linoserpaturev (CAN-3110) / Candel Therap - LARVOL DELTA

Integrative spatiotemporal proteomic and metabolomic characterization of immune infiltration following intracranial injection of oncolytic immunotherapy in glioblastoma patients (WFNOS 2025) - "These metabolic patterns suggest that purine metabolism plays a key role in shaping immunologically active tumor microenvironments following treatment.Together, these findings provide novel mechanistic insights into the evolving tumor-immune landscape during rQnestin34.5v.2 therapy in glioblastoma, highlighting purine metabolism as a potential driver of immune activation within the tumor microenvironment. This integrated spatial approach offers a powerful framework to guide the development of more effective immunotherapeutic strategies for this challenging malignancy."

Clinical • Oncolytic virus • Brain Cancer • Glioblastoma • Herpes Simplex • Solid Tumor • CD4 • OLIG2 • SOX2

On-Treatment Spatiotemporal Profiling of Glioblastoma During Oncolytic ImmunoTherapy (WFNOS 2025) - "To address this critical gap, we implemented a novel on-therapy, longitudinal, and multi-regional tissue sampling strategy in patients treated with rQNestin34.5v2, an engineered oncolytic biologic based on herpes simplex virus 1, to explore how tumor and immune ecosystems evolve during treatment.Using high-resolution spatial transcriptomics (Xenium) and targeted spatial proteomics (CyCIF), we profiled over 80 spatially and temporally distinct samples from six patients, capturing over half a million immune, stromal, and malignant cells...By the time of radiographic progression, these lymphoid structures had largely dissipated—underscoring the importance of on-treatment sampling in capturing transient, treatment-responsive immune architectures.While these findings are preliminary, they suggest a transient immune structure linked to early therapeutic response, whose collapse may contribute to treatment resistance. Our study illustrates how integrative, on-therapy spatial..."

Oncolytic virus • Brain Cancer • Glioblastoma • Herpes Simplex • Solid Tumor

Immune profiling of GBM tumor tissues collected longitudinally from patients treated with an oncolytic virus (WFNOS 2025) - "To evaluate safety of accessing the brain multiple times and to interrogate immune responses with an immunomodulatory agent, we are conducting a trial in which GBM patients receive intra-tumoral injections with oncolytic herpesvirus (HSV) (CAN-3110, aka rQNestin34.5v.2)...At day 90, we observed a shift in TAMs from pro-inflammatory to a more immunosuppressive phenotype with an increase in Trem2+SPP1+ TAMs and HIF1a+ hypoxic microglial cells, suggesting a compensatory inhibitory response to the initial immune response.Our studies highlight a dynamic immune response of both effector and immunosuppressive cells. These data suggest that immunotherapeutic strategies should be further developed and evaluated in the context of serial biopsies to guide our understanding of human immune responses, which may enable an iterative process to identify agents that will drive effective anti-tumor responses."

Clinical • Oncolytic virus • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CCR7 • CD4 • CD8 • CD86 • CDK1 • CTLA4 • CXCL10 • CXCL9 • GZMK • HIF1A • IFNG • LAG3 • PD-1 • SPP1

Integrative spatiotemporal proteomic and metabolomic characterization of immune infiltration following intracranial injection of oncolytic immunotherapy in glioblastoma patients (WFNOS 2025) - "These metabolic patterns suggest that purine metabolism plays a key role in shaping immunologically active tumor microenvironments following treatment.Together, these findings provide novel mechanistic insights into the evolving tumor-immune landscape during rQnestin34.5v.2 therapy in glioblastoma, highlighting purine metabolism as a potential driver of immune activation within the tumor microenvironment. This integrated spatial approach offers a powerful framework to guide the development of more effective immunotherapeutic strategies for this challenging malignancy."

