EO2401 / Enterome - LARVOL DELTA

EO2401 peptide immunotherapy + nivolumab +/- bevacizumab in first recurrent glioblastoma: treatment strategy optimization in the phase 1/2 study EOGBM1-18 / ROSALIE (NCT04116658) (SNO 2025) - P1/2 | "For external validation, application of the same model to the CM-143 dataset (1st glioblastoma progression randomized to nivolumab [n=83] vs bevacizumab [n=77]) revealed no associations with OS for bevacizumab while MGMT status (HR=1.95, 95%-CI 1.12–3.17, p=0.007) and baseline corticosteroid use (HR=2.30, 95%-CI 1.42–3.71, p=0.001) associated with OS for nivolumab. Our data indicate that a randomized trial further evaluating EO2401 is warranted and also suggest that surgery prior to triplet therapy, along with baseline dexamethasone use, should be further investigated."

P1/2 data • Brain Cancer • Glioblastoma • Solid Tumor • BIRC5 • CD8 • FOXM1 • IL13RA2 • MGMT

Enterome…announces new survival analyses from Cohort 3 of the Phase 1/2 ROSALIE clinical trial (GlobeNewswire) - "The data were reported at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting....The analyses demonstrated a statistically significant survival benefit for patients who underwent a second surgery after their first glioblastoma recurrence when treated with EO2401 in combination with nivolumab and bevacizumab, compared with patients who did not undergo surgery (p = 0.027). Importantly, no survival benefit was observed for the supportive therapies, nivolumab or bevacizumab on a stand-alone basis after surgery, compared with no surgery."

P1/2 data • Glioblastoma

EO2401 peptide immunotherapy + nivolumab +/- bevacizumab in first recurrent glioblastoma: treatment strategy optimization in the phase 1/2 study EOGBM1-18 / ROSALIE (NCT04116658) (WFNOS 2025) - P1/2 | "For external validation, application of the same model to the CM-143 dataset (1st glioblastoma progression randomized to nivolumab [n=83] vs bevacizumab [n=77]) revealed no associations with OS for bevacizumab while MGMT status (HR=1.95, 95%-CI 1.12–3.17, p=0.007) and baseline corticosteroid use (HR=2.30, 95%-CI 1.42–3.71, p=0.001) associated with OS for nivolumab. Our data indicate that a randomized trial further evaluating EO2401 is warranted and also suggest that surgery prior to triplet therapy, along with baseline dexamethasone use, should be further investigated."

P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Solid Tumor • BIRC5 • CD8 • FOXM1 • IL13RA2 • MGMT

EO4010 (EO) + nivolumab (N) ± bevacizumab (B) in patients (pts) with microsatellite stable (MSS) metastatic colorectal carcinoma (mCRC) (ESMO-IO 2024) - P1/2 | "This phase 1/2 trial, EOCRC2-22, assesses safety and efficacy of EO + N ± B in MSS mCRC based on clinical effects in other MSS tumors by EO2401, a similar compound to EO.Methods Pts were HLA-A2 and had MSS mCRC, previously treated with FU, oxaliplatin, irinotecan and anti-VEGF/EGFR. In C3, 3 SD (2 ongoing w13/w16; 1 normalized CEA) and 2 PD in TLs.Conclusions EO4010 + N promotes expansion of TAA specific CD8 T cells and shows good safety and interesting preliminary efficacy in previously treated MSS mCRC. B can be safely added and might improve efficacy."

Clinical • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BIRC5 • CA 19-9 • CD4 • CD8 • CDC20 • EGFR • FOXM1 • KIF2C • UBE2C

ROSALIE: First-in-Human, Phase 1b/2a Trial of a Multipeptide Therapeutic Vaccine in Patients With Progressive Glioblastoma (clinicaltrials.gov) - P1/2 | N=100 | Completed | Sponsor: Enterome | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Mar 2024 | Trial primary completion date: Dec 2024 ➔ Jan 2024

Trial completion • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Spencer: A Novel Therapeutic Vaccine (EO2401) in Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma (clinicaltrials.gov) - P1/2 | N=70 | Terminated | Sponsor: Enterome | Active, not recruiting ➔ Terminated; Strategic decision

Checkpoint block • Combination therapy • Metastases • Trial termination • Adrenal Cortex Carcinoma • CNS Tumor • Endocrine Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Spencer: A Novel Therapeutic Vaccine (EO2401) in Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma (clinicaltrials.gov) - P1/2 | N=70 | Active, not recruiting | Sponsor: Enterome | Trial completion date: Nov 2025 ➔ Oct 2024

