HI-Bio Announces Positive Phase 2 Data on Felzartamab for the Treatment of Primary Membranous Nephropathy

• Felzartamab showed dose-dependent reduction in pathogenic antibody levels across two clinical studies
• Proteinuria remission observed across patient groups, including those starting with high aPLA2R titers or refractory to prior immunosuppressive therapies
• Company intends to advance felzartamab into late-stage development in Primary Membranous Nephropathy and other autoantibody-driven immune-mediated diseases
• Primary Membranous Nephropathy is a rare, high burden, immune-mediated kidney disease with no approved therapies

SOUTH SAN FRANCISCO, Calif. – April 11, 2023 – Human Immunology Biosciences (HI-Bio™), a clinical-stage biotechnology company developing targeted therapies for patients with severe immune-mediated diseases (IMDs), today announced positive data from two Phase 2 studies of felzartamab, M-PLACE and NewPLACE. Felzartamab is an investigational monoclonal antibody designed to deplete CD38+ plasma cells, which are believed to drive Primary Membranous Nephropathy (PMN) through the production of anti-PLA2R (aPLA2R) autoantibodies. The company intends to advance felzartamab into late-stage studies.

PMN is a rare IMD affecting kidney function that impacts more than 36,000 patients in the United States. There are currently no approved therapies for PMN. Standard of care comprises off-label use of a variety of agents, including immunosuppressive cyclophosphamide and CD20-targeted B-cell depleting agents. Even with these strategies, half of PMN patients continue to have nephrotic syndrome and nearly one third progress to end-stage renal disease (ESRD). aPLA2R autoantibodies are thought to be drivers of disease in as much as 80% of PMN cases. Persistent elevated aPLA2R levels are associated with worse response to immunosuppressive therapy, longer time to remission and high risk of progression to kidney failure.

M-PLACE was a Phase 1b/2a proof-of-concept, open-label, multinational study to assess safety and efficacy in adults with aPLA2R-positive PMN using a five-month (nine-dose) course. The study enrolled 31 patients who were newly diagnosed and relapsed or refractory to immunotherapies. 

NewPLACE is a two-arm, multi-center, open-label, parallel-group Phase 2 trial that enrolled 24 patients to assess the efficacy, safety, pharmacokinetics and pharmacodynamics of alternative two- and five-dose courses, over two weeks and two months respectively, and retreatment of felzartamab in patients with aPLA2R-positive PMN indicated for immunosuppressive therapy. The studied dose level across both studies and all arms was consistent with the target dose for felzartamab at 16 mg/kg.

The most durable reductions in aPLA2R levels were observed in the nine-dose arm as studied in M-PLACE, as compared to the two- and five-dose regimens studied in NewPLACE. Together, these studies enrolled a population of patients with the highest median aPLA2R serum titers as measured with an FDA-cleared immunoassay in a therapeutic clinical study to date (median [IQR]: 197 RU/mL [83-298 RU/mL]). 

In the final analysis of M-PLACE, early and substantial reductions in aPLA2R titers were observed in most patients as early as one week (median reduction of 45%), with deep responses (>50% reduction) in most patients at six months at end-of-treatment. A deepening or maintenance of response in the majority of responders after end-of-treatment through month 12 was observed. Robust reduction of autoantibody levels was measured regardless of initial aPLA2R titer including in patients with high baseline titers, who typically have increased risk of disease severity and progression, and lower expected response to standard of care therapies. 

In M-PLACE, improvements in proteinuria and serum albumin levels were observed with administration of felzartamab, highlighting potential renal recovery. Proteinuria remissions included patients previously found to be refractory to anti-CD20 therapies (e.g., rituximab) and cyclophosphamide. 

Across both studies, felzartamab was found to be generally well tolerated. The majority of treatment emergent adverse events (TEAEs) reported were mild to moderate and consistent with the known mechanism of action of felzartamab in the PMN population. The most common TEAE was infusion-related reactions on the first infusion that were mostly mild to moderate in intensity. In all, four of 55 patients (7.3%) had a TEAE leading to treatment discontinuation that was deemed related to study drug. Further, as published in Kidney International Reports in 2022, humoral response to immunization with SARS-CoV-2 vaccines was preserved with felzartamab use. 

