Harbour posts preclinical data on would-be rival to Eli Lilly’s $1.9B obesity bet

The preclinical studies looked at LET003, an ACVR2A/2B-targeting monoclonal antibody developed using Harbour’s Hu-mAtrIx platform. Bimagrumab, which Lilly acquired in its $1.9 billion Versanis takeover in 2023, binds the same receptors and is being studied in combination with GLP-1 drugs. By blocking activin and myostatin signaling, bimagrumab could enhance fat loss while preserving muscle mass. 

With bimagrumab showing promise in a clinical trial, Harbour pursued the molecular optimization and functional enhancement of LET003 through structural biology and its Hu-mAtrIx platform. The company uses Hu-mAtrIx to prioritize candidates, support affinity maturation and identify risks such as instability.

Applied to LET003, the platform has delivered a candidate that Harbour said achieved significantly slower blood clearance than comparator molecules in mouse and monkey models. The data suggest the drug candidate may match the efficacy of rival molecules while supporting longer dosing intervals or lower doses.

Harbour shared data comparing weekly subcutaneous injections of LET003 and an unnamed competitor molecule. After three weeks, mice maintained on a normal diet had a 13.5% increase in lean mass on LET003 compared with the comparator molecule. Body weight increased 11.1% on LET003 and 9.3% on the rival molecule. Harbour framed the data as evidence that LET003 is better at promoting lean mass.

The biotech also presented data on the effect of co-administering LET003 with semaglutide, the GLP-1 receptor agonist that Novo Nordisk sells as Ozempic and Wegovy. In an obesity model using wild-type mice, the LET003 combination decreased fat mass by 34.7% compared with semaglutide monotherapy. Lean mass increased by 5.7% on the combination compared with semaglutide monotherapy.

In a high-fat diet-induced obesity mouse model, the fat-to-body weight ratio in the combination group fell by 6.0% compared with semaglutide monotherapy. The lean mass-to-body weight ratio in the LET003 combination group increased by 5.3% compared with semaglutide alone.

Harbour’s Dutch roots

Harbour plans to advance LET003 into clinical development on the strength of the data. The progress of the molecule illustrates how the biotech has built on the capabilities it acquired when it bought Harbour Antibodies in 2016. Harbour Antibodies was a Dutch biotech with two transgenic mouse platforms for discovering fully human antibodies.

After the acquisition, Harbour had a headquarters in Shanghai, business operations in Massachusetts and an antibody platform site in the Netherlands. The biotech has retained a presence in the Netherlands as it has developed its antibody discovery capabilities, including by building Hu-mAtrIx on its mouse platform.