To evaluate the absorption, metabolism, and excretion of [14C]-simufilam in healthy male subjects following a single oral administration of 100 mg of (approximately 100 µCi) [14C]-simufilam.

Start Date07 Feb 2024

Sponsor / Collaborator

Cassava Sciences, Inc.

NCT05575076

/ TerminatedPhase 3

An Open-label, Long-term Extension Study to Evaluate the Safety and Tolerability of Simufilam 100 mg Tablets in Participants With Mild to Moderate Alzheimer's Disease

The goal of this open-label extension study is to assess long-term safety and tolerability of simufilam 100 mg in subjects who have completed the RETHINK-ALZ or REFOCUS-ALZ Phase 3 clinical trials.

Start Date07 Nov 2022

Sponsor / Collaborator

Cassava Sciences, Inc.

100 Clinical Results associated with Sumifilam

100 Translational Medicine associated with Sumifilam

100 Patents (Medical) associated with Sumifilam

Literatures (Medical) associated with Sumifilam

01 Jan 2026·JPAD-Journal of Prevention of Alzheimers Disease

Phase 3 randomized clinical trials of simufilam in mild-to-moderate Alzheimer’s disease

Article

Author: Khan, Arifulla ; Hernandez, Antonio M ; Hendrix, Suzanne ; Park, Kee Hyung ; Cohen, Ian ; Porsteinsson, Anton P ; Mallinckrodt, Craig ; Turner, Raymond S ; Burns, Lindsay H ; Liss, Jonathan ; Kupiec, James W ; Clarnette, Roger

BACKGROUND:

Soluble amyloid β_1-42 (Aβ₄₂) signals via the α7 nicotinic acetylcholine receptor to hyperphosphorylate tau in Alzheimer's disease (AD). Simufilam disrupts this pathogenic signaling by binding filamin A and disrupts its linkages with inflammatory receptors to reduce neuroinflammation. We assessed simufilam in two Phase 3 clinical trials in mild-to-moderate AD.

METHODS:

Participants were age 50-87 with Stage 4 or 5 CE, a mini-mental state exam (MMSE) ≥16 and ≤27 and a Clinical Dementia Rating Global Score (CDR-GS) of 0.5, 1 or 2. The criterion supporting AD pathology was plasma phosphorylated (p)-tau181 or prior amyloid PET. RETHINK randomized participants to simufilam 100 mg or placebo for 52 weeks. REFOCUS evaluated simufilam 50 and 100 mg versus placebo for 76 weeks. Co-primary endpoints were change from baseline on ADAS-Cog12 and ADCS-ADL. Sub-studies assessed exploratory plasma biomarkers and, in REFOCUS only, CSF and imaging biomarkers.

RESULTS:

Both trials failed to meet co-primary, secondary or exploratory biomarker endpoints. REFOCUS was terminated early, with 22% of participants still active in the trial. In the predefined mild subgroup in REFOCUS, simufilam was associated with slower cognitive decline than placebo through Week 64 (p = 0.019). This finding disappeared at Week 76 with 45% missing data and did not replicate in RETHINK. Favorable nominal exploratory post-hoc findings amongst participants with the highest half of screening plasma p-tau181 levels occurred in RETHINK but not REFOCUS. The plasma p-tau181 entry criterion did not reliably exclude amyloid PET negativity in the sub-study.

CONCLUSIONS:

Simufilam did not meet co-primary or secondary endpoints in these Phase 3 trials. Simufilam was safe and well tolerated. Trials registered at clinicaltrials.gov: NCT04994483 and NCT05026177.

01 Mar 2025·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Progress in the study of anti-Alzheimer's disease activity of pyrimidine-containing bioactive molecules

Review

Author: Zhang, Di ; Zhang, Qi ; Zhang, Lin-Lin ; Liu, Yu-Lin ; Chui, Rui-Hao ; Zhang, Qian ; Ma, Li-Ying ; Li, Bing-Qian

Pyrimidines are aromatic, heterocyclic organic compounds characterized by a six-membered ring that contains four carbon atoms and two nitrogen atoms. They have been reported to exhibit a variety of biological activities such as antifungal, antiviral, and anti-Parkinsonian effects. Recently, there has been an increased focus on their potential anti-Alzheimer's properties. Several pyrimidine-based drugs and their analogs are currently undergoing various phases of clinical trials, indicating pyrimidine as a promising chemical structure for drug development. Notably, modifications to the pyrimidine structure significantly influence their activity against Alzheimer's disease. For instance, the introduction of heteroatoms into the pyrimidine ring or alternations in the length of the linkage region have been shown to enhance therapeutic efficacy. This review provides a comprehensive overview of pyrimidine derivatives as potential therapeutics for Alzheimer's disease, with a focus on structure-activity relationship (SAR) studies, design strategies, and binding mechanisms. These insights could pave the way for the development of more effective anti-Alzheimer's medications.

