CAR-T is a new type of therapy that has shown stunning responses in certain blood cancers and may be replicable in other types of cancers as well. It is ‘the most personalised medicine’. CAR-T therapy works by taking immune cells from the patient’s body that fight infection – called T-cells – and training them outside the body to recognise cancer cells. They’re then grown in large numbers and reinjected into the patient whereby they can track down, fight and kill the patient’s cancer cells. CAR-T cell therapy has been extensively tested on certain blood cancers, producing some truly incredible results. In trials on B cell acute lymphoblastic leukemia, tests produced up to a 90% complete remission rate. Prescient has recently gained intellectual property rights in our collaboration with Carina Biotech.
OmniCAR is a universal immune receptor platform enabling controllable T-cell activity and multi-antigen targeting with a single cell product. OmniCAR’s modular CAR system decouples antigen recognition from the T-cell signalling domain. It is the first universal immune receptor allowing post-translational covalent loading of binders to T-cells. OmniCAR is based on technology licensed from CAR-T leaders UPenn; the SpyTag/SpyCatcher binding system licensed from Oxford university; and other assets.The targeting ligand can be administered separately to CAR-T cells, creating on-demand T-cell activity post infusion and enables the CAR-T to be directed to an array of different tumour antigens. OmniCAR provides a method for single-vector, single cell product targeting of multiple antigens simultaneously or sequentially, whilst allowing continual re-arming to generate, regulate and diversify a sustained T-cell response over time.
PTX-200 is a novel PH domain inhibitor that inhibits an important tumor survival pathway known as Akt, which plays a key role in the development of many cancers, including leukemia, breast cancer and ovarian cancer. Unlike other drug candidates that target Akt inhibition which are non-specific kinase inhibitors that have toxicity problems, PTX-200 has a novel mechanism of action that specifically inhibits Akt whilst being comparatively safer. This highly promising compound has encouraging Phase 2a data in HER2-negative breast cancer, Phase lb/2 in relapsed and refractory AML and Phase lb in recurrent or persistent platinum-resistant ovarian cancer. A new study in this field will focus on ER+ breast cancer.
PTX-100 is a first in class compound with the ability to block an important cancer growth enzyme known as geranylgeranyl transferase-1 (GGT-1). It disrupts oncogenic Ras pathways by inhibiting the activation of Rho, Rac and Ral circuits in cancer cells, leading to apoptosis (death) of cancer cells. PTX-100 is believed to be the only RhoA inhibitor in the world in clinical development. PTX-100 is currently in a PK/PD basket study of hematological and solid malignancies, focusing on cancers with Ras and RhoA mutations. In a previous Phase 1 trial in advanced solid tumors, PTX-100 was well-tolerated and achieved stable disease. An additional Australian trial site has recently been added to this study.
OmniCAR offers control and flexibility that is beyond the reach of current generation CAR-T cell therapy. OmniCAR is expected to provide clinicians with unprecedented control over safety aspects of CAR-T, by allowing them to tune CAR-T cell activity either up or down post-infusion, and also enables them to switch off CAR-T activity altogether by ceasing administration of the targeting ligand (i.e. a built-in “kill switch”).
Unlike conventional CAR-T, which is limited to a single target, OmniCAR-T cells are able to be armed against multiple targets sequentially or simultaneously by simply switching out the targeting ligand, which will be especially important in CAR-T making headway into the large field of solid tumours.
As the industry attempts to drive down the cost and time of delivering CAR-T therapy to patients, OmniCAR’s flexibility and control will be an increasingly valuable tool, by removing the need for multiple manufacturing runs per patient, and its compatibility with allogeneic (“off the shelf”) T-cells. OmniCAR is potentially compatible with many other CAR approaches including NK cells; macrophages and stem cells.