Enabling translational studies and clinical entry plan in gastro-intestinal inflammatory diseases and cancers for human GPR35 antagonist lead molecules.

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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. In the UK, ~300,000 people are affected by IBD, costing the NHS ~£1bn/year (~£3,352/year cost/patient).In this project, ThirtyFiveBio will develop potent human-GPR35-active antagonists with properties commensurate with dosing to rodent models of disease expressing the human target. Subsequently validating/guiding deployment of ThirtyFiveBio's advanced small-molecule human-GPR35-antagonists towards clinical applications in diseases identified through preclinical studies. This will guide and accelerate progress of human-GPR35 antagonists to patients.