Roche returns AC Immune’s Alzheimer’s antibodies after years of setbacks

2024-01-22

交易

临床2期疫苗临床3期

AC Immune regained rights to a pair of monoclonal antibodies (mAbs) from Roche’s Genentech unit on Monday after neither candidate showed a functional benefit in early Alzheimer’s disease (AD) across a series of mid- and late-stage studies.

Genentech in-licensed anti-amyloid beta mAb crenezumab in 2006; the partners expanded their collaboration in 2012 to include semorinemab, an anti-tau mAb.

In 2019, Genentech halted two Phase III studies of crenezumab after an interim analysis suggested they were unlikely to meet their primary endpoints in early sporadic AD patients. Meanwhile, semorinemab missed its primary and secondary endpoints of the Phase II TAURIEL trial in 2020, failing to slow both cognitive and functional decline in patients with early AD. That drug also later failed to slow functional decline in the Phase II LAURIET trial, although it did delay the worsening of patients' cognitive abilities, lending credence to the theory that targeting tau could be a viable strategy for changing the course of AD.

AC Immune CEO Andrea Pfeifer said the company may explore combination therapies with crenezumab and semorinemab, and added that the two mAbs could also be enhanced with the company’s platform technologies. “Later this year we will present new data to illustrate the full potential of these and other monoclonal antibody assets,” Pfeifer said.

Immunisation for AD

Since out-licensing the mAb programmes for Alzheimer's, AC Immune has developed a trio of vaccines for neurodegenerative diseases.

The company is partnered with Johnson & Johnson on ACI‑35.030, an AD vaccine that targets phosphorylated Tau. In December, the drugmaker’s Janssen unit started the Phase IIb ReTain trial to slow or prevent progression of AD in pre-symptomatic people, triggering a milestone payment of CHF15 million ($17 million) to AC Immune.

Internally, AC Immune is also developing ACI‑24.060, an anti-amyloid beta vaccine for AD, and ACI‑7104.056, an anti-alpha synuclein vaccine alpha synuclein vaccine for Parkinson’s disease. Both are in Phase II testing.

Roche’s other AD hopes

Monday’s pipeline divestiture leaves Roche with three clinical AD programmes.

The most advanced is bepranemab (RG6416/UCB0107), an anti-tau mAb in-licensed from UCB that’s in a Phase II trial in patients with early-to-mild AD.

Next is trotinemab (RG6102/RO7126209), a reformulation of anti-amyloid beta mAb gantenerumab to improve its ability to cross the blood-brain barrier, thanks to Roche’s Brainshuttle technology. The candidate is in a Phase I/II trial in early AD.