Immunometabolism is a rapidly growing field which has emerged from recent findings that cellular metabolism has a direct role in influencing immune function and disease, and that switches between alternative metabolic pathways allow immune cells to adapt to their environment by changing phenotype, responsiveness and longevity.
Istesso’s pipeline consists of drugs that reprogramme metabolism in target immune cells, thereby offering novel treatments for autoimmune conditions such as rheumatoid arthritis, multiple sclerosis and ulcerative colitis, as well as cancer.
Rheumatoid Arthritis (RA) is a chronic, progressive and disabling auto-immune disease affecting 165 million people worldwide, or one per cent of the global population. It is a painful condition that, unchecked, can cause severe disability. Metabolic changes have been detected in T-cells from patients with RA compared with healthy volunteers and modulating metabolic pathways to change immune responses has been suggested as an approach to treat Rheumatoid Arthritis without immunosuppression.
MBS2320 is a first-in-class metabolic reprogramming agent for the treatment of RA and is distinguished from existing RA treatments by its dual mode-of-action which not only reduces inflammation, thereby preventing the progression of disease, but may also promote bone and joint remodelling. MBS2320 is the subject of a £176m Option and Licensing Agreement with Janssen Biotech Inc., part of Johnson & Johnson.
Multiple Sclerosis (MS) is a chronic, autoimmune, inflammatory disease of the central nervous system affecting approximately 2.3 million people worldwide. It causes progressive neurological deterioration over time, and 50% of patients will require help walking within 15 years of onset of the disease.
IST3 is a novel, once-daily oral treatment for MS which acts against a novel target linking glutamate signalling to glycolysis. Early data shows that inhibiting this target inhibits signs and symptoms of the condition, protects against demyelination and, importantly, offers the potential to rescue established demyelination.
Psoriasis is a chronic, inflammatory disease of the skin and joints which affects 1-3% of the general population. It significantly impacts quality of life and is associated with multiple co-morbidities, such as cardiovascular disease and malignancy, as well as having extensive emotional and psychosocial effects on patients. Ulcerative colitis is a chronic inflammatory condition resulting in ulceration and bleeding of the colon and rectum.
IST4 modulates the activity of a key target critical to mediating immune-cell activation and metabolic flux and has been shown to have strong anti-inflammatory effects in models of ulcerative colitis, psoriasis, rheumatoid arthritis and cancer.