Slide 1: Topline Results from the PORTOLA Phase 2a Trial in Autoimmune Hepatitis
Topline Results from the PORTOLA Phase 2a Trial in Autoimmune Hepatitis (AIH) Exhibit 99.2
Slide 2: Forward-Looking Statements and Topline Data Disclaimer
Forward-Looking Statements and Topline Data Disclaimer The material in this presentation (this “Presentation”) regarding Kezar Life Sciences, Inc. (“Kezar”) is for informational purposes only. This Presentation contains forward-looking statements within the meaning of the Private Securities Litigati
Slide 3: Agenda and Speakers
Christopher J. Kirk, PhD Chief Executive Officer, Co-founder Craig Lammert, MD Associate Professor of Medicine Indiana University School of Medicine Director, Autoimmune Hepatitis Association Agenda 8:00 AM – 8:05 AM ET Opening Remarks Christopher J. Kirk, PhD 8:05 AM – 8:20 AM ET PORTOLA Clinical T
Slide 4: Successful Outcome in PORTOLA Study
Successful Outcome in PORTOLA Study 4 Ph 2 Trial of zetomipzomib vs. placebo in AIH patients with relapsed disease or inadequate response to prior therapy • Intent to Treat Population (ITT; n=24) • Pre-specified subgroup of patients entering study on steroid-based therapy (likely registrational popu
Slide 5: Autoimmune Hepatitis is a Complex Disease with Poor Treatment Options
Autoimmune Hepatitis (AIH) is a Complex Disease with Poor Treatment Options ~100,000 cases in US (similar prevalence in EU) 4:1 female to male • Diagnosis involves presence of elevated liver enzymes (ALT/AST) and immunoglobulin G (IgG), inflammatory cell infiltration in the liver, elevated autoantib
Slide 6: Treatment Goals in Newly Diagnosed AIH
Treatment Goals in Newly Diagnosed AIH are Focused on Biochemical Normalization and Low Daily Steroid Dose Abbreviations: AASLD, American Association for the Study of Liver Diseases; ALT, alanine aminotransferase; AST, aspartate aminotransferase; EASL, European Association for the Study of the Liver
Slide 7: Selective Inhibition of the Immunoproteasome Impacts Multiple Drivers of AIH
Broad Therapeutic Potential • Rapid onset of activity • Minimal risk for immunosuppression • Steroid sparing agent • No lab monitoring required • Active in patients with severe and treatment refractory disease Broad Immunomodulatory Activity • Reduction of multiple inflammatory cytokines from APC •
Slide 8: PORTOLA: Phase 2a Placebo-Controlled Trial Design
Evaluating the Safety and Efficacy of Zetomipzomib in Relapsed or Insufficient Responding Autoimmune Hepatitis PORTOLA: Phase 2a Placebo-Controlled Trial Adult patients with AIH (N=24) Optional Open-Label Extension Treatment Period Randomization 2:1 Up to 24 weeks of treatment Zetomipzomib 60 mg onc
Slide 9: PORTOLA Efficacy Endpoints
9 PORTOLA Efficacy Endpoints Primary Efficacy Endpoint • Proportion of patients who achieve a complete biochemical response (CR) by Week 24 • CR defined as normalization of ALT, AST and IgG levels (if IgG levels were elevated at Baseline) with steroid dose not higher than Baseline dose Key Secondary
Slide 10: PORTOLA Patient Disposition
Completed OLE N=3 OLE Ongoing* N=1 Entered OLE N=9 Completed DBTP N=13 Zetomipzomib QW N=16 Discontinued Treatment† N=3 †Reasons for discontinuation: AIH flare (treatment failure per protocol), fatigue, hives, PORTOLA Patient Disposition *As of 01-March 2025. Abbreviations: DBTP, double-blind treatm
Slide 11: PORTOLA Demographics and Baseline Characteristics
PORTOLA Demographics and Baseline Characteristics (ITT Population) Placebo N=8 Zetomipzomib N=16 Total N=24 Age, median (min, max), years 54.0 (26, 72) 59.0 (25, 75) 57.5 (25, 75) Female, n (%) 6 (75.0) 8 (50.0) 14 (58.3) Race, n (%) White 7 (87.5) 13 (81.3) 20 (83.3) Ethnicity, n (%) Hispanic or La
Slide 12: Historic ALT Levels and Daily Steroid Use Higher in Zetomipzomib Arm
