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

Rhea-AI Summary

Cassava (NASDAQ: SAVA) announced publication of a peer-reviewed JPAD article reporting detailed results from the Phase 3 RETHINK-ALZ (N=804) and REFOCUS-ALZ (N=1,125) trials of simufilam in mild-to-moderate Alzheimer’s disease, dated January 13, 2026. The paper confirms the studies did not meet prespecified co-primary, secondary, or exploratory biomarker endpoints, but reports a favorable safety profile and exploratory/post-hoc signals in predefined mild subgroups and pooled analyses at weeks 4–52 (nominal p-values reported). The company has discontinued development and plans no further investment in the Alzheimer’s program.

Positive

• Favorable safety profile reported across RETHINK-ALZ and REFOCUS-ALZ
• Pooled mild-subgroup showed nominally significant differences at weeks 4 and 28
• Phase 3 trials were the first to rely primarily on plasma p-tau181 for biological confirmation

Negative

• Both trials failed to meet prespecified co-primary, secondary, and exploratory endpoints
• Cassava has discontinued the Alzheimer’s program and will make no further investment
• Amyloid PET sub-study found 21% amyloid-negative participants, suggesting plasma p-tau181 cutoff was insufficient

News Market Reaction

-3.30%

12 alerts

-3.30% News Effect

+2.1% Peak in 14 min

-$4M Valuation Impact

$106M Market Cap

0.3x Rel. Volume

On the day this news was published, SAVA declined 3.30%, reflecting a moderate negative market reaction. Argus tracked a peak move of +2.1% during that session. Our momentum scanner triggered 12 alerts that day, indicating notable trading interest and price volatility. This price movement removed approximately $4M from the company's valuation, bringing the market cap to $106M at that time.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

RETHINK-ALZ enrollment: 804 patients REFOCUS-ALZ enrollment: 1,125 patients MMSE mild range: 21–27 +5 more

8 metrics

RETHINK-ALZ enrollment 804 patients Phase 3 mild-to-moderate Alzheimer’s trial

REFOCUS-ALZ enrollment 1,125 patients Phase 3 mild-to-moderate Alzheimer’s trial

MMSE mild range 21–27 Predefined mild subgroup in trials

ADAS-Cog12 p-values p = 0.01, 0.01, 0.02, 0.02, 0.02 Mild subgroup, Weeks 4, 28, 40, 52, 64 in REFOCUS-ALZ

Pooled mild p-values p < 0.01; p = 0.03, 0.001, 0.006, 0.066 Pooled mild subgroups through Week 52

Amyloid-negative rate 21% (33 of 160) Amyloid PET sub-study in REFOCUS-ALZ baseline

Plasma p-tau181 cutoff ≥ 67 Entry criterion; highest half in pooled mild analysis

Missing data at Week 76 45% REFOCUS-ALZ due to early study termination

Market Reality Check

Price: $1.99 Vol: Volume 689,740 is below t...

low vol

$1.99 Last Close

Volume Volume 689,740 is below the 20-day average of 1,020,504, suggesting muted pre-news positioning. low

Technical Shares at $2.12 trade below the 200-day MA of $2.41 and sit 57.43% under the 52-week high, but 84.35% above the 52-week low.

Peers on Argus

Pre-news, peers showed mixed moves: HLVX (-0.48%), MGNX (-3.24%), SPRO (-0.79%),...

Pre-news, peers showed mixed moves: HLVX (-0.48%), MGNX (-3.24%), SPRO (-0.79%), ANRO (+3.74%), PLRX (0%). With no momentum-clustered peers, trading appeared company-specific.

Historical Context

5 past events · Latest: Dec 23 (Positive)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Dec 23	Litigation settlement	Positive	-7.6%	Definitive agreement to settle securities class action for $31.25M.
Nov 12	Earnings update	Positive	+4.8%	Q3 2025 loss narrowed and cash of $106.1M with lower R&D spend.
Oct 22	Board change	Positive	-7.0%	Addition of experienced biopharma executive to support TSC strategy.
Aug 25	Conference participation	Neutral	-1.8%	Announcement of corporate presentation at H.C. Wainwright conference.
Aug 14	Earnings & update	Negative	+5.7%	Q2 2025 $44.2M net loss driven by $31.25M litigation contingency.

Pattern Detected

News flow has often seen price divergence, especially around litigation, governance changes, and earlier Alzheimer’s setbacks, while positive financial or TSC-related updates saw more alignment.

Recent Company History

Over the last six months, Cassava shifted from Alzheimer’s disease toward TSC-related epilepsy while managing legal and financial overhangs. A Q2 2025 update highlighted a $44.2M net loss tied to a $31.25M litigation contingency but also strong cash. Subsequent Q3 2025 results showed operating expenses down to $11.9M and cash of $106.1M. Clinical-trial news in March 2025 confirmed failure of Phase 3 Alzheimer’s studies, and by late 2025 the company agreed to a $31.25M class‑action settlement. Today’s peer‑reviewed Phase 3 publication consolidates those earlier clinical findings into the scientific record.

Regulatory & Risk Context

Active S-3 Shelf · $200,000,000

Shelf Active

Active S-3 Shelf Registration 2025-11-12

$200,000,000 registered capacity

An effective S-3 shelf filed on Nov 12, 2025 permits primary offerings of up to $200,000,000 in various securities, including an at-the-market program of up to $50,000,000 in common stock, providing flexibility to raise capital over time.

Market Pulse Summary

This announcement formalizes prior Phase 3 Alzheimer’s outcomes for simufilam in a peer-reviewed jou...