Checkpoint block • Combination therapy • Metastases • Trial completion date • Adrenal Cortex Carcinoma • CNS Tumor • Endocrine Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

EO2401, a novel immunotherapy, plus nivolumab induces a strong and robust immune response in patients with recurrent glioblastoma (CIMT 2024) - P1/2 | "Methods Patients with GBM at first progression after standard treatment received EO2401 with nivolumab ± bevacizumab. Commensal-derived peptides with molecular mimicry to TAAs lead to the expansion of commensal-specific CD8+ T cells which cross-react with homologous TAAs. This is a promising approach to generate broad immune responses in tumors with low neoantigen expression and poor T cell priming, as is the case of GBM."

Clinical • IO biomarker • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • B3GAT1 • BIRC5 • CD4 • CD8 • FOXM1 • IFNG • IL13RA2 • LAG3 • PD-1

Enterome Announces Successful Completion of Phase 2 ROSALIE Study of EO2401 in Recurrent Glioblastoma (GlobeNewswire) - P1b/2a | N=100 | ROSALIE (NCT04116658) | Sponsor: Enterome | "EO2401, a pioneering OncoMimics peptide-based immunotherapy, has demonstrated rapid activation and significant expansion of existing effector memory T cells against tumor-associated driver antigens due to their strong cross-reactivity with OncoMimics peptides; Clinical benefits were observed in approximately one-third of patients (vs. one-tenth with Standard of Care); The full results are expected to be presented in a peer-reviewed journal by the end of 2024....Enterome...announced database lock of its Phase 2 study of EO2401, in combination with an immune checkpoint inhibitor (nivolumab) +/- an anti-VEGF therapy (bevacizumab), for the treatment of patients with recurrent glioblastoma (EOGBM1-18/ROSALIE trial)."

P2a data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

ROSALIE: First-in-Human, Phase 1b/2a Trial of a Multipeptide Therapeutic Vaccine in Patients With Progressive Glioblastoma (clinicaltrials.gov) - P1/2 | N=100 | Active, not recruiting | Sponsor: Enterome | Phase classification: P1b/2a ➔ P1/2

Phase classification • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Spencer: A Novel Therapeutic Vaccine (EO2401) in Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma (clinicaltrials.gov) - P1/2 | N=70 | Active, not recruiting | Sponsor: Enterome | Recruiting ➔ Active, not recruiting | N=120 ➔ 70 | Trial completion date: Dec 2024 ➔ Nov 2025

Enrollment change • Enrollment closed • Trial completion date • Adrenal Cortex Carcinoma • CNS Tumor • Endocrine Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Enterome’s OncoMimics Immunotherapy EO2401 Significantly Improves Survival Rate in Recurrent Glioblastoma (GlobeNewswire) - P1b/2a | N=100 | ROSALIE (NCT04116658) | Sponsor: Enterome | "Enterome...announced updated efficacy data from its Phase 1/2 clinical trial of EO2401, in combination with an immune checkpoint inhibitor (nivolumab) +/- an anti-VEGF therapy (bevacizumab), for the treatment of patients with first progression/recurrence of glioblastoma (ROSALIE trial)....The combination demonstrated encouraging results including a median survival of 14.5 months, median duration of response of 13.1 months, and median progression-free survival (PFS) of 5.5 months. The survival rate of 57.4% and 43.1% was observed at 12 months and 18 months respectively....In Cohort 3, 23 patients (92% of tested, 88% of total) had a specific CD8+ T cell response against EO2401 and all of those patients (100%) had CD8+ T cells cross-reactive with the targeted TAAs, i.e., recognizing IL13Rα2, BIRC5/survivin, and/or FOXM1."

P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Enterome to Present Updated Data From Phase 1/2 ROSALIE Trial of its Peptide-Based Immunotherapy EO2401 in Recurrent Glioblastoma at SNO 2023 (GlobeNewswire) - "Enterome...announced it will present updated efficacy data from its Phase 1/2 trial of EO2401 in combination with nivolumab +/- bevacizumab, in patients with first progression/recurrence of glioblastoma (the EOGBM1-18/ROSALIE study), in an oral presentation at the Society for Neuro-Oncology (SNO) 28th Annual Meeting which will be held in Vancouver, British Columbia, Canada on November 15-19, 2023."

