This analysis reaffirms the emerging nature of IRAK4, NIK, Tyk2, ZAP-70 as intriguing targets.

FORBES: Immunokinase Drug Candidates: $12B in Value Creation and Counting

IRAK4 is a critical signaling protein downstream of IL1R, IL18R, IL33R, and a set of Toll-Like Receptors.

FORBES: Immunokinase Drug Candidates: $12B in Value Creation and Counting

Furthermore, a human mutation leading to IRAK4-deficient individuals has been well characterized.

FORBES: Immunokinase Drug Candidates: $12B in Value Creation and Counting

Furthermore, recent data suggests that IRAK4 inhibition synergizes with inhibition of other B-cell receptor signaling pathways, like BTK ( here).

FORBES: Immunokinase Drug Candidates: $12B in Value Creation and Counting

These data and others have caused several companies to initiate programs against IRAK4, but few have succeeded in drugging its shallow and unique pocket.

FORBES: Immunokinase Drug Candidates: $12B in Value Creation and Counting

Like most of these next generation immunokinase targets, IRAK4 is not new to the industry: it was cloned over a decade ago at Millenium and Tularik.

FORBES: Immunokinase Drug Candidates: $12B in Value Creation and Counting

Upon ligand engagement, these receptors in turn engage MyD88 which signals through IRAK4 to turn on a variety of pathways, including NF-kB and the secretion of pro-inflammatory cytokines.

FORBES: Immunokinase Drug Candidates: $12B in Value Creation and Counting