Overview

Cassava Sciences, Inc. is a clinical-stage biotechnology company based in Austin, Texas. The company’s mission is to detect and treat central nervous system disorders, such as Tuberous Sclerosis Complex (TSC)-related epilepsy. Cassava’s lead therapeutic drug candidate is simufilam, which was previously under clinical evaluation for the treatment of Alzheimer’s disease. However, in 2024, the company discontinued all ongoing clinical trials for simufilam in Alzheimer’s disease and announced the decision to phase out the Alzheimer’s disease development program.

Tuberous Sclerosis Complex (TSC)

TSC is a genetic disorder that results in the development of non-malignant tumors in various organs, including the brain. It is estimated to affect around 1 in 6,000 live births, with approximately 50,000 people affected in the United States and more than one million worldwide. TSC is associated with a high rate of epilepsy, with about 84% of patients experiencing seizures, often starting in the first year of life. Approximately 60% of TSC patients suffer from treatment-resistant seizures despite the use of multiple anti-seizure medications.

Preclinical Studies with Simufilam in Tuberous Sclerosis Complex

Preclinical research conducted at Yale University has indicated that simufilam (previously known as PTI-125) may be effective in reducing TSC-related seizure activity. Studies have found that overexpression of a protein called filamin A (FLNA) is linked to neuronal abnormalities and epileptic seizure activity in TSC. Treatment with simufilam was shown to limit neuronal abnormalities and reduce seizure activity in a mouse model of TSC, similar to the effects of genetically normalizing FLNA expression.

License Agreement with Yale

On February 26, 2025, Cassava entered into a License Agreement with Yale University, granting the company exclusive worldwide rights to develop and commercialize simufilam for the treatment of TSC-related epilepsy and other potential indications. Under the agreement, Cassava has agreed to use reasonable commercial efforts to implement a development and commercialization plan for simufilam in TSC-related epilepsy.

Clinical Trials in Alzheimer’s Disease (Discontinued)

Cassava had conducted two randomized placebo-controlled Phase 3 clinical trials of oral simufilam in patients with mild-to-moderate Alzheimer’s disease, called RETHINK-ALZ and REFOCUS-ALZ. However, the top-line results from both studies did not meet the pre-specified co-primary, secondary, and exploratory biomarker endpoints. As a result, the company announced the decision to phase out its Alzheimer’s disease development program, which is expected to be completed by the end of the second quarter of 2025.

Leadership Updates

On April 15, 2025, the company’s Chief Medical Officer, James W. Kupiec, M.D., informed the company of his intent to retire and tendered his resignation, effective May 9, 2025. On April 18, 2025, R. Christopher Cook, previously the Senior Vice President and General Counsel, was appointed as the Chief Operating and Legal Officer.

Our Scientific Approach

Cassava’s scientific approach is to treat central nervous system diseases by targeting the scaffolding protein FLNA. The company believes that FLNA is a promising target for drug development, particularly in the context of TSC-related epilepsy. Cassava’s lead small molecule therapeutic product candidate, simufilam, was designed in-house and characterized by the company’s academic collaborators.

Expansion of Our Science to Other Indications

Cassava may leverage its scientific insights in neurodegeneration and neuroinflammation to expand its science to other central nervous system disorders, initially focusing on TSC-related epilepsy. The company plans to conduct exploratory preclinical studies in collaboration with the Tuberous Sclerosis Alliance and other researchers to better understand simufilam’s potential as a treatment for TSC-related seizures.

Financial Overview

Cassava has yet to generate any revenues from product sales and has an accumulated deficit of $428.5 million as of March 31, 2025. The company expects its cash requirements to be significant in the future, primarily due to the continued development of simufilam, including for potential use in TSC-related epilepsy, as well as the phase-out of the Alzheimer’s disease development program. Cassava believes that its current cash and cash equivalents will be sufficient to fund its operations for at least the next 12 months.

Key Points

• Cassava is focused on developing simufilam, a novel small molecule oral treatment, for the potential treatment of TSC-related epilepsy.
• Preclinical studies have shown that simufilam may be effective in reducing seizure activity in TSC by targeting the scaffolding protein FLNA.
• The company has entered into a License Agreement with Yale University to support the development and commercialization of simufilam for TSC-related epilepsy and other potential indications.
• Cassava has discontinued its Alzheimer’s disease development program for simufilam after the Phase 3 trials did not meet their endpoints.
• The company’s financial position remains challenging, with an accumulated deficit of $428.5 million and significant future cash requirements for its ongoing research and development activities.