SAR-442999

One of the key programs that inspired Sanofi’s $2.5 billion buyout of Synthorx in late 2019 is now the subject of a $1.6 billion writedown. Sanofi disclosed in its Q3 earnings that it’s closing down Phase II platform trials for SAR444245, an IL-2 candidate that it had hoped would serve as a next-gen foundation of the oncology franchise. An early look at the data, it said, suggests efficacy that’s “lower than projected.” IL-2 has long been notorious as a target. While the cytokine can activate immune cells against cancer, those effects are a double-edged sword, triggering dangerous side effects for patients. Multiple companies have struggled to tread the fine line between safety and efficacy — with Nektar representing the latest and perhaps most high-profile implosion when it shuttered its Bristol Myers Squibb-partnered program. Hit by 2 more flops, Bristol Myers and Nektar wind down IL-2/PD-1 program at the center of $3.6B deal Those news stories may have influenced Sanofi’s thinking. The company said the decision to record €1.59 billion in impairment was “based on emerging external and internal data that led to updated cash flow projections due to delays in launch timelines in key indications.” The company is, however, sure to note that it was not based on any safety-related issues. Here’s what it has to say in the update: Based on emerging external and internal data about non-alpha IL2’s mechanism of action and therapeutic potential, a new Phase 1/2 program is planned to be initiated for SAR444245, focused on schedule intensification to solidify the foundation for a best-in-class target profile. In parallel, the decision was made to discontinue the ongoing phase 2 platform trials with the current every 3-week dose schedule as the efficacy observed in the early look of the data was lower than projected. Analysts were largely unimpressed by the early data that Sanofi showcased on SAR444245, formerly THOR-707, writing back in April 2021 that the low response rates posted then wouldn’t be enough. And that was when Nektar’s bempeg was still the leading contender in the race. In other news, Sanofi noted that it’s also discontinued SAR443726 and SAR442999, two nanobodies from the Ablynx acquisition, “due to their clinical profile and portfolio considerations.” SAR443726 targets IL-13/OX40L and was being tested for atopic dermatitis; SAR442999, which hits TNFa/IL-23A, was in a trial for an unspecified inflammatory indication.