8-K

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): June 27, 2022

Kezar Life Sciences, Inc.

(Exact name of Registrant as Specified in Its Charter)

Delaware	001-38542	47-3366145
(State or Other Jurisdiction of Incorporation)	(Commission File Number)	(IRS Employer Identification No.)
4000 Shoreline Court, Suite 300
South San Francisco, California		94080
(Address of Principal Executive Offices)		(Zip Code)

Registrant’s Telephone Number, Including Area Code: 650 822-5600

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, $0.001 par value	KZR	The NASDAQ Stock Market LLC

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒

Item 7.01 Regulation FD Disclosure.

On June 27, 2022, Kezar Life Sciences, Inc. (the “Company”) is hosting a conference call and webcast, where it will present topline results from the MISSION Phase 2 clinical trial of zetomipzomib (KZR-616). A copy of the slide presentation to be presented during this event is attached to this Current Report on Form 8-K as Exhibit 99.1 and is incorporated herein by reference. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.1.

The information provided in Item 7.01 of this Form 8-K, including Exhibit 99.1 hereto, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any of the Company’s filings under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.

Item 8.01 Other Events.

On June 27, 2022, the Company issued a press release reporting topline results from the MISSION Phase 2 clinical trial of zetomipzomib. A copy of the press release is filed as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits.

Exhibit No.	Description
99.1	Presentation, dated June 27, 2022
99.2	Press Release, dated June 27, 2022
104	Cover Page Interactive Data File (embedded within the Inline XBRL document)

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.

			KEZAR LIFE SCIENCES, INC.
Date:	June 27, 2022	By:	/s/ Marc L. Belsky
			Marc L. Belsky Chief Financial Officer and Secretary

EX-99.1

INVESTOR & ANALYST EVENT JUNE 27, 2022 Exhibit 99.1

Forward-Looking Statements and Topline Data 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,” “believe”, “plan” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Kezar’s expectations and assumptions as of the date of this presentation. Each of these forward-looking statements involves risks and uncertainties that could cause Kezar’s clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Forward-looking statements contained in this presentation include, but are not limited to, statements about the design, progress, timing, scope and results of clinical trials, the preliminary nature of topline data, the anticipated regulatory development and future clinical trials involving Kezar’s product candidates, the likelihood that data will support future development and therapeutic potential, the association of data with treatment outcomes and the likelihood of obtaining regulatory approval of Kezar’s product candidates. Many factors may cause differences between current expectations and actual results, including the performance of audit and verification procedures on topline data, unexpected safety or efficacy data observed during clinical studies, changes in expected or existing competition, the uncertainties and timing of the regulatory approval process, and unexpected litigation or other disputes. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this presentation are discussed in Kezar’s filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” contained therein. Except as required by law, Kezar assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

Agenda 4:30 PM – 4:35 PM Welcome, Introductions and Opening Remarks | John Fowler, MBA 4:35 PM – 5:05 PM MISSION Phase 2 Clinical Update | Noreen R. Henig, MD 5:05 PM – 5:10 PM Zetomipzomib Clinical Development Next Steps | Noreen R. Henig, MD 5:10 PM – 5:15 PM Summary and Closing Remarks | John Fowler, MBA 5:15 PM – 5:30 PM Question and Answer (sell side only) KEZAR SPEAKERS John Fowler, MBA Chief Executive Officer Noreen R. Henig, MD Chief Medical Officer

Builds on 10+ years of R&D work in proteasome biology and protein secretion led by Kezar’s scientific co-founders, Chris Kirk & Jack Taunton Deep Expertise in Immunology and Oncology A novel approach to harmonizing the immune system via immunomodulation. Potential to be a pipeline in a drug Zetomipzomib (KZR-616): First-in-Class Immunoproteasome Inhibitor $253M cash, cash equivalents and marketable securities; 60.4M common shares outstanding Strong Financial Position (as of 4/30/2022) First-in-class inhibitor of Sec61 translocon. Impacts tumor proliferation, metastasis and immune invasion. Currently being evaluated in a Phase 1 study in solid tumors KZR-261: First Clinical Candidate from Protein Secretion Platform The Kezar Opportunity: First-in-Class, Small Molecule Therapies That Tackle Immune-Mediated Diseases and Cancer

