Sanofi moves into Alzheimer's with Denali bet

Add Sanofi to the big players seeing promise in Denali’s early-stage CNS candidates. The San Francisco-based company will receive $125m up front in a deal covering its small-molecule Rip1 kinase inhibitors. This target, which plays a role in inflammation, could be useful in a range of disorders, not just brain diseases – which might help explain the interest from Sanofi, hardly a big hitter in the CNS space. The companies have named two compounds, the brain-penetrating DNL747, and DNL758, which does not get through the blood-brain barrier. The groups will jointly develop the former in indications such as Alzheimer’s, while Sanofi will fund development of the latter for systemic inflammatory diseases. These are crowded areas, but at least the French group is trying something new; the only other group with Rip kinase inhibitors in clinical development, according to EvaluatePharma, is Glaxosmithkline. The UK company's new chief scientific officer, Hal Barron, highlighted both of its projects during an R&D update in July. The Sanofi-Denali deal is unlikely to tread on Takeda's toes: Denali already has an agreement with the Japanese company dating back to January, but this covers brain-penetrating antibodies for Alzheimer’s, which are currently at the preclinical stage.

RIP kinase inhibitors in development
Project Company Indication(s) Mechanism Status
GSK2982772 Glaxosmithkline Rheumatoid arthritis, psoriasis, ulcerative colitis RIP1 kinase inhibitor  Phase II
GSK2983559 Glaxosmithkline Inflammatory bowel disease RIP2  kinase inhibitor Phase I
DNL747 Denali/Sanofi Alzheimer’s, ALS, MS RIP1 kinase inhibitor  Phase I
DNL758 Denali/Sanofi Rheumatoid arthritis, psoriasis RIP1 kinase inhibitor  Phase I to begin 2019
Source: EvaluatePharma.

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