Prior to Screening, Historic ALT Levels and Daily Steroid Use Were Higher in Patients Assigned to Zetomipzomib Arm †Mean Historical ALT ≤3 months prior to Screening. | *Two patients in the placebo arm did not have available prescreening values. ^Placebo patient randomized but not dosed, and did not
Slide 13: Zetomipzomib Results in Higher Complete Remission Rates with Steroid Taper
AASLD and EASL Guidelines Target Treatment Goals Placebo (3/8) Zetomipzomib (8/16) 0 20 40 60 Complete Response (CR) Pr op or tio n of P at ie nt s (% ) 37.5% 50% Placebo (1/8) Zetomipzomib (5/16) 0 10 20 30 40 50 CR with Steroid Taper to ≤5 mg/d Pr op or tio n of P at ie nt s (% ) 31.3% 12.5% Place
Slide 14: Steroid Sparing Remissions in Patients on Daily Steroid Dose
• 21 of 24 patients entered screening on daily steroid therapy • Median steroid dose was 10 mg in the placebo arm vs. 20 mg in the zetomipzomib arm at screening Zetomipzomib Treatment Results in Steroid Sparing Biochemical Remissions in Patients Entering PORTOLA on Daily Steroid Dose ITT Population
Slide 15: Exploratory Endpoints: Remission Correlates with Histologic Improvements
Exploratory Endpoints *3 patients shown (2 patients had identical pre- and post-treatment mHAI scores) Biochemical Remission Correlates with Histologic Improvements 0 24 0 5 10 15 Complete Response (CR) Week Is ha k Sc or e 2 pts overlap 0 24 0 5 10 15 Treatment Failure/ No Response (NR) Week Is ha
Slide 16: PORTOLA Safety: Favorable Safety and Tolerability Profile
PORTOLA Safety: Favorable Safety and Tolerability Profile with Zetomipzomib Treatment (Safety Population) Adverse Events in Double Blind Treatment Period Placebo N=7 n (%) Zetomipzomib N=16 n (%) Participants with at least 1 Treatment Emergent Adverse Event (TEAE) 7 (100.0) 16 (100.0) Most common TE
Slide 17: Safety of Zetomipzomib Consistent Across Multiple Clinical Trials
Trial/Treatment arm/ Dose (N) MISSION Ph 2 Zeto 60 mg N=21 PALIZADE Placebo N=28 PALIZADE Zeto 60 mg N=29 Indication Lupus Nephritis Treatment Period (Weeks) 24 52† At least one TEAE, n (%) 21 (100.0) 17 (60.7) 25 (86.2) Serious TEAEs, n (%) 2 (9.5) 3 (10.7) 8 (27.6) Grade 3 or 4 TEAEs, n (%) 6 (28.
Slide 18: Zetomipzomib: Potentially Transformative Steroid-Sparing Agent for AIH
Zetomipzomib is a potentially transformative steroid-sparing agent for patients struggling with AIH • 36% of zetomipzomib-treated patients (5/14) that were on steroid-based therapy at the time of screening achieved steroid-sparing biochemical remission by Week 24 vs. 0% of patients in placebo arm (0
Slide 19: PORTOLA Experience
INDIANA UNIVERSITY SCHOOL OF MEDICINE PORTOLA Experience Craig S. Lammert, MD Assistant Professor of Medicine, Indiana University School of Medicine Executive Director of the Autoimmune Hepatitis Association Principal Investigator of the PORTOLA Clinical Trial
Slide 20: Investigator Perspective: PORTOLA Experience
INDIANA UNIVERSITY SCHOOL OF MEDICINE Investigator Perspective: PORTOLA Experience • Autoimmune Hepatitis: Immunologic chess • Why PORTOLA matters: Limited novel therapeutic options for relapsed/refractory AIH patients and are often steroid-dependent; no new advances beyond steroids and immunosuppre
Slide 21: PORTOLA Case: Patient with Complete Response
INDIANA UNIVERSITY SCHOOL OF MEDICINE PORTOLA Case: Patient with Complete Response (Zetomipzomib) Medical History and Baseline Characteristics • 66 y/o white male, AIH since 2022 (7.7 months), ANA+ • Mean ALT, IgG prior to screen: 242 U/L, 978 mg/dL • Prior meds: MMF (1500 mg PO BID) + Prednisone: m
Slide 22: Patient Achieved CR with Steroid Taper to 0 mg/d
INDIANA UNIVERSITY SCHOOL OF MEDICINE Patient Case: Patient with CR (Zetomipzomib) Patient Achieved CR with Steroid Taper to 0 mg/d and Maintained 0 mg/d During OLE -4 0 4 8 12 16 20 24 0 50 100 150 200 250 0 10 20 30 500 1000 1500 2000 28 32 36 40 44 48 52 56 60 Week A ST /A LT ( U /L ) G C D os e
