Fierce Next Gen: Amgen avoids 'low-hanging fruit' in quest to tackle undruggable targets

Where there’s challenge lies opportunity, and Amgen is not letting the idea of undruggable disease targets stop it.

The company is taking the challenge head-on, investing in multispecific medicines and its induced proximity platform (IPP), which mobilizes natural biological mechanisms to bring two things together in hopes of creating new therapies.

“From a strategic point of view, I think that we have differentiated ourselves from much of this field,” Ryan Potts, Ph.D., executive director and head of Amgen’s IPP, said during the Fierce Next Gen event. “I think much of the target protein degradation space has taken a sort of the low-hanging fruit approach.”

By leveraging the natural protein degradation machinery in a cell, the IPP sidesteps grappling with the difficult-to-drug target on its own.

Because IPP is a key piece of developing multispecific medicines, Amgen is investing heavily in the platform, with the current focus on expanding its team, Potts said. The company is also actively seeking new partnerships related to the science, with Potts citing a recent $75 million upfront research collaboration with Arrakis Therapeutics as an example. The partnership, announced in January, aims to create targeted RNA degrader therapeutics with Amgen's IPP and Arrakis' RNA drug discovery platform.

"It's such a fun time to be in this field," Potts said of the potential partnerships out there. He wouldn't say what exactly Amgen is looking for, but "there are so many creative ways that we can harness induced proximity to achieve desired effects that wouldn't have been dreamed of five or 10 years ago."

While other companies are testing out the new modality and working to get proof of concept, Amgen has decided not to apply the science to every possible target, Potts explained. Instead, target protein degradation and induced proximity modalities are being deployed when the target, disease biology, drug ability of the protein and pharmacology all align.

Pfizer's leukemia therapy Mylotarg and Bristol Myers Squibb's blockbuster multiple myeloma med Revlimid are examples of approved multispecific drugs. As for a two-pronged attack, Amgen's blinatumomab, sold under brand name Blincyto, is a bi-specific drug targeting acute lymphoblastic leukemia.

Most of Amgen’s early-stage pipeline is made up of molecules directed at two or more targets. Examples include the phase 1 small-cell lung cancer and prostate cancer candidate tartalamab or multiple myeloma therapy pavurutamab, also in phase 1 development.

Given that Amgen is trying to break new ground with the so-called next wave of drug development, the company has rolled out a short animated video directed at the public that explains multispecific medicines. The company has also put together a five-part serial podcast in collaboration with The Scientist's Labtalk called "Undruggable."

"We felt that was important to explain our next wave of drug discovery and what the future may hold for medicines in this area," Potts said. The video is designed to be "very digestible and approachable" for any audience.