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An Independent Data and Safety Monitoring Board (DSMB) Recently Evaluated the Interim Patient Safety Database for Oral Simufilam in On-going Phase 3 Trials. The DSMB Recommended Both Phase 3 Trials Continue as Planned, Without Modification. Final Clinical Safety Data for Simufilam Are Expected at the Conclusion of the Phase 3 Program. Sept. 24, 2024 -- Cassava Sciences, Inc. (Nasdaq: SAVA), a biotechnology company focused on Alzheimer’s disease, today announced the completion of a third interim safety review of simufilam in on-going Phase 3 clinical trials in patients with Alzheimer’s disease. A routine, scheduled meeting of a Data and Safety Monitoring Board (DSMB) resulted in a recommendation that both of Cassava Sciences’ on-going Phase 3 studies continue as planned, without modification. “We are pleased to have satisfactorily completed this safety review, the last before the expected top-line read out for our first Phase 3 study.” said Jim Kupiec, Chief Medical Officer. “We look forward to announcing top-line efficacy, safety and biomarker data for our 12-month Phase 3 study before the end of 2024.” The DSMB is composed of independent clinical research experts who periodically review interim patient safety data for Cassava Sciences’ on-going Phase 3 trials of simufilam in Alzheimer’s disease. This DSMB only reviews patient safety. It does not assess drug efficacy. Cassava Sciences’ simufilam is a novel, small molecule drug candidate for the proposed treatment of Alzheimer’s disease dementia. The drug is in late-stage clinical evaluation in a pair of pivotal Phase 3 trials. These Phase 3 trials are fully enrolled. Over 1,900 patients with mild-to-moderate Alzheimer’s disease who also met other study eligibility criteria were randomized into the trials. The first Phase 3 trial (NCT04994483) has a 52-week treatment period; 804 Alzheimer’s patients were randomized into this trial. Top-line results for the 52-week Phase 3 trial are currently expected by year-end 2024. The second Phase 3 trial (NCT05026177) has a 76-week treatment period; 1,125 Alzheimer’s patients were randomized into this trial. Top-line results for the 76-week Phase 3 trial are currently expected approximately mid-year 2025. Patients with mild-to-moderate Alzheimer’s disease dementia who met study eligibility criteria were recruited into the Phase 3 program from clinical sites in the U.S., Puerto Rico, Canada, Australia and South Korea. Cassava Sciences is conducting its on-going Phase 3 program in collaboration with Premier Research International, a global contract research organization (CRO). Today’s news follows interim safety MRI data announced in October 2023, which suggests simufilam is not associated with treatment-emergent amyloid-related imaging abnormalities (ARIA). In addition, September 2023 and March 2024 meetings of the DSMB recommended that both Phase 3 trials continue as planned, without modification. Final safety data are expected at the conclusion of the Phase 3 program. Cassava Sciences is a clinical-stage biotechnology company based in Austin, Texas. Our mission is to detect and treat neurodegenerative diseases, such as Alzheimer’s disease. Simufilam is Cassava Sciences’ small molecule oral drug candidate currently in Phase 3 clinical trials for the treatment of Alzheimer's disease. Simufilam targets a specific site on filamin A, a scaffolding protein that is critical to certain receptor interactions in the brain. Cassava Sciences believes that simufilam interrupts amyloid-β42 binding to receptors in the brain and may affect the Alzheimer's disease process. Cassava Sciences owns exclusive, worldwide rights to its investigational product candidates and related technologies, without royalty obligations to any third party. The content above comes from the network. if any infringement, please contact us to modify.

