Back in 2015, Merck penned a $450 million R&D pact with little NGM Bio for a broad range of early-stage assets, and today Merck is extending this pact, although it’s also tidying up shop with the culling of one particular therapy that didn’t work out.
The original deal saw Merck pay NGM $94 million upfront and trade $106 million for a 15% stake in the company. In exchange, the pharma giant got the chance to collaborate on NGM's wide range of preclinical biologics, committing up to $250 million to bankroll development.
The terms of the agreement were particularly favorable for NGM, as the biotech remained in charge of all R&D and have the autonomy to kick off new discovery projects on Merck’s dime.
Once NGM establishes human proof of concept with an asset, its partner then gets the option of stepping in with a license deal covering global development and commercialization. And, before Merck starts a phase 3 on any such candidate, NGM gets to choose whether it wants to get milestone and royalty payments or co-fund development in return for up to 50% of revenue.
At the time, details were thin on the ground, with the collaboration's only initial disclosed asset being NP201, a preclinical candidate with potential in obesity, diabetes and nonalcoholic steatohepatitis (NASH).
Beyond that, the biotech has hinted at a pipeline of potential treatments for other cardiometabolic diseases, cancer, central nervous system disorders and kidney ailments, otherwise keeping details under wraps.
NGM's lead asset, the fatty liver treatment NGM282, which has had some positive data out in the past few years, is not part of the Merck deal and remains wholly owned by the biotech.
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Today, Merck has decided to extend its work for another two years, as allowed in its initial 2015 pact, and will go on until 2022.
During these additional two years, Merck: “Will continue to fund NGM’s research and development efforts at similar levels to the original collaboration terms and, in lieu of the $20 million extension fee payable to NGM, Merck will make additional payments totaling up to $20 million in support of NGM’s research and development activities during the two-year extension period in 2021 and 2022,” the pair said in a joint statement.
This comes several months after the Big Pharma also pressed go on an option to license NGM313, an investigational monoclonal antibody agonist of the β-Klotho/FGFR1c receptor complex in NASH. Merck plans to hustle the drug into a phase 2b trial to assess the effect of the drug on liver histology and glucose control in NASH patients with or without diabetes.
The stage of development of that drug, now renamed MK-3655, puts Merck behind a host of companies in the congested race to bring a treatment for NASH to market. Biotechs such as Genfit and Intercept Pharmaceuticals and big companies including Allergan and Gilead Sciences have drugs that are well ahead of MK-3655. The first phase 3 data on these frontrunners are being dropped this year.
Merck’s pitch for a come from behind success rests on the β-Klotho/FGFR1c receptor complex. MK-3655 acts as an agonist of the complex, binding to an epitope of β-Klotho to selectively activate FGFR1c. Notably, NGM thinks the pharmacokinetics of the drug lend themselves to a once-monthly dosing schedule.
But it’s not all good news, as the biotech also disclosed today that Merck has decided to walk away from its growth differentiation factor 15 (GDF15) receptor agonist program, which is being developed in obesity.
As part of the original collab, Merck signed up to an exclusive worldwide license to NGM’s GDF15 analogs, including NGM386 and NGM395, protein variants of GDF15.
Last year the pharma finished off the dosing of a Phase 1 multiple ascending dose clinical trial for NGM386, where it was found to be bit of a dud, given that it did not result in body weight loss when pitted against a dummy therapy. NGM was keen to point out this doesn’t affect the rest of its extended deal.
“We are pleased that Merck has extended its collaboration with NGM, ensuring that the important work we are doing together to discover and develop novel medicines across a range of therapeutic areas and high unmet needs will continue,” said David Woodhouse, CEO of NGM.
“The deep resources and scientific autonomy provided by this collaboration have enabled NGM to amplify the output of our powerful discovery engine and maximize our ambitious research and development goals. Together, we have progressed several potential first-in-class drug candidates into clinical development, including NGM313, now known as MK-3655, and we look forward to sustaining this productivity on behalf of patients.”
“Merck and NGM scientists have established a strong collaboration based on our mutual commitment to scientific excellence and the pursuit of novel meaningful therapeutics for the treatment of disease,” added. Joe Miletich, senior vice president, preclinical and early development, Merck Research Laboratories. “We look forward to continuing this productive collaboration.”
On the cutting of NGM386, which will be going back to NGM, Woodhouse added: “We continue to believe that the biology of GDF15 and its cognate receptor, GFRAL, can play an important role in human disease with potential effects on lipolysis and energy expenditure in metabolic disease states. Upon transition of the programs back to NGM, we will conduct an analysis of the clinical data and make a decision about whether to pursue further development of NGM386 and/or NGM395.”