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Selective Targets. Broad Impact.
Uniquely powerful approaches to tackling the toughest diseases
Corporate Overview
www.kezarlifesciences.com

Forward-Looking Statements Disclaimer
This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "should," "expect," "plan," "anticipate," "target," and similar expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. Each of these forward-looking statements involves substantial risks and uncertainties that could cause actual results to differ significantly from those expressed or implied by such forward-looking statements. Forward-looking statements contained in this presentation include, but are not limited to, statements regarding the disruption of our business and clinical trials from the global outbreak of a novel strain of coronavirus (COVID-19), the potential use of our product candidates to treat patients, the association of data with treatment outcomes, the design, timing of initiation, progress, enrollment and scope of clinical trials for our product candidates, the expected timing of program updates and data disclosures, the timing of filing INDs and other regulatory documents, the timing and likelihood of seeking regulatory approval for our product candidates, and the patient prevalence, regulatory pathway and competitive landscape for our product candidates.
These forward-looking statements reflect Kezar's current beliefs and expectations. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, clinical site activation rates or clinical trial enrollment rates that are lower than expected, changes in expected or existing competition, changes in the regulatory environment, and unexpected litigation or other disputes. Other factors that may cause our actual results to differ from current expectations are discussed in Kezar's most recent Form 10-K or Form 10-Q filed with the U.S. Securities and Exchange Commission (SEC), under the caption "Risk Factors" and elsewhere in such reports. Except as required by law, we assume no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.
1

The Kezar Opportunity: Harnessing Master Regulators of Cellular Function to Tackle Immune-mediated Diseases and Cancer

2 distinct scientific programs with potential across multiple indications of high unmet need

Rich Platform & Growing Pipeline

KZR-616: First-in-Class Immunoproteasome
Inhibitor

A novel approach to harmonizing the immune system; Potential to be a pipeline in a drug

First in class agent with broad antitumor activity; Potential to inhibit multiple targets with a single small molecule

KZR-261: First candidate from
Protein Secretion Platform

Strong Financial Position
(as of 9/30/2020)

$150M cash, cash equivalents, and marketable securities; 46.3M common shares outstanding
2

Our Programs Employ Uniquely Powerful Approaches to Address a Diverse Pipeline of Indications

KZR-616 and KZR-261 are first-in-class small molecules that harness master regulators of cellular function to inhibit multiple drivers of disease via single targets

COMPOUND

THERAPEUTIC INDICATION

Selective Immunoproteasome Inhibition

KZR-616

Lupus Nephritis (LN)
Dermatomyositis (DM) / Polymyositis (PM)

Protein Secretion Inhibition

KZR-261

Oncology

DISCOVERY

DEVELOPMENT STAGE

PRECLINICAL

PHASE 1

PHASE 2

MISSION PRESIDIO

IND-enabling activities

PHASE 3

KZR-TBD

Oncology & Autoimmunity

3

Kezar's Novel, Complementary Programs Target Master Regulators of Cellular Function to Achieve Broad Therapeutic Activity

PROTEIN DEGRADATION: The Immunoproteasome

PROTEIN SECRETION: The Sec61 Translocon

The target of selective immunoproteasome inhibitor KZR-616

· Modulates multiple drivers of inflammation
· Active in broad array of autoimmune disease models
· Restores normal immune responses in autoimmune disorders, while potentially avoiding immunosuppression

· Broad anti-tumor activity in preclinical models
· Applications in oncology, immuno-oncology, N
and autoimmunity · Potential for small molecules to replace
certain biologics
4

The Immunoproteasome Acts as a Master Regulator of Cellular Function in the Body's Immune System ­ its Dysfunction Underlies the Pathogenesis of Immune-mediated Diseases

Immunoproteasome

Proteins to be
degraded

Class 1 Antigen Presentation

Lymphocyte migration & adhesion

Lymphocyte proliferation

Cytokine expression
5

Selective Immunoproteasome Inhibition is not Cytotoxic and Results in Broad Immunomodulatory Activity

Dual-Targeting Proteasome Inhibitors

Selective Immunoproteasome Inhibitors

Dual proteasome inhibitors

Myeloma Cell

Macrophage

TNF- 
IL-23 IL-6

· Dual inhibition required for cell death
· Death induced by protein buildup (UPR)

