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):

October 3, 2019

 

 

KEZAR LIFE SCIENCES, INC.

(Exact name of registrant as specified in its charter)

 

 

 

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 (see General Instruction A.2. below):

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

 

 

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.  ☒

 

 

 

 

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Item 7.01. Regulation FD Disclosure

On October 3, 2019, John Fowler, the Chief Executive Officer of Kezar Life Sciences, Inc. (the “Company”), presented a corporate and strategic update at the 2019 Cantor Global Healthcare Conference in New York, NY. A copy of the slide presentation is attached to this Current Report on Form 8-K as Exhibit 99.1. 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 9.01. Financial Statements and Exhibits.

(d) Exhibits.

 

 

 

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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 hereunto duly authorized.

 

 

Dated:  October 3, 2019

 

Revolutionizing the Treatment of Autoimmune Disorders and Malignancies Investor Presentation October 2019 Exhibit 99.1

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 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, 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.

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 trials Strong Clinical and Safety Data w/KZR-616 Phase 2 trial in LN recruiting; initial Phase 1b data presented at EULAR 2019; additional data in Q4 2019 Trials in DM and PM, AIHA and ITP open for enrollment Value Drivers in Multiple Indications Potential to be a first-in-class selective immunoproteasome inhibitor Uniquely broad immunomodulatory approach, with target expressed across all immune cell types Potential to bring clinical benefit without immunosuppression Builds on strong clinical data with non-selective proteasome inhibitors KZR-616: A Novel, Differentiated Approach KZR-616 is a pipeline in a drug, targeting a wide range of unmet needs in both rare and large market autoimmune indications Protein secretion platform offers significant potential to generate novel drugs; 1st oncology clinical candidate nomination by YE 2019 Rich Platforms & Growing Pipeline Strong Cash Position Cash, cash equivalents, and marketable securities: $93.4M (as of 6/30/19)

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 Secretion Program will address a diverse pipeline of indications Phase 1b in SLE patients Clinical Candidate in Q4 MISSION – Phase 2 MARINA – Phase 2 PRESIDIO – Phase 2

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 activity in preclinical models Applications in oncology, immuno-oncology, and autoimmunity Protein Degradation: The Immunoproteasome Protein Secretion: The Sec61 Translocon The target of selective immunoproteasome inhibitor KZR-616 Sec61 translocation channel Lumen Cytosol ER membrane Signal sequence binding site

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 and liver) Expressed in Immune System (e.g. T-cells) Primary targets of approved drugs VELCADE and KYPROLIS Primary targets of KZR-616

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 Th1 Th17 auto- Ab Dual-Targeting Proteasome Inhibitors Selective Immunoproteasome Inhibitors Treg Parlati et al. Blood 2009

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 patients Targeted therapies (e.g. biologics) may not address needs of all patients with diseases characterized by defects in multiple arms of the immune system Dermatomyositis (DM)/ Polymyositis (PM) Prevalence: ~70K US patients Treatment: No approved treatments in US/EU Autoimmune Hemolytic Anemia (AIHA)/Immune Thrombocytopenia (ITP) Prevalence: ~140K US patients Treatment: No approved treatments for AIHA in US/EU; limited available treatments for ITP Almani S et al. CJASN 2017 Oddis C et al. Nat Rev Rheumatol 2018 Barcellini W et al. Expert Rev Clin Immunol 2018 Lambert MP et al. Blood 2017 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386579/figure/Fig4

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 models Distinct Safety Profile vs. Dual Inhibitors No prolonged hematologic AEs or laboratory abnormalities Normal renal function Single case of transient CV changes at 1st dose No peripheral neuropathy Encouraging Safety and Tolerability Profile Tolerable doses up to 75mg Most (>75%) AEs related to transient injection site reactions 1st dose effect (transient nausea/vomiting) managed with step-up dosing

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 Interim Analysis 1H 2021 Potential Interim Analysis Q4 2020 Final Data Mid-2021 Final Data 2H 2021 Final Data 2H 2021

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 12 weeks Study NCT03393013 Cohort 2a (n=14) ONGOING 616 (30à45à60mg) 13 weeks Follow Up 12 weeks 13 weeks Follow Up 12 weeks Cohort 2b ENROLLING BILAG=British Isles Lupus Assessment Group Index; DLT=dose-limiting toxicity; PD=pharmacodynamics; Pred=prednisone; SLEDAI-2K=SLE Disease Activity Index 2000; SOC=standard of care Phase 1b Dose Escalation SLE 616 (30à60mg)* 616 (45mg) 13 weeks Follow Up 12 weeks Poster presentation at ACR 2019 on 11/12/2019 Abstract #2520 *lyophilized drug product

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 supports advancement into Ph 2 trials across multiple indications Efficacy Consistent and broad improvement seen across all measures of disease activity at week 13 PK and PD Consistent, dose proportional PK Target levels of immunoproteasome inhibition were reached with all dose levels

