8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

___________________

FORM 8-K

___________________

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the

Securities Exchange Act of 1934

Date of Report (Date of earliest event reported) November4, 2020

___________________

Cassava Sciences, Inc.

(Exact name of registrant as specified in its charter)

___________________

Delaware	000-29959	91-1911336
(State or other jurisdiction of incorporation)	(Commission File Number)	(I.R.S. Employer Identification Number)

7801 N Capital of Texas Highway, Suite 260

Austin, Texas 78731

(Address of principal executive offices, including zip code)

(512) 501-2444

(Registrant’s telephone number, including area code)

Not Applicable

(Former name or former address, if changed since last report.)

___________________

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2 below):

	Written communication pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
	Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
	Pre-commencement communication pursuant to Rule 14d-2(b) under the Exchange Act (17CFR 240.14d-2(b))
	Pre-commencement communication pursuant to Rule 13e-4(c) under the Exchange Act (17CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

0
Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, $0.001 par value	SAVA	NASDAQ Capital Market

Indicate by check mark whether the registrant is an emerging growth company as defined in as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company   

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.

Item 7.01. Regulation FD Disclosure.

A copy of the Cassava Sciences, Inc. presentation at the 13thClinical Trials on Alzheimer’s Disease (CTAD) is furnished as Exhibit 99.1 to this Form 8-K and is incorporated herein by reference.

Item 8.01. Other Events.

On November 4, 2020, Cassava Sciences, Inc. issued a press release, a copy of which is attached hereto as Exhibit 99.2 and is incorporated herein by reference.

Item 9.01 Financial Statements and Exhibits.

(d)    Exhibit No.    Description
99.1	Cassava Sciences, Inc. CTAD 2020 presentation
99.2	Cassava Sciences, Inc. CTAD press release dated November 4,  2020

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.

	CASSAVA SCIENCES, INC.
	a Delaware corporation
Date:   November4, 2020
	By:	/s/ ERIC J. SCHOEN
		Eric J. Schoen
		Chief Financial Officer

EX-99.1

Exhibit 99.1

Sumifilam Significantly Improves Eleven CSF Biomarkers in a Randomized, Placebo-controlled, One-month Clinical Trial in Alzheimer’s Disease Patients Lindsay BURNS, Hoau-Yan WANG, Zhe PEI, Kuo-Chieh LEE, Yaneicy GONZALEZ-ROJAS, Tamara DOEHNER, John PUENTE, Patrick SCIARA, Brian BECK, Evelyn LOPEZ-BRIGNONI, Boris NIKOLOV, Carrie CROWLEY, Nadav FRIEDMANN November 7, 2020 CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 1

Forward-Looking Statements This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. To identify such forward-looking statements, in some cases we use terms such as “predicts, “believes,” “potential,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “should” or other words that will convey risk or uncertainty of future events or outcomes. All statements other than statements of historical fact contained in this presentation including, but not limited to, statements regarding plans or timing for future Phase 3 clinical studies with sumifilam; the interpretation of prior or current results of our Phase 2 clinical studies, including the measured effects of sumifilam on cognition; plans to publish results in a peer-reviewed journal; potential health benefits, if any, of changes in levels of CSF biomarkers; verbal commentaries made by Cassava Sciences’ employees; and potential benefits, if any, of the Company’s product candidates for Alzheimer’s disease are forward-looking statements. Such statements are based largely on our current expectations and projections about future events. Such statements speak only as of the date of this presentation 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, to demonstrate the specificity, safety, efficacy or potential health benefits of our product candidates, the severity and duration of health care precautions given the international outbreak of an infectious disease and including those described in the section entitled “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2019 and future reports to be filed with the SEC. In light of these risks, uncertainties and assumptions, forward-looking statements and events discussed in this presentation are inherently uncertain and may not occur. Actual results could differ quickly, materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should never rely upon forward-looking statements as predictions of future events. We do not undertake any obligation to update this corporate presentation or any forward-looking statements included therein, except as required by law. The content of this presentation is solely our responsibility and does not necessarily represent the official views of the National Institutes of Health (NIH). CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 2

