NEW YORK – AC Immune on Monday announced the termination of two research and collaboration deals with Roche focused on developing the anti-beta-amyloid drug crenezumab and the anti-tau agent semorinemab for treating Alzheimer's disease.
The Lausanne, Switzerland-based AC Immune exclusively out-licensed its anti-beta-amyloid program to Genentech in 2006, under which the biotech giant could develop crenezumab for the treatment and prevention of Alzheimer's. AC Immune inked a second worldwide license and research collaboration focused on the development and commercialization of anti-tau antibodies in 2012 with Genentech and Roche, which included semorinemab. In 2009, Genentech became a subsidiary of Roche.
Now that Roche has decided not to continue with these longstanding deals, AC Immune will regain global rights to crenezumab and semorinemab.
Crenezumab is a monoclonal antibody designed to target and neutralize misfolded beta-amyloid. AC Immune expects that the agent's antibody backbone will minimize inflammatory responses in the brain and lower the risk of side effects, including amyloid-related imaging abnormalities. However, in 2022, crenezumab failed to slow cognitive decline in the Alzheimer's Prevention Initiative's Colombian study involving patients with the PSEN1 E280A autosomal dominant mutation.
"While the Colombian autosomal-dominant [Alzheimer's disease] prevention trial was not sufficiently powered to show significant cognitive benefits, crenezumab was proven to be safe with numeric trends on the primary and vast majority of secondary and exploratory endpoints in its favor," AC Immune said in a statement. "The lessons from this study provided useful insights regarding the desired anti-amyloid immunotherapy profile and designs for prevention trials."
Semorinemab targets and binds to the N-terminal portion of the tau protein and is designed to slow its spread between neurons. The anti-tau monoclonal antibody, though, failed to meet the primary endpoint in the Phase II Tauriel trial in prodromal-to-mild Alzheimer's patients but did demonstrate a positive effect on one of two primary cognitive endpoints as well as on tau biomarkers in the Lauriet trial involving patients with mild-to-moderate Alzheimer's.
Upon the termination of its deals with Roche on these two drugs, AC Immune is also regaining rights to all the data generated in these programs, which the firm said it will review, including the open-label extension results from the Lauriet trial when they become available. Based on a careful evaluation of these data, the company said it will make decisions about how to develop these assets.
"Regaining the global rights to crenezumab, semorinemab, and the intellectual property surrounding these targets may offer alternative routes to new growth opportunities, including combination therapies," AC Immune CEO Andrea Pfeifer said in a statement. "We are confident that, with full ownership and the learnings from these programs, they could be enhanced using AC Immune's proprietary next-generation technologies. Later this year, we will present new data to illustrate the full potential of these and other monoclonal antibody assets."
AC Immune is also developing an anti-amyloid immunotherapy, dubbed ACI-24.060, which recently received fast-track designation from the US Food and Drug Administration for treating prodromal Alzheimer's disease and adults with Down syndrome, who must have amyloid-beta pathology confirmed by a PET scan. The firm expects to have interim safety and immunogenicity data in the second half of 2024 and initial data on amyloid plaque clearance in the first half of the year.
Pfeifer indicated that the company is now focused on advancing its precision immunotherapies in potentially registrational Phase II clinical trials in patients with neurodegenerative diseases, including ACI-24.060; the anti-alpha-synuclein active immunotherapy ACI-7104.056 in Parkinson's disease; and ACI-35.030, a selective pathological phosphorylated tau agent under development with Janssen in preclinical Alzheimer's.
Earlier this year, AC Immune announced the receipt of CHF 15 million ($17.22 million) in milestone payments from Janssen related to the ACI-35.030 program and that it had raised $50 million in equity financing. As such, "we are well financed into 2026, and able to advance multiple high-value development programs," Pfeifer said.