“PMN is one of the most common causes of nephrotic syndrome, resulting in severe proteinuria, edema, fatigue, progression to ESRD and increased risk of thromboembolism and infection,” said Dr. Brad Rovin, M.D., Director of the Division of Nephrology at Ohio State University. “We need to advance clinical immunology to a point where diseases like PMN can be turned into manageable conditions with deep and durable remissions. I am excited to continue studying felzartamab in that context, to further evaluate its potential to help PMN patients who are at high risk of serious complications and currently have very limited treatment options.”

The company intends to present further data on the M-PLACE and NewPLACE studies at an upcoming medical meeting. 

“These data are very encouraging, demonstrating robust responses with proteinuria remissions in high-risk treatment naïve and refractory patients,” said Travis Murdoch, M.D., CEO of HI-Bio. “These results, the tolerability profile observed, and the fact that PMN is a high burden disease with no approved therapies all support our intention to advance felzartamab into late-stage development and discuss the path forward with regulators. We are focused on developing felzartamab in PMN and other autoantibody driven IMDs where patients have serious unmet needs.”

About Primary Membranous Nephropathy (PMN)

PMN is a rare autoantibody-mediated autoimmune kidney disease and a leading cause of nephrotic syndrome (NS) in adults worldwide. Disease onset and diagnosis typically occurs between 40 and 50 years of age, with 80% of patients presenting with Nephrotic Syndrome (i.e., edema, >3.5 g/day proteinuria, hypoalbuminemia). PMN is characterized by a thickening of the glomerular basement membrane (GBM) due to the formation and deposition of immune complexes in this space between podocytes and the glomerular endothelium of the kidney. 

Approximately 80% of PMN cases arise due to autoantibodies that recognize the phospholipase A2 receptor (PLA2R) antigen expressed on podocytes. Anti-PLA2R is both a diagnostic and prognostic biomarker, and total aPLA2R antibody level has been shown to be a biomarker for prognosis of outcome in patients with PMN. Other autoantibodies have been identified in patients with PMN including anti-THSD7A, NELL-1 and Sema3B, further supporting the role of antibody-secreting plasma cells in the pathophysiology of PMN. CD38+ long lived plasma cells and plasmablasts are a main source of autoantibodies. 

There are no approved therapies for PMN. The current standard of care comprises off-label use of supportive care measures (e.g., angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, statins, and diuretics), conventional immunosuppressive treatments (ISTs) (e.g. cyclophosphamide combined with steroids and calcineurin inhibitors) or B-cell depleting agents (e.g. anti-CD20 antibodies). However, these treatments are not effective in all patients, with a significant proportion of patients not achieving remission or relapsing. In addition, conventional immunosuppressive treatments are associated with a high risk of toxicity.

About Felzartamab

Felzartamab is an investigational therapeutic human monoclonal antibody directed against CD38, a protein expressed on mature plasma cells. In PMN, CD38+long-lived plasma cells drive pathogenic antibody production, contributing to functional damage to the glomeruli in the kidney. By targeting CD38, felzartamab has the potential to deplete CD38+ plasma cells while leaving other functionally important plasma cells intact, which may ultimately improve clinical outcomes in a broad range of autoantibody driven diseases.

HI-Bio is currently evaluating the safety and efficacy of investigational felzartamab for patients with aPLA2R antibody-positive membranous nephropathy (in the M-PLACE and NewPLACE trials) and Immunoglobulin A Nephropathy (IGNAZ trial). Felzartamab is also being evaluated in investigator-initiated studies for PMN in patients who have had inadequate response to anti-CD20 and for antibody mediated rejection (AMR) of renal allograft transplants. HI-Bio in-licensed felzartamab from MorphoSys in June 2022, and holds executive worldwide rights for felzartamab with the exception of Greater China.  

In 2017, MorphoSys entered into an exclusive regional licensing agreement with I-Mab Biopharma to develop and commercialize felzartamab in Greater China which encompasses Mainland China, Hong Kong, Macau and Taiwan. I-Mab is evaluating felzartamab in relapsed/refractory multiple myeloma. 

Felzartamab is an investigational drug that has not yet been approved by any regulatory authorities.

About HI-Bio
Human Immunology Biosciences, Inc. (HI-Bio™) is a clinical-stage biotechnology company focused on discovering and developing precision medicines for people suffering from immune-mediated diseases (IMDs). HI-Bio is leading clinical immunology into its next chapter with more targeted therapies that target cellular drivers of disease. To learn more about HI-Bio, visit us at www.hibio.com or follow us on LinkedIn and Twitter.