iStock/ wildpixel The next generation of Alzheimer’s therapeutics is moving away from amyloid plaques and tau tangles, offering multiple approaches to slow cognitive decline. Over the past two years, Eisai and Biogen’s Leqembi and Eli Lilly’s Kisunla, both anti-amyloid antibodies, made history as the first real options to slow cognitive decline associated with Alzheimer’s disease. For years, amyloid plaques and tau tangles have been a primary target of Alzheimer’s disease research and drug development, but while affecting these proteins may yield some benefit, the illness continues to progress. Today, multiple therapeutics are in Phase III trials with other targets, suggesting that within the next few years it may become possible to treat Alzheimer’s via multiple pathways. There are currently 32 Alzheimer’s therapeutics in 48 Phase III trials, according to a recent paper by neuroscientist Jeffrey Cummings, a professor at the University of Nevada. Six of those target amyloid-β and one targets tau, but the others aim to affect neuroprotection growth factors, neurotransmitters, neurogenesis, inflammation and proteinopathies. Of those, 21 are meant to be disease-modifying. “Alzheimer’s disease is quite complex in its biology and diagnosis,” Rebecca Edelmayer, vice president of scientific engagement for the Alzheimer’s Association, told BioSpace. “We’re moving to a point where we have better understanding of the disease and what contributes to its symptomology, so those biological underpinnings become targets.” These approaches won’t necessarily replace Leqembi and Kisunla, but they could increase therapeutic options to better manage the disease. The First Anti-Amyloid Antibodies for Alzheimer’s In January 2023, the FDA approved Leqembi as the second disease-modifying treatment for Alzheimer’s disease. The third, Kisunla , followed in July 2024. (The first drug, Eisai and Biogen’s Aduhelm, was discontinued earlier this year.) While Leqembi and Kisunla are a positive step forward, experts suggest there is room for improvement. As measured by the Clinical Dementia Rating Sum of Boxes (CDR-SB), Leqembi reduced clinical decline by 27%, whereas Kisunla reduced clinical decline by 29%. In addition to limited efficacy, the drugs both have notable side effects, specifically, the risk of amyloid-related imaging abnormalities (ARIA), the increase in lateral ventricular volume and the simultaneous loss of whole brain volume. A finding of ARIA on imaging tests is indicative of a brain bleed or swelling. When physician online community Sermo questioned 268 neurologists, it found a diversity of opinion on how to best determine clinical benefit. Forty percent of those surveyed have treated Alzheimer’s patients with Leqembi or Kisunla. “There’s debate about whether the two already approved therapeutics are that compelling, so the bar is low,” Andrew Tsai, senior vice president of equity research for the biopharma analyst Jefferies, told BioSpace . A major difference between the two is that Leqembi is infused intravenously twice monthly, while Kisunla is infused only once per month. But any infusion is a pain point for many patients, not to mention a cost to the healthcare system, so easier administration is the goal for several next- gen Alzheimer’s therapeutics. Lilly’s drug is also designed to stop treatment once plaque clearance is achieved. Phase III Alzheimer’s Candidates Athira’s Fosgonimeton Athira Pharma’s fosgonimeton is a small-molecule therapeutic that may be injected daily at home. The company recently reported data from a Phase II/III trial of the drug, which enhances signaling by neurotrophic hepatocyte growth factor (HGF). The trial, which included 315 patients with mild-to-moderate Alzheimer’s disease, failed to meet its primary and key secondary endpoints regarding improvements in cognition and function at the 26-week point. However, pre-specified subgroups experienced rapid disease progression, while both cognition and function either stabilized or improved. Biomarkers also showed improvement, according to the company. In preclinical models of Alzheimer’s disease, fosgonimeton has “been shown to reduce inflammation, improve mitochondrial and synaptic function and reduce amyloid toxicity and p-tau aggregation,” Chief Medical Officer Javier San Martin told BioSpace in an email. “[While] Leqembi and Kisunla are monoclonal antibodies targeting removal of amyloid plaque from the brain with the expectation that by removing amyloid the neurons will be preserved . . . fosgonimeton focuses on improving neuronal health regardless whether the insult is amyloid, tau or other misfolded proteins,” he said. Anavex’s ANAVEX 2-73 In New York, Anavex Life Sciences Corp. is targeting neuronal homeostasis in an ongoing Phase IIb/III study with blarcamesine, an oral, once-daily therapeutic that works “through autophagy through SIGMAR1 activation .” “Blarcamesine’s ability to reduce pathological brain volume loss could be defined as disease-modifying,” Andrew Barwicki, company spokesperson, told BioSpace . In the Phase IIb/III trial , blarcamesine slowed clinical progression of Alzheimer’s by 38.5% at 48 weeks, compared to placebo. Analysis of the Phase IIb/III trial showed no associated neuroimaging adverse events and, unlike Kisunla and Leqembi , blarcamesine is not expected