CheckMab aims at creating value by targeting surface molecules selectively expressed in tissue-resident regulatory T cells (Treg cells) and contributing to the pathological state of immune-mediated diseases. The company will develop monoclonal antibodies (mAbs) against Treg cells present in diseased tissues as tools for safer and efficacious immunotherapies against cancers and autoimmune diseases.
Concerning cancer, immunotherapy based on mAbs against immunological checkpoints (e.g., anti-CTLA4, PD-1, PD-L1) represents a very promising therapeutic opportunity. However, these mAbs show efficacy only in a limited portion of cancers, often characterized by a high mutational load. Moreover, they can cause autoimmune adverse events in many organs in a significant fraction of patients. As a consequence, a conspicuous part of patients receiving checkpoint inhibitor mAbs must discontinue this therapy due to untreatable high grade adverse events. Moreover, many cancer patients are ineligible for immunotherapy due to pre-existing autoimmune disorders or familiar history for them. Adverse events caused by immune checkpoint inhibitor mAbs likely occur because they promote a generalized derepression of the immune systems. In doing so, they counteract the immunological homeostasis exerted by Treg cells in all anatomical districts of the body.
We believe that innovative and safer immunotherapeutic strategies should selectively deplete tumor-infiltrating Treg cells by targeting molecules specifically over-expressed in these cells. Indeed, a selective targeting of tumor-infiltrating Treg cells should unleash immune response only in the tumor microenvironment, so as to avoid a generalized derepression of effector lymphocytes throughout the body.
mAbs targeting tumor-infiltrating Treg cells should have safer therapeutic profiles than the approved checkpoint inhibitors, so to offer a novel and safe therapeutic opportunity to oncologic patients who have to discontinue currently approved immunotherapy due to autoimmunity adverse events, and to patients ineligible to the available therapy due to pre-existing autoimmune diseases or familiar history for them.