Positive preclinical data on IRAK4 inhibitor compounds presented at AACR 2015

Preclinical data demonstrating single agent and combination activity of two of TG Therapeutics’ IRAK4 inhibitor compounds has been presented at the American Association for Cancer Research (AACR) annual meeting.

IRAK4 is a serine/threonine protein kinase that is a key downstream signalling component of the interleukin-1 receptor and multiple toll-like receptors. Signalling through IRAK4 is important for both innate immunity and inflammation. Ligand Pharmaceuticals discovered novel compounds that selectively and potently inhibit IRAK4 activity. These inhibitors may have therapeutic potential in oncology and a number of autoimmune diseases. Ligand originally acquired the rights to the IRAK4 programme at a discovery stage via its 2008 acquisition of Pharmacopeia. In June 2014, Ligand and TG Therapeutics entered into an exclusive worldwide license for the development and commercialisation of IRAK4 inhibitors.

Both compounds are potent inhibitors of IRAK4

Highlights and conclusions of the latest study include:

• Both compounds are potent inhibitors with single-digit nanomolar potency
• Data demonstrated inhibitors inhibited cell proliferation and induced apoptosis as single agents in various B-cell lymphoma cell lines, potentially elucidating the mechanism of action of and clinical rationale for IRAK4 inhibition
• Compounds demonstrated marked synergy when combined with the novel targeted kinase inhibitors TGR-1202, TG Therapeutics’ proprietary PI3K delta inhibitor, and the BTK inhibitor, ibrutinib

“We entered into our IRAK4 partnership with TG Therapeutics last year knowing the promise of IRAK4 as a target in both oncology and inflammation, as well as the opportunities for treatment synergies between IRAK4 inhibitors and TG’s other best-in-class clinical-stage programs,” commented Matt Foehr, President and Chief Operating Officer of Ligand Pharmaceuticals. “These studies now further illustrate that potential, and we congratulate our partners at TG on their progress as they continue to quickly advance the IRAK4 program toward the clinic.”