Eli Lilly Bets Nearly $500M on Metabolic Disease Pact with Nimbus (Updated)

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Nimbus Therapeutics scored a $496 million payday through a collaboration and licensing deal with pharma giant Eli Lilly for potential therapeutics for metabolic diseases, the companies announced Tuesday.

The two companies will collaborate on the development of novel targeted therapies designed to activate a specific isoform of AMPK for the potential treatment of metabolic diseases. AMPK (AMP-activated protein kinase) is considered a high-value target in this indication due to its role in glucose, lipid metabolism, and inflammation. 

In partnership with Eli Lilly, Nimbus will identify isoform-selective, small molecule activators of AMPK heterotrimers.

On its website, Nimbus noted that activating AMPK in the liver, skeletal muscle, kidney, and other tissues has a “profound impact in metabolic disease models.” Nimbus first announced it was delving into AMPK two years ago. The company noted that AMPK is a heterotrimer comprised of α, β and γ subunits, and there are two known isoforms of β. 

When Nimbus unveiled its intentions to explore this approach to treating disease, Nimbus said its drug development expertise provided it with a new understanding of the AMPK subunit.

These understandings enabled it to identify activators that are selective for β2 subtype of the AMPK protein, and Nimbus believes it can improve glucose and lipid homeostasis while mitigating safety concerns.

While its programs remain preclinical, Eli Lilly is intrigued enough to initiate collaboration in this space. Ruth Gimeno, senior vice president of diabetes research and clinical investigation at Eli Lilly, said therapies that target AMPK can address a critical need in the metabolic disease space. 

Targeting metabolic-induced diseases, such as obesity-related diseases, diabetes or nonalcoholic steatohepatitis with AMPK activation has had some challenges. Nimbus Therapeutics believes it has overcome these issues. 

With its computational drug discovery engine, the company is uniquely positioned to develop isoform-selective small molecule AMPK activators applicable in a broad range of metabolic diseases, a space where Eli Lilly is well versed. 

Peter Tummino, Nimbus Therapeutics’ chief scientific officer, noted the company has established a successful track record in developing highly-selective small molecules against hard-to-interrogate targets. 

“Nimbus has established a successful track record in developing and progressing highly-selective small molecules to the clinic against hard-to-interrogate targets, which is a demonstration of the power of our computational and structural approach to drug discovery,” Tummino said in a statement.

Nimbus Chief Executive Officer Jeb Keiper told BioSpace AMPK has been known for a long time and is a valid target. It’s their understanding of this target that Eli Lilly found compelling for potential therapeutics for metabolic diseases, he said. Keiper noted there are numerous clinical possibilities for AMPK-targeted therapeutics but currently the companies are keeping the details of the collaboration under wraps.

“It was our understanding of AMPK that brought them to us. They found a kindred spirit,” he said.

Later this year, Nimbus anticipates data from its mid-stage psoriasis program. Keiper called it an exciting program, particularly given the FDA’s September approval of Bristol Myers Squibb’s Sotyktu. He said BMS’ oral treatment is a “good molecule” but believes that Nimbus’ TYK2 asset is a “great molecule.”

For Nimbus, the partnership comes about a month after the company received a $125 million investment backed by Pfizer Ventures, the investment arm of the pharma giant, as well as Bain Capital, Ra Capital and others. At the time, Keiper told BioSpace the investment will support the development of its TYK2 inhibitor, which is in Phase IIb studies for plaque psoriasis.

A portion of the funds will also be used to assess the TYK2 asset in inflammatory bowel disease and lupus, two indications where significant inhibition of TYK2 can be critical. 

Under the terms of the agreement, Nimbus is eligible to receive up to $496 million, which will cover research expenses and developmental milestones. The company will also be eligible for potential royalties on commercial sales. 

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