Slide 23: Patient Achieved CR and Maintained 0 mg/d During OLE
INDIANA UNIVERSITY SCHOOL OF MEDICINE Patient Achieved CR with Steroid Taper to 0 mg/d and Maintained 0 mg/d During OLE • Achieved a CR during DBTP and was able to taper steroids to 0 mg/d at W24 • Maintained CR with no flares and remained off steroid throughout OLE treatment period • Experienced Gr
Slide 24: Investigator Perspective: Zetomipzomib Has Potential to Transform AIH Landscape
INDIANA UNIVERSITY SCHOOL OF MEDICINE Investigator Perspective: Zetomipzomib Has Potential to Transform AIH Landscape Clinical observations: • Quick, durable response with no flares on PORTOLA with ability to taper off steroid completely with zetomipzomib treatment highlights the potential for zetom
Slide 25: Autoimmune Hepatitis: We Can and Should Do Better
Presented by Gideon Hirschfield, Autoimmune and Rare Liver Disease Programme AUTOIMMUNE HEPATITIS: WE CAN AND SHOULD DO BETTER Gideon Hirschfield, PhD, MB BChir, FRCP Lily and Terry Horner Chair in Autoimmune Liver Disease Research Director, Francis Family Liver Clinic, Toronto General Hospital
Slide 26: Our Expertise and Experience
Presented by Gideon Hirschfield, Autoimmune and Rare Liver Disease Programme 26 Our Expertise and Experience Rare but not infrequent Middle age/Female predominant/Lifelong High burden of cirrhosis High burden of corticosteroid use Low use of ‘advanced’ therapies Au to im m un e He pa tit is Take hom
Slide 27: AIH: A Significant Unmet Need
Presented by Gideon Hirschfield, Autoimmune and Rare Liver Disease Programme Autoimmune Hepatitis (AIH): A Significant Unmet Need • AIH is a chronic autoimmune disease with unresolving inflammation of the liver of unknown cause • Complex interplay of genetic predisposition and environmental triggers
Slide 28: Presented by Gideon Hirschfield, Autoimmune and Rare Liver Disease Programme Fig. 2 Trivedi P
Presented by Gideon Hirschfield, Autoimmune and Rare Liver Disease Programme Fig. 2 Trivedi P et al. 2019 28
Slide 29: AIH: Real World Challenges
Presented by Gideon Hirschfield, Autoimmune and Rare Liver Disease Programme AIH: Real World Challenges • Limited options with standard of care - lack of choice • Adverse effects of corticosteroids and immunosuppressant individually and together • Tolerability • Weight, diabetes, osteoporosis, cosme
Slide 30: AIH: Current Unmet Needs
Presented by Gideon Hirschfield, Autoimmune and Rare Liver Disease Programme AIH: Current Unmet Needs • Inadequate therapy choices • Bad disease, ineffective drug, or intolerable treatment • Need for therapies that reliably induce durable remission with safety and tolerability that are on-label • La
Slide 31: Need for Novel Targeted Therapies
Presented by Gideon Hirschfield, Autoimmune and Rare Liver Disease Programme Need for Novel Targeted Therapies: Zetomipzomib Has Opportunity to Add Value • Broad immunomodulatory activity targeting AIH pathophysiology – relevant niche/alignment of opportunities to enter AIH • B-cells/T-cells • Lack
Slide 32: Thank you
Presented by Gideon Hirschfield, Autoimmune and Rare Liver Disease Programme Thank you Gideon Hirschfield
Slide 33: Next Steps & Closing Remarks
Presented by Gideon Hirschfield, Autoimmune and Rare Liver Disease Programme NEXT STEPS & CLOSING REMARKS Christopher J, Kirk, PhD Chief Executive Officer, Co-Founder
Slide 34: Next Steps for Zetomipzomib Program in AIH
Next Steps for Zetomipzomib Program in AIH Pending removal of partial clinical hold, Kezar looks forward to aligning with the FDA and EMA on a potential registrational study in AIH Kezar will respond to all FDA Division of Hepatology partial clinical hold comments as quickly as possible Biochemical
Slide 35: Question & Answer Session
QUESTION & ANSWER SESSION
Slide 36: Contact Us
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