igrelimogene litadenorepvec (TILT-123) / Tilt Biotherap - LARVOL DELTA

Intravenous oncolytic adenovirus encoding tumor necrosis factor and interleukin 2 with immunomodulatory metronomic cyclophosphamide in patients with advanced solid tumors (ESMO-IO 2025) - P1 | "Funding TILT Biotherapeutics Ltd. TILT-123 was detected in tumors by qPCR.Conclusions Combination treatment of fully i.v. oncolytic adenovirus TILT-123 and metronomic CP shows a tolerable safety profile in addition to early signs of efficacy. Transduction of tumors with fully intravenous delivery was observed.Clinical trial identification NCT04695327.Legal entity responsible for the study TILT Biotherapeutics Ltd."

Clinical • Immunomodulating • Metastases • Oncolytic virus • Eye Cancer • Melanoma • Oncology • Ovarian Cancer • Solid Tumor • Uveal Melanoma • IL2 • TNFA

Neutralizing antibodies as functional effectors and predictive biomarkers in oncolytic adenovirus therapy (ESMO-IO 2025) - P1, P1/2 | "This study investigates the kinetics, composition, and functional roles of nAbs, and association with overall survival (OS) and response rate in patients treated with TILT-123 (igrelimogene litadenorepvec), an Ad5/3 oncolytic adenovirus encoding tumor necrosis factor and interleukin-2.Methods Multiple serum samples from 59 patients enrolled in four TILT-123 clinical trials (NCT04695327, NCT04217473, NCT05271318, NCT05222932) were analyzed for anti-Ad5/3 nAbs using a cell-based functional neutralization assay...These results suggest a major role for nAbs beyond sole neutralization, and a potential use as biomarkers and future targets for enhancing virotherapy efficacy. Further analysis will be performed in larger upcoming cohorts and phase II trials.Clinical trial identification NCT04695327 (TUNIMO), NCT04217473 (TUNITIL), NCT05271318 (PROTA), NCT05222932 (AVENTIL).Legal entity responsible for the study TILT Biotherapeutics Ltd."

Biomarker • IO biomarker • Oncolytic virus • Oncology • IL2 • TNFA

Natural IgM and dyslipidemia enhance the efficacy of tumor necrosis factor and interleukin-2 encoding oncolytic adenovirus in solid tumors (ESMO-IO 2025) - P1, P1/2 | "Validation in 58 additional patients confirmed the link between elevated serum oxLDL, prolonged survival, and positive imaging responses.Conclusions IgM antibodies that cross-react with both TILT-123 and oxLDL are linked to improved outcomes, potentially via antibody-dependent enhancement in hyperlipidemic patients. Elevated oxLDL may help identify optimal candidates for TILT-123, supporting immunometabolic biomarkers for personalized oncolytic therapy.Clinical trial identification NCT04695327; NCT05271318; NCT04217473.Legal entity responsible for the study The authors."

Clinical • Oncolytic virus • Oncology • Solid Tumor • IL2 • TNFA

Split-dose intravenous delivery of igrelimogene litadenorepvec enhances viral levels in blood and tumours compared with conventional intratumoral injection (ESMO-IO 2025) - P1 | "Prolonged circulation correlates with greater viral positivity and immune presence within tumours. Additionally, practical and clinical advantages over intratumoral delivery (less restricted population, reduced procedural risk and discomfort, fewer healthcare resources, etc) make this approach an attractive way to use igrelimogene litadenorepvec.Clinical trial identification NCT04695327.Legal entity responsible for the study TILT Biotherapeutics Ltd."

Oncology • CD4 • CD8

Biomarker insights and long-term outcomes of TILT-123 oncolytic adenovirus combined with tumor-infiltrating lymphocytes in refractory metastatic melanoma: results from the TUNINTIL phase 1 trial (SITC 2025) - P1 | "All approvals were obtained prior to inclusion of the first patient in the trial.Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal."

