Multiple sclerosis (MS) represents a substantial worldwide economic burden and urgent unmet clinical need lacking effective curative therapeutics. Current clinical management of MS distinguishes between relapse-remitting MS (RRMS) and primary progressive MS (PPMS) and involves expensive and ineffective treatments with mild to extremely severe side-effects with an inverse correlation between efficacy and safety. The global market for MS therapies is predicted to be worth $23 billion USD by 2022 and is undergoing maturation, resulting in increased pricing pressure on existing and novel therapeutics.
The DIDO-MS project was granted in order to assess the commercial viability of a novel IDO1 drug, VIS-110, as a therapy for MS. VIS-110, discovered along the Advanced ERC DIDO project studies, targets a novel pathway (immunoregulatory signaling via indoleamine 2,3-dioxygenase or IDO1) in dendritic cells (DCs; the most important immune cells in the organism capable of activating an immune response or of inducing a state of immune tolerance), has a cheap manufacturing as being a small compound, has the potential of being administered orally, promotes immune tolerance over the long-term rather than immunosuppression (cause of severe adverse effects of currently used drugs), and protects mice from an acute experimental model of MS.
In DIDO-MS, we aimed at validating the therapeutic potential and safety of the VIS-110 compound and its newly synthesized analogues with better pharmacokinetic and pharmacodynamics profile in a mouse model of RRMS and defining its commercial and financial feasibility as well as developing the optimal business strategy for calculating the feasibility and market value. Regarding the first aim, we found that VIS-110 and two of the three synthesized analogues show a good pharmacodynamics in vitro and pharmacokinetic profile in vitro. In vivo, only one of the two novel analogues (i.e. VIS-129) with good pharmacologic properties exerted protective effects in an experimental model of acute MS. When administered in the RRMS model, VIS-129 but VIS-110 exerted significant yet mild therapeutic effects in terms of reduction of the intensity and number of relapses. No significant adverse effects could be detected for VIS-129. Regarding the second aim, a pitch deck with an extensive market and competitor analysis was prepared. This pitch deck outlined the possible target markets (RRMS or PPMS) and the pitfalls of the current state-of-the-art in terms of MS therapy. The analysis also identified the likely best routes to market as out-licensing to an industrial and/or pharmaceutical partner or creation of a spin-off company provided a clinical-grade compound can be developed in the future. Thus, despite the setbacks in technical validation of in vivo performance, the concept remains commercially feasible, meaning future technical development activities could result in commercialization of a transformative, entirely novel compound for the treatment of MS and other autoimmune diseases. Moreover, we filed a patent for VIS-110 and its analogues that is currently at the stage of PCT extension and presented results of DIDO-MS at European leading showcasing events of life science technologies such as Biovaria and Techshare Day, wherein contacts have been established with some investors.
In summary, the data obtained in this project demonstrate that activating the immunoregulatory IDO1 signaling pathway and thus promoting therapeutic effects without significant adverse drug reactions in autoimmune diseases such as MS is a valid therapeutic strategy from a technical perspective. Market mapping and competitor analyses consolidated the lucrative nature of such a development and outlined clear routes for commercialization and critical barriers to be overcome to ensure this in the context of regulatory pathways and emerging competitors. However, further studies will be needed to identify and develop a strong drug candidate with the potential to be brought to market.
