From the President & CEO of Cassava Sciences Inc

“Six months of simufilam treatment robustly improved brain biomarkers,” said Remi Barbier, President & CEO, Cassava Sciences Inc. “In this same study simufilam also improved cognition. These data suggest simufilam has potential to provide durable treatment effects for people living with Alzheimer’s.”

About Cerebrospinal Fluid Biomarkers

A key objective of this analysis was to measure changes in levels of biomarkers in patients before and after 6 months of treatment with open-label simufilam. Biomarker data were analyzed from CSF collected from 25 patients with mild-to-moderate Alzheimer’s disease who are enrolled in an ongoing open-label study and who agreed to undergo a lumbar puncture at baseline and again after 6 months of treatment.

All bioanalyses were conducted blind by an outside lab. Simufilam robustly improved all measured CSF biomarkers (all p-values are baseline vs. 6-month levels by paired t-test):

Core markers of Alzheimer’s pathology are total tau (T-tau), phosphorylated tau (P-tau181), and amyloid beta42 (Aβ42). In Alzheimer’s, tau levels are elevated and Aβ42 is low.

T-tau decreased 38% (p<0.00)

P-tau181 decreased 18% (p<0.00001)

CSF Aβ42 increased 84% (p<0.00001)

Elevated CSF levels of two proteins, neurogranin (Ng) and neurofilament Light Chain (NfL) indicate neurodegeneration.

Ng decreased 72% (p<0.00001)

NfL decreased 55% (p<0.00001)

Elevated levels of marker YKL-40 indicate neuroinflammation.

YKL-40 decreased 44% (p<0.00001)

sTREM2 is a biomarker of microglia-induced neuroinflammation that has commanded substantial recent attention from researchers for its role in Alzheimer’s and frontotemporal dementia.

sTREM2 decreased 65% (p<0.00001)

HMGB1 protein is a damage-related protein sometimes called a ‘danger molecule’ because it triggers additional neuroinflammation and loss of neurons.

HMGB1 decreased 53% (p<0.00001)

In February 2021, Cassava Sciences reported that simufilam improved cognition scores by 1.6 points on ADAS-Cog11, a 10% mean improvement from baseline, following six months of open-label treatment.

Another Press Release

This press release is contemporaneous with another press release titled, “Cassava Sciences Announces Positive Cognition Data with Simufilam in Alzheimer’s Disease”, which reports simufilam improved cognition scores by 3.0 points on ADAS-Cog at 9 months (p<0.001). 

About Today’s Oral Presentation at AAIC

Lindsay Burns, Senior VP, Neuroscience at Cassava Sciences, is scheduled to give a live podium presentation today at the Alzheimer’s Association International Conference (AAIC) in Denver, CO and virtually. Dr. Burns’ presentation is titled, “Encouraging Interim Results at 9 Months from an Open-label Study of Simufilam in Alzheimer’s Disease” (AAIC abstract #54395).

Today’s AAIC presentation can be accessed on the ‘Investors’ page of the Company’s website: https://www.CassavaSciences.com.

About the Open-label Study

In March 2020, Cassava Sciences initiated a long-term, open-label study to evaluate simufilam in patients with Alzheimer’s disease. This study is funded by a research grant award from the National Institutes of Health (NIH). The open-label study is intended to monitor the long-term safety and tolerability of simufilam 100 mg twice daily for 12 months or longer in patients with Alzheimer’s disease. Another study objective is to measure changes in cognition on ADAS-Cog, a standard test of cognition in Alzheimer’s disease. The study protocol has pre-specified interim analyses on safety and cognition for the first 50 subjects who complete 6, 9, and 12 months of drug treatment. The study protocol also specifies two biomarker measurements: i) from baseline to Month 6 in 25 study subjects, and ii) baseline to Month 12 in another 25 study subjects. The open-label study has completed its target enrollment of 150 subjects. By physician and patient request, clinical sites may continue to enroll additional subjects up through the upcoming initiation of the Company’s Phase 3 pivotal program of simufilam. 

Cassava Sciences Inc Next Steps

Cassava Sciences believes clinical results support advancing simufilam into a Phase 3 clinical program in Alzheimer’s disease. Phase 3 program initiation is scheduled for Fall 2021.