Clinical • Oncolytic virus • Brain Cancer • Glioblastoma • Herpes Simplex • Solid Tumor • CD4 • OLIG2 • SOX2

Multi-omic and single cell assessment of serial biopsies reveals responses to CAN-3110 oncolytic immunotherapy in recurrent glioblastoma that are not evident by routine clinical analyses (WFNOS 2025) - P1 | "These results show that longitudinal tissue sampling during rGBM clinical trials is well tolerated and, even with a small number of patients, can reveal critical mechanistic insights into a therapy's impact that would be missed via routine clinical monitoring. (clinicaltrials.gov NCT03152318)"

Biopsy • Clinical • IO biomarker • Oncolytic virus • Brain Cancer • Glioblastoma • Glioma • Solid Tumor • CD4

Candel Therapeutics Announces Positive Interim Data After Repeated Administration of CAN-3110 in Recurrent Glioblastoma and Announces Publication in Science Translational Medicine (GlobeNewswire) - "Biopsy analyses demonstrated that CAN-3110 induced dynamic spatial and temporal remodeling of the tumor microenvironment, where tumor cells are replaced by immune cells....Updated median OS (mOS) was 11.8 months (CI: 8.3–14.9) for arm A (n = 41) and 12.0 months (CI: 10.0–NA) for arm B (n = 9), respectively, after a single injection of CAN-3110....'We expect to present mature mOS data and an update on long-term survivors in Q4 2026'."

P1 data • Glioblastoma

Serial multiomics uncovers anti-glioblastoma responses not evident by routine clinical analyses. (PubMed, Sci Transl Med) - "Here, we obtained 97 serial rGBM biopsy cores over 4 months from the first two patients participating in a clinical trial of repeated intratumoral dosing of the immunotherapeutic agent CAN-3110...Clinically, the two treated patients achieved a pathologic response or stable clinical disease, respectively. These results show the value of longitudinal tissue sampling to understand rGBM's evolution during administration of an investigational therapy."

IO biomarker • Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Anticipated Milestones (GlobeNewswire) - "Additional clinical and biomarker activity data from an ongoing phase 1b clinical trial evaluating repeat doses of CAN-3110 in patients with recurrent high-grade glioma (rHGG), is expected in Q4 2025; Candel plans to host a virtual Research and Development event in Q4 2025; Submission of BLA for CAN-2409 in prostate cancer expected in Q4 2026."

FDA filing • P1 data • Glioma • Prostate Cancer

A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2 (clinicaltrials.gov) - P1 | N=62 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Jun 2026 ➔ Jan 2027 | Trial primary completion date: Jun 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Anaplastic Oligoastrocytoma • Astrocytoma • Brain Cancer • Ependymoma • Ganglioglioma • Glioblastoma • Glioma • High Grade Glioma • Immunology • Oligodendroglioma • Oncology • Solid Tumor • IDH1

Candel Therapeutics Reports First Quarter 2025 Financial Results and Recent Corporate Highlights (GlobeNewswire) - "Anticipated Milestones: Clinical and biomarker activity data from an ongoing phase 1b clinical trial evaluating repeat doses of CAN-3110 in patients with rHGG expected in Q4 2025; Submission of BLA for CAN-2409 in prostate cancer expected in Q4 2026."

FDA filing • P1 data • Glioma • Prostate Cancer

Preclinical toxicology and efficacy of NG34C: A novel oncolytic HSV-1 expressing truncated GADD34 gene for the treatment of glioblastoma (AACR 2025) - "We recently completed a Phase I clinical trial of rQNestin34.5v2 (CAN-3110), an oncolytic virus encoding the viral neurovirulence gene ICP34.5 under the nestin promoter, demonstrating safety at doses up to 1 x 1010 PFU (Ling et al., Nature, 2023)...These results establish NG34C as a safe, hypoxia-adapted, and effective oncolytic virus for GBM. NG34C is now being produced under GMP for an upcoming INS-clinical study."

