Novel targeted therapy for treating Leukemia.

The main goal of the project is to develop a new disease-specific drug candidate for the treatment of leukemia. A successful end result will be the starting point for a potentially curative therapy with minimal side effects compared to today's situation - a "first-in-class" drug candidate that is completely cancer specific. A type of white immune cell called T cells is the command centre of the immune system that determines when and against what the immune system should respond to protect us from infections, but also against the development of cancer. They have this ability by expressing unique receptors on the surface called T cell receptors (TCR). TCR recognizes the cancer-specific target complexes and can therefore instruct the immune system to eradicate the cancer cells. When cancer develops, it is partly because this system has failed. With today's technology, however, we can leverage this natural property to develop enhanced TCR to become highly effective and safe cancer treatment. This is the starting point for the project. Through work done by Nextera and our partner at Oslo University Hospital (OUS), the project has validated TCR from healthy donors and cancer patients who respond to cancer-specific target complexes. TCR has then been modified using Nextera's unique phage display technology. We are now focusing on a TCR main candidate where we increase both the sensitivity and the specificity to target the cancer-specific target complex. We have investigated several therapeutic BiTe and cellular CAR-T formats to prepare for further development towards human therapy with optimal efficacy. The results show that we have succeeded in improving the specificity of the TCR candidate to a level where we now only react with the given cancer specific target, and retained the original sensitivity. The effect we see is best in a CAR-T format. In parallel, we have also verified a robust expression of the selected cancer-specific target complex within the type of leukemia we have selected as the main indication. The project has therefore obtained a good starting point for further industrial development of the drug candidate for the treatment of this type of leukemia.

The lessons learnt and results obtained during the project have put Nextera in a good position for further development and entering into commercial partnering discussions with a novel cancer specific drug lead candidate. The project has both allowed an improved insight into specific leukemia disease pathogenesis, as well as providing a framework for drug development using highly disease-specific immunotherapy. The method development conducted as part of the project has jointly improved the technological capabilities of both Nextera and our OUS partner, and further given us insight into the likely most productive therapeutic format for the type of drug candidates that the project has focused on. Thus, the impact the project may have further down the path, is both value creation for Nextera stakeholders, and thus also our OUS project partner, when further commercial development is initiated. Ultimately, improved cancer treatment and patient quality of life may be envisioned.

Nextera AS is a biotechnology company developing novel immunotherapies for autoimmune diseases, chronic infections and cancer. The core technology of the company is our unique phage display engine, which we apply in protein engineering and evolution of T cell receptors and MHC class II molecules. The primary goal of the project is to develop a novel drug candidate for treatment of Leukemia. Upon cancer cell binding, the drug candidate will kill cancer cells in a highly specific manner. The expected effect will be durable remission of disease with minimal side effects. The project is a collaborative effort between Nextera and the groups of Professor Ludvig A. Munthe and Geir Tjønnfjord at UiO/OUS. Support for the project will enable Nextera to continue to strengthen and utilize the technology platform within the immune-oncology field. A successful project may further establish a novel concept for the treatment of other cancers through pMHC class II targeting.