Periodic Reporting for period 1 - TK-NEO (Personalized Cancer Immunotherapy through DNA-EP vaccines)
Reporting period: 2019-08-01 to 2020-01-31
NEOMatrix, the new commercial name of TK-NEO, is an R&D initiative of Takis, a Biotechnology Company with a scientific group with more than 10 years of experience in drug discovery, including the validation of new targets for the treatment of chronic viral diseases and cancer and to a number of IND/CSA filings in the areas of virology and oncology. The new frontier in Oncology is Cancer Immunotherapy, i.e. a therapy that stimulates the immune system to attack cancer cells, likewise vaccines can fight infectious diseases. Existing immunotherapies based on Immune Checkpoint Inhibitors (ICI) have been approved and commercialized with good results for many different cancers since 2011. However, the response rate of ICIs is still not so high and they still fail to achieve long-lasting responses in patients with metastatic disease, due to patient-specific mutations and intra-tumor heterogeneity (TH), i.e. treatment-resistant emerging variants in the same tumor typology. As a result, researchers are increasingly looking to attack neoantigens: protein fragments found only on cancer cells. Due to their unique nature, targeting them would allow a patient’s immune systems to find and attack cancer cells, while leaving healthy cells alone. NEOMatrix is a patent pending process for the production of patient specific DNA-based Neoantigen Cancer Vaccine (NCV) based on sequencing the genetic map of the tumor, identification of specific mutations that are present, production of the NCV and delivery to the patient in combination with ICIs. NEOMatrix, endowed with high poly-specificity and poly-functionality, was demonstrated in preclinical setting to be very efficient in preventing tumor growth, and has the potential to broaden the repertoire of immune responses against cancer, a feature that could be particularly relevant in the treatment of tumors with high heterogeneity, such as melanoma and lung cancer. The targeted procedure for production and delivery of NEOMatrix is based on a 6-week process, from sampling and sequencing the specific tumour DNA, synthesis of the right DNA sequence for the specific tumour, delivery through the DNA-EP device.
The work carried out in the Feasibility study allowed to: 1) clarify the technical concept and validate in preclinical setting the competitive advantage of the application in the treatment of complex cancers in combination with Immune Checkpoint Inhibitor, which was patented by Takis during the study; 2) define the validation and exploitation strategy, by designing a clinical trial plan to reach the clinical validation of the solution and license it to pharma; 3) found a dedicated spin-off company named NEOMatrix, which is the commercial name identified for the solution, and define a Business Plan for the investment required and financial strategy; 4) Validate the solution in the 2019 European Health Catapult competition organized by EIT Health, where NEOMatrix concept was awarded the second prize in the Biotech category from a jury of investors and scientific experts.
The alternative solutions for production of NCVs are mostly based on peptides and virus platforms, which present several disadvantages, e.g. requiring an adjuvant to work properly and activate an immune response, or limitation to single delivery per patient. NEOmatrix being based on plasmid DNA, can be used in multiple deliveries for treating different metastasis in the same patient. Moreover, plasmid DNA is easier to produce and does not require storage at -80 as they are generally stable at standard cold temperatures. DNA plasmid is indeed an ideal platform for bringing individualized neoantigen vaccines to the market at reasonable COGS and with good manufacturing success rate also with high number of neoepitopes. A dozen of competitors globally are developing NCVs, mostly at pre-clinical stage with few that started clinical validation. There are only 2 direct competitors working on the same platform (DNA-based NCV). Takis intends to spin-out the NEOmatrix and get support of investor to bring the validation of the solution up to completion of clinical trial Phase I-II. NEOMatrix is meant to be used as immunotherapy in patients with locally advanced or metastatic solid cancers in combination with anti-CTLA4 Immune Checkpoint Inhibitor, preventing tumor growth. This will broaden the repertoire of immune responses against cancer, a feature that could be particularly relevant in the treatment of tumors with high heterogeneity, such as melanoma and lung cancer.