Palleon Pharmaceuticals Reports Early Proof-of-Concept Results for HLX79/E-602 in Primary Membranous Nephropathy
Palleon Pharmaceuticals, a clinical-stage biotechnology company developing innovative glycan-editing therapeutics for autoimmune diseases and cancer, has announced encouraging early proof-of-concept results from a Phase 2 clinical trial evaluating HLX79/E-602 (efgitasialase alfa) in patients with primary membranous nephropathy (pMN). The investigational sialidase-Fc fusion protein demonstrated the potential to accelerate remission when administered in combination with rituximab.
Patients receiving the 30 mg/kg combination regimen achieved complete or partial remission in a median of three weeks, compared with 11 weeks among patients treated with rituximab alone. By Week 36, all seven patients receiving the highest combination dose had achieved complete or partial remission, including three complete remissions. The findings were presented during an oral presentation at the American College of Rheumatology (ACR) Convergence 2026 in Orlando, Florida.
Palleon Pharmaceuticals announced preliminary clinical findings from its investigational glycan-editing therapeutic HLX79/E-602, also known as efgitasialase alfa, highlighting the potential of this approach to address underlying mechanisms of autoimmune-related organ damage.
The Phase 2 clinical study was conducted by Palleon’s development partner, Shanghai Henlius Biotech (2696.HK), in China. The randomized study, registered under ClinicalTrials.gov identifier NCT07038382, evaluated the safety and preliminary efficacy of HLX79/E-602 in combination with rituximab biosimilar therapy in patients diagnosed with primary membranous nephropathy.
The study enrolled 26 patients and compared treatment with rituximab biosimilar alone against combination regimens incorporating different doses of HLX79/E-602. The investigational therapy was administered at doses of 10 mg/kg, 20 mg/kg and 30 mg/kg alongside rituximab.
The preliminary findings showed that the highest evaluated dose of HLX79/E-602, when combined with rituximab, was associated with a substantially shorter time to remission than rituximab treatment alone. Patients receiving the 30 mg/kg combination achieved complete or partial remission in a median of three weeks, compared with 11 weeks among those receiving rituximab monotherapy.
At Week 36, all seven patients in the 30 mg/kg combination group had achieved complete or partial remission. This included three patients who achieved complete remission. In comparison, three of the six patients receiving rituximab alone, representing 50% of that treatment group, achieved remission by the same time point.
The combination treatment was reported to be safe across all evaluated dose levels, with no severe adverse events attributed to HLX79/E-602.
These preliminary findings support further investigation of glycan editing as a potential therapeutic strategy for autoimmune diseases characterized by persistent inflammation and progressive organ damage.
Addressing Unmet Needs in Primary Membranous Nephropathy
Primary membranous nephropathy is an autoimmune kidney disease characterized by damage to the glomerular filtration barrier, the specialized structures within the kidneys responsible for filtering waste products and excess fluid from the blood.
The condition occurs when the immune system produces antibodies that target components associated with the kidney’s filtration structures. This immune response can result in inflammation and damage to the glomerular basement membrane, leading to the accumulation of immune deposits.
As the disease progresses, patients may experience proteinuria, a condition characterized by excessive protein leakage into the urine. Other potential manifestations include swelling, reduced kidney function, low blood protein levels and an increased risk of cardiovascular complications.
The severity and progression of primary membranous nephropathy can vary considerably among patients. While some individuals may experience spontaneous remission, others develop persistent proteinuria and progressive kidney damage that can eventually lead to chronic kidney disease or kidney failure.
Treatment generally focuses on controlling the underlying autoimmune response, reducing protein loss and preserving kidney function.
Rituximab is an established treatment option for primary membranous nephropathy. It is a monoclonal antibody that targets CD20, a protein expressed on the surface of B cells. By depleting these antibody-producing immune cells, rituximab helps reduce the autoimmune activity responsible for kidney damage.
However, despite its clinical utility, rituximab does not produce rapid or complete responses in every patient. Clinical improvement can take several months, and approximately half of treated patients achieve remission.
This creates an important unmet medical need for therapeutic approaches that can improve treatment responses, accelerate remission and address additional biological mechanisms contributing to ongoing organ damage.
Palleon’s HLX79/E-602 is being investigated as a complementary treatment approach designed to target another component of the immune response that may continue contributing to tissue injury even after B-cell depletion.
Phase 2 Trial Evaluates HLX79/E-602 in Combination With Rituximab
The randomized Phase 2 clinical trial conducted by Shanghai Henlius Biotech enrolled 26 patients with primary membranous nephropathy in China.
The study was designed to evaluate whether adding HLX79/E-602 to rituximab treatment could improve clinical outcomes compared with rituximab administration alone.
Participants were assigned to treatment regimens involving rituximab biosimilar HANLIKANG, developed by Henlius, either as monotherapy or in combination with different doses of the investigational glycan-editing therapeutic.
The combination treatment groups received HLX79/E-602 at three dose levels:
- 10 mg/kg in combination with rituximab.
- 20 mg/kg in combination with rituximab.
- 30 mg/kg in combination with rituximab.
Treatment was administered weekly for four consecutive weeks, with an additional round of dosing planned at six months.
