Twelve-month durability data from Metagenomi’s ongoing nonhuman primate (NHP) study
in hemophilia A remains generally consistent with data previously released at 4.5 months
NHPs remain healthy and exhibit normal weight gain; treatment is generally well tolerated
Program on track for IND filing in 2026
Company to host conference call with management and Dr. Glenn Pierce, international thought leader in hemophilia A
EMERYVILLE, CA, USA I September 03, 2024 I Metagenomi, Inc. (Nasdaq: MGX), a precision genetic medicines company committed to developing curative therapeutics for patients using its proprietary gene editing toolbox, today announced data from an ongoing preclinical study designed to provide evidence supporting the potential durability and safety of the company’s hemophilia A gene editing investigational therapy, MGX-001.
“We are thrilled to achieve this preclinical milestone supporting our recent decision to declare MGX-001 as our development candidate for hemophilia A,” said Brian C. Thomas, PhD, CEO and founder of Metagenomi. “We conducted this NHP study in response to a competitive landscape where gene therapies have been unable to achieve long term persistence of FVIII activity levels in patients. Establishing proof-of-concept of site specific gene integration and durable activity levels of FVIII in NHPs over twelve months in hemophilia A represents an important validation of our platform. Our goal for MGX-001 is to provide a one-time, curative treatment for adults and children with hemophilia A. Furthermore, we intend to leverage the MGX-001 editing platform to pursue additional therapies for secreted protein disorders.”
The NHP study involved treating three NHPs with a single intravenous dose of an adeno associated virus (AAV) containing a FVIII donor template followed 35 days later by a single intravenous dose of a lipid nanoparticle (LNP) containing a novel Metagenomi nuclease and associated guide RNA targeting the first intron of the albumin gene. Each animal received only a single dose of dexamethasone prior to the AAV and LNP doses. The NHPs were then followed for safety and donor FVIII activity. The NHPs also underwent liver biopsy on Day 7 to evaluate editing and integration efficiency. The study remains ongoing.
All NHPs demonstrated durable FVIII activity levels over the twelve-month period. At the twelve-month time point two of the NHPs had FVIII activity levels within normal/near normal range (82% and 41%) while the third NHP had FVIII activity level in the mild hemophilia range (9%). Comparisons of mean values from the three to six month time points to the nine to twelve month time points were highly consistent, demonstrating no significant decline in donor-derived FVIII activity levels. Liver biopsy data demonstrated gene integration in the forward orientation at a frequency of 0.7% to 2.9%; these values positively correlated with FVIII activity levels. Treatment was generally well tolerated with findings limited to moderate transient elevation of liver transaminases following AAV and LNP administration. There were no notable findings in total bilirubin or albumin levels or adverse clinical observations.
This early NHP study was conducted without the benefit of several subsequent optimizations of the therapeutic candidate designed to enhance safety and efficacy in the clinic. For the development candidate MGX-001, the company selected a bioengineered FVIII construct designed to improve FVIII activity levels, optimized the ratio of different LNP components and timing between AAV and LNP administration, and enhanced aspects of the manufacturing processes.
“The treatment of hemophilia, which has undergone many transformative changes over the past 60 years, is poised for yet another disruptive change: the use of genome editing, with site specific integration of FVIII, to produce functional cures in patients with hemophilia A. I am encouraged by the preclinical progress in the genome editing space to potentially provide a new path to a one-time, curative treatment option for both adults and children in hemophilia A in the future,” said Dr. Glenn Pierce, member of the Metagenomi Scientific Advisory Board.
The company will host a conference call at 8:30am ET, on Wednesday, September 4, 2024. The registration link to the webcast can be found at https://ir.metagenomi.co/.
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 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). 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.
SOURCE: Metagenomi
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Twelve-month durability data from Metagenomi’s ongoing nonhuman primate (NHP) study
in hemophilia A remains generally consistent with data previously released at 4.5 months
NHPs remain healthy and exhibit normal weight gain; treatment is generally well tolerated
Program on track for IND filing in 2026
Company to host conference call with management and Dr. Glenn Pierce, international thought leader in hemophilia A
EMERYVILLE, CA, USA I September 03, 2024 I Metagenomi, Inc. (Nasdaq: MGX), a precision genetic medicines company committed to developing curative therapeutics for patients using its proprietary gene editing toolbox, today announced data from an ongoing preclinical study designed to provide evidence supporting the potential durability and safety of the company’s hemophilia A gene editing investigational therapy, MGX-001.
“We are thrilled to achieve this preclinical milestone supporting our recent decision to declare MGX-001 as our development candidate for hemophilia A,” said Brian C. Thomas, PhD, CEO and founder of Metagenomi. “We conducted this NHP study in response to a competitive landscape where gene therapies have been unable to achieve long term persistence of FVIII activity levels in patients. Establishing proof-of-concept of site specific gene integration and durable activity levels of FVIII in NHPs over twelve months in hemophilia A represents an important validation of our platform. Our goal for MGX-001 is to provide a one-time, curative treatment for adults and children with hemophilia A. Furthermore, we intend to leverage the MGX-001 editing platform to pursue additional therapies for secreted protein disorders.”
The NHP study involved treating three NHPs with a single intravenous dose of an adeno associated virus (AAV) containing a FVIII donor template followed 35 days later by a single intravenous dose of a lipid nanoparticle (LNP) containing a novel Metagenomi nuclease and associated guide RNA targeting the first intron of the albumin gene. Each animal received only a single dose of dexamethasone prior to the AAV and LNP doses. The NHPs were then followed for safety and donor FVIII activity. The NHPs also underwent liver biopsy on Day 7 to evaluate editing and integration efficiency. The study remains ongoing.
All NHPs demonstrated durable FVIII activity levels over the twelve-month period. At the twelve-month time point two of the NHPs had FVIII activity levels within normal/near normal range (82% and 41%) while the third NHP had FVIII activity level in the mild hemophilia range (9%). Comparisons of mean values from the three to six month time points to the nine to twelve month time points were highly consistent, demonstrating no significant decline in donor-derived FVIII activity levels. Liver biopsy data demonstrated gene integration in the forward orientation at a frequency of 0.7% to 2.9%; these values positively correlated with FVIII activity levels. Treatment was generally well tolerated with findings limited to moderate transient elevation of liver transaminases following AAV and LNP administration. There were no notable findings in total bilirubin or albumin levels or adverse clinical observations.
This early NHP study was conducted without the benefit of several subsequent optimizations of the therapeutic candidate designed to enhance safety and efficacy in the clinic. For the development candidate MGX-001, the company selected a bioengineered FVIII construct designed to improve FVIII activity levels, optimized the ratio of different LNP components and timing between AAV and LNP administration, and enhanced aspects of the manufacturing processes.
“The treatment of hemophilia, which has undergone many transformative changes over the past 60 years, is poised for yet another disruptive change: the use of genome editing, with site specific integration of FVIII, to produce functional cures in patients with hemophilia A. I am encouraged by the preclinical progress in the genome editing space to potentially provide a new path to a one-time, curative treatment option for both adults and children in hemophilia A in the future,” said Dr. Glenn Pierce, member of the Metagenomi Scientific Advisory Board.
The company will host a conference call at 8:30am ET, on Wednesday, September 4, 2024. The registration link to the webcast can be found at https://ir.metagenomi.co/.
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 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). 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.
SOURCE: Metagenomi
Post Views: 850