Biomarker • IO biomarker • Metastases • Oncolytic virus • P1 data • Tumor-infiltrating lymphocyte • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • TNFA

PROTA: Oncolytic Adenovirus Coding for TNFa and IL2 (TILT-123) With Pembrolizumab or Pembrolizumab (Phase 1a) and Pegylated Liposomal Doxorubicin (Phase 1b) as Treatment for Ovarian Cancer. (clinicaltrials.gov) - P1/2 | N=29 | Recruiting | Sponsor: TILT Biotherapeutics Ltd. | N=76 ➔ 29

Enrollment change • Platinum resistant • Allergy • Fallopian Tube Cancer • Immunology • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor

Novel tumor-infiltrating lymphocytes therapy in solid tumors: latest updates from 2025 ASCO annual meeting. (PubMed, Exp Hematol Oncol) - "Notably, innovative TIL-based monotherapies and combination regimens have provided durable clinical responses and survival benefits for patients with various solid tumors. This article summarizes recent advances in TIL therapy for solid tumors presented at the 2025 ASCO Annual Meeting, highlighting monotherapies such as Lifileucel, LM103, OBX-115, GT101, GT300, GT201, and HS-IT101, as well as combination strategies with the oncolytic adenovirus TILT-123 or pembrolizumab."

Journal • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor

Clinical correlations and long-term survival in PROTA: Platinum-resistant or refractory ovarian cancer treated with an oncolytic adenovirus encoding TNF and IL2 in combination with pembrolizumab (ESMO 2025) - P1/2 | "These results may help identify patients likely to benefit from combined TILT-123 and pembrolizumab. A phase 2 is ongoing (NCT05271318)."

Clinical • Combination therapy • IO biomarker • Oncolytic virus • Platinum resistant • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • IL2

Fully intravenous split-dose administration of oncolytic adenovirus TILT-123 in advanced solid tumors (ESMO 2025) - P1, P1/2 | "Conclusions Fully i.v. dosing of TILT-123 is feasible and results in tumor transduction and immune activation, warranting further evaluation. A phase 2 trial utilizing fully i.v. dosing is ongoing (NCT05271318)."

IO biomarker • Metastases • Oncolytic virus • Oncology • Solid Tumor • CD4 • CD8 • CXCL11 • CXCL9 • FASLG • IL18 • IL2 • TNFSF12

Oncolytic adenovirus encoding TNF and IL2 (TILT-123): from preclinical development to clinical trials with tumor infiltrating lymphocyte therapy and checkpoint inhibitors (ESGCT 2025) - No abstract available

Checkpoint inhibition • Oncolytic virus • Preclinical • Tumor-infiltrating lymphocyte • Oncology • IL2

TUNINTIL: TNFalpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 During TIL Treatment of Advanced Melanoma (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: TILT Biotherapeutics Ltd. | Active, not recruiting ➔ Completed

Trial completion • Melanoma • Oncology • Solid Tumor • BRAF • IL2

AVENTIL: Oncolytic Adenovirus TILT-123 and Avelumab for Treatment of Solid Tumors Refractory to or Progressing After Anti-PD(L)1 (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: TILT Biotherapeutics Ltd. | Recruiting ➔ Active, not recruiting | Trial primary completion date: Dec 2024 ➔ Dec 2026

Enrollment closed • Trial primary completion date • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Neutralizing antibodies and lymphocyte count as biomarkers in patients receiving oncolytic adenovirus TILT-123 and adoptive cell transfer of tumor-infiltrating lymphocytes for metastatic melanoma refractory to immune checkpoint inhibitors. (ASCO 2025) - P1 | "ICI refractory melanoma patients receiving TILT-123 and ACT-TILs without preconditioning show signs of CD8+ T cell trafficking to the tumor microenvironment. nAbs and lymphocyte count decrease can be further investigated as biomarkers."

