Our Science

Selective Targeting, Thoughtful Design

Our comprehensive cell therapy platform was designed to generate allogeneic, iPSC-derived NK and T cell products for the treatment of both hematological and solid tumor malignancies with significant unmet medical need.

We are leveraging our expertise in cellular reprogramming, genetic engineering, and manufacturing to develop therapies with the potential to overcome many of the challenges inherent to cell therapy and provide a significant advantage over existing cell therapy technologies.

Evolution of Targeted Cell Therapy in Cancer

Century’s approach builds on a foundation of proven allogenic and autologous therapy research to transform cell therapy as we know it today.

Autologous CAR-T therapies have many characteristics that we believe limit their therapeutic potential. These therapies necessitate an individualized and lengthy manufacturing process, resulting in increased wait times for patients, limited product availability and increased supply chain complexity and cost. Additionally, patients may have undergone multiple therapeutic regimens such as chemotherapy or radiation treatment that may negatively impact the health of the donor cells. Damaged or weakened donor cells may not be able to properly proliferate, resulting in manufacturing failure or insufficient potency.

Allogeneic CAR-T therapies overcome some of the limitations of autologous-based treatments – mainly by using healthy donor cells, but such approaches can cause unwanted reactions in patients like graft versus host disease (GvHD) or host versus graft rejection, and donor cells only have a finite replication capacity with restricted gene editing potential.

iPSC-derived cell products offer what we believe are significant technical and manufacturing advantages compared to both autologous and other allogeneic approaches. IPSC cells can propagate indefinitely and can act as a progenitor cell for other cell types, including the different types of immune cells.

We believe that iPSCs are far more amenable to multiple genetic manipulations than donor-derived NK cells and T cells because iPSC cells can undergo multiple rounds of replication without loss of functionality. In contrast, differentiated cells used in donor derived allogeneic approaches are limited to just a few genetic edits, which can impact their overall functionality. The number of edits that can be introduced into the genome of differentiated NK cells or T cells is limited because each engineering step requires cells to replicate and too many expansion cycles often result in cell exhaustion and loss of functionality.

iPSCs are derived from single cell clones, which are used to construct a master cell bank capable of providing a sufficient number of doses for the life of a product due to the unlimited replicative capacity of iPSCs. The use of a single master cell bank allows iPSC-derived products to be produced with greater consistency, at the greatest possible scale and at reduced cost compared to donor-derived NK cells or T cells. We believe that iPSC-derived cell therapies provide meaningful advantages over other modalities and have the potential to disrupt the oncology treatment paradigm.

Century Core Competencies

Century Approach and Core Competencies

We have developed highly efficient gene engineering processes to generate our product candidates. We are currently using the CRISPR-MAD7 nuclease to enable precise cutting of the iPSC genome, and have developed proprietary applications of the CRISPR-MAD7 technology to genetically modify iPSCs by simultaneously removing target genes or adding transgenes of interest at precise genetic loci. Our approach preserves genome integrity and achieves more predictable and consistent transgene expression as compared to approaches driven by viruses or transposable segments called transposons, which result in varied gene copy number and random integration events that risk mutations, namely insertional mutagenesis.

We are leveraging our Allo-EvasionTM technology to design cells capable of evading identification and destruction by the host immune system, which may permit dosing in patients with limited or no immune preconditioning regimens. The technology was designed to reduce allogeneic immune-reactivity, thereby potentially helping to prevent rejection by the patient’s immune system, allowing repeat dosing of our CAR-modified cell therapies and sustaining therapeutic efficacy over a long period of time.

CAR design is a critical component of innovative cell therapy product candidates. We believe that targeting multiple antigens on tumor cells will help address tumor heterogeneity and antigen loss, which are frequently observed in tumor cells. We have created a proprietary synthetic library to enable in-house binder screens and multiple campaigns against several tumor antigens are ongoing to generate the CAR constructs for future product candidates.

Century is uniquely able to accelerate new product candidate generation by bulk editing progenitor cells to share a core set of common features that increase their functionality, safety and persistence. We believe this approach will significantly shorten the time required to develop subsequent product candidates, unlike existing cell therapy platforms, which require making individual gene engineering steps – a time and resource intensive process.

We believe our use of iPSCs, which have the potential to propagate indefinitely, will allow us to develop a streamlined manufacturing process with scalability advantages while producing consistent, high quality, off-the-shelf products at reduced manufacturing costs. Given the indefinite propagation potential of iPSC-derived allogeneic cells, we believe that a single master cell bank can be used for the lifetime of the product.

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