Kezar Life Sciences, Inc. · NASDAQ:KZR
Kezar Life Sciences — Investor Presentation (October 2019)
21 slides from Kezar Life Sciences's investor presentation, Oct 3, 2019
Slide 1: Revolutionizing the Treatment of Autoimmune Disorders and Malignancies
Revolutionizing the Treatment of Autoimmune Disorders and Malignancies Investor Presentation October 2019 Exhibit 99.1
Slide 2: Forward-Looking Statements Disclaimer
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
Slide 3: The Kezar Opportunity
The Kezar Opportunity: Pioneering immunoproteasome inhibition, a new approach in autoimmunity Phase 1b in SLE patients shows favorable safety profile over nonselective proteasome inhibitors Clinical activity seen across multiple disease parameters Consistent pharmacology seen across three clinical t
Slide 4: KZR-616 and Protein Secretion Program address a diverse pipeline of indications
Program Therapeutic Indication Development Stage Discovery Preclinical Phase 1 Phase 2 KZR-616 Lupus Nephritis (LN) Dermatomyositis (DM) Polymyositis (PM) Autoimmune Hemolytic Anemia (AIHA) Immune Thrombocytopenia (ITP) Protein Secretion Oncology Oncology & Autoimmunity KZR-616 and our Protein Secre
Slide 5: Novel programs targeting protein homeostasis
Kezar’s novel, complementary drug discovery and development programs target protein homeostasis Modulates multiple drivers of inflammation Restores normal immune responses in autoimmune disorders, while avoiding immunosuppression Active in broad array of autoimmune disease models Broad anti-tumor ac
Slide 6: The immunoproteasome is expressed only in the immune system
The immunoproteasome is a unique type of proteasome expressed only in the immune system and at sites of inflammation Groettrup, Kirk, and Basler Nat Rev Immunol 2010 *Active sites inducing protein degradation are highlighted Constitutive proteasome Immunoproteasome Ubiquitous Expression (e.g. heart
Slide 7: Selective immunoproteasome inhibition is not cytotoxic and immunomodulatory
Selective inhibition of the immunoproteasome is not cytotoxic and results in broad immunomodulatory activity Myeloma Cell Apoptosis VELCADE (bortezomib) KYPROLIS (carfilzomib) Dual inhibition required for cell death Death induced by protein buildup (UPR) B-cell T-cell Macrophage KZR-616 TNF-α IL-23
Slide 8: KZR-616 could address significant unmet needs in severe autoimmune diseases
KZR-616 has the potential to address significant unmet needs in severe autoimmune diseases Lupus Nephritis (LN) Prevalence: ~150K US patients Treatment: No approved treatments in US/EU Prolonged corticosteroid use results in significant complications Existing therapies are ineffective in many patien
Slide 9: Healthy volunteer results support development in autoimmune disorders
Results from 100 healthy volunteers receiving KZR-616 support development in autoimmune disorders Consistent and reproducible pharmacology Target inhibition achieved at doses ≥30mg Similar PK and PD with 2 distinct drug product formulations Biologic activity established; consistent with preclinical
Slide 10: KZR-616 in three Phase 2 clinical trials
KZR-616 is being evaluated in 5 separate autoimmune indications across 3 different Phase 2 clinical trials 2019 2020 2021 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Potential for further dosing DM PM Phase 2 MISSION Study Phase 2 PRESIDIO Study Phase 2 MARINA Study Phase 1b MISSION Study SLE AIHA ITP LN Potential I
Slide 11: Ph1b/2 MISSION Study design
Ph1b/2 MISSION Study: Modulator of the Immunoproteasome for Systemic Lupus with and without Nephritis Endpoints 1o: Safety 2o: Recommended Phase 2 doses, Plasma PK Exploratory: Efficacy, PD, Biomarkers, Pharmacogenomics Cohort 2 (n=5) completed Cohort 1 (n=8) completed 616 (60mg) 13 weeks Follow Up
