Regeneration of radiation-damaged salivary glands using neurogenicstimulation of stem cells

ABSTRACT Xerostomia (dry mouth) is a disease caused by reduced or lost salivary gland function that leads to a significantly diminished quality of life and poor oro-digestive health. Dry mouth has been reported to affect as many as 1 in 4 adults over 50 years of age. Disease severity ranges from significant to tolerable based, in part, on the cause of xerostomia, which include radiation therapy for head and neck cancer, the autoimmune disease Sjogren’s syndrome, as a side-effect of over 5000 medications, or simply natural aging. Current treatments are primarily palliative and associated with significant side effects that result in patients predominately choosing simple solutions such as constantly drinking milk or water to address disease symptoms. Importantly, there are no regenerative therapies on the market that address the underlying cause of xerostomia. This leaves xerostomia patients without any sustainable or effective treatment options and an unmet clinical need for a long-term, curative treatment. Hydronovo’s solution is an innovative product, Ceviginate (CVGN8), which is an injectable neuromimetic hydrogel that regenerates the salivary gland by restoring the function of salivary stem cells. Importantly, we have established the mechanism of action and efficacy of CVGN8 in high- impact, peer-reviewed scientific publications to show that the long-term secretory function of the salivary gland can be restored in radiation-damaged tissue. The regulatory pathway of CVGN8 is simplified by utilizing an active compound that has already secured FDA clearance and a biomaterial excipient that has been established as safe for food and other medical applications. Hydronovo has received verification in pre-IND correspondences with the FDA that the accelerated 505(b)2 pathway is appropriate for CVGN8. In response to NOSI NOT-EB-24- 001 “Translating Biomaterials-Based Technologies to Commercially Viable Products”, the goal of this SBIR direct to phase II (D2P2) application is to complement our current grant funding – an NIH NIDCR C-Doctor Technology Development Grant (NIDCR U24DE026914) and a California Institute of Regenerative Medicine (CIRM) Translational Grant (TRAN1-15330) – to conduct critical IND-enabling studies in preparation for our full IND package. Hydronovo’s existing funding is currently supporting the development and production of GMP- grade CVGN8 and a first-species (rabbit) GLP safety study. For this proposal, we will complete three independent objectives: (1) Conduct the FDA-requested second-species large animal GLP safety study, (2) develop packaging and complete shelf life testing for CVGN8, and (3) establish a CVGN8 testing plan in response to FDA correspondence. Hydronovo’s mission is to regenerate tissue by restoring crosstalk between the nerve and organ-specific stem cells. With our first product, CVGN8, we aim to improve the quality of life and survivorship of head and neck cancer patients suffering from debilitating xerostomia. Hydronovo’s evidence- based therapeutic and FDA-reviewed IND-enabling pathway has been de-risked and is positioned to complete a successful SBIR D2P2 in preparation for our first-in-human study.