Interius BioTherapeutics has announced the first patient has been dosed with INT2104, marking a significant step forward in the field of in vivo CAR-T cell therapy. This lentivirus-based gene therapy aims to create CAR-T and CAR-NK cells directly within the patient to target CD20-positive B cells, offering a potentially transformative approach for treating B-cell malignancies. The company anticipates releasing early clinical data in the first half of 2025.
The Promise of In Vivo CAR-T Therapy
Traditional ex vivo CAR-T cell therapy has shown remarkable success in treating blood cancers. However, its high cost and complex manufacturing process limit its accessibility. A study surveying 17 centers revealed a median wait time of seven months for a CAR-T therapy slot, during which an estimated 25% of patients died while waiting. Interius BioTherapeutics aims to address these challenges with its in vivo approach.
Phil Johnson, MD, CEO of Interius BioTherapeutics, emphasized the potential benefits of INT2104: "The simplicity of this is that you simply call the pharmacy, they send a vial down, and the virus gets infused directly into the patient. The patient can go home... [Interius] will be able to provide a drug for at least the cost of goods for less than $10,000. It’s faster, cheaper, and better."
INT2104: Targeting CD20 In Vivo
INT2104 leverages a lentiviral vector engineered to target and transduce CD7-positive cells, which are present on T cells and NK cells. This approach generates both CAR-T and CAR-NK cells, broadening the attack on lymphoma cells. While ex vivo CAR-T therapies purify target cells before modification, INT2104's in vivo method requires careful consideration of cell targeting specificity.
Interius has yet to find off-target transduction in their preclinical in vitro and in vivo testing. The company is also closely monitoring insertion sites in preclinical work and will continue to do so in human patients to mitigate any potential risks of insertional oncogenesis or mutagenesis.
Addressing Safety Concerns
As with any gene therapy, safety is paramount. The Phase 1 trial is primarily focused on assessing the safety of INT2104. "We’re in the early days of a phase one trial, which focuses primarily on the safety of the approach, especially with a first-in-human very novel modality like this," Johnson stated. Following this initial phase, Interius plans to conduct a dose-escalation trial over the next year.
Lentiviral Delivery for Long-Term Effect
Interius chose a lentiviral approach over non-viral methods like lipid nanoparticles (LNPs) because of the need for a long-term effect. Lentiviruses integrate into the genome, providing a more permanent solution compared to the transient mode of action offered by LNPs, which are better suited for RNA delivery.
Expanding Beyond Hematologic Malignancies
Interius is also exploring the potential of its platform to treat autoimmune diseases. A second program targeting CD19, another B cell marker, is being developed for conditions like lupus and myasthenia gravis, with clinical trials expected to begin in 2025. "You’ve seen all the ex vivo companies slide into [the autoimmune disease] space, which makes sense because there’s a huge need for patients," Johnson noted.
The Future of CAR-T Therapy
While the "faster, cheaper, better" mantra of in vivo CAR-T therapy is appealing, the true potential of this approach will be determined by clinical data. Interius believes that in vivo and ex vivo CAR-T therapies are not mutually exclusive and can provide optionality for patients. "We view [the two approaches] as providing optionality for patients... So, our goal is to provide patients and their families with options they have not had before," Johnson concluded.