Slide 12: Safety and Tolerability
Safety and Tolerability KZR-616 dosed at both 45 and 60 mg (with step-up dosing) well tolerated for 13 weeks of treatment Largely avoided toxicities seen with dual proteasome inhibitors Encouraging early data suggests low infection rate Initial data from the Ph 1b portion of the MISSION study suppor
Slide 13: Treatment Emergent Adverse Events in the MISSION Study
Treatment Emergent Adverse Events (TEAEs) in the MISSION Study are consistent with those seen in Healthy Volunteer Study (HVS) n (%, # of AEs) Cohort 1 45 mg N=8 Cohort 2 60 mg N=5 Cohort 2a 30→60 mg N=11 All KZR-616 N=24 TEAEs 8 (100, 44) 5 (100, 58) 7 (64, 47) 20 (83, 149) TEAEs ≥Grade 3 0 (0, 0)
Slide 14: Broad immunomodulatory activity in evaluable patients at 13 weeks
KZR-616 shows broad immunomodulatory activity in evaluable patients at 13 weeks (n=11) Efficacy Measures 82% of evaluable pts had a decrease ≥2 points; 45% had a decrease ≥4 points CLASI-A (mucocutaneous) TJC/SJC (joints) 55% of evaluable pts had ≥50% improvement on either TJC OR SJC SLEDAI 57% of e
Slide 15: Improvement across all efficacy measures at 13 weeks
Broad and consistent improvement shown across all measures of efficacy in evaluable patients at 13 weeks TJCSJCCLASI-ASLEDAI PhGAPtGAPtP BL: 13.8 Mean Change in Efficacy Measures Across Cohorts: BL-W13 BL: 10.9 BL: 58.3 BL: 63.9 BL: 63.9 TJC=tender joint count; SJC=Swollen Joint Count; CLASI-A=Cutan
Slide 16: Ph2 MISSION Study: enhanced trial design
Randomize 1:1:1:1 Ph2 MISSION Study: Enhanced clinical trial design is more robust and in line with other LN studies Amended Phase 2 Design Endpoints 1o: Safety 2o: Efficacy (Complete and partial renal response rates, SLEDAI-2K, corticosteroid use) Exploratory: PD, Biomarkers, Pharmacogenomics Study
Slide 17: Key protocol changes should improve recruitment and data
Key protocol changes should improve recruitment and garner a more robust and meaningful data read on ‘616 Trial Feature Original New Treatment duration 3 months 6 months + (separate 6-month open-label extension) Number of patients 48 64 Dose levels 30 and 45mg 30, 45, 60mg Background medication MMF
Slide 18: PRESIDIO Study in dermatomyositis and polymyositis
Ph 2 PRESIDIO Study: Placebo-controlled Study of the Efficacy and Safety of Treating Dermatomyositis and Polymyositis with the Selective Immunoproteasome Inhibitor KZR-616 KZR-616 45mg* SC once weekly Placebo SC once weekly Placebo SC once weekly KZR-616 45mg* SC once weekly Treatment Period 1 Treat
Slide 19: MARINA Study in AIHA and ITP
Ph 2 MARINA Study: Modulator of the Immunoproteasome for Autoimmune Hemolytic Anemia and Immune Thrombocytopenia Endpoints 1o: Efficacy: Hematologic Improvement 2o: Safety and tolerability; PK Exploratory: Biomarkers, PK/PD relationship Safety Follow Up KZR-616 30mg SC once weekly (N=10/cohort) KZR-
Slide 20: Multiple approaches to modulating protein secretion at the Sec61 Translocon
Kezar has multiple small molecule approaches to modulating protein secretion at the Sec61 Translocon Sec61 translocation channel Lumen Cytosol ER membrane Signal sequence binding site SR SRP Multiple Protein Secretion Inhibitors Specific Protein Secretion Inhibitors Compelling anti-cancer activity i
Slide 21: The Kezar Opportunity
The Kezar Opportunity: Pioneering immunoproteasome inhibition, a new approach in autoimmunity Phase 1b in SLE patients shows favorable safety profile over nonselective proteasome inhibitors Clinical activity seen across multiple disease parameters Consistent pharmacology seen across three clinical t
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