Kezar Life Sciences, Inc. · NASDAQ:KZR
Kezar Life Sciences — Investor Day (November 2021)
62 slides from Kezar Life Sciences's investor day presentation, Nov 15, 2021
Slide 1: Uniquely Powerful Approaches to Tackling the Toughest Diseases
November 15, 2021 Uniquely Powerful Approaches to Tackling the Toughest Diseases SELECTIVE TARGETS. BROAD IMPACT. Kezar Life Sciences 1 Exhibit 99.1
Slide 2: Forward-looking statements
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
Slide 3: Analyst Day Agenda
Analyst Day Agenda a 4:30 PM— 4:35PM — Welcome, Introductions, and Opening Remarks John Fowler, MBA 4:35 PM- 4:50PM — KZR-616 for LN: MISSION Phase 2 Interim Data Noreen R. Henig, MD 4:50 PM — 5:05 PM Investigator-led IND Update Samir V. Parikh, MD 5:05 PM — 5:20 PM KZR-616 for DM/PM: PRESIDIO Overv
Slide 4: The Kezar Opportunity
The Kezar Opportunity: Harnessing Master Regulators of Cellular Function to Tackle Immune-mediated Diseases and Cancer A novel approach to harmonizing the immune system via immunomodulation; Potential to be a pipeline in a drug First in class agent with broad anti-tumor activity; Potential to inhibi
Slide 5: Kezar's Novel, Complementary Programs Target Master Regulators of Cellular Function
Kezar’s Novel, Complementary Programs Target Master Regulators of Cellular Function to Achieve Broad Therapeutic Activity Modulates multiple drivers of inflammation Restores normal immune responses, without evidence of immunosuppression PROTEIN DEGRADATION: The Immunoproteasome PROTEIN SECRETION: Th
Slide 6: Potential to restore normal immune responses while avoiding immunosuppression
Potential to restore normal immune responses while avoiding immunosuppression Modulates multiple drivers of inflammation across immune cell types Avoids cytopenias; favorable safety profile for chronic use based on Phase 1 studies Active in broad array of autoimmune disease models Immunoproteasome I
Slide 7: Immunoproteasome Inhibition with KZR-616 Targets Multiple Cytokines and Cells
Inflammatory Disorders are Currently Treated One Cytokine or Cell at a Time, but the Inhibition of Immunoproteasome with KZR-616 Targets Them All Macrophages Dendritic Cells Monocytes T-cell B-cell Rituxan/Gazyva Benlysta IVIg/FcRn Inhibitor Orencia Lupkynis Xeljanz Cytokines IL-17 Cosentyx/Taltz KZ
Slide 8: Our Clinical Programs Inhibit Multiple Drivers of Disease
Our Clinical Programs Inhibit Multiple Drivers of Disease via Selective Targets to Address a Diverse Pipeline of Indications 8
Slide 9: MISSION: Phase 1b/2 Study in SLE/Lupus Nephritis
Noreen R. Henig, MD Chief Medical Officer MISSION: Phase 1b/2 Study to Evaluate the Safety and Efficacy of KZR-616 in Systemic Lupus Erythematosus/Lupus Nephritis 9 Interim data reported and are subject to audit and verification procedures that could result in material changes in the final data.