Apoptosis

T-cell
KZR-616
B-cell

Th1 Th17 Treg
autoAb

Parlati et al. Blood 2009
6

KZR-616, A First-in-Class Selective Immunoproteasome Inhibitor Offers a Novel Approach for Harmonizing the Immune System for Immense Disease-Modifying Benefit

KZR-616

Strong Pharmaceutical Properties Exhibited in Studies to Date
· Ideal clinical pharmacology parameters
· Low DDI risk
· 100% bioavailability with subcutaneous administration
· Amenable to patient selfadministration
· Experienced CMC team prepared for commercial grade manufacturing with low COGS
· Extensive IP coverage and lifespan (2034+)

7

We are Leveraging KZR-616's Broad Immunomodulatory Potential to Initially Address Severe, Chronic Autoimmune Diseases

DM/

LN

PM

Prevalence: ~150K US patients Treatment: No approved treatments in US/EU

Prevalence: ~70K US patients Treatment: Limited approved
treatments in US/EU

CURRENT TREATMENT PARADIGMS ARE INADEQUATE

· Prolonged corticosteroid use results in significant complications · Existing therapies are ineffective in many patients

Almani S et al. CJASN 2017 Oddis C et al. Nat Rev Rheumatol 2018 Barcellini W et al. Expert Rev Clin Immunol 2018

· Targeted therapies (e.g., biologics) may not address needs of all patients with Lambert MP et al. Blood 2017

diseases characterized by defects in multiple arms of the immune system

https://www.ncbi.nlm.nih.gov/pmc/articles/P MC4386579/figure/Fig4

8

Data From 130+ Healthy Volunteers and SLE Patients* Receiving KZR-616 Support Advancement into Ph2 Trials in Chronic Autoimmune Diseases

Safety & Tolerability

Efficacy & Biomarkers

PK & PD

· Well-tolerated for 13 weeks of treatment
· Safety profile does not indicate need for patient monitoring

· Improvement across all measured parameters of disease activity
· Rapid and sustained immunomodulatory gene expression changes
· Reduction in anti-dsDNA antibody titers in 7/7 patients with elevated levels at BL

· Consistent PK and PD across subjects and with repeat dosing
· Target levels of immunoproteasome inhibition at doses  30mg

· Rapid reduction in UPCR in 2/2 patients with active, proliferative LN

*data as of Sept 24, 2020

Furie et al, EULAR 2019, ACR 2019, ASN 2020, and ACR 2020

9

KZR-616 is Now Being Evaluated Phase 2 Clinical Trials for the treatment of Chronic, Severe Autoimmune Diseases

Phase 1b

SLE / LN

2020 2H

Phase 2

LN

Phase 2

DM / PM

2021

1H

2H

2022 1H

OLE OLE
Anticipated data updates 10

PRESIDIO Phase 2 Placebo-Controlled Cross-over Study for the Treatment of Dermatomyositis and Polymyositis Designed to Inform Late Stage Studies

Adult patients with DM or PM
(n=24)

Randomize 1:1

TREATMENT PERIOD 1

TREATMENT PERIOD 2

KZR-616 45mg* SC once weekly

t

Placebo SC once weekly

*1st 2 doses are 30mg

Placebo SC once weekly

t

KZR-616 45 mg* SC once weekly

*1st 2 doses are 30mg

12 ­month Extension Study or 8week Safety Follow-up

Week 16 Secondary Endpoint

Week 32 Primary Endpoint

ENDPOINTS

1o: Efficacy: Total Improvement Score (TIS)

2o: Safety and tolerability; Patient Reported Outcomes (PROs), PK

Exploratory: Biomarkers, PK/PD relationship

Study NCT04033926
11

KZR-616 Improved Muscle Function in a Mouse Model of Polymyositis and Dermatomyositis*

CIM MODEL
· Gold standard model for PM and DM (Sugihara 2007)
· Replicates multiple features of clinical disease

Tx (2 weeks)

· KZR-616 treatment of diseased animals restored normal muscle function
· Significant reduction in tissue damage (histology and circulating enzyme levels)

Muscle Strength

Histopathology score Grip Strength
(Relative to Body Weight) CK Activity (units/L)

