Metagenomi Presents Updated Preclinical Data in Hemophilia A at American Society of Hematology (ASH) 66th Annual Meeting
10 Dicembre 2024 - 3:16AM
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 71%, 7%, and
27% compared to mean FVIII activity of months 3-6 of 76%, 8% and
30%, and mean FVIII activity of months 7-12 of 77%, 8% and 32%
respectively, in animals 1001, 1002 and 1003. At the 16.5-month
time point, FVIII levels were 72%, 9%, 30% in each of the three
animals, respectively. FVIII activity levels correlated with gene
integration frequency from day 7 liver biopsy of 0.7%, 1.3%, 3.1%
in each of the three animals, respectively. The FVIII knock-in was
achieved with only transient elevation of liver transaminases at
the time of AAV and LNP administration, and with no other safety
findings and no impact to circulating albumin levels and no
significant change in total bilirubin post AAV and LNP.
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
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obligation or undertaking to release publicly any updates or
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conditions or circumstances on which any such statement is based,
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Securities Litigation Reform Act of 1995.
Contact:Simon Harnest - CIO, SVP
Investor RelationsIR@metagenomi.co
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