Pipeline

Preferentially expressed Antigen in Melanoma (PRAME) is a protein that is not widely expressed in normal tissues but is highly expressed in melanoma, ovarian cancer and neuroblastoma. Myrio is testing binders against a number of different epitopes presented by different HLA types.

Human papillomavirus (HPV) is known to cause a number of cancers notably those of the cervix, head and neck. While the rates of infection are falling due to the wide deployment of vaccines that protect  against the virus, there are still infections in unvaccinated people and a large number of people who were infected before the vaccines became available. Incidence of HPV-associated squamous cell  carcinoma of the head and neck is increasing rapidly. Affinity has generated scFvs against the HPV16 E7 protein and is in the process of testing them in bispecific formats on cancer cells.

PSA is the biomarker used to identify men who may have prostate cancer being only expressed in the epithelial cells of the prostate gland. While it would appear to be a perfect marker for targeting prostate cancer, it is a secreted protein that is found in seminal fluid and in blood. Normal antibodies would just bind to the soluble protein and would not be useful for targeting. However, cells that secrete a particular protein also present peptides from that protein complexed to MHC on their surface. Affinity has generated scFvs specific for a peptide from PSA presented by HLA-A*02:01 and is currently evaluating the binders in bispecific format.

The protein p53 is often referred to as ‘the guardian of the genome’. It is directly involved in the killing of a cell when it has accumulated genetic damage – a process called apoptosis. Cells that have mutations in p53 or in other proteins important in apoptosis are able to accumulate genetic damage which may transform the cell into a cancer. Hence, mutations in p53 are among the most common found in tumors. The cells often try to compensate for this ‘loss of function’ by making more p53 which leads to more p53 peptides being presented on the cell surface. Affinity has a number of antibodies targeting wild-type p53 presented by a number of HLA types.

The rat sarcoma protein family: KRAS (p21), NRAS and HRAS are the most commonly mutated proteins in cancer, being implicated in up to 30% of cases. RAS mutations account for over 90% of pancreatic, 40% of colorectal and 30% of lung cancers. Nearly 80% of RAS mutations are of the glycine in position 12 where it is often mutated to valine (G12V) aspartic acid (G12D) and less frequently to cysteine (G12C) and others. Affinity has successfully screened G12V mutations and is in the process of screening G12C.

AFP is an oncofetal antigen in that it is expressed in the developing fetus but not in normal adult tissues. It is however expressed in a number of cancers, most frequently in hepatocellular cancer (HCC, liver cancer), where over half of cases express high levels. AFP is frequently used as a biomarker to detect disease. HCC is very common throughout east Asia due to hepatitis B (HBV) which is endemic in the region. Affinity has successfully generated binders against AFP presented by HLA-A*02:01 and will screen for peptides presented in the most common HLA types in east Asia.

Neoantigens are literally new antigens that occur in cancer through mutation. Unfortunately, few neoantigens are immunogenic and a high number of mutations are needed in the cancer before the immune system will ‘see’ the tumor either naturally or when boosted with checkpoint inhibitors. Affinity has successfully screened a number of neoantigens. These include ‘shared’ neoantigens, such as those of KRAS or p53 which occur frequently, and ‘private’ neoantigens which are unique to an individual’s tumor.