Curis Expands Cancer Drug Pipeline With Small Molecule PD-L1/ VISTA Immune Checkpoint Antagonist and IRAK4 Kinase Inhibitors

Curis, Inc. CRIS, a biotechnology company focused on the development and commercialization of innovative drug candidates for the treatment of human cancers, today announced the expansion of its pipeline with the addition of two programs, the first of which is an oral, small molecule immune checkpoint antagonist targeting programmed death ligand-1 (PD-L1) and V-domain Ig suppressor of T cell activation (VISTA), and the second is focused on inhibitors of Interleukin-1 receptor-associated kinase 4 (IRAK4). The additions to the pipeline come through the Company's exercise of its options under a collaboration agreement with Aurigene announced earlier this year. In the area of immuno-oncology, Curis exercised its option to exclusively license a first-in-class oral, small molecule antagonist designated as CA-170 that targets PD-L1 and VISTA, which function as negative checkpoint regulators of immune activation. CA-170 was selected from the broad PD-L1 antagonist program that the companies have been engaged in since the collaboration was established in January 2015. Curis also exercised its option to exclusively license a program of orally available small molecule inhibitors of IRAK4 kinase. IRAK4 is a serine/ threonine kinase involved in the regulation of innate immune responses and also plays an important role in certain hematologic cancers. IRAK4 is inappropriately activated, and drives pro-survival and cytokine mediated pathways in cancers such as activated B cell-diffuse large B cell lymphoma (ABC-DLBCL), an aggressive form of lymphoma with poor prognosis. Targeting IRAK4 has potential therapeutic implications in both cancer and cytokine-driven inflammatory and autoimmune diseases. The exercise of options for the PD-L1/VISTA and IRAK4 programs resulted in an aggregate one-time payment of $6 million by Curis to Aurigene in exchange for an exclusive, royalty-bearing license to develop, manufacture and commercialize compounds from the programs, including the development candidate, CA-170 and products containing such compounds, anywhere in the world with the exception of India and Russia, where Aurigene will hold an exclusive, royalty-free, fully paid license to commercialize such compounds. Additionally, Curis has selected a second preclinical program within the immuno-oncology collaboration with Aurigene that is focused on evaluating small molecule antagonists with dual PD-L1 and T-cell immunoglobulin and mucin domain containing protein-3 (TIM-3) targeting properties. TIM-3 is an inhibitory checkpoint molecule that plays an important role in immune suppression and is co-expressed with programmed cell death-1 (PD-1) receptors on highly exhausted cytotoxic T cells in tumor tissues as well as expressed on certain regulatory T cells. Curis expects that Aurigene scientists will present data from the PD-L1/VISTA immuno-oncology and the IRAK4 programs at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, which will take place Nov. 5-9 in Boston. "We are pleased with the progress in our collaboration with Aurigene and the small molecule candidates emerging from the PD-L1 antagonist program," said Ali Fattaey, Ph.D., Curis' President and CEO. "Based on its preclinical profile in multiple in vitro and in vivo activity and safety models, we have selected CA-170 as our clinical candidate. By targeting both PD-L1 and VISTA with CA-170, we potentially have the opportunity to address exhausted T cells as well as other inhibitory immune cells such as myeloid derived suppressor cells or MDSCs, in the tumor microenvironment with one drug candidate. We believe that this property of targeting two unique checkpoint regulators provides CA-170 with the potential to not only address, but potentially expand beyond tumors with PD-L1 overexpression or those that may have relapsed after PD-1/ PD-L1 targeting therapies. Development of CA-170 is a priority for Curis, and we and Aurigene are working diligently to complete the required IND-enabling studies in the coming months. We expect to file an IND and initiate Phase 1 clinical testing of CA-170 during the first half of 2016. We also expect to file an IND for development of the IRAK4 inhibitor within the first half of 2016." Dr. Fattaey continued, "We are also encouraged with the progress in our second immuno-oncology program that is generating small molecules targeting PD-L1 and TIM3, which may provide for additional opportunities to relieve the inhibitory effects of multiple immune checkpoints on exhausted T cells using our small molecule antagonist approach." The development of the Company's immuno-oncology programs will be led by David Tuck, M.D., the Company's Vice President, Clinical and Translational Sciences. Dr. Tuck joined Curis from EMD Serono in May 2015, where he served as Senior Medical Director in the Oncology Translational Innovation program. Prior to that, Dr. Tuck was employed by Bristol-Myers Squibb Global Oncology Research in the role of Translational Physician for ipilimumab, with a primary focus on external development of immune checkpoint inhibitors in solid tumors and hematological malignancies. Dr. Tuck was previously an Associate Professor at Yale University and Associate Director of the Yale Cancer Center. Dr. Tuck earned his Medical Degree at the University of Vermont School of Medicine and is board certified in internal medicine, medical oncology and hematology. Dr. Tuck said, "I am excited to lead the development of our immuno-oncology drug candidates and believe that oral, small molecule checkpoint inhibitors may provide a favorable drug profile to better address immune-related adverse events and the potential for combination with other therapies in a convenient manner for patients."