EO2463 / Enterome - LARVOL DELTA

EO2463 (EO) peptide immunotherapy in patients (pts) with newly diagnosed asymptomatic follicular lymphoma (FL) and marginal zone lymphoma (MZL): Study EONHL1-20/sidney (NCT04669171) primary endpoint lugano objective response analysis (ASH 2025) - P1/2 | "The speed and level of expansion of both EO mimic and B celltarget peptide specific CD8 memory T cells are associated with objective response. Results will beupdated."

Clinical • IO biomarker • Extranodal Marginal Zone Lymphoma • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • CD20 • CD22 • CD4 • CD8 • IFNG • TOP1

EO2463 (EO) peptide immunotherapy combined with rituximab (R) for first-line treatment of low-tumor burden follicular lymphoma (FL): A feasibility evaluation in Study EONHL1-20/sidney (NCT04669171) (ASH 2025) - P1/2 | "In this feasibility cohort all evaluable ptsdeveloped a specific immune response against EO and B cell targets, and a Lugano objective response.The combination of EO and R is feasible and can be evaluated in further trials. Updated results will bepresented at the meeting."

Clinical • IO biomarker • Dermatology • Follicular Lymphoma • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Novel Coronavirus Disease • Oncology • Urticaria • CD20 • CD22 • CD4 • CD8

Enterome presents strengthened interim Phase 2 results for lead OncoMimics immunotherapy EO2463 to treat follicular lymphoma at ASH (GlobeNewswire) - "In Cohort 3, 100% (6/6) ORR was achieved with EO2463 plus rituximab as first-line treatment for previously untreated patients with low tumor-burden follicular lymphoma in need of treatment. In this feasibility assessment among the 6 patients, 5 had a complete response, and one a partial response. The median time to OR was 17 weeks, and to CR 18 weeks....Data from Cohort 2 continue to show that EO2463 monotherapy produces excellent response rates when offered to patients with newly diagnosed follicular lymphoma or marginal zone lymphoma....Previously undisclosed data from 19 evaluable patients with follicular lymphoma showed a 52.6% ORR as of October. The ORR in the total group of 21 patients with follicular lymphoma or marginal zone lymphoma was 47.6% (14.3% CR and 33.3% PR)."

P2 data • Follicular Lymphoma • Marginal Zone Lymphoma

Registrational Phase 3 trial could start in 2026 in the watch-and-wait setting (Yahoo Finance)

New P3 trial • Follicular Lymphoma

Enterome to present positive interim Phase 2 data for lead OncoMimics immunotherapy EO2463 in follicular lymphoma at American Society for Hematology (ASH) meeting (Yahoo Finance) - "New data from cohort 3 show EO2463 can be safely added to rituximab in first-line low-tumor-burden follicular lymphoma in need of treatment; All six patients responded positively to the combination; Overall response data in cohort 2 confirm EO2463 monotherapy produces marked efficacy in patients in watch-and-wait setting"

P2 data • Follicular Lymphoma

EO2463 Peptide Immunotherapy in Patients with Newly Diagnosed Asymptomatic Follicular Lymphoma Results in Monotherapy Objective Clinical Responses Linked with Anti-Peptide Specific CD8 Memory T Cell Responses: The EONHL1-20/Sidney Study (ASH 2024) - P1/2 | "Results will be expanded at the meeting. Study EONHL1-20/SIDNEY also includes cohorts, not covered in this abstract, exploring EO2463 plus rituximab for 1st line FL/MZL, and EO2463 plus lenalidomide/rituximab in relapsed FL/MZL."

Clinical • IO biomarker • Monotherapy • Cognitive Disorders • Dermatology • Fatigue • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • Pruritus • CD20 • CD22 • CD4 • CD68 • CD8 • IFNG • TNFRSF13C

EO2463 Peptide Immunotherapy in Patients with Indolent NHL: A Phase 1 Exploration of a Response Biomarker for EO2463 Monotherapy and EO2463 in Combination with Lenalidomide/Rituximab (ASH 2024) - P1/2 | "Conclusions The current preliminary assessment indicates that direct ex vivo tetramer staining for specific CD8 T cells after short term (5 w) treatment with EO2463 monotherapy could be a possible biomarker for clinical response, both for EO2463 monotherapy response, and for response to EO2463 in combination with lenalidomide/rituximab. We plan to validate these findings in the ongoing study cohorts of the trial; expansion phase 2 cohorts, exploring EO2463 monotherapy in the "watch & wait" setting, EO2463 plus rituximab for 1st line FL/MZL, and EO2463/lenalidomide +/- rituximab in relapsed FL/MZL."

