Palleon Pharmaceuticals has reported Phase 2 findings showing that its investigational glycan editing therapy HLX79/E-602 (efgitasialase alfa), administered with rituximab, produced faster clinical responses and higher remission rates than rituximab alone in a small study involving patients with primary membranous nephropathy. Presented at the American Society of Nephrology Kidney Week 2026 meeting in Denver on October 23, the results showed complete or partial remission in all seven patients receiving the highest evaluated combination dose at Week 36, compared with three of six patients in the rituximab-only group.
The results provide early clinical evidence supporting a therapeutic strategy designed to modify the sugar structures that influence immune-cell behaviour. Unlike treatments that directly block a conventional cytokine or receptor, HLX79/E-602 is an engineered enzyme intended to remove sialic acid from cell-surface glycans, potentially changing how disease-associated immune cells interact with their surroundings and respond to antibody-based treatment.
The findings are relevant because rituximab, a B-cell-depleting monoclonal antibody used in primary membranous nephropathy, can require several months to produce clinical remission, while some patients experience incomplete responses or relapse. However, the new study enrolled only 26 patients across multiple treatment groups, and the most striking results came from a seven-patient high-dose cohort. The evidence is therefore sufficient to support further investigation but not to establish superior efficacy or long-term kidney protection.
What do the Phase 2 HLX79/E-602 results reveal about remission rates and treatment response?
The randomised Phase 2 study, registered as NCT07038382, was conducted in China by Palleon’s development partner Shanghai Henlius Biotech. The trial enrolled 26 patients with primary membranous nephropathy and evaluated Henlius’ rituximab biosimilar HANLIKANG alone or in combination with HLX79/E-602 at doses of 10, 20 or 30 milligrams per kilogram. Treatment involved weekly dosing over four weeks, followed by repeat treatment at approximately six months.
The principal efficacy findings disclosed by Palleon focused on the highest-dose combination group. At 30 milligrams per kilogram, the combination produced a median time to first clinical response of three weeks, compared with 11 weeks for rituximab alone. This difference represents a potentially important acceleration in treatment response, although the small sample and limited disclosure of the response criteria constrain the strength of the conclusion.
At Week 36, all seven patients receiving the high-dose combination had achieved complete or partial remission, including three complete remissions. In the rituximab-only group, three of six patients had achieved complete or partial remission, representing a 50% response rate. The observed difference is substantial, but a result involving seven patients remains highly sensitive to the outcome of even one additional participant.
Earlier findings at Week 24 offer additional context. Before the scheduled repeat treatment, six of seven patients in the high-dose combination group had achieved remission, compared with four of six receiving rituximab alone. This corresponds to response rates of approximately 86% and 67%, respectively, indicating that the numerical separation between treatment groups was smaller at that assessment.
The change between Week 24 and Week 36 is relevant to interpreting response durability and the potential contribution of repeat treatment. The company has not provided sufficient patient-level information to determine why the proportion in remission declined in the comparator group or whether individual patients experienced relapse, fluctuating laboratory measurements or other changes. Similarly, the later improvement in the combination group cannot be attributed specifically to redosing without more detailed longitudinal evidence.
The company did not disclose a confirmatory statistical comparison establishing superiority of the combination over rituximab alone. The findings should consequently be regarded as an encouraging early efficacy signal rather than definitive evidence of a treatment advantage. Their principal value is in identifying a dose and treatment strategy that may justify evaluation in a larger, adequately powered study.
Why could faster clinical remission matter in primary membranous nephropathy?
Primary membranous nephropathy is an autoimmune kidney disease in which antibodies directed against proteins associated with glomerular cells contribute to inflammation and damage to the kidney’s filtration barrier. The condition often causes substantial protein leakage into urine, which can lead to low blood albumin, swelling and other complications associated with nephrotic syndrome. Persistent disease activity can contribute to progressive kidney injury and, in some patients, kidney failure.
