When Nimbus Therapeutics set up shop in 2009, it had to convince the industry—including its founding chief scientific officer—that virtual drug discovery could be a viable approach.
"At the time, computational methods and structural methods existed," Jeb Keiper, who joined Nimbus as chief business officer in 2014, told FierceBiotech. "Computational methods especially were adjunct tools people used to augment what they were doing, but rarely led discovery."
A well-known piece of Nimbus’ story was Gilead Sciences' acquisition of its acetyl-CoA carboxylase inhibitor in 2016 for $400 million upfront, with the promise of many more millions in milestones.
"It really built the basis of structure-based drug design to drive development," said Keiper, now Nimbus’ CEO. Now, with its Tyk2 inhibitor in the clinic and a second asset close behind, the company is ready to prove that it’s "not just a one-hit wonder."
Nimbus is unveiling four new programs it's been working on, which could lead to treatments for metabolic disorders, cancer and autoimmune diseases. These include CTPS1, an enzyme that plays a role in immune activation, and AMPKβ2, which regulates metabolic homeostasis in many tissues. The other two, WRN and Cbl-b, are both immuno-oncology targets. All four are difficult to drug.
"We like to pick targets with really well-known biology. We’re not taking a huge biological risk: if you’re able to successfully drug the target, you will have an effect," Keiper said.
Nimbus will spend the next year pushing those programs forward with the goal of landing on development candidates. It’s also working on an IND for its HPK1 inhibitor as well as taking its Tyk2 program into a phase 2b study in 2021, Keiper said.
It’s doing all this with a different team than the one that steered Nimbus toward the Gilead deal. Keiper, who joined Nimbus from GlaxoSmithKline in 2014, became its chief financial officer in 2017 and CEO in 2018. Chief Scientific Officer Peter Tummino, Ph.D., had a similar path, landing at Nimbus after leading discovery at Johnson & Johnson’s Janssen unit.
"To answer another question people ask—was it all about the magic of the first team—the first team for most companies is magical" Keiper said. "It’s not that first team now, but there’s something about Nimbus that had a bit of staying power. We have a culture, or approach, or mission that has allowed us to repeat success with new people that have come in."
Part of that magic is focus, an oft-repeated advantage that smaller biotech has over Big Pharma.
"Most of my career has been in large organizations and I enjoyed much of it,” said Tummino, who’s put in time at AstraZeneca, Millennium Pharmaceuticals, GSK and Janssen.
“My attraction to Nimbus is more on the side of drug discovery veterans. People want to get away from maybe a bigger system to one where the focus is discovery," Tummino added. Since he joined Nimbus early last year, he’s hired people from pharma and biotech who are seeking that focus.
"Other organizations that are larger—or that get larger—have more and more ancillary things. We don’t have that," he said. As Tummino says, that’s another ingredient of the "secret sauce."
A virtual company, Nimbus has grown slowly and deliberately over the years.
"When I joined, I was lucky No. 13," Keiper said. "We are still less than 40, 11 years later … We do a lot of our work through academic collaborations and contract research groups we have developed long-standing relationships with.”
Because it has no lab-based personnel, it's weathered the effects of the COVID-19 pandemic "quite well," Keiper said.
The pandemic and social distancing rules have had a small effect on the company’s discovery work, Tummino said. But it did hit pause on a phase 1a/b study of its lead program in the U.S. That study, in psoriasis patients, is now back up and running.
Keiper is part of a group of biotech CEOs trying to figure out what a post-pandemic world might look like, including how to keep their employees safe, move programs forward and finance companies.
"It is a group that’s all trying to help each other, and it’s not feeling at all competitive," he said.
"A second fundamental shift is how to use technology and whether we need to be in the office all the time," he added. Because it already works remotely with its academic and CRO partners, Keiper thinks Nimbus would adapt easily to a more flexible model. That said, "human interaction is really important."
"It'll change the dynamic, but I do think that in-person contact will slowly return. Just the pendulum will have moved a bit," he said.