Zetomipzomib, a First-in-Class Inhibitor of the Immunoproteasome, Acts Across the Innate and Acquired Immune System Immunoproteasome Inhibition with Zetomipzomib* Zetomipzomib Advantage Decreases pro-inflammatory cytokine production, plasma cell activity and autoantibody production, while increasing regulatory T cells activity Inflammatory disorders are currently treated by targeting a single immune signal but zetomipzomib affects a broad spectrum of immune regulators TNF-α IL-6 IL-23 IFN-α auto-Ab Plasma cells Th1 Th17 Treg Rituxan/Gazyva Benlysta IVIg/FcRn Inhibitor Humira, et al Actemra Skyrizi/Stelara Saphnelo Orencia Lupkynis Xeljanz Cosentyx/Taltz Zetomipzomib Macrophage T Cell B Cell *Some preclinical studies were conducted with ONX 0914, a first-generation selective immunoproteasome inhibitor.

MISSION: Topline Data MISSION Phase 2 Study Evaluating Zetomipzomib 60 mg SC QW for 24 Weeks in Lupus Nephritis Abbreviations: SC, subcutaneously; QW, weekly.

MISSION Phase 1b (Complete): Zetomipzomib Demonstrated Safety, Tolerability and Preliminary Efficacy in Patients with SLE with and without LN  Treatment with zetomipzomib demonstrated improvements in multiple exploratory measures of disease activity across organ systems including SLEDAI-2K 2 of 2 subjects with active LN showed >50% reduction in UPCR and decreases in uCD163, a marker for inflammatory activity in LN Anti-dsDNA antibody titers improved over time in 8 of 8 patients with elevated levels at baseline Sustained or deepened improvement (tail-effect) in disease activity measures and key biomarkers in the post-treatment follow-up period observed The most common treatment-emergent adverse event was injection site erythema Favorable safety profile, with hematologic analysis showing no suppression of leukocytes through the duration of the study MISSIONPhase 1b inSLE ± LN Furie R et al. EULAR 2021. Data on file.Abbreviations: SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index-2000; LN, lupus nephritis; UPCR, urine protein to creatinine ratio; uCD163, urinary CD163.

MISSION Phase 2 Topline: HighlightsZetomipzomib Achieves Clinically Meaningful Overall Renal Response (ORR) in Refractory or Hard-to-Treat LN Patients without Standard Induction Therapy 11/17 (64.7%) patients demonstrated an ORR of ≥50% UPCR reduction following 24 weeks of treatment (primary endpoint) 6/17 (35.2%) patients achieved a CRR with UPCR ≤0.5 Treatment benefit was maintained or deepened following end-of-treatment period (measured at W29) Prednisone (or prednisone-equivalent) mean daily dose was decreased by 53% from baseline to end-of-treatment and continued to decrease following the end-of-treatment period Use of other standard immunosuppressive therapy was stable Mean eGFR remained stable  Improvements observed in key SLE disease activity and disease biomarkers Favorable safety and tolerability profile observed, with no reports of opportunistic infections or immune cell depletion, supporting chronic administration MISSIONPhase 2 in LN Patients received 24 weeks of zetomipzomib; End-of-treatment assessments performed at Week 25. Abbreviations: LN, lupus nephritis; CRR, complete renal response; UPCR, urine protein to creatinine ratio, eGFR, estimated glomerular filtration rate; SLE, systemic lupus erythematosus. Topline data is subject to audit and verification procedures that could result in material changes in the final data.

MISSION Phase 2: Study DesignOpen-Label Clinical Study to Evaluate the Efficacy and Safety of Zetomipzomib in Patients with Active Proliferative Lupus Nephritis Adult patients with LN^ (N=21) ^LN patients (Class III or IV +/- Class V) with significant proteinuria (UPCR ≥1.0 measured in 24-hour urine collection) despite standard therapy *1st dose 30 mg Zetomipzomib 60 mg* SC QW Added to stable background therapy[No standard induction therapy] 24 weeks of treatment EOT (W25) EOS (W37) 12-week SFU 0 2 4 6 8 10 12 14 16 18 20 22 24 Patients in MISSION Phase 2 did not receive standard induction therapy or protocol-mandated steroid taper Lack of induction therapy is a significant difference compared to recently published trials in LN https://clinicaltrials.gov/ct2/show/NCT03393013. *Patients received 24 weeks of zetomipzomib; End-of-treatment assessments performed at Week 25.Abbreviations: UPCR, urine protein to creatinine ratio; LN, lupus nephritis, SC, subcutaneous; SFU, safety follow-up; QW, every week; W, week; EOT, end of treatment; EOS, end of study.

