xFEFF; CASSAVA SCIENCES One-month Oral Treatment with PTI-125, a New Drug Candidate, Reduces CSF & Plasma Biomarkers of Alzheimer's Disease Late Breaking Oral Communication 12th Clinical Trials on Alzheimer's Disease (CT

CASSAVA SCIENCES One-month Oral Treatment with PTI-125, a New Drug Candidate, Reduces CSF & Plasma Biomarkers of Alzheimer's Disease Late Breaking Oral Communication 12th Clinical Trials on Alzheimer's Disease (CTAD) December 5, 2019 - San Diego, CA Lindsay H. Burns, PhD; Hoau-Yan Wang, PhD; Zhe Pei, PhD; Kuo-Chieh Lee; Carrie Crowley; Michael Marsman, PharmD; Nadav Friedmann, PhD, MD 1

Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical fact contained in this presentation including, but not limited to, statements regarding the status of Phase 2 clinical studies; the interpretation of clinical results, including potential health benefits, if any, of changes in levels of biomarkers; commentaries made by Cassava Sciences' employees; and other 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 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 trials on expected timelines, to demonstrate the specificity, safety, efficacy or potential health benefits of our product candidates 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, 2018 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 presentation 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. The content of this presentation is solely the responsibility of the Company and does not necessarily represent the official views of the National Institutes of Health. The Company does not undertake any obligation to update this presentation or any forward-looking statements included therein, except as required by law. Cassava Sciences 2

Disclosures and Contributions PTI-125 is a proprietary compound of Cassava Sciences, Inc. Lindsay H. Burns, PhD; Nadav Friedmann, PhD, MD; and Carrie Crowley are employees of Cassava Sciences. Michael Marsman, PharmD and Hoau-Yan Wang, PhD are consultants to Cassava Sciences. Hoau-Yan Wang, PhD; Zhe Pei, PhD; and Kuo-Chieh Lee performed biomarker assays and are affiliated with City University of New York School of Medicine. J Neurosci, Neurobiol Aging and Neuroimmunol Neuroinflammation publications on PTI-125 are online: www.CassavaSciences.com. Research reported in this presentation was supported by the National Institute on Aging of the NIH under award AG060878. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 CU NY The City University of New York Cassava Sciences 3

Phase 2a Clinical Trial of PTI-125 I. Background II. Clinical Results III. Mechanism of Action IV. Conclusions Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 4

PTI-125 A Novel Drug for Alzheimer's disease PTI-125 is our proprietary, small molecule drug candidate to treat Alzheimer's disease (AD) and other dementias. Our AD program benefits from significant, long-term scientific and financial support from the National Institutes of Health (NIH). By binding a single target, PTI-125 reduces both neurodegeneration and neuroinflammation. Clinical results from a first-in-patient study support PTI-125's mechanism of action. Clinical biomarker results are consistent with > 10 years of basic science and preclinical data. Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 5

The Target of PTI-125 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. The AD brain carries an ALTERED conformation of FLNA. Altered FLNA is critical to amyloid beta's toxicity. Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 6

PTI-125 Mechanism of Action Altered FLNA enables A 42 signaling via two different receptors: i. 7-nicotinic acetylcholine receptor ( 7nAChR) hyperphosphorylates tau ii. Toll-like receptor 4 (TLR4) releases inflammatory cytokines PTI-125 preferentially binds altered FLNA, restores its proper shape/function, potently suppressing A 42 signaling via 7nAChR and TLR4. Through a single target, PTI-125 reduces both neurodegeneration and neuroinflammation. Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 7

Phase 2a Clinical Trial of PTI-125 I. Background II. Clinical Results III. Mechanism of Action IV. Conclusions Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 8

Phase 2a Study Design Objective: Safety, PK and biomarkers under an IND filed by Cassava Sciences Study Design: First-in-patient, open-label treatment at 5 sites in the US Patients: Mild-to-moderate AD, MMSE 16 24, age 50-85 Key Inclusion: CSF Total tau/A 42 0.30 Enrollment: Thirteen (13) patients PTI-125 Dose: 100 mg oral tablets, b.i.d. for 28 days Biomarkers: CSF samples collected at screening and Day 28 Blood samples for plasma/lymphocyte markers at Days 1, 14 and 28 Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 9

Phase 2a Safety and Pharmacokinetics Drug was well-tolerated, no drug-related adverse events observed PK parameters of PTI-125 100 mg b.i.d. in AD patients: Day Cmax (ng/mL) Tmax (h) Clast (ng/mL) Tlast (h) z (1/h) AUClast (h*ng/mL) T1/2 (h) CSF/Plasma Day 1 1,020 2.00 176 12 0.176 5,320 4.51 Day 28 1,100 2.06 238 12 0.174 6,700 4.35 0.61 Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 10

