Patients receiving nine-dose regimen over five months experienced deep and durable reduction in proteinuria, reaching up to ~50% mean reduction in UPCR at end of study at month 24 and over 18 months after last dose

Patients across treatment arms exhibited stabilization in eGFR through 24 months, while patients in placebo arm showed a rapid decline in eGFR

Prolonged IgA reductions observed out to 24 months while IgG and IgM recovered to baseline shortly after last dose, potentially enabling a sustained treatment benefit without the need for chronic immunosuppression

SOUTH SAN FRANCISCO, May 24, 2024 /PRNewswire/ -- Human Immunology Biosciences (HI-Bio™), a clinical-stage biotechnology company developing targeted therapies for patients with severe immune-mediated diseases (IMDs), today announced positive interim results from the randomized, placebo-controlled Phase 2 IGNAZ study of the investigational CD38 antibody felzartamab in the treatment of IgA nephropathy (IgAN).

Patients receiving a nine-dose regimen over five months experienced a deep and durable decrease in proteinuria levels, reaching up to ~50% mean reduction in UPCR at month 24, which was more than 18 months after the last dose. In addition, patients exhibited stabilization of kidney function as measured by eGFR through 24 months. Administration of felzartamab was generally well tolerated with a safety profile consistent with prior studies.

"Demonstrating a treatment effect that persists for more than 18 months after last dose of felzartamab represents a potential departure from plasma- or B-cell-modulating agents that require chronic dosing," commented Study Investigator and lead author Jürgen Floege, M.D., RWTH Aachen University, Germany. "The reduction in proteinuria and stabilization of eGFR we are seeing represent clinically meaningful outcomes for patients with IgA nephropathy. The results also suggest the potential for felzartamab in helping to preserve kidney function while avoiding the need for chronic immunosuppression. In addition, we are seeing selective and durable reductions in IgA antibody levels with the recovery of IgG and IgM, which represents a potential safety profile advantage for patients, as felzartamab may allow maintenance of important immune functions that protect against infection. The results of this study highlight felzartamab's promise as a durable therapy and support its continued investigation in IgA nephropathy."

"The results of the IGNAZ study are the first data investigating the application of felzartamab in the treatment of IgA nephropathy and the effects we have seen are highly encouraging," said Uptal Patel, M.D., Chief Medical Officer at HI-Bio. "Because felzartamab can selectively deplete CD38+ plasma cells, upstream contributors to disease progression and producers of Gd-IgA1 and anti-Gd-IgA1 antibodies, we believe treatment with felzartamab may represent a potentially disease-modifying approach that could help preserve kidney function. We look forward to receiving final data from the IGNAZ study later this year, which we expect to submit for presentation in an appropriate peer-reviewed forum, and are evaluating next steps in development for felzartamab in this indication."

Patients in the nine-dose group experienced a prolonged pharmacodynamic effect of IgA reduction while IgG and IgM levels showed recovery, with selective and durable reductions in IgA levels maintained for more than 18 months following the last dose. Felzartamab was generally well tolerated with no dose-dependent adverse events and no exposure-safety relationship. Most adverse events (AEs) were mild, and the most common type of AE was infusion-related reactions (IRRs). There were two (5%) serious adverse events in felzartamab-treated subjects (IRR, tendon rupture) and infections were mostly mild and balanced across the active treatment groups. Of the total number of patients treated with felzartamab, five patients discontinued treatment due to IRRs or hypersensitivity; for four of five patients, the infusion rate was higher than protocol-specified or had an error in pre-medication.

The Phase 2 IGNAZ study (NCT05065970) is a randomized, placebo-controlled, multi-center, proof-of-concept and dose evaluation study designed to assess safety and efficacy in adult patients with high-risk IgAN. Patients were enrolled with proteinuria (UPCR) of at least 1.0 g/d and eGFR of at least 30 ml/min/1.73 m² and were assigned to one of four groups receiving either placebo, two doses, five doses or nine doses over a 24-week treatment phase of 16 mg/kg of felzartamab provided by intravenous infusion. The study also included an open-label treatment arm in Japan provided with the nine-dose schedule. The study enrolled 54 patients in total and data were analyzed on a per-protocol basis.

Data from the IGNAZ study were presented today at the 61^st European Renal Association (ERA) Congress in Stockholm. The full presentation from the ERA Congress will be made available on HI-Bio's website.

About IgA Nephropathy
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is a leading cause of chronic kidney disease with up to 40% of IgAN patients progressing to end stage kidney disease about 20 years after diagnosis. IgAN accounts for about 40% of all native-kidney biopsies in Japan, 25% in Europe, 12% in the United States, but less than 5% in central Africa.¹

About Felzartamab 
Felzartamab is an investigational therapeutic human monoclonal antibody directed against CD38, a protein expressed on mature plasma cells. Felzartamab has been shown in clinical studies to selectively deplete CD38+ plasma cells, which may allow applications that ultimately improve clinical outcomes in a broad range of diseases driven by pathogenic antibodies. Felzartamab was originally developed by MorphoSys AG for multiple myeloma. HI-Bio exclusively licensed the rights to develop and commercialize felzartamab across all indications in all countries and territories excluding China (including Macau and Hong Kong and Taiwan), where TJ Biopharma retains the rights. 

Felzartamab is an investigational therapeutic candidate that has not yet been approved by any regulatory authority.

About HI-Bio
Human Immunology Biosciences, Inc. (HI-Bio™), was incubated by ARCH Venture Partners and Monograph Capital to develop precision therapies for immune-mediated diseases and to bring clinical immunology into its next chapter. Inspired by the rise of targeted therapies in clinical oncology, the company pursues a therapeutic strategy of targeting and depleting the immune cell types that drive IMDs. The company's most advanced candidate, felzartamab, is a CD38-targeted antibody shown in clinical studies to deplete CD38+ cells, including plasma and natural killer (NK) cells, which are implicated in a range of indications including antibody-mediated rejection (AMR), IgA nephropathy (IgAN), lupus nephritis (LN) and primary membranous nephropathy (PMN). Other investors include Alpha Wave Global, Arkin Bio Capital, Jeito Capital and Viking Global Investors.

To learn more about HI-Bio, visit www.hibio.com or follow the company on LinkedIn and X.

References:

1. Rajasekaran et al. (2021) IgA nephropathy: An interesting autoimmune kidney disease. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577278/. Hastings et al. (2018) Clinical Research, Life Expectancy for Patients From the Southeastern United States With IgA Nephropathy. Available at https://www.kireports.org/article/S2468-0249(17)30362-5/fulltext

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