MISSION Phase 2: Study Design Endpoints Number of patients with ≥50% reduction in UPCR compared to baseline after 24 weeks of treatment with zetomipzomib Primary Endpoint: Overall Renal Response (ORR) Safety and tolerability of zetomipzomib The number of patients with a complete renal response (CRR) and partial renal response (PRR) after 24 weeks of treatment as defined by: Global SLE disease monitoring and key biomarkers Key Secondary Endpoints CRR: UPCR ≤0.5 eGFR ≥60 mL/min/1.73m2 or no worsening of eGFR from baseline of ≥25% Prednisone (or equivalent) ≤10 mg No use of prohibited medication PRR: 50% reduction in UPCR and/or UPCR <1 (if baseline UPCR <3) and/or UPCR <3 (if baseline UPCR >3) eGFR ≥60 mL/min/1.73m2 or no worsening of eGFR from baseline of ≥25% No use of prohibited medication Abbreviations: eGFR, estimated glomerular filtration rate; UPCR, urine protein to creatinine ratio; SLE, systemic lupus erythematosus.

MISSION Phase 2 Topline: Safety PopulationKey Demographics and Baseline Characteristics Safety Population (N=21) Age, mean (years), range 35.3 (19 - 69) Female, n (%) 19 (90.5) Race, n (%) White Black or African AmericanAsianAmerican Indian/Alaska Native Other Unknown 7 (33.3) 1 (4.8) 1 (4.8) 4 (19.0) 7 (33.3) 1 (4.8) Ethnicity, n (%) Hispanic or Latino 11 (52.4) Country, n (%) AustraliaColombia Peru Russia Ukraine USA 3 (14.3) 4 (19.0) 6 (28.6) 4 (19.0) 1 (4.8) 3 (14.3) Safety Population (N=21) SLE duration (years), median (min, max), N=20 8.7 (0.7, 26.4) LN duration (years), median (min, max) 3.1 (-0.06*, 16.1) LN class type, n          Class III only          Class IV only          Class III + V          Class IV + V 6 11 3 1 24-hour UPCR (mg/mg)          Mean (SD)          Median (Min, Max) 2.6 (2.6) 1.9 (0.93, 13.4) eGFR (mL/min/1.73 m2)          Mean (SD)          Median (Min, Max) 104.7 (32.8) 115.0 (36.5, 150) Disease Activity Parameter, mean (SD)          SLEDAI-2K 11.0 (4.7) Corticosteroid (prednisone or equivalent) dose (mg), mean (min, max) 18.9 (5, 50) Concomitant medications, n          MMF/MPA          Prednisone (or equivalent)          Hydroxychloroquine          Azathioprine 20 21 14   2 *LN biopsy confirming diagnosis was performed during screen period. Abbreviation: SLE, systemic lupus erythematosus; LN, lupus nephritis; UPCR, urine protein to creatinine ratio; eGFR, estimated glomerular filtration rate; SLEDAI, Systemic Lupus Erythematosus Disease Activity index-2000; MMF, mycophenolate mofetil; MPA, mycophenolic acid. Topline data is subject to audit and verification procedures that could result in material changes in the final data.

Received 18 doses Received 12 doses Received 2 doses Received 3 doses MISSION Phase 2 Topline: Patient Disposition* End of Treatment End of Study * Each bar represents one patient in the study. Topline data is subject to audit and verification procedures that could result in material changes in the final data.

MISSION Phase 2 Topline: Evaluable PopulationZetomipzomib Without Standard Induction Therapy Achieves ORR in 65% and CRR in 35% of Patients at Week 25 Evaluable population (n=17) are patients that did not withdraw before Week 25; Patients received 24 weeks of zetomipzomib; End-of-treatment assessments performed at Week 25. Abbreviation: ORR, overall renal response; CRR, complete renal response; UPCR, urine protein to creatinine ratio. Topline data is subject to audit and verification procedures that could result in material changes in the final data. 5 Weeks Post-Treatment 6 CRR 15 UPCR <1 5 Weeks Post-Treatment Increase / no reduction UPCR reduction0% to <25% UPCR reduction25% to <50% UPCR reduction>50% (ORR) CRR 6 CRR 6 CRR 4 CRR End of Treatment