CSF Biomarker Methods CSF biomarkers were measured by CUNY using commercial ELISA kits (LifeSpan BioSciences, Inc.) according to manufacturer's instructions. Samples were pre-treated with protease and phosphatase inhibitors. Screening and Day 28 samples were run in the same ELISA plate, in triplicate, for each biomarker. Assays used 50 l CSF per well (YLK40 used 100 l), subtracting background for chromogen and the no-CSF control. Values were fit to standard curves; standard curves had R2 values of 0.85-0.99. CSF samples were tested blind to Baseline/Day 28. Statistical analyses were conducted by an independent biostatistician. Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 11

Phase 2a Summary Results - CSF Biomarkers Change from Baseline to Day 28 Neurogranin Nfl T-tau P-tau181 YKL40 IL-6 IL- 1 TNFa -32% -22% -20% -34% -9% -14% -11% -5% * p < 0.0001; + p < 0.001 by paired t-test Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 12

Slight Increase in CSF Amyloid-beta (A 42) Levels of CSF A 42 (pg/mL) CSF concentration (pg/mL) Screening Day 28 Note: Low CSF levels of A 42 indicates Alzheimer's disease. Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 13

Phase 2a Biomarkers CSF vs. Plasma Change from Baseline to Day 28 T-tau 4% 8% NfL Neurogranin YKL40 -20% -16% A 42 -22% -11% -32% -41% -9% -4% CSF Plasma * p < 0.0001; + p < 0.001 Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 14

CSF Biomarkers Individual Patient Responses CSF (pg/mL) Neurofilament Light Chain Phospho-tau(T181) CSF (pg/mL) Total tau A 42 YKL40 Screening Day 28 Screening Day 28 Screening Day 28 0 200 400 600 800 1000 1200 0 100 200 300 400 500 600 700 800 0 2 4 6 8 10 12 0 100 200 300 400 500 0 50 100 150 200 250 300 350 400 450 0 10 20 30 40 50 60 70 80 90 Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 15

CSF Cytokines Individual Patient Responses CSF concentration (pg/mL) IL-6 IL-1 TNFa CSF concentration (pg/mL) 0 5 10 15 20 25 0 10 20 30 40 50 60 0 5 10 15 20 25 30 35 40 45 Screening Day 28 Screening Day 28 Screening Day 28 Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 16

Plasma Biomarkers Individual Patient Responses Plasma (pg/mL) Plasma (pg/mL) Plasma Neurogranin Plasma Neurofilament Light Chain Plasma P-tau(T181) by immunoblot Plasma Total Tau Plasma A 42 Plasma YKL40 0 20 40 60 80 100 0 10 20 30 40 50 60 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0 10 20 30 40 50 60 70 80 26 27 28 29 30 31 32 33 34 35 36 50 55 60 65 70 75 Screening Day 28 Screening Day 28 Screening Day 28 Screening Day 28 Screening Day 28 Screening Day 28 Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 17

P-Tau and Nitrated Tau Reduced in Plasma Reductions in Tau, P-tau and N-tau: Baseline to Day 14 & Day 28 IP: Anti-Tau Dosing days: 0 14 28 0 14 28 28 14 0 70- 100- 70- 100 70- 100- 70- 100- 70- 100 IB nY29Tau pT21Tau pT181Tau pS202Tau Tau Relative to Day 0 Tau level 0 0.4 0.8 1.2 Dosing days 0 14 28 Tau pS202Tau pT181Tau pT231Tau nY29Tau * p < 0.001 Baseline vs. Day 28 Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 18

Phase 2a Clinical Trial of PTI-125 I. Background II. Clinical Results III. Mechanism of Action IV. Conclusions Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 19

Altered FLNA links to 7-nicotinic acetylcholine receptor A 42 binds 7nAChR with femtomolar affinity. Altered FLNA linkage to 7nAChR enables A 42 signaling through 7nAChR to hyperphosphorylated tau. Altered FLNA A 42 a7nAChR ERK/JNK1 Hyperphosphorylated tau and destabilized microtubule Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 20

Altered FLNA links to 7-nicotinic acetylcholine receptor A 42 binds 7nAChR with femtomolar affinity. Altered FLNA linkage to 7nAChR enables A 42 signaling through 7nAChR to hyperphosphorylated tau. PTI-125 binds altered FLNA, restores its normal shape, stops A 42 signaling and tau hyperphosphorylation. A 42 7nAChR PTI-125 Stable microtubule FLNA, shape restored Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 21

