Merck KGaA, Domain to Develop Adenosine Receptor Inhibitors for Immuno-Oncology
Merck KGaA will support research and gain global rights to Domain Therapeutics’ next generation of adenosine receptor inhibitors, through a collaboration designed to develop the compounds as novel immuno-oncology agents.
The value of the collaboration and licensing agreement was not disclosed.
Adenosine receptor antagonists are small molecules that are believed to slow tumor progression and improve the response to combination immunotherapies by inhibiting adenosine, a compound generated by cancer cells that inhibits antitumor responses by binding to T cells.
According to Domain, adenosine receptor antagonists have been shown previously to increase responses of standard immune checkpoint inhibitors, such as anti-programmed cell death protein-1 (PD1) or anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4), in preclinical animal models of cancers.
"We plan to explore the promise of adenosine receptor antagonists and develop novel compounds to potentially use in new combination immunotherapies for cancer,” Laszlo Radvanyi, svp and head of research in immuno-oncology at the biopharma business of Merck KGaA, said in a statement. “This new generation of adenosine receptor antagonists is an important addition to our immuno-oncology pipeline.”
Merck KGaA’s immuno-oncology pipeline is led by avelumab (also known as MSB0010718C), the immune checkpoint inhibitor being co-developed with Pfizer through an alliance launched in 2014 that could generate up to $2.85 billion for the German drug developer.
In November, Merck KGaA and Pfizer disclosed that the FDA accepted for Priority Review the Biologics License Application (BLA) of Merck entity EMD Serono for avelumab in metastatic Merkel cell carcinoma (MCC). The Priority Review status shortens FDA’s expected review time from 10 months to a goal of 6 months.
Avelumab is a fully human anti-programmed cell death ligand 1 (anti-PD-L1) immunoglobulin G1 (IgG1) monoclonal antibody. By inhibiting PD-L1 interactions, avelumab is thought to potentially enable the activation of T cells and the adaptive immune system. Avelumab may also help white blood cells such as natural killer (NK) cells find and attack tumors through a process called antibody-dependent cell-mediated cytotoxicity (ADCC).
Domain’s pipeline is led by CVXL-0107, a glutamate release inhibitor licensed to CleveXel Pharma in 2015. Last year, CleveXel launched a Phase IIa clinical trial assessing CVXL-0107 in patients with advanced Parkinson’s disease with motor fluctuations and dyskinesia.