On May 12, 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 first quarter ended March 31, 2022 and provided a business update (Press release, Kezar Life Sciences, MAY 12, 2022, View Source [SID1234614349]).
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"I want to thank my colleagues at Kezar for their excellent execution across both of our novel programs so far this year," said John Fowler, Kezar’s Co-founder and CEO. "We are excited to present the topline results from our Phase 2 MISSION trial in lupus nephritis this June and remain committed to exploring zetomipzomib’s potential in inflammatory diseases with high unmet need. Our strengthened balance sheet is key in supporting both of our programs, including our Phase 1 trial of KZR-261 in solid tumors."
Zetomipzomib: Selective Immunoproteasome Inhibitor
MISSION – Phase 2 clinical trial of zetomipzomib (KZR-616) in patients with lupus nephritis (LN) (NCT03393013)
In November 2021, Kezar reported interim data from the MISSION Phase 2 open-label trial in patients with active, proliferative LN. The interim data showed that, of the five patients who completed the full 24 weeks of weekly treatment with zetomipzomib 60mg doses, two achieved partial renal responses (PRRs) and two achieved complete renal responses (CRRs). The primary efficacy endpoint for the trial is the number of patients achieving a renal response measured by a 50% or greater reduction in UPCR at the end of treatment compared to baseline.
Kezar reiterates prior guidance and expects to report Phase 2 topline data in June 2022
An abstract featuring zetomipzomib has been selected for poster presentation as part of the EULAR Science Exhibit session at the upcoming Annual European Congress of Rheumatology (EULAR), taking place June 1-4, 2022, in Copenhagen, Denmark. The virtual presentation will be available beginning Wednesday, June 1, 2022, at 2:00 am Eastern Time through July 31, 2022.
POS0715: Treatment of SLE Patients with Zetomipzomib (KZR-616), a Selective Inhibitor of the Immunoproteasome, Results in Circulating Gene Expression, Protein Level, and Immune Cell Phenotypic Changes with Potential Correlations to Clinical Response, presented by Andrea Fan, PhD, Vice President, Head of Biology and Translational Research, Kezar Life Sciences
PRESIDIO – Phase 2 clinical trial of zetomipzomib (KZR-616) in patients with active dermatomyositis (DM) or polymyositis (PM) (NCT04033926)
On May 3, 2022, Kezar reported topline data from the PRESIDIO Phase 2 clinical trial of zetomipzomib in patients with DM (n=13) and PM (n=12). 20 of the 25 patients enrolled in the study completed end-of-treatment (Week 32). Topline results from PRESIDIO showed that most DM and PM patients saw clinically meaningful improvements in total improvement score (TIS), but zetomipzomib demonstrated no significant differentiation from placebo. The overall safety and tolerability of zetomipzomib was favorable and consistent with previous results.
KZR-616-003E (NCT04628936) is an open-label extension (OLE) study available to patients who completed 32 weeks in the PRESIDIO trial. Following completion of PRESIDIO, 18 out of 20 patients enrolled in the OLE. For the first time, patients have the option to self-administer zetomipzomib in the OLE. As of the release date, active participation in the OLE ranged from 2 to 77 weeks, and six patients had discontinued for reasons unrelated to zetomipzomib. No additional safety or tolerability issues have been observed, and mean TIS scores have improved over scores observed at the 32-week conclusion of PRESIDIO.
KZR-261: Protein Secretion Inhibitor
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.
At the American Association of Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting, held in April 2022 in New Orleans, LA, Kezar presented data on its proprietary small molecule inhibitors of the Sec61 translocon, specifically KZR-834, a working analog of KZR-261.
Financial Results
Cash, cash equivalents and marketable securities totaled $242.6 million as of March 31, 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 by the company in operations to advance its clinical stage programs and preclinical research and development.
Research and development expenses for the first quarter of 2022 increased by $1.7 million to $11.0 million compared to $9.3 million in the first quarter of 2021. This increase was primarily related to advancing the KZR-616 clinical program and the KZR-261 Phase 1 clinical trial.
General and administrative expenses for the first quarter of 2022 increased by $1.1 million to $4.9 million compared to $3.8 million in the first quarter of 2021. The increase was primarily due to an increase in personnel expenses, including non-cash stock-based compensation.
Net loss for the first quarter of 2022 was $16.0 million, or $0.26 per basic and diluted common share, compared to a net loss of $13.0 million, or $0.25 per basic and diluted common share, for the first quarter of 2021.
Total shares of common stock outstanding were 59.6 million shares as of March 31, 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 and outstanding options to purchase 8.9 million shares of common stock at a weighted average exercise price of $7.94 per share as of March 31, 2022.
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 KZR-261 and the Inhibition of Protein Secretion
KZR-261 is a first-in-class small molecule compound, derived from Kezar’s research and discovery platform of protein secretion pathway inhibitors. This broad-spectrum anti-tumor agent directly targets the Sec61 translocon and inhibits multiple cancer drivers both within tumor cells and the tumor microenvironment. A Phase 1 clinical trial is underway for the treatment of solid tumor malignancies.
Kezar’s drug discovery platform of protein secretion pathway inhibitors is a novel approach with broad application. The protein secretion pathway is a highly conserved and ubiquitously functioning pathway in all cells in the body and involves a conserved protein complex called the Sec61 translocon, the target of Kezar’s compounds. In preclinical models, Kezar’s library of protein secretion inhibitors have demonstrated broad activity with far-reaching potential in oncology, immune-oncology, and autoimmunity.