Slide 10: KZR-616 Clinical Program Overview
KZR-616 Clinical Program Overview Abbreviations: DM, dermatomyositis; LN, lupus nephritis; PM, polymyositis; SLE, systemic lupus erythematosus. 10
Slide 11: MISSION: Phase 1b/2 Open-Label Multi Center Study Design
MISSION: Phase 1b/2 Open-Label, Multi Center Study to Evaluate the Safety and Efficacy of KZR-616 in SLE/LN Part 1: Phase 1b Part 2: Phase 2 Abbreviations: CRR, complete renal response; LN, lupus nephritis; PD, pharmacodynamics; PK, pharmacokinetics; PRO, patient reported outcomes; PRR, partial rena
Slide 12: KZR-616: Phase 1 Findings to Date
Modulates innate and acquired immune responses without signs of immunosuppression to date Weekly administration results in consistent pharmacokinetics and pharmacodynamics Selective inhibition of the immunoproteasome via targeting of specific subunits LMP2 and LMP7 Weekly dose leads to consistent ex
Slide 13: MISSION Phase 1b: Safety and Tolerability
MISSION Phase 1b [Complete]: Safety and Tolerability Supports Extended Use in Chronic Diseases *Cohorts 2b, 2c, and 3 received a lyophilized formulation of KZR-616. Furie et al, EULAR 2021. Abbreviations: d/c, discontinuation; TEAE, treatment-emergent adverse event. 13
Slide 14: MISSION Phase 1b: Reduced UPCR and uCD163 in 2 Patients With LN
MISSION Phase 1b [Complete]: Reduced UPCR and uCD163* in 2 of 2 Patients With LN Baseline stable treatment regimen of leflunomide, hydroxychloroquine, and prednisone (10 mg/d); failed prior tacrolimus Nephrotic range >50% reduction in UPCR at week 17 Reduced anti-dsDNA at week 13 Baseline stable tre
Slide 15: Interim Data MISSION Phase 2
Interim Data MISSION Phase 2 Data from the MISSION Phase 2 clinical trial are preliminary and will require confirmation in additional patients as well as longer follow-up to draw any clinical conclusion. Interim top-line and preliminary data from our clinical trials that we announce or publish from
Slide 16: MISSION Phase 2: Open-Label Study in Active Proliferative Lupus Nephritis
*Patients received 24 weeks of KZR-616; End of treatment assessments performed at Week 25. Abbreviations: UPCR, urine protein to creatinine ratio; CRR, complete renal response; EOT, end of treatment; PRR, partial renal response; PRO, patient reported outcomes; SC, subcutaneous; QW, every week. MISSI
Slide 17: MISSION Phase 2: Endpoints
Open-label study evaluating KZR-616 60mg weekly for 24 weeks in patients with active, proliferative lupus nephritis (LN, Class III or IV, +/- V) Primary endpoint: Number of patients with 50% reduction in UPCR compared to baseline after 24 weeks of KZR-616 Key secondary endpoints: Safety and tolerabi
Slide 18: Target enrollment met; interim analysis basis
Target enrollment of 20 patients met for MISSION Phase 2 study Interim analysis is based on laboratory and safety analysis; a full data analysis will occur at the completion of the study 10 patients who completed at least 13 weeks of treatment with KZR-616 SC QW were included in the analysis 5 of th
Slide 19: KZR-616 60mg SC QW Associated with Clinically Important Renal Response
KZR-616 demonstrates a safety and tolerability profile favorable for long-term administration 4 of 5 patients completing end of treatment (Week 25) demonstrated clinically meaningful reduction in proteinuria: 2 patients with CRR (complete renal response) 2 patients with PRR (partial renal response)
Slide 20: MISSION Phase 2 Interim Data: Patient Disposition
MISSION Phase 2 [Interim Data]: Patient Disposition Weeks EOT^ n=5 W13 n=10 Patients* *Each bar represents one patient in the study. ^Patients received 24 weeks of KZR-616; end of treatment assessments performed at Week 25. 20 Interim data reported as of 01-Oct 2021 and are subject to audit and veri
Slide 21: Key Demographics and Baseline Characteristics
MISSION Phase 2 [Interim Data]: Key Demographics and Baseline Characteristics of 10 Patients Who Reached ≥13 Weeks Abbreviations: MMF, mycophenolate mofetil; MPA, mycophenolic acid. 21 Interim data reported as of 01-Oct 2021 and are subject to audit and verification procedures that could result in m
Slide 22: Overall Renal Response at EOT
MISSION Phase 2 [Interim Data]: Overall Renal Response in 4 out of 5 Patients at EOT (n=5) 22 Interim lab data reported as of 12-Oct 2021 and are subject to audit and verification procedures that could result in material changes in the final data. Patients received 24 weeks of KZR-616; end of treatm
