Novo Nordisk taps start-up for small-molecule weight-loss collaboration

Wegovy maker Novo Nordisk has hired the start-up Deep Apple Therapeutics to develop small molecules as its next weight-loss play.

Novo will pay Deep Apple up to $812 million, including an unspecified up-front amount and milestone payments, to identify and begin developing drug candidates that go after a new, nonincretin G protein–coupled receptor, or GPCR. Deep Apple will be responsible for discovery and early-stage research, and Novo will oversee human testing and commercial efforts.

Deep Apple founding CEO Spiros Liras tells C&EN that the contract involves up to two compounds that may be pursued for development against “a single target that is driving the focus of the collaboration.”

“Broadly, the target is in the cardiovascular, metabolic disease, obesity area,” Liras says.

Deep Apple was founded about 2.5 years ago and publicly launched at the end of 2023; the start-up is based on work by Stanford University structural biologist Georgios Skiniotis and University of California, San Francisco, computational biologists Brian Shoichet and John Irwin. The firm’s scientists use ensemble cryogenic electron microscopy (cryo-EM) to find binding pockets on GPCRs and then use virtual screening to identify drug candidates that would best fit those pockets.

In the short time since its founding, Deep Apple has expanded its pipeline to seven programs that span potential treatments for inflammatory and immunological disorders, weight loss, and endocrine disease, among other areas.

“Because of this progress, we were quite confident in demonstrating the efficacy of this platform, and we were engaged in conversations with multiple partners,” Liras says. “Then came the Novo partnership. For us, it was quite attractive because obviously, they are the world leader in cardiovascular disease and obesity. They know the patient. They have incredible development and commercialization resources and, of course, a depth of biology that is matched by few organizations.”

Liras says the collaboration came together in about 3 months. For Novo, it’s a way to expand its reach in the highly competitive weight-loss space, where it’s been lagging behind competitor Eli Lilly and Company. Both companies market GPCR-targeting drugs called glucagon-like peptide 1 (GLP-1) receptor agonists as treatments for weight loss and diabetes, but Lilly has recently pulled ahead. Novo ousted its CEO only last month over concerns that the company had lost its first-mover advantage.

Novo also recently partnered with another biotech start-up, Septerna, to develop small molecules for weight loss and metabolic disorders. That collaboration is worth up to $2.2 billion between up-front and milestone payments.

Liras says the Novo partnership is a way for Deep Apple to expand its commercial reach beyond what would be possible as a small biotech firm. In the meantime, Deep Apple will continue developing its technology with the goal of expanding past GPCRs.

“While our approach right now is focused on G protein–coupled receptors, our technology is broadly applicable to many [other] targets, including transporters and channels—targets for which there is richness in biology but adversity in drug discovery,” he says. “We see an exceptional breadth of opportunity, and we will be guided by the strength of biology to target solutions against multiple disease areas going forward.”