Biomarker • Checkpoint inhibition • Clinical • IO biomarker • Metastases • Oncolytic virus • Tumor-infiltrating lymphocyte • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • CD4 • CD8 • IL2 • PD-L1

Assessment of tumors, blood, and ascites to establish correlations with treatment benefit in platinum resistant or refractory ovarian cancer patients treated with igrelimogene litadenorepvec and pembrolizumab combination therapy. (ASCO 2025) - P1/2 | "Igrelimogene litadenorepvec and pembrolizumab are therapies designed to attract, activate and/or protect lymphocyte-mediated antitumor activity. These findings suggest that having a fit immune system able to mobilize effector immune cells as well as responding to immunostimulant agents increases therapeutic success. As a disease with few therapeutic options, ovarian cancer patients often receive multiple lines of chemotherapy that might decrease the efficacy of immediate immunotherapies."

Clinical • Combination therapy • IO biomarker • Platinum resistant • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • IL2

TILT Biotherapeutics Announces Closing of USD 25 Million Series B Financing (GlobeNewswire) - "TILT Biotherapeutics...announces it has raised USD 25.6 million (EUR 22.6 million) in a Series B financing...It will support a Phase 2 clinical trial of Tiltbio’s lead product, TILT-123, in patients with platinum-resistant epithelial ovarian cancer, a Phase 1b trial in melanoma in combination with TILs and other Phase 1b trials...The Company recently published data from its Phase 1a clinical trial (PROTA) in platinum-resistant ovarian cancer...Interim results from ongoing Phase 1b trials are expected to read out in H2 2026...'We’ve been making good progress in ovarian cancer and this financing will support the roll out of our Phase 2 clinical trials. We’re excited to have already opened the first site in the USA and are looking forward to dosing our first patients soon and opening at least five more sites this year.'"

Financing • New P2 trial • Platinum resistant • Ovarian Cancer

TUNINTIL-2: TNFα and IL-2 Coding Oncolytic Adenovirus TILT-123 With Lymphocyte-depleting Chemotherapy and TILs in the Treatment of Melanoma (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: TILT Biotherapeutics Ltd.

New P1 trial • Melanoma • Oncology • Solid Tumor

Clinical-immunological correlates in platinum resistant or refractory ovarian cancer patients treated with chimeric oncolytic adenovirus encoding TNFa and IL-2 (TILT-123) in combination with pembrolizumab (AACR 2025) - P1/2 | "These preliminary results identify a key role of circulating lymphocyte re-distribution and humoral immune response as markers of treatment benefit. Initial phenotyping implicates IgM producing plasma cells as a potentially relevant immune cell population. Additionally we observed a correlation between the coagulation cascade and OS."

Clinical • Combination therapy • Oncolytic virus • Platinum resistant • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • IL2 • TNFA

PROTA: Oncolytic Adenovirus Coding for TNFa and IL2 (TILT-123) With Pembrolizumab or Pembrolizumab (Phase 1a and 2) and Pegylated Liposomal Doxorubicin (Phase 1b) as Treatment for Ovarian Cancer. (clinicaltrials.gov) - P1/2 | N=76 | Recruiting | Sponsor: TILT Biotherapeutics Ltd. | Trial completion date: Jun 2026 ➔ Aug 2027 | Trial primary completion date: Mar 2026 ➔ Mar 2027 | Phase classification: P1 ➔ P1/2 | N=29 ➔ 76

Enrollment change • Phase classification • Platinum resistant • Trial completion date • Trial primary completion date • Allergy • Fallopian Tube Cancer • Immunology • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor

PROTA: Oncolytic Adenovirus Coding for TNFa and IL2 (TILT-123) With Pembrolizumab or Pembrolizumab and Pegylated Liposomal Doxorubicin as Treatment for Ovarian Cancer. (clinicaltrials.gov) - P1 | N=29 | Recruiting | Sponsor: TILT Biotherapeutics Ltd. | Trial completion date: Jan 2027 ➔ Jun 2026 | Trial primary completion date: Jan 2025 ➔ Mar 2026

