Rabeximod (formerly Rob 803) for RA

A screening program has been carried out aimed at optimizing the lead compound B-220 by chemical modifications for determining structure/activity relationship in order to obtain more efficient compounds for treatment of RA. The mAb/LPS model was used in the screening for the structure related efficacy, and a selected number of active compounds were screened for other structure related properties (lead optimization) e.g. chemical, kinetic and toxicity.

The mAb-LPS Model
The mAb-LPS model in mice is ideal for screening anti-inflammatory therapeutic agents. The model is faster compared to the CIA model and consequently requires a smaller amount of test substance. This model is also ideal for studying inflammatory mediators such as cytokines, chemokines and metalloproteinases and other factors such as the role of bacterial flora and their byproducts in triggering and exacerbating arthritis. Arthritis develops in mice within 24 - 48 hours after an intravenous injection of arthritogenic mAbs alone or after an injection of LPS following a subarthritogenic dose of mAbs. The results reflect an evaluation of the thickness of the test animals' paw joints expressed in millimeters.

Screening Results
In the screening for the structure related efficacy, a number of carefully selected analogues were tested in the mAb/LPS model. In this initial screening phase, evaluation of anti-arthritic activity yielded a number of candidates with greater effect than B-220. After the lead optimization phase was completed Rabeximod was selected as candidate drug.

Future Development
OxyPharma intends to bring Rabeximod to proof of concept in man, i.e. complete phase IIa studies to evaluate efficacy in patients. A phase II study in RA patients is ongoing..

Pre-Clinical Safety Program
Work related to the investigation of the safety profile up to phase II of Rabeximod is completed and reported.