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This next generation A2A antagonist was originally discovered by a Vernalis in-house research programme. In June 2004, Vernalis and Biogen Idec entered into an agreement whereby Biogen Idec would develop molecules within the adenosine A2A receptor antagonist programme in exchange for milestone payments and subsequent royalties on future sales. Vernalis successfully regained the programme in April 2011 and partnered with Corvus in February 2015.


A2A receptors have been identified on a range of immune and inflammatory cell types, including macrophages, dendritic cells, myeloid-derived suppressor cells, T cells and NK cells. The binding of adenosine to A2A receptors suppresses the effector functions of these immune cells.  Antagonism of A2A signalling has been demonstrated to increase anti-tumour immunity predominantly through the enhancement of CD8+ T cell and NK cell dependent cytotoxicity.


Pre-clinical studies


Pre-clinical studies were completed by Biogen Idec in a partnership established with Vernalis in June 2004. Vernalis successfully regained the rights to the programme in April 2011. Pre-clinical studies were completed in readiness for Phase I.


Clinical studies


Phase I SAD/ MAD study was successfully completed in May 2012. A receptor occupancy study was initiated in August 2012, with positive results reported in December 2012.

Data from these studies was presented at the World Congress of Neurology meeting in August 2013.


With Phase I SAD/ MAD and receptor occupancy studies successfully completed, Vernalis initiated a Phase Ib/II proof-of-concept study in 2013. Positive results of this study were announced in April 2014 showing V81444 achieved significant improvement in the number of correct scores in PERMP measure (P=0.9) compared to placebo. Although not statistically significant, V81444 also showed improvements in both ADHD Rating Scale and CGI. There were no drug related serious adverse events and no other new or significant safety findings.

In February 2015, the Company licensed exclusive, worldwide rights in its adenosine receptor antagonist (A2A) programme for use in all therapeutic applications to Corvus, a US-based biotechnology company. At the time, the name of the company was not disclosed and nor was the initial therapeutic focus. Corvus is a development-stage company listed on NASDAQ (CRVS). Corvus brings a wealth of clinical and commercial expertise and is looking to develop CPI-444 for immuno-oncology. Corvus is currently enrolling up to 50 patients with renal cell carcinoma (RCC) in an amended phase 1/1b clinical trial evaluating CPI-444 administered alone or in combination with Genentech’s Tecentriq® (atezolizumab), an anti-PD-L1 antibody. Another study is currently enrolling up to 60 patients with non-small cell lung cancer (NSCLC) in a phase 1b/2 clinical trial being conducted by Genentech. The study is evaluating CPI-444 and Tecentriq® in patients who have failed no more than two prior regimens.

2021-01-19T12:17:17+00:00January 19th, 2021|