P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

EO2401 peptide immunotherapy + nivolumab +/- bevacizumab in first recurrent glioblastoma: the phase 1/2 EOGBM1-18/ROSALIE study (NCT04116658) (SNO 2023) - P1b/2a | "C2a/1vsC2a/2vsC3: median treatment duration 1.4vs3.2vs4.8 months, disease control rate 22%vs40%vs88%, median PFS 1.6vs3.6vs5.5 months; median survival 9.0vs12.6vstoo early (C3 median FU 8.3 mo, survival ongoing up to 2 years). Further follow-up will be presented."

P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • BIRC5 • CD4 • CD8 • FOXM1 • IL13RA2

Characterisation of the immune response to EO2401, a new immunotherapy approach against cancer, plus nivolumab in recurrent glioblastoma: The EOGBM1–18/ROSALIE study (SITC 2023) - P1b/2a | "Methods Patients with GB at first progression following standard treatment received EO2401 with nivolumab ± bevacizumab. Expansion of commensal-specific CD8+ T cells that cross-react with TAAs is a promising approach to create broad immune responses against tumors with low neoantigen expression and poor T cell priming, such as GB. Further phenotypic analyses of antigen-specific T cells and other immune subsets are ongoing and will be correlated with clinical outcome."

IO biomarker • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • B3GAT1 • BIRC5 • CD4 • CD8 • FOXM1 • IFNG • IL13RA2 • LAG3 • PD-1

EO2401, a new peptide immunotherapy against cancer, in combination with nivolumab, induces a strong and durable immune response in patients from the EOADR1–19/SPENCER study (SITC 2023) - P1/2 | "Conclusions EO2401, in combination with nivolumab induces fast, strong and long-lasting immune response, with detection of bacterial peptide- and TAA- specific functional CD8+ T cells in almost all patients. These results highlight the potential of this innovative approach to overcome the limitations of current cancer vaccine strategies."

Clinical • Combination therapy • Adrenal Cortex Carcinoma • CNS Tumor • Endocrine Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • BIRC5 • CD8 • FOXM1 • IFNG • IL13RA2

Enterome Presents Immune-Monitoring Data on EO2401 at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (GlobeNewswire) - "Enterome...announced the presentation of immune-monitoring data from the ongoing trials of EO2401 in adrenal tumors and recurrent glioblastoma at the 38th Society for Immunotherapy of Cancer (SITC) Annual Meeting taking place from November 1-5, 2023, in San Diego, California, and virtually....In addition, research collaborator from Tübingen University, Germany, presents immune response data from the ongoing Phase 1/2 ROSALIE study of EO2401 in combination with nivolumab in recurrent glioblastoma."

Clinical data • P1/2 data • Adrenal Cortex Carcinoma • Brain Cancer • CNS Tumor • Endocrine Cancer • Genito-urinary Cancer • Glioblastoma • Kidney Cancer • Oncology • Solid Tumor

EO2401 (E) peptide immunotherapy + nivolumab (N) in adrenocortical carcinoma (ACC) and metastatic pheochromocytoma/paraganglioma (MPP): EOADR1-19/SPENCER (ESMO 2023) - P1/2 | "Post-hoc analyses identified predictors of lack of efficacy (no mitotane, ECOG > 1, ACC 1st diagnosis ≤9 months(mo), lesion size >125 mm, >3 organs involved, lymphopenia >grade 1); C2-post hoc group was created applying these factors. Conclusions EO2401/N was well tolerated generating durable immune responses correlating with efficacy. Based on the greater efficacy in C2-post hoc group a randomized extension is currently recruiting."

IO biomarker • Metastases • Adrenal Cortex Carcinoma • CNS Tumor • Endocrine Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • BIRC5 • CD4 • CD8 • FOXM1 • IL13RA2 • MSI • PD-L1

Enterome Presents Positive Data from Phase 1/2 SPENCER Trial of EO2401 in Adrenal Tumors at ESMO 2023 Congress (GlobeNewswire) - P1/2 | N=120 | Spencer (NCT04187404) | Sponsor: Enterome | "Enterome...announced updated, encouraging results from Phase 1/2 SPENCER trial of EO2401 in combination with nivolumab in adrenocortical carcinoma (ACC) and metastatic pheochromocytoma/paraganglioma (MPP), two forms of adrenal tumors....EO2401 in combination with nivolumab was generally well tolerated in patients with advanced/metastatic adrenal tumors; Encouraging results in pretreated patients with ACC; median duration of disease control of 9 months, and 3 of 26 patients stopped study treatment at 2 years only due to protocol; Longer follow-up needed to interpret results in pheochromocytoma/paraganglioma patients; EO2401 in combination with nivolumab achieved long term stabilizations of 'cold tumors' (TMB-low, MSS, PDL1-low adrenal tumors; ACC and MPP); Specific CD8 T cell immune responses could be a biomarker."

