Cassava Sciences, Inc.

Simufilam did not show a significant reduction in co-primary endpoints of cognitive or functional decline versus placebo in patients with mild-to-moderate Alzheimer’s disease Simufilam continued to demonstrate an overall favorable safety profile Cassava’s Alzheimer’s disease development program with simufilam will be completely discontinued by the end of Q2 2025 March 25, 2025 -- Cassava Sciences, Inc. (NASDAQ: SAVA, “Cassava”, the “Company”), a clinical-stage biotechnology company focused on developing a novel, investigational treatment for central nervous system disorders, including Alzheimer’s disease (AD) dementia and tuberous sclerosis complex (TSC)-related epilepsy, today shared topline results from the Phase 3 REFOCUS-ALZ study of simufilam in mild-to-moderate AD. Topline data indicate that REFOCUS-ALZ did not meet each of the prespecified co-primary, secondary and exploratory biomarker endpoints. The co-primary endpoints were the change in cognition and function from baseline to the end of the double-blind treatment period at week 76, assessed by the ADAS-COG12 and ADCS-ADL scales, comparing simufilam to placebo. REFOCUS-ALZ enrolled 1,125 patients and was discontinued on November 25, 2024, following the report that a prior 52-week Phase 3 study, RETHINK-ALZ, did not meet its co-primary endpoints. A large portion of subjects enrolled in REFOCUS-ALZ completed their final study visit prior to the termination of the trial. Simufilam continued to demonstrate an overall favorable safety profile. “We are disappointed that the results of REFOCUS-ALZ and RETHINK-ALZ showed no treatment benefit for patients with mild-to-moderate Alzheimer’s disease. These results were unambiguous. Working with patients, their families and their caregivers has brought a special dignity to our Phase 3 Alzheimer’s disease clinical trial program and to each of us at Cassava. We are deeply grateful for the dedication and committed efforts of study investigators and site teams, who enabled us to conduct these trials with integrity and scientific rigor and whose efforts provided a clear data read out,” said Rick Barry, President and Chief Executive Officer of Cassava. “Cassava will discontinue all efforts to develop simufilam for Alzheimer’s disease and we expect to phase out the program by the end of Q2 2025,” continued Mr. Barry. “We remain dedicated to our mission of developing novel medicines for central nervous system disorders. While we have initiated preclinical studies to evaluate simufilam’s potential as a treatment for TSC-related epilepsy, we maintain ongoing strategic expense management efforts.” Eric Schoen, Chief Financial Officer of Cassava commented, “We remain focused on the interests of Cassava shareholders and are committed to enhancing shareholder value. Cassava is well-capitalized with approximately $128.6 million in cash and cash equivalents as of December 31, 2024.” REFOCUS-ALZ (NCT05026177) is a Phase 3 trial designed as a multi-center, double-blinded, placebo-controlled, randomized parallel group study to evaluate the safety and efficacy of two doses of simufilam compared to a placebo in a study involving over 75 clinical trial sites in the U.S., Canada, Puerto Rico and South Korea. The clinical trial sites that conducted REFOCUS-ALZ were completely distinct from the clinical trial sites that conducted RETHINK-ALZ. REFOCUS-ALZ randomized approximately 1,125 people utilizing the same eligibility criteria as RETHINK-ALZ. Subjects were randomized 1:1:1 to receive simufilam, dosed in 50 mg or 100 mg tablets, or a matched placebo, dosed orally twice daily (BID) for 76 weeks. On November 25, 2024, the Company announced plans to discontinue the REFOCUS-ALZ study and its intention to report topline data from that trial, including the complete 52-week dataset and a large portion of 76-week data. The prespecified co-primary endpoints for this study included the change in cognition and function from baseline to the end of the double-blind treatment period at week 76, assessed by the ADAS-COG12 and ADCS-ADL scales, comparing each dose of 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. The study also included an evaluation of changes in plasma and cerebrospinal fluid biomarkers from baseline to week 76, including P-tau217 (phosphorylated tau at threonine 217), GFAP (glial fibrillary acidic protein) and NFL (neurofilament light chain), as well as an evaluation of various brain volumes using MRI (magnetic resonance imaging) and amyloid and tau deposition using PET (positron emission tomography) scans from baseline to week 76. Simufilam is a proprietary, investigational oral small molecule that targets the filamin A protein. Cassava Sciences, Inc. (NASDAQ: SAVA), a clinical-stage biotechnology company focused on developing novel, investigational treatments for central nervous system disorders, including Alzheimer’s disease and tuberous sclerosis complex (TSC)-related epilepsy. Simufilam is a proprietary, investigational oral small molecule that targets the filamin A protein. The Company is based in Austin, Texas. 