AACR21: Sanofi rolls out new data for early-stage 'non-alpha' IL-2. Early feedback? Interesting, but mostly meh
When Paul Hudson over at Sanofi inked a $2.5 billion buyout of cancer player Synthorx in late 2019, one of the centerpieces of the deal was an IL-2 the French drugmaker envisioned as the perfect partner to its immunotherapy portfolio. Now, Sanofi is ready to roll out human data for that candidate, and the results have earned a resounding “meh.”
Sanofi’s engineered “non-alpha” IL-2 THOR-707 posted a meager three partial responses across two cohorts as a monotherapy and in combination with Merck’s Keytruda for a range of advanced or metastatic solid tumors, according to Phase I data presented Saturday at the virtual AACR meeting.
On Friday, Sanofi rolled out a placeholder release for THOR-707 at the November data cutoff, and by March not much had changed in terms of efficacy. Those data weren’t enough to impress analysts, particularly the team at Stifel, which called the results “interesting, but clearly still a work in progress” in a note to clients.
The Stifel team said a lack of complete responses wouldn’t do much to instill confidence that Sanofi’s drug has what it takes to measure up to Bristol Myers Squibb and Nektar’s bempeg, the clear leader in the clubhouse with multiple Phase III programs alongside Opdivo and Keytruda. The drug is also competing with Neoleukin’s NL-201, from which THOR-707 didn’t do a great job of differentiating itself in preclinical studies, Stifel said.
But Sanofi does have some reason for applause. THOR-707 saw consistent safety data across dose escalation both as monotherapy and in combination with Keytruda and is advancing up to the higher end of its range. Stifel analysts said a tolerable higher dose and a longer dosing window could eventually help drive up THOR-707’s efficacy, much like it did for bempeg as a combination with Opdivo in melanoma.
“So with higher dose, and longer exposure, we think this could evolve for the better,” the analysts wrote.
Sanofi also turned out positive biomarker signals that could bode well for further studies, including increased CD8+ effector T cell and NK cell counts without an associated increase in alpha-mediated immune responders, including CD4+ regulatory T cells or eosinophils. The drug also showed promise in avoiding vascular leak syndrome, another alpha-mediated side effect common to activation of the IL-2 pathway.
On top of studying THOR-707 as both a monotherapy and in combination with Keytruda and anti-EGFR therapies, Sanofi is also testing the drug paired with PD-1 blocker Libtayo for various tumor types and anti-CD38 antibody Sarclisa for myeloma.