InFlectis BioScience and Aix Marseille Université Expand IFB-088 Efficacy to Axonal Charcot-Marie-Tooth Disease

InFlectis BioScience and Aix Marseille Université have achieved a significant breakthrough with IFB-088, demonstrating efficacy in animal models of axonal Charcot-Marie-Tooth disease type 2A (CMT-2A), the most prevalent axonal form of this neurodegenerative disorder. This expansion beyond previous proof-of-concept in demyelinating CMT subtypes (CMT1A and CMT1B) marks a crucial advancement for addressing multiple CMT variants through modulation of the Integrated Stress Response (ISR) and mitochondrial dysfunction pathways.

Researchers from Aix Marseille Université, collaborating with InFlectis, showed that IFB-088 reverses pathological cellular phenotypes in human CMT2A induced pluripotent stem cell-derived motor neurons carrying MFN2Arg94Gln and MFN2Arg707Trp mutations. Importantly, the compound prevented locomotor impairments in mouse models of axonal CMT2A with MFN2Arg94Gln mutations, validating its therapeutic potential across different genetic variants of the disease. These findings position IFB-088 as a promising candidate for CMT subtypes lacking approved treatments, including CMT1B, CMT1E, and CMT2A.

The research received support through NeuroSchool, Aix Marseille Université's Graduate School in Neuroscience, which funded a one-year postdoctoral fellowship as part of a joint innovation program. This initiative, backed by the France 2030 national investment plan and the Amidex university foundation, promotes industry-academic collaboration and supports early-career neuroscientists' employability. Dr. Zeinab Hamze was selected for this position, contributing to the translational development of IFB-088 through the MMG/U1251 Inserm unit at the Faculty of Medical and Paramedical Science in Marseille.

Pierre Miniou, Chief Operating Officer of InFlectis, emphasized the importance of these findings as IFB-088 prepares for Phase 2 clinical development for CMT. The compelling preclinical data, combined with previously published results for CMT1A and CMT1B, aims to attract pharmaceutical partners or investors to finance upcoming clinical trials in Europe and the United States. This partnership approach is essential in the current economic climate to ensure promising therapeutic candidates reach patients with high unmet medical needs.

IFB-088 represents a first-in-class, multi-functional, brain-penetrant, orally-administered small molecule that selectively inhibits eIF2α dephosphorylation, amplifying the integrated stress response while antagonizing NMDA receptors containing the GluN2B subunit. This dual mechanism addresses key pathological features of neurodegeneration, including endoplasmic reticulum stress, glutamate excitotoxicity, mitochondrial dysfunction, and oxidative stress, offering potential disease-modifying effects for intractable conditions like ALS and CMT.