Development of off-the-shelf cell therapies for cancer treatment

Cancer therapies based on genetically engineered and guided T-cells have recently shown extraordinary clinical performance in liquid tumors, providing curative treatment to patients who previously had no treatment options. Such therapies are personal and based on the patients own T cells, genetic engineering to introduce a guiding system (e.g. chimeric antigen receptors), expansion to billions of cells and then reinfusion back to the original patient. At the same time, this type of therapy is difficult to scale, has a long lead time and is very expensive. Furthermore, despite the great benefit to liquid cancer patients, cell therapies based on CAR engineered T cells have so far not made inroads into the solid tumor space which constitute 85-90% of the patient population. The aim of this project is to develop a novel and unique type of cell therapies that addresses these issues. We are developing a cell therapy platform where we combine NK cells and a targeting unit (T cell receptor - TCR) that has proven to be highly suited to target solid tumors. By combining a TCR with an NK cell (TCR-NK) we are able to attack tumor cells using two different mechanisms, which may be highly important when it comes to observed clinical response. Our TCR-NK platform is based on donor cells and we can produce up to 30-70 times more doses to a substantially lower cost and make this type of treatment accessible to a larger patient population. During the project we have shown that the TCR-NK treatment concept works as intended and that it has several key competitive advantages over existing types of therapies. We have developed our lead product candidate (ZI-MA4-1) and finalized initial pre-clinical testing. We have also developed a plug-in manufacturing process that can be used with all our TCR-NK products, and we have initiated upscaling and transfer to GMP together with an industrial partner. We aim to submit our first clinical trial application for ZI-MA4-1 for treatment of different cancer types towards the end of 2024.

We have demonstrated that the TCR-NK concept is feasible and that it has a number of important competitive advantages over other cancer therapies in development. We have optimized and initiated development of our first TCR-NK product candidate and we have conducted preclinical research showing compelling safety and efficacy potential. We have also developed a plug in manufacturing process for our lead product that is being scaled up and transferred to GMP in collaboration with an industrial partner, and that will serve as a manufacturing platform for future TCR-NK products. We are continuing the development of our lead product beyond this project and aim to submit a clinical trial application towards the end of 2024. We have filed two new patent applications that protects our lead product and key components of our manufacturing platform. Overall, this project has so far generated substantial value for Zelluna and laid the ground for further value creation, importantly for cancer patients.

Cellular immunotherapies for the treatment of cancer have received a lot of attention in recent years driven by their tremendous efficacy and patient benefit seen in haematological cancers. These therapies commonly consists of autologous (patient’s own) T-cells that have been genetically engineered to express either a chimeric antigen receptor (CAR-T) or a T cell receptor (TCR-T) that provide the T cells with the ability to recognize cancer cells and kill them. However, patient access and thus commercial success is hampered by a complex and expensive logistics and manufacturing process, as each product is based on the patients' own T-cells as starting material. In this project we aim to develop a novel Natural Killer-cell based platform for allogeneic cell therapies that will transform a highly personalized therapy into "off-the-shelf" products for the treatment of cancer. This approach will overcome many of the current challenges in autologous cell therapies and unlock access of potent cellular therapies to a much larger patient population. To achieve this, we have a two-pronged strategy. The first is to engage in a partnership with a commercial NK-cell manufacturer where we will perform process development and establish GMP manufacturing capabilities to serve clinical trials and commercial supply. Second, we are collaborating with a renowned academic group to further strengthen our platform and to develop improvements and second generation products. This project will take us to the doorstep of clinical translation by submitting a clinical trial application, which is a significant milestone and value inflection point for the technology. At this point we will also be in a position to raise funding to conduct the clinical development program.