Three novel MAbs will offer therapeutic advantages in autoimmune and oncology indications

John Hodkinson. Biotest UK Ltd, 28 Monkspath Business Park, Highlands Rd, Shirley. B90 4NZ, UK.

Three monoclonal antibodies in current development demonstrate the utility that biologics now offer and are indicative of the exciting progress currently apace in this field. All three of these Mabs offer a distinct mechanism of action and will target severe forms of rheumatoid arthritis, psoriasis, myeloma, systemic lupus erythematosus as well as potential in other oncology and autoimmune indications.

BT061 targets T regulatory cells causing activation and subsequent immunomodulation. This MAb selectively binds to CD4 inducing Treg signalling. BT061 is currently in phase II clinical trials and up to this stage trials have revealed that BT061 suppresses production of pro-inflammatory cytokines and increases the production of anti-inflammatory cytokines. A randomised, placebo controlled, multicentre trial confirmed the clinical activity of BT061 in a patient cohort suffering from severe rheumatoid arthritis who were previously refractory to at least two DMARDs. No serious safety concerns were apparent in the patient group investigated. This MAb is likely to offer utility in a range of autoimmune conditions.

BT062 is an immunoconjugate consisting of a potent cytotoxic and a targeting Mab. This MAb targets CD138, which is highly expressed on myeloma cells and the cytotoxic is the potent maytansinoid, DM4. Upon binding to CD138 on the surface of a myeloma cell the immunoconjugate is internalised. Upon internalisation DM4 is released and becomes potently cytotoxic. When conjugated BT062 does not exhibit cytotoxicity.

Preclinical trials have demonstrated the significant specificity and anti-myeloma activity of BT062 in vitro and in experimental animals. Phase I trials have indicated significant activity in patients suffering from refractory myeloma while demonstrating a favourable safety profile. Phase I trials have been undertaken with BT062 in isolation and in combination with lenalidomide or bortezomib. This is a promising therapy in an area of unmet medical need.

BT063 is a Mab which binds to a messenger molecule that is key to the development of systemic lupus erythematosus symptoms. Pre-clinical studies have been completed and formed the basis for phase I studies which indicated that a significant improvement in symptoms was experienced by patients over the course of six months, and a conspicuous symptomatic improvement experienced within three weeks.