Promoting the development
Isofol Medical AB was founded in 2008 and was based on a research partnership between Professor Bengt Gustavsson and Merck & Cie, the world’s leading manufacturers of folate-based therapies. In 1978, the research team discovered that the folate-based treatment, leucovorin (LV), significantly increased the effect of the cytotoxic antimetabolite, fluorouracil (5-FU). This discovery subsequently led to the 5-FU/LV combination that now lies at the core of colorectal cancer treatment.
Professor Gustavsson formulated the hypothesis that the reason why only a few of his patients responded fully to the leucovorin treatment was due to their genetic ability to use enzymes to convert and metabolically activate the treatment. Merck & Cie was first successful in producing a chemically stable (diastereomeric) mixture [6RS]-MTHF (CoFactor®), which contained [6R]-MTHF, the active metabolite from leucovorin. However, this mixture also included the inactive [6S]-isomer. Although many judged it as almost impossible, Merck & Cie, at about 2005 after much research effort, made the remarkable achievement of synthesising the chemically highly stable hemisulfate salt of [6R]-MTHF. The active ingredient [6R]-MTHF of this salt constitutes arfolitixorin.
A developmental programme in which the active component of arfolitixorin could be tested clinically was designed in order to confirm the original hypothesis. The programme was expensive and Isofol Medical AB was founded in order to finance the development work and enable any potential commercialisation. The original founders were Professor Gustavsson and Yield Life Science (publ.) AB, but the company has since grown, and by 2016, over 100 new shareholders had joined in the hope of realising the vision of improving the efficacy and minimising the side effects of treating cancer with antimetabolites.
The Phase III AGENT Study
Isofol has now initiated the pivotal phase 3 AGENT study in order to demonstrate the efficacy of arfolitixorin in the treatment of patients with colorectal cancer.