Alpine Immune Sciences Presents Initial Clinical Data on Povetacicept in Autoimmune Glomerulonephritis in a Late-Breaking Poster Session at the American Society of Nephrology Kidney Week 2023

Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for autoimmune and inflammatory diseases, announced that the Company today presented the first clinical data of povetacicept in autoimmune glomerulonephritis during a late-breaking poster session at the American Society of Nephrology (ASN) Kidney Week in Philadelphia, Pennsylvania. In addition, the Company plans to host an investor event today at 4:30 pm ET.

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Figure 1. Clinically Meaningful Improvements in Proteinuria, Suggesting Remission (Graphic: Business Wire)

Povetacicept is a potent dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines, which play key roles in pathogenesis of multiple autoimmune diseases via their roles in the activation, differentiation and/or survival of B cells, particularly antibody-secreting cells, as well as T cells and innate immune cells. RUBY-3 is a multiple ascending dose, multi-cohort, open label, phase 1b/2a study of povetacicept in autoimmune glomerulonephritis, where povetacicept is administered subcutaneously (SC) once every four weeks for up to 48 weeks.

Key Highlights from the Late-Breaking ASN Poster Include:

• As of October 25th, 20 participants with IgA nephropathy (IgAN) have been enrolled, 12 at the 80 mg dose level, of whom 5 have UPCR data available at 24 weeks.
• In IgAN, treatment with low-dose povetacicept, 80 mg SC every four weeks was associated with clinically meaningful improvements in proteinuria, with a 53.5% reduction from baseline in urine protein to creatinine ratio (UPCR; n=5) at 24 weeks. In addition, at 24 weeks, 4/5 (80%) had achieved remission, as defined as UPCR < 0.5 g/g and ≥50% reduction in UPCR from baseline with stable renal function (≤ 25% reduction in eGFR from baseline). (Fig. 1)
• In IgAN, treatment with low-dose povetacicept was also associated with a >60% reduction in the key disease-related biomarker galactose-deficient IgA1 (Gd-IgA1), as well as stable renal function as assessed by estimated glomerular filtration rate (eGFR) (+7.1% from baseline at 24 weeks; n=5).
• The first participant with primary membranous nephropathy (pMN), also treated with povetacicept 80 mg SC every four weeks, achieved an immunological remission, defined as a reduction in the highly disease-relevant biomarker anti-PLA2R1 to an undetectable level, from a baseline of 209 to < 2 RU/mL by 22 weeks.
• Povetacicept has been well tolerated, with no reported administration-associated reactions, no instances of IgG < 3 g/L, and no severe infections.
• A higher dose of povetacicept, 240 mg SC every four weeks, continues to enroll, with initial data expected in 1H 2024.

“In this initial experience, low-dose povetacicept at 80 mg has been well tolerated and demonstrates highly encouraging improvements in UPCR and disease biomarkers in IgA nephropathy, with early evidence suggesting remission," noted James Tumlin, M.D., Professor of Medicine at Emory University School of Medicine, Founder and Chief Executive Officer of NephroNet Clinical Trials Consortium. “These findings suggest a highly compelling development profile for povetacicept based upon a rapid reduction in the key pathogenic biomarker Gd-IgA1, marked and clinically meaningful reductions in UPCR, and a once-a-month dosing regimen. A higher dose of povetacicept 240 mg every four weeks is currently being explored and will be of great interest. Further clinical development of povetacicept in glomerulonephritis, particularly IgAN, is therefore strongly supported.”