GHENT, Belgium—Biotech company Ablynx has announced the establishment of its second research collaboration and licensing agreement with a subsidiary of Merck & Co., known as MSD outside of the United States and Canada. The companies will work together to discover and develop several predefined Nanobody candidates, including bi- and tri-specifics, that work on immune checkpoint modulators.
Per the terms of the agreement, Merck will pay Ablynx €20 million (approximately $27.5 million) upfront, as well as up to €10.7 million (approximately $14.7 million) in research funding during the three-year research term of the collaboration. Ablynx will also be eligible for tiered royalties as well as development, regulatory and commercial milestone payments if certain sales thresholds are achieved for a number of products—all told, said payments could total as much as €1.7 billion (approximately $2.3 billion). Merck will be responsible for developing, manufacturing and commercializing any products that result from this agreement.
“This collaboration positions Merck to expand our early oncology pipeline by developing innovative candidates based on Ablynx’s Nanobody technology,” Dr. Roger M. Perlmutter, president of Merck Research Laboratories, noted in a news release. “This second agreement builds beyond our ongoing collaboration in neuroscience and is consistent with Merck’s focus on developing candidates with the potential to make a meaningful difference in the lives of patients.”
Immune checkpoints are a range of pathways in the immune system that play a critical role in modulating the duration and extent of immune responses. Research has revealed that tumors can co-opt several different immune checkpoint pathways in order to escape anti-tumor immune responses. One way to think of these immune checkpoints, Ablynx CEO Edwin Moses explains, is like volume controls—they can affect the activity or volume of T cells when they’re fighting tumors.
“The idea of these checkpoint inhibitors is that by blocking them, as you can with antibodies and then potentially with Nanobodies, you can allow the T cells to become more active and turn up the volume and in that way attack and destroy cancer cells directly,” says Moses. “So instead of putting toxins into the body—poisonous chemotherapeutic agents—you’re actually just switching up or turning up the amplitude of a particular mechanism in these T cells, which allows them to fight the tumor cells more effectively.
“The particular application that we’re interested in with our technology is that there are many of these checkpoint inhibitor-type proteins, and there is a growing view that it will be by interacting with a combination of these different inhibitors that will make the most promising effects, and that’s the theory here,” he adds.
That’s where Ablynx’s technology comes in, as it makes it possible to link Nanobodies together to target multiple checkpoint inhibitors simultaneously. To date, Moses says, “We haven’t found a protein target against which we can’t generate Nanobodies,” as seen in their success with generating them against ion channels, which he notes “have proven quite intractable for antibodies in the past.” The Nanobodies also offer “the same levels of affinity and selectivity as you can get with typical, classical antibodies.”
With regards to the deal, Jan De Kerpel, an analyst with KBC Securities, noted that “Altogether, [Ablynx gets] some 30 million euros. This is not just Merck trying something. That was the first deal in 2012. The conclusion from that first project is that they are very pleased with how Ablynx works and they are now coming with a much bigger project.”
The first deal between Ablynx and Merck was signed in October 2012, when the companies pursued an ion channel target in neurology. Ablynx now has some 30 programs in its pipeline, with seven Nanobodies in clinical development. The company is also collaborating with other industry leaders such AbbVie, Boehringer Ingelheim, Eddingpharm and Novartis, in indications that include inflammation, Alzheimer’s disease and osteoporosis.