Biomarker • Clinical • Combination therapy • IO biomarker • Monotherapy • P1 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD22 • CD4 • CD68 • CD8 • TNFRSF13C

Enterome receives FDA Fast Track designation in follicular lymphoma for lead OncoMimics immunotherapy EO2463 (GlobeNewswire) - "EO2463 is ready for Phase 3 testing in watch-and-wait patients after showing marked efficacy as a monotherapy in interim data from the watch-and-wait population in the ongoing Phase 2 SIDNEY trial. The treatment was well tolerated, suggesting Enterome’s EO2463 immunotherapy may offer a safe and effective treatment option for patients in this setting, who have been diagnosed with a type of cancer they know is likely to progress, but show no troublesome symptoms and do not usually receive treatment."

Fast track • Follicular Lymphoma

EO2463 (EO) PEPTIDE IMMUNOTHERAPY IN COMBINATION WITH LENALIDOMIDE (L) AND RITUXIMAB (R) IN PATIENTS (PTS) WITH FOLLICULAR (FL) AND MARGINAL ZONE LYMPHOMA (MZL) (ICML 2025) - P1/2 | "EO2463 combined with lenalidomide + rituximab is well tolerated with encouraging clinical activity. The EO2463-driven expansion of BAA-specific CD8 T cells correlates with the complete response probability. Independence between baseline T cell activation potential and immune response indicates that EO2463-induced CD8 T cell expansion occur irrespective of T cell status."

Clinical • Combination therapy • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • CD20 • CD22 • CD4 • CD68 • CD8 • IFNG • TNFRSF13C

Enterome presents positive Phase 2 interim results in relapsed/refractory indolent non-Hodgkin lymphoma after EO2463 OncoMimics immunotherapy treatment at ICML (GlobeNewswire) - P1/2 | N=60 | SIDNEY (NCT04669171) | Sponsor: Enterome | "Enterome SA...presented positive interim results for its OncoMimics immunotherapy EO2463 from Cohorts 1 and 4 of the ongoing open label Phase 1/2 SIDNEY trial in patients with indolent non-Hodgkin lymphoma (iNHL), at the International Conference on Malignant Lymphoma (ICML) in Lugano. Interim data including 24 patients with follicular and marginal zone lymphoma (relapsed/refractory iNHL) showed that treatment with EO2463 in combination with lenalidomide and rituximab (R²) was well tolerated and demonstrated encouraging signs of efficacy that appear better than historical data in similar patients treated with R²....Moreover, once lenalidomide and rituximab were added, the effect of EO2463 appeared to support a deepening of responses, resulting in a complete response rate of 60%, higher than would have been expected with R² alone, based on historical data."

P1/2 data • Follicular Lymphoma • Marginal Zone Lymphoma

Enterome raises $19 million to fund clinical development of its OncoMimics immunotherapy to treat Follicular Lymphoma (GlobeNewswire) - "Enterome SA...has raised $19 million in a new private financing to advance its lead clinical program EO2463 OncoMimics immunotherapy to treat indolent non-Hodgkin lymphoma (iNHL). The new funds will be used to expand and finalize the ongoing Phase 1/2 SIDNEY clinical trial of EO2463 and prepare the candidate for a registrational trial. New U.S. investor The Institute for Follicular Lymphoma Innovation (IFLI), a global non-profit foundation dedicated to advancing research and treatment for follicular lymphoma, invested $9 million in the round, of which $5 million will be allocated to Enterome upon closing and an additional $4 million in conditional tranched funding."

Financing • Follicular Lymphoma

Enterome to present positive Phase 2 indolent non-Hodgkin lymphoma data for its OncoMimics EO2463 at ICML (GlobeNewswire) - "Enterome SA...will present positive data from its Phase 1/2 clinical study with EO2463, its lead clinical program, as monotherapy and in combination with lenalidomide and/or rituximab to treat indolent Non-Hodgkin lymphoma (iNHL) at the International Conference on Malignant Lymphoma (ICML) in Lugano on June 21, 2025.....Separately, Enterome recently held a positive Type-C meeting with the FDA, outlining a clear regulatory path to marketing approval for EO2463 in iNHL after constructive discussion with the regulator."

