Luigi Aurisicchio, CEO,

Takis Biotech

"Together with Rottapharm Biotech, we are developing the only DNA-based SARS-CoV-2 vaccine in Europe."

Can you briefly introduce Takis Biotech to our audience? Takis Biotech was founded at the end of 2009 by a group of scientists from the Merck Research Laboratories (MRL), where I was leading the cancer vaccine research. Over a decade later, Takis has grown into a 30 people team. Our expertise is genetic vaccination. We started from gene therapy, developing vectors able to express a therapeutic gene, such as interferon, to correct diseases, but then adapted the adenoviral vectors platform from gene therapy to develop cancer vaccines against tumor antigens. We already demonstrated that our genetic vectors can activate a potent, pleiotropic immune response against cancers. Could you elaborate on your unique expertise in electroporation? Takis is a pioneer in the in-vivo electro-gene transfer of plasmid DNA (DNA-EGT) using electroporation. Electroporation is a technology that permits the entry of the DNA into muscle cells to stimulate the immunological process; this facilitates a greater DNA cell uptake and enhanced protein expression, which translates to a longer-term immune response. This technology is adapted from IGEA, based in Italy. IGEA uses electroporation for electro-chemotherapy, whereby they inject surface tumors like melanomas with a chemotherapeutic agent which is then electroporated; the chemotherapeutic agent enters the cells, shrinking the tumors in 90% of the cases. We modified IGEA’s device for electro-gene-transfer, through which we electroporate the muscle. We can create an “e-gun,” a syringe injecting the vaccine and electroporating at the same time with an electric field. We have already started developing this technique for other infectious diseases such as malaria. What is the potential of genetic vaccines therapies in the treatment of cancers? When we started working on cancer vaccines, there was not enough knowledge about the immunogenicity of tumor-associated antigens; scientists focused on using molecules that were expressed by both the tumors and the normal tissues, which made it very challenging to channel the immune response to the cancer only - and not the healthy tissue. With the advent of bioinformatics and next-generation sequencing, we can now identify specific antigens found only in tumors and induce a much stronger immune response. What is the progress in the development of your anti-Covid vaccine? Together with Rottapharm Biotech, we are developing the only DNA-based SARS-CoV-2 vaccine in Europe; after receiving AIFA’s authorization, the Covid-eVax is now undergoing Phase I clinical trials. DNA-based vaccines do not necessitate cold chain storage and transportation. Another advantage of the vaccine is that it can be administered several times to increase the immunological response thanks to our unique electroporation technique. Takis is associated with two more spin-offs. Can you tell us more about these companies? In 2016, we had our first spin-off, Evvivax, which stands for Engineered Veterinary Vectored Immunotherapy and Vaccines, and it uses the same genetic technology mentioned before but applied to animals. Evvivax was born while developing human-focused cancer vaccines: Typically, vaccines are tested in clinical trials on rodents before moving to primates; however, for cancers, there isn’t a model in non-human primates on which to test for an antitumoral effect. Therefore, we started using dogs as a model for testing the vaccines because dogs are exposed to exactly the same environmental factors as humans, and they have a genetic predisposition to develop cancers. This made for more real-life, complex, and heterogeneous testing. When we published our first paper demonstrating that our vaccine, in combination with chemotherapy, was able to double the survival of dogs suffering from cancer, many US veterinary practitioners got in touch. This is how we discovered a large market for cancer vaccines in the animal health space and created Evvivax. Evvivax is also working on a Covid-19 vaccine for animals because cats and minks get infected by the virus. In 2020, we established our second spin-off, Neomatrix. Neomatrix's specific mission is neo-antigen-based cancer vaccines, following a 9-weeks process that begins with the biopsy of the tumor, characterization of that tumor by sequencing the DNA and the RNA, identification of the so-called neo-antigen (so those visible to the immune system and that are specifically mutated for that kind of tumor), and finally the creation of a vaccine around these specific mutations. The therapeutic vaccine is used in patients with locally advanced or metastatic solid tumors. We have produced the proof of concept in mice and in human biopsies, and we are looking for investors to move to GMP preparation and clinical trials.