Disclosures Sumifilam is under clinical development by Cassava Sciences, Inc. L.H. Burns, PhD, N. Friedmann, PhD, MD, and C. Crowley are employees of Cassava Sciences. H-Y. Wang, PhD, is a consultant to Cassava Sciences. H-Y. Wang, PhD, Z. Pei, PhD, and K-C. Lee are employees of City University of New York School of Medicine. Sumifilam benefits from long-term scientific & financial support from the National Institute on Aging (AG050301, AG056166, AG060878, AG065152).
CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 3

Introduction to Sumifilam Sumifilam is a proprietary, small molecule drug candidate to treat Alzheimer’s disease (AD) and other neurodegenerative diseases. Drug was discovered and developed in-house, 2008 to present. Sumifilam binds a single target, has a dual mechanism of action: Reduces neurodegeneration and neuroinflammation. Published preclinical and mechanism of action data support sumifilam’s potential as a disease-modifying drug for AD that may also enhance cognition.
CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 4

Sumifilam: A Journey of Basic Research to Clinical Research 1 <2008 Basic research around neurobiology of Filamin A (FLNA). 2 2009 Discovery that altered FLNA associates with ��7nAChR when A signals. 3 2010 Screening/testing of compounds that bind altered FLNA and block ��7nAChR/A interaction. 4 2011 Sumifilam (formerly, PTI-125) binds altered FLNA with high affinity, blocks 7nAChR/A interaction. Preclinical testing of sumifilam. 5 2017 - present Clinical testing of sumifilam. Positive results reported in Alzheimer’s patients. CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 5

Phase 2b Clinical Study of Sumifilam I. Mechanism of Action II. Phase 2b Study Results II. Study Conclusions CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 6

Target of Sumifilam is Altered Filamin A (FLNA) FLNA is an intracellular scaffolding protein anchored in the cell membrane. FLNA interacts with > 90 proteins, influencing many signaling pathways. Filamin Actin-binding domain Actin filaments The AD brain carries an ALTERED conformation of FLNA. Altered FLNA is critical to amyloid beta’s toxicity. CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 7

Sumifilam Mechanism of Action Altered FLNA enables A42 signaling via two different receptors: 1) α7-nicotinic acetylcholine receptor (α7nAChR)  hyperphosphorylates tau 2) Toll-like receptor 4 (TLR4)  releases inflammatory cytokines Sumifilam preferentially binds altered FLNA, restores its proper shape/function, potently suppressing α42 signaling via α7nAChR and TLR4. Through a single target, sumifilam reduces both neurodegeneration and neuroinflammation. CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 8

Altered FLNA links to α7-nicotinic acetylcholine receptor  Aβ42 binds α7nAChR and recruits FLNA, altering its shape. Altered FLNA linkage to α7nAChR enables a femtomolar affinity of Aβ42 for α7nAChR and the signaling that hyperphosphorylates tau. Sumifilam binds altered FLNA, restores its normal shape, stops Aβ42 signaling and tau hyperphosphorylation. Aβ42 extracellular α7nAChR intracellular Alterned FLNA RK1/JNK Hyperphosporylated tau and destablized microtubule CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 9

Altered FLNA links to α7-nicotinic acetylcholine receptor  Aβ42 binds α7nAChR and recruits FLNA, altering its shape. Altered FLNA linkage to α7nAChR enables a femtomolar affinity of Aβ42 for α7nAChR and the signaling that hyperphosphorylates tau. Sumifilam binds altered FLNA, restores its  normal shape, stops Aβ42 signaling and tau hyperphosphorylation. Aβ42 extracellular α7nAChR intracellular sumifilam FLNA, shape restored Stable microtubule CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 10

Altered FLNA links to toll-like receptor 4 (TLR4) Altered FLNA linkage to TLR4 enables Aβ42 to activate TLR4. Persistent TLR4 activation results in chronic neuroinflammation. MD2 MD2 TLR4 CD14 Co-receptor intraceulluar Alterned FLNA Inflammatory cytokine release CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 11

Altered FLNA links to toll-like receptor 4 (TLR4) Altered FLNA linkage to TLR4 enables Aβ42 to activate TLR4. Persistent TLR4 activation results in chronic neuroinflammation. Sumifilam binds altered FLNA, restores its normal shape, stops Aβ42-induced neuroinflammation. MD2 MD2 CD14 Co-receptor intracellular TLR4 Aβ42 sumifilam FLNA, shape restored Inflammatory cytokine release CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 12

