Single agent: gastric, biliary & pancreatic cancer
Combination with anti-PD-1: melanoma
RXC004 – best-in-class porcupine inhibitor
Porcupine is a key enzyme in the WNT signalling pathway. This pathway is involved in a range of hard-to-treat cancers with poor prognoses, such as pancreatic, biliary and gastric cancers. Our Porcupine inhibitor, RXC004, is a potent inhibitor of this enzyme and pathway, leading to strong inhibitory effects on tumour growth in a variety of cancer models.
There were estimated to be 107,000 new cases of pancreatic cancer in the US and the five largest EU countries (Germany, France, Spain, Italy and UK – 5EU) in 2016. By comparison, an estimated 324,000 people were diagnosed with gastric cancer in 2016 in the US, 5EU, China and Japan. Biliary cancer is fortunately quite rare with around 8,000 people diagnosed with it in the US and 1,800 people in the UK each year.
RXC004 has the potential to be used as a biomarker-guided, targeted therapy in hard to treat cancers and as a combination partner in immune-oncology treatment paradigms with immune checkpoint inhibitors. Immune checkpoint inhibitors have been approved in a broad array of tumour types, for example non-small cell lung cancer (NSCLC) and melanoma.
Redx is developing RXC004 for cancer therapy
The first patient in the Phase 1 first-in-man study was treated at the Christie Hospital, Manchester in February 2018.
RXC004 had received approval from the UK Medicines and Healthcare Products Regulatory Agency (MHRA) and the Ethics Review Committee for its Clinical Trial Application (CTA). The approval provides permission for Redx to initiate a Phase I/2a study of RXC004 in patients suffering from cancer.
In the Phase I component of the clinical programme, we will look to establish the optimal dose of RXC004 to use going forward. As a part of this, we will look at side effects of the drug as well as the pharmacokinetics of the drug in cancer patients. This phase of the study is planned to take place at leading cancer hospitals across the UK. In the Phase 2a part of the study we will look for potential efficacy of RXC004 in patients with pancreatic, biliary and gastric cancers.
Targeted therapy – Development of a predictive clinical response biomarker
Our scientists have identified specific genetic alterations in the RNF43 gene in types of gastric, pancreatic and biliary cancer which can be used to predict which patients are most likely to benefit from treatment with RXC004. In order to translate these finding to the clinic our scientists, working with diagnostic testing experts at NewGene Ltd, have developed a cutting edge clinical biomarker assay which will be used to guide patient selection during clinical trials. This test analyses small fragments of DNA released by tumour cells into the patient’s blood to detect cancer-specific RNF43 mutations which are predictive of drug response. This technology, which only requires a simple blood sample from patients, allows a precision medicine approach to be taken for our RXC004 clinical programme, benefiting patients and also improving the efficiency with which studies can be carried out. Initial data describing aspects of test development were recently presented at the ESMO congress 2017.
RXC004: Enhancing immuno-oncology drug response
Immune checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 antibodies, have revolutionised the treatment of cancer; but they don’t work in all patients. Many tumours are “cold” in that the tumour-killing immune cells are not present at the tumour site. Evidence is emerging that the WNT signalling pathway is relevant in this process such that inhibition of the pathway may make the tumours “hot” by facilitating tumour-killing immune cells into the tumour.
Our scientists have demonstrated the ability of RXC004 to enhance the immune system response to cancer in pre-clinical models. These data suggest RXC004 in combination with checkpoint inhibitors (such as anti-PD-1, anti-PD-L1 antibodies) may enhance the already impressive results observed for this exciting class of therapies by increasing the response rates and the duration of the response. In line with these data, Redx is exploring clinical opportunities for a RXC004 combination approach with anti-PD-1 and anti-PD-L1, with the ultimate aim of increasing patient response rates to immuno-oncology therapy.