We are constantly working to build on our unique technology platform and expand the areas where our antibody-cleaving enzymes can make a real difference. We see opportunities to expand our platform beyond the indications currently in our development pipeline, and we are working to develop new enzymes to further broaden our horizon.
Beyond imlifidase, our next generation IgG-cleaving enzyme program for more frequent dosing, NiceR, is designed to enable expansion into a large spectrum of potential indications, including relapsing autoimmune diseases and gene therapy, as well as oncology indications. With our EnzE program, we are exploring the combined use of approved antibody-based cancer treatments with IgG-modulating enzymes.
Our Enzyme-based antibody Enhancement, or EnzE, program is a preclinical research and development program to explore the combined use of antibody-based cancer treatments with IgG-modulating enzymes. Most therapeutic antibodies have a mode of action substantially dependent on interaction between the Fc-part of the IgG to receptors on effector cells called Fc-gamma receptors, or FcγRs. When the therapeutic antibody is bound to FcγRs on effector cells, they can target tumor cells and kill them through various immune reactions.
High levels of endogenous plasma IgG have been associated with limiting the efficacy of therapeutic antibodies, as plasma IgG can compete with therapeutic antibodies by saturating the FcγRs of the patient’s immune cells and prevent them from effectively killing the cancer cells.
IgG-modulating enzymes can be utilized to empty both high and low affinity FcγRs and eliminate the endogenous antibody pool1. We believe that these enzymes can be a potent tool to reboot the human antibody repertoire and to generate a window to preferentially load therapeutic antibodies onto effector cells, thereby creating a large number of dedicated tumor-seeking immune cells.
We are evaluating this concept and its potential clinical benefit under the EnzE program, where we are exploring opportunities within oncology, including potential collaborations, to establish a clinical development plan for this concept.
Allogenic hematopoietic stem cell transplantation
For patients with various forms of cancer, cell therapies such as allogeneic hematopoietic stem cell transplantation, or allo-HSCT, or bone marrow transplantation are potentially lifesaving treatments. Allo-HSCT is the only curative treatment for many patients with high-risk hematologic malignancies or non-malignant disorders. However, identifying a suitable donor for such therapies is challenging, requiring a genetic match between the donor and the recipient’s HLAs. As a result, the donor pool is often expanded to include HLA mismatched donors. The use of HLA mismatched donors increases the risk that the patients have IgG antibodies that react negatively to the donor, reducing the efficacy of the stem cell transplant. We believe that cell therapies such as HSCT transplantation may benefit from use of imlifidase.
1. Järnum et al. Mol Cancer Ther. 2017 Sep;16(9):1887-1897