MIF As A Therapeutic Target

Cortical’s focus is on the development of small molecule inhibitors of the pro-inflammatory molecule MIF (macrophage migration inhibitory factor).

MIF is a unique cytokine-like molecule which has been validated as a therapeutic target in a wide range of inflammatory diseases and cancers. Cortical has taken a structure-based approach, aided by novel proprietary Xray crystallography and assays, to develop leads in several structural classes.

Cortical’s program is aimed to yield first-in-class oral cytokine inhibitor drugs for use in diseases such as rheumatoid arthritis, lupus, colitis, asthma, psoriasis and MS.

MIF is well established as a therapeutic target.

Evidence in support of the value of targeting MIF therapeutically includes

• Demonstration of MIF overexpression in serum or tissue from human disease
• Studies using MIF-deficient mice demonstrating reduced severity of multiple models of human inflammatory diseases
• Studies using anti-MIF antibodies demonstrating preventive of therapeutic effects in vivo in models of human inflammatory diseases
• Association of MIF gene polymorphisms with disease predisposition or severity

Inflammatory diseases in which MIF has been validated as a therapeutic target include

• Rheumatoid arthritis
• Atherosclerosis
• Systemic lupus erythematosus (SLE)
• Multiple sclerosis
• Colitis
• Asthma

MIF also has a unique relationship with glucocorticoids, strongly supporting the hypothesis that MIF inhibitory therapies would exert a broad spectrum ‘steroid sparing’ effect in disease.

MIF has also been validated as a therapeutic target in numerous cancers.