04 Oct 2024·SCIENCE

Firm misled investors on Alzheimer’s drug, SEC charges

Author: Piller, Charles

Agency fines Cassava Sciences $40 million for touting flawed research on simufilam

120

News (Medical) associated with Sumifilam

13 Jan 2026

·www.biospace.com

Cassava Announces Publication of Peer-Reviewed Phase 3 Results for Simufilam in Alzheimer’s Disease in the Journal of Prevention of Alzheimer’s Disease

As previously disclosed, the studies did not meet pre-specified co-primary, secondary, or exploratory biomarker endpoints The paper provides a detailed analysis of the RETHINK-ALZ and REFOCUS-ALZ studies and confirms simufilam’s favorable safety pro these studies Exploratory post-hoc analyses offer informative insights AUSTIN, Texas, Jan. 13, 2026 (GLOBE NEWSWIRE) -- Cassava Sciences, Inc. (NASDAQ: SAVA, “Cassava”, the “Company”), a biotechnology company focused on developing novel, investigational treatments for central nervous system (CNS) disorders such as Tuberous Sclerosis Complex (TSC)-related epilepsy, today announced publication of the article Phase 3 randomized clinical trials of simufilam in mild-to-moderate Alzheimer’s disease in an upcoming issue of the Journal of Prevention of Alzheimer’s Disease (JPAD). The paper provides a detailed analysis of data from two Phase 3 clinical trials, RETHINK-ALZ and REFOCUS-ALZ. While, as previously disclosed, the two studies did not meet their pre-specified co-primary, secondary, or exploratory biomarker endpoints, exploratory post-hoc analysis of the studies offers informative insights. The paper is publicly available on the JPAD website: Topline results of RETHINK-ALZ (NCT04994483), which randomized 804 people with mild to moderate Alzheimer’s disease, were originally reported in November 2024, and topline results from REFOCUS-ALZ (NCT05026177), which randomized 1,125 patients, were reported in March 2025. As previously disclosed, the Company has discontinued development of, and plans no further investment in, the Alzheimer’s disease program. “In keeping with our commitment to report the detailed results, we are pleased to make the data from the RETHINK-ALZ and REFOCUS-ALZ studies available to the Alzheimer’s disease scientific community through publication in the highly respected Journal of Prevention of Alzheimer’s Disease. We hope the paper can serve as a foundation for further research in the field,” said Rick Barry, President and Chief Executive Officer of Cassava. “The detailed safety observations reported in the article provide heartening encouragement for our ongoing development program in TSC-related epilepsy, as we work to initiate a proof-of-concept study in collaboration with leading investigators.” Exploratory Findings Although the trials failed to meet their co-primary, secondary, and exploratory biomarker endpoints, some prespecified secondary endpoints and post hoc hypothesis-generating analyses showed potential treatment differences between the higher dose of simufilam and placebo in the predefined mild subgroup (mini-mental state exam (MMSE) score 21-27) on the 12-item Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog12), including: Mild Patients in REFOCUS-ALZ : Simufilam (100 mg) was associated with slower cognitive decline than placebo in the prespecified mild subgroup, with differences at Week 4 and Weeks 28, 40, 52, and 64 (nominally significant at p = 0.01, 0.01, 0.02, 0.02, and 0.02, respectively). This potential treatment difference did not replicate in RETHINK-ALZ and was no longer evident at Week 76 of REFOCUS-ALZ (which had 45% missing data due to early study termination). Pooled Mild Patients in REFOCUS-ALZ and RETHINK-ALZ: A prespecified pooled analysis of mild patients administered simufilam (100 mg) or placebo in both trials through week 52 showed potential treatment group differences at weeks 4 and 28 (nominally significant at p < 0.01). An exploratory post hoc analysis of the pooled mild subgroups using a plasma p-tau181 cutoff of ≥ 67 (the highest half of all patients) showed a difference in the slowing of decline at Weeks 4, 28, and 40 (nominally significant at p = 0.03, 0.001, 0.006, respectively), with a trend at Week 52 (p = 0.066). These clinical trials were the first Phase 3 Alzheimer’s disease studies to rely primarily on a plasma biomarker (p-tau181) for biological confirmation of disease. The authors of the paper observed that an amyloid PET (positron emission tomography) sub-study in REFOCUS-ALZ showed that 21% of participants (33 of 160) were unexpectedly amyloid negative at baseline, indicating an absence of Alzheimer’s disease pathology. This suggests that the plasma p-tau181 assay cut-off used as an entry criterion in both trials was insufficient to screen effectively for Alzheimer’s disease pathology in trial participants. James Kupiec, MD, Retired Chief Medical Officer of Cassava and primary publication author, commented, “Exploratory and post hoc analyses identified specific subgroups of patients with an observed treatment difference between the higher dose of simufilam and placebo. While Cassava does not intend to conduct further studies in this indication, we believe these observations are informative. We have made our data and analyses accessible through JPAD with the hope that this paper can serve as a valuable resource for the Alzheimer’s community’s mission to improve patient care.” Dr. Anton Porsteinsson, Director of the University of Rochester’s Alzheimer’s Disease Research, Care and Education Program, commented, “I am very pleased that the results of the REFOCUS-ALZ and RETHINK-ALZ studies have been meticulously written and peer reviewed. Publication of the results from these large, rigorously designed and conducted Phase 3 studies plays an essential role in shaping future