Preclinical studies have shown that systemically administered BiP has potent anti-inflammatory and immunomodulatory properties

IRL201805 (‘1805)

‘1805 has demonstrated long duration of activity and a good tolerability profile in a phase I/2a study in patients with rheumatoid arthritis who have failed previous therapies.

‘1805 can be administered via intravenous or sub-cutaneous injection.

Early development

The chaperonin Binding immunoglobulin Protein (BiP) is responsible for the correct manufacture and transport of proteins in cells. BiP is found in cells and synovial fluid in samples taken from RA, ankylosing spondylitis and osteoarthritis patients suggesting association with joint disease and has shown a reduction in joint destruction and bone erosion in animal models. Preclinical studies have shown that systemically administered BiP has potent anti-inflammatory and immunomodulatory properties.

‘1805 is a modified analogue of the BiP protein initially discovered at King’s College, London with functional benefits over the human protein and developed by Immune Regulation through preclinical and phase I/IIa clinical trials.

Preclinical and clinical studies

Preclinical in vivo studies have shown that a single dose of ‘1805 can prevent the development of collagen-induced arthritis (a model for human rheumatoid arthritis) in mice and delay the onset and reduce the severity of arthritis in rats6 and mice.7 Additionally, adoptive cell transfer experiments have shown that spleen and lymph node cells from ‘1805-treated mice are able to prevent arthritis induction in untreated mice, supporting the hypothesis that ‘1805 induces regulatory immune cells.7

In arthritis mouse models, ‘1805 significantly downregulates inflammatory markers and bone deterioration.6-8 The anti-inflammatory cytokines IL-10, IL-4 and IL-5 have been shown to be increased for up to 7-8 weeks following a single dose of ‘1805. In both human and animal models, ‘1805 has demonstrated a reduction in not only the number of osteoclasts, but also their ability to resorb bone.[data on file]

A Phase I/IIa study at Guy’s and St. Thomas’ Hospitals, London in patients with active rheumatoid arthritis who had failed one or more standard therapies showed a good tolerability profile for ‘1805, with no drug-related toxicities.9 Clinical remission of disease was achieved in some patients, correlating to early reductions in C-Reactive Protein, a well-known biomarker for rheumatoid arthritis. Activity of ‘1805 appeared to be durable, with effects on biomarkers lasting for up to 12 weeks following a single dose. This study may represent early proof of concept for ‘1805 as a safe and effective immunomodulating treatment for rheumatoid arthritis.