LB-001 / CANbridge Pharma, AstraZeneca - LARVOL DELTA

First-in-human nuclease-free homologous recombination-dependent gene editing in pediatric patients with methylmalonic acidemia: results of a phase 1/2 study. (PubMed, Gene Ther) - "SUNRISE, a first-in-human phase 1/2 open-label study, evaluated the safety/tolerability (primary endpoints) of liver-targeted hLB-001 in four pediatric participants (ages 20-114 months) with mitochondrial methylmalonyl-CoA mutase (MMUT)-deficient MMA...These results provide proof-of-concept for use of liver-targeted gene editing without nucleases for MMA and other genetic metabolic disorders. ClinicalTrials.gov identifier: NCT04581785Target journal: Gene Therapy (Springer Nature)."

First-in-human • Journal • P1/2 data • Gene Therapies • Genetic Disorders • Inflammation • Metabolic Disorders • Ophthalmology • Pediatrics • FGF21

Demonstration of Nuclease-Free Genome Editing (GeneRide™) in Pediatric Patients with Methylmalonic Acidemia (ASGCT 2024) - P, P1/2 | "A phase 1/2 dose escalation trial (NCT04581785) evaluated the safety and efficacy of a single hLB-001 intravenous infusion in pediatric MMA patients...This study was the first to demonstrate successful in vivo homologous recombination genome editing without the use of nucleases or promotors in a pediatric population. Future efforts will focus on methods to increase the integration rate of a corrective gene to accelerate time to efficacy with increased safety."

Clinical • Diabetes • Gene Therapies • Genetic Disorders • Hepatology • Metabolic Disorders • Ophthalmology • Pediatrics • Transplantation

SUNRISE: Gene Therapy With hLB-001 in Pediatric Patients With Severe Methylmalonic Acidemia (clinicaltrials.gov) - P1/2 | N=4 | Terminated | Sponsor: LogicBio Therapeutics, Inc | Trial completion date: Dec 2023 ➔ Jan 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2023 ➔ Jan 2023; Due to low likelihood of clinical benefit in treated participants.

Gene therapy • Trial completion date • Trial primary completion date • Trial termination • Gene Therapies • Genetic Disorders • Metabolic Disorders • Ophthalmology • Pediatrics • FGF21

SUNRISE: Gene Therapy With hLB-001 in Pediatric Patients With Severe Methylmalonic Acidemia (clinicaltrials.gov) - P1/2 | N=8 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene therapy • Gene Therapies • Genetic Disorders • Metabolic Disorders • Ophthalmology • Pediatrics • FGF21

Long-term Follow-up Study of Patients Who Received hLB-001 Gene Therapy (clinicaltrials.gov) - P=N/A | N=8 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene therapy • Gene Therapies • Genetic Disorders • Metabolic Disorders • Ophthalmology

Novel AAV-mediated genome editing therapy improves health and survival in a mouse model of methylmalonic acidemia. (PubMed, PLoS One) - "In mice with a humanized liver, treatment with a human homolog of mLB-001 resulted in site-specific genome editing and transgene expression in the transplanted human hepatocytes. Taken together, these findings support the development of hLB-001 that is currently in clinical trials in pediatric patients with severe forms of MMA."

Journal • Preclinical • Genetic Disorders • Metabolic Disorders • Ophthalmology • Pediatrics • Transplantation

SUNRISE: Gene Therapy With hLB-001 in Pediatric Patients With Severe Methylmalonic Acidemia (clinicaltrials.gov) - P1/2 | N=8 | Recruiting | Sponsor: LogicBio Therapeutics, Inc. | Trial completion date: Jun 2023 ➔ Dec 2023 | Trial primary completion date: Jun 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Gene Therapies • Genetic Disorders • Metabolic Disorders • Ophthalmology • Pediatrics • FGF21

Long-term Follow-up Study of Patients Who Received hLB-001 Gene Therapy (clinicaltrials.gov) - P=N/A | N=8 | Recruiting | Sponsor: LogicBio Therapeutics, Inc.

New trial • Gene Therapies • Genetic Disorders • Metabolic Disorders • Ophthalmology

Assembling a Comprehensive Potency Assay Matrix for Late-Stage Manufacturing of AAV Viral Vectors (ASGCT 2022) - "SUNRISE is a Phase I/II clinical trial which is exploring the use of hLB-001 to potentially treat pediatric patients with methylmalonic acidemia characterized by methlmalonyl-CoA mutase gene (MMUT) mutations...Here, a combination of mRNA expression and enzymatic activity assays are used to show comparable levels of potency when both genomic integration and functional activity are required to effectively treat the disease. The assays were initially assessed by performing linearity and inter/intra-assay precision experiments, and then were further evaluated using different batches of drug substance and heat-treated samples to demonstrate alignment of the two analytical methods in measuring vector potency."

Gene Therapies • Genetic Disorders • Metabolic Disorders • Ophthalmology • Pediatrics

SUNRISE: Gene Therapy With hLB-001 in Pediatric Patients With Severe Methylmalonic Acidemia (clinicaltrials.gov) - P1/2; N=8; Recruiting; Sponsor: LogicBio Therapeutics, Inc.; Trial completion date: Feb 2023 ➔ Jun 2023; Initiation date: Feb 2021 ➔ Jun 2021; Trial primary completion date: Feb 2023 ➔ Jun 2023

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Pediatrics • FGF21

"#EULAR2020 Abstr#LB001 Coming soon...another indication for @Rinvoq? Favorable response in phase III trial of upadacitinib vs. ADA vs. PCB for PsA (SELECT-PsA-1) @abbvie @rheumnow" (,@KDAO2011)

P3 data

"#EULAR2020 #LB0001 SELECT-PsA-1 Upadacitinib vs PBO vs ADA: UPA 15/30 mg non-inferior &UPA 30 superior to ADA for ACR20. At wk12 ACR 20 70.6% UPA15, 78.5% UPA30 vs 36.2%PBO & 65%ADA. Better ACR50/70 &MDA va PBO. No new safety signals. @RheumNow" (,@DrPetryna)

Clinical