studies and ensuring a complete scientific record for the betterment of drug development and public health.” Overview of the RETHINK-ALZ and REFOCUS-ALZ Studies The Phase 3 RETHINK-ALZ (NCT04994483) and REFOCUS-ALZ (NCT05026177) trials were designed as multi-center, double-blinded, placebo-controlled, randomized parallel group studies to evaluate the safety and efficacy of simufilam compared to placebo across distinct clinical sites in the U.S., Canada, and Asia. The prespecified co-primary endpoints for the studies included the change in cognition and function from baseline to the end of the double-blind treatment period, assessed by the ADAS-Cog12 and ADCS-ADL scales, comparing simufilam to placebo. Secondary endpoints included several well validated measures of neuropsychiatric symptoms and caregiver burden. Safety was evaluated by adverse event monitoring, as well as standard laboratory and ECG assessments. REFOCUS-ALZ also included an evaluation of changes in plasma and cerebrospinal fluid biomarkers as well as an evaluation of MRI and PET scans. About Simufilam Simufilam is a proprietary, investigational oral small molecule believed to modulate activity of the filamin A protein, which regulates diverse aspects of neuronal development 1 . About Cassava Sciences, Inc. Cassava Sciences, Inc. (NASDAQ: SAVA), is a biotechnology company focused on developing novel, investigational treatments, including simufilam, for central nervous system disorders, such as tuberous sclerosis complex (TSC)-related epilepsy, and potentially other indications. Simufilam is a proprietary, investigational oral small molecule believed to modulate activity of the filamin A protein, which regulates diverse aspects of neuronal development 1 . The Company is planning a Phase 2 proof-of-concept study to evaluate simufilam in patients with TSC-related epilepsy, collaborating closely with the TSC Alliance and key opinion leaders. The program is based on a method of treatment patent issued in 2025 and in-licensed from Yale University. Cassava is based in Austin, Texas. For more information, please visit: References: Zhang L, Bartley CM, Gong X, Hsieh, LS.; LinTV, Feliciano DM, Bordey A. "MEK-ERK1/2-Dependent FLNA Overexpression Promotes Abnormal Dendritic Patterning in Tuberous Sclerosis Independent of mTOR. Neuron (2014) 84 (1), 78-91. DOI: 10.1016/j.neuron.2014.09.009 For More Information Contact: Investors Sandya von der Weid svonderweid@lifesciadvisors.com Company Eric Schoen, Chief Financial Officer (512) 501-2450 ESchoen@CassavaSciences.com IR@cassavasciences.com Cautionary Note Regarding Forward-Looking Statements: add a few notes on the paper This news release contains forward-looking statements that may include but are not limited to statements regarding the implications of safety observations in the REFOCUS-ALZ and RETHINK-ALZ studies for the Company’s ongoing development program in TSC-related epilepsy and the potential for the observations in the published paper to contribute to Alzheimer’s disease research. Forward-looking statements may be identified by words such as “anticipate”, “before”, “believe”, “could”, “expect”, “forecast”, “intend”, “may”, ”pending”, “plan”, “possible”, “potential”, “prepares for”, “will”, and other words and terms of similar meaning. Such statements are based on our current expectations and projections about future events. Such statements speak only as of the date of this news release and are subject to a number of risks, uncertainties and assumptions, including, but not limited to, those risks inherent in drug discovery and development or specific to Cassava Sciences, Inc., as described in the section entitled “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2024 and Quarterly Report on Form 10-Q for the period ended September 30, 2025, and subsequent reports periodically filed and to be filed with the SEC. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from expectations in any forward-looking statement. In light of these risks, uncertainties and assumptions, the forward-looking statements and events discussed in this news release are inherently uncertain and may not occur, and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements as predictions of future events. Except as required by law, we disclaim any intention or responsibility for updating or revising any forward-looking statements. For further information regarding these and other risks related to our business, investors should consult our filings with the SEC, which are available on the SEC's website at . All of our pharmaceutical assets under development are investigational product candidates. These have not been approved for use in any medical indication by any regulatory authority in any jurisdiction and their safety, efficacy or other desirable attributes, if any, have not been established in any patient population. Consequently, none of our product candidates is approved or available for sale anywhere in the world. Our clinical results from earlier-stage clinical trials or preclinical studies may not be indicative of future results from later-stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements or any scientific data we present or publish. We are in the business of new drug discovery and development. Our research and development activities are long, complex, costly and involve a high degree of risk. Holders of our common stock should carefully read our Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q and any other SEC filings in their entirety, including the risk factors therein. Because risk is fundamental to the process of drug discovery and development, you are cautioned to not invest in our publicly traded securities unless you are prepared to sustain a total loss of the money you have invested.

