Our focus is on using bispecific antibody approaches
Bispecific antibodies are rapidly emerging as a powerful new class of therapeutics due to their ability to interact with two different antigens at the same time and therefore facilitate the targeting of multiple disease pathways simultaneously. This ability raises the prospect of successful treatment of complex disorders such as cancer and inflammation. Our bispecific antibodies targeting novel receptors have the potential to enable therapeutic advancements across a range of indications.
NVG-111, is a first in class T cell engager (TCE) that targets the natural immune system to destroy cancer cells. Using this unique, targeted approach leveraging the body’s own immune system and T cell responses, NVG-111 has the potential to transform the treatment of an array of hard-to-treat cancers.
NVG-111 is a small flexible molecule composed of two antibody-derived single chain variable fragments (scFv) linked in tandem. NVG-111 targets and enhances the power of a patient's T cells cell to kill tumour cells (See diagram 1).
Diagram 1: Structure of NVG-111 bispecific antibody T cell engager
The bispecific antibody T cell engager can redirect endogenous T cells to sites of tumors where, upon engagement with tumor antigen, they promote the formation of immunological synapses. This is followed by the release of perforins, granzyme B, and cytokines, and selective killing of tumor cells independently of MHC, costimulatory molecules, and antigen presentation (See diagram 2).
Diagram 2: Mechanism of action for NVG-111, a ROR1 targeting bispecific antibody T cell engager for the treatment of both hematologic malignancies and solid tumors.
Click to enlarge image
We consider our bispecific antibody T cell engager as ‘next generation’ as it builds on our emerging understanding of ROR1 targeting approaches using CAR-T cells and monoclonal antibodies and offers an improvement. Our bispecific molecules are custom-made for specific disease targets. Our NVG-111 bispecific antibody is active in nanogram quantities, can potentially penetrate tumors better and be used in combination with standard of care including chemotherapy, radiotherapy, CPI antibodies or small molecules.
Receptor tyrosine kinase-like orphan receptor 1
We have developed a bispecific antibody T cell engager that targets ROR1 (See diagram 3). ROR1 is a cell surface antigen which is present on a range of malignancies and cancer initiating cells, driving their growth and spread. ROR1 is absent or expressed at low levels in healthy adult tissues
It has been shown that ROR1 acts as a receptor for ligands potentially promoting tumor growth and our ambition is to inhibit tumor cell growth and kill the cancer cells. ROR1 has been shown to be present in >20 hard-to-treat hematologic malignancies and solid tumors.
Diagram 3: Targeted extracellular domain of the ROR1 receptor
One of the key advantages for bispecific antibodies is the ability to use an “Off-the-shelf” product enabling a lower cost of goods as there is no need for ex vivo manipulation and engineering of T cells, unlike some personalized cancer treatments. As the molecule is highly potent, lower doses are required which further reduces the manufacturing burden.