• Beneficial clinical responses observed with EO2463 monotherapy already at 6 weeks and complete response rate of 78% in patients treated with EO2463 upon addition of lenalidomide ± rituximab
• EO2463 rapidly expands memory CD8⁺ T cells specific for OncoMimics^™ peptides and B cell antigens evoking a fast and robust cytotoxic response that is maintained for up to 94 weeks
• Expansion cohort evaluating EO2463 monotherapy in the “watch-and-wait” setting ongoing with initial results expected by end of 2024

 Paris, France – May 24^th, 2024

Enterome, a clinical-stage company developing first-in-class immunomodulatory drugs for solid and liquid malignancies and inflammatory diseases based on its unique Mimicry platform, today announces updated immune-monitoring and clinical data from the ongoing EOHNL1-20/SIDNEY trial evaluating EO2463 in monotherapy and in combination with lenalidomide and/or rituximab in indolent non-Hodgkin lymphoma (NHL). The results will be featured in a poster session on Monday, June 3^rd, 2024, at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, USA.

“We are extremely encouraged by these results, which validate our OncoMimics^™ approach to targeting liquid tumors,” said Dr. Jan Fagerberg, Chief Medical Officer of Enterome. “In addition to the standalone activity seen with EO2463 during the first six weeks of treatment, the 78% complete response rate observed with the subsequent combination therapy supports our belief that EO2463 can significantly add to the patients’ care. Thanks to its unique safety and efficacy profiles, we believe EO2463 has the potential to become a valuable long-term treatment option for non-Hodgkin B cell lymphomas.”

Pierre Bélichard, CEO of Enterome, added: “Building on the promising findings that are presented at ASCO 2024, we look forward to continuing the SIDNEY trial and reporting results from the monotherapy expansion cohort which focuses on the “watch-and-wait” setting. Despite a confirmed cancer diagnosis and being ultimately likely to progress to symptomatic condition, a large portion of patients with indolent Follicular Lymphoma and Marginal Zone Lymphoma are not receiving immediate treatment due to the absence of safe and effective therapies. EO2463 appears ideally suited to address this significant unmet medical need.”

Key Highlights from the EONHL1-20/SIDNEY presentation, entitled Phase 1/2 of EO2463 immunotherapy as monotherapy and in combination with lenalidomide and/or rituximab in indolent NHL:

The Phase 1/2 EONHL1-20/SIDNEY evaluates the safety and preliminary efficacy of EO2463 as monotherapy and in combination with lenalidomide and/or rituximab for the treatment of patients with indolent NHL. Patients in cohort 1 received EO2463 once every two weeks for a total of four doses followed by once every four weeks for up to 15 doses. After 6 weeks of EO2463 monotherapy oral lenalidomide was added, and if no complete remission was achieved at week 19, rituximab was also included.

• EO2463 was well-tolerated with no grade ≥3 related events in monotherapy (events attributed to EO2463 only were local administration site reactions and headache)
• Metabolic marker/tumor size reduction observed in 4 of 9 patients (44%) at week 6 on EO2463 monotherapy
• Complete Response rate in 7 of 9 patients (78%) achieved on combination therapy (response assessment per Lugano, 2014, and Lyric, 2016, Classifications), including 5 radiologic complete responses (56% radiologic CRs)
• Expansion of specific CD8+ T cells against the OncoMimics^™ peptides and targeted B cell antigens in a significant portion of patients with up to 5.3% of all peripheral blood CD8⁺ T cells being specific for OncoMimics^™ peptides
  • Specific CD8⁺ T cells could be detected ex vivo early as well as in long-term follow-up, currently until 94 weeks after the study treatment start
  • On-target immune activation observed with cytotoxic T cells of memory phenotype, remaining polyfunctional long-term
• Study ongoing with three extension cohorts:
  • EO2463 monotherapy in patients with newly diagnosed, previously untreated follicular lymphoma (FL) or marginal zone lymphoma (MZL), not in need of therapy (“watch-and-wait” setting)
  • EO2463 + rituximab (from week 7) in patients with newly diagnosed, previously untreated FL/MZL and low tumor burden, in need of therapy, and
  • EO2463 + lenalidomide (from week 1) + rituximab (from week 19) in patients with relapsed/refractory, previously treated FL/MZL

 

Presentation details:

Title: Phase 1/2 of EO2463 immunotherapy as monotherapy and in combination with lenalidomide and/or rituximab in indolent NHL (EONHL1-20/SIDNEY)

Presenting Author: J.C. C. Villasboas, M.D., Division of Hematology, Mayo Clinic

Session Name: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Session Date and Time: June 3^rd, 9:00 AM-12:00 PM CDT

Abstract #7058 is available here and the Poster will be available on Enterome’s website following the session.

About Phase 1/2 SIDNEY

SIDNEY (EONHL1-20) is a Phase 1/2 multicenter, open-label, first-in-human study of EO2463 as monotherapy and in combination with lenalidomide and/or rituximab for the treatment of patients with indolent non-Hodgkin lymphoma (NHL). The study aims to assess the safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 monotherapy and combination therapy in approximately 60 patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL). For more information on the study, refer to Clinicaltrials.gov identifier: NCT04669171.

About Indolent non-Hodgkin lymphoma (iNHL)

Non-Hodgkin lymphoma is the seventh most common cause of new cancer cases among both men and women, accounting for 4% to 5% of new cancer cases, and 3% to 4% of cancer-related deaths. Indolent non-Hodgkin lymphoma (iNHL) constitutes a distinct subset where, even though currently available treatments are efficacious, the main disease subtypes, such as follicular lymphoma (FL) and marginal zone lymphoma (MZL), are considered non-curable in most patients. Thus, novel therapeutic approaches are still needed to enhance treatment outcomes and limit or delay the use of potentially more toxic therapies.

About EO2463:

EO2463 is an innovative, off-the-shelf immunotherapy candidate that combines four synthetic OncoMimic™ peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that exhibit molecular mimicry with the B lymphocyte-specific lineage markers CD20, CD22, CD37, and CD268 (BAFF receptor). EO2463 also includes the helper peptide (CD4+ epitope) universal cancer peptide 2 (UCP2). The unique ability of EO2463 immunotherapy to selectively target multiple B cell markers enables the destruction of malignant B lymphocytes that are abundant in NHL. By ensuring broad target coverage across malignant B cells while avoiding a detrimental impact on normal peripheral B cells, this novel approach aims to simultaneously improve safety and maximize efficacy, reducing the tumor cells’ capacity to develop immune escape mechanisms.

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