Enterome's EO2463 Achieves 100% Response Rate in Follicular Lymphoma Phase 2 Trial
核心洞察
Enterome's OncoMimics (搜索)™ immunotherapy EO2463 achieved a 100% objective response rate (6/6 patients) when combined with rituximab in previously untreated follicular lymphoma (搜索) patients, with 5 complete responses and 1 partial response.
The SIDNEY Phase 2 trial also demonstrated a 52.6% objective response rate with EO2463 monotherapy in follicular lymphoma (搜索) patients in the watch-and-wait setting, offering an alternative to standard watchful waiting.
EO2463 represents a novel off-the-shelf immunotherapy that targets multiple B-cell markers (CD20 (搜索), CD22 (搜索), CD37 (搜索), CD268 (搜索)) through bacteria-derived peptides that mimic tumor antigens and expand memory T-cells.
Enterome presented highly encouraging interim Phase 2 data for its lead OncoMimics (搜索)™ immunotherapy EO2463 at the 67th American Society for Hematology (ASH) meeting in Orlando, Florida. The SIDNEY trial demonstrated remarkable efficacy in treating follicular lymphoma (搜索) patients across two distinct treatment settings.
Exceptional Response Rates in First-Line Treatment
In Cohort 3 of the SIDNEY trial, EO2463 combined with rituximab achieved a 100% objective response rate (6/6 patients) in previously untreated patients with low tumor-burden follicular lymphoma (搜索) requiring treatment. Among these six patients, five achieved complete responses and one achieved a partial response. The median time to objective response was 17 weeks, with complete responses occurring at a median of 18 weeks.
"These new results are encouraging, despite the limited number of patients. The potent and rapid expansion of specific CD8 T-cells induced by EO2463 supports our understanding that OncoMimics (搜索)™ trigger memory T-cells to generate sustained immune responses," said Dr. Stephen Smith, principal study investigator at the Fred Hutchinson Cancer Center, University of Washington, who presented the data.
Promising Monotherapy Results in Watch-and-Wait Setting
Cohort 2 evaluated EO2463 monotherapy as an alternative to the standard watch-and-wait approach in newly diagnosed patients. Previously undisclosed data from 19 evaluable patients with follicular lymphoma (搜索) showed a 52.6% objective response rate as of October. In the total group of 21 patients with follicular lymphoma or marginal zone lymphoma (搜索), the objective response rate was 47.6%, comprising 14.3% complete responses and 33.3% partial responses.
Current standard practice involves watchful waiting for patients with visibly swollen lymph nodes who lack troublesome symptoms. However, these patients often experience anxiety about their disease, which progresses in the majority of cases and leads to decreased quality of life.
Novel Mechanism of Action
EO2463 represents an innovative off-the-shelf OncoMimics (搜索)™ active immunotherapy combining four synthetic peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that exhibit molecular mimicry with B lymphocyte-specific lineage markers CD20 (搜索), CD22 (搜索), CD37 (搜索), and CD268 (搜索) (BAFF receptor (搜索)). The therapy also includes the helper peptide universal cancer peptide 2 (UCP2).
The unique ability of EO2463 to selectively target multiple B-cell markers enables destruction of malignant B lymphocytes while ensuring broad target coverage across malignant B cells. This approach aims to simultaneously improve safety and maximize efficacy while reducing tumor cells' capacity to develop immune-resistance mechanisms such as antigen escape.
OncoMimics™ Platform Technology
OncoMimics (搜索)™ consist of bacteria-derived peptide antigens that closely mimic tumor-associated antigens or cell lineage markers. These antigens induce fast and potent in vivo expansion of cytotoxic memory CD8+ T cells that were primed by gut bacteria and are cross-reactive with tumor antigens and B-cell markers. Because the peptides are "non-self," OncoMimics™ avoid the self-tolerance that limits many cancer immunotherapies, enabling rapid, potent, and durable responses to tumors.
The synthetically produced peptides are designed in silico, mining Enterome's proprietary database of 23 million commensal bacteria genes. Each product combines multiple high-affinity peptides to broaden target coverage and mitigate tumor heterogeneity.
Clinical Development Progress
OncoMimics (搜索)™ are administered as off-the-shelf subcutaneous injections that are easy to manufacture, store, and distribute. The platform has achieved rapid and potent responses in clinical testing across over 230 patients to date, demonstrating a benign safety profile.
"These new data with EO2463 contribute more compelling evidence and further strengthen our belief in the potential of our OncoMimics (搜索)™ multi-targeted in vivo immune therapies for blood cancers. I'm looking forward to initiating Phase 3 testing of EO2463 in patients in the watch-and-wait setting in 2026," said Pierre Belichard, CEO of Enterome.
Addressing Unmet Medical Need
Follicular lymphoma (搜索), one of several types of indolent Non-Hodgkin lymphoma (搜索), is a difficult-to-treat chronic condition characterized by relapses, slow progression, few symptoms, and reduced life expectancy. The disease is usually diagnosed by the appearance of swollen lymph nodes, with early stages characterized by a lack of troublesome symptoms such as night sweats, fever, or weight loss.
There is widespread consensus among leading investigators on the need for a well-tolerated and effective monotherapy to stop or slow progression for patients in the watch-and-wait setting. Enterome's three most advanced OncoMimics (搜索)™ product candidates have shown positive early data in Phase 2 clinical development across solid tumors and hematological malignancies, demonstrating correlation between clinical efficacy and induced immunogenicity.