Eli Lilly signs up new Tau aggregation inhibitor candidates from AC Immune with USD 12.5m upfront

Oral small molecule Tau aggregation inhibitors from Switzerland-based AC Immune SA's (Nasdaq: ACIU) Morphomer platform are at the center of an amended license and collaboration agreement with Eli Lilly and Company (NYSE: LLY). The amendment extends a 2018 agreement to cover new lead Tau Morphomer candidates and potential back-up compounds targeting Alzheimer's disease and other neurodegenerative diseases. IND-enabling studies are expected to commence in H1 2026, with a Phase I dosing milestone triggering an additional payment under the revised terms.

Under the amendment, AC Immune receives a CHF 10 million (USD 12.5 million) upfront payment and a separate milestone payment tied to Phase I dosing. The company remains eligible for development, regulatory, and commercial milestones exceeding CHF 1.7 billion (USD 2.1 billion), plus tiered royalties in the low double digits, terms that were disclosed in the original 2018 agreement and carried forward through prior amendments. The specific value of the Phase I dosing milestone was not disclosed.

Deal context

The Morphomer platform generates conformation-selective small molecules designed to bind pathological aggregates of Tau protein rather than its normal soluble form. AC Immune describes the compounds as engineered for oral bioavailability and CNS penetration, with preclinical data the company says supports inhibition of Tau aggregation and prion-like seeding across disease stages. Tau neurofibrillary tangles are a defining pathological feature of Alzheimer's disease and a range of other tauopathies including progressive supranuclear palsy and frontotemporal dementia.

The lead compound covered by the collaboration has not been assigned a public identifier. AC Immune states that candidates in the series were selected for brain penetrance following oral dosing and for selective binding to the pathological conformation of Tau, as opposed to the normally folded protein. These claims are based on company-generated preclinical data and have not yet been evaluated in published peer-reviewed clinical studies for the specific compound advancing under this amendment.

The small molecule approach addresses a structural limitation of anti-Tau biologics, which cannot access intracellular Tau aggregates — the primary site of pathology within neurons. Antibody-based programs targeting extracellular Tau, including those from other developers, do not reach this compartment. Tau kinase inhibitors, which reduce phosphorylation upstream of aggregation, and antisense oligonucleotides targeting total Tau expression represent alternative mechanistic approaches but carry distinct delivery and selectivity challenges.

For Lilly, the collaboration adds a small molecule intracellular Tau program to a neuroscience portfolio that has included amyloid-targeting biologics. The amendment's explicit extension to back-up compounds indicates the collaboration functions as a compound-generation engine rather than a single-asset license, providing pipeline resilience if the lead candidate does not advance.

AC Immune's broader pipeline includes programs at Phase II and Phase III using its SupraAntigen platform for immunotherapy approaches to neurodegeneration, as well as diagnostic tracers from the Morphomer platform. The Lilly collaboration is the company's most financially material partnership, with the milestone pool representing the largest single component of AC Immune's disclosed potential deal value across all partnerships.

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