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

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

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

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

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

SOUTH SAN FRANCISCO, Calif., May 25, 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 results from a Phase 2 investigator-sponsored clinical trial of felzartamab for late antibody-mediated rejection (AMR) in kidney transplant recipients.

Felzartamab is an investigational monoclonal antibody designed to specifically target and deplete CD38+ cells, which can include plasmablasts, plasma cells and natural killer (NK) cells, which are believed to drive AMR and other IMDs. This double-blind, placebo-controlled Phase 2 study was designed to assess the safety and tolerability of felzartamab in adults with late 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 an observation period of 32 weeks. Biopsies were taken at baseline, 24 weeks and 52 weeks. The study enrolled 22 patients.

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

Key secondary endpoints demonstrated potential for felzartamab to be the first effective therapeutic for late AMR, resolving disease according to the Banff Classification. The classification is the international standard for characterizing kidney transplant-related disease, including late rejection.

In the treatment arm, 82% (n=9/11) of patients experienced resolution of AMR at week 24, compared to 20% (n=2/10) who received placebo. One placebo patient had a graft loss at week 14, likely due to persistent, chronic 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 achieving an MVI score of 0. Of those who experienced resolution at 24 weeks, 67% (n=6/9) maintained resolution at 52 weeks, with no drug being administered during the observation period. Additionally, deep reduction in donor-derived cell-free DNA (dd-cfDNA), a marker of allograft injury, was observed.

Both stabilization of eGFR, an indicator of kidney function, and reductions in NK cells, key mediators of downstream inflammation and tissue damage, were shown relative to placebo.

"There is a large unmet need for a therapy that resolves disease by the Banff Classification and preserves kidney function in patients with antibody-mediated rejection," said Principal Investigator Georg Böhmig, M.D., Associate Professor of Medicine at the Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna. "The data presented in this study are very compelling and represent the potential for significant progress to be made in this high burden disease."

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

"We believe these data demonstrate the potential for felzartamab to help preserve the transformative and often life-saving benefit of a kidney transplant by resolving a leading cause of rejection," said Uptal Patel, M.D., Chief Medical Officer at HI-Bio. "Based on the observed activity and concurrence of results across key biomarkers of graft damage and function, we continue to be confident in our anti-CD38 depletion strategy with felzartamab. We intend to advance felzartamab to late-stage studies in antibody-mediated rejection and other immune-mediated diseases, where patients have serious unmet needs."

The data were simultaneously published in the New England Journal of Medicine and presented as a late-breaking presentation by lead author Katharina Mayer, M.D., of the Division of Nephrology and Dialysis at the Medical University of Vienna, 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 Antibody-Mediated Rejection (AMR) in Kidney Transplant Recipients
Antibody-mediated rejection (AMR) is a major cause of kidney transplant failure, with chronic AMR affecting ~12% of patients that receive kidney transplants annually in the U.S.¹ AMR has emerged as 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 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. Schinstock et al. (2018) Kidney Transplant with Low Levels of DSA or Low Positive B-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 a poor prognosis in kidney transplantation: Results from a single center. Available at: https://onlinelibrary.wiley.com/doi/10.1111/ctr.13392
2. Rodriguez-Ramirez et al. (2022) Antibody-mediated rejection: prevention, monitoring and treatment dilemmas (Page 1). Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9475491/

SOURCE HI-Bio