Lilly focuses on tau with AC Immune Alzheimer's R&D tie-up

Eli Lilly has paid $81m to develop drugs targeting aggregation of tau proteins associated with Alzheimer’s with Swiss biotech AC Immune, as focus shifts away from therapies targeting clumps of amyloid proteins found in the brains of patients with the disease.

There have been a string of trial failures in drugs targeting amyloid, most notably solanezumab from Lilly, which failed in two phase 3 trials in 2012, and again in 2016 in a phase 3 trial in patients in the early stages of the disease.

Two years on from the failure of EXPEDITION 3, and after Lilly finally gave up developing solanezumab, the company is hoping changing its approach could produce a drug that stays or slows disease progression.

Lilly has also ended development of lanabecestat with AstraZeneca, which worked by inhibiting an enzyme known as BACE, thought to play a role in the build-up of the starch-like amyloid plaques thought to cause the disease to develop.

As doubts about the so-called ‘amyloid hypothesis’ mount – notably among investors wanting a return on billions of dollars in R&D spend – Lilly is now targeting tau, rogue proteins linked with Alzheimer’s that build up within the neurons of patients with the disease.

Lilly agreed to develop tau targeting molecules from Switzerland’s AC Immune for $81m up front, plus $60 million in near-term development milestones.

The US pharma will also pay low-double digit royalties on sales and has purchased a $50 million note that is convertible into equity in AC Immune.

AC Immune will be responsible for phase 1 development, after which time Lilly will take charge.

Preclinical tests in cells and mice suggest that compounds developed at AC Immune inhibit aggregation of tau, with the most promising potential drug being lead candidate ACI-3024.

Professor Andrea Pfeifer, CEO of AC Immune, said: “This landmark partnership with Lilly is transformational for the future of AC Immune. Lilly's substantial experience in neurology, and particularly in Alzheimer's disease, is a major validation of our small molecule platform for CNS therapeutics.

“It also demonstrates the potential of our pre-clinical assets and adds substantial value to our pipeline. We look forward to working closely with Lilly in this exciting field over the coming years.”

Alessio Brunello, pharma analyst at data and analytics company GlobalData, noted that other companies leading research into Alzheimer’s such as Eisai are also looking towards tau, which has an anti-tau monoclonal antibody in development with University College London.

There are eight clinical trials ongoing in tau immunotherapies, four in phase 2 and four in phase 1 and several more that are in late-stage preclinical development.

Brunello noted that key opinion leaders in a GlobalData report into Alzheimer’s were enthusiastic about the potential of anti-tau monoclonal antibodies in Alzheimer’s.

He said: “No new drug for AD has been approved in the past 16 years, despite more than 400 clinical trials and billions of dollars being spent in an attempt to tackle the disease. Pharma companies and researchers understand the necessity and importance to look beyond amyloid approaches to treat the most significant unmet needs in AD.”