Metagenomi Presents Updated Preclinical Data in Hemophilia A at American Society of Hematology (ASH) 66th Annual Meeting
Metagenomi (MGX) presented updated preclinical data for its hemophilia A program at the ASH 66th Annual Meeting. The company's gene editing approach demonstrated sustained Factor VIII (FVIII) activity levels through more than 16 months in nonhuman primates (NHPs). The study involved three NHPs receiving a single treatment, showing FVIII activity maintenance at 72%, 9%, and 30% at the 16.5-month timepoint.
The company's lead candidate, MGX-001, which uses a B-domain deleted bioengineered FVIII construct, achieved higher FVIII activity compared to wild type FVIII at similar integration rates. The program is on track for IND filing in 2026. The treatment showed only transient elevation of liver transaminases with no other safety concerns, positioning it as a potential one-time curative treatment for both adults and children with hemophilia A.
Metagenomi (MGX) ha presentato dati preclinici aggiornati per il suo programma sulla emofilia A durante il 66° Congresso Annuale dell'ASH. L'approccio di editing genetico dell'azienda ha dimostrato di mantenere livelli di attività del Fattore VIII (FVIII) per oltre 16 mesi in primati non umani (NHP). Lo studio ha coinvolto tre NHP che hanno ricevuto un trattamento singolo, mostrando il mantenimento dell'attività FVIII al 72%, 9% e 30% al punto temporale di 16,5 mesi.
Il candidato principale dell'azienda, MGX-001, che utilizza un costrutto di FVIII bioingegnerizzato con delezione della B-domain, ha raggiunto livelli di attività FVIII superiori rispetto al FVIII di tipo selvatico a tassi di integrazione simili. Il programma è in linea per la presentazione della domanda IND nel 2026. Il trattamento ha mostrato solo un'elevazione transitoria delle transaminasi epatiche senza altre preoccupazioni per la sicurezza, posizionandosi come un potenziale trattamento curativo una tantum per adulti e bambini con emofilia A.
Metagenomi (MGX) presentó datos preclínicos actualizados para su programa de hemofilia A en la 66ª Reunión Anual de la ASH. El enfoque de edición genética de la compañía demostró niveles sostenidos de actividad del Factor VIII (FVIII) durante más de 16 meses en primates no humanos (NHP). El estudio involucró a tres NHP que recibieron un solo tratamiento, mostrando mantenimiento de la actividad FVIII del 72%, 9% y 30% en el punto temporal de 16,5 meses.
El candidato principal de la compañía, MGX-001, que utiliza un constructo de FVIII bioingenierizado con eliminación de la B-domain, logró una mayor actividad de FVIII en comparación con el FVIII salvaje a tasas de integración similares. El programa está en camino para la presentación de la solicitud IND en 2026. El tratamiento mostró solo una elevación transitoria de las transaminasas hepáticas sin otras preocupaciones de seguridad, posicionándose como un posible tratamiento curativo de una sola vez para adultos y niños con hemofilia A.
Metagenomi (MGX)는 ASH 제66차 연례 회의에서 혈우병 A 프로그램에 대한 업데이트된 전임상 데이터를 발표했습니다. 회사의 유전자 편집 접근법은 비인간 영장류(NHP)를 대상으로 16개월 이상 지속된 혈액 응고 인자 VIII (FVIII) 활성 수준을 보였습니다. 연구에는 단일 치료를 받은 세 마리의 NHP가 포함되었으며, 16.5개월 시점에서 각각 72%, 9%, 30%의 FVIII 활성 유지가 나타났습니다.
회사의 주요 후보인 MGX-001은 B-domain이 삭제된 생체공학 FVIII 구조체를 사용하며, 유사한 통합 속도에서 야생형 FVIII보다 높은 FVIII 활성을 달성했습니다. 프로그램은 2026년 IND 제출을 목표로 진행되고 있습니다. 치료는 간 효소 수치의 일시적인 상승만을 나타냈으며 다른 안전성 우려는 없어서, 성인과 어린이 모두의 혈우병 A에 대한 잠재적인 일회성 치료제로 자리매김하고 있습니다.