Clinical ResultPhase 3Phase 2

23 Dec 2025

·www.globenewswire.com

Cassava Announces Agreement to Settle Securities Class Action Litigation

AUSTIN, Texas, Dec. 23, 2025 (GLOBE NEWSWIRE) -- Cassava Sciences, Inc. (NASDAQ: SAVA, “Cassava”, the “Company”), a biotechnology company focused on developing novel, investigational treatments for central nervous system (CNS) disorders such as Tuberous Sclerosis Complex (TSC)-related epilepsy, today announced that it has reached a definitive agreement to resolve the previously disclosed consolidated securities class action litigation pending in the United States District Court for the Western District of Texas Austin Division (In re Cassava Sciences, Inc. Securities Litigation, No. 1:21-cv-00751-DAE) (the “Consolidated Securities Action”). This lawsuit was originally filed in 2021. Under the agreement, Cassava will pay $31.25 million to achieve a complete settlement and release of all claims and causes of action that have been or could be asserted by the plaintiffs and the plaintiff class, which is defined as all purchasers or acquirers of Company common stock or call options on Company common stock or sellers of put options on Company common stock between September 14, 2020 and October 12, 2023 (subject to certain exclusions). The court will decide whether later-filed securities class action litigation should be consolidated into the Consolidated Securities Action. The settlement is not an admission of fault or wrongdoing by the Company. Cassava fully reserved a loss contingency of $31.25 million in the second quarter of 2025 relating to the Consolidated Securities Action. “We are pleased to announce that we have reached an agreement to resolve our most significant, legacy litigation,” said Rick Barry, President and Chief Executive Officer of Cassava. “With this agreement, we can dedicate our attention and resources to the continued development of simufilam as a potential treatment for TSC-related epilepsy.” About Simufilam Simufilam is a proprietary, investigational oral small molecule believed to modulate activity of the filamin A protein, which regulates diverse aspects of neuronal development1. About Cassava Sciences, Inc. Cassava Sciences, Inc. (NASDAQ: SAVA), is a biotechnology company focused on developing novel, investigational treatments, including simufilam, for central nervous system disorders, such as tuberous sclerosis complex (TSC)-related epilepsy, and potentially other indications. Simufilam is a proprietary, investigational oral small molecule believed to modulate activity of the filamin A protein, which regulates diverse aspects of neuronal development1. The Company is planning a Phase 2 proof-of-concept study to evaluate simufilam in patients with TSC-related epilepsy, collaborating closely with the TSC Alliance and key opinion leaders. The program is based on a method of treatment patent issued in 2025 and in-licensed from Yale University. Cassava is based in Austin, Texas. For more information, please visit: https://www.CassavaSciences.com References: Zhang L, Bartley CM, Gong X, Hsieh, LS.; LinTV, Feliciano DM, Bordey A. "MEK-ERK1/2-Dependent FLNA Overexpression Promotes Abnormal Dendritic Patterning in Tuberous Sclerosis Independent of mTOR. Neuron (2014) 84 (1), 78-91. DOI: 10.1016/j.neuron.2014.09.009 For More Information Contact:InvestorsSandya von der Weidsvonderweid@lifesciadvisors.com CompanyEric Schoen, Chief Financial Officer(512) 501-2450ESchoen@CassavaSciences.comIR@cassavasciences.com Cautionary Note Regarding Forward-Looking Statements: This news release contains forward-looking statements that may include but are not limited to statements regarding: the potential resolution of certain securities litigation and our loss contingency estimates related thereto, plans to conduct clinical studies with simufilam, our plans to conduct additional preclinical studies of simufilam relating to seizures in TSC, the potential for simufilam as a treatment for TSC-related epilepsy and other potential indications, the timing of anticipated milestones, the timing of payment of an estimated loss contingency related to the settlement of the Consolidated Securities Action, recorded in second quarter 2025, and expected cash balances and cash use in future periods. These statements may be identified by words such as “anticipate”, “before”, “believe”, “could”, “expect”, “forecast”, “intend”, “may”, ”pending”, “plan”, “possible”, “potential”, “prepares for”, “will”, and other words and terms of similar meaning. Such statements are based on our current expectations and projections about future events. Such statements speak only as of the date of this news release and are subject to a number of risks, uncertainties and assumptions, including, but not limited to, those risks relating to the ability to advance preclinical and clinical studies related to TSC-related epilepsy, and other potential indications, the ability to successfully carry out the Company’s obligations under the Yale License Agreement, the ability to initiate an initial proof-of-concept study of simufilam in TSC-related epilepsy, and other risks inherent in drug discovery and development or specific to Cassava Sciences, Inc., as described in the section entitled “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2024 and Quarterly Report on Form 10-Q for the period ended September 30, 2025, and subsequent reports to be filed with the SEC. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from expectations in any forward-looking statement. In light of these risks, uncertainties and assumptions, the forward-looking statements and events discussed in this news release are inherently uncertain and may not occur, and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements as predictions of future events. Except as required by law, we disclaim any intention or responsibility for updating or revising any forward-looking statements. For further information regarding these and other risks related to our business, investors should consult our filings with the SEC, which are available on the SEC's website at www.sec.gov. All of our pharmaceutical assets under development are investigational product candidates. These have not been approved for use in any medical indication by any regulatory authority in any jurisdiction and their safety, efficacy or other desirable attributes, if any, have not been established in any patient population. Consequently, none of our product candidates is approved or available for sale anywhere in the world. Our clinical results from earlier-stage clinical trials or preclinical studies may not be indicative of future results from later-stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements or any scientific data we present or publish. We are in the business of new drug discovery and development. Our research and development activities are long, complex, costly and involve a high degree of risk. Holders of our common stock should carefully read our Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q in their entirety, including the risk factors therein. Because risk is fundamental to the process of drug discovery and development, you are cautioned to not invest in our publicly traded securities unless you are prepared to sustain a total loss of the money you have invested.

