IGC Pharma announces in-vitro preclinical data for IGC-1C

IGC Pharma (IGC) announced in-vitro findings for IGC-1C, a low-molecular weight compound. The data are consistent with IGC-1C acting as a modulator of the tau protein’s liquid-liquid phase separation, an emerging and critical pathway implicated in the earliest stages of Alzheimer’s disease and related tauopathies.The LLPS pathway represents a potential paradigm shift in neurodegenerative research. When dysregulated, tau protein separates into liquid-like droplets, or condensates, which serve as the pathological “seeds” that mature into neurotoxic fibrillar aggregates. By targeting the initial LLPS stage, IGC-1C offers the potential to halt the disease progression before irreversible damage occurs, a therapeutic approach distinct from late-stage plaque or tangle inhibitors. Preclinical experimental findings suggest IGC-1C’s mechanism of action and demonstrate powerful efficacy markers: Inhibition & Dissolution Observed: IGC-1C was shown to inhibit the formation of zinc-mediated tau condensates and, critically, promote their dissolution. This dual-action ability suggests IGC-1C can both prevent and potentially reverse the initial pathological step. High Therapeutic Affinity: IGC-1C demonstrated a strong binding affinity to tau, exhibiting a dissociation constant with tau of (Kd) 3.95 +/- 0.32 muM. This low micromolar-range affinity is a positive signal in drug development, reinforcing IGC-1C’s efficacy in modulating the tau protein crucial for neurofibrillary tangle formation. Targeting Key Drivers: Microscopy and fluorescence assays demonstrated that IGC-1C reduces both the size and number of tau-zinc condensates and reduced their conversion into toxic amyloid fibrils. Cellular Compatibility: In neuroblastoma cell cultures, IGC-1C was well tolerated and permeable, confirming cellular compatibility. Designed for Efficacy: Its structure integrates three distinct chemical motifs to maximize efficacy: Zinc Chelation: Binds to zinc via a dipicolylamine group, a critical element often implicated in driving tau condensation. Interaction Disruption: Disrupts hydrophobic and interactions through a naphthalimide and aromatic ring. Multivalency Stabilization: Stabilizes multivalent interactions with its cyclic dipeptide core. This program explores an approach to Alzheimer’s disease and tauopathies by: Creating a Unique Pipeline Asset: IGC-1C represents a therapeutic concept, distinctly positioned from classical tau aggregation inhibitors or tau-targeted immunotherapies currently in development. Expanding Therapeutic Reach: Given that LLPS is also implicated in other conditions such as cancer and other neurodegenerative diseases, the platform behind IGC-1C holds potential to expand the company’s pipeline across multiple therapeutic areas. IGC Pharma is advancing the IGC-1C program and intends to move forward with additional validation studies in animal models, with the long-term goal of accelerating this candidate toward clinical trials.