Drug candidates developed within our CUE-100 framework selectively stimulate the interleukin 2 (IL-2) receptor, a potent activator of the pathway critical to the growth, expansion and survival of T cells. We have engineered the framework to activate specific T cell populations through peptide-MHC complex (pMHC) targeting of T cell receptors (TCRs) and selective deployment of the IL-2 signal. The IL-2 has been attenuated to enable our Immuno-STATs to preferentially activate tumor specific T cells without systemically activating other T cell populations, thereby potentially mitigating the dose-limiting toxicities associated with current IL-2-based therapies. Data demonstrating the selective stimulation of IL-2 was presented at the 2019 Keystone Symposia Conference.
Our lead drug from the CUE-100 framework, CUE-101, contains IL-2 and a pMHC composed of HLA-A*02:01 complexed with a dominant peptide derived from the human papilloma virus E7 protein (HPV-E7). It is a fusion protein biologic designed to target and activate antigen-specific T cells to fight HPV-driven cancers.
In preclinical studies, CUE-101 has demonstrated selective binding and preferential activation and expansion of antigen-specific T cells, dose-dependent effector cytokine production and inhibition of tumor growth both as a monotherapy and in combination with a PD-1 inhibitor. These findings were previously presented at the Society for Immunotherapy of Cancer’s (SITC) 33rd Annual Meeting.
In September 2019, we commenced our first-in-human, dose-escalation and expansion Phase 1 clinical trial of CUE-101 in patients with HPV-positive relapsed or refractory head and neck squamous cell carcinoma (NCT03978689). Cue Biopharma has engaged a network of nationally recognized clinical investigators and 13 Phase 1 sites are actively recruiting patients.
HPV cancers account for more than 20,000 deaths each year in the US and Europe. The majority of these cancers are driven by HPV 16 which carries the E7 antigen targeted by CUE-101. Despite treatment with current standards of care, approximately 50% of patients with advanced disease will experience recurrence and significant quality of life impact. Patients with HPV-related head and neck, cervical and genitoanal cancers represent an important unmet clinical need and underscore the opportunity for promising new therapeutics.
CUE-102 leverages the CUE-100 framework and a pMHC derived from the Wilms’ Tumor protein (WT1), a non-viral antigen known to be over-expressed in a number of cancers, including solid tumors and hematologic malignancies. We plan to initiate preclinical studies in collaboration with our partner LG Chem Life Sciences in 2019.
CUE-103 will leverage the CUE-100 framework and target an antigen to be selected in collaboration with LG Chem Life Sciences.