Metagenomi (MGX) a présenté des données précliniques mises à jour pour son programme sur l'hémophilie A lors de la 66e Réunion Annuelle de l'ASH. L'approche d'édition génique de l'entreprise a montré des niveaux d'activité soutenus du facteur VIII (FVIII) pendant plus de 16 mois chez des primates non humains (NHP). L'étude a impliqué trois NHP ayant reçu un traitement unique, montrant un maintien de l'activité FVIII à 72 %, 9 % et 30 % au point temporel de 16,5 mois.
Le candidat principal de l'entreprise, MGX-001, qui utilise un construct de FVIII bio-ingénierie avec délétion du B-domain, a atteint une activité FVIII supérieure par rapport au FVIII sauvage à des taux d'intégration similaires. Le programme est sur la bonne voie pour le dépôt d'une demande IND en 2026. Le traitement a montré uniquement une élévation temporaire des transaminases hépatiques sans autres préoccupations en matière de sécurité, se positionnant comme un traitement potentiel curatif unique pour les adultes et les enfants atteints d'hémophilie A.
Metagenomi (MGX) hat aktualisierte präklinische Daten für sein Programm zur Hämophilie A auf der 66. Jahrestagung der ASH präsentiert. Der gentechnische Ansatz des Unternehmens zeigte über 16 Monate hinweg stabile Aktivitätsniveaus des Faktors VIII (FVIII) bei nichtmenschlichen Primaten (NHP). In der Studie erhielten drei NHP eine einmalige Behandlung, bei der die FVIII-Aktivität bei 72%, 9% und 30% zum Zeitpunkt von 16,5 Monaten aufrechterhalten wurde.
Der Hauptkandidat des Unternehmens, MGX-001, der ein bioengineering Konstrukt von FVIII mit deletiertem B-domain verwendet, erreichte im Vergleich zum Wildtyp-FVIII bei ähnlichen Integrationsraten eine höhere FVIII-Aktivität. Das Programm ist auf Kurs zur IND-Anmeldung im Jahr 2026. Die Behandlung zeigte nur eine vorübergehende Erhöhung der Lebertransaminasen ohne weitere Sicherheitsbedenken, wodurch es sich als potenzielle einmalige Heilbehandlung für Erwachsene und Kinder mit Hämophilie A positioniert.
- Sustained FVIII activity levels through 16+ months in NHP study
- MGX-001 demonstrated higher FVIII activity vs wild type FVIII
- No significant safety concerns observed in preclinical studies
- Program on track for IND filing in 2026
- No identifiable off-target editing detected in MGX-001
- Significant variability in FVIII activity levels among test subjects (ranging from 9% to 72%)
- Transient elevation of liver transaminases observed during treatment
Insights
The updated preclinical data for Metagenomi's hemophilia A program shows promising results with significant implications. The sustained Factor VIII activity levels over 16 months in non-human primates, ranging from
The bioengineered MGX-001 construct's ability to achieve higher FVIII activity with similar integration rates compared to wild-type FVIII is a important technological advancement. This could enable lower dosing requirements, potentially improving the safety profile while maintaining therapeutic efficacy. The absence of significant safety concerns and off-target editing in preliminary studies further strengthens the program's prospects.
From a development perspective, the data presents several compelling advantages. The single-dose administration protocol with minimal immunosuppression (one dose of dexamethasone) could significantly improve patient compliance and reduce treatment burden. The sustained therapeutic levels without significant liver toxicity address key concerns in gene therapy approaches.
The 2026 IND filing timeline provides a clear development pathway. The comprehensive safety profile, including transient liver enzyme elevations and stable albumin levels, aligns with regulatory expectations. The potential application in both adult and pediatric populations could significantly expand the addressable market, though this will require additional safety validation.
Therapeutically relevant levels of Factor VIII (FVIII) activity sustained in ongoing nonhuman primate (NHP) study through more than sixteen months of follow up
MGX-001 bioengineered FVIII construct exhibited higher FVIII activity at similar integration rates compared to wild type FVIII construct in preclinical studies; program on track for IND filing in 2026
EMERYVILLE, Calif., Dec. 09, 2024 (GLOBE NEWSWIRE) -- Metagenomi, Inc. (Nasdaq: MGX), a precision genetic medicines company committed to developing curative therapeutics for patients using its proprietary gene editing toolbox, today presented updated preclinical NHP data for its hemophilia A program in an oral presentation (link here) at the American Society of Hematology (ASH) 66th Annual Meeting and Exposition in San Diego.
