CD8 T-Cell Expansion With EO2463 Tied to PFS in Indolent NHL

Interim data from the phase 1/2 SIDNEY trial (NCT04669171) suggest that EO2463, an off-the-shelf active immunotherapy, induced CD8 T-cell expansion that correlated significantly with progression-free survival (PFS) in patients with indolent non-Hodgkin lymphoma (iNHL) managed in the watch-and-wait setting.¹

In the EO2463 monotherapy cohort consisting of patients with iNHL under \observation, greater magnitude of CD8 T-cell expansion was significantly associated with longer PFS (HR, 0.18; 95% CI, 0.03-0.82; log-rank P =.020). In a separate cohort of patients with relapsed/refractory iNHL treated with EO2463 in combination with lenalidomide (Revlimid) and rituximab (Rituxan; R2), higher CD8 T-cell expansion was significantly associated with complete response rate (P =.0073). The data were presented at the Pan Pacific Lymphoma Conference.

“The correlation between the robust CD8 T-cell expansion induced by EO2463 and PFS is a landmark finding that creates an imperative for further study and offers new hope for patients suffering from iNHL. It suggests that EO2463, which has been well-tolerated to date, may effectively extend PFS as a standalone therapy without hurting quality of life in this generally older and fragile patient population,” said Pierre Belichard, CEO of EO2463 developer Enterome, in a news release.¹ “We want to prioritize patients classified for watch-and-wait, an observational protocol, because they currently receive no active treatment, despite having to live with the grave psychological impact of their cancer diagnosis.”

The findings extend earlier biomarker analyses from SIDNEY, an ongoing open-label trial evaluating the safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 as monotherapy and in combination regimens in patients with follicular lymphoma and marginal zone lymphoma.² The study includes a dedicated watch-and-wait monotherapy cohort, a first-line low-tumor-burden combination cohort with rituximab, and relapsed/refractory cohorts treated with the combination of EO2463 plus R2.

The Unmet Need in Indolent NHL

Few effective options exist for altering the natural history of iNHL, a disease that typically progresses slowly and causes limited symptoms early on but is not considered curable with current therapies. For patients with low-tumor-burden, asymptomatic disease, observation until progression, or “watch-and-wait,” is the standard management approach. This approach leaves a substantial population without any active anticancer intervention, highlighting a need for treatments that could delay progression while sparing patients—who are often older and less tolerant of intensive regimens—from added toxicity.

About EO2463 and Next Steps

EO2463 is developed with sponsor Enterome’s proprietary OncoMimics™ platform and composed of 4 synthetic microbial-derived peptides designed to mimic the B-cell lineage markers CD20, CD22, CD37, and BAFF receptor (CD268), combined with a helper peptide. Its mechanism of action is intended to expand preexisting memory CD8 T cells, target malignant B cells, broaden antigen coverage, and reduce the potential for antigen escape.

In May 2026, the agent was awarded orphan drug designation by the FDA in recognition of its potential to address rare diseases in the United States, conferring 7 years of market exclusivity upon approval. It also holds an FDA fast track designation in follicular lymphoma, granted in October 2025.

Taken together, the SIDNEY data reported to date—spanning objective response rate in the watch-and-wait cohort, complete response rate in the combination cohorts, and now PFS in the monotherapy setting—support continued evaluation of EO2463-induced CD8 T-cell expansion as a predictive biomarker of clinical benefit in iNHL. Enterome has stated its intention to advance EO2463 into registrational development for patients with iNHL managed under watch-and-wait.

REFERENCES

1. Enterome Phase 2 data show EO2463-induced CD8 T-cell expansion correlates with progression-free survival in patients with indolent non-Hodgkin lymphoma in the watch-and-wait setting. News release. Enterome. July 21, 2026. Accessed July 21, 2026. https://tinyurl.com/kttj9avd

2. A Novel Vaccine (EO2463) as Monotherapy and in Combination, for Treatment of Patients With Indolent Non-Hodgkin Lymphoma (SIDNEY). ClinicalTrials.gov. Updated January 30, 2026. Accessed July 21, 2026. https://www.clinicaltrials.gov/study/NCT04669171