to require routine MRI monitoring. “Blarcamesine could be appealing because of its route of administration and good comparative safety profile,” Barwicki suggested. Anavex anticipates submitting a full regulatory package to the European Medicines Agency by the end of this year. Novo Nordisk’s Semaglutide Novo Nordisk is testing semaglutide , its wildly popular glucagon-like peptide-1 (GLP-1) receptor agonist for weight loss and other indications, in patients with early Alzheimer’s. Completion of the Phase III study is expected in October 2026. Early studies by independent scientists suggest semaglutide reduces neuroinflammation , which impairs cell signaling. It also may improve vascularization. Neurim’s Piromelatine At Neurim Pharmaceuticals, a Phase III trial in Alzheimer’s patients with mild dementia will determine whether piromelatine can improve cognition and function by improving sleep quality. The hypothesis is that sleep disturbances increase synaptic and metabolic activity, impairing the brain’s ability to clear wastes, which then increases amyloid beta aggregation. Piromelatine works by activating certain melatonin and serotonin receptor agonists. Cassava Sciences’ Simufilam Finally, Austin, Texas–based Cassava Sciences seeks to restore the brain’s shape and function by stabilizing the scaffolding protein filamin A (FLNA), thus purportedly blocking signaling from soluble amyloid beta. But Cassava’s conduct around simufilam has spurred an investigation by the U.S. Department of Justice. The company’s former science advisor, Hoau-Yan Wang, was indicted in June for allegedly falsifying scientific data that led to the awards of some $16 million in NIH grants between 2015 and 2023. The charges include allegedly misconstruing data about how “a potential treatment” and its diagnostic test would work. The company’s August corporate overview reiterates a February news release , noting that patients with mild Alzheimer’s who were treated with its oral therapeutic, simufilam , continuously for two years had no decline in their ADAS-Cog scores. Non-continuous treatment resulted in a one-point ADAS-Cog decline. In late July, Cassava added an open-label extension to its ongoing Phase II and III clinical trials for Alzheimer’s, which attracted 89% of its Phase III patients. According to August’s corporate overview, Cassava expects topline results from its 804-patient RETHINK-ALZ trial by year’s end. Combinations Are Key Alzheimer’s is a very hetergeneous disease and there is no magic bullet for treatment. Given the many different mechanisms of action of emerging Alzheimer’s therapeutics, “there may be a case for teaming up and using certain therapeutics in combination,” Tsai said. “We’re excited to see the clinical trial pipeline diversity over time,” Edelmayer added, but the solution may involve more than therapeutics. Ultimately, “Treatment may require a combination of powerful, FDA-approved therapies in conjunction with brain-healthy lifestyles. We envision a future where there are many treatments that address the disease in multiple ways.”

$207.3 Million in Cash and Cash Equivalents at June 30, 2024.Company in Advanced Discussions to Resolve SEC Investigation. $40 Million Estimated Loss Contingency Recorded in Q2 for Resolution.Conference Webcast Scheduled for Today at 8:30AM ET. AUSTIN, Texas, Aug. 08, 2024 (GLOBE NEWSWIRE) -- Cassava Sciences, Inc. (Nasdaq: SAVA), a biotechnology company focused on a novel treatment for Alzheimer’s disease, today reported financial results for the second quarter ended June 30, 2024. Net income was $6.2 million compared to a net loss of $26.4 million for the same period in 2023. Net cash used in operations was $37.4 million during the first half of 2024, consistent with previous guidance. Net cash use in second half 2024 is expected to be $80 to $90 million, which includes an estimated $40 million loss contingency related to advanced discussions to resolve the SEC’s investigation of the Company recorded in the second quarter. “We have made significant progress over the last few months,” Rick Barry, Cassava’s Executive Chairman said. “The Cassava Clinical Operations team in conjunction with Premier Research have done a brilliant job in executing our Phase 3 program. We expect our last patient/last visit for our ReTHINK trial in early Q4 and a top-line read out from the trial by year-end. We also expect our second Phase 3 trial, ReFOCUS, to read out in mid-year 2025. The success of our warrant program earlier in the second quarter – which provided over $123 million net in equity capital to Cassava – has provided the Company with a strong balance sheet with enough liquidity to get well past our Phase 3 readouts. We are very grateful for the confidence that investors, principal investigators, patients and their loved ones have shown in Cassava. Our team’s urgent focus is to deliver a best-in-class therapy for Alzheimer’s patients.” Current Updates on Phase 3 Clinical ProgramBackground - Our Phase 3 program consists of two global, double-blind, randomized, placebo-controlled studies of simufilam in patients with mild-to-moderate Alzheimer’s disease dementia. The goal is to evaluate overall risk/benefit for oral simufilam twice-daily versus placebo in a large population of people with Alzheimer’s disease over 12 and 18 