“The distinguishing feature of our gene editing approach to hemophilia A, compared to conventional gene therapies, lies in our ability to achieve durable Factor VIII activity levels through precise in vivo integration of the FVIII gene. Today, we shared updated preclinical data demonstrating durable FVIII activity over 16 months in an ongoing NHP study. Additionally, we are pleased to highlight our lead development candidate, MGX-001, which uses a B domain deleted bioengineered FVIII construct, achieved higher levels of FVIII activity versus wild type FVIII, with preclinical evidence of durable FVIII activity levels. Together, these studies help support proof-of-concept as we progress MGX-001 toward the clinic. MGX-001 represents a potentially one-time curative treatment for both adults and children, with the goal to change the treatment paradigm for patients living with hemophilia A,” said Brian C. Thomas, PhD, CEO and Founder of Metagenomi.
NHP durability study update:
In a preclinical study, a cynomolgus version of the FVIII gene (cFVIII), used to avoid the confounding effects of anti-human FVIII antibodies, was administered to three NHPs via AAV at a dose of 2.0E13 vg/kg. Five weeks later, each NHP was administered an LNP at a dose of 1.0 mg/kg, delivering the MG29-1 nuclease mRNA and associated guide RNA. Each animal received only a single dose of dexamethasone prior to the AAV and LNP doses. Plasma was collected and assayed for safety parameters and FVIII activity. Data was generated over 16 months and the study remains ongoing.
Results of the study suggest that FVIII activity was maintained over the 16-month study duration. Mean FVIII activity of months 13-16.5 following LNP dosing was
MGX-001 update:
A separate NHP study designed to support the company’s lead hemophilia A development candidate, MGX-001, which uses a B-domain deleted bioengineered FVIII construct, demonstrated significantly higher FVIII activity compared to wild type FVIII, despite similar integration frequency between the bioengineered construct and wild type gene. This result suggests the MGX-001 bioengineered construct may enable therapeutic FVIII activity at lower AAV doses with the potential for associated safety benefits. In addition, MGX-001 showed no identifiable off-target editing to-date in a series of orthogonal assays employed to discover and validate potential off-target sites.
About Hemophilia A
Hemophilia A is the most common X-linked inherited bleeding disorder, caused by a large variety of mutations in the FVIII gene leading to a loss of functional FVIII protein. Intracranial bleeding is of greatest concern as this can lead to major morbidity and mortality. Bleeding into joints leads to cumulative joint damage and is a major cause of morbidity. Diagnosis of severe disease typically occurs in infancy due to exaggerated bleeding in response to minor injury or routine medical procedures. Prevalence is estimated to be up to 26,500 patients in the US and more than 500,000 patients globally according to the World Federation of Hemophilia (WFH), with the vast majority of patients being male.
About Metagenomi
Metagenomi is a precision genetic medicines company committed to developing curative therapeutics for patients using its proprietary, comprehensive metagenomics-derived toolbox. Metagenomi is harnessing the power of metagenomics, the study of genetic material recovered from the natural environment, to unlock four billion years of microbial evolution to discover and develop a suite of novel editing tools capable of correcting any type of genetic mutation found anywhere in the genome. Its comprehensive genome editing toolbox includes programmable nucleases, base editors, and RNA and DNA-mediated integration systems (including prime editing systems and clustered regularly interspaced short palindromic repeat associated transposases (CAST)). Metagenomi believes its diverse and modular toolbox positions the company to access the entire genome and select the optimal tool to unlock the full potential of genome editing for patients. For more information, please visit https://metagenomi.co.
Cautionary Note Regarding 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. Such statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “look forward to,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions, include, but are not limited to, any statements relating to product development programs, including the timing of and our ability to conduct IND-enabling studies, make regulatory filings such as INDs, statements concerning the potential of therapies and product candidates, including our development candidate, MGX-001, and any other statements that are not historical facts. Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect our 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 our growth strategy; our ability to obtain, perform under, and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; risks relating to the timing of starting and completing clinical trials; uncertainties relating to preclinical and clinical testing; our dependence on third party suppliers; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in “Risk Factors,” in our most recent Form 10-K and our most recent 10-Qs on file with the Securities and Exchange Commission. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995.
Contact:
Simon Harnest - CIO, SVP Investor Relations
IR@metagenomi.co
FAQ
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