Slide 23: Patients Achieving ≥50% Reduction in UPCR at EOT
MISSION Phase 2 [Interim Data]: 3 out of 5 Patients Achieved ≥50% Reduction in UPCR at EOT 23 * UPCR reduction 25% to <50% UPCR reduction ≥50% *n=5 patients with 25 weeks data; patients received 24 weeks of KZR-616; end of treatment assessments performed at Week 25. Abbreviation: EOT, end of treatme
Slide 24: Early, Meaningful Reduction in UPCR at Week 13
MISSION Phase 2 [Interim Data]: KZR-616 Showed Early, Meaningful Reduction in UPCR at Week 13 * UPCR reduction 25% to <50% UPCR reduction ≥50% UPCR reduction >0% to <25% *N=10 patients with ≥13 weeks data. 24 Interim lab data reported as of 12-Oct 2021 and are subject to audit and verification proce
Slide 25: Improvement in Key Serologic Biomarkers at Week 13
No abnormal disease biomarkers, including cell counts, emerged in patients on study MISSION Phase 2 [Interim Data]: Improvement in Key Serologic Biomarkers Observed at Week 13 in Patients with Abnormal Levels at Baseline 25 Week 25 data pending. Reference ranges: dsDNA <20 IU/mL; C3 90 - 180 mg/dL;
Slide 26: Safety and adverse events summary
All reported AEs were mild to moderate (≤Grade 2) except 1 related SAE of Grade 3 migraine occurred, which led to temporary interruption of study drug. Patient fully recovered and resumed study treatment at the same 60mg dose level. 1 unrelated SAE of worsening PAH and AKI; led to discontinuation No
Slide 27: EULAR/ERA-EDTA Goals of Treatment for Patients with LN
EULAR/ERA-EDTA Goals of Treatment for Patients with LN MISSION Phase 2 [Interim Data] Patients With Persistent Proteinuria Despite SOC Achieved Clinically Meaningful Benefit per EULAR/ERA-EDTA Treatment Goals With Addition of KZR-616 and Without Induction or Higher Doses of Immunosuppressive Therapy
Slide 28: KZR-616 Interim Analysis Learnings and Later Phase Planning
KZR-616 MISSION Phase 2 interim data learnings KZR-616 60mg SC QW dosing (starting with “step-up” dose) demonstrates a favorable safety and tolerability profile KZR-616 60mg SC QW demonstrated meaningful reductions in proteinuria in patients with LN, including those who are refractory or hard to tre
Slide 29: Introduction to Investigator-led IND Study
MISSION 1b enrolled two patients with active LN, which were reported as Patient #1 and Patient #2 Following completion of the MISSION 1b study, the site investigator treating Patient #1 approached Kezar about re-starting KZR-616 as the patient reported improvements in SLE symptoms and showed reduced
Slide 30: Investigator-led IND Study: KZR-616 for Refractory LN
Investigator-led IND Study: KZR-616 for the Treatment of Refractory LN Samir V. Parikh, MD, FASN Associate Professor, Division of Nephrology The Ohio State University Wexner Medical Center November 15, 2021 30
Slide 31: Case Report: Past Medical History
Case Report: Past Medical History 29-year-old Asian female diagnosed with SLE and LN in 2015-Jan LN Biopsy (2019-May): Class IV/V LN Treatment: Initially treated with high dose steroids and MMF. Developed leukopenia on MMF so discontinued Failed prior therapy with tacrolimus and no improvement on le
Slide 32: OSU Patient Presented From MISSION 1b
OSU Patient was “Patient 1” Presented From MISSION 1b Serologic biomarkers: Disease activity assessment: Patient had drug holidays (weeks 2-4, 11) due to AE of Systemic Inflammatory Response Syndrome, and KZR-616 was reinitiated in this trial. Abbreviations: EOS, end of study; EOT, end of treatment.
Slide 33: Worsening Course of Disease Following MISSION Phase 1b
Patient 1 Experienced Worsening Course of Disease Following Completion of MISSION Phase 1b Study No significant changes to medications UPCR: 0.56 (3 months following completion of MISSION Ph1b) 5.5 (9 months following completion of MISSION Ph1b) Symptoms at 9 months following completion of MISSION P
Slide 34: UPCR Reduced <0.5 With Cessation of Corticosteroids
UPCR Reduced <0.5 in Investigator-Sponsored IND Patient with Complete Cessation of Corticosteroids Within 12 Weeks of Initiation of KZR-616 Serologic biomarkers: Anti-dsDNA antibody: Baseline: 7 IU/mL; Negative throughout the study C3/C4 values normalized after KZR-616 treatment Disease activity ass
Slide 35: Summary: Patient Improves on KZR-616 Treatment