MISSION Phase 2 Topline: Evaluable PopulationCRRs Are Maintained and Additional ORRs are Observed at Week 29, Post-Treatment with Zetomipzomib Evaluable population (n=17) are patients that did not withdraw before Week 25; Patients received 24 weeks of zetomipzomib; End-of-treatment assessments performed at Week 25. Abbreviation: ORR, overall renal response; CRR, complete renal response; UPCR, urine protein to creatinine ratio. Topline data is subject to audit and verification procedures that could result in material changes in the final data. Increase / no reduction UPCR reduction0% to <25% UPCR reduction25% to <50% UPCR reduction>50% (ORR) CRR 5 Weeks Post-Treatment 15 UPCR <1 4 Weeks Post-End of Treatment 6 CRR 6 CRR 4 CRR End of Treatment 6 CRR

CONFIDENTIAL – DO NOT DISTRIBUTE MISSION Phase 2 Topline: Evaluable Population Mean UPCR Decreases with 24 Weeks of Zetomipzomib Treatment Evaluable population (n=17) are patients that did not withdraw before Week 25; Patients received 24 weeks of zetomipzomib; End-of-treatment assessments performed at Week 25.*Outliers are not shown on the plot but are incorporated in the mean/median values. Abbreviation: UPCR, urine protein to creatinine ratio. Topline data is subject to audit and verification procedures that could result in material changes in the final data.

MISSION Phase 2 Topline:With Zetomipzomib, Reductions in Proteinuria Achieved with 53% Less Corticosteroids Mean Daily Steroid Dose End of Treatment No protocol-mandated steroid taper Other background immunosuppressive doses remained stable 19.2 9.1 8.6 9.9 4 Weeks Post- End of Treatment End of Treatment Evaluable population (n=17) are patients that did not withdraw before Week 25; Patients received 24 weeks of zetomipzomib; End-of-treatment assessments performed at Week 25. Topline data is subject to audit and verification procedures that could result in material changes in the final data.

MISSION Phase 2 Topline: Evaluable PopulationMean eGFR Remains Stable  End of Treatment 103.9 94.2 101.5 Evaluable population (n=17) are patients that did not withdraw before Week 25; Patients received 24 weeks of zetomipzomib; End-of-treatment assessments performed at Week 25.Stable eGFR defined as ≥60 mL/min/1.73m2 or no worsening of eGFR from baseline of ≥25%Abbreviations: eGFR, estimated glomerular filtration rate.Topline data is subject to audit and verification procedures that could result in material changes in the final data.

MISSION Phase 2 Topline: Evaluable PopulationReduction in Signs and Symptoms of SLE with Zetomipzomib Treatment Tool Baseline Mean (SD) EOT (Week 25) Mean (SD) SLEDAI-2K 11.1 (4.7) 6.5 (3.1) Physician Global Assessment Score 57.2 (21.7) 23.9 (19.2) Patient Global Assessment Score 23.6 (21.1) 10.7 (12.2) HAQ-pain 20.8 (18.2) 12.1 (18.1) CLASI-A 3.7 (7.3) 1.9 (4.1) Tender Joint Count 1.3 (2.6) 0.1 (0.5) Swollen Joint Count 0.1 (0.5) 0.1 (0.2) Evaluable population (n=17) are patients that did not withdraw before Week 25. Abbreviations: CLASI-A, Cutaneous Lupus Erythematosus Severity Index-Activity; EOT, end of treatment; HAQ, Health Assessment Questionnaire; SD, standard deviation; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000.Topline data is subject to audit and verification procedures that could result in material changes in the final data.

MISSION Phase 2 Topline: Evaluable PopulationImprovement in Key Serologic Biomarkers Observed at Week 25 (EOT) in Patients with Abnormal Levels at Baseline Biomarker Patients with Abnormal Levels at Baseline Patients with Improvement at W25 (EOT) Patients with Normalizationat Week 25 (EOT) Anti-dsDNA 12 10 5 C3 5 4 2 C4 4 2 2 Cell counts remained stable in patients on study Evaluable population (n=17) are patients that did not withdraw before Week 25. Reference ranges: dsDNA <20 IU/mL; C3 90 - 180 mg/dL; C4 10 - 40 mg/dL. Abbreviations: EOT, end of treatment. Topline data is subject to audit and verification procedures that could result in material changes in the final data.

