Interius BioTherapeutics receives greenlight from Australian Agency to commence a Phase 1 Clinical Trial for Its First-in-Class In Vivo CAR T for B Cell Malignancies
Interius BioTherapeutics, a leading developer of in vivo cell-specific gene medicines, announced that it has been granted Human Research Ethics Committee (HREC) approval and Clinical Trial Notification (CTN) clearance by the Australian Therapeutic Goods Administration (TGA) to commence a first-in-human Phase 1 clinical trial of INT2104, its lead in vivo CAR candidate for treatment of B-cell malignancies.
Interius intends to begin the trial in the fourth quarter of 2024 and is well positioned to deliver key program milestones as early as the first quarter of 2025.
INT2104 Clinical Program
Interius’s Phase 1 trial (INVISE, Injectable Vectors for In Situ Engineering) will evaluate the safety of a single INT2104 infusion in adults with refractory/relapsing B cell malignancies. The Phase 1 study is a global, two-part, multicenter, open-label, single dose design with a dose escalation portion designed to inform the dose of INT2104 to be used in the dose confirmation part of the trial and future studies.
The targeting specificity of the vector is accomplished via engineered fusogen and binder components. Preclinical data demonstrating the potential of INT2104 were previously presented at the Cellicon Valley 2023 Meeting, held June 21 to 23, in Philadelphia. Complete tumor clearance was reported in mouse models of systemic lymphoma following treatment with the viral vector across a wide dose range. Furthermore, when INT2104 was used in nonhuman primates (NHPs), the NHPs showed significant depletion of B-cells with no toxicity reported. In 1 individual NHP, the B-cell depletion was noted to have been maintained for more than 6 months post-treatment.
In vitro preclinical work also demonstrated dose dependent transduction of CD7-positive cells, and a lack of transduction when INT2104 was administered to CD7-negative B-cell lines.2 Furthermore, transduction of both CD7-positive T-cells and CD7-positive NK cells was observed, and the CAR-positive cells demonstrated dose-dependent killing of B-cells when cocultured with B-cell tumor targets. Additional in vitro testing in 6 B-cell tumor lines and primary peripheral blood mononuclear cells from patients with B-cell malignancies indicated that off-target transduction by B-cells treated with INT2104 did not occur.
INT2104
INT2104 is a wholly-owned investigational gene therapy candidate, which specifically targets CD7-positive T and NK cells and delivers a CAR transgene to create effector CAR-T and CAR-NK cells in vivo. The CAR cells target CD20-positive B cells for the treatment of B cell malignancies. Unlike ex vivo CAR-T therapies, INT2104 is an off-the-shelf, single dose treatment, administered systemically through intravenous infusion without the need for lymphodepletion or for any special equipment or training.