A substantial proportion of patients with primary membranous nephropathy have antibodies against the M-type phospholipase A2 receptor, commonly known as PLA2R. These antibodies are useful in evaluating disease activity and treatment response, although they do not account for every case. Clinical management generally combines supportive kidney-protective treatment with immunosuppression in patients whose risk profile warrants it.
Rituximab has become an important treatment option because it targets CD20-positive B cells involved in antibody-mediated immune activity. The drug can reduce circulating autoantibody levels, but improvements in proteinuria may occur only after a prolonged interval. This delay reflects the time required for immunological changes and recovery of the damaged filtration barrier to translate into measurable clinical improvement.
The distinction between immunological remission and clinical remission is central to understanding the new findings. A decline in disease-associated antibodies may precede a meaningful improvement in urinary protein excretion by several months, meaning that early changes in one measurement do not necessarily demonstrate immediate structural kidney recovery. The exact definition of first clinical response used in the HLX79/E-602 comparison will therefore influence how its three-week median response time should be interpreted.
Earlier remission could potentially reduce the duration of heavy proteinuria and the associated burden of nephrotic syndrome. However, demonstrating that benefit would require evidence of sustained proteinuria improvement, changes in serum albumin, reduced complications and preservation of kidney function. The current disclosure does not establish that the faster response resulted in lower rates of hospitalisation, thrombotic complications or kidney failure.
How does HLX79/E-602 use glycan editing to influence autoimmune disease?
HLX79/E-602 is a sialidase-Fc fusion protein designed to enzymatically remove sialic acid residues from glycans located on cell surfaces. Glycans are sugar-containing structures that participate in cell recognition, adhesion, signalling and immune regulation. Their composition can influence how immune cells respond to activation signals and interact with other components of the immune system.
Sialic acid-containing glycans can participate in regulatory pathways involving proteins known as Siglecs, which influence immune-cell activity. Palleon’s therapeutic approach seeks to alter these interactions by removing selected cell-surface sugar residues. In the context of autoimmune disease, the company has investigated whether this process can make pathogenic immune-cell populations more susceptible to antibody-mediated elimination.
The scientific rationale for combining HLX79/E-602 with rituximab involves the possibility of improving the depletion of disease-associated B cells. Rituximab binds CD20 on B cells and recruits immune mechanisms that contribute to their elimination, while glycan editing could potentially modify the signals and cell-surface characteristics that influence those processes. Palleon’s preclinical research has supported investigation of this combination approach.
The company has also described the potential role of glycan structures in supporting the persistence of inflammatory immune cells, including macrophages, within affected tissues. Changing the glycan environment may therefore affect more than one component of an autoimmune response, although the magnitude and clinical relevance of these effects remain to be established in patients with membranous nephropathy.
The available Phase 2 disclosure does not demonstrate precisely which immune-cell changes account for the observed clinical responses. It also does not establish that glycan editing directly reverses glomerular injury or eliminates the disease-specific autoantibodies responsible for primary membranous nephropathy. Those mechanistic conclusions would require accompanying biomarker analyses, cellular studies and longitudinal clinical evidence.
The broader scientific attraction is that glycan editing represents a different method of immune modulation from directly inhibiting cytokines or depleting B cells alone. Its development potential will depend on whether researchers can demonstrate a reproducible therapeutic effect without unacceptable consequences from altering sugar structures involved in normal immune regulation.
How should the small patient population influence interpretation of the 100% remission result?
The reported 100% remission rate is the most attention-grabbing result from the study, but its statistical and clinical interpretation requires considerable care. Seven patients achieving remission is encouraging, particularly when the comparator group recorded three responses among six participants. Nevertheless, a seven-patient sample provides limited precision for estimating the treatment response expected in a much larger population.
The trial also involved several dose groups within a total enrolment of 26 participants. As a result, the number of patients contributing to each individual dose comparison was small, limiting the ability to assess whether the apparent benefit follows a consistent dose-response relationship. The company did not provide detailed comparative outcomes for the 10 and 20 milligram-per-kilogram groups in its October announcement.