FDA event • P2 data • Indolent Lymphoma

SIDNEY: A Novel Vaccine (EO2463) as Monotherapy and in Combination, for Treatment of Patients With Indolent Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: Enterome | Trial completion date: Sep 2029 ➔ May 2032 | Trial primary completion date: Jun 2025 ➔ May 2026

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Enterome’s Immunotherapy EO2463 Shows Early Clinical Response in Newly Diagnosed Follicular Lymphoma Suggesting a Potential Alternative to 'Watchful Waiting' (GlobeNewswire) - P1/2 | N=60 | SIDNEY (NCT04669171) | Sponsor: Enterome | "46% objective response rate, with 15% complete responses and 31% partial responses in patients with early-stage follicular lymphoma reported at the ASH 2024 meeting; Well-tolerated treatment with no severe adverse events; Early CD8+ T cell expansion may predict positive clinical outcomes; Findings support EO2463 as a proactive treatment option for asymptomatic patients who typically go untreated."

P1/2 data • Follicular Lymphoma

Enterome to Host Webinar on New Clinical Data From the Ongoing Phase 1/2 ‘SIDNEY’ Trial of Lead Programme, EO2463 (Businesswire) - "Enterome...will be holding a webinar to run through new clinical data from the ongoing Phase 1/2 ‘SIDNEY’ trial of EO2463, for the treatment of patients with either newly diagnosed, previously untreated follicular lymphoma (FL) [EO2463 monotherapy], or FL and marginal zone lymphoma relapsed/refractory disease [EO2463 in combination with lenalidomide/rituximab]."

P1/2 data • Follicular Lymphoma • Hematological Malignancies • Marginal Zone Lymphoma • Oncology

Enterome to Present New Clinical Data and Biomarker Findings for EO2463 at the 2024 American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "These presentations will disclose the first data from Phase 2 Cohort 2, evaluating EO2463 as monotherapy for newly diagnosed patients with asymptomatic follicular lymphoma, where EO2463 may offer a safe, proactive immune therapy alternative to the usual 'watch-and-wait' observation strategy. The data also report initial findings on a biomarker with potential to predict long-term response to EO2463, both as monotherapy, and in combination with standard treatments, in relapsed/refractory iNHL....SIDNEY (EONHL1-20) is a Phase 1/2 multicenter, open-label, first-in-human study of EO2463 as a monotherapy and in combination with lenalidomide and/or rituximab for the treatment of patients with iNHL."

Biomarker • P2 data • Follicular Lymphoma • Non-Hodgkin’s Lymphoma

Phase 1/2 of EO2463 immunotherapy as monotherapy and in combination with lenalidomide and/or rituximab in indolent NHL (EONHL1-20/SIDNEY). (ASCO 2024) - P1/2 | "EO2463 (300 μg/peptide) monotherapy, EL, and ER 2 are well tolerated, with encouraging clinical activity with EO2463 monotherapy and with subsequent CR in 5/9 pts on combo. Rapid and durable expansion of specific CD8+ T cells was seen in all responding pts, consistent with the preclinical hypothesis. Additional cohorts investigate EO2463 alone or in combination in newly diagnosed or R/R pts."

Combination therapy • IO biomarker • Monotherapy • P1/2 data • Indolent Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • CD22 • CD4 • CD68 • CD8 • TNFRSF13C

Enterome Highlights High Complete Response Rate in Clinical Study of EO2463 for Indolent Non-Hodgkin Lymphoma at ASCO 2024 (GlobeNewswire) - P1/2 | N=60 | SIDNEY (NCT04669171) | Sponsor: Enterome | "Enterome...announces updated immune-monitoring and clinical data from the ongoing EONHL1-20/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 3rd, 2024, at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, USA....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)."