Summary of Preclinical Effects Sumifilam Intracerebro-ventricular (ICV) Aβ42 infusion mouse model Triple transgenic AD mouse model Postmortem human AD brain tissue Postmortem human age-matched control brain tissue treated with Aβ42 in vitro Reduced FLNA linkage to α7nAChR/TLR4 √ √ √ √ Reduced Aβ42 bound to α7nAChR √ √ √ √ Reduced amyloid deposits and NFTs √ √ – – Reduced tau hyperphosphorylation √ √ – √ Improved function of α7nAChR, NMDAR and insulin receptors √ √ √ √ Improved synaptic plasticity (activity-dependent Arc expression) – √ – √ Reduced inflammatory cytokine levels √ √ – – Improved cognition/behavior – √ – – CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 13

Phase 2b Clinical Study of Sumifilam I. Mechanism of Action II. Phase 2b Study Results III. Study Conclusions CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 14

Hypothesis and Objective Clinical Hypothesis Published preclinical effects and mechanism of action suggest sumifilam is a disease-modifying drug for AD and may enhance cognition. Phase 2b Study Objective Evaluate safety, biomarkers and cognition in a well-controlled study of sumifilam. CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 15

Phase 2b Study Design Randomized, placebo-controlled, multi-center, multi-dose study. Screening Mild-to-moderate AD, age 50-85 MMSE ≥16 and ≤26 Key Inclusion Criterion: CSF Total tau/Aβ42 ≥ 0.28 Sixty (64) patients recruited across 9 sites in the US Day 1 Baseline Cognition Test 1:1:1 Randomization 28-Day Treatment Period Sumifilam 50 mg oral, twice daily Sumifilam 100 mg oral, twice daily Matching placebo, twice daily Day 28 CSF Draw & Cognition Test Primary Endpoint: Biomarkers of disease Secondary Endpoint: Cognition CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 16

Phase 2b – Safety Sumifilam was well-tolerated No serious adverse events No drug-related patient discontinuation No drug-related adverse events Common, non-persistent AEs observed in both placebo & drug groups. CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 17

Phase 2b Results – CSF Total Tau and P-Tau181 Decreased  Total Tau P-Tau181 Change - Baseline to Day 28 0%-5% -10% -15% -20% -25% * * Placebo 50 mg 100 mg #p ≤ 0.001, *p < 0.0001 vs. placebo CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 18

Phase 2b Results – CSF Aβ42, Low in AD, Increased Change - Baseline to Day 28 25% 20% 15% 10% 5% 0% -5% Placebo 50 mg 100 mg #p = 0.0015, *p = 0.0003 vs. placebo CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 19

Phase 2b Results - Neurodegeneration Biomarkers in CSF Decreased  Neurofilament Neurogranin Light Chain Change - Baseline to Day 28 0% -10% -20% -30% -40% -50% * + * Placebo 50 mg 100 mg +p = 0 .048, #p = 0.001, *p < 0.0001 vs. placebo CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 20

Phase 2b Results - Neuroinflammation Biomarkers in CSF Decreased Change - Baseline to Day 28 YKL-40 IL-6 sTREM2 20% 10% 0% -10% -20% -30% -40% -50% -60% † † # Placebo 50 mg 100 mg †p < 0.01, #p ≤ 0.001 vs. placebo CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 21

Elevated Levels of HMGB1 Trigger Loss of Neurons High-Mobility Group Box 1 (HMGB1) is a pathogenic protein that induces neuroinflammation, neurite degeneration and cell death. Actively secreted by glia; released by necrotic cells. Induces cytokine production, activates immune cells, stimulates auto-antibodies, regulates gene transcription. Described as a ‘danger molecule.’ HMGB1 elevated in AD, other diseases of neuroinflammation and neuronal loss. HMGB1 activates TLR4 and Receptor for Advanced Glycation End products (RAGE). TBI neuro inflammation Epilepsy Cognitive dysfunction HMGB1 translocation Upregulation of pro-inflammatory cytokines ia RAGE?TLR4/TLR2 RAGE/TLR4 actiation and BBB disruption RAGE upregulation/BBB disruption CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 22