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) 1 (20, 1) 1 (9, 1) 2 (8, 2) TEAEs leading to drug discontinuation 0 (0, 0) 1 (20, 1) 2 (18, 2) 3 (13, 3) Serious TEAEs 0 (0, 0) 1 (20, 1)* 1 (9, 1)^ 2 (8, 2) Serious infectious TEAE 0 (0, 0) 0 (0, 0) 1 (9, 1)^ 1 (4, 1) Non-serious infectious TEAE 1 (13, 1) 0 (0, 0) 2 (18, 2) 3 (13, 3) Any injection site reaction (ISR) TEAE 6 (75, 35) 4 (80, 19) 4 (36, 24) 14 (58) Any non-ISR TEAE in ≥2 pts Nausea 2 (25, 2) 4 (80, 6) 3 (27, 4) 9 (38, 12) Vomiting 1 (13, 1) 5 (100, 7) 2 (18, 3) 8 (33, 11) Headache 1 (13, 1) 2 (40, 13) 1 (9, 1) 4 (17) Dizziness 1 (13, 1) 2 (40, 2) 0 (0, 0) 3 (13) Pyrexia 0 (0, 0) 2 (40, 2) 1 (9, 4) 3 (13) Chills 0 (0,0) 1 (20, 1) 1 (9, 2) 2 (8) *1 case of thrombotic microangiopathy ^1 case of herpes zoster 1st dose effect

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 evaluable pts with CLASI-A ≥4 at BL (n=7) had decrease ≥4 points 55%, 91%, and 91% of evaluable pts had ≥10-point reduction, respectively PhGA/PtGA/PtP Biomarker 50% of evaluable pts with low complement levels at BL (n=6) had resolution KZR-616 Safety population (received ≥1 dose of KZR-616) (N=24) Pts receiving ≥1 month of dosing with KZR-616 (n=16) Pts completing 13 weeks of treatment (n=11)

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=Cutaneous Lupus Erythematosus Severity Index-Activity ; SLEDAI=Systemic Lupus Erythematosus Disease Activity Index 2000; PhGA/PtGA/PtP=Physician Global Assessment/Patient Global Assessment/Patient assessment of pain (see Appendix for definitions of each)

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 NCT03393013 PD=pharmacodynamics; Pred=prednisone; CYC= cyclophosphamide; MMF=Cellcept/mycophenolate mofetil; SLEDAI-2K=SLE Disease Activity Index 2000 Participants will have the option to enroll in a separate 24-week Open Label Extension KZR-616 60mg*+ MMF/Pred or CYC/Pred KZR-616 45mg *+ MMF/Pred or CYC/Pred KZR-616 30mg + MMF/Pred or CYC/Pred Placebo + MMF/Pred or CYC/Prednisone Adults w/LN (N=64) 6-month Primary Endpoint, with potential for interim analysis *1st dose is 30mg (pending approval of protocol amendment)

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 + steroids only MMF + steroids or CYC + steroids Inclusion/Exclusion criteria Enrollment 1-3 months into induction Enrollment 0-3 months into induction 6-month biopsy window 12-month biopsy window Site Expansion 16 (predominantly US) 60+ (global) Data analysis Primary endpoint @3 mo Primary endpoint @6 mo w/potential interim analysis

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 Treatment Period 2 Week 16 Endpoint Week 32 Endpoint Week 40 End of study Randomize 1:1 Endpoints 1o: Efficacy: Total Improvement Score (TIS) 2o: Safety and tolerability; Patient Reported Outcomes (PROs), PK Exploratory: Biomarkers, PK/PD relationship Safety Follow Up Adult patients with DM or PM (N=24) *1st 2 doses are 30mg *1st 2 doses are 30mg Study NCT04033926

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-616 45mg* SC once weekly (N=10/cohort) Adult patients with active AIHA (Cohort 1) or ITP (Cohort 2) (N=40) Week 13 Efficacy Endpoint, with potential for interim analysis Randomize 1:1 Week 25 End of Study *1st 2 doses are 30mg Study NCT04039477

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 in pre-clinical models Potential for multiple clinical candidates Tunable selectivity Target selective approach High value / validated targets Applications in oncology and autoimmunity Clinical candidate nomination expected in Q4 2019

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 trials Strong Clinical and Safety Data w/KZR-616 Phase 2 trial in LN recruiting; initial Phase 1b data presented at EULAR 2019; additional data in Q4 2019 Trials in DM and PM, AIHA and ITP open for enrollment Value Drivers in Multiple Indications Potential to be a first-in-class selective immunoproteasome inhibitor Uniquely broad immunomodulatory approach, with target expressed across all immune cell types Potential to bring clinical benefit without immunosuppression Builds on strong clinical data with non-selective proteasome inhibitors KZR-616: A Novel, Differentiated Approach KZR-616 is a pipeline in a drug, targeting a wide range of unmet needs in both rare and large market autoimmune indications Protein secretion platform offers significant potential to generate novel drugs; 1st oncology clinical candidate nomination by YE 2019 Rich Platforms & Growing Pipeline Strong Cash Position Cash, cash equivalents, and marketable securities: $93.4M (as of 6/30/19)