Sanofi’s Synthorx turkey comes home to roost

In April, despite lacklustre data, Sanofi was still talking up the non-alpha IL-2 project SAR444245 it had acquired through Synthorx. Today the group accepted reality, discontinuing its current phase 2 programme and writing off the remaining €1.6bn ($1.6bn) of the $2.5bn Synthorx takeover price through its accounts.

There is better news for a separate acquisition, Sanofi’s $1.1bn move on Kymab, whose lead asset is in phase 2. But, while SAR444245 is not being discontinued entirely, the setback comes after Sanofi scrapped development of an mRNA vaccine it picked up with the $3.2bn purchase of Translate Bio, and raises more questions about Paul Hudson’s M&A nous.

This is not a new phenomenon. The Sanofi chief exec has been under fire for some time over deals that have not panned out, and in August, when his company discontinued the Serd amcenestrant, it almost seemed as though oncology was being deprioritised.

Earlier the group had claimed that attrition in the IL-2 space, namely the failure of Nektar’s bempegaldesleukin, spelled good news for SAR444245. But today the mask of confidence slipped as Sanofi’s third-quarter report revealed an intangibles impairment of €1.6bn related to SAR444245; this amount equals the remaining Synthorx value that Sanofi had been carrying, confirming that the group had spent $2.5bn on something now worth zero.

Sanofi has discontinued ongoing phase 2 trials, using every-three-week dosing, admitting that “efficacy observed in the early look of the data was lower than projected”. This must at least partly refer to late-breaking data presented at last year’s AACR, which marked the first doubts over the Synthorx acquisition.

Two months ago Mr Hudson said Sanofi would decide on SAR444245’s phase 3 programme by the end of the year. The decision, the group said today, is to go back to the drawing board, planning a new phase 1/2 programme focusing on “schedule intensification”. On an analyst call Mr Hudson insisted that he remained optimistic about SAR444245.

Other acquisitions

The separate $3.7bn purchase of Principia is also in trouble, with its two BTK inhibitors, rilzabrutinib and tolebrutinib, respectively failing in pemphigus and being placed on clinical hold over drug-induced liver injury. Sanofi today said it had provided the FDA with data, with the aim of lifting the tolebrutinib hold as early as in the current quarter.

This would offer Mr Hudson some respite, as would progress with a separate asset, the anti-Ox40L MAb amlitelimab. This is the lead from Sanofi’s January 2021 acquisition of Kymab, having at that time been known as KY1005, and in the past few months it has entered phase 2 trials in atopic dermatitis and asthma.

As far as this mechanism goes amlitelimab appears to be being prioritised, with Sanofi today revealing the discontinuation of SAR443726, an anti-IL-13/Ox40L nanobody that had entered a first-in-human study in atopic dermatitis a year ago.