A new class of modality selective antagonistic TRPV1 antibodies for pain treatment

Important results from the project

The aim of this project is to address the clinical need for treatment of chronic pain by targeting the TRPV1-channel with a selective antagonistic monoclonal antibody. Earlier small molecules targeting TRPV1 have failed due to heat related side effects resulting from blocking this ion channels capability to respond to heat. We set out to develop monoclonal antibodies that inhibit capsaicin activation of TRPV1 while avoiding inhibiting heat activation and with Oblique Therapeutics antibody discovery platform, we developed mAbs with this modality selective activity profile.

Expected long term effects

Unrelieved chronic pain is one of the biggest disease related economic burdens for society with most of the cost resulting from loss of productivity. The antibodies targeting TRPV1 that have been developed during this project, have great future potential of addressing chronic pain. While having a modality selective profile, they can inhibit TRPV1 potentially without causing heat related side effects. These antibodies will, in the nearest future, be further advanced through preclinical development with the aim of reaching the clinic and a new pain therapy.

Approach and implementation

We had previously identified accessible epitopes for high affinity antibodies on the extracellular region of TRPV1 that if targeted by an antibody, could yield modality selective inhibition. We developed mAbs targeting these epitopes using the hybridoma technology. Hybridomas were selected based on TRPV1 binding using FACS and the activity profile of the resulting antibodies were evaluated using a combination of electrophysiology and calcium imaging. Using this combination of FACS and functional evaluation we identified several antibodies with a modality selective profile.