Inflammation
Oral Nrf-2 activators and IL-17 inhibitors for the treatment of Inflammatory disorders

C4X Discovery has two drug discovery programmes targeting inflammatory disorders: oral Nrf-2 activators for the treatment of Chronic Obstructive Pulmonary disease (COPD) and oral/topical IL-17 inhibitors for the treatment of Psoriasis.

Oral NRF-2 Activators for COPD

COPD, an umbrella term for a group of progressive lung diseases including chronic bronchitis and emphysema (or smokers cough), is an area of substantial unmet medical need. It is a $41bn market which requires effective anti-inflammatory therapy to be added to currently prescribed bronchodilator therapy as disease severity progresses.

AstraZeneca currently market the oral PDE4 inhibitor Daliresp® (roflumilast) as an anti-inflammatory for COPD which has been shown to be effective on exacerbation rates but its degree of efficacy is disappointing, probably due to being dose limited due to its narrow therapeutic window. Nrf-2 activators have the potential to be more efficacious on exacerbation rate and improve quality of life in COPD with much a better tolerability profile.

Oral IL-17 Inhibitor, Psoriasis

IL-17 is implicated in multiple inflammatory and autoimmune diseases and is the subject of numerous clinical studies. The first significant market to be targeted by anti-IL-17 therapies is psoriasis, which is estimated to be worth $9bn per annum with Cosentyx® (Novartis) being approved in Jan 2015. Other significant IL-17 market opportunities include psoriatic arthritis and ankylosing spondylitis, together estimated to be worth a further $6bn per annum.

Current attempts to target IL-17 are largely based around monoclonal antibodies, which have the necessary size required to inhibit the IL-17/IL-17R engagement. Historically, identifying small molecules that specifically inhibit the IL-17 pathway has been extremely challenging, but our technology has enabled identification of small molecules that can selectively block the IL-17/IL-17R interaction. These are more conventional, drug-like compounds, for oral and/or topical use, which would offer benefits over injectable therapies such as IL-17 antibodies.