Phase 2b Results – CSF HMGB1 Decreased Placebo 50 mg 100 mg Change - Baseline to Day 28 20% 10% 0% -10% -20% -30% -40% # # # p < 0.001 vs. placebo CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 23

Phase 2b Results - BBB Integrity Improved CSF Albumin  CSF Immunoglobulin G % Change - Baseline to Day 28 5% 0% -5% -10% -15% -20% -25% -30% -35% -40% CSF Albumin CSF Immunoglobulin G Placebo 50 mg 100 mg +p < 0.05 #p = 0.0002 vs. placebo CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 24

Phase 2b Summary of Results - CSF Biomarkers % Change - Baseline to Day 28 Aβ42 T-tau P-tau151 Neurogranin NfL YKL40 IL-6 sTREM2 HMGB1 Albumin lgG * * * + * t # t t # + # + + Placebo 50 mg 100 mg +p < 0.05, †p < 0.01, # p ≤ 0.001, *p < 0.0001 vs. placebo CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 25

Cognition CANTAB (Cambridge Neuropsychological Test Automated Battery) is a widely used, computer-based battery of memory tests sensitive to subtle changes in cognition. Tests are independent of language skills, speed, gender or education. Cognitive assessments were made on Day 1 (pre-dose) and again on Day 28. Patients were tested on ‘Episodic Memory’ and ‘Spatial Working Memory’. Patients advance through progressively more difficult levels. Outcome measure = total errors, with errors imputed for more difficult levels not reached, so……. Lower score is better! CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 26

Phase 2b Results - Episodic Memory Change – Baseline to Day 28 Placebo 50 mg 100 mg 0 -1 -2 -3 -4 -5 -6 -1.5 -5.7 -4.5 7% EffectSize 23% Effect Size Episodic Memory Endpoint: Lower score is better in Total Errors on Paired Associates Learning (PAL). CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 27

Phase 2b Results - Spatial Working Memory Change – Baseline to Day 28 Placebo 50 mg 100 mg 0 -0.5 -1 -1.5 -2 -2.5 -3 -3.5 -0.41 -1.65 -3.33 17% Effect Size 46% Effect Size Spatial Working Memory Endpoint: Lower score is better in Total Errors on Spatial Working Memory task. CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 28

Phase 2b Results - Cognition/Biomarker Correlation Cognitive Improvement Correlates Most (R2 = 0.5) with Decreases in CSF P-tau181 Cognition/Biomarker Correlations (R2) 0.30 0.36 0.37 0.37 0.41 0.48 YKL-40 NfL T-tau Albumin IL-6 P-tau181 CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 29

Phase 2b Results - Target Engagement in Lymphocytes Reduced FLNA linkages: FLNA – α7nAChR FLNA – TLR4 Change – Baseline to Day 28 0% -5% -10% -15% -20% -25% -30% -35% -40% * (*) * * Placebo 50 mg 100 mg *p < 0.05, ( ) p = 0.076 vs placebo CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 30

Phase 2b Results - Summary of Drug Effects 98% of patients treated with sumifilam 50 mg or 100 mg b.i.d. for 28 days showed improvements in validated biomarkers of AD pathology; neuroinflammation; and neurodegeneration; with no safety issues. Sumifilam appears to enhance cognition. 37% and 23% effect sizes in Episodic Memory vs. placebo 17% and 46% effect sizes in Spatial Working Memory vs. placebo Improved cognition correlated most strongly with reduction in levels of P-tau181 (R2 = 0.5) Target engagement and mechanism of action were demonstrated in this Phase 2b and in prior clinical and pre-clinical studies. CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 31

Phase 2b Clinical Study of Sumifilam I. Mechanism of Action II. Phase 2b Study Results III. Study Conclusions CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 32

Study Conclusions A well-controlled study of sumifilam showed promising treatment effects in mild-to-moderate AD patients. Sumifilam improved an entire panel of validated biomarkers of disease, neuroinflammation, and BBB integrity, and appeared to enhance cognition. Phase 2b treatment effects replicate prior clinical results and are consistent with published preclinical data and the drug’s mechanism of action. These data highlight sumifilam’s potential as a disease-modifying treatment for Alzheimer’s disease. CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 33