A larger study would need to determine whether the 30 milligram-per-kilogram dose offers the most favourable balance between activity, tolerability and treatment burden. The highest evaluated dose is not necessarily the optimal clinical dose, particularly for an enzyme-based therapy intended to influence widespread cell-surface structures. Additional pharmacodynamic evidence could help establish whether lower doses provide sufficient biological activity.
Baseline characteristics will also matter. Patients with membranous nephropathy can differ in autoantibody status, baseline proteinuria, kidney function, disease duration and previous immunosuppressive treatment. These factors may influence the likelihood and timing of remission, particularly in small groups where randomisation does not guarantee close balance across every clinically important variable.
Another important consideration is the duration of follow-up. A Week 36 response provides evidence of treatment activity within the observation period, but membranous nephropathy may follow a prolonged course involving remission, persistent proteinuria and subsequent relapse. Demonstrating sustained benefit would require longer evaluation and a clear description of how repeat treatment contributes to maintaining remission.
The next phase of development should therefore prioritise a sufficiently powered controlled comparison with prespecified efficacy endpoints, appropriate adjustment for baseline risk and a follow-up period capable of evaluating sustained remission. Such evidence would establish whether the numerical advantages observed in this early trial are reproducible.
What does the safety disclosure establish about combining glycan editing with rituximab?
Palleon reported that HLX79/E-602 was generally well tolerated across the evaluated dose groups and that no severe adverse events were attributed to the investigational therapy. The company also described the treatment as compatible with outpatient administration, suggesting that the observed acute tolerability did not create an obvious barrier to delivering the regimen in that setting. These are favourable initial observations, but the limited number of exposed patients restricts the conclusions that can be drawn.
The October announcement did not provide a complete numerical breakdown of adverse events, serious adverse events, treatment interruptions, laboratory abnormalities or discontinuations. Without those details, it is not possible to conduct a comprehensive comparison of the combination’s safety against rituximab alone. The absence of treatment-attributed severe events in a small study does not exclude less frequent or delayed complications.
The combination deserves careful evaluation because rituximab already modifies immune function through B-cell depletion. Adding an agent designed to influence immune-cell interactions could potentially alter infection susceptibility or other immunological responses, depending on the extent and duration of pharmacological activity. These possibilities require prospective assessment rather than assumptions about either safety or harm.
An enzyme-based therapy may also introduce considerations related to immunogenicity and repeat exposure. Investigators will need to understand whether anti-drug antibodies develop, whether repeated dosing changes pharmacological activity and whether immune reactions affect tolerability. Such questions become especially relevant when the treatment regimen includes redosing after several months.
The appropriate safety comparison will ultimately need to weigh any incremental treatment risk against the potential benefit of faster or more durable remission. Larger studies and longer follow-up will be necessary before determining whether the combination is suitable for broad use in patients with primary membranous nephropathy.
What role does Shanghai Henlius Biotech play in Palleon’s development strategy?
The Phase 2 study forms part of a collaboration between Palleon Pharmaceuticals and Shanghai Henlius Biotech, the Hong Kong-listed biotechnology company responsible for conducting the Chinese clinical programme. The companies expanded their relationship in December 2024 through a licensing agreement covering E-602 development in China, including combination treatment with Henlius’ rituximab biosimilar HANLIKANG.
Under that agreement, Henlius obtained exclusive rights to E-602 in China, while Palleon retained rights in other territories. The arrangement placed local clinical development and associated funding responsibilities with Henlius for the agreed programme, allowing Palleon to advance a potential autoimmune indication through a regional development partner. It also established a route for future economic participation if contractual milestones are achieved.
The agreement provides for up to $95.3 million in specified development and commercial milestone payments, together with royalties linked to commercialisation in China. These amounts represent potential contractual consideration rather than payments already received. The milestone structure and applicable conditions would need to be considered before assigning financial value to the Phase 2 findings.
