Merck’s backing of NGM Bio yields NASH drug deal

Merck & Co’s four-year R&D collaboration with NGM Biopharmaceuticals has borne its first fruit, a license deal for a drug with potential to treat non-alcoholic steatohepatitis (NASH) and type 2 diabetes.

The mid-stage candidate, called NGM313, is an antibody targeting the beta-Klotho/FGFR1c receptor complex that Merck describes as a “once-monthly injectable insulin sensitizer” and could represent a whole new drug class for NASH and diabetes.

NASH has been ‘the next big thing’ for a few years now, with a slew of big pharma licensing deals for new treatments for the fatty liver disease, and racing with a handful of small biotech pioneers in the field to bring the first treatment to market.

It causes fatty build-up and fibrosis in the liver, sometimes leading to cirrhosis and the need for a liver transplant, and so far has no approved treatments with some analysts predicting the market for NASH drugs could go from a standing start to more than $20bn in just a few years.

Merck says NGM313 has potential in both NASH and diabetes – another big potential market – because both conditions are linked to insulin resistance. Around two-thirds of type 2 diabetics go on to develop NASH, and there are an estimated 17.5m people with both conditions in the US alone.

NGM Bio and Merck started working together in 2015, when the big pharma signed a $450m development deal with the biotech, including $200m in upfront fees and equity investment, to tap into its biologic drug discovery expertise. The lead NASH candidate at that time was NP 201, but seems to have been leapfrogged by NGM313, now renamed MK-3655.

Merck us paying $20m upfront for rights to NGM313 and follow-up compounds, with the deal following a phase 1b trial readout which showed that the antibody was able to reduce levels of fat in the liver and improve metabolic measures such as blood glucose control in obese NASH patients. A phase 2b trial is now on the way in NASH patients with or without diabetes.

NGM Bio has retained an option to co-develop the drug once phase 3 trials start, sharing costs and revenues, or alternatively could go down the conventional milestone and royalties route.

NGM313 works by activating FGFR1c signalling, a pathway that seems to play a key role in maintaining metabolic balance in the body.

A number of pharma companies are trying to develop drugs targeting this pathway, including FGF21, a circulating protein that in animals has been shown to promote anti-diabetic, lipid-lowering, and weight-reducing effects.

Teva recently licensed an FGF21 analogue to 89Bio called BIO89-100 (formerly TEV-47948) that is in phase 1 testing, while Akero Therapeutics has another analogue (AKR-001) licensed from Amgen that is also in early development.

NGM Bio reckons its approach with NGM313 is a better option as it bypasses regulatory mechanisms that can limit the effect of FGF21-targeting drugs.