Immunic (IMUX) Corporate presentation summary

Scientific rationale and discovery

• SIRT6 is a key regulator of transcription, genome stability, inflammation, metabolism, and epithelial homeostasis, highly expressed in the gut epithelium and central to barrier function in diseases like celiac disease and IBD.

• IMU-856 was discovered through high-throughput screening and optimized for potency, selectivity, metabolic stability, and oral bioavailability as a SIRT6 modulator.

• X-ray crystallography confirmed IMU-856's novel NAD+-dependent binding mode, forming a covalent ADP-ribose conjugate in the SIRT6 active site, supporting a mechanism-based inhibition concept.

Pharmacological and safety profile

• IMU-856 demonstrates high selectivity for SIRT6 over other sirtuins and HDACs, with potent inhibition across species and minimal off-target activity.

• Favorable ADME properties include high metabolic stability, strong permeability, minimal efflux, and low drug-drug interaction or genotoxicity risk.

• Pharmacokinetic studies show low-to-moderate clearance, sustained half-lives, and high oral bioavailability across multiple animal species, supporting once-daily dosing.

Preclinical and clinical efficacy

• In murine models of DSS-induced colitis, oral IMU-856 reduced disease severity, preserved colon length, and showed dose-dependent efficacy in both injury and recovery phases.

• Phase 1b clinical trial in celiac disease patients showed IMU-856 was well-tolerated, achieved dose-linear PK, and improved gut architecture, biomarkers, nutrient absorption, and symptoms without immune suppression.