Out to revive R&D, a resurgent Sanofi pays $150M cash to partner up with a pioneering protein degradation player
Frank Nestle was appointed Sanofi’s global head of immunology and inflammation research therapeutic area just days before dupilumab, the blockbuster-to-be IL-4 antibody, would be accepted for priority review. After four years of consolidating immunology expertise from multiple corners of the Sanofi family and recruiting new talents to build the discovery engine, he’s set eyes on a Phase I-ready program that he believes can grow into a Dupixent-sized franchise.
And — with the blessing of CEO Paul Hudson and R&D chief John Reed — he’s reaching deep into the purse.
IRAK4 is the headliner for the collaboration with the protein degradation specialists at Kymera, which is bagging $150 million cash and $2 billion in potential milestones. The Cambridge, MA-based biotech is tasked with completing first-in-human studies and retains the option to share US development costs and revenue following the Sanofi-led Phase II.
The target sits downstream of “one of the most validated pathways in innate immunity,” Kymera CEO Nello Mainolfi said: It’s where the IL-1 cytokine family (think IL-1, IL-33, IL-36) and toll-like receptor signaling converges. While kinase inhibitors can take out the kinase function, it also has a scaffolding function which continues to enable signaling.
“In order to fully block the signaling, you need to remove IRAK4,” he said.
Leveraging E3 ligases to tag the target protein for disposal, Kymera’s degrader promises to pack the biological effect of blocking all cytokine signaling with a single oral pill.
Because it sits at a critical node, IRAK4 has been on Sanofi’s radar screen, Nestle said. They are also well aware of the inadequacies of a small molecule approach — such as the one taken by Pfizer.
“At the moment a lot of protein degradation is in cancer, and there’s nothing yet in the chronic inflammatory disease space,” he said. “As far as I’m aware, there’s no other company out there who we could have partnered with to exactly get to that point.”
While the potential applications are broad, dermatology looms large among the initial plans. There’s atopic dermatitis, the itchy skin condition that accounts for a large portion of Dupixent’s $2.32 billion annual sales. Nestle is also keen on hidradenitis suppurativa, which can cause long-term abscesses and scarring.
Sanofi first added protein degradation to its R&D playbook in January, anting up $55 million upfront to access Nurix Therapeutics’ cancer drug platform. The subsequent months have proven to be boom times for the protein degradation field, as Roche waded into the race, a pioneer biotech loaded up and more new players emerged.
Kymera itself raised $102 million during this time, ushering the IRAK4 program and another targeting STAT3 toward the clinic — for both inflammation/immunology and oncology.
“Obviously when you’re working outside of targeted oncology, you actually bring a lot more complexity given that you’re going after a variety of cell population and not just the one cancer cell population,” Mainolfi said.
But just like their research blueprinting a E3 ligase whole body atlas, the CTO-turned-CEO sees it as essential investment to create a leading, fully integrated protein degradation-focused company. He’s also looking to add somewhere between 20 and 40 staffers to the 60-strong team within the next six months or so.
For Sanofi, it’s a bet that aligns well with a newly revamped R&D structure where speciality care and vaccines take center stage.
“We’re coming from where there was not a lot of immunology, but we’ve built a high quality team and that doesn’t mean we have the not invented here syndrome. If we see a great compound, a great collaboration with some of the best in the industry like Kymera, we go for it,” he said. “As you know, pharma can be a slow moving train, so we’re building this foundation but once the foundation is built, there’s one clinical candidate after another which is going to come into the immunology/inflammation space.”