Grifols : research lines in Alzheimer's move forward with both treatment and prevention

• Grifols has an integrated Alzheimer's approach consisting of three lines of research: therapy based on plasma-derived proteins, prevention and early diagnosis of this neurodegenerative disease
• In 2018, the company plans to present the results of phase III of its AMBAR clinical trial (Alzheimer Management By Albumin Replacement), and, in October 2017, to start the recruitment of patients for phase II of the ABvac40 vaccine, developed by Araclon Biotech, in which Grifols has a majority holding
• To date, Grifols has invested more than 154 million euros in Alzheimer's research, including both in-house projects and through its investee companies, as part of the group's commitment to patients

Barcelona (Spain), 14 September 2017.- Grifols (MCE:GRF, MCE:GRF.P and NASDAQ:GRFS) one of the world's largest manufacturers of plasma-derived medicines and a pioneer in the research and development of therapeutic solutions which contribute to both scientific and social development, currently supports three lines of research in Alzheimer's disease, designed to improve the treatment, prevention and diagnosis of this neurodegenerative disease. The company has supported Alzheimer's research since 2004.

The AMBAR study (Alzheimer Management By Albumin Replacement) is one of Grifols most ambitious clinical trials and seeks to expand the therapeutic potential of plasma-derived proteins. AMBAR aims to stabilize the progress of Alzheimer's disease through a combination of plasma extraction using the plasmapheresis technique, and its replacement with albumin solution (Albutein), a process known as plasma exchange. This treatment is based on the hypothesis that most of amyloid-β, one of the proteins that it is accumulated in the brain of a person with Alzheimer's disease, is bound to albumin and circulates in plasma. Extracting this plasma might flush Aβ peptide from the brain into the plasma, limiting the disease's impact on the patient's cognitive functions.

In 2018, the AMBAR phase III clinical trial is scheduled to finish and then the results will be published. This will conclude a study that began in 2013, with the recruitment of the first patients. Grifols presented intermediate results in November 2015, which confirmed safety and tolerability of the treatment. One year later, in December 2016, the last of nearly 500 patients was enrolled in the study. The trial is being conducted in 40 hospitals in Spain and the United States. Prior to the start of the AMBAR, the company conducted several pre-clinical studies, two pilot studies and one phase II study.

In addition, Grifols promotes other research projects through acquiring stakes in research companies with projects that complement its core activity. Amongst these, it includes Alkahest (CA, US), a R&D company founded by a group of researchers from the Stanford University, which focuses on the R&D of therapeutic applications of age-related plasma proteins to treat illnesses associated with ageing, including neurodegenerative disorders such as Alzheimer's disease. As part of its research program, Alkahest also works in a large study to eventually identify all the proteins are in the plasma (Plasma Proteome Project).

Prevention and early diagnosis of the disease

Over the longer term, Grifols integrated approach to Alzheimer's disease includes two further research lines, a vaccine and an early diagnosis test.

In October 2017, first patients will be recruited to phase II of the trial of active immunotherapy (vaccine) against Alzheimer's disease (ABvac40) developed by Araclon Biotech. The innovative feature of this vaccine is the use of the C-terminus of the amyloid-β 40 peptide as an immunogen, a differentiated approach compared to other proposals currently in clinical development.

The company expects phase II to take place over the next two years at 22 centers in Spain (18 centers), France (2), Sweden (1) and Italy (1). The trial will include 120 patients who have not yet developed symptoms of dementia or have mild cognitive impairment.

The objectives of this phase II are to establish the product dose to be administered in subsequent phases, and to expand the safety and tolerability data obtained from the phase I, which results were presented in July 2016 and showed a good profile in both aspects. In addition, phase II is designed to evaluate responses at both the cognitive and molecular levels, providing the first data regarding a possible clinical impact.

The company's other research line explores the early diagnosis of Alzheimer's disease. Araclon Biotech has developed a diagnostic test that offers the possibility of direct detection and quantification in the blood of some variants of amyloid-β in different plasma fractions. This test is already available for research uses and, over the coming years and based on the results of studies currently in progress, it is expected to be of great assistance in the identification of individuals at risk of developing Alzheimer's disease, so that they can receive preventive treatment to stop its advance.

About Alzheimer's disease

Alzheimer's disease is a neurodegenerative pathology characterized by the death of neurons in the brain. It is currently incurable and has been described as a 21st-century epidemic, destined to have an increasing impact on the elderly population in the developed world.

Alzheimer's is the most common cause of dementia and involves memory loss, intellectual impairment, behavioral change, and a deterioration in the ability to perform daily activities. It also has a major psychological, physical, social and economic impact on cares, society, and the health system.

The World Health Organization (WHO) estimates that approximately 47.5 million people currently suffer from Alzheimer's disease across the globe, with 7.7 million new cases each year. Alzheimer's disease is the leading cause of dementia, accounting for between 60 and 80 percent of all cases. Experts predict that by 2030 there will be over 75 million patients worldwide, and that this figure will exceed 135 million in 2050. In Spain, the situation is similar to that of other developed countries. According to the estimates of Spain's National Epidemiology Center, 7.3% of the population aged over 65 could currently suffer from this disease, and the gradual ageing of the population means that the number of patients would be around one million by 2050.