SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company discovering and developing breakthrough treatments for immune-mediated and oncologic disorders, today highlighted the broad therapeutic potential of KZR-616, a first-in-class immunoproteasome inhibitor, in two poster sessions during the American College of Rheumatology Annual Meeting (ACR Convergence 2020). Both posters can be found on Kezar’s website under the “Science” section.
Richard Furie, M.D., Chief, Division of Rheumatology, Northwell Health in New York, is presenting updated results from the MISSION Phase 1b study (NCT03393013) evaluating KZR-616 in patients with systemic lupus erythematosus (SLE) with and without lupus nephritis (LN). The presentation by Dr. Furie includes additional patient-weeks of safety and tolerability data compared to prior data presentations. Encouraging trends in early efficacy signals continue, including improvement of SLE-specific disease activity scores. No new safety signals have been observed, and KZR-616 administered subcutaneously (SC) once weekly has been consistently well tolerated for 13 weeks. KZR-616 has been studied at doses of 45 mg, 60 mg and 75 mg SC weekly. Previously, Kezar has identified 45 mg and 60 mg as likely therapeutic doses to advance in its clinical development program.
Kezar’s collaborator, Marta Del Rio Oliva, Ph.D. candidate of the University of Konstanz, is presenting an evaluation of KZR-616 in a well-accepted preclinical mouse model of inflammatory myositis. In this model of myositis, KZR-616 treatment was associated with significant improvement in muscle function and reduced levels of muscle tissue damage. It is also demonstrated that an active immunoproteasome is necessary for the disease to occur. These data suggest that selective inhibition of the immunoproteasome with KZR-616 could have a meaningful clinical impact in patients with inflammatory myopathies, such as dermatomyositis (DM) and polymyositis (PM). Kezar is actively enrolling the PRESIDIO Phase 2 study (NCT04033926), a placebo-controlled, cross-over study of patients with DM and PM. The open-label extension study for PRESIDIO is also enrolling.
“These two presentations strengthen our understanding of how KZR-616 can be an effective treatment for patients with a variety of autoimmune diseases. The preclinical data show the importance of the immunoproteasome in the pathology of myositis and the ability of KZR-616 to selectively inhibit this important regulator of immune function for therapeutic benefit. The clinical data continues to show that KZR-616 is well- tolerated and improves multiple signs and symptoms of SLE. We continue to build a strong foundation for KZR-616 as a novel and important therapeutic for patients living with LN, dermatomyositis and polymyositis and other immune-mediated diseases,” said Noreen Henig, M.D., Kezar’s Chief Medical Officer.
MISSION (NCT03393013) is a Phase 1b/2 clinical trial evaluating KZR-616 in SLE patients with and without nephritis. The study consists of two parts. The Phase 1b portion is an open-label dose escalation study which is evaluating doses up to 75 mg of KZR-616 across 6 cohorts, which has completed enrollment. The primary objective of the Ph1b portion of MISSION is to assess safety and tolerability. Secondary objectives include evaluating pharmacokinetics (PK) and pharmacodynamics (PD) and selecting dose levels for the Phase 2 trials. Several exploratory efficacy measures are also being assessed: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), Cutaneous Lupus Erythematosus Severity Index-Activity (CLASI-A), Tender and Swollen Joint Counts (TJC/SJC), Physician Global Assessment (PhGA), Patient Global Assessment (PtGA) and Patient Assessment of Pain (PtP). The Phase 2 portion of the MISSION study evaluating KZR-616 in patients with LN is currently enrolling.
PRESIDIO (NCT04033926) is a Phase 2 randomized, double-blind, placebo-controlled, crossover, multicenter study to evaluate the safety, tolerability, efficacy, PK and PD of treatment with KZR-616 in patients with active polymyositis or dermatomyositis. During the 32-week treatment period, patients will receive either KZR-616 or placebo subcutaneously once weekly for 16 weeks followed by a crossover to the other treatment arm for an additional 16 weeks. The study is expected to enroll 24 patients. An open-label extension study of PRESIDIO is now also enrolling.
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 1a and 1b trials provide evidence that KZR-616 exhibits a favorable safety and tolerability profile for development in severe, chronic autoimmune diseases. Phase 2 trials are underway in severe autoimmune diseases.
About Kezar Life Sciences
Based in South San Francisco, Kezar Life Sciences is combining courage, conviction and cutting-edge science to develop 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 and inhibit multiple drivers of disease via a single target. KZR-616, a first-in-class selective immunoproteasome inhibitor, is being evaluated in severe and underserved autoimmune diseases. Additionally, KZR-261, the first clinical candidate for the treatment of cancer from the company’s protein secretion program targeting the Sec61 translocon, is undergoing IND-enabling activities. For more information, visit www.kezarlifesciences.com, and follow us on Twitter at @KezarBio, Facebook and LinkedIn.
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