Cassava Sciences Announces Additional Clinical Data from a Phase 2b Study of Sumifilam in Alzheimer’s Disease - Seite 2

• BBB permeability can be clinically evaluated by comparing levels of albumin in CSF and plasma. The albumin ratio is a test for BBB permeability because albumin protein is not synthesized in CSF. Hence, albumin in CSF necessarily comes from plasma through the BBB. The albumin ratio is frequently elevated in patients with dementia and various other disorders.
  
  
• In the Phase 2b study, the albumin ratio was unchanged for Alzheimer’s patients on placebo. The albumin ratio improved by approximately 5 and 7 points for patients treated with sumifilam, 50 mg and 100 mg, respectively, over 28 days.
  

Changes in the Albumin Ratio by Treatment Group

Treatment	Day 0	Day 28	Change-Day 0 to 28
Placebo	24	24	No change
50 mg sumifilam	25	20	- 5
100 mg sumifilam	25	18	- 7

About HMGB1
HMGB1 is an endogenous and potent pro-inflammatory protein that is sometimes called a ‘danger molecule.’ HMGB1 is elevated in patients with Alzheimer’s disease and other neurodegenerative disorders and many other disorders. Elevated levels of HMGB1 induce neuroinflammation, tissue damage and, eventually, cell death. Preclinical research has shown that inhibiting HMGB1 improves outcomes in neurodegenerative disease models, decreasing neuroinflammation and improving learning and memory. PubMed reports nearly 6,000 scientific publications of HMGB1 research in the past decade, highlighting the molecule’s potential importance in clinical research.

About the Blood-brain Barrier (BBB)
The BBB is a complex border of cells along blood vessels that prevent unwanted substances in blood from entering the brain. BBB integrity is essential to brain health. A healthy BBB system selectively allows the passage of some molecules into the brain, such as water and glucose, while blocking passage to molecules that may damage the brain. Levels of IgG antibodies and albumin protein in the cerebrospinal fluid (CSF) are an index of BBB integrity, with elevated levels evidence of a ‘leaky’, impaired BBB. Albumin protein is found at high levels in plasma and low levels in CSF because it does not normally cross the BBB.