Precision Medicine Approach and Enhanced Patient Stratification for Ulcerative Colitis and Colorectal Cancer via GPR35 inhibition

Lead Participant: THIRTYFIVEBIO LIMITED

Abstract

ThirtyFiveBio has developed a world-leading understanding of how GPR35-signalling promotes gastrointestinal inflammatory metaplasia and cancer disease biology.

In recent years, immunotherapy agents, such as checkpoint inhibitors, have led to dramatic survival benefits in some cancer patients. However, the majority of patients still do not respond adequately to these new treatments. This is because tumours are able to put up multiple barriers to prevent immune system attack and many of these are not addressed by currently approved therapies. Secondly, despite an array of options for inflammatory disorders of the gastrointestinal tract, 10%-30% of patients don't respond to initial treatments and 23%-46% lose response over-time. There's a significant need for an emergent game-changer.

Cancer represents a significant healthcare challenge: it's one of the leading causes of death worldwide with 10m deaths in 2020, 17m new cases diagnosed per annum and a total annual economic cost of ~£930bn in 2021\. In the UK alone there are \>350,000 new cases of cancer a year. The total economic burden of cancer in the UK is a staggering ~£7.6bn.

Inflammatory disorders can lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. Inflammatory bowel disease (IBD) is one of the most common autoimmune diseases.

This project will include the collaboration of internationally-recognised University of Cambridge. The consortium will focus on identifying subsets of patients in ulcerative colitis (UC) and metastatic (stage-IV) colorectal cancer (mCRC) predictive for GPR35-modulators responsiveness and validating their biomarker strategy experimentally. This will subsequently support precision patient selection and human clinical trial design.

75% of treated CRC patients relapse after 1st-line therapies, 63% after 2nd and 45% after 3rd, with overall survival ~30-36 months. This highlights the large unmet need to develop new precision therapies in CRC.

UC patients have a 6x greater risk of developing CRC, with incidence expected to increase to 3.2m patients by 2040\. Overall survival-rates for digestive tract cancers ranks among the lowest across all cancer-types, with CRC having a 5-year survival-rate of just 13%. Current therapeutic interventions for these cancers focus on inflammatory pathways.

ThirtyFiveBio's disruptive approach will provide a unique mechanism to block a GPR35-driven gastrointestinal inflammatory-metaplasia and pro-oncogenic disease-biology. This will significantly increase the chances of successful therapy by targeting the underlying causal-biology.

Lead Participant

Project Cost

Grant Offer

THIRTYFIVEBIO LIMITED £560,928 £ 392,650
 

Participant

UNIVERSITY OF CAMBRIDGE £82,443 £ 82,443

Publications

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