4

3

2

***

Naive

1

Vehicle

KZR-616 0
13 15 17 19 21 23 25 27 29

Days Post Immunization

Muscle Histology

Muscle Enzymes

10

***

8

6

4

2

0 Vehicle

KZR-616

500

*

400

300

200

100

0 Naive Vehicle KZR-616

CIM=C protein-induced myositis *Oliva MDR et al, ACR 2020

Vehicle

KZR-616

Triceps Histology
(H&E Staining)
12

MISSION Phase 2 Trial to Demonstrate Responder Rate of KZR-616 60 mg Weekly and Inform Late Stage Studies in LN

Adult patients with Lupus Nephritis (n=20)

1 Immunosuppressive + KZR-616 60mg* SC
once weekly (n=20)

*1st dose is 30mg

KZR-616 45 mg* SC once weekly

Week 24 Primary Endpoint

12-month extension study or 12week safety follow-up

KEY INCLUSION CRITERIA:

Biopsy-proven Class III or IV +/- Class V LN w/significant proteinuria (UPCR 1) despite standard therapy

Must be on stable therapy for at least 8 weeks prior to study entry

ENDPOINTS

1o: Efficacy Number of patients with  50% reduction in UPCR

2o: Safety and tolerability; Additional renal response parameters (e.g. CRR); Extra-renal SLE disease indices; PROs

Exploratory: Biomarkers
NCT03393013
13

MISSION Phase 1b is Designed to Evaluate Safety, Tolerability, and Early Efficacy Signals Enrollment Complete

Cohort 1 (n=8) COMPLETED
Cohort 2 (n=5) COMPLETED
Cohort 2a (n=14) COMPLETED
Cohort 2b* (n=6) COMPLETED
Cohort 2c* (n=8) ACTIVE
Cohort 3* (n=6) ACTIVE
WEEK 0

Tolerability Strategies Cohort

WEEK 13

30 mg KZR-616 QW 45 mg KZR-616 QW 60 mg KZR-616 QW 75 mg KZR-616 QW

12-week safety follow-up

2

4

6

8

10

12

*Cohorts 2b/2c/3 use lyophilized formulation

ENDPOINTS

1o: Safety

2o: Recommended Phase 2 doses, Plasma PK

Exploratory: Efficacy, PD, Biomarkers, Pharmacogenomics

14

Results Observed in 2 of 2 LN Patients Treated in the MISSION Phase 1b Showed Rapid Improvement in Renal Function

Cohort 2a patient
3.9

Cohort 2c patient

2.4

Week

0.7 0.6

Baseline Week 13 Week 17 Week 25

SLEDAI-2K 17 8 8 8

anti-dsDNA(IU/ml) 137 53 73 61

0.69 0.7

Week

Baseline Week 13 Week 17 Week 25

SLEDAI-2K 14 8 8 NA

anti-dsDNA(IU/ml) 123.5 52 40 53

· Baseline stable treatment regimen of leflunomide, hydroxychloroquine, and prednisone (10mg/day); failed prior tacrolimus
· Nephrotic range · >50% reduction in UPCR at week 17 · Reduced anti-dsDNA at week 13 · Drug holiday due to AE W2-4 & W11

· Baseline stable treatment regimen of MMF (2g), hydroxychloroquine, and prednisone (10mg/day) Nephrotic range
· >50% reduction in UPCR at week 5 · Improve symptom scores at week 5
· Reduced anti-dsDNA at week 5

End of Treatment W13; End of Study=W25

15

KZR-616 Demonstrated Improvement on Exploratory Efficacy Measures of Disease Activity Across Organ Systems in SLE

Tool
SLEDAI-2K

Improvement

Baseline (n=33)a

Mean Patient Score*

EOT -W13 (n=32) ab

EOS -W25 (n=27) a

9.2

6.7

7.2

CLASI-A

5.8

2.9

3.4

Tender Joint Count

11.2

5.0

5.6

Swollen Joint Count

7.7

2.5

2.1

Physician Global Assessment Score

57.0

40.4

39.6

Patient Pain Assessment

59.3

37.8

44.7

Patient Global Assessment Score

59.3

44.2

44.6

aNot all completing patients were evaluable because data had not been entered at the time of the data cut; b SLEDAI-2K at W13 is n=31
BL=Baseline; EOT=End of Treatment; EOS=End of Study; W13=week 13; W25=week 25; CLASI-A, Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity; SD, standard deviation; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000.

