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Amgen look to develop DNA-encoded libraries to increase new drug design innovation

Amgen, after the acquisition of Nuevolution and its world-class DNA-encoded library (DEL) platform, Amgen has a team of expert’s adept at making and screening billions to trillions of compounds to find promising leads. The huge increase in screening power will fuel Amgen’s search for bispecific small molecules that use the body’s cellular machinery to tackle tough drug targets.

For Amgen’s Research organization, DEL could be the key to advancing the next big idea in small molecule drug discovery—bispecific compounds that can spur proteins to eliminate hard-to-drug targets. To pursue this vision aggressively, Amgen acquired Nuevolution, a DEL pioneer with deep experience and superior technology. The Denmark-based team of about 45 scientists and professionals will now be known as Amgen Research Copenhagen (ARC).

Before buying the company, Amgen and Nuevolution collaborated on research that yielded promising leads against a challenging cancer target. “Given the power of DNA-encoded libraries, we realized we should be using them in all of our small molecule drug discovery projects,” said Ray Deshaies, senior vice president of Global Research.

“We surveyed the whole landscape and concluded that Nuevolution was clearly the best company. In working with them, we learned that world leadership in this realm is not about technology alone, it’s about the people. Multiple companies have DEL technology, and we could have chosen to do multi-target deals or technology transfers. But that wouldn’t have given Amgen the most valuable resource—the passionate and experienced team of scientists in Copenhagen.”

“Our approach has really proven its value over the last 18 years in multiple partnerships, including the successful partnership with Amgen,” said Alex Gouliaev, former CEO at Nuevolution, now vice president, Amgen Research Copenhagen. “We believe Amgen represents the perfect home due to its innovative approach to discovery and a cultural match that offers a good fit for our team.”

Screening technology plays a major role in small molecule drug discovery, where the general goal is to find “hits”—compounds that interact with drug targets. In conventional high-throughput screening systems, compounds are stored, tracked, and tested in microplates with 384 or 1536 wells per plate. Robots transfer compounds from storage plates to test plates that hold a drug target, and various technologies are used to read the strength of the resulting interactions and identify hits that chemists can then optimize to create investigational drugs.

A conventional library can hold several million distinct compounds, but time and cost constraints make it difficult to go beyond that scale. In DEL technology, those constraints don’t apply. Each individual compound is linked to a unique strand of DNA, which functions like a barcode to identify that compound. The tagging allows diverse compounds to be stored and tested together, so plates are no longer needed to differentiate compounds on a spatial grid. Given the physical size of chemical compounds—quadrillions of drug-like molecules can fit in a single drop of liquid—even the largest libraries can be stored in a few milliliters of liquid.

DEL technology has some limits. It can identify compounds that bind to a target, but it’s not designed to provide functional data, such as how much a compound inhibits or increases a target’s biological activity. For those insights, we still need the versatility of conventional high-throughput screening technology, and the scientists who design and execute these functional assays will continue to play a big role in drug discovery at Amgen.

Amgen has a strong record of acquiring smaller research companies and weaving their technology and talent into the R&D organization, from the fully human monoclonal antibodies that originated at Amgen Research Burnaby (formerly Abgenix) to the BiTE® molecules pioneered at Amgen Research Munich (formerly Micromet). Deshaies said he was equally confident that Amgen Research Copenhagen would deliver a steady stream of promising leads, which our chemists, including those at ARC, can transform into medicines patients are waiting for.

“There’s an almost limitless number of potential combinations we can envision for induced-proximity inactivators. Our only limit will be our own creativity.”

Source: Science Business

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