P1/2 data • Adrenal Cortex Carcinoma • Endocrine Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Enterome to Present Data on EO2401 in Adrenal Tumors at the European Society for Medical Oncology (ESMO) 2023 Congress (GlobeNewswire) - "Enterome...announced that updated data from its Phase 1/2 SPENCER study on EO2401, in combination with nivolumab in patients with adrenal tumors, will be presented in an oral session at the European Society for Medical Oncology (ESMO) Congress 2023, to take place on October 20-23, 2023 in Madrid, Spain."

P1/2 data • Adrenal Cortex Carcinoma • Endocrine Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

EO2401 (E) peptide immunotherapy + nivolumab (N) +/- bevacizumab (B) in recurrent glioblastoma (GB): EOGBM1-18/ROSALIE. (ASCO 2023) - P1b/2a | "EN +/- B was well tolerated and generated fast and durable immune responses. EN survival like current standards. Delayed N was not advantageous for outcome."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • BIRC5 • CD4 • CD8 • FOXM1 • IL13RA2

Enterome announces sustained positive clinical outcomes with EO2401, its lead OncoMimics immunotherapy, in combination therapy in Glioblastoma at ASCO (GlobeNewswire) - P1b/2a | N=100 | ROSALIE (NCT04116658) | Sponsor: Enterome | "Enterome...announces the presentation of new clinical data from its Phase 2 trial (ROSALIE) evaluating its lead OncoMimics™ immunotherapy candidate EO2401 in combination with an immune checkpoint inhibitor (nivolumab) +/- an anti-VEGF therapy with anti-edema properties (bevacizumab), in patients with first progression/recurrence of glioblastoma (GBM), at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting.....Immune monitoring in peripheral blood demonstrated the ability of EO2401 to expand OncoMimic™-specific CD8+ T cells with cross-reactivity against the targeted human tumor-associated antigens (TAAs) in a significant portion of patients. Memory specific CD8+ T cell responses were found as early as two weeks after the first vaccination and maintenance of a strong and stable immune response could be detected for up to 23 months."

P2a data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

EO2401 therapeutic vaccine for patients with recurrent glioblastoma: phase 1/2 ROSALIE study (NCT04116658) (SNO 2022) - P1b/2a | "Patients with glioblastoma at first progression received EO2401 (300µg/peptide, q2weeks x4 then q4weeks), EO2401+nivolumab (3mg/kg q2weeks), or E02401+nivolumab+bevacizumab (10mg/kg q2weeks). Symptom driven low-dose-bevacizumab supported longer treatment durations. Outcome of study part 2 will be presented."

Clinical • P1/2 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • BIRC5 • CD4 • CD8 • FOXM1 • IL13RA2

Interim analysis of the EOGBM1-18 study: Strong immune response to therapeutic vaccination with EO2401 microbiome derived therapeutic vaccine + nivolumab (ESMO-IO 2022) - P1b/2a | "Methods Patients with glioblastoma at first progression after radiotherapy/temozolomide received EO2401 (300μg/peptide, q2w x4 then q4w) with nivolumab (3 mg/kg q2w; EN), or EN with bevacizumab (10 mg/kg q2w; ENB) (NCT04116658). Activation of specific T cells cross-reacting with commensal antigens and TAAs is thereby validated as an efficient approach to activate strong immune responses in a difficult to treat tumor. Updated immuno-monitoring data will be presented."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • BIRC5 • CD4 • CD8 • FOXM1 • IFNG • IL13RA2 • LAMP1 • TNFA

EO2401 microbiome derived therapeutic vaccine + nivolumab +/- bevacizumab, in neoadjuvant, adjuvant and non-surgery linked treatment of recurrent glioblastoma: phase 1-2 EOGBM1-18/ROSALIE study (ESMO-IO 2022) - P1b/2a | "Methods Patients with glioblastoma at first progression after radiotherapy/temozolomide received EO2401 (300 μg/peptide, q2w x4 then q4w) with nivolumab (3 mg/kg q2w; EN), or EN with bevacizumab (10 mg/kg q2w; ENB). Updated data from all parts of the trial will be presented. NCT04116658."

Clinical • P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • BIRC5 • CD4 • FOXM1 • IFNG • IL13RA2