We have an experienced team of scientists and researchers evaluating small molecules that may be utilized as potential treatment options for back of the eye diseases. This work often entails developing a suspension formulation for delivery into the suprachoroidal space via our SCS Microinjector. Suprachoroidal delivery of a new suspension could provide targeting, compartmentalization and durability advantages over topical or intravitreal delivery, similar to what we observed with XIPERE and CLS-AX.
Once a formulation is confirmed, we proceed with conducting non-human studies until enough data is collected to warrant submitting an IND for such a product candidate.
POTENTIAL BENEFITS
Preclinical Data Supports Durability Potential of Small Molecule Suspensions Delivered into the Suprachoroidal Space
SCS Microinjector® Expands the SCS Circumferentially and Posteriorly to Deliver Drugs to the Macula
- A natural pressure gradient exists such that IOP > Anterior SCS Pressure > Posterior SCS Pressure
- This gradient drives injectate towards the lower pressured posterior SCS
- OCT images demonstrate expansion of the SCS after injection, including the macula SCS in humans
- Suprachoroidally injected drug levels are similar peripherally and centrally in the retina and SCS in a preclinical model
References:
Sources for in-vitro IC50 range*: Stellato et al. J Allergy Clin Immol. 1999 volume 104, number 3, part 1 | Yuan et al. Haematologica 2017 Mar, 102(3) 466-475 | Inlyta, EMA 2012 May; CHMP assessment report | 2014 R13 HAE conference, Che, Wilson, Babu, Preclinical Characterization of BCX4161, an oral plasma kallikrein inhibitor, for the treatment of Hereditary Angioedema.
Lampen SIR, Khurana RN, Noronha G, Brown DM, Wykoff CC. Suprachoroidal Space Alterations Following Delivery of Triamcinolone Acetonide: Post-Hoc Analysis of the Phase 1/2 HULK Study of Patients With Diabetic Macular Edema. Ophthalmic Surg Lasers Imaging Retina. 2018;49(9):692-697. doi:10.3928/23258160-20180831-07, | Kansara VS, Cooper M, Sesenoglu-Laird O, Muya L, Moen R, Ciulla TA. Suprachoroidally Delivered DNA Nanoparticles Transfect Retina and Retinal Pigment Epithelium/Choroid in Rabbits. Transl Vis Sci Technol. 2020;9(13):21. Published 2020 Dec 15. doi:10.1167/tvst.9.13.21 | Leroy Muya, Viral Kansara, Thomas Ciulla; Pharmacokinetics and Ocular Tolerability of Suprachoroidal CLS-AX (axitinib injectable suspension) in rabbits. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4925 | Emi K, Pederson JE, Toris CB. Hydrostatic pressure of the suprachoroidal space. Invest Ophthalmol Vis Sci. 1989;30(2):233-238. Willoughby et al., Choroidal Changes After SuprachoroidalInjection of Triamcinolone Acetonide in EyesWith Macular Edema Secondary to Retinal VeinOcclusion, American Journal of Ophthalmology, Feb 2018.