
Insights
The Phase 1 results for MBX 1416 represent a significant milestone in addressing post-bariatric hypoglycemia (PBH). The data reveals three important elements: favorable safety profile, promising pharmacokinetics with a 90-hour half-life supporting weekly dosing and evidence of target engagement through increased GLP-1 levels post-meal.
The trial's design was robust, incorporating both SAD and MAD components with 69 subjects across multiple dose cohorts. The observed dose-proportional pharmacokinetics and lack of drug-drug interaction with rosuvastatin are particularly encouraging for clinical application. While injection site reactions were common, their predominantly mild-to-moderate nature and resolution within a week suggest manageable tolerability.
For investors, this positions MBX favorably in the competitive landscape of metabolic disorders. PBH represents an underserved market with significant growth potential and the successful completion of Phase 1 reduces early-stage development risk. The planned Phase 2 initiation in 2H 2025 provides a clear catalyst timeline.
From a market perspective, MBX 1416's development addresses a important gap in the $2.7 billion bariatric surgery complications market. With bariatric procedures increasing globally, the incidence of PBH is expected to rise, creating expanded market opportunities. The once-weekly dosing regime, if maintained through later trials, would offer a significant competitive advantage over potential daily treatments.
The company's
Phase 1 results support proceeding to Phase 2 in patients with post-bariatric hypoglycemia (PBH), which is expected to begin in 2H 2025
Phase 1 trial in healthy volunteers showed MBX 1416 was generally well-tolerated with a favorable safety profile
Pharmacokinetic results demonstrated sustained dose-dependent exposure and support once-weekly dosing
Company to host conference call to discuss results today at 8:30 am ET
CARMEL, Ind., Jan. 07, 2025 (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 positive results from its Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) clinical trial of MBX 1416 in healthy adult volunteers. MBX 1416 is the Company’s investigational long-acting glucagon-like peptide 1 (GLP-1) receptor antagonist, being developed for the treatment of PBH.
“We are encouraged by the positive topline Phase 1 results in healthy volunteers that showed MBX 1416 was generally well-tolerated with a favorable safety profile and a promising pharmacokinetic profile supportive of once-weekly dosing,” said Kent Hawryluk, President and Chief Executive Officer of MBX Biosciences. “We also observed an apparent increase in GLP-1 peak during the first hour after a mixed meal tolerance test, which is an encouraging signal that we believe may translate into a therapeutic benefit in patients with PBH. Based on these results, we intend to initiate a Phase 2 study in patients with PBH in the second half of 2025 to further optimize dosing, pending alignment with the FDA on our proposed study design.”
Phase 1 Trial Topline Results
Key results from the study are as follows:
- MBX 1416 was generally well-tolerated with a favorable safety profile.
- No MBX 1416 dose-related serious adverse events were observed and the majority of treatment-emergent adverse events were mild or moderate in severity.
- Injection site reactions (ISR), predominantly characterized by erythema, were commonly observed in both single and multiple ascending dose cohorts. These reactions were mild or moderate in
88% of the subjects with ISRs and resolved within approximately seven days in the MAD cohort. - MBX 1416 concentrations increased dose-proportionally in both the SAD and MAD cohorts.
- In the MAD cohort, MBX 1416 median half-life was approximately 90 hours, supporting once-weekly administration, and at steady state the median Tmax was between 36 and 48 hours.
- In the MAD cohort, MBX 1416 appeared to increase GLP-1 within 60 minutes of a mixed meal tolerance test, suggesting a pharmacodynamic (PD) effect in healthy volunteers that may translate into a therapeutic benefit in PBH patients.
- Consistent with known GLP-1 antagonism effect on gastric motility, a slight acceleration of gastric emptying was observed with MBX 1416 based on acetaminophen exposure.
- In the drug-drug interaction (DDI) portion of the trial, MBX 1416 was observed to have no meaningful effect on rosuvastatin exposure, a commonly prescribed statin.
Phase 1 Trial Design
The Phase 1 clinical trial was a randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MBX 1416 in healthy adult volunteers. The trial was conducted in the United States and enrolled a total of 69 subjects. The single ascending dose (SAD) portion of this Phase 1 trial evaluated 32 healthy adults randomized to receive placebo (n=8) or subcutaneous MBX 1416 doses of 10 mg (n=6), 30 mg (n=6), 100 mg (n=6) and 200 mg (n=6). The multiple ascending dose (MAD) portion of the trial evaluated 23 healthy adults randomized to receive placebo (n=5) or subcutaneous MBX 1416 doses of 10 mg (n=6), 30 mg (as two injections; n=6) and 30 mg (as one injection; n=6). An additional cohort evaluated rosuvastatin and acetaminophen pharmacokinetics in the presence and absence of MBX 1416 (n=14).
MBX Biosciences intends to discuss these results with the U.S. Food and Drug Administration (FDA) in an End-of-Phase 1 meeting in mid-2025. Pending alignment with the FDA, a Phase 2 study of MBX 1416 in patients with PBH is anticipated to initiate in the second half of 2025.
MBX Biosciences will host a conference call and webcast today, January 7, 2025, at 8:30 am Eastern Time to discuss the results from the MBX 1416 Phase 1 trial. Participants can register here to access the live webcast of the conference call. Those who prefer to join the call via phone can register using this link receive a dial-in number and unique PIN. Following the live event, a replay will be available on the Investors section of the Company’s website.
About MBX 1416
MBX 1416 is an investigational long-acting glucagon-like peptide-1 (GLP-1) receptor antagonist in development as a potential treatment for PBH. It was designed using the Company’s novel, proprietary PEP™ platform to prevent the occurrence of severe hypoglycemia in individuals with PBH so they can lead healthier and more independent lives.
About Post-bariatric Hypoglycemia
Post-bariatric hypoglycemia (PBH) is a rare and serious complication of bariatric surgery. PBH is characterized by repeated episodes of symptomatic hypoglycemia, triggered by exaggerated secretion of GLP-1 levels following a meal, and can present as early as six months after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy. Hypoglycemic episodes can occur multiple times per day and can periodically manifest with severe symptoms, such as dizziness, confusion, loss of consciousness or seizure. The unpredictability of hypoglycemic episodes and their associated risks may meaningfully hinder daily activities. As a result, the patient burden can be substantial, and many individuals cannot drive, work or live alone. To date, there are no approved pharmacotherapies to treat PBH. As the use of surgery to address metabolic conditions continues to rise, the incidence of PBH is expected to increase, reinforcing the need for safe and effective therapies.
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: trial results from MBX’s Phase 1 trial of MBX 1416, including topline results, statements relating to the ability of MBX 1416 to treat patients with PBH, expectations regarding future clinical evaluation of MBX 1416 in PBH, statements relating to MBX 1416 having a favorable safety profile, and statements relating to a potential meeting with the FDA and the intention to initiate a Phase 2 study in patients with PBH in the second half of 2025.
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 and that early-stage trials may not be predictive of later-stage trials; 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
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