IconOVir Announces New Preclinical Data Showcasing Best-in-Class Potential of ICVB-1042, its Lead Oncolytic Virus, at SITC 2022
- Category: DNA RNA and Cells
- Published on Thursday, 10 November 2022 18:40
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-- ICVB-1042 demonstrates selective replication, broad tropism and anti-tumor activity across multiple in vitro and in vivo models --
-- Proprietary Ad5/Ad34 mutation improves viral entry into target tumor cells, enhancing tropism --
-- On track to initiate Phase 1 trial in solid tumors in 1H 2023 --
SAN DIEGO, CA; USA I November 10, 2022 I IconOVir Bio, Inc. (IconOVir), a preclinical-stage biotechnology company pioneering the next generation of oncolytic virus (OV) therapy to improve the treatment of patients with cancer, today announced new preclinical data demonstrating proof-of-concept for its lead program ICVB-1042. ICVB-1042 is an oncolytic adenovirus (Ad), rationally designed with genomic modifications to confer tumor selective replication and enhanced tumor cell killing, as well as allow for either intravenous (IV) or intratumoral (IT) delivery. The data will be presented in three posters at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2022), which is being held in Boston, MA and virtually from November 8-12, 2022.
“The new data presented at SITC reaffirm the power of our differentiated approach to OV development, which allows us to create and combine proprietary mutations to optimize OVs, and to translate this engineering into potentially best-in-class product candidates,” said Mark McCamish, M.D., Ph.D., President and Chief Executive Officer of IconOVir. “Based on preclinical testing across a range of tumor types and preclinical model systems, we believe ICVB-1042 offers superior tumor selectivity, broader tropism and more effective anti-cancer activity compared to earlier-generation OVs, which could transform the care and treatment of people living with a range of solid tumors. We look forward to advancing ICVB-1042 into Phase 1 studies next year, as we work toward our mission of curing cancer and restoring life to every patient, everywhere.”
Preclinical Data Demonstrate ICVB-1042’s Selective Replication, Broad Tumor Tropism, Safety and Anti-Tumor Activity
IconOVir presented two abstracts describing the results of in vitro and in vivo studies. These data demonstrate that ICVB-1042 selectively replicates in tumor cells compared to normal cells, while also benefiting from enhanced tropism, anti-tumor activity and tolerability.
In a poster presentation titled, “Nonclinical characterization of ICVB-1042, a novel E2F-tumor selective oncolytic virus with the potential to treat solid tumors,” 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.
In a poster presentation titled, “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,” 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 Proof-of-Concept Data for Proprietary Mutations Designed to Improve Tropism
IconOVir presented an abstract demonstrating proof-of-concept for a proprietary mutation made to Ads to enhance tropism to malignant cells. This mutation, the replacement of wild-type fiber with a chimeric Ad5/Ad34 fiber, is incorporated into ICVB-1042.
Viral entry into target cells through interactions with surface receptor proteins is a key determinant of viral tropism. Ads contain a trimeric fiber protein with a central shaft and globular knob that help tether it to the cell surface receptor. Ad5, which was used in first-generation OV therapies, utilizes the coxsackie Ad receptor (CAR) for cell entry, however CAR downregulation during cancer progression limits the therapeutic effect of OVs that rely on this surface protein. Group B Ads instead use CD46, a receptor frequently overexpressed in cancer, for cell entry, creating an opportunity to equip OVs with chimeric fibers to enhance tropism to malignant cells. IconOVir engineered ICVB-1042 to include an Ad5/34 chimeric fiber, which enables viral entry via CD46 instead of CAR proteins, with the goal of addressing limitations of first-generation Ad5-based OVs.
In a poster presentation titled, “The chimeric Ad5/Ad34 fiber of ICVB-1042 oncolytic virus requires the CD46 cell surface receptor for efficient tumor entry,” 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.
Based in part on these results, IconOVir is developing ICVB-1042 for delivery both IV and IT. IconOVir plans to advance into a Phase 1 clinical study evaluating ICVB-1042 delivered IV in patients with advanced solid tumors in the first half of 2023.
IconOVir is a preclinical-stage biotechnology company pioneering the next generation of oncolytic virus therapy to improve the treatment of patients with cancer. IconOVir’s proprietary oncolytic virus platform is based on technology developed by scientific founder Clodagh O’Shea, Ph.D., of the Salk Institute. It is designed to address key limitations of first- and second-generation oncolytic viruses and provide a personalized therapy for cancer patients. For more information, please visit www.iconovir.com and follow IconOVir on LinkedIn.