Phase 2

12 Nov 2025

·www.globenewswire.com

Cassava Reports Q3 2025 Financials Results and Provides Business Update

Simufilam advancing towards a clinical study expected to begin in H1 2026 for the potential treatment of TSC-related epilepsyFurther fortified our strategic capabilities with the appointment of Dawn C. Bir to the Board of Directors$106.1 million in cash and cash equivalents at September 30, 2025. Expected to support operations into 2027 AUSTIN, Texas, Nov. 12, 2025 (GLOBE NEWSWIRE) -- – Cassava Sciences, Inc. (NASDAQ: SAVA, “Cassava”, the “Company”), a biotechnology company focused on developing novel, investigational treatments for central nervous system (CNS) disorders such as Tuberous Sclerosis Complex (TSC)-related epilepsy, today reported financial results for the third quarter ended September 30, 2025 and provided a business update. Net loss was $10.8 million, or $0.22 per share, compared to net loss of $27.9 million, or $0.58 per share, for the same period in 2024. Net cash used in operations was $22.5 million during the first nine months of 2025. The Company estimates cash at year-end 2025 in a range from $92 to $96 million, including incremental cash use of $10 to $14 million expected in Q4 2025. This represents a downward revision from previous guidance for net cash use in operations for second half 2025. While the Company maintains a $31.25 million estimated loss contingency related to a potential settlement of certain securities litigation recorded in Q2 2025, the timing of such potential settlement payment is unclear. Payment of a potential settlement was previously included in the cash use guidance for 2025. “2025 has been a year of significant progress for Cassava. We launched a program for simufilam focused on TSC-related epilepsy, building on the results of two sophisticated animal studies that support simufilam’s potential use as a first-in-class treatment. We enhanced our development capabilities with top-tier experts in neuroscience and medicine, and we expanded our Board to strategically guide this important new initiative,” said Rick Barry, President and Chief Executive Officer of Cassava. “We are excited to be working with the TSC Alliance and key opinion leaders in the field of TSC to create a proof-of-concept study which we intend to initiate in the first half of 2026.” Corporate Highlights:The Company is advancing simufilam as a potential treatment for TSC-related epilepsy, with positive preclinical progress and the appointment of experienced neuroscience leaders. TSC-related epilepsy (Proof-of-concept study planned for H1 2026)The program builds on groundbreaking work by Angélique Bordey, PhD, published in Neuron1 and Science Translational Medicine2 which showed treatment with simufilam alleviated neuronal abnormalities and reduced seizure frequency by 60% compared to vehicle in a mouse model of focal onset seizures. Target indication: Tuberous sclerosis complex (TSC)-related epilepsy. TSC affects approximately 50,000 people in the US and epilepsy is one of the most common neurological features of TSC, occurring in 84% of patients with TSC.3Positive preclinical data: In addition to the findings from the Bordey lab, simufilam also demonstrated positive preclinical results (August 2025) in a well-accepted mouse model of TSC-related epilepsy provided by the TSC Alliance. Simufilam attenuated the progression of seizure activity with a statistically significant correlation between simufilam dose and the number of seizures by the end of the study. Not all parameters measured reached statistical significance. The study, conducted in collaboration with the TSC Alliance and the TSC Preclinical Consortium, provides further support for the potential use of simufilam as a first-in-class treatment for TSC-related epilepsy. The Company intends to present data and analyses in an upcoming scientific conference and publication.Collaboration: Yale University license agreement (February 2025)Current status: Preparations are underway to initiate a proof-of-concept study in H1 2026 for TSC-related epilepsy, including development of the regulatory strategy. Corporate Updates: Joseph Hulihan, MD, MSHP, appointed Chief Medical Officer, bringing substantial clinical development experience advancing novel therapies for TSC-related epilepsy and other neurological disorders. Dr. Hulihan will devote approximately half of his professional time to Cassava (August 2025).Ms. Dawn C. Bir appointed as Independent Director, bringing a proven track record of aligning clinical development with strategic commercial goals to the Cassava Board of Directors (October 2025). Financial Results for Third Quarter 2025: Cash and cash equivalents were $106.1 million, with no debt, as of September 30, 2025. This compares to cash and cash equivalents of $128.6 million as of December 31, 2024.Total shares outstanding as of November 10, 2025 were 48.3 million.Net loss for the quarter ended September 30, 2025 was $10.8 million or $0.22 per share. This compares to a net loss of $27.9 million or $0.58 per share, for the same period in 2024.Net cash used in operations was $22.5 million during the first nine months of 2025.The Company estimates cash at