HI-Bio Announces Positive Results from Phase 2 Study of Felzartamab for Antibody-Mediated Late Rejection in Kidney Transplant Recipients

82% (n = 9/11) of patients on felzartamab experienced resolution of antibody-mediated rejection by Banff criteria on biopsy at 24 weeks compared to 20% (n = 2/10) who received placebo, and patients treated with felzartamab showed a reduction in disease-related biomarkers and stabilization of eGFR

63% (n=7/11) of patients treated with felzartamab had a microvascular inflammation (MVI) score of 0 and 100% (n=11/11) of patients treated with felzartamab had an improvement in MVI score.

Results published in the New England Journal of Medicine and presented at the 61^st Congress of the European Renal Association (ERA)

Results support advancement of felzartamab into late-stage development as a novel therapeutic approach for antibody-mediated rejection

SOUTH SAN FRANCISCO, CA., May 25, 2024 /PRNewswire/ — Human Immunology Biosciences (HI-Bio™), a clinical-stage biotechnology company developing targeted therapies for patients with serious immune-mediated diseases (IMD), today announced positive results from an investigator-sponsored phase 2 clinical trial. felzartamab for late antibody-mediated rejection (AMR) in kidney transplant recipients.

Felzartamab is an investigational monoclonal antibody designed to specifically target and eliminate CD38+ cells, which may include plasmablasts, plasma cells, and natural killer (NK) cells, which are thought to drive AMR and other IMDs. This double-blind, placebo-controlled, Phase 2 study was designed to evaluate the safety and tolerability of felzartamab in adults with late-onset AMR occurring at least 180 days after kidney transplantation. Patients were randomized 1:1 to receive nine infusions of felzartamab (16 mg/kg) or placebo over 20 weeks, followed by a 32-week observation period. Biopsies were performed at baseline, 24 weeks, and 52 weeks. The study recruited 22 patients.

Felzartamab had acceptable safety and side effect profiles in patients with late-onset AMR. Most adverse events were mild or moderate in severity. Mild to moderate infusion reactions, usually during the first infusion, occurred in patients in the felzartamab group (n=8). There were no treatment-related discontinuations.

Key secondary endpoints demonstrated the potential of felzartamab as an effective first treatment for late-onset AMR, resolving the disease according to the Banff classification. The classification is the international standard for characterizing kidney transplant-related diseases, including late rejection.

In the treatment group, 82% (n=9/11) of patients experienced resolution of AMR at week 24, compared to 20% (n=2/10) who received placebo. One patient on placebo experienced graft loss at week 14, likely due to chronic and persistent active AMR. The median microvascular inflammation (MVI) score was lower in the felzartamab group than in the placebo group (0 vs. 2.5) at week 24, with 64% (n = 7/11) of felzartamab-treated subjects reaching a MVI score of 0. Of those who experienced resolution at 24 weeks, 67% (n=6/9) maintained resolution at 52 weeks, with no medications administered during the observation period. Additionally, a profound reduction in donor-derived cell-free DNA (dd-cfDNA), a marker of allograft injury, was observed.

Stabilization of eGFR, an indicator of kidney function, and reduction of NK cells, key downstream mediators of inflammation and tissue damage, were demonstrated compared to placebo.

“There is a large unmet need for a treatment that resolves Banff disease and preserves kidney function in patients with antibody-mediated rejection,” said the lead researcher. Georg Bohmig, MD, Associate Professor of Medicine at the Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna. “The data presented in this study are very compelling and represent the potential for significant progress in this high-burden disease.”

According to the United Network for Organ Sharing (UNOS), approximately 93,000 patients are on the waiting list for kidney transplants in the United States. United States, with one in 20 patients dying each year while waiting for a transplant. AMR occurs despite the use of standard immunosuppressive treatments and is a leading cause of post-transplant renal failure, affecting approximately 23,000 transplant recipients worldwide. United States and often leads to graft loss. There are currently no approved treatments for late-onset AMR.

“We believe these data demonstrate the potential of felzartamab to help preserve the transformative and often life-saving benefit of kidney transplantation by addressing a leading cause of rejection,” said Uptal Patel, MD, chief medical officer at HI-Bio. “Based on the observed activity and concordance of results on key biomarkers of graft damage and function, we remain confident in our anti-CD38 depletion strategy with felzartamab. We intend to advance felzartamab into late-stage studies in antibody-mediated rejection and other immune-mediated diseases, for which patients have serious unmet needs.

The data was published simultaneously in the New England Journal of Medicine and presented as a late-breaking presentation by the lead author. Catherine MayerMD, from the Division of Nephrology and Dialysis at the Medical University of Viennaat 61^st Congress of the European Renal Association (ERA) in Stockholm.

The full ERA conference presentation will be available on the HI-Bio website.

About Antibody-Mediated Rejection (AMR) in Kidney Transplant Recipients
Antibody-mediated rejection (AMR) is a leading cause of kidney transplant failure, with chronic AMR affecting approximately 12% of patients receiving kidney transplants each year in the United States.¹ AMR has become the leading cause of late graft loss in kidney transplant recipients. Effective treatment options for chronic AMR are currently limited.²

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 could enable applications that ultimately improve clinical outcomes in a wide range of diseases caused by pathogenic antibodies. Felzartamab was initially developed by MorphoSys AG for multiple myeloma. HI-Bio has obtained exclusive rights to develop and commercialize felzartamab in all indications in all countries and territories, excluding China (including Macau And Hong Kong And Taiwan), of which 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 is pursuing a therapeutic strategy of targeting and depleting the immune cell types that cause IMD. The company’s most advanced candidate, felzartamab, is a CD38-targeting antibody shown in clinical studies to deplete CD38+ cells, including plasma cells and natural killer (NK) cells, which are involved in a series 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

The references:

Schinstock et al. (2018) Kidney transplantation with low DSA levels or low B-positive flow crossmatch: an underappreciated option for highly sensitized transplant candidates (page 8). Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481511/pdf/nihms837168.pdf#page=8; Ciancio et al. (2018) Antibody-mediated rejection implies poor prognosis in kidney transplantation: results from a single center. Available at: https://onlinelibrary.wiley.com/doi/10.1111/ctr.13392
Rodriguez-Ramirez et al. (2022) Antibody-mediated rejection: dilemmas in prevention, monitoring and treatment (Page 1). Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9475491/

SOURCE HI-Bio