Development and Validation of Efficacy Biomarkers for QTE Therapy in Friedreich's Ataxia

ABSTRACT Friedreich's ataxia (FRDA), the most common inherited ataxia, leads to severe neurodegeneration, cardiac dysfunction, and often results in death by age 35. Despite the availability of omaveloxolone, the first FDA- approved treatment, its effectiveness is limited, and it is associated with several side effects. AnekaBio, in partnership with the University of Florida, is developing an innovative multi-targeted therapy called QTE therapy that addresses the complex molecular mechanisms underlying FRDA. Our preclinical studies demonstrate that QTE therapy significantly outperforms omaveloxolone, enhancing critical FRDA target proteins, improving cardiac function, reducing iron overload, and dramatically increasing survival rates in FRDAkd mice. A therapeutic alternative that is effective, safe, and which can outperform the existing treatment could significantly shift the treatment paradigm. The proposed Phase I STTR project focuses on identifying and validating efficacy biomarkers—specific biological indicators in blood and muscle—that reliably measure the effectiveness of QTE therapy. Utilizing advanced proteomic and transcriptomic technologies, we will conduct in-depth analyses in FRDAkd mouse model to discover biomarkers that can be used to monitor QTE's therapeutic impact. These biomarkers are essential for future clinical trials, as they will provide a reliable means of assessing treatment efficacy and safety in humans. During the Phase II STTR, we will validate these biomarkers across different species, including primates, and initiate human testing in collaboration with industry partners. This phase will also focus on refining QTE therapy for clinical application, guiding us toward IND submission and the initiation of clinical trials. Our ultimate goal is to transition QTE therapy from preclinical studies to clinical trials, establishing it as a safer and more effective treatment option for FRDA. Through the identification of robust efficacy biomarkers and collaboration with experts in drug development, we aim to transform the treatment landscape for FRDA, offering new hope to patients affected by this devastating disorder.