UGN-501 / UroGen - LARVOL DELTA

UGN-501 (investigational next-generation oncolytic virus) for use in high-grade non-muscle invasive bladder cancer (The Manila Times) - "...Company plans to initiate its Phase 1 clinical trial in NMIBC in the fourth quarter of 2026."

Trial status • Bladder Cancer

A Phase 1 Dose-escalation Study of UGN-501 Administered Intravesically in Adult Participants With Recurrent NMIBC (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: UroGen Pharma, Inc., a subsidiary of UroGen Pharma Ltd.

New P1 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

UroGen Announces FDA Clearance of the IND for UGN-501, an Investigational Next-Generation Oncolytic Virus for Non-Muscle Invasive Bladder Cancer (GlobeNewswire) - "The IND clearance enables initiation of a planned Phase 1 clinical study in patients with non-muscle invasive bladder cancer (NMIBC). The Phase 1 study is expected to begin in Q4 2026 and will evaluate the safety, tolerability, and feasibility of intravesical administration of UGN-501."

IND • New P1 trial • Bladder Cancer

UGN-501 (investigational next-gen oncolytic virus) for use in high-grade non-muscle invasive bladder cancer (GlobeNewswire) - "UGN-501 is a potent and fast-replicating investigational next-generation oncolytic virus being developed as a locally administered cancer treatment. Investigational New Drug (IND)-enabling studies are nearing completion, and UroGen plans to submit an IND in the second quarter of 2026 and initiate a Phase 1 clinical trial in NMIBC by year end....The Phase 1 trial will initially evaluate aqueous intravesical administration of UGN-501, and UroGen plans to evaluate delivery using its proprietary RTGel technology, which may enable prolonged dwell time and enhanced local activity. The initial focus is bladder cancer with the potential to expand into additional tumor types beyond the genitourinary system."

IND • New P1 trial • Bladder Cancer

UGN-501 (investigational next-gen oncolytic virus) for use in high-grade non-muscle invasive bladder cancer (HG-NMIBC) (GlobeNewswire) - "Investigational New Drug-enabling studies are currently ongoing, with the goal of submitting an IND and initiating a Phase 1 trial by the end of 2026. UroGen intends to evaluate several modes of administration, including delivery using its proprietary RTGel technology. The initial focus will be bladder cancer, and UroGen also intends to explore UGN-501's potential in a broader range of cancers beyond the genitourinary system."

IND • New P1 trial • Bladder Cancer

Safety and Tolerability of Intravenous Administration of ICVB-1042 (clinicaltrials.gov) - P1 | N=17 | Terminated | Sponsor: IconOVir Bio | N=44 ➔ 17 | Trial completion date: Dec 2026 ➔ Dec 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2026 ➔ Dec 2024; Lack of Demonstrated Clinical Activity

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Oncology • Solid Tumor

UroGen Advances Long-Term Growth Strategy by Acquiring a Next-Generation Investigational Oncolytic Virus (ICVB-1042) and Announces Multiple Strategic Research Collaborations (Businesswire) - "UroGen Pharma Ltd...announced expansion of its oncology pipeline portfolio through the acquisition of assets relating to a next-generation oncolytic virus ICVB-1042 from IconOVir Bio, Inc. (IconOVir). In addition, UroGen also announced that it has entered into multiple strategic research collaborations to explore the potential of its proprietary RTGel technology to enhance clinical effectiveness of multiple immunotherapies, including optimizing dwell time to improve treatment outcomes....On February 14, 2025, UroGen acquired certain assets of IconOVir, including product candidate ICVB-1042, and assumed certain liabilities and obligations of IconOVir arising under certain acquired contracts."

Licensing / partnership • Urothelial Cancer

Safety and Tolerability of Intravenous Administration of ICVB-1042 (clinicaltrials.gov) - P1 | N=44 | Active, not recruiting | Sponsor: IconOVir Bio | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor

Nonclinical characterization of ICVB-1042 as a selective oncolytic adenovirus for solid tumor treatment. (PubMed, Commun Biol) - P1 | "ICVB-1042 was well tolerated in mice compared to HAdV-C5 (Wt Ad5), with reduced liver sequestration, supporting safety of the drug for systemic delivery. These preclinical data demonstrating the safety and potency of ICVB-1042 for treatment of various solid tumors support the ongoing clinical investigation (NCT05904236)."

Journal • Oncolytic virus • Oncology • Solid Tumor

IconOVir Bio Announces First Patient Dosed in Phase 1 Clinical Trial of its Lead Product Candidate, ICVB-1042 (Businesswire) - "IconOVir Bio...announced that the first patient has been dosed in a Phase 1 dose escalation and expansion clinical trial evaluating intravenously (IV) administered ICVB-1042 for the treatment of advanced solid tumors....'We look forward to reporting initial safety data later this year, with potential biological proof-of-concept in the first half of 2024 and we are pleased that our first patient tolerated ICVB-1042 therapy well'."

