Orionis Biosciences Inc. has begun a four-year collaboration with Novartis AG to discover and design small-molecule therapeutics such as protein degraders that target several therapeutic areas, including cancer.

The agreement’s terms include research funding a convertible note investment, royalties and potential clinical milestones. No specific financial details were released.

Orionis, which has been in stealth since 2015, develops a class of allosterically acting small molecules that are designed to reprogram intracellular proteins to modulate disease target proteins. The form and function of the intracellular proteins are reprogrammed with the goal of modulating disease target proteins.

The trans-Atlantic company has its headquarters and a research site in Waltham, Mass., and an upgrading site in Ghent, Belgium. It began fundraising in 2015 with an undisclosed series A and a series B, then started operations in 2016. During that time, the company entertained potential partners who were interested, including Novartis.

Nikolai Kley, president and CEO, Orionis

Nikolai Kley, one of the co-founders, has spent more than 25 years discovering and developing drugs, with time at Forma Therapeutics Inc., of Watertown, Mass., GPC Biotech AG, Genome Therapeutics Corp. and the Bristol-Myers Squibb Co.’s Pharmaceutical Research Institute. He has also been a research professor of molecular biology at Princeton University, completed his postdoctoral fellowship at the Harvard Medical School, and has a doctorate from the Max Planck Institute-Maximilians-University in Munich.

Jan Tavernier, another Orionis co-founder, is also the founder and director of the Cytokine Receptor Laboratory at VIB-Ghent University in Belgium. While he has made studying the structure and function of human cytokines his life’s work, he spent time at Biogen Inc. and Roche Holding AG until he returned to the university in 1996 and has been there since.

Kley, who referred to Tavernier as a “longtime collaborator,” kept the company under wraps for the past five years so it could explore large-scale molecular technology to create a drug discovery platform by creating actionable datasets, the specialty of Orionis’ chief data scientist, Riccardo Sabatini, and also to create and hone a solid intellectual property portfolio.

“We wanted to take one step at a time,” Kley told BioWorld. “We didn’t need to go out and be more public in that sense. We had connections in the pharma and investor world.”

Ultimately, Kley and Tavernier wanted to develop molecules with minimal off-target effects. To do that, they had to bring rational design to a different level to actually see which targets it interacts with.

“We knew we had the technology to do it,” Kley said. “We had tested it in many different ways and modalities and ultimately we needed to scale it.”

The company’s technology and pipeline include A-Kine biologics and Allo-Glue small-molecule platforms to reprogram disease states. A-Kine is designed to harness the function of cytokines that regulate the immune system. The biologics platform integrates an assembly of modular, biomolecular building blocks into agents with conditional effector functions and cell-target selectivity with applications in cancer and other diseases. Allo-Glue platform enables high-throughput drug ligand screen and mapping of small-molecule drug-protein interactions in living cells to module receptor protein with other proteins. The small molecules are designed as molecular glues to form protein complexes resulting in target modulation, including the inhibition and degradation of disease-relevant proteins.

Orionis, in anticipation of the Novartis deal, continues to grow and advance its pipeline. The company has 34 employees, Kley said, a number that occasionally fluctuates. The company name is derived from the constellation that contains the stars Betelgeuse and Rigel. Kley said the name reflects the company’s “constellation of diverse skill sets.”

“We embrace complexity in what we do,” Kley said.”

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