“CDR-Life’s T cell engaging antibodies are potentially transformative in the field of cancer immunotherapies”
Prof. Markus G. Manz, MD, Head of Medical Oncology and Hematology at University Hospital and University of Zurich, Switzerland
Over the past decades, the emergence of immunotherapies has changed the game in cancer treatment. However, to date, immunotherapies have only shown efficacy in certain patient populations and suffer from a high degree of off-tumor activity due to lack of tumor selectivity. This severely compromises the efficacy and safety of these promising therapies.
CDR-Life is developing new immunotherapies that target antigens restricted to tumor cells, thereby solving the problem of non-tumor selectivity that is hindering existing treatments from achieving full therapeutic potential. Based on more than 20 years of expertise in cutting-edge antibody fragment design, engineering and production, we have developed a new antibody-based approach that specifically attacks the unique cancer protein targets existing inside tumor cells.
This is achieved by antibodies binding to peptides from tumor antigens on the major histocompatibility complex (MHC) with very high specificity. The MHC traffics proteins to the immune system and provides access to a new class of intracellular tumor antigens to engage T cells. Combined with our proprietary multi-specific format, we are developing truly tumor-specific and -eradicating T cell engagers.
The M-gager® platform is our proprietary technology that develops highly specific and effective peptide-MHC (pMHC)-targeting T cell engagers.
Based on a unique phage display library with a repertoire of billions of antibodies already binding to the pMHC of interest, the MHC-targeting T cell engager (M-gager®) format result in effective and selective recruitment of T cells and generates a specific cytotoxic T cell response against the cancer cell. M-gager® molecules are expected to be highly effective immunotherapies for challenging yet very attractive targets such as neoantigens and cancer testis antigens (CTA), providing minimal off-tumor activity.
M-gager® molecules have excellent drug properties and are well-producible in standard mammalian cell-based manufacturing.
Our diversified and growing pipeline of first-in-class therapy candidates addresses solid tumors and hematologic malignancies responsible for more than 50% of all cancer-related deaths:
CDR404, is our most advanced program for solid tumors. It is a potent and tumor-selective M-gager® targeting MAGE-A4, an intracellular oncogene with expression in several frequent and difficult to treat solid tumors including lung, esophageal, and ovarian cancer.
CDR101 is a trispecific next-generation BCMA targeting therapy for the treatment of relapsed/refractory multiple myeloma (RRMM). Multiple myeloma remains incurable and existing therapies are associated with significant shortcomings in terms of durability of response in RRMM. Response duration has improved beyond 12 months Progression Free Survival with a recently approved BCMA targeting cell therapy; however, manufacturing remains a significant challenge. Off-the-shelf bispecific BCMAxCD3 targeting therapies have shown good efficacy but median time to relapse is limited to under 12 months.
Preclinical results for CDR101 have shown it to be up to 100 times more potent in vitro and in vivo than existing bispecifics in clinical development without inducing PD-L1-related cytotoxicity. In vivo and patient ex vivo data presented at ASH2021 show full tumor eradication and longer response compared to BCMA targeting bispecific antibodies. CDR101 has the potential to be a novel off-the-shelf therapeutic approach offering more durable response and the prospect of higher cure rates in MM. CDR101 has excellent drug-like properties with high stability and CHO-based production yield.