*There are patients still active in cohorts 2c and 3 as of Sept 24, 2020
16

Whole Blood RNASeq Data from MISSION Phase 1b Patients Support Potential Broad Immunomodulatory Activity of KZR-616

GENE S I G N AT U R E C O M PA R I S O N S

4 wks post 12 wks post last dose last dose
BL vs HV W5 vs BL W17 vs BL W25 vs BL

downregulated

upregulated

Enriched inflammatory gene signatures in SLE pts (n=16)

Rapid decrease in inflammatory gene expression
Fan et al.,ACR 2019
17

All Patients with Elevated Anti-dsDNA Levels at Baseline (n=7) Experienced Reductions After Treatment with KZR-616

Patients Completing Study w/Elevated anti-dsDNA at BL*

Individual

Mean anti-dsDNA level, IU/mL (baseline)

Patient A Patient Ba

1015 87

Patient C

32

Patient Db

134

Patient Ea

90

Patient Fb

98

Patient G

29

aHistory of nephritis. bActive nephritis. Abbreviation: anti-dsDNA, anti­double-stranded DNA antibody

% Change from baseline, week 13 (end of treatment)
-64.0 -20.7 -6.3 -60.4 -76.7 -46.9 -17.2

% Change from baseline, week 25
(end of study)
-82.0 -33.3 -18.8 -54.5 -68.9 -45.9 -24.1

*Elevated levels of anti-dsDNA antibodies are highly specific markers of SLE disease activity (>20 IU/mL considered elevated)

18

KZR-616 Continues to Demonstrate a Favorable Safety and Tolerability Profile at Higher Doses

Lyophilized formulation

Measures, N% of patients

Cohort 2aa (n=14)

Cohort 2b (n=6)

Cohort 2c (n=8)

All patients* (Cohorts 1-3)
(n=46)

At least 1 Treatment Emergent Adverse Event (TEAE)

12 (85.7)

4 (66.7)

7 (87.5)

38 (82.6)

Injection Site Erythema

5 (35.7)

2 (33.3)

6 (75.0)

20 (43.5)

Nausea

5 (35.7)

1 (16.7)

4 (50.0)

18 (39.1)

Vomiting

4 (28.6)

1 (16.7)

2 (25.0)

14 (30.4)

TEAEs  Grade 3

3 (21.4)

0 (0.0)

0 (0.0)

4 (10.3)

Infectious TEAEs  Grade 3

1 (7.1)

0 (0.0)

0 (0.0)

1 (2.2)

Infectious TEAEs; All Grades

5 (37.5)

2 (33.3)

2 (25.0)

10 (21.7)

Serious TEAEs

2 (14.3)

1 (16.7)

0 (0.0)

4 (8.7)

TEAEs leading to discontinuation

2 (14.3)

0 (0.0)

aPatients received 4 doses to reach target dose. *All patients are inclusive of patients from Cohort 1. 47 patients were enrolled, but data for one patient were not entered at time of data cut. Cohorts 2b, 2c and 3 utilize a lyophilized formulation of KZR-616, prophylactic oral electrolyte solution, non-sedating antihistamines, and antiemetics and/or dose escalation

0 (0.0)

10 (21.7)

*No patients in Cohort 3 had completed treatment as of Sept 24, 2020

Furie et al, EULAR 2019, ACR 2019, ASN

2020, ACR 2020

19

KZR-261, Our First Protein Secretion candidate, is Currently in IND-enabling Studies

COMPOUND

THERAPEUTIC INDICATION

Selective Immunoproteasome Inhibition

DISCOVERY

DEVELOPMENT STAGE

PRECLINICAL

PHASE 1

PHASE 2

KZR-616

Lupus Nephritis (LN)
Dermatomyositis (DM) / Polymyositis (PM)

Protein Secretion Inhibition

MISSION PRESIDIO

KZR-261 Oncology

IND-enabling activities

KZR-TBD Oncology & Autoimmunity

PHASE 3

20

The Sec61 Translocon Represents Initiation of the Protein Secretion Pathway

· Highly conserved process
· Nearly all secreted and transmembrane proteins (5,000 ­ 7,000 proteins) utilize Sec61 to enter the endoplasmic reticulum (ER)
· Each protein expresses a unique signal sequence or transmembrane domain

· Kezar tool compounds block functional interaction of signal sequences and Sec61
· Blocking functional interaction of signal sequences inhibits the expression of a selected protein or proteins

21

Targets of Most Biologics Utilize Sec61 for Secretion or Membrane Expression

A plethora of validated targets utilize the Sec61 translocon. Kezar's program holds the potential for superior small molecule therapeutics against these targets.

