Methotrexate (MTX), small molecular drug, is the current gold-standard for treatment of rheumatoid arthritis, it is suffering from low efficacy, frequent cases of non-responsiveness and a variety of adverse events. Biologics often exhibit reasonable efficacy, but high costs, limited administration routes (injection), immunogenicity and potential tumor formation are points of concern in using them. Also, many patients are non-responsive to biologics. Therefore, the key unmet needs for rheumatoid arthritis therapy are achievement of adequate therapeutic efficacy for RA patients who are non-responsive to DMARDs and Biologics, management of adverse events to a lower level, and improvement in convenience via oral administration.
Patient with rheumatoid arthritis who are non-responsive to MTX and biologics
SKI-O-703 is currently in phase IIa clinical trial in US, EU, and Korea.
First-in-class SYK inhibitor for rheumatoid arthritis
Fostamatinib (R788, Rigel Pharmaceuticals, Inc) was discontinued after Phase III clinical trials due to low efficacy and severe adverse events which were caused by low selectivity. P505-15 (PRT062607, Portola pharmaceuticals Inc) exhibited high selectivity, but revealed a high level of toxicity and low bioavailability.
SKI-O-703 demonstrated a superior selectivity to SYK, an improved bioavailability (BA 60%) and a low level of toxicity (ED50 1.4 mg/kg in animal with safety margin of over 80 folds)