MISSION Phase 2 Topline Data: Safety Population (N=21)Zetomipzomib Continues to Show Favorable Safety and Tolerability Profile Acute protracted migraine (related) Worsening pulmonary arterial hypertension, AKI and UTI (unrelated) Injection site infiltration (related) Asthenia (related) Reticulocytes increase (related) Worsening pulmonary arterial hypertension (unrelated) Safety population (N=21) are patients that received at least one dose of study drug. Abbreviations: TEAE, treatment-emergent adverse event; UTI, urinary tract infection; AKI, acute kidney injury. Topline data is subject to audit and verification procedures that could result in material changes in the final data. No opportunistic or Grade 3 infections reported Treatment-Emergent Adverse Events TEAEs were generally mild to moderate (≤Grade 2) consistent with previous reports Most Common TEAEs occurring in >25% of patients: Injection site reaction, pyrexia (fever), headache, or nausea with or without vomiting Serious Adverse Events: ​2 Patients ​ Early Terminations:​4 Patients

MISSION Phase 2 Topline: HighlightsZetomipzomib Achieves Clinically Meaningful Overall Renal Response (ORR) in Refractory or Hard-to-Treat LN Patients without Standard Induction Therapy 11/17 (64.7%) patients demonstrated an ORR of ≥50% UPCR reduction following 24 weeks of treatment (primary endpoint) 6/17 (35.2%) patients achieved a CRR with UPCR ≤0.5 Treatment benefit was maintained or deepened following end-of-treatment period (measured at W29) Prednisone (or prednisone-equivalent) mean daily dose was decreased by 53% from baseline to end-of-treatment and continued to decrease following the end-of-treatment period Use of other standard immunosuppressive therapy was stable Mean eGFR remained stable  Improvements observed in key SLE disease activity and disease biomarkers Favorable safety and tolerability profile observed, with no reports of opportunistic infections or immune cell depletion, supporting chronic administration MISSIONPhase 2 in LN Patients received 24 weeks of zetomipzomib; End-of-treatment assessments performed at Week 25. Abbreviations: LN, lupus nephritis; CRR, complete renal response; UPCR, urine protein to creatinine ratio, eGFR, estimated glomerular filtration rate; SLE, systemic lupus erythematosus. Topline data is subject to audit and verification procedures that could result in material changes in the final data.

ZETOMIPZOMIB: Clinical Development Next Steps

Zetomipzomib, A First-in-Class Inhibitor of the Immunoproteasome:Key Attributes Modulates innate and acquired immune responses without signs of immunosuppression to date Once weekly subcutaneous administration leads to intermittent inhibition of the immunoproteasome with no accumulation observed with repeat dosing Consistent exposure and clearance (T1/2 <5 hours) Not predicted to result in clinically significant drug-drug interactions No teratogenicity observed at any dose tested in animal models No monitoring required No immediate rebound of signs and symptoms of disease activity upon discontinuation of zetomipzomib in Mission Ph1b safety follow-up period Zetomipzomib Furie R et al, EULAR 2021 and Data on File.

Zetomipzomib for the Treatment of Lupus Nephritis:Next Steps 1 2 3 4 Zetomipzomib is Well Positioned for Use as a Chronic Therapy for the Treatment of LN Potential to be used without induction therapy  Potential to be steroid-sparing Potential treatment for renal and extra-renal manifestations of SLE Late Phase LN Trial  Following the November 2021 interim data release, Kezar initiated preparations for registrational studies in LN Design will be informed by completion of the MISSION Phase 2 trial (EOS, July 2022) and discussions with regulatory authorities Patient-Based Education Initiatives  In recognition of the significant unmet need in reaching patients with LN, Kezar will commence patient-based education initiatives  Additional Indication Exploration Given the extra-renal findings in the MISSION Phase 1b and Phase 2 studies, we are considering opportunities in SLE Further guidance will be available later this year Abbreviations: EOS, end of study; LN, lupus nephritis; SLE, systemic lupus erythematosus.