IO biomarker • Late-breaking abstract • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CDKN2A • EGFR • NES • PPP1R15A • PTEN

Assessing Nectin and Nestin Expression in Diffuse Midline Gliomas: A Step Toward HSV-Based Oncolytic Viral Immunotherapy (USCAP 2025) - P1 | "Additionally, the oncolytic adenovirus DNX-2401 has shown promising results in treating diffuse intrinsic pontine gliomas (DIPG), a subset of DMGs, in pediatric patients (NCT03178032). The co-expression of Nectin and Nestin in DMGs is significant, as it suggests that these tumors may be suitable candidates for CAN-3110 oncolytic immunotherapy. Further studies are needed to explore the therapeutic potential and clinical application of this approach in DMGs."

IO biomarker • Oncolytic virus • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioblastoma • Glioma • Malignant Glioma • Oncology • Pediatrics • Solid Tumor • NES

Candel Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Recent Corporate Highlights (GlobeNewswire) - "On track to report biomarker and initial survival data from ongoing phase 1b trial evaluating multiple doses of CAN-3110 in patients with recurrent high-grade glioma (rHGG), expected in Q4 2025."

P1 data • Glioma

Candel Therapeutics Provides Corporate Update and Highlights Strong Pipeline Momentum and Key Value Drivers for 2025 (GlobeNewswire) - "CAN-3110 – Recurrent High-Grade Glioma: Overall survival data from ongoing phase 1b clinical trial evaluating multiple doses, expected in Q4 2025."

P1 data • Brain Cancer • Glioma

Characterizing changes in antigen presentation of glioblastoma tumors in response to oncolytic viral therapy (SITC 2024) - "Methods We used mass spectrometry based immunopeptidomics to characterize the immunopeptidome of serial tumor biopsies from 6 GBM patients treated with up to six intratumoral injections of CAN-3110, an oncolytic viral immunotherapy.1 We also used mass spectrometry to profile changes in protein expression...Understanding the evolution of the immunopeptidome longitudinally can inform the development of therapeutic agents that target tumor associated antigens. Ethics Approval The study was approved by DFCI IRB 16-557."

IO biomarker • Oncolytic virus • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IFNG

Therapeutic potential of CAN-3110 in Ras-Raf pathway altered melanoma (SITC 2024) - "Ethics Approval Studies involving animals were conducted in compliance with Charles River Laboratories IACUC under IACUC No. I041."

IO biomarker • Brain Cancer • CNS Tumor • Glioma • Melanoma • Oncology • Solid Tumor • CDKN2A • NECTIN1 • NES

Candel Therapeutics to Present Preclinical Data at SITC Annual Meeting Showing Promise for CAN-3110 in Melanoma, Signaling Potential Indication Expansion Beyond Recurrent High-Grade Glioma (GlobeNewswire) - "The poster...will focus on new data demonstrating the mechanism of action and antitumor activity of CAN-3110 in preclinical models of melanoma, a tumor characterized by high Nestin expression, frequent loss-of-function in CDKN2A, and additional alterations in the Ras-Raf signaling pathway....Data presented at SITC showed potent monotherapy, anti-tumor activity of CAN-3110 in both in vitro human cell lines and in vivo murine models of melanoma. In vivo, CAN-3110 exhibited tumor-specific cytotoxicity with dose-dependent inhibition of tumor growth and tumor regression observed in a subset of tumors treated with a high dose of CAN-3110..."

Preclinical • Melanoma • Oncology • Skin Cancer • Solid Tumor

Candel Therapeutics Showcases Innovative Cancer Therapy Candidates at 16th Annual International Oncolytic Virotherapy Conference (IOVC) (GlobeNewswire) - P1b | N=62 | NCT03152318 | "The presentation will review safety and tolerability data from the multiple injection cohort of the ongoing phase 1b clinical trial of CAN-3110 in rHGG and will describe early clinical data and biomarker analysis from the first six patients enrolled in this cohort. The investigators observed ongoing improved survival compared to historical controls, with 3 out of 6 patients still alive after more than one year (12.2, 13.0, and 18.7 months, respectively) after initiation of experimental treatment with repeated CAN-3110 injections. The data also show discrepancies between imaging and histologic findings, suggesting radiologic pseudo-progression: there was a near absence of tumor cells alongside dense lymphocyte infiltrates in biopsies obtained after CAN-3110 administration, especially in patients with enhancement on post-treatment MRI scans."

