Oxford, UK, 20th August 2018 – Celleron Therapeutics, the UK-based company developing personalised medicine for cancer patients, has today announced the initiation and first patient enrolment of its clinical study that will evaluate the effect of a novel combination therapy approach for colorectal cancer.
The Medicines and Healthcare products Regulatory Agency (MHRA) granted Celleron Therapeutics Clinical Trial Authorisation to conduct a Phase Ib/II clinical trial with CXD101, a highly potent class 1 histone deacetylase inhibitor, in combination with an immune oncology (IO) agent, nivolumab. Celleron appointed Syneos Health as the CRO to support the trial which is investigating the clinical activity of CXD101 in combination with nivolumab, measuring the anti-tumour effect on a type of colorectal cancer (microsatellite stable) which typically does not respond to IO agents alone. The clinical trial strategy rests on compelling pre-clinical results which provide novel insights into how CXD101 and IO drugs work together to re-engage recognition of tumours by the immune system. The trial will also allow exploration of a range of new biomarkers to help select those patients likely to benefit most from combination therapy.
Professor Nick La Thangue, Founder and Chief Executive of Celleron Therapeutics, and Professor of Cancer Biology in the Department of Oncology at Oxford University, commented:
“CXD101 is a very interesting drug with great clinical potential. The new trial is a major step forward in understanding its therapeutic application. We have observed striking effects on late stage cancer patients in previous studies. This trial exploits our deep scientific understanding of how CXD101 exerts anti-cancer activity, which underpins the hypothesis being tested in the novel combination approach.”
Professor David Kerr CBE, Founder and Chief Medical Officer, Celleron Therapeutics and Professor of Cancer Medicine, University of Oxford commented:
“There is a very significant unmet need for novel therapy for patients with advanced colorectal cancer. As colorectal tumours progress, they find a variety of ways to avoid recognition and destruction by the immune system, increasing their potential to grow and spread. We have discovered that CXD101 can reverse this process of “immune silencing” making it, potentially, an ideal partner for existing immune oncology agents.”
Professor Mark Middleton, Consultant Medical Oncologist and Professor of Experimental Cancer Medicine at the University of Oxford commented:
“We are delighted to be part of this important trial, which has the potential to bring immunotherapy to patients who hitherto have not benefitted from this approach. It is also very satisfying to see CXD101, a drug first given to patients at the Experimental Cancer Medicine Centre here in Oxford, developed further in the clinic based upon scientific insights made here in the city.”
NOTES
Celleron Therapeutics is advancing a clinical and pre-clinical pipeline of precision therapies for different cancer indications. The company has built a proprietary platform around epigenetic control and immune modulation, providing its drugs with a two-pronged attack
on cancer. Celleron’s approach seeks to align the right drug with the right patient enabling a personalised approach to cancer therapy. The company is a spin-out from Oxford University and located on the Oxford Science Park. Celleron has a global license partnership with Astra Zeneca and is initiating new trials in China through its Chinese partner Nuance. The company secured investment in 2016 from a consortium of South Korean investors. For more information see www.cellerontherapeutics.com
CXD101 is Celleron Therapeutics’ next generation epigenetic immune-regulator representing a class of drug that kills cancer cells by blocking certain vital functions involved in gene expression and reactivates the patient’s immune system so that cancer cells can no longer evade immune recognition.
Colorectal cancer is the second most common tumour type in women, and the third most common in men, globally. The approximate 5-year survival rate for colorectal cancer patients in the United States (all stages included) is 65% (SEER, 2016). Survival is inversely related to stage: approximate 5-year survival rates are 95% for patients with stage I disease, 60% for those with Stage III disease, and 10% for those with Stage IV (metastatic) disease.
A subset of colorectal cancers is characterized with deficient DNA mismatch repair (dMMR or microsatellite instability, MSI). Detection of MSI has become important for treatment for metastatic colorectal cancers, as those with MSI-H expression respond favourably to immune checkpoint inhibition, a type of biologic therapy. These tumours tend to have a high mutational burden and expression of checkpoint proteins, including programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), which interfere with the body’s anti-tumour T-cell response. By disabling these proteins, checkpoint inhibitors (such as pembrolizumab and nivolumab) allow the immune system to function properly, and T-cells to kill tumour cells. Where patients have a normal Mismatch Repair proficient expression, the microsatellite phenotype is stable (MSS), antigen presentation is much decreased and the tumour is thus resistant to checkpoint inhibition.