August 6, 2020
Biogen and Denali Therapeutics announced an agreement to co-develop and co-commercialize Denali’s small molecule LRRK2 franchise for PD. Biogen receives the rights to opt into two programs, and rights of first negotiation for two other programs – both related to Denali’s blood-brain barrier technology, Transport Vehicle. Under terms of the agreement, Biogen will make an upfront payment of $560M, with a $465M equity investment in Denali (through stock purchase of 11.2% outstanding stock). Denali is eligible to receive up to $1.125B in potential milestones.
On the heels of this collaboration, Denali/Biogen announced that it has selected DNL151 to advance into two late stage PD studies, supported by ongoing phase 1/1b safety and biomarker studies that have demonstrated tolerability and desired target engagement. An IND was cleared by the FDA in July, which enables global studies. Both DNL201 and DNL151 were deemed to have met requirements to proceed into late stage studies, but DNL151 was chosen due to PK properties that provide additional dosing regimen flexibility.
Denali and Biogen intend to start two separate studies, one that looks at PD patients with a kinase-activating LRRK2 mutaiton, and the other looking at patients with sporadic PD. The studies are expected to begin in 2021.
Based on the collaboration, Biogen and Denali will co-commercialize DNL151 in the U.S. and China, while Biogen will have the rights to commercialize in all other markets. Biogen and Denali will share 60/40 (Biogen/Denali) responsibility for global development, 50/50 responsibility for U.S. commercialization, and 60/40 for China commercialization. Outside of these two regions, Biogen will pay Denali tiered royalties.
In the deal, Biogen also receives an exclusive option to license two preclinical programs from Denali’s BBB TV platform, including its Antibody Transport Vehicle:Abeta program (ATV enabled anti-amyloid beta), and a second program to be named later.
This further cements Biogen’s lead in the neurodegenerative space with its phase 3 programs in Alzheimer’s, including aducanumab which is pending FDA approval, and alpha-synuclein targeting cinpanemab in a phase 2 study for PD.
With the Denali agreement, Biogen increases its investment in PD by capturing the most promising LRRK2-targeting agent currently in development. Importantly, the studies for DNL151 will look at patients with sporadic disease, rather than just those with LRRK2 mutations, which increases its significance and marketability if ultimately successful. The study in sporadic disease will be immensely important for the field, since experts are torn as to whether LRRK2 inhibition can benefit the broader PD population.
Just as important as DNL151, Biogen gains rights to Denali’s innovative Transport Vehicle platform that aims to enable brain exposure for drugs that normally cannot cross the blood-brain barrier. This technology may have a larger long-term ceiling than the LRRK2 program, due to its ability to cross into multiple indications.
Lastly, the addition of the LRRK2 franchise should be seen as fully complementary to Biogen’s alpha-synuclein franchise, which may even lead to potential combination therapy far down the road.