The trial evaluated the potential benefits of combining B-cell depletion with targeted modulation of macrophage populations involved in inflammation and tissue damage.
This approach reflects the growing understanding that autoimmune diseases can involve multiple interacting immune-cell populations. Although B cells play an important role in antibody-mediated autoimmune activity, other immune cells may continue contributing to tissue inflammation and structural damage after B-cell-directed treatment.
By combining rituximab with HLX79/E-602, the study aims to investigate whether addressing these additional disease mechanisms can improve the depth and speed of clinical response.
Combination Therapy Demonstrates Faster Remission
One of the most notable findings from the Phase 2 study was the difference in the median time required for patients to achieve complete or partial remission.
Patients receiving the highest dose of HLX79/E-602, 30 mg/kg, alongside rituximab achieved remission in a median of three weeks.
In comparison, patients receiving rituximab alone achieved complete or partial remission in a median of 11 weeks.
MEDIAN TIME TO COMPLETE OR PARTIAL REMISSION
3 weeks
HLX79/E-602 + rituximab
30 mg/kg combination group
11 weeks
Rituximab alone
Monotherapy group
The difference suggests that the addition of HLX79/E-602 may help accelerate the clinical response to rituximab in patients with primary membranous nephropathy.
The findings are particularly relevant because conventional B-cell depletion may require an extended period before patients experience meaningful improvements in disease activity.
An approach that addresses additional immune mechanisms could potentially contribute to earlier disease control and reduce the period during which patients remain vulnerable to ongoing kidney injury.
However, these findings are preliminary and come from a relatively small Phase 2 study. Additional clinical research will be necessary to determine whether the observed improvement in time to remission can be consistently demonstrated in larger patient populations.
All Patients in the Highest-Dose Group Achieved Remission by Week 36
The study also reported encouraging results for the proportion of patients achieving complete or partial remission by Week 36.
Among the seven patients receiving HLX79/E-602 at 30 mg/kg in combination with rituximab, all seven achieved complete or partial remission, representing a 100% remission rate within this treatment cohort.
Three patients in the group achieved complete remission, while the remaining four achieved partial remission.
In comparison, three of the six patients receiving rituximab monotherapy achieved complete or partial remission by Week 36, representing a 50% remission rate.
WEEK 36 REMISSION RESULTS
Percentage of patients achieving complete or partial remission in the reported treatment groups.
These results indicate a difference in remission outcomes between the two reported treatment groups.
The achievement of complete remission in three patients receiving the highest combination dose is also an important observation because complete remission represents a more substantial treatment response than partial remission.
For patients with primary membranous nephropathy, achieving remission is an important therapeutic objective because it can help reduce proteinuria and potentially support the preservation of kidney function.
Nevertheless, the results should be interpreted in the context of the limited number of participants in each treatment group. Larger studies will be needed to establish the consistency and durability of the observed responses and to determine the appropriate dose and treatment schedule.
Understanding the Novel Mechanism of HLX79/E-602
HLX79/E-602 (efgitasialase alfa) is a first-in-class investigational sialidase-Fc fusion protein developed using Palleon’s proprietary glycan-editing technology.
The therapeutic is designed to modify the glycan structures present on cell surfaces through the enzymatic removal of sialic acid.
Sialic acids are sugar molecules commonly found at the outermost ends of complex carbohydrates attached to proteins and lipids on cell surfaces. These molecules play important roles in regulating cell interactions, immune recognition and inflammatory responses.
Changes in cell-surface glycosylation can influence how immune cells behave within different tissue environments.
Palleon’s approach is based on the observation that sialylation can contribute to the regulation of immune-cell activity and that certain glycan-dependent mechanisms may support the persistence of harmful inflammatory cell populations in diseased tissues.
HLX79/E-602 uses a sialidase enzyme to remove sialic acid from cell surfaces. Through this process, the investigational therapeutic is designed to reduce populations of pro-fibrotic CD163-positive macrophages in inflamed tissues.
Macrophages are specialized immune cells involved in multiple biological processes, including immune defense, inflammation regulation, tissue repair and removal of damaged cellular material.
Although macrophages perform important protective functions, certain macrophage populations can contribute to chronic inflammation and fibrosis when their activity becomes dysregulated.
In autoimmune diseases, persistent activation of these cells may promote tissue remodeling, excessive extracellular matrix deposition and progressive organ damage.
HLX79/E-602 is designed to selectively influence macrophage populations associated with these harmful processes while preserving beneficial macrophage functions elsewhere in the body.
This targeted approach is intended to address disease-associated immune activity without broadly suppressing the entire macrophage population.
Targeting Macrophage-Driven Inflammation and Fibrosis
A key element of Palleon’s therapeutic strategy is the recognition that autoimmune organ damage may continue even after the immune mechanisms responsible for initiating the disease have been suppressed.
In primary membranous nephropathy, rituximab reduces B-cell populations involved in antibody production. However, the elimination of B cells does not necessarily resolve every inflammatory process occurring within the kidney.
Macrophages may remain present in affected tissues and continue contributing to inflammation, fibrosis and structural damage.