months. The target study population is people with mild-to-moderate Alzheimer’s (MMSE score of 16-27) who are biomarker-positive for Alzheimer’s disease pathology, and who meet other inclusion/exclusion eligibility criteria of the study protocols. Phase 3 Trials – Our first Phase 3 study, called RETHINK-ALZ, is designed to evaluate the safety and efficacy of simufilam 100 mg tablets twice-daily versus matching placebo over 52 weeks (NCT04994483). Our second Phase 3 study, called REFOCUS-ALZ, is designed to evaluate the safety and efficacy of oral simufilam 100 mg and 50 mg tablets twice-daily versus matching placebo over 76 weeks (NCT05026177). Clinical sites are in the United States, Canada, Puerto Rico, Australia, and South Korea. Premier Research International is the clinical research organization (CRO) supporting the conduct of our Phase 3 clinical program. Patient Enrollment – Both Phase 3 studies are fully enrolled. Approximately 1,900 patients are randomized in these studies, with approximately 800 patients randomized in the 52-week study (RETHINK-ALZ) and approximately 1,100 patients randomized in the 76-week study (REFOCUS-ALZ). Approximately 90% of patients are recruited from clinical sites in the U.S. and Canada. The overall drop-out rate for both Phase 3 studies is in the range of 20% to 23%, which is generally consistent with expectations. A longer study will generally have a higher dropout rate versus a similar shorter study. Patient Completion – Over 555 patients have completed the 52-week RETHINK-ALZ study. Over 420 patients have completed the 76-week REFOCUS-ALZ study, for a total of over 975 completers. Data and Safety Monitoring Board (DSMB) – The DSMB is composed of independent clinical research experts who periodically review interim patient safety data. Routine, scheduled DSMB meetings were held September 2023 and March 2024. Both DSMB meetings recommended that the Phase 3 studies continue as planned, without modification. Co-primary Efficacy Outcomes – The pre-specified efficacy endpoints for the Phase 3 studies are ADAS-Cog12, a cognitive scale, and ADCS-ADL, a functional scale. Phase 3 Efficacy Results – All efficacy data from our Phase 3 program remain blinded. No interim analyses on efficacy outcomes are planned. We anticipate top-line data readout for our 52-week study (RETHINK-ALZ) by the end of 2024. We anticipate top-line data readout for our 76-week study (REFOCUS-ALZ) approximately mid-year 2025. Open-label Extension Study – This study is designed to provide no-cost access to oral simufilam to Alzheimer’s patients who have successfully completed a Phase 3 study of simufilam and who meet other entry criteria. Approximately 89% of patients who’ve completed treatment in a Phase 3 study have opted to enter the open-label extension study. To date, over 870 patients have entered the open-label extension study. The open-label study is intended to continue for up to 36 months or until a new drug application for simufilam has been reviewed by FDA. Cassava also plans to add cognition and plasma biomarker monitoring to its open-label extension trial for patients who have completed the Phase 3 trials in order to gather additional long-term data on the potential impact of simufilam treatment. Financial Results for Second Quarter 2024 At June 30, 2024, cash and cash equivalents were $207.3 million, with no debt.Cash balance includes total gross proceeds received from the cash-exercise of common stock warrants in 2024 totaling $126.3 million, inclusive of approximately $104.0 million received in second quarter 2024. Holders exercised warrants for approximately 5.74 million common shares at a price of $22 per share in 2024. There are no remaining common stock warrants currently outstanding.Net income was $6.2 million compared to a net loss of $26.4 million for the same period in 2023. Net income resulted from the change in fair value of warrant liabilities, a non-cash item. This warrant gain was partially offset by an estimated $40.0 million loss contingency recorded in respect of a potential resolution of the SEC’s investigation and costs to conduct the Phase 3 clinical program, as well as other studies with simufilam.Net cash used in operations was $37.4 million during the first six months of 2024, consistent with previous guidance.Net cash use in operations for second half 2024 is expected to be $80 to $90 million, which includes an estimated $40 million loss contingency related to advanced discussions to resolve the SEC’s investigation. The Company estimates cash at year-end 2024 in a range from $117 to $127 million.Research and development (R&D) expenses were $15.2 million. This compared to $25.0 million for the same period in 2023. R&D expenses decreased due primarily to the completion of patient screening and enrollment for our Phase 3 clinical program in the fall of 2023.General and administrative (G&A) expenses were $46.2 million. This compared to $3.8 million for the same period in 2023. G&A expenses increased due primarily to the estimated loss contingency in respect of a potential SEC resolution as well as a $1.2 million increase in stock-based compensation expense due to new grant awards in late 2023 and 2024, increased compensation costs and higher legal related expenses. Webcast DetailsDate: Thursday, August 8th Time: 