TIGER was planned to deliver proof of principle (PoP) in humans for a novel best-in-class mRNA cancer vaccine platform optimized for intravenous (IV) administration, with the aim to show major clinical efficacy.
The antigens to be used used for the PoP consisted of mRNAs encoding the proteins E6 and E7 of Human Papilloma Virus strain 16 (HPV16), and TriMix mRNAs that stimulate dendritic cells to start strong T cell responses. The mRNAs were to be formulated in a novel patented lipid nanoparticle format shielding the mRNA, and delivering it to immunoactive antigen presenting cells, vastly enhancing T-cell response.
Safety and best-in-class efficacy of our IV mRNA product have been demonstrated in rodent experiments. Furthermore, preclinical to clinical translation has been shown for our TriMix based vaccines using different delivery strategies. Based on the preclinical and prior clinical data, our platform has the potential to cure cancer patients.
The PoP study was to be in patients with recurrent HPV16 positive cancer, which is categorised as a non-communicable disease by the WHO, without and with a PD-1 checkpoint inhibitor. Safety, immunogenicity and clinical benefit will be key endpoints of the study. Biomarker and PROM research will allow future informed therapeutic and care decisions by both patient and care team. Recruitment and stratification plans were put in place. Interactions with regulatory, reimbursement and ethical authorities together with patients and carers were planned to help laying out the route to the patient not only for our product but also for all other mRNA cancer vaccines. The set-up and regulatory approvals were in place for multiple sites. A strategic change in project planning led to the cancellation of the clinical trial.
Additionally, the project encompasses all essential elements for preparing therapy validation in later stage clinical studies, while addressing patient needs, values and choices. Upscaling mRNA vaccine GMP-productionwas planned to enable these further clinical studies. Once validated, our platform was to be easily translatable to a wide range of cancers using other tumour antigens, be they TAAs or neoantigens.
The project successfully developed biomarkers to early stages of testing. This included advances exciting and innovative biomedical diagnostics to provide new tools to support later stage clinical studies, future oncology therapy development and patient stratification. This included a ctDNA assay, radiomics based approaches and immune monitoring. In addition successful outreach work included online and printed materials and a workshop on cancer biomarkers.