P1 data • Glioma

Candel Therapeutics to Present Preclinical Data on Therapeutic Potential of CAN-3110 in Melanoma at SITC 2024 Annual Meeting (GlobeNewswire) - "Candel Therapeutics, Inc...announced the Company will present a poster at the Society for Immunotherapy of Cancer’s (SITC) 39th Annual Meeting taking place November 6-10, 2024 in Houston, Texas and virtually."

Preclinical • Melanoma • Oncology • Skin Cancer • Solid Tumor

Synergistic effects of herpes oncolytic virus and cyclophosphamide for recurrent malignant glioma: a narrative review. (PubMed, Ann Med Surg (Lond)) - "Oncolytic herpes viruses (oHSVs), particularly HSV1716, G207, and rQNestin34.5v, show promise in glioma treatment by selectively replicating in tumor cells. Preclinical and clinical studies demonstrate the safety and efficacy of oHSVs, with T-Vec being FDA-approved...CPA's immunomodulatory effects, suppressing regulatory T cells, improve oHSV efficiency. While obstacles remain, this synergistic approach offers hope for improved outcomes, necessitating further research and clinical validation."

IO biomarker • Journal • Oncolytic virus • Review • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2 (clinicaltrials.gov) - P1 | N=62 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Immunomodulating • Trial completion date • Trial primary completion date • Anaplastic Oligoastrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Ependymoma • Ganglioglioma • Glioblastoma • Glioma • Immunology • Oligodendroglioma • Oncology • Solid Tumor • IDH1

Candel Therapeutics Reports Second Quarter 2024 Financial Results and Recent Corporate Highlights (GlobeNewswire) - "Anticipated Milestones: (i) Updated phase 1b data (Arm C) for CAN-3110 in rHGG expected in H2 2024; (ii) Phase 2b topline data for CAN-2409 in low-to-intermediate-risk, localized, non-metastatic prostate cancer expected in Q4 2024; (iii) Phase 3 topline disease-free survival data for CAN-2409 in localized intermediate/high-risk prostate cancer expected in Q4 2024."

P1 data • P2b data • P3 data • Glioma • Prostate Cancer

Longitudinal stereotactic injections of oncolytic immunoactivating rQNestin34.5v.2 (CAN-3110) with concomitant biopsies for "-omic" analyses in recurrent glioblastoma (GBM). (ASCO 2024) - P1 | "Cohort 2 is scheduled to start enrollment in the spring of 2024 (NCT03152318). This abstract is submitted on behalf of the Break Through Cancer Accelerating Glioblastoma Therapies Team Lab (breakthroughcancer.org)."

Biopsy • IO biomarker • Oncolytic virus • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Targeting IGF2-IGF1R Signaling to Reprogram the Tumor Microenvironment for Enhanced Viro-Immunotherapy. (PubMed, Neuro Oncol) - P1 | "This is the first study reporting that oHSV-induced secreted IGF2 exerts a critical role in resistance to oHSV therapy, which can be overcome by oHSV-D11mt as a promising therapeutic advance for enhanced viro-immunotherapy."

Biomarker • IO biomarker • Journal • Oncolytic virus • Tumor microenvironment • Brain Cancer • Breast Cancer • CNS Tumor • Glioblastoma • Glioma • Herpes Simplex • Oncology • Solid Tumor • CD8 • IGF2

FDA Grants Orphan Drug Designation for CAN-3110 for the Treatment of Recurrent High-Grade Glioma (GlobeNewswire) - "Candel Therapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to CAN-3110, a next generation oncolytic viral immunotherapy, for the treatment of recurrent high-grade glioma (rHGG). Glioblastoma (GBM) is the most common and aggressive form of high-grade glioma....Candel is currently evaluating CAN-3110 in a multi-institutional phase 1b clinical trial in rHGG."

Orphan drug • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology