Development of T-cell based cancer therapy

T-cells is a crucial part of the human immune system and one of their main tasks is to eradicate cells that are either infected by virus or have become cancerous. Scientists have over the past few years attempted to utilize these specialized killers in cancer therapy, termed immunotherapy. This field of cancer therapy has shown extraordinary results in terminally staged cancer patients and is of many regarded as the future of cancer therapy. Zelluna is a recently established company developing T cell receptor (TCR) based immunotherapies for the treatment of a wide range of the deadliest cancer types known today. A TCR can be regarded as a targeting unit that can be used to guide effector cells, such as T cells and NK cells, to tumor cells in order to kill them. Zelluna?s treatment concept is to arm a large number of effector cells (T or NK cells) with the right targeting unit (TCR) in order to transform these cells into TCR guided missiles that seek out and destroy cancer cells wherever they are in the body. The aim of this project was to prepare our first product candidate, based on T-cells as the effector cell, ready for testing in human patients ? a first-in-human (FIH) trial. To reach this goal we established a range of sub-goals; deciding on the lead product (TCR) for development, perform preclinical testing, establish GMP (good manufacturing practice) compliant manufacturing, design the FIH study and submit a clinical trial application (CTA) to the relevant regulatory authorities. In addition, we aimed to develop our other TCR candidates in order to build a broader future clinical pipeline. During this project Zelluna has completed several of the defined sub-goals in the project. We have optimized and completed the manufacturing process for our leading T cell based product (ZI-H04), and completed the first successful GMP compliant production run. Furthermore, we have designed a FIH study and determined the types of cancer to be treated, number of patients to be included and established potential principle investigators and sites to run the trial. We are also close to finalizing the pre-clinical package. However, during execution of this project, there has been a change in how leading academic and industrial players and investors and partners view the cell therapy space, especially regarding how to make this type of therapies simpler and less costly to manufacture and therefore available to a larger patient population. Zelluna has in parallel continued the development of a second strategic arm based on NK cells, through securing important intellectual property rights and partnerships, and has therefor recently made a decision to focus further development activities on NK cell based therapies. How Zelluna may potentially further develop and generate value from ZI-H04 has not been decided yet.

Gjennom dette prosjektet har Zelluna oppnådd følgende virkninger og effekter: - Økt selskapets erfaring og kompetanse på produksjon av celleterapi-produkter, herunder plasmid- og virusproduksjon, prosessutvikling og endelig produksjonsprosess. - Utviklet og etablert en rekke eksperimenter som vil utgjøre vår fremtidige platform for preklinisk testing av T cellereseptor-baserte produkter - Økt erfaring og kompetanse på regulatorisk og klinisk utvikling av celleterapi-produkter - Etablert et verdifullt nettverk av samarbeidspartnere og rådgivere innen råmaterialer, produksjon, regulatorisk og klinisk. Selv om Zelluna, av flere årsaker, har valgt å sette på pause intern utvikling av produktet inntil videre, har prosjektet tilført verdifull kompetanse og nettverk som vil utgjøre et sterkt fundament for videre utvikling av nye produkter.

The use of the immune system to fight cancer - immunotherapy - has received a tremendous amount of attention recently due to clinical trials where patients with advanced deadly cancer types have been cured. One form of immunotherapy utilizes the patients' own T cells that are engineered to express cancer-targeting receptors such as chimeric antigen receptors (CARs) or T cell receptors (TCRs) to fight cancer in a process termed adoptive cell therapy (ACT). The recent few years, several big pharma and biotech companies have invested heavily in this field which is regarded as the future of cancer therapy. Zelluna Immunotherapy is founded on state-of-the-art competence, infrastructure and scientific and clinical experience built up over two decades at the Radiumhospital. We have engaged in a partnership with the Section for Cell Therapy at Radiumhospitalet and we have all the required competence and infrastructure in place. In this project we will isolate and develop TCRs for use in immunotherapy of cancers with high unmet need such as lung, colon and pancreatic cancer. Our unique competitive advantage is that we isolate TCRs from long term surviving patients from previous vaccine trials. Hence, in contrast to all our competitors, our TCRs have already demonstrated safety and clinical benefit to patients. In this project we will obtain clinical trial readiness and submit a clinical trial application (CTA) for our lead candidate, and we will generate a highly valuable panel of validated TCRs ready for clinical translation. The expected results are of high importance to the company and will serve as the basis for significant value creation.