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President Donald Trump continues to warn of tariffs on the pharmaceutical industry; Susan Monarez replaces Dave Weldon as CDC director nominee; Novo Nordisk joins the triple-G race; Alnylam wins approval for Amvuttra in ATTR-CM; and Cassava Sciences ends development of simufilam in Alzheimer’s. > Listen on Spotify > Listen on Apple Products > Listen on Amazon Music > Listen on iHeart President Donald Trump doubled down on tariff threats targeting pharma, saying additional levies on pharmaceuticals will come “at some point,” per CNBC. Meanwhile, Johnson & Johnson became the latest big pharma to respond to Trump’s warning of potential tariffs if companies don’t reshore their manufacturing, announcing a massive $55 billion U.S. manufacturing and R&D investment. Not all companies are on board, however: AstraZeneca is looking eastward, pumping $2.5 billion into a new research facility in Beijing. Also on the policy front, Trump nominated acting CDC director Susan Monarez for the top job after pulling his first nominee, Dave Weldon , days before his senate hearing was expected to begin. If confirmed, Monarez would be the first CDC director since 1953 to not have a medical degree; she holds a Ph.D. in microbiology and immunology from the University of Wisconsin. In weight loss news, Novo Nordisk is paying China-based United Laboratories $200 million upfront to license a triple agonist of the GLP-1, GIP and glucagon receptors that could one day compete with Eli Lilly’s retatrutide. And BioSpace examines the next great challenge for GLP-1s: oral formulation manufacturing. Two more therapeutic spaces in focus last week are Duchenne muscular dystrophy and spinal muscular atrophy , where companies including Dyne Therapeutics, REGENXBIO and Novartis presented new data on their respective candidates. And the Duchenne community continued to react to news of the death of a patient taking Sarepta’s approved gene therapy Elevidys . In cardiovascular news, Alnylam won a much-anticipated approval for Amvuttra as the first RNAi silencer for transthyretin amyloid cardiomyopathy, setting up a three-way race with Pfizer’s tafamidis—marketed as Vyndaqel and Vyndama—and BridgeBio’s Attruby. Next up is Milestone Therapeutics’ CARDAMYST in paroxysmal supraventricular tachycardia, which has a PDUFA date of March 27. Finally, the saga of Cassava Sciences’ Alzheimer’s hopeful simufilam is over, as the company announced it has ended development of the controversial candidate.

Shares in Cassava Sciences fell more than 20% to $2.20 when the markets opened Tuesday from a Monday closing price of $2.78.\n Cassava Sciences has given up on simufilam in Alzheimer’s disease. Months after seeing one phase 3 trial fail, the biotech is planning to stop development altogether after chalking up another late-stage flop.Texas-based Cassava discontinued the second study, ReFocus-ALZ, when it reported the first failure late last year. But with all the patients completing 52 weeks of follow-up, and many making it to the 76-week assessments, before Cassava pulled the plug, ReFocus-ALZ still offered the biotech a final chance to show simufilam may be effective against Alzheimer’s.Instead, the failure of the trial sealed simufilam’s fate. Cassava said ReFocus-ALZ missed its prespecified co-primary, secondary and exploratory biomarker endpoints. The co-primary endpoint data left no room for optimistic interpretations. On ADAS-COG12, where lower numbers mean less cognitive impairment, scores rose by 4.97 and 5.26 points in the two simufilam cohorts and by 4.70 points in the placebo group. Similarly, on ADCS-ADL, where higher numbers mean less functional impairment, scores fell by 6.27 and 6.43 points on simufilam arms and by 5.32 points on placebo.  The failures on the co-primary endpoints and broader dataset led Cassava CEO Rick Barry to conclude the trial “showed no treatment benefit for patients.” Barry was blunt about the data and the next steps.“These results were unambiguous,” Barry said. “Cassava will discontinue all efforts to develop simufilam for Alzheimer’s disease and we expect to phase out the program by the end of Q2 2025.”Having recently entered a license agreement, Cassava has begun preclinical studies to assess simufilam as a potential treatment of tuberous sclerosis complex-related epilepsy. While the biotech is investing in those studies, it is maintaining its “ongoing strategic expense management efforts,” Barry said. Cassava ended last year with $128.6 million in cash and cash equivalents.Shares in Cassava fell more than 20% to $2.20 when the markets opened Tuesday from a Monday closing price of $2.78.