8:30 a.m. Eastern Time Audio Webcast: https://www.CassavaSciences.com/company-presentations Or https://edge.media-server.com/mmc/p/zjvmjjcr About SimufilamSimufilam is Cassava Sciences’ proprietary oral drug candidate. This investigational drug binds to altered filamin A protein in the brain and restores its normal shape and function. By targeting altered filamin A, simufilam may help patients with Alzheimer’s achieve better health outcomes. Cassava Sciences owns exclusive, worldwide rights to its investigational product candidates and related technologies, without royalty obligations to any third party. About Cassava Sciences, Inc.Cassava Sciences is a clinical-stage biotechnology company based in Austin, Texas. Our mission is to detect and treat neurodegenerative diseases, such as Alzheimer’s disease. Our novel science is based on stabilizing—but not removing—a critical protein in the brain. For more information, please visit: https://www.CassavaSciences.com For More Information Contact: Sitrick And Company1-800-550-7521Mike_Sitrick@Sitrick.comSeth Lubove: slubove@sitrick.comNY: Rich Wilner: rwilner@sitrick.com 800-699-1481 Cautionary Note Regarding Forward-Looking Statements: This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, that may include but are not limited to statements regarding: the potential for advanced discussions with SEC to result in a resolution of the SEC investigation and our loss contingency estimates related thereto; our ability to extend our existing open-label extension trials, as contemplated or at all; the design, scope, conduct, continuation, completion, intended purpose, or future results of our on-going Phase 3 program of simufilam in patients with Alzheimer's disease; the timing of anticipated milestones; the assessment of interim safety data for the Phase 3 program at prior DSMB meetings; the treatment of people with Alzheimer’s disease dementia; the safety or efficacy of simufilam in people with Alzheimer’s disease dementia; expected cash balances and cash use in future periods; comments made by our employees regarding simufilam, drug effects, and the treatment of Alzheimer’s disease; and potential benefits, if any, of our product candidates. These statements may be identified by words such as “anticipate,” “believe,” “could,” “expect,” “forecast,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” and other words and terms of similar meaning. Such statements are based largely 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 conduct or complete clinical studies on expected timelines, the ability to demonstrate the specificity, safety, efficacy or potential health benefits of our product candidates, the apparent ability of simufilam to favor patients with mild Alzheimer’s disease; the apparent safety or tolerance of simufilam in our open-label clinical trials; our current expectations regarding timing of clinical data for our Phase 3 studies; any expected clinical results of Phase 3 studies; the treatment of people with Alzheimer’s disease dementia; and comments made by our employees regarding simufilam, drug effects, and the treatment of Alzheimer’s disease; potential benefits, if any, of our product candidates and including those described in the section entitled “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent reports 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 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 are approved or available for sale anywhere in the world. Our clinical results from earlier-stage clinical trials 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 filings with the SEC 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 June 30, Six months ended June 30, 2024 2023 2024 2023 Operating expenses Research and development$15,198 $24,969 $31,431 $47,089 General and administrative 46,204 3,808 49,905 8,200 Total operating expenses 61,402 28,777 81,336 55,289 Operating loss (61,402) (28,777) (81,336) (55,289)Interest income 2,316 2,198 4,092 4,249 Other income, net 99 203 259 393 Gain from change in fair value of warrant liabilities 65,142 — 108,183 — Net income (loss)$6,155 $(26,376) $31,198 $(50,647) Net income (loss) per share, basic$0.13 $(0.63) $0.70 $(1.21)Net income (loss) per share, diluted 0.13 (0.63) (1.72) (1.21) Weighted-average shares used in computing net income (loss) per share, basic 46,202 41,793 44,601 41,766 Weighted-average shares used in computing net income (loss) per share, diluted 46,202 41,793 45,152 41,766 CONDENSED CONSOLIDATED BALANCE SHEETS(unaudited, in thousands) June 30, 2024 December 31, 2023Assets Current assets Cash and cash equivalents $207,291 $121,136 Prepaid expenses and other current assets 14,831 8,497 Total current assets 222,122 129,633 Property and equipment, net 21,364 21,854 Intangible assets, net 82 176 Total assets $243,568 $151,663 Liabilities and stockholders' equity Current liabilities Accounts payable and accrued expenses $52,552 $10,573 Accrued development expense 1,596 3,037 Accrued compensation and benefits 218 200 Other accrued liabilities 228 385 Total current liabilities 54,594 14,195 Stockholders' equity Common Stock and additional paid-in-capital 538,545 518,237 Accumulated deficit (349,571) (380,769)Total stockholders' equity 188,974 137,468 Total liabilities and stockholders' equity $243,568 $151,663