Inflammation and ulceration of mucosal tissue, called mucositis, is a severe side effect of many commontreatments in oncology, including chemo- and radiotherapy. Mucositis development is costly to the health caresystem and can lead to poorer outcomes for patients. Mucositis of the mouth and esophagus, called oralmucositis, is particularly common in head and neck cancer patients receiving radiation therapy, where roughly80% of patients develop this side effect. Treating oral mucositis remains a large clinical unmet need with no FDAapproved treatments for patients with solid tumors. Using Sinopia Biosciences' computational platform, weidentified a unique target class and an associated small molecule for preventing and/or treating mucositis. Thetarget class has an established safety profile in patients with solid tumors. In two studies with the acute radiation-induced hamster model of oral mucositis, we observed promising results that oral administration of the compoundsignificantly decreased the duration of ulcerative mucositis and in some animals completely prevented thedevelopment of ulcers. The observed effect size was as large or larger than other compounds currently in theclinic tested in the same model. The test compound is a pan-inhibitor of several targets in the target class, eachwith multiple binding domains. In this Phase I proposal, we will test three additional compounds with differentselectivity to these targets and domains in order to understand the pharmacology of this target class to determinethe target that most contributes to mucositis amelioration. If successful, in Phase II of this proposal we willdevelop a novel compound selective for the most effective target. We will then characterize this new compoundin the fractionated radiation model of oral mucositis and the chemotherapy-induced gastrointestinal mucositis toadvance towards the clinic.
Public Health Relevance Statement: Project Narrative
Inflammation of the mouth and esophagus, called oral mucositis, is a common and severe side-
effect of chemo- and radiation therapy used in cancer treatment that has significant implications
on outcomes and health care costs. Sinopia Biosciences has identified a target class and an
associated compound that shows efficacy in reducing both the duration and severity of oral
mucositis in an established model. This proposal will test which specific protein domains within
the target class will be most effective in alleviating mucositis to aid development of a novel
therapeutic for oral mucositis.
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