year-end 2025 in a range from $92 to $96 million, including incremental cash use of $10 to $14 million expected in Q4 2025. This represents a downward revision from previous guidance for net cash use in operations for second half 2025. While the Company maintains a $31.25 million estimated loss contingency related to a potential settlement of certain securities litigation recorded in Q2 2025, the timing of such potential settlement payment is unclear. Payment of a potential settlement was previously included in the cash use guidance for 2025.Research and development (R&D) expenses for the quarter ended September 30, 2025 were $4.0 million. This compared to $17.7 million for the same period in 2024. This 78% decrease was due primarily to the phase out of the Alzheimer's disease development program, which was completed in the second quarter of 2025.General and administrative (G&A) expenses for the quarter ended September 30, 2025 were $7.9 million. This compared to $12.9 million for the same period in 2024. The 39% decrease was due primarily to a $2.5 million decrease in legal related costs compared to the prior year period. In addition, compensation costs decreased $1.3 million as severance costs recorded in the prior year period were not repeated in 2025. General and administrative expense in the third quarter of 2025 included approximately $3.2 million of legal related fees and costs as well as $3.1 million in non-cash stock-based compensation expense. About TSC and TSC-related Epilepsy TSC is a rare genetic disorder resulting from a mutation in the TSC1 or TSC2 gene in the mechanistic target of rapamycin (mTOR) pathway and involves multiple organs including the brain, heart, kidney, eye, skin, and lung2,4. Clinical findings range from minor skin abnormalities to more severe manifestations such as focal brain malformations, epileptic seizures, and TSC-Associated Neuropsychiatric Disorders (TAND)5. Symptoms typically change over time, making disease management challenging. Lifelong care and advocacy are important, especially for children with TSC6. TSC affects approximately 50,000 people in the US3. Epilepsy is the most common medical condition in people with TSC7, with median seizure onset occurring in the first few months of life8. Between 80% and 90% of TSC patients experience seizures1. Two-thirds of TSC patients have refractory epilepsy and experience life-long seizures1. Current therapies, including antiepileptic drugs and mTOR inhibitors, are not fully effective, and are associated with serious adverse events2. About Cassava Sciences, Inc. Cassava Sciences, Inc. (NASDAQ: SAVA), is a biotechnology company focused on developing novel, investigational treatments, including simufilam, for central nervous system disorders, such as tuberous sclerosis complex (TSC)-related epilepsy, and potentially other indications. Simufilam is a proprietary, investigational oral small molecule believed to modulate activity of the filamin A protein, which regulates diverse aspects of neuronal development1. The Company is based in Austin, Texas. For more information, please visit: https://www.CassavaSciences.com References: Zhang L, Bartley CM, Gong X, Hsieh, LS.; LinTV, Feliciano DM, Bordey A. "MEK-ERK1/2-Dependent FLNA Overexpression Promotes Abnormal Dendritic Patterning in Tuberous Sclerosis Independent of mTOR. Neuron (2014) 84 (1), 78-91. DOI: 10.1016/j.neuron.2014.09.009Zhang L, Huang T, Teaw S, Nguyen LH, Hsieh LS, Wong X, Burns LH, Bordey A. Filamin A inhibition reduces seizure activity in a mouse model of focal cortical malformations. Science Translational Medicine. (2020) 12(531):eaay0289. DOI: 10.1126/scitranslmed.aay0289https://www.tscalliance.org/understanding-tsc/what-is-tsc/Crino P, Nathanson K, Petri Henske, E. The Tuberous Sclerosis Complex. N Engl J Med. (2006) 355 (13):1345-56. DOI: 10.1056/NEJMra055323https://www.massgeneral.org/neurology/tsc/patient-education/how-tsc-affects-mental-health#:~:text=Nearly%20all%20people%20with%20TSC%20experience%20some%20form%20of%20mental,for%20people%20who%20have%20themhttps://www.massgeneral.org/neurology/tsc/patient-education/medical-care https://www.massgeneral.org/neurology/tsc/patient-education/how-tsc-affects-brain-seizureshttps://www.massgeneral.org/neurology/tsc/patient-education/how-tsc-affects-brain-seizures#:~:text=Although%20seizures%20can%20begin%20at,or%20neurons%2C%20of%20the%20brain For More Information Contact:InvestorsSandya von der Weidsvonderweid@lifesciadvisors.com CompanyEric Schoen, Chief Financial Officer(512) 501-2450ESchoen@CassavaSciences.comIR@cassavasciences.com Cautionary Note Regarding Forward-Looking Statements: This news release contains forward-looking statements that may include but are not limited to statements regarding: the potential resolution of certain securities litigation and our loss contingency estimates related thereto, the timing and plans to conduct clinical studies with simufilam in H1 2026, our plans to conduct additional preclinical studies of simufilam relating to seizures in TSC, the potential for simufilam as a treatment for TSC-related epilepsy and other potential indications, plans to present preclinical results in an upcoming scientific conference