Nimbus picks 4 preclinical targets for the next chapter of its pioneering computational drug discovery work
Big name partnerships were critical for Nimbus Therapeutics’ first decade. With a head-turning $1.2 billion — $600 million of which were paid within months — deal from Gilead and a returning customer in Celgene, the biotech emerged as a prolific pioneer of computational chemistry and structure-based drug discovery while the industry went through a seismic shift in its thinking of the role that algorithms play in engineering new therapies.
As the second of the initial batch of programs enter the clinic, Nimbus is unveiling the headings that will define what it calls its second chapter.
Their team of 20-plus scientists has identified four new targets — AMPKβ2, CTPS1, Cbl-b and WRN — which they have been probing with academic collaborators and experts at Schrödinger. And this time around, they plan to keep all four in-house for at least a little longer, focusing on recruiting new staffers and friendly researchers rather than buyers.
At the same time, Nimbus has dropped its STING efforts after a slew of biotechs reached for it and came up empty.
“One of the compliments we’ve been paid by our peers in the broader drug discovery and development community has been in our ability to select really interesting targets that are quite compelling,” Jeb Keiper — the former BD chief who took over as CEO from Don Nicholson less than two years ago — told Endpoints News. “We care a lot about being able to do that.”
Aside from the usual suspects in target selection, such as genetic validation and medical need, Nimbus zoomed into ones for which a selective, structure-based approach is particularly helpful, CSO Peter Tummino said.
In AMPK (AMP-activated protein kinase), that means finding activators selective for the β2 subunit, which could translate into a better safety profile as metabolic drugs. Similarly, the challenge in CTP is to find compounds selective for the S-1 isoform. Cbl-b (Cbl proto-oncogene B) is an E3 ubiquitin ligase — a natural protein degrader — that’s garnered attention from both small companies like Nurix and big ones like Roche. Finally, the goal with WRN (Werner syndrome ATP-dependent helicase) is to come up with a new treatment option for tumors vulnerable to disruptions in DNA repair.
“What isn’t new is we’re looking for small molecule agents,” he said.
Although these are targets of high interest, he added, much is still unknown about their structures, and Nimbus is working with leading biologists to elucidate them with techniques like cryo-EM and crystallography.
These are “not things you can simply outsource to contract research groups,” Keiper added. “You really are doing fundamental academic discovery work.” That’s the kind of special sauce — mixing dyed in the wool drug discovery veterans with computational experts — that Nimbus believes will keep it going for many years more.