Single intravenous administration of mLB-001 in neonatal or adult MMA mice correlated with prevention of severe weight loss and mortality when challenged with a high protein diet.
LEXINGTON, Mass., Sept. 21, 2022 /PRNewswire/ -- LogicBio Therapeutics, Inc. (Nasdaq: LOGC), a clinical-stage genetic medicine company, today announced that results from the company's preclinical research study entitled "Novel AAV-mediated genome editing therapy prevents metabolic decompensation in a mouse model of methylmalonic acidemia" have been published in the peer-reviewed journal PLOS ONE.
MMA is a metabolic disorder most commonly caused by mutations in the methylmalonyl-CoA mutase (MMUT) gene. Patients with MMUT deficiency are currently treated with strict life-long dietary management to mitigate acute illness that worsens the patient's basal condition, particularly with respect to metabolic brain injury. Early-stage research has indicated that restoration of Mmut enzymatic activity by gene addition mediated by recombinant adeno-associated virus (rAAV) could be a promising approach in the treatment of MMUT deficiency in pediatric patients.
In the study, researchers developed a novel protein-controlled diet regimen in a MMUT deficient mouse model of MMA that mimics the metabolic crises that MMA patients experience. Mice were treated with a single administration of mLB-001, a nuclease-free, promoterless recombinant AAV vector designed based on LogicBio's proprietary GeneRide® platform to deliver the mouse MMUT into the endogenous albumin locus. Mice deficient in MMUT that were treated with the Generide AAV vector had attenuated body weight loss and were protected from mortality when challenged with a high protein diet.
GeneRide-edited hepatocytes also expressed functional MMUT protein and expanded over time in the MMUT deficient mice, suggesting a selective growth advantage over the diseased cells. The expansion of the edited cells was detected over time in the MMA mice by measuring increasing levels of Alb-2A, the same technology-specific biomarker that is being used in LogicBio's SUNRISE trial, a first-in-human, open-label, multi-center, Phase 1/2 clinical trial designed to assess the safety, tolerability, and preliminary efficacy of a single intravenous infusion of LB-001 in pediatric patients with MMA.
"There are no approved therapies to treat the underlying cause of MMUT deficiency. Currently, pediatric patients are managed with strict life-long dietary restrictions designed to help mitigate acute illness that worsens the patient's basal condition, particularly with respect to metabolic brain injury," said Mariana Nacht, chief scientific officer at LogicBio. "These new preclinical results provide strong additional support for the continued development of LB-001 in this indication with the potential to deliver significant benefits to pediatric patients."
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About LogicBio® Therapeutics
LogicBio® Therapeutics is a clinical-stage genetic medicine company pioneering genome editing and gene delivery platforms to address rare and serious diseases from infancy through adulthood. The company's genome editing platform, GeneRide®, is a new approach to precise gene insertion harnessing a cell's natural DNA repair process potentially leading to durable therapeutic protein expression levels. The company's gene delivery platform, sAAVy™, is an adeno-associated virus (AAV) capsid engineering platform designed to optimize gene delivery for treatments in a broad range of indications and tissues. The company's proprietary system, mAAVRx™, aims to overcome some of the current limitations of AAV manufacturing by optimizing the transfection process to improve yields and product quality. The company is based in Lexington, MA. For more information, visit www.logicbio.com, which does not form a part of this release.
Statements in this press release regarding LogicBio®'s plans, expectations, beliefs, intentions and goals are forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended, including but not limited to statements regarding whether certain approaches could be promising in the treatment of MMUT deficiency in pediatric patients; and the potential of the GeneRide® platform. The terms "aim," "anticipate," "designed," "enables," "evaluate," "expects to," "look forward to," "will," and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement, including the risk that existing preclinical data may not be predictive of the results of ongoing or later preclinical and/or clinical results; the risk that the potential direct or indirect impact of the COVID-19 pandemic on our business, operations, and the markets and communities in which we and our partners, collaborators and vendors operate; manufacturing risks; risks associated with management and key personnel changes and transitional periods; the actual funding required to develop and commercialize product candidates, including for safety, tolerability, enrollment, manufacturing or economic reasons; the timing and content of decisions made by regulatory authorities; the actual time it takes to initiate and complete clinical studies; the competitive landscape; changes in the economic and financial conditions of LogicBio; and LogicBio's ability to obtain, maintain and enforce patent and other intellectual property protection for LB-001 and any other product candidates. Other risks and uncertainties include those identified under the heading "Risk Factors" in LogicBio's Annual Report on Form 10-K for the year ended December 31, 2021 and other filings that LogicBio may make with the U.S. Securities and Exchange Commission in the future. These forward-looking statements (except as otherwise noted) speak only as of the date of this press release, and LogicBio does not undertake, and specifically disclaims, any obligation to update any forward-looking statements contained in this press release.
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SOURCE LogicBio Therapeutics, Inc.