P1 data • Trial status • Oncology • Solid Tumor

Safety and Tolerability of Intravenous Administration of ICVB-1042 (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: IconOVir Bio

Metastases • New P1 trial • Oncology • Solid Tumor

Characterizing the tumor selectivity of oncolytic adenovirus ICVB-1042: Analysis of S-phase induction, viral replication, and cytolytic activity in human primary normal cell types. (ASCO 2023) - "Viral function and killing were assessed in primary normal human renal (HRE) and bronchial (BrE) epithelial cells in the presence of the inhibitor palbociclib to pharmacologically block S-phase entry via host cell signaling. The improved tumor selectivity of ICVB-1042 results in protection of normal, non-proliferative cells from viral-mediated toxicity. The conventional approach of ICVB-2006 with a single E1A mutation leaves viral replication and cell death in normal human cells mostly intact. Together, these observations support that ICVB-1042 presents normal cell protection and reduced toxicity risks associated with OV therapy."

IO biomarker • Oncolytic virus • Infectious Disease • Oncology

Development of a novel ddPCR assay for nonclinical and clinical pharmacokinetic characterization of ICVB-1042. (ASCO 2023) - "ICVB-1042 viral genomes can be detected using ddPCR. This assay can be used to assess viral replication in vitro and PK and distribution in vivo. Use of ddPCR to detect ICVB-1042 in patient samples will be key to the characterization of clinical efficacy."

Clinical • PK/PD data • Infectious Disease • Oncology

ICVB-1042, an oncolytic adenovirus, infects and kills bladder, breast, and glioblastoma human dissociated tumor cells (AACR 2023) - "ICVB-1042 infection, replication, and cytolysis were evident across all diverse primary patient tumor types and multiple donor genotypes, with superior cytolysis compared to other indication specific OVs. ICVB-1042 maintains potent activity in vivo in patient GBM DCTs.Table 1 - Percentage OV-Mediated Cytolysis of Primary Human DTCs by Indication, Donor, and MOIIndication Bladder Breast GBMDonorMOIICVB-1042Comparator OV-1 (E1A promoter swap for tumor selectivity; hGMCSF transgene expression)MOIICVB-1042Comparator OV-2 (Ad11/Ad3 chimera; Generated by directed evolution for tumor selectivity)MOIICVB-1042Comparator OV-3 (E1A mutation for tumor selectivity; RDG-4C fiber mutation for enhanced tropism)Donor 130100%89.2%3083.4%8%30100%97.3%6100%0%690.7%0%7.5100%71.6%1.268.6%0%1.262.3%0%1.8886%5.9%Donor 230100%94.4%3078%6.9%3069.1%53.9%614.6%0%697.6%9.6%7.549.5%0%1.20%0%1.2100%8.8%1.8836.7%0%"

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

Evaluation of the anti-tumor activity of ICVB-1042, a novel E2F-tumor selective oncolytic virus, selectively targeting tumor cells in an established human glioblastoma mouse model (SITC 2022) - "All treatments were well-tolerated, resulting in no deaths or group mean body weight loss in the treatment window. Conclusions ICVB-1042, a novel E2F-tumor selective rationally designed OV engineered with enhanced tropism and tumor killing potency, produced higher anti-tumor activity in vitro and in vivo in GBM tumors compared to the D24RGD virus ICVB-940."

Oncolytic virus • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Nonclinical characterization of ICVB-1042, a novel E2F-tumor selective oncolytic virus with the potential to treat solid tumors (SITC 2022) - "Ethics Approval All procedures carried out were conducted in compliance with the applicable laws, regulations and guidelines of the National Institutes of Health (NIH) and with the approval of Labcorp Drug Development PCO’s Animal Care and Use Committee. Labcorp Drug Development (Greenfield) is an AAALAC accredited facility."

Oncolytic virus • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD46

The chimeric Ad5/Ad34 fiber of ICVB-1042 oncolytic virus requires the CD46 cell surface receptor for efficient tumor entry (SITC 2022) - "High YPET fluorescence intensity in mouse LL/2 cells harboring human CD46 transgenes was observed, denoting that human CD46 expression by LL/2 cells enabled transduction by a vector version of ICVB-1042 (figure 2A-B). Conclusions These results demonstrate that replacing wild-type fiber with the chimeric Ad5/Ad34 fiber of ICVB-1042 results in a potent OV that relies on CD46 expression for tumor entry."

IO biomarker • Oncolytic virus • Lung Cancer • Oncology • Solid Tumor • CD46

IconOVir Announces New Preclinical Data Showcasing Best-in-Class Potential of ICVB-1042, its Lead Oncolytic Virus, at SITC 2022 (Businesswire) - "In a poster presentation...IconOVir presents new preclinical data from studies comparing the anti-tumor activity and selectivity of ICVB-1042 with that of ICVB-940, a comparator virus engineered by IconOVir that is based on an adenovirus type-5 (Ad5) clinical-stage OV under evaluation for treatment of glioblastoma. The data show that: ICVB-1042 demonstrates enhanced tumor cell killing over ICVB-940 in 11 of 13 human glioma tumor cell lines; ICVB-1042 induces significant decreases in tumor volume and increases in time to progression over ICVB-940; and; ICVB-1042 is well-tolerated, resulting in no deaths or group mean body weight loss in the treatment window."

Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology

IconOVir Announces New Preclinical Data Showcasing Best-in-Class Potential of ICVB-1042, its Lead Oncolytic Virus, at SITC 2022 (Businesswire) - "On track to initiate Phase 1 trial in solid tumors in 1H 2023...IconOVir Bio, Inc... announced new preclinical data demonstrating proof-of-concept for its lead program ICVB-1042....Preclinical Data Demonstrate ICVB-1042’s Selective Replication, Broad Tumor Tropism, Safety and Anti-Tumor Activity: In a poster presentation...IconOVir describes key therapeutic properties of IV-administered ICVB-1042, including its high tumor selectivity and ability to replicate effectively in tumor tissue. The data show: ICVB-1042 is well-tolerated and induces tumor-selective replication and cell killing across a broad range of human tumor cell lines, including breast, prostate, bladder, lung and glioblastoma; ICVB-1042 is 100-fold more cytotoxic in tumor cells compared to normal cells; and; ICVB-1042 virus particles increase in both tumors and plasma over time, in a manner correlative with efficacy."

New P1 trial • Preclinical • Bladder Cancer • Brain Cancer • Breast Cancer • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor

IconOVir Announces New Preclinical Data Showcasing Best-in-Class Potential of ICVB-1042, its Lead Oncolytic Virus, at SITC 2022 (Businesswire) - "Preclinical Proof-of-Concept Data for Proprietary Mutations Designed to Improve Tropism: In a poster presentation....IconOVir describes the cell entry requirements for ICVB-1042 compared to ICVB-421 (wtAd5 + YPET). The data showed: The Ad5/34 fiber of ICVB-1042 effectively binds CD46 and not CAR; CD46 expression is required for efficient infection by ICVB-1042; CD46 deficiency induces resistance to ICVB-1042-induced cytotoxicity; and; The expression of human CD46 on mouse cells allows viral entry, but not replication of ICVB-1042."

Preclinical • Oncology

IconOVir Bio to Present Preclinical Data on Lead Candidate ICVB-1042 at SITC 2022 (Businesswire) - "IconOVir Bio...announced that it will present preclinical data on ICVB-1042 in three poster presentations at the upcoming Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2022)....In preclinical studies, ICVB-1042 demonstrated superior potency and selectivity compared to wildtype adenovirus (Ad) and other clinical-stage Ad-based oncolytic viruses, with potent lytic replication in cancer cell lines across a broad range of tumor types. IconOVir is developing both intravenous (IV) and intratumoral (IT) formulations of ICVB-1042 and plans to advance into Phase 1 studies evaluating IV-administered ICVB-1042 in solid tumors in the first half of 2023."

New P1 trial • Preclinical • Oncology • Solid Tumor

[VIRTUAL] Highly selective and potent p16-CDK-RB-E2F targeted oncolytic virus therapies. (ASCO 2021) - "Leveraging extensive research into the overlapping logic of viral and cancer pathways, we have engineered OVs, including ICVB-1042, that distinguish between tumor and normal cell proliferation . Furthermore, unlike therapies that target a single component, ICVB-1042 targets tumors with different p16-CDK-RB mutations, which all converge in activating oncogenic E2F transcription, driving exponential and tumoricidal viral replication."

IO biomarker • Oncolytic virus • Oncology • E2F1 • EP300

IconOVir Bio Announces Preclinical Proof-of-Concept Data for Proprietary Mutations Designed to Improve Selectivity of Novel Oncolytic Viruses, Including Lead Product Candidate ICVB-1042 (Businesswire) - "IconOVir Bio, Inc...announced new preclinical data demonstrating proof-of-concept for a proprietary combination of two selectivity mutations, made to Adenovirus (Ad) proteins E1A and E4-ORF6/7, both of which are incorporated into its rationally designed OV product candidates. The data, which were generated by IconOVir’s partners at the Salk Institute for Biological Studies, were shared in an abstract (e14543)...which was included in the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting Proceedings, an online supplement to the Journal of Clinical Oncology...We look forward to advancing ICVB-1042 into clinical studies in 2022...with plans to file an Investigational New Drug application with the U.S. Food and Drug Administration in the first half of 2022."

IND • New trial • Preclinical • Oncology

IconOVir Bio Raises $77 Million in Series A Financing to Develop Next-Generation Oncolytic Viruses to Treat Solid Tumors (Businesswire) - “IconOVir Bio, Inc…announced it has raised $77 million in a Series A financing….IconOVir’s lead candidate, IOV-1042 is derived from the common cold virus. Preclinical research has shown that IOV-1042 infects and kills a broad range of tumor cells, including head and neck, bladder, lung and breast, suggesting that it could have potential utility in a wide range of solid tumor indications. IconOVir expects to submit an Investigational New Drug Application (IND) for IOV-1042 in the first half of 2022.”

Commercial • IND • Oncology • Solid Tumor