Nomlabofusp for Friedreich's ataxia
phase 2drug program · high · Fri Dec 06 2024 00:00:00 GMT+0000 (Coordinated Universal Time)
Deliver human frataxin intracellularly, including to mitochondria and Friedreich's ataxia-relevant tissues, to treat Friedreich's ataxia.
Subcutaneous recombinant cell-penetrating human frataxin fusion protein evaluated in single-ascending-dose, multiple-ascending-dose, dose-exploration, open-label long-term, and pediatric/adolescent clinical studies.
Clinical program includes an open-label long-term study and a study assessing nomlabofusp in adolescents and children with Friedreich's ataxia.
Nonclinical and clinical evidence reports increased nomlabofusp-derived human frataxin in target and peripheral tissues, cross-tissue frataxin correlations, dose-dependent distribution to Friedreich's ataxia-relevant organs, and nonclinical cardiac function and survival benefits in a knockout mouse model.
Friedreich's ataxia tissue frataxin and biomarker assessment
exploratorybiomarker · high · Wed Aug 04 2021 00:00:00 GMT+0000 (Coordinated Universal Time)
Characterize tissue frataxin concentrations, RNA, proteins, specialized lipids, and other potential biomarkers in Friedreich's ataxia and healthy volunteers to support disease assessment and nomlabofusp monitoring.
Clinical biomarker studies using buccal cells, blood, skin cells, tissue frataxin assays, RNA, protein, lipid profiling, and surrogate tissue sampling.
Publications and abstracts report tissue frataxin characteristics, nomlabofusp effects on tissue frataxin, lipid profiles and gene expression, modeling of long-term tissue frataxin levels, and cross-tissue correlations supporting peripheral surrogate sampling.
Evidence indicates peripheral tissues, particularly skin and buccal cells, may support cross-sectional and longitudinal monitoring of human frataxin supplementation in Friedreich's ataxia.
Intracellular protein replacement therapy platform
exploratoryplatform · high
Develop therapies that deliver missing proteins inside cells for complex rare diseases.
Protein replacement therapy platform using cell-penetrating fusion proteins, exemplified by nomlabofusp delivery of human frataxin into mitochondria.
Platform is represented by the lead Friedreich's ataxia candidate nomlabofusp in Phase 2 clinical development.
Published nomlabofusp studies support intracellular delivery of mature and functional frataxin into mitochondria and distribution of human frataxin to disease-relevant tissues.
TAT-Frataxin preclinical research program
preclinicalresearch program · medium
Evaluate whether a TAT-frataxin fusion protein can improve disease-relevant outcomes in Friedreich's ataxia models and support therapeutic development.
Preclinical mouse model studies of a TAT-frataxin fusion protein, including lifespan and cardiac function assessment.
The program supported an IND-enabling development goal to advance TAT-Frataxin into Phase I trials.
A 2012 study reported that TAT-Frataxin increased lifespan and cardiac function in a conditional Friedreich's ataxia mouse model.
