Inflammatory bowel diseases (IBD) involve chronic inflammation of all or part of the digestive tract. Symptoms may include abdominal pain, severe diarrhea and malnutrition. IBD primarily includes ulcerative colitis (UC) and Crohn's disease (CD). In the West, the prevalence has increased in the past 50 years to 120-200/100,000 persons for UC and 50-200/100,000 persons for CD. Incidence rates for both UC and CD are highest among individuals who are 20-30 years old. Thus, IBD affects individuals in the most healthy and productive years of life, resulting in long-term cost to the patient, health-care syste and society. Current drugs for treating UC and CD have not shown consistent effects, especially for chronic maintenance therapy. New agents are needed to treat UC and CD and prevent relapse. Vitamin D receptor (VDR), once activated by its endogenous hormone calcitriol (1,25(OH) 2D3), modulates signaling pathways in the inflammation pathway. Pre-clinical and clinical studies have also shown that the vitamin D-VDR axis plays an important role in regulating many inflammatory factors involved in IBD. Despite encouraging data on VDRM's benefits for the cardiovascular, CNS, immune, and renal systems, currently VDRMs are mainly indicated for managing secondary hyperparathyroidism in chronic kidney disease, and to a lesser degree used to treat osteoporosis and psoriasis. One of the reasons for this is due to the narrow therapeutic window of current VDRMs in the 1-4-fold range as determined by comparing doses required for efficacy vs. the hypercalcemic toxicity. Consequently, current on-market VDRMs require frequent dose titration and serum calcium monitoring, which causes considerable challenges in clinical management. An ideal VDRM should be with little or no hypercalcemic toxicity in the efficacious dose range. Vidasym has taken a unique drug discovery/development approach to discover novel VDRMs that are highly differentiated from existing VDRMs. Vidasym's VS-110 has a therapeutic window of >50-fold with no detectable hypercalcemic toxicity in the efficacious dose range. We hypothesize that VS-110 has potent therapeutic efficacy for the treatment of IBD.
Specific Aim 1 : To assess the therapeutic efficacy of VS-110 in blocking the development of colitis using experimental colitis models.
Specific Aim 2 : To elucidate the anti-colitic mechanism underlying the therapeutic effects of VS-110. Once this phase I study is completed, the data will allow the advancement of VS-110 into Phase II IND-enabling studies including VS-110 synthesis scale-up, process development and pharmacokinetics, metabolism, safety and toxicology. The completion of Phase II studies will allow VS-110 to enter human clinical trials. Vidasym plans to develop VS-110 into an oral, once daily capsule (0.2 - 5 ?g/day) for treating IBD. Currently drugs for anti-inflammatory diseases in the GI tract such as mesalamine (Asacol, Lialda, Pentasa) and budesonide achieved US$2.9 billion in annual worldwide sales in 2011. Assuming VS- 110 has a 20% penetration into the IBD market, the estimated annual sales will be ~US$0.58 billion.
Vidasym's phase I STTR study will investigate the feasibility of using VS-110, Vidasym's novel vitamin D receptor modulator, to treat inflammatory bowel diseases (IBD). Up to 600,000 individuals in the US have IBD, and incidence rates are highest among individuals who are 20-30 years old. Thus, IBD affects individuals in the most healthy and productive years of life, resulting in long-term cost to the patient, health-care system and society. Current drugs for IBD have not shown consistent effects. There is an urgent medical need for the development of an effective and novel resuscitation approach for the treatment of IBD. VS-110, once developed to treat IBD, will help patients regain control of their health and lives. Even a modest 20% reduction in the number of patients with IBD would bring a minimum of $1+ billion annual savings in medical costs in the US.