Sanofi teams up with Merck to pair Keytruda with a next-gen IL-2 candidate from the Synthorx buyout
Nearly a year after snapping up a next-gen immuno-oncology candidate in its $2.5 billion Synthorx buyout, Sanofi is joining forces with Merck to pair the drug with blockbuster Keytruda.
The pharmas are planning a Phase II trial of Sanofi’s non-alpha IL-2 candidate THOR-707 in combination or sequenced administration with Keytruda for various cancers. While the companies are keeping mum about the financial terms and targets, they said the trials will be Sanofi-sponsored.
THOR-707 is currently in a Phase I open-label dose escalation and expansion trial assessing safety and tolerability. Researchers are looking to nail down a recommended dose for Phase II, both for the drug alone and in combination with anti-PD-1 and anti-EGFR antibodies.
Synthorx developed THOR-707 under the guidance of then-CEO Laura Shawver as an alternative to Proleukin, which is known for its bad tox profile, including vascular leak syndrome. According to its 2018 S-1 filing, the drug utilizes synthetic genetic alphabets and is designed to “kill tumor cells by increasing CD8+ T and NK cells without causing VLS (vascular leak syndrome) that has been observed with aldesleukin.” The biotech added that when combined with checkpoint inhibitors, the drug could have “greater anti-tumor effects” than PD-1 inhibitors alone.
A year after landing a $131 million public debut, Synthorx was bought by Sanofi for $68 a share. The deal, CEO Paul Hudson said at the time, “is aligned with our goal to build our oncology franchise with potentially practice-changing medicines and novel combinations.”
In addition to the Keytruda combo, Sanofi is also studying THOR-707 in combination with other anti-PD-1 antibodies such as Libtayo, and with anti-EGFR and anti-CD38 antibodies. In preclinical studies, the drug was shown to trigger the expansion of CD8+ T cells both alone and with an anti-PD-1 mAb, according to Sanofi.
“We believe that THOR-707 has the potential to become a foundation of the next generation of immuno-oncology therapies,” Peter Adamson, Sanofi’s global head of oncology development and pediatric innovation, said in a statement. “This collaboration with MSD will enable us to explore whether THOR-707 can increase and expand the effectiveness of Keytruda and improve the outcomes for patients with cancer.”
The pharma expects to read out full Phase I results and announce recommended Phase II dose by 2021.
Nektar’s second-gen IL-2 candidate was granted breakthrough designation in combination with Opdivo in August 2019. But controversial explanations for waning response rates posed a setback. And at this year’s virtual ESMO, Alkermes read out results from a Phase I/II trial of their ALKS-4230, which is also being tested in combination with Keytruda. The biotech said results showed “encouraging single-agent activity of ALKS-4230 in melanoma and durable responses in multiple tumor types in combination with pembrolizumab.”