Next Steps On-going: One-year, open-label safety study of sumifilam Enrolling 100 patients with mild-to-moderate AD, including ADAS-Cog assessments. Planned for 2021: Large-scale safety & efficacy study of sumifilam THANK YOU! CTAD Clinical Trials on Alzheimer’s Disease CASSAVA sciences 33

EX-99.2

Exhibit 99.2

Cassava Sciences Announces Additional Clinical Data from a Phase 2b Study ofSumifilam inAlzheimer’sDisease

Alzheimer’s Patients Treated with Sumifilam Showed a Statistically Significant (p<0.001) Treatment Benefit on HMGB1,

a Protein that Triggers Neuroinflammation and Loss of Neurons

Alzheimer’s Patients Treated with SumifilamAlso Showed

a  Treatment Benefit (p<0.05) onBlood-brain  Barrier Integrity

Clinical Dataset to be Presented November 7that CTAD 2020Conference

AUSTIN, TX – November 4, 2020 – Cassava Sciences, Inc. (Nasdaq: SAVA)  today announced additional clinicaldataof a Phase 2b study with sumifilam, its lead drug candidate,in patients with Alzheimer’s disease.In a  clinical study funded by the National Institutes of Health (NIH),  sumifilam decreased levels of a  protein called HMGB1 and improvedmeasurements of the integrity of the blood-brainbarrier (BBB).  The ability of a drug candidateto decrease HMGB1 and improve BBB integrity in patients withAlzheimer’s disease has not been previously reported in the science literature.Sumifilam is a proprietary, small molecule (oral) drug that restores the normal shape and function of altered filamin A protein in the brain.

Cassava Sciences, Inc.

November 4, 2020

Page 2 of 6

“The ability to improve multiple biomarkers of disease with one drug is a unique achievement,” said Remi Barbier, President & CEO of Cassava Sciences. “We believe these exciting clinical results create a time of rapid strategic momentum for the Company, to include development plans to evaluate sumifilam in a Phase 3 clinical program in patients with Alzheimer’s disease.”

Additional Phase 2b Study Results

Additional clinical data include changes in levels of HMGB1 proteinand measurements of the integrity of the blood-brain  barrierfrom baseline to Day 28 (all p-values versus placebo):

Sumifilam Significantly Reduced Levels of HMGB1 in Cerebrospinal Fluid (CSF):

· HMGB1 decreased 33% (p<0.001)  in patients treated with 50 mg sumifilam

· HMGB1 decreased 32% (p<0.001) in patients treated with 100 mg sumifilam

Sumifilam Significantly Improved the Integrity of the Blood-brainBarrier (BBB):

· CSF IgG decreased 30% (p<0.05) in patients treated with 50 mg sumifilam

· CSF IgG decreased 30% (p<0.05) in patients treated with 100 mg sumifilam

· CSF albumin decreased 15% (p<0.05) in patients treated with 50 mg sumifilam

· CSF albumin decreased 28% (p<0.05) in patients treated with 100 mg sumifilam

Sumifilam Improvedthe Albumin Ratio, a  Test of Blood-brain Barrier (BBB) Permeability:

· BBB permeability can beclinically evaluated by comparing levels of albumin in CSF and plasma. The albumin ratiois a  test for BBB permeability because albumin protein is not synthesized in CSF. Hence, albumin in CSF necessarily comes from plasma through the BBB. The albumin ratio is frequently elevated in patients with dementia and various other disorders.

· In the Phase 2b study, the albumin ratio was unchanged for Alzheimer’s patients on placebo. The albumin ratioimproved by approximately 5 and 7 points for patients treated with sumifilam, 50 mg and 100 mg, respectively, over 28 days. 

Cassava Sciences, Inc.