Membrane protein

Extracellular

Sec6 1 Ribosom e
mRN A

Golgi apparatus

Traditional biologics bind with proteins outside of the cell

DN A
E R Nucleu s

Cytos ol

Secreted proteins

Membrane Proteins
(partial list)
EGFR (ERBITUX) IL-6R (ACTEMRA) PD-1 (OPDIVO) PDL1 (TECENTRIQ) CTLA4 (YERVOY)
Secreted Proteins
(partial list)
TNF- (HUMIRA) IL-17 (COSENTYX) PCSK9 (REPATHA)
IL-6 (SYLVANT) BAFF (BENLYSTA)

22

Kezar has Multiple Small Molecule Approaches to Modulating Protein Secretion at the Sec61 Translocon

Multiple Protein Secretion
Inhibitors

Specific Protein Secretion
Inhibitors

· Potential for multiple clinical candidates
· Broad anti-tumor activity in vitro and in vivo
· KZR-261-first protein secretion clinical candidate; anticipated IND filing Q1 2021

Potential to inhibit multiple therapeutically relevant targets
with a single small molecule

· Small molecule replacement of biologic therapies
· Target selective approach · High value / validated
targets · Potential applications in
oncology and autoimmunity
23

KZR-261 Blocked Expression of Therapeutically Relevant Targets and Inhibited Tumor Growth In Vivo; IND Anticipated Q1 2021

In vitro Protein Secretion Assays

Cytokines & Cytokine Receptors

Immune Checkpoints

Oncogenic Factors

IC50 (nM) 1
100 250 500 750 900 >1000

TNFR1 TNFR2 IL-17A IL-17RA IL-23A IL-12B IL-23R
IL-6 IL-6R GP130 IL-1R1 IL-1R2 IL-1RA IL-2RA IFN-A1 IFN-A2 IFN-A4 IFN-B IFNG IFNAR1 IFNAR2 CTLA-4 PD-1 PD-L1 LAG3 TIM3 TIGIT CD96 VISTA B7H3 CD73 CD47 PDGFRa VGFR2 IL-7R EGFR VEGF HER3 Prolactin

In vivo Tumor Xenografts

Lowe et al. ASCO 2020

24

Gene Expression Profiling Reveals Differential ER Stress Response: Potential Gene Signature Biomarker

Sensitive Resistant

CCLE Gene Expression

TCGA Gene Expression

· Sensitive and resistant myeloma cell lines were treated with a Sec61 inhibitor
· RNASeq analysis used to find gene modules that differed between the cell lines
· Sensitive cells: Increased expression of ER stress genes
· Enriched expression of ER stress genes in multiple solid tumor types

ER Stress Gene Module Expression Levels: log10(Wilcox P-Value)
25

Positioned for Growth and Delivering Shareholder Value

Q4 2020

· Updated MISSION Phase 1b data (through Sept 2020) · Initiate PRESIDIO Open-label Extension Study

1H 2021

· IND Submission for KZR-261 · Initiate Phase 1 basket study in solid tumors (KZR-261) · Final Data from MISSION Phase 1b study (KZR-616 in SLE) · Initiate MISSION Phase 2 Open-label extension study (KZR-616 in LN)

2H 2021 · Interim data from MISSION Phase 2 study (KZR-616 in LN)

1H 2022

· Top-line data from MISSION Phase 2 study (KZR-616 in LN) · Top-line data from PRESIDIO Phase 2 study (KZR-616 in DM/PM)

26

The Kezar Opportunity: Harnessing Master Regulators of Cellular Function to Tackle Immune-mediated Diseases and Cancer

2 distinct scientific programs with potential across multiple indications of high unmet need

Rich Platform & Growing Pipeline

KZR-616: First-in-Class Immunoproteasome
Inhibitor

A novel approach to harmonizing the immune system; Potential to be a pipeline in a drug

First in class agent with broad antitumor activity; Potential to inhibit multiple targets with a single small molecule

KZR-261: First candidate from
Protein Secretion Platform

Strong Financial Position
(as of 9/30/2020)

$150M cash, cash equivalents, and marketable securities; 46.3M common shares outstanding
27

THANK YOU
28