Biogen licenses Denali’s ATV platform for Alzheimer’s candidate

Biogen will develop and commercialise an Alzheimer’s candidate using Denali’s Antibody Transport Vehicle (ATV).

Following the original $1 billion deal forged in 2020, Biogen has licensed Denali’s Antibody Transport Vehicle (ATV) Amyloid beta (ATV:Aβ) program through an additional upfront exercise payment, granting Biogen access to Denali’s technology to treat Alzheimer’s disease.

Biogen has not disclosed the licensing cost, but Denali has potential to receive additional development and commercial payments, dependent on future sales.

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Biogen will be responsible for developing and commercialising the program. “Additional preclinical development is ongoing with the goal to progress the program towards an IND application,” a Biogen spokesperson told BioProcess Insider.

The ATV platform  

Alzheimer’s is caused by the build-up of amyloid-beta (Aβ) protein plaques in the brain.

Traditionally, therapeutics must be delivered in large doses to cross the BBB and ensure enough of the drug reaches the brain, but this can cause harmful side effects such as bleeds in the brain, known as amyloid-related imaging abnormalities (ARIA).

Denali’s technology is designed to overcome these challenges through effectively delivering large therapeutic molecules across the blood-brain barrier (BBB). Engineered Fc domains bind to specific natural receptors expressed on the BBB cells, allowing the Transport Vehicle and therapeutic cargo to enter the brain through receptor-mediated transcytosis. Potential therapeutic cargo includes proteins, antibodies, and enzymes.

Animal models have shown therapeutic cargo engineered with this technology have a greater exposure and broader distribution in the brain, potentially increasing the therapeutic efficacy of the drug candidates.

Biogen is therefore hopeful Denali’s platform will deliver drugs in small doses, improve Aβ plaque clearance, and reduce ARIA in patients. However, therapeutic delivery is administered intravenously which could limit accessibility to patients.

Biogen’s history of Alzheimer’s

“This decision is an important next step of our collaboration with Denali on ATV:Aβ that aims to advance the next generation of Aβ immunotherapies for the treatment of Alzheimer’s disease,” said Dominic Walsh, head of the Neurodegenerative Research Unit at Biogen. “This program reinforces the importance of targeting Aβ and our commitment to Alzheimer’s disease.”

This is the latest development in Biogen’s history of developing Alzheimer’s therapeutics. Earlier this year the FDA approved Leqembi (lecanemab), an antibody treatment targeting Aβ plaques, co-developed by Biogen and Eisai. Whilst a win for Biogen, this has received some controversy with patient group UsAgainstAlzheimer’s criticizing the unaffordable price for many patients.

Additionally, last year the US government’s Center for Medicare & Medicaid Services (CMS) limited the availability of Biogen’s Aduhelm (aducanumab), following questions surrounding its efficacy. This came only a year after being FDA approved and negatively impacted Biogen which lost $45 million due to “idle capacity” and minimal sales.