or publication, the timing of anticipated milestones, the timing of payment of an estimated loss contingency related to a potential settlement of certain securities litigation recorded in second quarter 2025, if realized, expected cash balances and cash use in future periods. These statements may be identified by words such as “anticipate”, “before”, “believe”, “could”, “expect”, “forecast”, “intend”, “may”, ”pending”, “plan”, “possible”, “potential”, “prepares for”, “will”, and other words and terms of similar meaning. Such statements are based on our current expectations and projections about future events. Such statements speak only as of the date of this news release and are subject to a number of risks, uncertainties and assumptions, including, but not limited to, those risks relating to the ability to advance preclinical studies related to TSC-related epilepsy, and other potential indications, the ability to successfully carry out the Company’s obligations under the Yale License Agreement, the ability to initiate an initial proof-of-concept study of simufilam in TSC-related epilepsy, and other risks inherent in drug discovery and development or specific to Cassava Sciences, Inc., as described in the section entitled “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2024 and Quarterly Report on Form 10-Q for the period ended September 30, 2025, and subsequent reports to be filed with the SEC. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from expectations in any forward-looking statement. In light of these risks, uncertainties and assumptions, the forward-looking statements and events discussed in this news release are inherently uncertain and may not occur, and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements as predictions of future events. Except as required by law, we disclaim any intention or responsibility for updating or revising any forward-looking statements. For further information regarding these and other risks related to our business, investors should consult our filings with the SEC, which are available on the SEC's website at www.sec.gov. All of our pharmaceutical assets under development are investigational product candidates. These have not been approved for use in any medical indication by any regulatory authority in any jurisdiction and their safety, efficacy or other desirable attributes, if any, have not been established in any patient population. Consequently, none of our product candidates is approved or available for sale anywhere in the world. Our clinical results from earlier-stage clinical trials or preclinical studies may not be indicative of future results from later-stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements or any scientific data we present or publish. We are in the business of new drug discovery and development. Our research and development activities are long, complex, costly and involve a high degree of risk. Holders of our common stock should carefully read our Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q in their entirety, including the risk factors therein. Because risk is fundamental to the process of drug discovery and development, you are cautioned to not invest in our publicly traded securities unless you are prepared to sustain a total loss of the money you have invested. – Financial Tables Follow – CASSAVA SCIENCES, INC.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(unaudited, in thousands, except per share amounts) Three months ended September 30, Nine months ended September 30, 2025 2024 2025 2024 Operating expenses Research and development$3,955 $17,676 $22,737 $49,107 General and administrative 7,905 12,947 59,101 62,852 Total operating expenses 11,860 30,623 81,838 111,959 Operating loss (11,860) (30,623) (81,838) (111,959)Interest income 1,167 2,618 3,646 6,710 Other income (loss), net (114) 62 (242) 321 Gain from change in fair value of warrant liabilities — — — 108,183 Net income (loss)$(10,807) $(27,943) $(78,434) $3,255 Net income (loss) per share, basic$(0.22) $(0.58) $(1.62) $0.07 Net loss per share, diluted (0.22) (0.58) (1.62) (0.88) Weighted-average shares used in computing net income (loss) per share, basic 48,308 47,976 48,293 45,734 Weighted-average shares used in computing net loss per share, diluted 48,308 47,976 48,293 46,101 CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited, in thousands) September 30, 2025 December 31, 2024 Assets Current assets Cash and cash equivalents$106,080 $128,574 Prepaid expenses and other current assets 2,830 7,958 Total current assets 108,910 136,532 Property and equipment, net 20,823 21,001 Total assets$129,733 $157,533 Liabilities and stockholders' equity Current liabilities Accounts payable and other accrued expenses$46,092 $7,654 Accrued development expense 1,366 2,440 Accrued compensation and benefits 362 1,357 Other current liabilities 226 299 Total current liabilities 48,046 11,750 Other non- current liabilities 119 79 Total liabilities 48,165 11,829 Stockholders' equity Common Stock and additional paid-in-capital 565,113 550,815 Accumulated deficit (483,545) (405,111) Total stockholders' equity 81,568 145,704 Total liabilities and stockholders' equity$129,733 $157,533

