T-CURX
Democratizing CAR-T Cell Therapy

Immunotherapy is paving the way for a paradigm shift in the treatment of cancers and preventing relapse. Yet, only a portion of patients benefit from this transformative therapy. Current cell therapy products in the market are barely accessible due to limitations in scalability and cost in manufacturing CAR-T cells with lentiviral and retroviral gene transfer.

T-CURX is addressing this compelling market need through its proprietary CAR-T cell manufacturing technology aimed at increasing the accessibility of cancer immunotherapy for patients around the world. The technology is a non-viral gene transfer method centred around a novel sleeping beauty (SB) transposon. The solution is more cost-effective than viral gene transfer, as it does not require the manufacturing of lentiviral particles but only small amounts of DNA and mRNA, making it unlimited in scalability.

“We want to democratize CAR-T cell therapies and offer potentially the first, best-in-class, curative cell therapies for more cancer patients by lowering costs and making it essentially unlimited in scalability,” says Dr. Ulf Grawunder, CEO of T-CURX.

Unlike me-too companies, T-CURX is on an ambitious mission to develop novel cell therapies that address cancer indications with high and unmet medical needs, lymphomas, leukaemia, and solid tumours, for which it is challenging to develop successful CAR-T therapies.

T-CURX prepares the CAR-T cells from primary T cells isolated from the patient, making it an “off-the-shelf” autologous cell therapy. The T cells are inserted with a minicircle DNA cargo encoding the CAR construct in combination with an mRNA molecule that encodes the SB transposase enzyme. This combination is proven to have the highest gene transfer efficiency and viability for the T cells. T-CURX employs electroporation for the transfer process.

By using an SB transposase instead of piggyBac transposase, T-CURX increases safety in the gene transfer methods.

piggyBac transposase inserts into actively transcribing genes, which has led to the onset of leukemia in two patients in a clinical trials. T-CURX uses the SB transposase with the insertion performed through a random integration pattern into safe harbor regions in the genome to avoid any safety issues that were visible in piggyBac transposase insertions.

In addition to the proprietary SB transposon feature, T-CURX’s manufacturing technology includes two more proprietary technologies—Matchmaker and an ON/OFF safety switch.

The matchmaker technology is designed to improve the efficacy of the CAR-T cells functionality by employing a novel modular spacer sequence derived from a natural sequence in immunoglobulin antibody IgG class three. This highly repetitive element makes the antibody very flexible and is a short motif present in serum, making it tolerable for the human immune system. By opting for a short motif, T-CURX proved through its in vitro and in vivo animal models that it can identify the ideal spacer length for the CAR-T cell’s optimal activity with higher efficacy in vivo and better tumour clearance.

Once the CAR-T cell is introduced into the patient, it must continue to kill tumours and not harm the healthy cells. At times, the CAR-T cells are potent enough to overreact, leading to a cytokine storm. It can also result in too rapid killing of tumor cells, causing the accumulation of cellular debris, which is the tumor lysis syndrome, interfering with blood circulation. T-CURX prevents this through a safety switch mechanism that uses a specific tyrosine kinase inhibitor—Dasatinib. By temporarily silencing the T cells with Dasatinib, T-CURX does not have to eliminate the CAR-T cells. The cells re-activate in presence of a cancer cell due to the T cells’ memory characteristics, ensuring its long-lasting effect.

T-CURX is bringing these features to the market through the development of a unique four-product pipeline of “off-the-shelf autologous cell therapies” targeting novel targets apart from CD-19 and BCMA for which CAR-T products already exist. The first product targets SLAMF7/CS1 in multiple myeloma and is currently in clinical development phase one. The second CAR-T program (novel target) is focused on AML and is ready for clinical trial application. Target programs three and four are for novel targets expressed in blood cancer or haematological and as well in solid tumour indications.

T-CURX’s first product is now at a dose level testing in phase one of clinical trials. It is currently testing out sentinel or lower doses at a sub-therapeutic level. The technology shows promise with zero toxicity, and T-CURX is looking forward to advancing to the trial’s second phase, taking them one step closer to saving the lives of numerous cancer patients.