About Simufilam

Simufilam (sim-uh-FILL-am) is a proprietary, small molecule (oral) drug that restores the normal shape and function of altered filamin A (FLNA), a scaffolding protein, in the brain. Altered FLNA in the brain disrupts the normal function of neurons, leading to Alzheimer’s pathology,

neurodegeneration, and neuroinflammation. The underlying science for simufilam is published in peer-reviewed journals, including Journal of Neuroscience, Neurobiology of Aging, Journal of Biological Chemistry, Neuroimmunology and Neuroinflammation and Journal of Prevention of Alzheimer’s Disease. Simufilam is substantially supported by peer-reviewed research grant awards from the National Institutes of Health (NIH).

Simufilam and SavaDx were both developed in-house. Cassava Sciences owns worldwide development and commercial rights to its research programs in Alzheimer’s disease, and related technologies, without royalty obligations to any third party.

About Alzheimer’s Disease

Alzheimer’s disease is a progressive brain disorder that destroys memory and thinking skills. As of 2020, there were approximately 50 million people worldwide living with dementia, a figure expected to increase to 150 million by 2050. The annual global cost of dementia is now above $1 trillion, according to Alzheimer’s Disease International, a charitable organization.

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Cassava Sciences Inc Press Release Related to COGNITION

In another press release Cassava Sciences announced that Simufilam has significantly improved cognition in patients with Alzheimer’s in Interim Analysis of Open-label Study at 9 Months.

We learned that the cognition has improved 3.0 Points on ADAS-Cog at 9 months, an 18% mean improvement baseline to month 9. There were no behavior disorders in over 50% of Patients and no safety issues.  The improvements in cognition, biomarkers, and behavior are highly encouraging treatment effects.

The positive encouraging results are from the clinical study funded by the National Institutes of Health (NIH), The interim analysis summarizes clinical data from the first 50 patients with mild-to-moderate Alzheimer’s disease who completed 9 months of open-label simufilam treatment.

Cassava Sciences believes that today’s data are the first to report significant cognitive improvements at 9 months, which also track with robust improvements in biomarkers in  Alzheimer’s patients, Cognition always declines over time. In patients with mild-to-moderate Alzheimer’s disease, cognition scores usually decline over 4 points on ADAS-Cog over 9 months with over 90% certainty, as reported by the scientific literature.

In the firm’s press release regarding cognition, we also learn that Simufilam improved ADAS-Cog scores in 66% of patients at 9 months. An additional 22% of patients declined less than reported in the scientific literature at 9 months. Cognition outcomes suggest simufilam’s treatment effects were broad-based.

More from Remi Barbier

Remi Barbier, President & CEO of Cassava said, “We are very pleased with the overall consistency of data. Simufilam improved cognition, biomarkers, and behavior, a triple-win for study participants. These clinical data combined with a clean safety profile and easy oral administration suggest highly encouraging and durable treatment effects for people living with Alzheimer’s disease.”

Anxiety, agitation or delusions become more frequent as Alzheimer’s disease progresses. Simufilam reduced dementia-related behavior at 9 months on the Neuropsychiatric Inventory (NPI), a clinical tool widely used to measure changes in dementia-related behavior.

• At baseline, 34% of study subjects had no neuropsychiatric symptoms.
• At month 6, 38% of study subjects had no neuropsychiatric symptoms.
• At month 9, over 50% of study subjects had no neuropsychiatric symptoms.

The safety profile of simufilam in the interim analysis is consistent with prior human studies. There were no drug-related serious adverse events. Adverse events were mild and transient.

Nadav Friedmann, Ph.D., MD, Chief Medical Officer, said, “Today’s data with simufilam suggests disease modification. It appears the drug’s unique mechanism of action has potential to provide transformative treatment benefits following 9 months of dosing.”

Lindsay Burns, Senior VP, Neuroscience at Cassava Sciences, has given a live podium presentation today at the Alzheimer’s Association International Conference (AAIC) in Denver, CO, and virtually. The presentation is titled, “Encouraging Interim Results at 9 Months from an Open-label Study of Simufilam in Alzheimer’s Disease” (AAIC abstract #54395).  

The presentation can be accessed at the ‘Investors’ page of Cassava Sciences’ website.

Prohost Observations

We love what we are witnessing. The press releases and the presentation further encourages us that Alzheimer’s disease will be defeated, and probably many other dementias.

Click here to read more about Cassava Sciences Inc.