FDA Orphan Drug Status Awarded to EO2463 in Indolent Non-Hodgkin Lymphoma

The FDA has granted orphan drug designation (ODD) to EO2463, a cancer peptide therapeutic vaccine, for the treatment of patients with indolent non-Hodgkin lymphoma (NHL) in the low-tumor-burden, watch-and-wait setting, according to a news release from Enterome.¹

EO2463, developed with sponsor Enterome’s proprietary OncoMimics™ platform, is an off-the-shelf, multitargeted active immunotherapy. It comprises 4 synthetic, microbial-derived peptides that mimic the B-cell lineage markers CD20, CD22, CD37, and CD268 (BAFF receptor), along with the helper peptide universal cancer peptide 2 (UCP2). The agent is intended to expand preexisting memory CD8 T cells, selectively target malignant B cells, broaden target coverage, and reduce the risk of antigen escape.

The ODD builds on a previous FDA fast track designation granted to EO2463 in follicular lymphoma (FL), granted in October 2025.

“Receiving FDA [o]rphan [d]rug [d]esignation is an important regulatory milestone for EO2463 and reaffirms our strong commercial potential,” Pierre Belichard, PhD, PharmD, MBA, CEO of Enterome, stated in a news release.¹ “Together with the [f]ast [t]rack designation granted late last year, FDA’s ODD further facilitates and validates our efforts to advance EO2463 toward registrational development in the watch-and-wait population. We are actively engaging with potential partners and investors to find the best path forward to rapidly advance EO2463 development in this indication.”

The ODD confers several regulatory and financial advantages to Enterome, including 7 years of market exclusivity in the United States upon potential marketing approval. The designation applies to therapies for rare diseases affecting fewer than 200,000 people in the United States.

Unmet Need in the Watch-and-Wait Approach

Indolent NHL, including FL and marginal zone lymphoma (MZL), is characterized by slow progression and, in early stages, limited symptoms. Current standard practice for patients with low–tumor burden asymptomatic disease involves observation without active treatment until symptoms or other criteria for intervention emerge, a strategy commonly referred to as “watch-and-wait.” Despite favorable near-term tolerability, this approach leaves patients without disease-modifying therapy during a period of documented psychological burden.

“Today, the only option for non-symptomatic low tumor burden “watch-and-wait” patients [with indolent NHL] is to go without treatment and be observed until the cancer progresses,” Belichard stated in the news release.¹ “We believe this places undue stress on patients and their families and is unacceptable; it is gratifying to see the US regulatory agency recognizes that ‘watch-and-wait’ patients deserve a real treatment option like EO2463.”

SIDNEY Trial Design and Upcoming Clinical Data

The regulatory milestone is supported by data from the ongoing SIDNEY trial (NCT04669171), an 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 FL and MZL.²

The trial includes a dedicated watch-and-wait monotherapy cohort, a first-line low–tumor burden combination cohort with rituximab (Rituxan), and relapsed/refractory cohorts treated with EO2463 plus lenalidomide (Revlimid) and rituximab.

Additional phase 2 data for EO2463 from the SIDNEY trial will be presented in a poster session at the upcoming 2026 European Hematology Association (EHA) Congress in June, where the sponsor has reported encouraging activity with the agent, including rapid induction of in vivo expansion of B-cell–target-specific CD8 T cells.³

REFERENCES

1. Enterome receives U.S. FDA Orphan Drug Designation for EO2463 OncoMimics™ to treat “watch-and-wait” indolent non-Hodgkin lymphoma. News release. Enterome. May 28, 2026. Accessed May 28, 2026. https://tinyurl.com/3af6pxv5

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 May 28, 2026. https://www.clinicaltrials.gov/study/NCT04669171

3. Enterome presents Phase 2 indolent non-Hodgkin lymphoma data at EHA showing EO2463 induces B cell target-specific CD8 T-cell expansion correlating with clinical outcomes. News release. Enterome. May 12, 2026. Accessed May 28, 2026. https://tinyurl.com/yc676y66