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These three technologies offer a platform of novel CAR-T cell enhancements for improving CAR-T persistence in the tumor microenvironment.

Specifically, they offer three solutions for failure of CAR-T proliferation and persistence, which remains a significant issue. This is achieved by co-expressing the CAR targeting sequence alongside domains involved in amino acid metabolism. These technologies are:

  • Engineering CAR-T cells to synthesise arginine precursors. We have strong in vivo efficacy data including enhanced proliferation, increased anti-tumour activity and prolonged survival (publication – PMID:32573723, patent application WO2019122936).
  • Promoting more efficient use by CAR-T cells of available arginine. The data demonstrate enhanced anti-tumour activity in vivo (patent application WO2020260908).
  • A universal approach to address amino acid limitations in the tumour microenvironment. Strong in vitro data establish enhanced CAR-T proliferation (patent application filed).

Cancer Research UK is looking to license these technologies individually or together.

Highly accurate and robust multiplexed sequencing assay for the stratification of tissue/tumours into microsatellite instability high (MSI-H) vs microsatellite instability suppressed (MSS) subtypes. This technology allows the stratification of cancer patients for immune checkpoint blockade therapy. Current sequencing and IHC based MSI analysis requires time consuming and costly expert analysis and is not designed to handle the volume of MSI analyses associated with new clinical guidelines (MHRA, FDA). Through the use of shorter markers than current tests and analysis using a proprietary algorithm, this assay offers the first reported automation-ready MSI testing for colorectal cancer and Lynch syndrome patients.

ORACLE is a new genetic test that combines machine learning with our understanding of tumour evolution to distinguish high- and low-risk lung tumours; it is also applicable to other tumours. This technology was developed by CRUK-funded scientists as part of the TRACERx study and was featured on the front cover of Nature Medicine. The underlying ORACLE methodology also has broader applicability for identifying biomarker signatures for prognostication in other cancer-types and predicting response to therapy (both targeted and immuno-oncology drugs). 

The BEST 2/3 Trial images are a database of clinically-linked digitised pathology slides, generated during the BEST 2 and and BEST 3 clinical trials. (See https://www.mrc-cu.cam.ac.uk/research/rebecca-fitzgerald/clinical-studies/BEST2Folder and https://www.mrc-cu.cam.ac.uk/research/rebecca-fitzgerald/clinical-studies/BEST3, respectively.) These trials were aimed at testing the feasibility of a new sampling method known as the Cytosponge. The Cytosponge is pill on a string which dissolves to release a sponge that can then be removed to gather samples from the oesophagus, and it has proven to be a successful alternative to endoscopy testing for patients at high risk of developing oesophageal cancer. During these trials, 3350 patient samples were collected and stained using standard H&E techniques, with additional staining for oesophageal cancer-related biomarker TFF3, and they were subsequently digitised. In addition to the digitised slides, biopsy results and the outcomes of complementary endoscopy testing can be provided upon approval from our clinical collaborator. We would be happy to discuss non-exclusive licensing of these assets with companies in the digital pathology space or other related areas.

We have developed a first-in-class, therapeutic-quality antibody that inhibits human Arginase-2 and are seeking a partner with interest in arginase in tumour immunosuppression and other areas. The rationale for exploring the role of Arginase-2 (Arg2) in tumour immunosuppression is based on Frank Mussai’s early work showing that AML creates an arginase-dependent immunosuppressive microenvironment (1). Since then, dysregulated expression of Arg2 in the tumour microenvironment resulting in an immunosuppressive niche has been reported in other papers as well. As a result of these findings, CRUK sought to explore the hypothesis that an Arg2-specific inhibitory monoclonal antibody might restore anti-tumour immunity in cancer patients. Originating from the CRUK–AstraZeneca Antibody Alliance Laboratory, lead molecule C0021061 was developed using phage display technology (2) and shown to demonstrate potent nM inhibition of Arg2 enzymatic activity in vitro, favourable pharmacokinetics and a novel allosteric mechanism of non-competitive Arg2 inhibition (as revealed by X-ray crystallographic studies). Data showing that C0021061 is able to reverse the Arg2-mediated suppression of T cell proliferation in vitro, taken with other information included in the attached slide deck, supports that these original findings indeed seem worth further exploration.

Licensing/collaborative opportunity around FcɣR-independent “super-agonistic” 4-IBB mABs containing a propriety hinge technology promoting CD8+ T cell activation and intratumoral Treg cell depletion.

CRUK has developed a potent, selective and orally bioavailable series of small molecules inhibiting glutaminase (GLS), with superior developability. We are seeking a co-development partner to support key in vivo data and drive rapid progression into clinical trials.

AZD3965 is a Phase 2 ready, first-in-class oral and highly selective inhibitor of MCT-1 that has shown promising signs of efficacy in early phase clinical trials in DLBCL. Initially developed by AstraZeneca, CRUK now holds exclusive rights to the programme. We are seeking a partner for out-licensing, with the opportunity to leverage the CRUK network to support further clinical development.

The Cox-2 Inflammatory Signature is a novel pan-cancer immuno-oncology predictive biomarker with strong proof of concept data on overall patient survival predictions across various malignancies.

We are seeking a commercial partner interested in pursuing the co-development or licensing of our imaging tracer 18F-FPIA.

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