November 4, 2020

Page 3 of 6

Changes in the Albumin Ratio by Treatment Group

Treatment	Day 0	Day 28	Change-Day 0 to 28
Placebo	24	24	No change
50 mg sumifilam	25	20	- 5
100 mg sumifilam	25	18	- 7

About HMGB1

HMGB1 is anendogenous and potent pro-inflammatory protein that is sometimes called a ‘danger molecule.’  HMGB1 is elevated in patients with Alzheimer’s disease and other neurodegenerative disorders and many other disorders. Elevated levels of HMGB1 induce neuroinflammation, tissue damage and, eventually, cell death. Preclinical research has shown that inhibiting HMGB1 improves outcomes in neurodegenerative disease models,  decreasing neuroinflammation and improving learning and memory. PubMed® reports nearly 6,000 scientific publications of HMGB1 research in the past decade, highlighting the molecule’s potential importancein clinical research.

About the Blood-brainBarrier (BBB)

The BBB is a complex border of cells along blood vessels that prevent unwanted substances in blood from entering the brain. BBB integrity is essential to brain health. A healthy BBB system selectively allows the passage of some molecules into the brain, such as waterand glucose, while blocking passage to molecules that may damage the brain.Levels of IgG antibodies and albumin protein in the cerebrospinal fluid (CSF) are an index of BBB integrity, with elevated levels evidence of a ‘leaky’,  impaired BBB. Albumin protein is found at high levels in plasma and low levels in CSF because it does not normally cross the BBB.

Late-breaking Presentation at CTAD 2020

Clinical results of a Phase 2b study of sumifilam were selected as a late-breaking oral presentation by the 13th international conference on Clinical Trials on Alzheimer’s Disease (CTAD). CTAD is a prestigious annual conference focused on Alzheimer’s clinical research and takes place this year as a virtual event on November 4-7th, 2020.

Cassava Sciences, Inc.

November 4, 2020

Page 4 of 6

On Saturday, November 7th, Company scientists will present an oral presentation titled,“SumifilamSignificantly Improves Eleven CSF Biomarkers in a  Randomized, Placebo-Controlled, One-Month Clinical Trial in Alzheimer’s Disease Patients.”

The Company’s CTADpresentation is available on its website: https://www.CassavaSciences.com

Phase 2b Study Design

Phase 2b was a double-blind, randomized, placebo-controlled, multi-center clinical study of sumifilam (formerly, PTI-125).  Sixty-four patients with mild-to-moderate Alzheimer’s disease, age 50-85, were randomized (1:1:1) to 100 mg or 50 mg oral sumifilam or matching placebo. Treatment was administered twice daily for 28 days. Nine U.S. study sites enrolled patients. A clinical diagnosis of Alzheimer’s disease was confirmed with the Mini-Mental State Examination (MMSE) ≥16 to ≤26 and a CSF T-tau/Aβ₄₂ ratio ≥0.28. Safety was assessed by ECGs, clinical labs, adverse event monitoring and physical examinations. 

Previously Announced Clinical Phase 2b Data

As previously announced in September 2020, sumifilam was safe and well-tolerated, with no drug-related patient discontinuations. Alzheimer’s patients treated with 50 mg or 100 mg sumifilam twice-daily for 28 days showed statistically significant (p<0.05) improvements in eight biomarkers of disease pathology, neurodegeneration and neuroinflammation, versus Alzheimer’s patients who took placebo.In addition, Alzheimer’s patientstreated with sumifilam showed improvements in validated tests of Episodic Memory and SpatialWorking Memory, versus patients who took placebo (Effect Sizes 17-46%). Cognitive improvements correlated most strongly (R2=0.5) with decreases in P-tau181, a biomarker thatleads to tangles in the brain. Sumifilam decreased brain levels of Ptau-181 by 8-11%, versus placebo. The study achieved a 98% response rate, defined as the proportion of study participants taking sumifilam who showed improvements in biomarkers.

Cassava Sciences, Inc.

November 4, 2020

Page 5 of 6

On-going Open-label Study

InMarch 2020, we announced the initiation of an open-label study to evaluate sumifilam in patients with Alzheimer’s disease. This is an open-label, multi-center, extension study to monitor the long-term safety and tolerability of sumifilam 100 mg twice-daily for 12 months. The study’s target enrollment is approximately 100 patients with mild-to-moderate Alzheimer’s disease.  This study has exceeded 60% enrollment.The open-label study employs The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-11) to assess cognitive symptoms of dementia and The Neuropsychiatric Index (NPI) to assess behavioral symptoms.  Cassava Sciences plans to announce results of an interim analysis as additional safety and cognition data is collected from patients enrolled in the open-label study.