Summary and Closing Remarks

Q&A SPEAKERS John Fowler, MBA Chief Executive Officer Noreen R. Henig, MD Chief Medical Officer Christopher J. Kirk, PhD Chief Scientific Officer

THANK YOU

EX-99.2

Exhibit 99.2

Kezar Life Sciences Announces Positive Topline Results from the MISSION Phase 2 Trial Evaluating Zetomipzomib for the Treatment of Patients with Lupus Nephritis

•11 of 17 patients (64.7%) achieved an overall renal response of 50% or greater reduction in urine protein to creatinine ratio (UPCR) at 6 months

•6 of 17 patients (35.2%) achieved a complete renal response, including a UPCR of 0.5 or less at 6 months

•Zetomipzomib continues to demonstrate a favorable safety and tolerability profile for administration over the 6-month treatment period

•Improvement seen in exploratory measures of extra-renal disease activity associated with systemic lupus erythematosus (SLE) in patients who completed treatment

•Company-hosted conference call and webcast to be held today at 4:30 p.m. ET

SOUTH SAN FRANCISCO, Calif. – June 27, 2022-- Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company discovering and developing breakthrough treatments for immune-mediated and oncologic disorders, today reported positive topline results from the MISSION Phase 2 clinical trial evaluating zetomipzomib, a novel, first-in-class selective immunoproteasome inhibitor, in patients with active lupus nephritis (LN).

“The MISSION Phase 2 topline results show a clinically meaningful overall renal response to zetomipzomib after 6 months, without high-dose induction therapy. Patients in the trial also experienced reductions in extra-renal manifestations of lupus. Zetomipzomib appears to be immunomodulatory, well-tolerated and steroid-sparing – all important attributes for patients with autoimmune disease who are often young and active,” said Noreen R. Henig, M.D., Kezar’s Chief Medical Officer. “Based on the strength of these results, we plan to continue developing zetomipzomib for patients with lupus nephritis, as well as evaluate development opportunities for systemic lupus erythematosus.”

The MISSION Phase 2 clinical trial is an open-label study designed to demonstrate the responder rate of zetomipzomib in patients with active LN. During the 24-week treatment period, patients received 60 mg of zetomipzomib subcutaneously once weekly (first dose of 30 mg) in addition to stable background therapy. End-of-treatment (EOT) assessments occurred at Week 25, with completion of study at Week 37. Patients in the MISSION Phase 2 clinical trial received zetomipzomib without induction therapy, which represents a significant difference from other recently published trials in LN.

The primary efficacy endpoint for the trial was the proportion of patients achieving an overall renal response (ORR), measured as a 50% or greater reduction in urine protein to creatinine ratio (UPCR) at EOT. A key secondary efficacy endpoint was the number of patients with a complete renal response (CRR), measured as an absolute reduction in proteinuria values to a UPCR of 0.5 or less, with preserved renal function (eGFR), and corticosteroid use of 10 mg or less prednisone/prednisone equivalent and no use of prohibited medication.

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Summary of Topline Results

In this Phase 2 topline analysis, 17 of 21 patients enrolled in the trial reached end of treatment:

•11 of 17 patients (64.7%) achieved an ORR measured as a 50% or greater reduction in UPCR at EOT compared to baseline, the primary efficacy endpoint of the clinical trial.

•6 of 17 patients (35.2%) achieved a CRR of 0.5 UPCR or less, with all other protocol definitions satisfied.

•Treatment benefit of zetomipzomib was maintained or deepened following the end of treatment, based on assessments at Week 29.

o16 of 17 patients (94.1%) reached an ORR at Week 29, and 6 patients maintained a CRR.

•Mean daily prednisone background dosage was reduced from 19.2 mg at baseline to 9.1 mg at EOT and was further reduced at Week 29.

•Mean eGFR (estimated glomerular filtration rate) remained stable from baseline to EOT.

Additionally, exploratory measures of extra-renal disease activity associated with SLE improved in patients completing the trial. Patients showed mean reduction in key SLE disease activity scores and normalization in biomarkers consistent with reduction in SLE disease activity.

Safety

Zetomipzomib was well tolerated over the course of the treatment period. Adverse events were generally mild-to-moderate (Grade 1 or 2) consistent with previous reports. Most common treatment-emergent adverse events (TEAEs) were injection site reaction, pyrexia (fever), headache, or nausea with or without vomiting. As previously reported, two patients experienced serious adverse events (SAEs) on the study. One patient had an acute protracted migraine related to zetomipzomib but completed treatment. The other patient discontinued following worsening pulmonary arterial hypertension, a urinary tract infection and an acute kidney injury, which were all deemed unrelated to zetomipzomib. Early terminations occurred in 4 out of 21 patients. No opportunistic or Grade 3 infections were reported in the trial.

