Development of a novel and unique disease-specific treatment for ANCA vasculitis

Purpose and goal:

TOL3 is a drug candidate for ANCA vasculitis, an autoimmune disease lacking safe and effective therapies. The goal is to develop an improved TOL3 through an innovative approach consisting of identifying the specific epitopes that ANCA vasculitis patients present and react to and designing a novel TOL3 that contains multiple disease-specific epitopes comprising the peptides identified.

This version of TOL3 is considered to have potential to induce immunological tolerance providing long-lasting or curative effect across an immunologically heterogenous patient population. Expected results and effects:

A successful project may result in two highly innovative outcomes: i) a new, improved TOL3, which will be the first disease-specific treatment with potential to provide long-term remission or even cure of ANCA vasculitis, and ii) a completely new technology platform for design of novel drugs for autoimmune diseases.

Approach and implementation:

MHC-II MPO epitopes that ANCA vasculitis patients present and respond to will be identified in a Swedish cohort of patients by an advanced LC-MS approach. These will be used to design and recombinantly produce an improved TOL3 containing multiple disease-specific epitopes, potentially inducing tolerance in a majority of patients with different genetic backgrounds.

The immunogenicity risk will be assessed by in silico screening, and the new version of TOL3 will be evaluated in an animal model of ANCA vasculitis.