SUMMARY: Patient Improves on KZR-616 Treatment Rapid improvement in proteinuria and clinical disease activity seen in the MISSION Phase 1b Patient experienced worsening of disease with a return to nephrotic range proteinuria 9 months following completion of MISSION Phase 1b Improvements seen early o
Slide 36: KZR-616 Potential in the LN Treatment Landscape
KZR-616 Potential in the LN Treatment Landscape Preclinical and early clinical data suggest that KZR-616 has broad immunomodulatory potential, with no major safety signals to date Possible role as: Potent anti-inflammatory Anti-autoimmunity therapy Steroid-sparing Consolidation therapy to limit numb
Slide 37: PRESIDIO: Phase 2 Trial in Dermatomyositis and Polymyositis
Noreen R. Henig, MD Chief Medical Officer PRESIDIO: Phase 2 Trial to Evaluate the Safety and Efficacy of KZR-616 in Dermatomyositis and Polymyositis 37
Slide 38: KZR-616 Clinical Program Overview
KZR-616 Clinical Program Overview Abbreviations: DM, dermatomyositis; LN, lupus nephritis; PM, polymyositis; SLE, systemic lupus erythematosus. 38
Slide 39: Significant Unmet Need in Dermatomyositis and Polymyositis
KZR-616 has the Potential to Address the Significant Unmet Need in Dermatomyositis (DM) and Polymyositis (PM) Prevalence: up to ~120K US patients Limited effective treatment options KZR-616 has been granted ODD by the US FDA for both indications Women 2x as likely to have DM/PM Prevalence is highest
Slide 40: Large Unmet Medical Need Despite Available Therapies
Despite Currently Available Therapies, Most of Which Have Been Available for Decades, There Remains a Large Unmet Medical Need and Increased Health Care Utilization for Patients with DM and PM ACR 2021 Convergence [08-Nov 2021] KZR-616 is the only agent in the US granted Orphan Drug Designation (ODD
Slide 41: KZR-616 Improved Muscle Function in a Mouse Model of PM and DM
KZR-616 Improved Muscle Function in a Mouse Model of PM and DM* KZR-616 Vehicle Triceps Histology (H&E Staining) CIM MODEL Gold standard model for PM and DM (Sugihara 2007) Replicates multiple features of clinical disease Validated with IVIg approval Tx (2 weeks) KZR-616 treatment of diseased animal
Slide 42: PRESIDIO Placebo-Controlled Cross-over Study Design
PRESIDIO Phase 2 Placebo-Controlled Cross-over Study for the Treatment of DM and PM Designed to Inform Late-Stage Studies TREATMENT PERIOD 1 TREATMENT PERIOD 2 Week 16 Secondary Endpoint Week 32 Primary Endpoint *1st 2 doses are 30mg ENDPOINTS Study NCT04033926 1o: Efficacy: Total Improvement Score
Slide 43: KZR-616 for DM/PM: Top-Line Results Q2 2022
TIS is the same endpoint used in label expansion study for Octagam 10% [immune globulin intravenous (human)] for the treatment of DM. Also used in the Phase 3 trial of lenabasum for the treatment of DM TIS is a composite score which includes measures of muscle strength, serum enzymes which correspon
Slide 44: Next Steps for Development of KZR-616 in DM and PM
Next Steps for the Development of KZR-616 in DM and PM PRESIDIO study achieved target enrollment in August 2021 Top-line results anticipated in the second quarter of 2022 Kezar is currently planning registrational studies of KZR-616 in inflammatory myositis based on High unmet need Strong preclinica
Slide 45: Development in Other Inflammatory Myopathies
Kezar Will Consider Development in Other Inflammatory Myopathies if PRESIDIO Generates Positive Results Dermatomyositis and polymyositis are two of four subtypes of the idiopathic inflammatory myositis Dermatomyositis has a bimodal age distribution with one peak in adults and the other in pediatric
Slide 46: KZR-261 & Protein Secretion Platform
Christopher Kirk, PhD President and Chief Scientific Officer, Co-Founder KZR-261 & Protein Secretion Platform 46
Slide 47: KZR-261 Began Phase 1 Trial in Advanced Solid Malignancies
KZR-261, Our First Protein Secretion Candidate, Began a Phase 1 Trial in Patients With Advanced Solid Malignancies in October 2021 47
Slide 48: The Sec61 Translocon: Novel Drug Target in Oncology
The Sec61 Translocation Channel (Translocon) is the Initiation of the Protein Secretion Pathway and a Novel Drug Target in Oncology Highly conserved process, functional in all cells Nearly all secreted and transmembrane proteins (5,000 – 7,000 proteins) utilize Sec61 to enter the ER Each protein exp
Slide 49: Novel Platform for Drug Discovery Targets the Sec61 Translocon