Platinum resistant • Trial completion date • Trial primary completion date • Allergy • Fallopian Tube Cancer • Immunology • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor

Single-cell profiling of peripheral blood mononuclear cells from patients treated with oncolytic adenovirus TILT-123 reveals baseline immune status as a predictor of therapy outcomes. (PubMed, Cancer Gene Ther) - P1 | "Several T and B cell receptor segments matched those previously reported in other viral infections, suggesting possible cross-reactive immune responses. These findings emphasize that comprehensive biomarker analysis of peripheral blood should include not only cell frequencies but also transcriptional changes and distinct patterns of cellular and humoral immunity."

Journal • Infectious Disease • Oncology • Solid Tumor

Safety and efficacy of combined treatment with tumor-infiltrating lymphocytes and oncolytic adenovirus TILT-123 in metastatic melanoma. (PubMed, Cell Rep Med) - "In the initial TILT-123 monotherapy phase of the trial, disease control is observed in 6/17 (35%) and 10/16 (63%) in CT and PET, respectively. The study demonstrates good tolerability and preliminary efficacy."

Journal • Tumor-infiltrating lymphocyte • Cutaneous Melanoma • Eye Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Uveal Melanoma • IL2 • TNFA

Transient lymphocyte count decrease correlates with oncolytic adenovirus efficacy in humans: mechanistic and biomarker findings from TUNIMO phase I trial. (PubMed, J Immunother Cancer) - P1 | "TILT-123 therapy induced accumulation of effector lymphocytes in tumors. Peripheral lymphocyte count decrease is a promising biomarker for assessing oncolytic adenovirus therapy response."

Biomarker • IO biomarker • Journal • P1 data • Gene Therapies • Oncology • Solid Tumor • CD4 • CD8 • IL2 • TNFA

Transient lymphocyte count decrease correlates with oncolytic adenovirus efficacy in humans: mechanistic and biomarker findings from TUNIMO phase I trial (J Immunother Cancer) - P1 | N=18 | TUNIMO (NCT04695327) | Sponsor: TILT Biotherapeutics Ltd. | "TILT-123 induced cyclical decreases in blood lymphocyte count, and more substantial blood lymphocyte count correlated with better radiographical response and longer OS. Lymphocyte count findings were confirmed with external control dataset of 96 patients. More substantial lymphocyte count change was linked to stronger immune activation in plasma proteome after intravenous TILT-123 and the presence of TILT-123 mRNA in tumors. Regarding other assays, tumor biopsies profiled showed increased amounts of CD8+ T cells, CD4+ T cells and NK cells after intravenous TILT-123, but not after intratumoral TILT-123."

Biomarker • P1 data • Solid Tumor

Safety And Immunological Activity Of A Oncolytic Adenovirus Expressing TNFa And IL-2 In Combination With Pembrolizumab In Platinum-Resistant Or Refractory Ovarian Cancer Patients (ESGO 2025) - P1 | "TILT-123 (igrelimogene litadenorepvec, Ad5/3-E2F-D24-hTNFa-IRES-hIL-2) is a chimeric oncolytic adenovirus constructed to promote T-cell infiltration and activity therefore enabling ICI therapies. Doublet therapy induced systemic immune changes in blood and tumours. Further investigation continues in Phase Ib and II studies."

Clinical • Combination therapy • IO biomarker • Oncolytic virus • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • IL2 • MUC16 • TNFA

The oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trial. (PubMed, Nat Commun) - P1 | "Clinical responses were associated with higher serum anti-adenovirus neutralizing antibody titer at baseline and post-treatment. The phase 1b investigating TILT-123, pembrolizumab and PEGylated liposomal doxorubicin in a similar patient population is underway."

Journal • P1 data • Fatigue • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • IL2 • TNFA