Enterome has unveiled positive interim results from its ongoing Phase I/II SIDNEY trial evaluating EO2463, its immunotherapy, in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL).

Presented at the International Conference on Malignant Lymphoma (ICML) in Lugano, the data showed that 60% of patients achieved a complete response when EO2463 was combined with the standard R2 regimen (lenalidomide and rituximab).

The promising results bolster Enterome’s case for advancing EO2463 into late-stage development, backed by a fresh $19 million private financing round raised earlier this month to support clinical expansion. The company plans to launch a Phase III registrational trial targeting a “watch-and-wait” iNHL patient population while continuing to explore EO2463’s efficacy in relapsed or refractory settings.

“The EO2463 interim results are very encouraging,” said Enterome CEO Pierre Belichard. “They show exceptional tolerability and a clear complementary effect when combined with R2, suggesting a more robust response than R2 alone. These results offer new hope for patients who still experience suboptimal outcomes with existing therapies.”

HowEO2463 Works

EO2463 is an off-the-shelf, active immunotherapy leveraging Enterome’s proprietary OncoMimics technology. It consists of four synthetic peptides derived from microbial proteins that mimic B cell-specific antigens—CD20, CD22, CD37, and CD268 (BAFF receptor)—plus a universal cancer helper peptide (UCP2). This combination is designed to expand existing memory CD8+ T cells that recognize these bacterial mimic epitopes, triggering a targeted immune response against malignant B lymphocytes.

Interim data from the SIDNEY trial show that EO2463 drives rapid and sustained expansion of specific CD8+ T cells reactive to its synthetic peptides. Importantly, the magnitude of this T cell response correlated with the likelihood of complete remission, reinforcing the biological relevance of the therapy’s mechanism.

“The fast, robust, and durable expansion of EO2463-specific T cells—and the observed correlation with remission—are key indicators of the immunotherapy’s clinical potential,” noted Jan Fagerberg, Chief Medical Officer at Enterome. “Taken together, the SIDNEY data suggest broad potential for EO2463 across various hematologic malignancies.”

SIDNEY Trial Design and Interim Outcomes

SIDNEY is an open-label Phase I/II trial (NCT04669171) designed to assess EO2463’s safety, immunogenicity, and preliminary efficacy in up to 55 patients with follicular or marginal zone lymphoma. It includes four patient cohorts, stratified by treatment history and tumor burden:

• Cohorts 1 & 4: Patients with relapsed/refractory disease and at least one prior treatment; treated with EO2463 plus lenalidomide and rituximab (R2)
• Cohort 2: Patients with newly diagnosed, untreated low tumor burden iNHL, managed under a “watch-and-wait” approach; treated with EO2463 monotherapy
• Cohort 3: Patients with newly diagnosed low tumor burden disease in need of treatment; treated with EO2463 plus rituximab

The recently presented interim results focus on 24 patients from Cohorts 1 and 4 with relapsed/refractory follicular and marginal zone lymphoma. Among the 20 patients evaluated for efficacy, 12 (60%) achieved a complete response. Notably, the combination therapy was well tolerated, with no unexpected safety issues.

Enterome noted that a particularly significant observation is the partial responses to EO2463 monotherapy in the first six weeks of treatment—before lenalidomide and rituximab were introduced—suggesting that EO2463 itself possesses intrinsic anti-lymphoma activity. Following the addition of R2, the depth of responses improved, supporting the hypothesis of a synergistic effect.

These response rates appear to exceed historical outcomes associated with R2 therapy alone, which typically yield lower complete remission rates in similar patient populations, according to the company. This makes the EO2463 plus R2 combination a compelling candidate for future clinical development in the relapsed/refractory iNHL setting.