About Alzheimer's Disease

Alzheimer’s disease is a progressive brain disorder that destroys memory and thinking skills. Currently, there are no drug therapies to halt Alzheimer’s disease, much less reverse its course. In the U.S. alone, approximately 5.8 million people are currently living with Alzheimer’s disease, and approximately 487,000 people age 65 or older developed Alzheimer’s in 2019.1 The number of people living with Alzheimer’s disease is expected to grow dramatically in the years ahead, resulting in a growing social and economic burden.2

About Sumifilam

Sumifilam is a proprietary, small molecule (oral) drug that restores the normal shape and function of altered filamin A (FLNA), a scaffolding protein, in the brain. Altered FLNA in the brain disrupts the normal function of neurons, leading to Alzheimer’s pathology, neurodegeneration and neuroinflammation.The underlying science for sumifilam is published in  peer-reviewed journals, including Journal of Neuroscience,  Neurobiology of Aging,  Journal of Biological Chemistry, Neuroimmunology and Neuroinflammation and Journal of Prevention of Alzheimer’s Disease.The Company is also developing an investigational diagnostic, called SavaDx, to detect Alzheimer’s disease with a simple blood test.

_______________________

1,2  Source: Alzheimer’s Association. 2019 Alzheimer’s Disease Facts and Figures. Available online at: https://www.alz.org/media/documents/alzheimers-facts-and-figures-2019-r.pdf

Cassava Sciences, Inc.

November 4, 2020

Page 6 of 6

Sumifilam and SavaDx were both developed in-house. Both product candidates are substantially funded by peer-review research grant awards from the National Institutes of Health (NIH). Cassava Sciences owns worldwide development and commercial rights to its research programs in Alzheimer’s disease, and related technologies, without royalty obligations to any thirdparty. Patent protection in this area runs through 2037, plus extensions, and includes seven issued patents and related patent filings and applications.

About Cassava Sciences, Inc.

Cassava Sciences’ mission is to discover and develop innovations for chronic, neurodegenerative conditions. Over the past 10 years, Cassava Sciences has combined state-of-the-art technology with new insights in neurobiology to develop novel solutions for Alzheimer’s disease. For more information, please visit: https://www.CassavaSciences.com

For More Information Contact:

Eric Schoen, Chief Financial Officer

Cassava Sciences, Inc.

eschoen@CassavaSciences.com

(512) 501-2450

Cassava Sciences’ Phase 2b study of sumifilam in Alzheimer’s disease was funded by clinical research grant #AG060878 from the National Institutes of Health (NIH/NIA).The content of this press release is solely the responsibility of Cassava Sciences and does not necessarily represent the official views of the NIH/NIA.

Cautionary Note Regarding Forward-Looking Statements: This press release contains “forward-looking statements” for purposes of the Private Securities Litigation Reform Act of 1995 (the Act). Cassava Sciences claims the protection of the Safe Harbor for forward-looking statements contained in the Act. All statements other than statements of historical fact contained in this press release including, but not limited to,statements regarding the status of current and future clinical studies with sumifilam, including our intention to conduct a Phase 3 clinical program; the interpretation of results of our Phase 2 clinical studies including cognition data; plans to announce results of an interim analysis of an ongoing open-label study; potential health benefits, if any, of changes in levels of biomarkers; verbal commentaries made by Cassava Sciences’ employees; and potential benefits, if any, of the Company’s product candidates for Alzheimer’s disease are forward-looking statements.Such statements are based largely on the Company’s current expectations and projections about future events. Such statements speak only as of the date of this press 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, to demonstrate the specificity, safety, efficacy or potential health benefits of our product candidates, the severity and duration of health care precautions given the COVID-19 pandemic, any unanticipated impacts of the pandemic on our business operations, and including those described in the section entitled “Risk Factors” in Cassava Sciences’ Annual Report on Form 10-K for the year ended December 31, 2019 and future reports to be filed with the SEC. In light of these risks, uncertainties and assumptions, the forward-looking statements and events discussed in this press 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, the Company disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release.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.

###