AC Immune has amended its collaboration agreement with Eli Lilly to advance Tau-targeting small molecules for Alzheimer’s disease, with IND-enabling studies set to begin in H1 2026.

The updated agreement expands an existing 2018 partnership to include the development of new lead Morphomer candidates and potential back-up compounds targeting Tau aggregation, a key pathological feature in Alzheimer’s disease and other neurodegenerative conditions.

Tau proteins, which form aggregates inside neurons, are increasingly seen as a critical driver of disease progression. AC Immune’s Morphomer small molecules are designed to enter the brain when administered orally and selectively bind to pathological forms of Tau, with the aim of preventing aggregation and spread.

Andrea Pfeifer, chief executive officer of AC Immune, said: “The progress in this collaboration highlights the important breakthroughs we have made with Morphomer small molecules for intracellular targeting of Tau. We look forward to working with the team at Lilly to drive forward the development of these potentially disruptive small molecule therapeutics for early-stage treatment and long-term prevention of neurodegenerative diseases.”

She added: “Increasingly, the scientific evidence suggests that targeting intracellular Tau can slow or even completely halt the pathology. This collaboration exemplifies our work towards precision prevention of neurodegenerative diseases. We expect to initiate Investigational New Drug (IND)-enabling studies imminently.”

AC Immune said preclinical data support the potential of its Morphomer platform to inhibit Tau aggregation and seeding across different stages of disease, though clinical validation remains to be established.

Under the amended terms, AC Immune will receive a CHF10m upfront payment and is eligible for a milestone payment upon Phase 1 dosing. The company may also receive additional development, regulatory and commercial milestone payments exceeding CHF1.7bn, alongside tiered royalties in the low double digits.

The collaboration reflects continued industry focus on Tau as a therapeutic target, particularly as companies look beyond amyloid-based approaches in Alzheimer’s disease.

IND-enabling studies are expected to begin in the first half of 2026, marking the next step towards potential clinical development of the Morphomer candidates.