Inhibition of a single secreted/membrane protein Non-cytotoxic agents Indications: Many… Inhibition of multiple secreted/membrane proteins Combination therapy in a single molecule Multiple oncology indications (tumor agnostic) Inhibition of relevant subset secreted/membrane proteins Non-cytotoxic ag
Slide 50: KZR-261 Is the First Sec61 Inhibitor to Reach Clinical Trials
KZR-261 Is the First Sec61 Inhibitor to Reach Clinical Trials First clinical candidate from our novel discovery platform Optimized to inhibit a small subset of secreted proteins Inhibits ~9% of secreted/transmembrane proteins Inhibits only ~3% in non-transformed cells Broad anti-cancer activity in v
Slide 51: KZR-261 Blocks Expression of Immune Checkpoints and Oncogenic Factors
KZR-261 Blocks Expression of Immune Checkpoints and Oncogenic Factors In vitro Protein Secretion Assays In vivo Tumor Xenografts Lowe E et al. ASCO 2020 51
Slide 52: KZR-261: Unique MOA
KZR-261: Unique MOA Involving Direct Effects on Tumor Cells and the Microenvironment KZR-261 52
Slide 53: Novel Bioinformatics Approach to Identify Sensitive Tumor Types
Kezar Utilized a Novel Bioinformatics Approach to Identify Potentially Sensitive Tumor Types for Clinical Development Lowe E et al. AACR 2021 450+ cell lines treated with a Sec61 inhibitor Gene Module Expression Analysis (FGSEA) Gene Expression Databases Tumor Cell lines (CCLE) Tumor Tissues (TCGA)
Slide 54: Bioinformatics Indicates Selective Sensitivity of Tumor Types
Results of Bioinformatics Research Indicates Selective Sensitivity of Tumor Cells and Tumor Types for Prioritization in Phase 1 Study Tumors are predicted to be more sensitive than normal tissues Prostate Adenocarcinoma Uveal Melanoma Cutaneous Melanoma Mesothelioma HNSCC Colon Adenocarcinoma Urothe
Slide 55: First-in-Human Dose Escalation and Expansion Study of KZR-261
First-in-Human Dose Escalation and Expansion Study of KZR-261 Initiated RP2D** Anti-tumor efficacy Biomarker validation Key Outcome Measures 55 Goals for KZR-261-101 Establish single agent activity Maximize opportunities for success for KZR-261 Identify/confirm potential, predictive biomarkers
Slide 56: Novel Platform for Drug Discovery Targets the Sec61 Translocon
Inhibition of a single secreted/membrane protein Non-cytotoxic agents Indications: Many… Inhibition of multiple secreted/membrane proteins Combination therapy in a single molecule Multiple oncology indications (tumor agnostic) Inhibition of relevant subset secreted/membrane proteins Non-cytotoxic ag
Slide 57: Multi-Target I/O Agents as Combination Therapy in a Single Molecule
Generation of Multi-Target I/O Agents as Potential Combination Therapy in a Single Small Molecule Cytotoxic anti-cancer agents 57 Whang J et al. SITC 2019
Slide 58: Selective Small Molecule PD-1 Inhibitors
Kezar has Discovered Selective Small Molecule PD-1 Inhibitors Multiple chemical series may be tuned toward selective target inhibition Further refinement affords selective PD1-inhibitor 58 Data on file.
Slide 59: Sec61 Inhibitors Can be Tuned to Precision Oncology Agents
Sec61 Inhibitors Can be Tuned to Precision Oncology Agents KZR-8445 Broad anti-cancer potential KZR-9445 Selective Inhibition of HER3 59 McMinn D. Drug Discovery Chemistry 2020
Slide 60: Unique Platform to Identify and Drug Secreted and Transmembrane Proteins
Kezar has a Unique Platform to Identify and Drug High-Value Secreted and Transmembrane Proteins Small Molecule Replacements of Therapeutic mAb (50+ Targets) Proprietary Oncology Target ID Analysis Program (50+ Targets) Chemical tractability Identification of Kezar advantage (i.e., benefit of Sec61-t
Slide 61: KZR-261 Represents First of Multiple Protein Secretion Opportunities
KZR-261 Represents Kezar’s First of Multiple Opportunities to Bring Protein Secretion Inhibitors Into Clinical Development KZR-261: First-in-Class Protein Secretion Inhibitor Platform Potential of the Sec61 Translocon Phase 1 study initiated in Q4'21 Multiple oncology indications Potential to repres
Slide 62: The Kezar Opportunity
The Kezar Opportunity: Harnessing Master Regulators of Cellular Function to Tackle Immune-mediated Diseases and Cancer A novel approach to harmonizing the immune system via immunomodulation; Potential to be a pipeline in a drug First in class agent with broad anti-tumor activity; Potential to inhibi