P1/2 data • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Enterome to Present Clinical Data on EO2463 in B-cell Lymphoma at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - "Enterome...today announced that clinical data from the ongoing Phase 1/2 trial of EO2463 in monotherapy and in combination with lenalidomide and/or rituximab in indolent non-Hodgkin lymphoma (NHL) will be presented at 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, to take place May 31 - June 4, in Chicago, Illinois."

P1/2 data • Follicular Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma

SIDNEY: A Novel Vaccine (EO2463) as Monotherapy and in Combination, for Treatment of Patients With Indolent Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: Enterome | Trial primary completion date: Sep 2024 ➔ Jun 2025

Combination therapy • Monotherapy • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Novel immunotherapy based on commensal-derived peptides to drive an effective CD8 T Cell response against selected tumor-associated antigens (TAAs) (SITC 2023) - "Further support for this approach comes from ongoing clinical trials, since we displayed that CD8+ T cells from indolent Non-Hodgkin Lymphoma (iNHL) patients treated with EO2463 immunotherapy (SIDNEY, EONHL1–20 phase 1/2 trial) are cytotoxic against TAA protein-expressing tumor cell lines. 1 Conclusions These data provide compelling evidence that OncoMimic peptides sharing a high degree of homology with TAAps can be utilized to generate an effective anti-tumor immune response."

IO biomarker • Adrenal Cortex Carcinoma • Brain Cancer • CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • CD8

Enterome Selected to The Leukemia & Lymphoma Society’s Therapy Acceleration Program (GlobeNewswire) - "Enterome...announced that it received a €3 million investment from The Leukemia & Lymphoma Society’s Therapy Acceleration Program^® (LLS TAP). The funding will propel the Company’s ongoing Phase 2 SIDNEY study of EO2463 in indolent non-Hodgkin B-cell lymphoma (iNHL)."

Financing • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Enterome's new OncoMimics immunotherapy, EO2463, demonstrates early efficacy and favorable safety in Phase 1/2 trial for indolent non-Hodgkin lymphoma (GlobeNewswire) - P1/2 | N=60 | SIDNEY (NCT04669171) | Sponsor: Enterome | "Enterome...announces first clinical results from the Phase 1/2 (EONHL1-20/SIDNEY) trial of EO2463, an experimental treatment for indolent non-Hodgkin B cell lymphoma (iNHL)....EO2463 appears well tolerated as a monotherapy, and without additional safety signals when combined with lenalidomide and rituximab. Clinical activity (metabolic marker/tumor size reduction) observed in 4 of 9 (44%) patients after 6 weeks on EO2463 monotherapy and encouraging preliminary complete response rate on EO2463 combination therapy (50% in patients evaluable after 19 weeks). Expansion of specific CD8+ T cells against the OncoMimic™ peptides and targeted B cell antigens was detected in 6 of 8 tested patients, including in 2 patients with no measurable B cells at baseline."

P1/2 data • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Phase 1 trial of EO2463 peptide-based immunotherapy as monotherapy and in combination with lenalidomide and rituximab in indolent non-Hodgkin lymphoma; EONHL1-20/SIDNEY (ICML 2023) - P1/2 | "EO2463 is well tolerated as monotherapy, and without additional safety signals when combined with lenalidomide and rituximab. We find evidence of on-target immune activation, and preliminary complete response rate is encouraging. Expanded data to be presented."

Combination therapy • Monotherapy • P1 data • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD22 • CD4 • CD68 • CD8 • HLA-B • TNFRSF13C

A MULTICENTER PHASE 1/2 TRIAL OF EO2463, A MICROBIAL-DERIVED PEPTIDE THERAPEUTIC VACCINE, AS MONOTHERAPY AND IN COMBINATION WITH LENALIDOMIDE AND RITUXIMAB, FOR TREATMENT OF PATIENTS WITH INDOLENT NHL (EHA 2022) - "Results The safety lead-in dose-finding is currently ongoing, and no safety concerns have been observed thus far. Conclusion This is a first in human clinical trial to evaluate safety, determine the recommended phase 2 dose and estimate efficacy of a novel microbial-derived peptide therapeutic vaccine, EO2463, in patients with indolent non-hodgkin lymphoma as monotherapy and in combination with lenalidomide and rituximab."

Clinical • Combination therapy • Monotherapy • P1/2 data • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD22 • CD4 • CD68 • CD8 • TERT • TNFRSF13C