In a recent interview with PharmaShots, Noreen Henig, Chief Medical Officer at Kezar Life Sciences shared information on clinical and pre-clinical data supporting the potential of KZR-616 to positively affect multiple drivers of immune-mediated diseases.

Shots:

• The poster presented at ACR 2020 includes additional patient-weeks of safety and tolerability data compared to prior data presentations for our MISSION P-lb study in SLE patients with/out nephritis
• No new safety signals have been observed and KZR-616 (SC, qw) has been consistently well tolerated for 13wks. Additionally, the company has started the enrollment in its P-ll PRESIDIO study for DM and PM
• KZR-616 has the potential to reduce inflammation by targeting dysfunctional immune cells involved in autoimmunity without causing widespread immunosuppression in patients

Tuba: Can we have an overview of the posters presented at the American College of Rheumatology Annual Meeting (ACR) Convergence 2020?

Noreen: We presented both pre-clinical and clinical data with KZR-616, our first-in-class selective immunoproteasome inhibitor, during ACR. The presentation by Dr. Furie includes additional patient-weeks of safety and tolerability data compared to prior data presentations for our MISSION Phase 1b study in systemic lupus erythematosus (SLE) patients with and without nephritis. Encouraging trends in early efficacy signals continue, including improvement of SLE-specific disease activity scores and improvements in renal function and serum biomarkers in 2 of 2 patients with LN enrolled to the Phase 1b portion of the study. 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. We previously identified 45 mg and 60 mg as likely therapeutic doses to advance in our clinical development program.

In a well-accepted preclinical mouse 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 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). We are 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 (NCT04628936) for PRESIDIO is also enrolling. 

Source: Kezar

Tuba: How KZR-616 work to harmonize the immune system?

Noreen: Playing a critical role in the body's immune system, the immunoproteasome is abundantly expressed in immune cells and acts as a master regulator of cellular function by degrading intracellular proteins. Selective inhibition of the immunoproteasome with KZR-616 has the potential to reduce inflammation by targeting dysfunctional immune cells involved in autoimmunity, such as T -cells and B -cells , without causing widespread immunosuppression in patients.

Source: Kezar

In doing so, KZR-616 has the potential to affect multiple drivers of immune-mediated diseases and harmonize the body's immune system by restoring the immune response almost like hitting the reset button on one's immune system.

Tuba: Are you planning to explore the potential of KZR-616 beyond autoimmune disorders?

Noreen: Currently, we are focused on the autoimmune disorders of lupus nephritis, dermatomyositis, and polymyositis; however, we believe that there is strong scientific rationale to pursue KZR-616 for the treatment of a wide array of immune-mediated diseases and may do so in the future.

Tuba: When can we expect the results of the P-II portion of the MISSION study evaluating KZR-616 in patients with LN?

Noreen: We expect interim data towards the end of 2021 for the MISSION Phase 2.

Tuba: What are Kezar's other programs in a pipeline to help patients overcome their disease and live a better life?

Noreen: We are pioneering research and discovery efforts targeting protein secretion pathways as potential therapies for oncology and immuno-oncology indications. We intend to submit an Investigational New Drug (IND) application for our first clinical candidate from this platform next year where we plan to target a number of difficult to treat solid tumors.

Tuba: When can we expect the results of P-II PRESIDIO & an OLE study?

Noreen: We expect top-line data from the PRESIDIO study in the first half of 2022 and the results from the open-label study would be available approximately 1 year later.

Tuba: What would be the targeted geographies for seeking approval of KZR-616?

Noreen: Autoimmune diseases have different prevalences across the globe, and our goal is to make this treatment available to as many people as possible and would intend to have a global registration plan but anticipate initially pursuing an FDA approval in the U.S.

Tuba: Are you looking for any collaborations for the launch of KZR-616?

Noreen: While this program does lend itself to potential collaboration based on its broad applicability in a wide array of immune-mediated diseases, we currently have the resources to develop KZR-616 on our own. 

Tuba: Is Kezar planning to develop a digital solution for immune-mediated diseases?

Noreen: We do not currently have plans to develop a digital solution for immune-mediated diseases.

About Noreen Henig:

Noreen R. Henig is the Chief Medical Officer at Kezar Life Sciences and the board member of Avidity Biosciences. Dr. Henig received a doctorate and a graduate degree from Albert Einstein College of Medicine and an undergraduate degree from Yale University.

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