For Henlius, the programme offers an opportunity to investigate a differentiated combination involving its existing rituximab product. However, the use of HANLIKANG in this investigational combination does not establish that the new regimen is approved for primary membranous nephropathy. Separate clinical and regulatory evidence would be necessary for any new authorised indication or combination claim.
Palleon’s broader pipeline also includes E-688/HLX316, a B7-H3-targeted sialidase being investigated in a Phase 1 oncology programme. That asset involves a distinct investigational approach and patient population, although both programmes draw on the company’s glycan editing technology. Clinical activity observed with one programme cannot be assumed to establish the performance of the other.
The collaboration therefore has two potential dimensions. The immediate opportunity involves determining whether glycan editing improves outcomes when combined with B-cell depletion in autoimmune kidney disease, while the longer-term implication concerns whether the same technology can support therapeutically useful applications across different immune-mediated conditions.
Can HLX79/E-602 compete with established rituximab-based treatment strategies?
The competitive benchmark for HLX79/E-602 is not simply whether patients achieve remission, but whether adding the investigational medicine produces a meaningful improvement beyond rituximab-based care. Rituximab has established clinical evidence in membranous nephropathy, including results from the randomised MENTOR trial comparing it with cyclosporine. That study found complete or partial remission in 60% of rituximab-treated patients at 24 months, supporting its role in the management of appropriately selected patients.
The MENTOR findings cannot be compared directly with the new Palleon trial to establish a treatment advantage. The studies differ in patient numbers, treatment protocols, follow-up duration and potentially baseline disease characteristics. Their value in combination is to demonstrate that rituximab provides an established reference treatment against which improvements in remission depth and durability can be assessed.
For a new combination regimen, faster remission may represent a useful differentiator if accompanied by sustained improvement and acceptable safety. A larger development programme could also investigate whether the therapy reduces the proportion of patients requiring further immunosuppression or retreatment. Those benefits remain hypothetical until specifically demonstrated.
Commercial positioning will additionally depend on the complexity and cost of administering two biological therapies. The initial HLX79/E-602 regimen involved four weekly doses followed by repeat treatment at six months, potentially adding treatment visits and drug acquisition costs to existing rituximab therapy. A meaningful clinical advantage would be necessary to justify that additional burden.
The potential treatment population will also depend on which patients derive the greatest incremental benefit. Those with high disease activity, incomplete prior responses or particular immunological characteristics could represent research priorities, but the current small study does not establish any validated responder subgroup.
What evidence must Palleon provide before HLX79/E-602 can progress toward commercial use?
The most immediate development requirement is a larger clinical trial capable of testing the observed remission advantage with appropriate statistical power. Such a study should clearly define complete and partial remission, document changes in proteinuria and serum albumin, and evaluate whether the response persists after treatment. Kidney function outcomes and disease-specific antibody measurements would provide additional information about the relationship between clinical remission and underlying immunological activity.
Dose selection will be another priority. The company has disclosed encouraging results at 30 milligrams per kilogram but has not presented enough information from the lower-dose groups to establish the optimal regimen. Pharmacodynamic measurements of glycan editing, B-cell depletion and relevant immune biomarkers could help determine whether the combination effect is mechanistically consistent and reproducible.
Regulatory development will depend on the programme’s future trial results and the requirements of the jurisdictions where the companies seek authorisation. The investigational combination has not received marketing approval for primary membranous nephropathy, and the Phase 2 findings do not establish a filing timetable. A clear development plan will need to address efficacy, safety, manufacturing consistency and the intended patient population.
The October 2026 results position HLX79/E-602 as a promising early-stage application of glycan editing in autoimmune kidney disease. Its ability to produce rapid responses alongside rituximab provides a rationale for further development, but the seven-patient high-dose result must be replicated before it can support a reliable conclusion about treatment superiority. The decisive next step will be demonstrating that the apparent acceleration in remission is sustained, clinically meaningful and achievable with an acceptable benefit-risk profile in a substantially larger population.
