On November 10, 2022 Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company discovering and developing breakthrough treatments for immune-mediated and oncologic disorders, reported financial results for the third quarter ended September 30, 2022 and provided a business update (Press release, Kezar Life Sciences, NOV 10, 2022, View Source [SID1234623713]).
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"In the third quarter, the team at Kezar continued its tradition of strong execution across our clinical and portfolio development plans," said John Fowler, Kezar’s Co-founder and Chief Executive Officer. "Supported by the results from the MISSION study, our conviction remains high that zetomipzomib has the potential to be a non-immunosuppressive, steroid-sparing treatment for patients with lupus and lupus nephritis. In addition, our recently announced development plan in autoimmune hepatitis underscores our belief that zetomipzomib can help patients across a diverse range of autoimmune diseases. In parallel, we are excited by progress in our protein secretion inhibition platform and look forward to our SITC (Free SITC Whitepaper) poster presentation tomorrow on KZR-540, an oral small molecule that selectively blocks PD-1 expression."
Zetomipzomib: Selective Immunoproteasome Inhibitor
MISSION – Phase 2 clinical trial of zetomipzomib in patients with active lupus nephritis (LN) (NCT03393013)
Kezar presented positive complete results for the 37-week Phase 2 MISSION clinical trial at the American Society of Nephrology’s (ASN) Kidney Week 2022 Annual Meeting.
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 assessments occurred at Week 25 (EOT), with a safety follow up period and completion of the study at Week 37 (EOS). Patients in the MISSION Phase 2 clinical trial received zetomipzomib without induction therapy, which represents a difference from other recently published clinical 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 end-of-treatment. 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.
In the MISSION Phase 2 clinical trial, 17 of 21 enrolled patients reached end-of-treatment at Week 25 and end-of-study at Week 37:
ORRs were achieved in 11 of 17 patients (64.7%) at EOT. This benefit occurred with a 53% mean reduction of background corticosteroid use.
During the safety follow up period, clinical responses deepened, and ORRs increased to 16 patients (94.1%) at Week 29 and 15 patients (88.2%) at EOS. Of these responders, 12 patients (70.6%) also reached a UPCR of 0.7 or less at EOS.
CRRs were achieved in 6 of 17 patients (35.3%) at EOT, including a UPCR of 0.5 or less, stable eGFR, daily prednisone/prednisone equivalent dose of 10 mg or less, and no use of prohibited medication.
During the safety follow up period, an additional patient achieved a CRR, with the total CRRs increasing to 7 patients (41.2%) at both Week 29 and EOS.
Key measurements of SLE disease activity were reduced and key biomarkers of SLE improved. There was no evidence of early rebound of inflammation following discontinuation of zetomipzomib.
Kezar will also present the complete MISSION data set at the upcoming American College of Rheumatology (ACR) Convergence 2022, which is taking place November 10 – 14, 2022 in Philadelphia, PA. The ACR poster presentation details are available here.
PORTOLA – Phase 2 clinical trial of zetomipzomib in patients with autoimmune hepatitis (AIH) who have not benefited from standard-of-care treatment (NCT05569759)
In October 2022, Kezar received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration for zetomipzomib for the treatment of AIH. AIH is a rare, chronic disease in which the immune system attacks the liver and causes inflammation and tissue damage, severely impacting patients’ physical health and quality of life.
The PORTOLA trial (KZR-616-208) is a randomized, double-blind, placebo-controlled Phase 2a clinical trial evaluating the safety and efficacy of zetomipzomib in patients with AIH that are insufficiently responding to standard of care or have relapsed. The target enrollment will be 24 patients, who will be randomly assigned (2:1) to receive either zetomipzomib or placebo in addition to background corticosteroid therapy for 24 weeks and includes a protocol-mandated steroid taper by Week 14. The primary efficacy endpoint will measure the proportion of patients who achieve a complete response measured as normalization of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels with a successful corticosteroid taper by Week 24.
Protein Secretion Inhibition
KZR-261-101 – Phase 1 clinical trial of KZR-261 in patients with locally advanced or metastatic solid malignancies (NCT05047536)
KZR-261 is a novel, broad-spectrum agent that acts through direct interaction and inhibition of the Sec61 translocon. In preclinical studies, KZR-261 has been shown to induce a direct anti-tumor effect as well as modulate the tumor microenvironment, including enhancing anti-tumor immune responses.
The Phase 1 clinical trial of KZR-261 is being conducted in two parts: dose escalation, and dose expansion in subjects with selected tumor types. The trial is designed to evaluate safety and tolerability, pharmacokinetics and pharmacodynamics, as well as to explore the preliminary anti-tumor activity of KZR-261 in patients with locally advanced or metastatic disease.
KZR-540 – Kezar will introduce promising preclinical data on KZR-540, an oral small molecule inhibitor that selectively blocks PD-1 expression via inhibition of the Sec61 translocon, on November 11, 2022 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting in Boston, MA. KZR-540 illustrates that the Sec61 translocon can be selectively inhibited for specific anti-tumor effects and validates Sec61 inhibition as a platform for additional new chemical entities.
Details for the SITC (Free SITC Whitepaper) poster presentation are as follows:
Title: KZR-540 is a novel oral small molecule inhibitor of Sec61 cotranslational translocation that potently and selectively blocks PD-1 expression (#422)
Category: Checkpoint Blockade Therapy
Date/Time: November 11, 2022 from 9 AM – 8:30 PM ET
Presenter: Cristina Delgado-Martin, Senior Scientist, Biology
Financial Results
Cash, cash equivalents and marketable securities totaled $290.4 million as of September 30, 2022, compared to $208.4 million as of December 31, 2021. The increase was primarily attributable to net proceeds from the issuance of common stock under the "at-the-market" Sales Agreement with Cowen and Company, LLC, net of cash used in operations to advance clinical-stage programs and preclinical research and development.
Research and development expenses for the third quarter of 2022 increased by $3.4 million to $13.9 million compared to $10.5 million in the third quarter of 2021. This increase was primarily due to an increase in personnel-related expenses including non-cash stock-based compensation because of headcount growth, and higher research and clinical development expenses, to advance the zetomipzomib clinical programs and the KZR-261 Phase 1 clinical trial.
General and administrative expenses for the third quarter of 2022 increased by $1.0 million to $5.0 million compared to $4.0 million in the third quarter of 2021. The increase was primarily due to an increase in personnel-related expenses including non-cash stock-based compensation.
Net loss for the third quarter of 2022 was $17.8 million, or $0.25 per basic and diluted common share, compared to a net loss of $14.5 million, or $0.28 per basic and diluted common share, for the third quarter of 2021.
Total shares of common stock outstanding were 68.4 million shares as of September 30, 2022. Additionally, there were outstanding pre-funded warrants to purchase 3.8 million shares of common stock at an exercise price of $0.001 per share, 0.4 million outstanding restricted stock units and options to purchase 9.6 million shares of common stock at a weighted-average exercise price of $8.12 per share as of September 30, 2022.