Enterome EO2463 hits 74% ORR in iNHL combo cohort at EHA 2026
Enterome SA has presented interim Phase 1/2 data for its OncoMimics candidate EO2463 at the European Hematology Association Congress in Stockholm, reporting clinical activity across monotherapy and combination cohorts in indolent non-Hodgkin lymphoma (iNHL), alongside durable immunological responses that persisted for up to 34 months after the last dose.
The SIDNEY study (NCT04669171) enrolled patients across four cohorts covering previously untreated low-tumour-burden disease suitable for watchful waiting, first-line low-tumour-burden disease requiring treatment in combination with rituximab, and relapsed or refractory settings treated with EO2463 plus lenalidomide and rituximab (R2). In total, 90% of the 48 tested patients showed positive immune responses.
Clinical results
In the monotherapy cohort, which targeted patients typically managed with watchful waiting and no active therapy, EO2463 produced a 41% objective response rate by Lugano criteria. In the relapsed and refractory cohorts receiving EO2463 combined with R2, the objective response rate reached 74%, with a 61% complete response rate and a median duration of objective response of 35.2 months. The drug was reported as well tolerated across all settings, with no cohort-specific safety signals highlighted in the release.
Critically for the programme's long-term value, EO2463-induced CD8 T cell expansion was significantly associated with clinical response in both the monotherapy and combination settings. The company says this association supports development of a predictive biomarker, which, if validated, could allow patient selection in future registrational trials and potentially strengthen the product's commercial profile.
Jan Fagerberg, Chief Medical Officer of Enterome, said the data demonstrate that EO2463 "consistently induces rapid and durable expansions of CD8 T cells against the B-cell lineage markers targeted by EO2463 while having a favorable tolerability profile," adding that the link between immune expansion and clinical outcomes supports continued development.
Market context and competitive landscape
EO2463 occupies an unusual niche in the iNHL treatment landscape. Follicular lymphoma and marginal zone lymphoma, the two indications covered by SIDNEY, have seen significant advances from CD20-directed antibodies, PI3K inhibitors, and, more recently, bispecific antibodies such as mosunetuzumab and epcoritamab. CAR-T cell therapies have also gained approvals in relapsed follicular lymphoma, raising the bar for new entrants.
Enterome's off-the-shelf, peptide-based approach is mechanistically distinct from these modalities. Rather than engineering patient-derived cells or administering a monoclonal antibody, OncoMimics peptides are designed to expand pre-existing memory CD8 T cells primed by gut commensal bacteria that cross-react with B-cell lineage markers including CD20, CD22, CD37 and BAFF receptor. The multi-target design is intended to reduce the risk of antigen escape, a recognised clinical problem with single-target therapies. The FDA granted EO2463 Orphan Drug Designation for follicular lymphoma in May 2026, providing regulatory incentives and a degree of market exclusivity if the product reaches approval.
The watch-and-wait monotherapy cohort is strategically significant. No approved active therapy currently exists for this patient group, and a 41% ORR, if it holds in a larger registrational study, would represent a meaningful clinical advance. That said, Phase 1/2 interim data in open-label, multi-cohort studies carry inherent limitations: patient numbers remain small, particularly in Cohort 3 (N=6), and randomised controlled data have not yet been generated.
Enterome said it is actively seeking partners and investors to fund registrational development. Updated SIDNEY data are due at the Pan Pacific Lymphoma Conference in Hawaii in late July 2026. The company will also attend BIO International Convention in San Diego later this month, where business development discussions are likely to feature prominently.