The US Food and Drug Administration has granted Orphan Drug Designation to EO2463 immunotherapy for the treatment of patients with indolent non-Hodgkin lymphoma (iNHL) in the low-tumor-burden, “watch-and-wait” setting.
EO2463 is composed of four synthetic microbial-derived peptides designed to mimic the B-cell lineage markers CD20, CD22, CD37 and CD268 (BAFF receptor), plus the helper peptide UCP2.
The designation was based on data from SIDNEY, an ongoing open-label phase 1/2 study evaluating the safety, tolerability, immunogenicity and preliminary efficacy of EO2463 as monotherapy and in combination regimens in up to 55 patients with follicular lymphoma and marginal zone lymphoma. The trial includes a dedicated watch-and-wait monotherapy cohort, a first-line low-tumor-burden combination cohort with rituximab, and relapsed/refractory cohorts treated with EO2463 plus lenalidomide and rituximab.
In October 2025, EO2463 received the FDA Fast Track designation for follicular lymphoma in the watch-and-wait setting.
Data from SIDNEY suggest that EO2463 is particularly well suited for watch-and-wait iNHL patients because it has been well tolerated in clinical testing and has shown potentially disease modifying monotherapy activity in patients who generally are not eligible to receive anti-lymphoma treatment under current practice until their disease progresses.
In the low-tumor-burden watch-and-wait population of SIDNEY cohort 2, EO2463 monotherapy produced a 52.6% objective response rate in 19 evaluable patients with follicular lymphoma and a 47.6% objective response rate in the overall group of 21 evaluable patients with follicular lymphoma or marginal zone lymphoma, including 14.3% complete responses and 33.3% partial responses.
Outside of the watch-and-wait cohort, EO2463 combined with lenalidomide and rituximab achieved a 60% complete response rate in 20 patients with relapsed/refractory follicular and marginal zone lymphoma, was well tolerated, and showed CD8 T-cell expansion correlating with the probability of complete remission.
According to Enterome, the manufacturer of EO2463, the drug’smulti-target approach is intended to expand pre-existing memory CD8 T cells, selectively target malignant B cells, broaden target coverage and reduce the risk of antigen escape.
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