CAN-3110 / Candel Therap - LARVOL DELTA

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

A viral attack on brain tumors: the potential of oncolytic virus therapy. (PubMed, J Neurovirol) - "Furthermore, the discovery and creation of new OVs that can seamlessly integrate gene therapy strategies, such as cytotoxic, anti-angiogenic, and immunostimulatory, are promising advancements. This review presents an overview of the latest advancements in OVs transduction for brain cancer, focusing on the safety and effectiveness of G207, G47Δ, M032, rQNestin34.5v.2, C134, DNX-2401, Ad-TD-nsIL12, NSC-CRAd-S-p7, TG6002, and PVSRIPO. These are evaluated in both preclinical and clinical models of various brain tumors."

Journal • Oncolytic virus • Review • Brain Cancer • Gene Therapies • Oncology • Solid Tumor

Candel Therapeutics Reports First Quarter 2024 Financial Results and Recent Corporate Highlights (GlobeNewswire) - "Anticipated Milestones:...Updated Phase 1b data (Arm C) for CAN-3110 in rHGG expected in H2 2024."

P1 data • Glioma

The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene expression profiles. (PubMed, Mol Ther Oncol) - "In the current study, we employed four different species of OVs: adenovirus Delta24-RGD, herpes simplex virus rQNestin34.5v1, reovirus R124, and the non-virulent Newcastle disease virus rNDV-F0-GFP against three entities of PBTs (high-grade gliomas, atypical teratoid/rhabdoid tumors, and ependymomas) to determine their in vitro efficacy...In summary, our results demonstrate OV susceptibility of multiple patient-derived PBT entities and the ability to predict in vitro responses to OVs using unique expression profiles. Such profiles may hold promise for future OV preselection with effective oncolytic potency in a specific tumor, therewith potentially improving OV responses."

Heterogeneity • IO biomarker • Journal • Oncolytic virus • Brain Cancer • CNS Tumor • Ependymoma • Glioma • Herpes Simplex • Oncology • Pediatrics • Rhabdoid Tumor • Sarcoma • Solid Tumor

Candel Therapeutics Announces Upcoming Presentations at the 2024 ASCO Annual Meeting (GlobeNewswire) - "Candel Therapeutics...announced that two abstracts were accepted for presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting....The first presentation will feature data from the ongoing phase 1 clinical trial of CAN-3110 in patients with recurrent high-grade glioma. The presentation will focus on patients recruited in cohort C, treated with multiple injections of CAN-3110 (up to six), demonstrating that this approach is both feasible and well tolerated. The second presentation will show topline overall survival data from the phase 2 clinical trial of CAN-2409 plus valacyclovir, in combination with continued immune checkpoint inhibitor (ICI) treatment in patients with non-resectable, stage III/IV non-small cell lung cancer (NSCLC) who have an inadequate response to front line anti-PD(L)1 therapy."

P1 data • P2 data • Glioma • Non Small Cell Lung Cancer

Candel Therapeutics Announces Oral Presentation During the 5th Glioblastoma Drug Development Summit with Update on Phase 1b Clinical Trial of CAN-3110 in Recurrent High-Grade Glioma (GlobeNewswire) - P1b | N=62 | NCT03152318 | "Candel Therapeutics...announced the presentation of updated data from an ongoing phase 1b clinical trial of its herpes simplex virus-1 (HSV-1) replication-competent viral immunotherapy candidate, CAN-3110, in patients with rHGG that has recurred after standard of care (SoC) treatment. The data were presented today during the 5th Glioblastoma Drug Development Summit....The investigators observed a nearly doubling of the expected median overall survival (mOS) after a single CAN-3110 injection, achieving a mOS of ~12 months, compared to historical reports of less than 6 to 9 months in this therapy-resistant condition. Positive HSV-1 serology was a predictor of response and was associated with improved survival (mOS in this population reached 14 months)."

P1 data • Glioblastoma • Glioma

CAN-3110 Receives FDA Fast Track Designation for Treatment of Recurrent High-Grade Glioma (GlobeNewswire) - "Candel Therapeutics, Inc...today announced that the U.S. Food and Drug Administration (FDA) granted Fast Track Designation for CAN-3110 -- a first-in-class, replication-competent herpes simplex virus-1 (HSV-1) oncolytic viral immunotherapy candidate – for the treatment of patients with recurrent high-grade glioma (HGG) to improve overall survival....'We look forward to reporting additional data, including the potential benefits from multiple injections of CAN-3110, from the ongoing phase 1b clinical trial in the second half of 2024.'"

Fast track designation • P1 data • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Batavia and Candel Partner to Accelerate Development of CAN-3110 (Contract Pharma) - "Batavia Biosciences...has partnered with Candel Therapeutics, Inc...to accelerate the development and production of CAN-3110, an oncolytic viral immunotherapy for glioma brain tumors, based on a replication attenuated Herpes Simplex Virus (HSV)....Batavia Biosciences will use its HIP-Vax technology to develop a highly intensified, scalable and robust manufacturing process for Candel Therapeutics. This work will enable the production of CAN-3110 for toxicity studies and establish a Good Manufacturing Practice (GMP)-compatible process for the upcoming clinical trials."

Licensing / partnership • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

BostonGene Announces Publication in Nature (Businesswire) - P1 | N=62 | NCT03152318 | "BostonGene...today announced the online publication...in Nature...Utilization of immunotherapy for GBM has been challenging due to the scarcity of infiltrating antitumor lymphocytes caused by a highly immunosuppressive or 'lymphocyte-depleted' tumor microenvironment (TME)....The results demonstrated a single injection of CAN-3110 activated an antitumor immune response in GBM, inducing defined changes in T cell repertoires and tumor transcriptomic signatures. These findings are evidence that intralesional onolytic viruses can convert the immunosuppressive GBM TME to an immunoactivated state that is more responsive to immunotherapy."

Diagnostic • P1 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Candel Therapeutics Announces Restructuring to Prioritize Resources on Key Value Drivers for Expanded Development of CAN-3110, the enLIGHTEN Discovery Platform, and Key Clinical Readouts for CAN-2409 (GlobeNewswire) - "Candel Therapeutics, Inc...announced a strategic restructuring to focus on continuation and expansion of development of CAN-3110 as well as the enLIGHTEN Discovery Platform...The Company expects to present initial activity and biomarker data for repeated injections of CAN-3110 in recurrent high-grade glioma in the second half of 2024 and new data for the second drug candidate based on the enLIGHTEN Discovery Platform in Q3 2024. The Company plans to continue to collect clinical data for key readouts for CAN-2409 in non-small cell lung cancer (NSCLC), with topline overall survival data of the open label phase 2 clinical trial expected in Q2 2024; pancreatic cancer, with an update on overall survival based on an interim analysis of the randomized, open label clinical trial in Q2 2024; and prostate cancer, with topline data for both fully enrolled randomized, blinded, placebo-controlled phase 2 and phase 3 clinical trials in Q4 2024."

P1 data • P2 data • P3 data • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor