• Phase III trial will evaluate gantenerumab in cognitively unimpaired people with the earliest biological signs of Alzheimer's disease
• Roche and research institutions have jointly leveraged their scientific expertise on Alzheimer’s disease to design the new study

Basel, 3 March 2022 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced a new Phase III Alzheimer’s disease prevention trial (SKYLINE, NCT05256134) with gantenerumab, an investigational anti-amyloid antibody that is administered subcutaneously. Roche intends to enter into a collaboration agreement with Banner Alzheimer’s Institute’s Alzheimer’s Prevention Initiative, Massachusetts General Hospital, and the University of Southern California Alzheimer’s Therapeutic Research Institute to further exchange scientific insights and advance the trial goals.

SKYLINE, a secondary prevention trial, aims to evaluate the potential of gantenerumab to slow disease progression in people with the earliest biological signs of Alzheimer’s disease, before too much permanent neurological damage is done. The double-blind, placebo-controlled trial will enrol 1,200 participants aged 60 – 80 years who are amyloid positive confirmed by assessing cerebrospinal fluid (CSF) or positron emission tomography (PET), and who show no signs of cognitive impairment. The primary endpoint is change from baseline to Year 4 in the Preclinical Alzheimer’s Cognitive Composite-5 score – an endpoint designed to measure subtle changes in cognitive function.

“My colleagues, collaborators, and I are pleased about the chance to continue working with Roche, helping to inform the study design, endpoints, recruitment options, and promising blood-based biomarker tests used in this important prevention trial,” said Eric M. Reiman, MD, a leader of the Alzheimer’s Prevention Initiative and one of the study’s principal investigators. “We are eager to help find and support the widespread, appropriate, and affordable use of prevention therapies for people facing Alzheimer’s disease as soon as possible.”

Roche has adopted several strategies to address some of the challenges associated with running clinical trials in an Alzheimer’s disease prevention setting. This includes optional blood-based biomarker pre-screening, providing study participants the choice of dosing either every week or every two weeks and the flexibility of administration at home. Roche is also committed to enabling the recruitment of a diverse population for the study across 17 countries globally. The design of SKYLINE will be presented at the AD/PD congress in Barcelona on March 18, 2022.

“As populations continue to age, Alzheimer’s is a looming global health crisis. The possibility to detect this disease at scale more effectively and to intervene even earlier could potentially improve the lives of millions of people and those who care for them,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We are proud to collaborate with key experts in the field and the broader Alzheimer’s community on this study, and we look forward to sharing our learnings in the future.”

The SKYLINE secondary prevention trial will continue to expand the breadth of data being generated by the gantenerumab clinical programme in Alzheimer’s disease. The investigational medicine is also being evaluated in a primary prevention trial in people who are genetically predisposed to developing the disease before amyloid plaques form in the brain, and in people with early Alzheimer’s Disease. Results from GRADUATE 1 and 2, two Phase III trials investigating the safety and efficacy of gantenerumab in people with early Alzheimer’s disease, are expected in Q4 2022.

About Roche in Alzheimer’s Disease
For decades, advocacy groups, academia, industry and the broader healthcare community have collectively progressed our understanding of Alzheimer’s disease (AD) – with the hope that every step would help lead to advancements in treating this debilitating disease. Roche is harnessing its diagnostics and pharmaceutical capabilities to deliver tests to detect, diagnose and monitor the disease and progress research in our ongoing studies of investigational medicines for different targets, types and stages of Alzheimer’s disease. We are also working in over 70 partnerships with organisations from across the healthcare sector to accelerate progress and improve care for people with AD and their loved ones. We are hopeful that our ongoing efforts will lead to scientific progress that could impact millions of people.

About gantenerumab
Gantenerumab is an investigational IgG1 antibody designed to bind to aggregated forms of beta-amyloid and remove brain amyloid plaques, a pathological hallmark of AD. Learnings from previous gantenerumab studies have been applied to the current clinical programme, such as using a higher target dose of gantenerumab than first studied, in order to maximise exposure.

Gantenerumab is currently being investigated in eight clinical trials. In addition to SKYLINE this includes:

• GRADUATE 1 and 2, two Phase III studies investigating the efficacy and safety of gantenerumab compared with placebo in up to 1000 participants per study who have early AD over 27 months. Results are expected in the fourth quarter of 2022.
• GRADUATION, an open-label study to evaluate the pharmacodynamic effects of once weekly administration in participants with early AD.
• Post-GRADUATE, a rollover open-label study for GRADUATE 1 and 2 to continue assessing the efficacy and safety of gantenerumab in participants with early AD.
• Open RoAD, a rollover open-label study for the former SCarlet RoAD and Marguerite RoAD OLEs to continue to evaluate the safety and tolerability of long-term administration of gantenerumab in participants with AD.
• DIAN-TU-002 Primary Prevention, investigating whether AD can be prevented in people with a genetic predisposition to developing rare, early-onset forms of the disease called Autosomal Dominant AD (ADAD). Unlike most AD prevention studies, it enrols people up to 25 years before the disease has started in the brain.
• DIAN-TU-001 OLE, an exploratory study in people with ADAD who presented with or were close to the expected symptoms of AD, aiming to further investigate the relationship of biomarker changes with cognitive and clinical findings.

About Roche in neuroscience
Neuroscience is a major focus of research and development at Roche. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases. Roche is investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, spinal muscular atrophy, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and Duchenne muscular dystrophy. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today.

About Roche
Founded in1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.

In recognising our endeavor to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work.

Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.

For more information, please visit www.roche.com.

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