Neoantigens are tumor-specific targets that arise from mutations that tumor cells gain during their evolution. PIONEER™ is able to accurately and efficiently identify a patient's neoantigen targets in a personalized manner. Using proprietary computational AI models developed at Evaxion, PIONEER™ has been developed to select the neoantigens that are most likely to generate a strong T-cell response and anti-tumor effect in each patient. The goal of our immunotherapies, derived from the PIONEER™ model, is to deliver therapeutic neoepitopes to patients in a way that trains patients’ own immune systems to specifically target and kill tumor cells with no or very limited adverse effects on healthy non-cancer cells.

Mutation and expression: Once biopsies have been performed, PIONEER™ identifies cancer-specific mutations by comparing DNA sequencing data from the tumor sample(s) and normal tissue sample using our proprietary AI-based somatic variant caller. Then, the expression levels of the genes found within the mutation are determined by analyzing tumor RNA sequencing data. PIONEER™ also calculates the mutation-specific expression levels using an in-house developed computational model.

Translation: PIONEER™ determines the effects of each cancer-specific mutation, as not all mutations result in altered protein sequences. Once non-synonymous mutations (where both the DNA sequence and the encoded amino acid are altered) are identified, the surrounding coding regions are translated into amino acid sequences, generating cancer-specific neoantigen sequences.

Personalized cancer immunotherapy: The identified neoantigens are put into our proprietary AI-based tool along with the patient’s HLA type, to identify the neoantigens that will be presented on the patient’s MHC molecules. PIONEER™ also predicts the likelihood of these neoantigens eliciting a T-cell response, which will trigger an immune response and tumor cell death. Additionally, for patients where DNA sequencing data from multiple tumor biopsies is available, PIONEER™ seamlessly integrates the data from each biopsy to target tumor-defining neoantigens. This means that, even though tumors continuously acquire novel mutations and do not necessarily encode and express the same neoantigens, PIONEER™ allows for the systematic eradication of the whole tumor as well as potential metastases in the patient.

Neoantigen administration: The selected neoantigens are manufactured and administered alongside standard-of-care, producing an anti-tumor effect in the patient.

• PIONEER™ is able to identify therapeutic neoantigens that drive a T-cell response with higher accuracy compared to predictions done by state-of-the-art public tools. Clinical interim data from the Phase 1/2a trial of EVX-01 demonstrated induction of neoantigen-specific T-cells in 100% of patients with an overall response rate of 67% compared with a historical overall response rate of 33-40% with anti-PD-1 treatment alone.
• PIONEER™ identifies multiple neoantigens that can be incorporated in the immunotherapy to increase therapeutic effect and overcome issues related to cancer clonal heterogenicity and tumor immune escape.
• PIONEER™ is clinically applicable, automated and deployable anywhere in the world. It has been through a process of validation according to the International Society for Pharmacoepidemiology's (ISPE) latest revised guide for Good Manufacturing Practice, or GAMP5, to ensure compliance with legislation and good practice regulations to maintain a high standard of quality.