Conference Call and Webcast

Kezar Life Sciences will host a webcast and conference call today, June 27, 2022, at 4:30 p.m. ET to discuss topline data from the MISSION Phase 2 clinical trial. To access the audio webcast with slides, please visit the “Events & Presentations” page in the Investors & Media section of the Company’s website at https://ir.kezarlifesciences.com/news-events/events-presentations. The call can also be accessed by dialing +1 (800) 309-0220 (domestic) or+1 (805) 309-0220 (international) with conference ID 6423042#.

The live audio webcast with slides can also be accessed here: https://www.veracast.com/webcasts/kezar/webcasts/Kezar-Life-Sciences-June-27th.cfm

For those unable to participate in the conference call or webcast, a replay will be available for 90 days on the Company’s website.

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About Zetomipzomib (KZR-616)

Zetomipzomib (KZR-616) is a novel, first-in-class, selective immunoproteasome inhibitor with broad therapeutic potential across multiple autoimmune diseases. Preclinical research demonstrates that selective immunoproteasome inhibition results in a broad anti-inflammatory response in animal models of several autoimmune diseases, while avoiding immunosuppression. Data generated from Phase 1 clinical trials provide evidence that zetomipzomib exhibits a favorable safety and tolerability profile for development in severe, chronic autoimmune diseases.

About Lupus Nephritis

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE). LN is a disease comprising a spectrum of vascular, glomerular and tubulointerstitial lesions and develops in approximately 50% of SLE patients within 10 years of their initial diagnosis. LN is associated with considerable morbidity, including an increased risk of end-stage renal disease requiring dialysis or renal transplantation and an increased risk of death. There are limited approved therapies for the treatment of LN. Management typically consists of induction therapy to achieve remission and long-term maintenance therapy to prevent relapse.

About Kezar Life Sciences

Kezar Life Sciences is a clinical-stage biopharmaceutical company discovering and developing breakthrough treatments for immune-mediated and oncologic disorders. The company is pioneering first-in-class, small-molecule therapies that harness master regulators of cellular function to inhibit multiple drivers of disease via single, powerful targets. Zetomipzomib, its lead development asset, is a selective immunoproteasome inhibitor being evaluated in a Phase 2 clinical trial in lupus nephritis. This product candidate also has the potential to address multiple chronic immune-mediated diseases. KZR-261 is the first anti-cancer clinical candidate from the company’s platform targeting the Sec61 translocon and the protein secretion pathway. An open-label dose-escalation Phase 1 clinical trial of KZR-261 to assess safety, tolerability and preliminary tumor activity in solid tumors is underway. For more information, visit www.kezarlifesciences.com.

Cautionary Note on Forward-looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “should,” “expect,” “believe”, “plan” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Kezar’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause Kezar’s clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the design, progress, timing, scope and results of clinical trials, the preliminary nature of topline data, the anticipated regulatory development and future clinical trials involving Kezar’s product candidates, the likelihood that data will support future development and therapeutic potential, the association of data with treatment outcomes and the likelihood of obtaining regulatory approval of Kezar’s product candidates. Many factors may cause differences between current expectations and actual results, including the performance of audit and verification procedures on topline data, unexpected safety or efficacy data observed during clinical studies, changes in expected or existing competition, the uncertainties and timing of the regulatory approval process and unexpected litigation or

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other disputes. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Kezar’s filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” contained therein. Except as required by law, Kezar assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

Contacts:

Gitanjali Jain
Vice President, Investor Relations and External Affairs
650-269-7523
gjain@kezarbio.com

Liza Sullivan
Argot Partners
212-600-1902
kezar@argotpartners.com

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XML

Document And Entity Information	Jun. 27, 2022
Cover [Abstract]
Document Type	8-K
Amendment Flag	false
Document Period End Date	Jun. 27, 2022
Entity Registrant Name	Kezar Life Sciences, Inc.
Entity Central Index Key	0001645666
Entity Emerging Growth Company	true
Entity File Number	001-38542
Entity Incorporation, State or Country Code	DE
Entity Tax Identification Number	47-3366145
Entity Address, Address Line One	4000 Shoreline Court, Suite 300
Entity Address, City or Town	South San Francisco
Entity Address, State or Province	CA
Entity Address, Postal Zip Code	94080
City Area Code	650
Local Phone Number	822-5600
Written Communications	false
Soliciting Material	false
Pre-commencement Tender Offer	false
Pre-commencement Issuer Tender Offer	false
Entity Ex Transition Period	true
Title of 12(b) Security	Common Stock, $0.001 par value
Trading Symbol	KZR
Security Exchange Name	NASDAQ