IRAK4 Inhibitor Demonstrates Synergistic Effects with Kinase Inhibitors

Combination approach evaluated with inhibitors of Btk (ibrutinib), PI3Kdelta (GS-1101), and Syk (P505-15)

Data presented at the 55th American Society of Hematology Annual Meeting

CAMBRIDGE, Mass. – December 9, 2013 – Nimbus Discovery LLC, a biotechnology company discovering novel medicines against exciting but previously inaccessible drug targets, presented preclinical data today that show that the novel Nimbus IRAK4 inhibitor, ND-2158, when combined with the Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib, the PI3Kdelta inhibitor GS-1101 or the Syk inhibitor P505-15, works synergistically to induce selective cell death in hematological tumors with L265P activating MyD88 mutation. This genetically-defined patient population can be identified in the clinic prior to treatment, increasing the potential for a positive response.

The synergism of ND-2158 with these three immunokinase inhibitors was presented in ABC-DLBCL tumor cells at the 55th American Society of Hematology Annual Meeting being held at the Ernest N. Morial Convention Center, New Orleans, La. Nimbus previously demonstrated this synergistic benefit with ibrutinib. This current study extends the potential drug combinations in Nimbus’ ongoing pursuit of more efficacious, less toxic, treatments for lymphoid malignancies that broaden the magnitude and durability of response.

Abstract #3833
Title: Synergistic Blockade of Activated B Cell-Like DLBCL Proliferation with a Selective Inhibitor of IRAK4 in Combination with Inhibition of the B-Cell Receptor Signaling Network
Date: Monday, December 9, 2013
Presentation Time: 6:00 PM – 8:00 PM
Location: Ernest N. Morial Convention Center, Hall E

“Nimbus is working in one of the most exciting areas of oncology drug development. There is significant potential for drugs that are targeted at specific cancer-causing mutations and can be used in synergistic combinations.” said Rosana Kapeller, M.D., Ph.D., Chief Scientific Officer of Nimbus. “We are the first drug developer to identify and optimize highly selective IRAK4 inhibitors with robust potency, and we now have encouraging synergistic data that shows the opportunity for combination with other emerging targeted therapeutics. We currently have multiple, novel IRAK4 inhibitors under evaluation and look forward to moving one of the candidates into the first phase of clinical trials in the near future.”

About Nimbus

Nimbus Discovery, a biotechnology company, harnesses cutting-edge computational technologies to uncover breakthroughs in small molecule pharmacology. We focus on medically important and highly sought-after disease targets that have proven inaccessible to traditional industry approaches. Our robust pre-clinical pipeline includes novel agents for the treatment of cancer, metabolic disease and inflammation. Nimbus is organized as a constellation of small, nimble teams of experienced drug-hunters deployed across program-focused subsidiary companies. Each team is freed from conventional barriers to scientific success, chartered to create solutions, and geared for program asset deals with leading pharmaceutical companies. Founded in 2009, Nimbus partnered with Schrödinger to invent and apply a physics-based approach that establishes a new standard for rational drug design. Nimbus is backed by world-class life science investors, including Atlas Venture, SR One, Lilly Ventures and Bill Gates. The company has been named by FierceBiotech as one of 2013&tsquo;s Fierce 15, designating it as one of the most promising private biotechnology companies in the industry. For more information please visit