2.4 When is a deal not a deal. Sanofi makes a big bet in AATD

Sanofi’s partial acquisition of Inhibrx recalls earlier transactions, such as Pfizer’s acquisition of BioHaven or, to go back even further, Johnson & Johnson’s acquisition of Actelion, in which assets deemed surplus to the acquirer’s needs were spun out into new entities.

In the case of Inhibrx, Sanofi wanted just one programme, INBRX-101, its investigational drug for alpha1-anti-trypsin deficiency (AATD), a genetic condition arising from a point mutation in the SERPINA1 gene, which encodes alpha-1 antitrypsin. The protein is produced in and exported from the liver and plays a key protective rule in the lungs. 

Sanofi is paying $1.7 billion upfront and could pay another $296 million in connection with the programme’s progress. The rest of Inhibrx’s assets, which include several clinical-stage oncology programmes, will be spun out into a new company, Inhibrx Biosciences. This will have start-up capital of $200 million, and Sanofi will hold an 8% stake.

The dynamics that influence these asset-selective deals differ all the time – and reflect the specific strategies and needs of the acquirer and its target. Sanofi has, through its Genzyme acquisition, a large footprint in the rare disease market. Unlike Pompe disease, where its attempted deal with Maze Therapeutics fell foul of the Federal Trade Commission, it is unlikely to run into any problems with its Inhibrx transaction, given the depth of competition in the area. Several plasma-derived replacement products are already on the market, but they are sub-optimal as it is difficult to maintain appropriate levels of AAT. INBRX-101 is also designed to address the lack of functional AAT, but the protein is fused to the Fc portion of an antibody to increase the time it remains in circulation. 

A head-to-head phase 2 trial is underway, which will compare the effects of INBRX-101 with those of a plasma-derived product in maintaining functional levels of the protein. AAT protects the lungs from excessive neutrophil elastase activity. The latter enzyme protects against environmental irritants and infectious agents, but it causes severe lung damage if unchecked. People living with AATD can also develop liver disease, as the mutant, misfolded form of AAT cannot be exported from the organ but instead polymerizes and forms pathogenic aggregates that lead to inflammation, fibrosis, cirrhosis and potentially cancer. 

Several other approaches to managing the condition are also in development – these include short interfering RNAs and RNA editors, designed to suppress production of mutant AAT, as well as neutrophil elastase inhibitors, designed to minimize damage to the lungs. A number of gene therapy firms aim to promote localized production of AAT in the lungs by producing modified gene therapy vectors for inhalation. But Sanofi is betting that the relative simplicity of the Inhibrx approach will be a winner. 

Companies mentioned in this episode: 

Adverum Technologies, Alveologene, Arrowhead Pharmaceuticals, BioHaven, BioMarin, GSK, Inhibrx, Intellia Therapeutics, Korro Bio, Krystal Biotech, Mereo Biopharma, Pfizer, Sanofi, Takeda, Vertex Pharmaceuticals, Wave Life Sciences

Suggestion box (Suggestions on future episodes, points for clarification, comments, etc.)

Subscribe (Get notified when new episodes are available. NO marketing!)

Follow us on LinkedIn

Disclaimer