Esmo 2022 – Springworks aims to Defi expectations

Springworks Therapeutics looks on course to get its lead project, the gamma secretase inhibitor nirogacestat, approved for desmoid tumours, after presenting strong data over the weekend at Esmo.

However, this is a small niche, and the big hope for the group must be multiple myeloma, where nirogacestat is being trialled in combination with several BCMA-targeting agents – an approach underscored by the strengthened partnership between Springworks and GSK last week.

Still, there are doubts about this approach, with Allogene recently canning its ALLO-715/nirogacestat combo. And any investors seeking exposure to gamma secretase inhibitors might do well to look at Ayala Pharmaceuticals, which just reported early data with its contender, AL102, but which trades at a fraction of Springworks’ valuation.

Desmoid niche

Ayala’s $28m market cap is dwarfed by Springworks’ $1.4bn, even with the latter’s share price slide in spring, when reality hit for the group.  

At least Springworks is closing in on desmoid tumours, which it says affect around 30,000 people in the US, with 5,000-7,000 of these under active treatment.

The phase 3 Defi study, which was presented at Esmo on Saturday, showed an impressive 71% reduction in the risk of disease progression with nirogacestat versus placebo; the overall response rate was 41% with drug versus 8% with placebo.

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