Antibodies for the treatment of chronic kidney disease: Technical proof of concept

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"It is estimated that 15.1% of adults will develop advanced chronic kidney disease (CKD) during their lifetime. In the UK, NHS spends £1.23 billion treating CKD each year, with approximately £500 million being spent on dialysis for patients with end-stage renal failure. These patients need to visit hospital at least 3 times weekly for sessions of 4-6 hours, and are limited to 700 mL fluid intake per day. Keeping these patients off dialysis is a therefore a major healthcare challenge. However, even among CKD patients who do not need dialysis, the mortality rate is 36 times higher in patients aged 16-49, and 12 times higher in patients aged 50-64, than age matched controls.In spite of the enormous need, CKD patients are poorly served by current treatments. The only medications with any proven benefits are renin-angiotensin system inhibitors, which work by controlling blood pressure. However patients on these medications still experience progressive kidney loss. There is therefore an urgent need for new treatments that work through separate mechanisms, which can be layered on top of the existing standard-of-care.There is significant evidence for the role of a single cell membrane protein in fibrosis and vascular leak -- processes central to the progression of CKD. Unfortunately, this protein has proven difficult to drug. A small molecule inhibitor recently showed significant benefit in a Phase II clinical a different disease, where fibrosis and vascular leak are also pathological. However, the inhibitor also showed off-target toxicity. Other companies have struggled to produce molecules that fully inhibit signalling by this target.DJS Antibodies has addressed this target by leveraging our unique antibody discovery platform. In previous work, we discovered the world's first lead mAbs that bind to the target and have functional properties. Now we plan to develop these lead antibodies into development candidates, and test them in human and rodent models of disease to obtain a comprehensive preclinical proof-of-concept data package.Success in this project will directly result in DJS either partnering our antibody for development with a major pharma partner, or raising Series A investment to develop the lead candidate to IND approval. With a best-in-class therapeutic supported by rodent _in vivo_ and human _ex vivo_ data packages, DJS will be positioned to exploit the significant commercial opportunity associated with this huge unmet medical need."