A look at adenosine

DARMSTADT, Germany—Merck KGaA, known as EMD Serono in the Unites States and Canada, launched a collaboration and licensing agreement this week with a European neighbor—Strasbourg, France-based Domain Therapeutics. The companies will be investigating the potential of adenosine inhibition for developing novel immuno-oncology products.

Merck will support research activities in developing and testing agents that target key adenosine receptors, and will gain worldwide rights to Domain Therapeutics' next generation of adenosine receptor inhibitors. Per the terms of the deal, Domain stands to receive more than 240 million euros (approximately $258 million) in milestones, in addition to undisclosed royalties.

“With its growing portfolio of immuno-oncology agents, Merck KGaA, Darmstadt, Germany, is the ideal partner to develop our adenosine programs,” Pascal Neuville, CEO of Domain Therapeutics, remarked in a press release. “As a strong collaborator with a leading investigational checkpoint inhibitor, we are confident that through Merck KGaA, Darmstadt, Germany, our programs will progress rapidly.”

Adenosine receptor antagonists are small molecules. These agents are believed to slow tumor progression as well as improve responses to combination immunotherapies by inhibiting adenosine, a compound produced by cancer cells that suppresses anti-tumor responses by binding to T cells.

As Domain Therapeutics notes on its website, “Adenosine is a purine nucleoside which is produced under metabolic stress conditions to limit inflammation and immune responses. Many cancers are known to produce and sustain high concentrations of adenosine that, once in the tumor microenvironment, will exert various immunomodulatory effects via adenosine receptors (A1, A2A, A2B and A3) expressed on various immune cells.

One of the consequences of this adenosine receptor activation will be a reduced ability of the immune system to attack the tumor. Indeed, cancer-produced adenosine will act as a protective shield preventing the natural immune response. Adenosine receptor antagonists are small molecules that can block this anti-immune response. Such agents have been shown previously to increase responses of standard immune checkpoint inhibitors (such as anti-PD1 or anti-CTLA4) in preclinical animal models of cancers.”

"This new generation of adenosine receptor antagonists are an important addition to our immuno-oncology pipeline,” Laszlo Radvanyi, senior vice president and head of Research in Immuno-Oncology at the biopharma business of Merck, commented regarding the deal. “We plan to explore the promise of adenosine receptor antagonists and develop novel compounds to potentially use in new combination immunotherapies for cancer.”

This is the second licensing agreement with a large pharma company signed by Domain Therapeutics in as many months. In mid-December, the company reported that it had struck a deal for its GPCR BioSens-All technology with Alkermes. Under the terms of the agreement, Alkermes gains the ability to use BioSens-All as part of its drug discovery work. No financial details for the agreement were made available.

Domain Therapeutics' BioSens-All can monitor multiple signaling pathways in living cells in parallel assays and in a homogeneous format, allowing users to identify links between drug candidates' signaling signatures and their biological effects. In addition, Domain reports that BioSens-All “generates and analyzes comprehensive signaling data on GPCR drug candidates, potentially accelerating the discovery and development of biased drugs.”