Altered FLNA links to Toll-like Receptor 4 (TLR4) Altered FLNA linkage to TLR4 enables A 42 to activate TLR4. Persistent TLR4 activation results in chronic neuroinflammation. A 42 MD2 MD2 CD14 Co-receptor TLR4 Altered FLNA Inflammatory cytokine release Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 22

Altered FLNA links to Toll-like Receptor 4 (TLR4) Altered FLNA linkage to TLR4 enables A 42 to activate TLR4. Persistent TLR4 activation results in chronic neuroinflammation. PTI-125 binds altered FLNA, restores its normal shape, stops A 42 signaling and neuroinflammation. A 42 MD2 MD2 CD14 Co-receptor TLR4 FLNA PTI-125 Inflammatory cytokine release Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 23

Target Engagement & Mechanism of Action Evidence in patient lymphocytes from Day 0 to 14 to 28 by three methods: i. Reversal of altered conformation of FLNA Assessed by isoelectric focusing point ii. Reduced FLNA linkages to 7nAChR and TLR4 Assessed by co-immunoprecipitation iii. Reduced A 42 complexed with 7nAChR and CD14 Assessed by co-immunoprecipitation Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 24

FLNA's Native Shape Restored in Patient Lymphocytes pl 3.5- 4.2- 4.5- 5.3- 6.0- 6.9- 8.0- 9.5- Dosing days: 0 14 28 0 14 28 0 14 28 Percentage of Total 0% 25% 50% 75% 100% 0 14 28 pl:5.9 pl:5.3 * p < 0.0001 vs. pI 5.9; # p < 0.0001 vs. Day 0;+ p < 0.0001 vs. Day 14 Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 25

FLNA Linkages to 7 and TLR4 Reduced in Lymphocytes IP: Anti-FLNA 250- 55- 70- 100- 130- 250- 55-70- 100- 130- 250- IB TLR4 a7nAChr FLNA A 42 Dosing days: 0 14 28 0 14 28 Relative to FLNA 0 0.25 0.5 0.75 A 42 (0.1) Dosing days: 0 14 28 0 14 28 TLR4 a7nAChr * p < 0.001 vs. Day 0; + p < 0.01, ++ p < 0.05 vs. Day 14 Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 26

A 42 Bound to 7nAChR or CD14 Reduced in Lymphocytes IP: Anti- A 42/-Actin 55- 35- 55- 70- 100- 130- 35- 55- 70- 100- 130- A 42 Dosing Days 0 14 28 0 14 28 IB CD14 a7nAChR -Actin Relative to -Actin 0 0.25 0.5 0.75 A 42 (0.1) Dosing days: 0 14 28 0 14 28 a7AChr CD14 * p < 0.001 vs. Day 0; + p < 0.01, ++ p < 0.05 vs. Day 14 Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 27

Phase 2a Clinical Trial of PTI-125 I. Background II. Clinical Results III. Mechanism of Action IV. Conclusions Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 28

Summary of PTI-125 Effects Validated CSF biomarkers of AD pathology improved in all patients treated with PTI-125: Reduced post-synaptic damage: Reduced tau: Reduced axonal degeneration: Reduced neuroinflammation: Neurogranin -32% Total tau -20%, P-tau -34% Neurofilament light chain -22% YKL40, IL-6, IL-1 , TNF reduced 5-14% Consistent improvements in biomarkers across CSF, plasma and lymphocytes. PTI-125 at 100 mg b.i.d. for 28 days appeared to slow the rate of neurodegeneration and suppress neuroinflammation, consistent with the drug's mechanism of action and preclinical data. Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 29

Phase 2a data are .. Promising because: PTI-125 improved all biomarkers of AD pathology, neurodegeneration and neuroinflammation. Consistent effects across CSF, plasma, lymphocytes All patients responded to PTI-125 Drug was safe and well-tolerated Clinical results are consistent with PTI-125's mechanism of action and > 10 years of basic science. Biomarker data imply disease-modifying effects. Viewed conservatively because: Treatment was open-label. The number of patients is small. Dose-response remains undefined. Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 30

Conclusions This first-in-patient study of PTI-125, a new drug candidate, demonstrated: Evidence of target engagement and mechanism of action in AD patients Significant improvements in biomarkers of AD Clinical validation for FLNA as a target for AD drug development These data highlight PTI-125's potential as a disease-modifying drug therapy for Alzheimer's disease. Clinical results are being confirmed in an ongoing 60-patient, blinded, randomized, placebo-controlled clinical trial. Cassava Sciences COPYRIGHT Cassava Sciences, Inc. 2019 31