According to Palleon, these persistent macrophage populations represent an additional therapeutic target that could complement existing B-cell-directed treatments.
By reducing pro-fibrotic CD163-positive macrophages in inflamed tissue, HLX79/E-602 is intended to address a downstream mechanism of tissue injury.
This mechanism may have implications beyond primary membranous nephropathy because macrophage-driven inflammation and fibrosis are involved in several autoimmune and inflammatory conditions.
The company’s research strategy includes exploring the potential relevance of this mechanism in diseases such as lupus nephritis, systemic sclerosis and interstitial lung disease.
These conditions affect different organs and involve distinct disease processes, but persistent inflammation and tissue fibrosis are important contributors to disease progression in each.
A therapeutic approach capable of selectively modifying harmful macrophage activity could therefore offer opportunities for development across multiple autoimmune indications.
Further clinical investigation will be required to determine whether the mechanism demonstrated in pMN can translate into meaningful benefits in these other diseases.
Palleon Leadership Highlights Broader Therapeutic Potential
Jim Broderick, M.D., Chief Executive Officer and Founder of Palleon Pharmaceuticals, discussed the biological rationale behind the company’s approach and the potential importance of macrophages in autoimmune organ damage.
According to Broderick, growing evidence suggests that macrophages can persist in the kidney after B cells have been depleted and may continue driving tissue injury.
He explained that HLX79/E-602 is designed to reduce pro-fibrotic macrophages in inflamed tissues without compromising the beneficial functions performed by macrophages in other parts of the body.
Broderick also highlighted the potential relevance of this mechanism to additional autoimmune conditions, including lupus nephritis, systemic sclerosis and interstitial lung disease.
He noted that macrophages are important contributors to progressive organ damage in multiple autoimmune diseases, suggesting that glycan editing could provide a new therapeutic approach for conditions with significant unmet medical needs.
The company believes that the Phase 2 findings provide early clinical evidence supporting further development of its glycan-editing platform.
Development Partnership With Shanghai Henlius Biotech
The Phase 2 study was conducted by Shanghai Henlius Biotech, Palleon’s development partner, as part of the companies’ efforts to evaluate HLX79/E-602 in primary membranous nephropathy.
The collaboration combines Palleon’s expertise in glycan-editing therapeutics with Henlius’ clinical development capabilities.
Henlius is responsible for conducting the randomized clinical evaluation in China, including the comparison of rituximab biosimilar HANLIKANG alone against combination regimens incorporating HLX79/E-602.
The partnership represents an important step in translating Palleon’s investigational technology into clinical development programs targeting autoimmune diseases.
The presentation of the Phase 2 findings at ACR Convergence 2026 also provides an opportunity to share early clinical evidence with the rheumatology and broader medical research communities.
The oral presentation in Orlando highlighted the potential of targeting macrophage-driven tissue damage as a complementary approach to established immune-directed treatments.
Presentation at ACR Convergence 2026
Palleon announced the early proof-of-concept findings during an oral presentation at the American College of Rheumatology’s ACR Convergence 2026 meeting in Orlando, Florida.
The meeting brings together researchers, clinicians, healthcare professionals and biotechnology companies working across rheumatology and autoimmune disease research.
The presentation focused on the Phase 2 evaluation of HLX79/E-602 in primary membranous nephropathy, including the treatment response observed with the 30 mg/kg combination regimen.
The results contribute to the growing investigation of targeted immune modulation and glycan editing as potential approaches for treating autoimmune conditions.
The early Phase 2 findings provide preliminary evidence that combining HLX79/E-602 with rituximab may improve remission outcomes in patients with primary membranous nephropathy.
The observed reduction in median time to remission, together with the 100% complete or partial remission rate in the highest-dose cohort at Week 36, supports continued clinical evaluation of the combination approach.
The reported safety findings across all evaluated doses, including the absence of severe adverse events attributed to HLX79/E-602, also provide an encouraging initial assessment of the investigational therapeutic’s tolerability.
However, the study involved only 26 participants, and the reported outcomes from the highest-dose and monotherapy groups were based on seven and six patients, respectively. Larger and longer-duration studies will be important to confirm the efficacy, safety, optimal dosing and durability of treatment responses.
Palleon is also exploring the broader potential of glycan editing to address macrophage-associated inflammation and fibrosis in other autoimmune diseases.
With its first-in-class sialidase-Fc fusion protein, the company is investigating a therapeutic strategy that differs from conventional approaches focused primarily on suppressing antibody-producing B cells.
If further clinical research validates the mechanism and demonstrates meaningful patient benefits, HLX79/E-602 could potentially expand treatment options for primary membranous nephropathy and other autoimmune conditions associated with progressive organ damage.
About Palleon Pharmaceuticals
Palleon Pharmaceuticals is a clinical-stage biotechnology company developing glycan editing, a new approach to immune modulation in autoimmune disease and cancer. The company was founded on the glycobiology research of Carolyn Bertozzi, 2022 Nobel Laureate in Chemistry. Its pipeline includes E-602/HLX79 (Phase 2, membranous nephropathy) and E-688/HLX316 (Phase 1, advanced solid tumors). www.palleonpharma.com