Ocular Therapeutix presented data from preclinical studies evaluating the efficacy, tolerability, and pharmacokinetics of its sustained-release intravitreal tyrosine kinase inhibitor (TKI) depot (OTX-TKI) using the company’s proprietary bioresorbable hydrogel fiber technology at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in Baltimore.
Tyrosine kinase inhibitors have shown promise in the treatment of wet age-related macular degeneration (AMD). However, attempts to administer topical or systemic TKIs for AMD have been limited by bioavailability and off-target effects.
In this study, the OTX-TKI investigational drug product was well-tolerated, and high tissue levels of TKI were maintained for up to 6 months in Dutch belted rabbits. For the first time, the ability to deliver an efficacious dose of TKI to the posterior segment of the eye for the treatment of VEGF-induced retinal leakage was demonstrated for an extended duration of up to six months.
“These preclinical studies of OTX-TKI have demonstrated the ability to deliver and maintain high therapeutic tissue levels of TKI in the vitreous humor, retina and choroid,” Jonathan H. Talamo, MD, Chief Medical Officer of Ocular Therapeutix, said in a company news release. “With these positive results from our preclinical studies, we are looking forward to beginning our phase 1 trial of OTX-TKI later this year.”
Four posters evaluating the OTX-TKI depot were presented at the ARVO annual meeting:
- “Pharmacokinetics of a 6 month Sustained Hydrogel Delivery System for Tyrosine Kinase Inhibitors in Dutch Belted Rabbits” - Posterboard #B0488, Abstract #1984-B0488
The pharmacokinetics over 6 months of sustained-delivery from the OTX-TKI depot placed by intravitreal injection in Dutch belted rabbits were evaluated. OTX-TKI produced significant and increasing levels of TKI in the vitreous humor, retina and choroid at months 1 through 6 without clinical evidence of local toxicity. Plasma levels were below the level of quantification, suggesting minimal risk of systemic toxicity.
- “Tolerability of a 6 month Sustained Hydrogel Delivery System for Tyrosine Kinase Inhibitors in Dutch Belted Rabbits” - Posterboard #B0460, Abstract #1956-B0460
The tolerability of sustained delivery of OTX-TKI depot delivered via intravitreal injection through 6 months was evaluated in naïve Dutch belted rabbits (n=9). Serial clinical examinations showed that OTX-TKI was well-tolerated, with no sign of inflammatory response or other abnormalities, and showed minimal histopathologic changes at 1, 3 and 6 months.
- “Tolerability of a Shape Changing Intravitreal Hydrogel Depot” - Posterboard #B0484, Abstract #1980-B0484
The tolerability of an OTX-TKI depot delivered via intravitreal injection in Dutch belted rabbits through 6 months was investigated. Serial clinical examinations showed no sign of inflammatory response or abnormal chorioretinal morphology. At 1, 3 and 6 months, histopathologic analysis demonstrated minimal changes from baseline measurement in cornea, conjunctiva, sclera, choroid, retina, and vitreous humor, suggesting the hydrogel was well-tolerated in the Dutch belted model.
- “Efficacy of a 6 month Sustained Hydrogel Delivery System for Tyrosine Kinase Inhibitors in a VEGF Induced Retinal Leakage Model” - Posterboard #B0472, Abstract #1968-B0472
The efficacy over 6 months of sustained delivery of an OTX-TKI depot placed via intravitreal injection was investigated in a Dutch belted rabbit, vascular endothelial growth factor (VEGF) induced, retinal leakage model. Eyes were challenged with VEGF injection at 2, 3 and 6 months and were evaluated for leakage. OTX-TKI significantly suppressed leakage and showed minimal to no vascular leakage through 6 months. Blank control eyes showed high tortuosity and leakage at all time points. For the first time, this study demonstrated the ability to deliver an efficacious dose of TKIs to the posterior segment of the eye using the OTX-TKI delivery platform, and the potential to serve as an alternative to the once every 4-6 week injections which are the current standard of care.
About OTX-TKI (tyrosine kinase inhibitor)
OTX-TKI is a preformed, bioresorbable hydrogel fiber depot with anti-angiogenic properties delivered by intravitreal tyrosine kinase inhibitor injection. Currently OTX-TKI is under initial preclinical investigation as a novel extended release drug product candidate.