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100 Deals associated with Sumifilam

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 3	United States	Cassava Sciences, Inc.	03 Nov 2021
Alzheimer Disease	Phase 3	Australia	Cassava Sciences, Inc.	03 Nov 2021
Alzheimer Disease	Phase 3	Canada	Cassava Sciences, Inc.	03 Nov 2021
Epilepsy	Preclinical	United States	Cassava Sciences, Inc.	25 Mar 2025

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05026177 (REFOCUS-ALZ, CTgov)	Phase 3	Alzheimer Disease	1,125	Simufilam (Simufilam 50 mg)	phdmracnfx(spqbbytxqy) = ruprblcziw yudyhemmwj (qttrstyxni, 0.529) View more	-	22 Sep 2025
				Simufilam (Simufilam 100 mg)	phdmracnfx(spqbbytxqy) = abmhpzrnqf yudyhemmwj (qttrstyxni, 0.509) View more
NCT05352763 (CTgov)	Phase 2	Alzheimer Disease	90	simufilam	bgjjqaervk = jumpywkfan tpzhowgzbn (adpvqjcqdu, lechyjkvhr - buctxdbkhj) View more	-	15 Aug 2025
NCT04994483 (ReThink-ALZ, CTgov)	Phase 3	Alzheimer Disease	804	Simufilam (Simufilam 100 mg)	hmdzivnlet(awwjvcegof) = dyqrpxdshl rdibuqeomv (cslynrnenl, 0.363) View more	-	25 May 2025
				Placebo (Placebo)	hmdzivnlet(awwjvcegof) = dnqdrpscqe rdibuqeomv (cslynrnenl, 0.359) View more
NCT05575076 (CTgov)	Phase 3	Alzheimer Disease	1,081	Simufilam	kyijccztzh = uypcwsqwbs ebmexwzvce (vxebxtlsyp, sbqrrfeiut - jllenkvpzf) View more	-	14 May 2025
NCT05026177 (REFOCUS-ALZ, Company_Website) Manual	Phase 3	Alzheimer Disease	1,125	Simufilam 100 mg BID	etwwbfsroz(mhcfqyazco) = fsummvapce gflfvemcay (wcldmygrcc, 0.46) View more	Negative	25 Mar 2025
				Simufilam 50 mg BID	etwwbfsroz(mhcfqyazco) = mmjaaoznfl gflfvemcay (wcldmygrcc, 0.46) View more
NCT04994483 (ReThink-ALZ, Company_Website) Manual	Phase 3	Alzheimer Disease	804	Simufilam	rejlbcetmf(xkkgozjpfg) = kcxsjrkyji fxxuycxyik (zsyfdahuoy, 0.36) View more	Negative	25 Nov 2024
				Placebo	rejlbcetmf(xkkgozjpfg) = bsmufjbhqw fxxuycxyik (zsyfdahuoy, 0.36) View more
NCT04388254 (GlobeNewswire) Manual	Phase 2	Alzheimer Disease	-	Simufilam 100 mg (mild Alzheimer’s disease; treatment continuously for two years)	seqhvydqyc(senrcddoti) = ozptnqlitq fntppngpzn (rtqnsjydnd, 1.51) View more	Positive	07 Feb 2024
				Simufilam 100 mg (mild Alzheimer’s disease; treatment continuously for two years)	seqhvydqyc(senrcddoti) = gxwfpjebwc fntppngpzn (rtqnsjydnd, 1.65) View more
NCT04932655 (CTgov)	Phase 1	-	24	Simufilam (Fasted Phase 3 Simufilam)	zamehoqfva(xciimyaxjc) = hbrumntrfu xdorgcquem (ytymclaftq, 190) View more	-	22 Aug 2023
				Simufilam (Phase 3 High-fat Fed Simufilam)	zamehoqfva(xciimyaxjc) = oggervpesz xdorgcquem (ytymclaftq, 156) View more
NCT05026177 \| NCT04994483 (REFOCUS-ALZ \| RETHINK-ALZ, Corporate Publications) Manual	Phase 3	Alzheimer Disease	100	simufilam	lbqmydqaoc(roruzdklce) = vqxibrrtbh wqvayecray (qrwpyheyif ) View more	-	03 Aug 2022
NCT04388254 (Corporate Publications) Manual	Phase 2	Alzheimer Disease	50	simufilam	cgotrjfpjs(ekuycxhvkp) = cdssyjachz tjixtvszwh (bzxpdihtsw ) View more	Positive	22 Sep 2021
				Placebo	cgotrjfpjs(ekuycxhvkp) = ofptebblyn tjixtvszwh (bzxpdihtsw )

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