Our Toledo program
‘Toledo’ is a code name for a novel target class discovered by us. Molecules inhibiting this target family effectuate a dual mode of action on inflammation by stimulating anti-inflammatory cytokines and inhibiting pro-inflammatory cytokines. We have observed unprecedented activity in various inflammatory preclinical models with compounds targeting the class.
Below are the results for the first Toledo compound, GLPG3312, in three preclinical models, each demonstrating a different mechanism of IBD. These results were first reported at our R&D Update in October 2018. Prior to discovering Toledo, no single compound showed activity in all three of these preclinical models in our research:
We are now executing on a broad program to discover and develop multiple series of compounds acting on the Toledo class of targets, aimed at activity across numerous conditions, with a key focus on inflammation. We initiated our first Phase 1 trial with GLPG3312 in early 2019 to evaluate the efficacy, safety, tolerability, and pharmacokinetics and pharmacodynamics of GLPG3312 in up to 76 adult healthy male volunteers.
In the second half of 2019, we aim to report topline results for GLPG3312 as well as initiate a Phase 1 trial with the second Toledo compound, GLPG3970.
The development strategy for Toledo is to advance multiple Toledo candidates across different selectivity profiles, and to test these in a broad panel of in vivo disease models targeting a number of indications.
The graph below shows the current status of our Toledo program. The different disease areas that we are currently investigating are IBD, RA, psoriasis (Pso), systemic lupus erythematosus (SLE), OA, osteoporosis (OP), and fibrosis (Fib). The first generation Toledo, GLPG3312, has delivered promising preclinical results in IBD, RA, Pso, PsA and Fib, and we expect to generate preclinical data in SLE, OA and OP in 2019. The second generation, GLPG3970, has shown results in IBD, RA, Pso, SLE and fibrosis, with preclinical read-outs for PsA, SLE, OA and OP planned for 2019. The third, fourth and fifth generation are currently in the lead optimization (LO) stage.
As a next step, we plan on setting up multiple parallel-running proof-of-concept (PoC) trials in patients to investigate swiftly and efficiently the potential across the different Toledo compounds. A PoC trial for the 1st generation Toledo compound, GLPG3312, is planned for late 2019, pending satisfactory results of the Phase 1 trial currently ongoing.
Our Toledo development strategy
- Develop multiple candidates across different profiles
- Test in broad panel of in vivo disease models
- Plan multiple PoC’s in patients in parallel to maximize potential