“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, immunotherapies so far 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 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 with existing treatments. We designed a new antibody-based approach that targets highly cancer-specific proteins that exist inside the tumor cells. Intracellular tumor proteins are presented to the immune system as peptides on Major Histocompatibility Complex (MHC), which are natural targets of in cancer cells.
Based on more than 20 years of expertise in cutting-edge antibody fragment design, engineering and production, we have developed a technology to generate antibodies binding to tumor-specific peptides on MHC with very high specificity. 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 for making highly specific and effective pMHC-targeting T cell engagers.
It is based on a unique phage display library with a repertoire of billions of antibodies already binding to the pMHC of interest.
The MHC-targeting M-gager® format results in effective and selective recruitment of T cells generating a specific cytotoxic T cell response against the cancer cell. The M-gager® molecules are expected to be highly effective immunotherapies for challenging but very attractive targets like neoantigens and cancer testis antigens with 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 therapy candidates addresses the most common solid tumors and hematologic malignancies worldwide that are 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.