Ixaka’s targeted nanoparticles (TNPs) are immunotherapies that stimulate the patient’s immune system to eliminate cancer cells by enhancing the body’s own defences, unlike chemotherapies which attack cancer cells directly.
This immunotherapy strategy is based on several decades of ground-breaking research and is now a priority strategy for scientists around the world.
The momentum for immunotherapies pivots on spectacular results achieved with chimeric antigen receptor (CAR) T-cell technology, starting in 2012 and following the development of the first approved CAR T-cell therapies (Yescarta, Kymriah and Liso-cel). These therapies have resulted in dramatic results in some patients. For example, read the New York Times article here.
Our approach to TNP
To address the limitations of current products, Ixaka employs a more universal strategy (in vivo CAR T-cells).
Our approach involves the injection of a nanoparticle therapeutic (an encapsulated lentiviral vector) directly into the patient’s bloodstream to target and genetically modify the patient’s T cells within the body.
Our TNP platform
Ixaka’s TNP platform enables therapeutic cells to be targeted and genetic modifications to be performed directly inside the body.
Our nanoparticle contains a lentiviral vector that allows in vivo genetic modification of T cells and drives expression of the CAR, enabling recognition and elimination of cancer cells.
Our first application is the generation of CAR T-cell therapies for hematological malignancies. However, modification of the components offers the potential to target a broad range of therapeutic cells for the treatment of many serious diseases, including cancers, genetic disorders, neurological and ocular diseases.
Potential benefits of Ixaka’s TNP approach
Ixaka’s TNP approach allows targeting of specific cells and expression of the gene of interest directly within the patient’s body. This makes it possible to eliminate all stages of genetic modification carried out ex vivo, as required by currently marketed products.
Ixaka’s TNP technology and synthetic gene delivery platform is highly specific and controllable, offering potentially improved efficacy and safety. It is capable of targeting any type of cell expressing a specific receptor and can modify a broad range of genes.
Unlike recently authorized products, our in vivo technology does not require a dedicated manufacturing line for each patient for the modification and production of T cells. Our standardized manufacturing is less expensive, as it does not need dedicated manufacturing sites to expand cells before use (as is required for ex vivo cell therapies). This approach not only dramatically reduces the cost of treatment, but also allows patients to be retreated when they relapse.
TNP-based in vivo CAR T-cell therapies such as Ixaka’s represent a significant advance over recently approved ex vivo CAR T-cell therapies, with the potential to be a more effective, universal and safer treatment option for patients.
CELTIC for CD19 hematological malignancies
CELTIC (Chemically Encapsulated Lentiviral vector for Targeted In vivo CAR T-cell therapy) Is Ixaka’s lead TNP program for CD19 hematological malignancies.
CELTIC consists of a polymeric nanoparticle encapsulating a bald lentiviral vector encoding for a T-cell specific promoter and the chimeric antigen receptor (CAR).
The nanoparticle is coated with a CD3 binding molecule (aptamer) allowing the in vivo targeting and transduction of the T-cells. The overall construct can be infused systemically into the bloodstream to target and genetically modify T-cells within the body.
This approach is designed to generate CAR T-cells which are potentially more efficacious and safer and considerably less expensive to produce than established CAR T-cell therapies (Novartis’ Kymriah, Gilead’s Yescarta and BMS’s Lisocabtagene Maraleucel), which have been shown to be effective and have been approved for use in CD19-malignancies.
CELTIC has numerous advantages over established ex vivo CAR T-cell therapies as well as other nanoparticle approaches.
- in vivo targeting
- High specificity
- High transduction efficiency
- Retreatment possible
- No cytokine requirement
- No transduction following disruption of the nanoparticle (bald lentivirus)
- Persistent expression
- Cell-specific promoter