Analysis

This announcement formalizes prior Phase 3 Alzheimer’s outcomes for simufilam in a peer-reviewed journal, confirming that primary and key secondary endpoints were not met while detailing exploratory subgroup signals and a favorable safety profile. Historically, Cassava has redirected focus toward TSC-related epilepsy after these Alzheimer’s setbacks. Investors may watch for how the detailed biomarker and subgroup findings inform external research and any future development paths for the asset in other CNS indications.

Key Terms

phase 3 randomized clinical trials, mini-mental state exam (mmse), adas-cog12, plasma biomarker, +4 more

8 terms

phase 3 randomized clinical trials medical

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

A phase 3 randomized clinical trial is a large, late-stage study that tests whether a new drug or medical device actually works and is safe when given to many people; participants are assigned to different treatment groups by chance, like flipping a coin, to make comparisons fair. Investors watch these trials because positive results are often required for regulatory approval and wide sales, while negative results can stop a product and sharply affect a company’s value.

mini-mental state exam (mmse) medical

"mild subgroup (mini-mental state exam (MMSE) score 21-27)"

The Mini-Mental State Exam is a short, standardized questionnaire clinicians use to check basic thinking skills—memory, attention, language and orientation—much like a quick checklist to gauge mental sharpness. For investors, changes in average MMSE scores reported in clinical trials or regulatory filings act as a measurable signal of whether a treatment affects cognitive function, which can influence trial success, approval chances and the commercial outlook of related medical products.

adas-cog12 medical

"on the 12-item Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog12)"

ADAS-Cog12 is a 12-question test used in clinical trials to measure thinking, memory and language abilities in people with Alzheimer’s disease; it gives a single score that tracks whether a patient’s cognition is improving, staying the same, or declining. Investors watch changes in this score because drug candidates that meaningfully slow or reverse decline on ADAS-Cog12 are more likely to win regulatory approval and drive future sales, much like a report card indicating whether a treatment is working.

plasma biomarker medical

"first Phase 3 Alzheimer’s disease studies to rely primarily on a plasma biomarker"

A plasma biomarker is a measurable molecule or substance in blood plasma that indicates a biological condition, such as disease presence, progression, or response to treatment. Like a dashboard light in a car, it gives clinicians and researchers a quick, objective signal about what’s happening in the body. For investors, reliable plasma biomarkers can speed drug development, improve diagnostic tests, guide patient selection, and reduce regulatory and commercial risk, affecting a company’s valuation and market opportunity.

p-tau181 medical

"using a plasma p-tau181 cutoff of ≥ 67 (the highest half of all patients)"

p-tau181 is a specific, modified form of the brain protein tau that shows up in spinal fluid or blood when nerve cells are degenerating, and it serves as a biomarker for Alzheimer’s disease and related disorders. Think of it like a smoke alarm: its presence and level give doctors and researchers an early signal of pathological changes in the brain, which matters to investors because it drives demand for diagnostic tests, informs drug development and trial outcomes, and can affect regulatory approval and health‑care markets.

amyloid pet medical

"an amyloid PET (positron emission tomography) sub-study in REFOCUS-ALZ"

Amyloid PET is a specialized imaging scan that detects the buildup of certain proteins called amyloid in the brain, which are associated with Alzheimer's disease. For investors, it signals advancements in diagnosing neurological conditions early, potentially impacting the demand for related medical treatments and diagnostic tools. This technology can influence healthcare companies' prospects and the development of therapies targeting memory-related illnesses.

double-blinded, placebo-controlled, randomized parallel group medical

"multi-center, double-blinded, placebo-controlled, randomized parallel group studies"

A clinical trial where participants are randomly assigned by chance to one of two or more groups that run at the same time, with some getting the experimental treatment and others receiving a dummy treatment (placebo); neither the participants nor the people administering or assessing the treatment know who is in which group (double-blinded). This design reduces bias and chance effects, so its results carry more weight for regulators, doctors and investors deciding a drug or therapy’s likely value and approval prospects.

ecg medical

"Safety was evaluated by adverse event monitoring, as well as standard laboratory and ECG assessments"

An ECG (electrocardiogram) records the heart’s electrical activity through small sensors on the skin and produces a waveform that shows heart rate, rhythm and signs of stress or damage—think of it as a seismograph for the heart’s electrical signals. Investors care because ECGs are central to diagnosing and monitoring cardiac safety in clinical trials, required for regulatory approval of many drugs and devices, and drive demand for related medical equipment and services.

AI-generated analysis. Not financial advice.

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 profile in 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: https://www.sciencedirect.com/science/article/pii/S2274580725004108.

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 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:

1. 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 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 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.

FAQ

What did Cassava (SAVA) publish on January 13, 2026 about simufilam Phase 3 results?

Cassava published a JPAD article detailing RETHINK-ALZ and REFOCUS-ALZ results, noting the trials did not meet prespecified endpoints but reported a favorable safety profile and exploratory subgroup signals.

Why did Cassava (SAVA) stop developing simufilam for Alzheimer’s disease in 2026?

The company discontinued the Alzheimer’s program because both Phase 3 trials failed to meet their prespecified co-primary, secondary, and exploratory biomarker endpoints.

What exploratory clinical signals did the simufilam Phase 3 pooled mild-subgroup show for SAVA?

Pooled mild patients showed potential treatment differences at weeks 4 and 28 (nominal significance), and pooled analyses using plasma p-tau181 ≥67 showed signals at weeks 4, 28, and 40.

How did biomarker screening perform in the REFOCUS-ALZ and RETHINK-ALZ trials (SAVA)?

An amyloid PET sub-study found 21% of tested participants were amyloid-negative at baseline, indicating the plasma p-tau181 cutoff used was insufficient to exclude non-AD pathology.

Do the JPAD results affect Cassava’s other programs such as TSC-related epilepsy (SAVA)?

The paper notes detailed safety observations provide encouragement for the company’s ongoing TSC-related epilepsy development, which the company intends to pursue.