Stealth BioTherapeutics Inc. has presented new preclinical data for bevemipretide (SBT-272), showcasing its potential as a topical treatment for age-related macular degeneration (AMD). The data, revealed at the Keystone Symposium, demonstrated that bevemipretide can be effectively delivered to the retina via eye drops, offering protective effects in AMD models. The company aims to advance bevemipretide as a next-generation therapeutic option for patients with this debilitating condition.
Bevemipretide's Mechanism of Action
Bevemipretide targets the inner mitochondrial membrane, where it binds to cardiolipin. This interaction is believed to improve mitochondrial function and reduce the production of reactive oxygen species (ROS). The study aimed to evaluate the ocular and systemic distribution of topical bevemipretide and its potential protective effects in models of AMD.
Study Design and Results
The study involved administering bevemipretide eye drops (up to 5% concentration, twice daily) to New Zealand white rabbits and Yucatan minipigs for 28 days. Tissue and plasma concentrations of bevemipretide were measured after this period. The results indicated that bevemipretide eye drops were well-tolerated and demonstrated desirable ocular posterior segment and systemic exposure profiles, with optimized delivery to the retina and low plasma concentrations.
In a separate experiment, rats were treated twice daily with topical bevemipretide (2%) to assess retinal thickness following bright light-induced retinal degeneration. The rats were treated for two days before light exposure and for an additional two weeks afterward. Exposure to 10,000 lux of bright light for one hour on day three induced retinal damage. On day 17, total retinal thickness was measured using OCT imaging. The bright light significantly reduced total retinal thickness in rats, but treatment with topical bevemipretide partially mitigated this reduction.
Protective Effects on RPE Cells
The protective effects of bevemipretide were also investigated using iPSC-derived retinal pigment epithelial (RPE) cells from patients with AMD. The viability of patient-derived RPE cells cultured on a nitrite-modified extracellular matrix was significantly improved by treatment with bevemipretide. Additionally, mitochondrial ROS production by ARPE-19 cells treated with hydroquinone, a model used to mimic cigarette smoke-induced oxidative stress in AMD, was significantly reduced by bevemipretide.
Future Clinical Development
Reenie McCarthy, CEO of Stealth BioTherapeutics, highlighted the potential of bevemipretide, stating, "We demonstrated in our ReCLAIM-2 study of elamipretide, our lead investigational compound, that our mitochondrial-targeted approach may reduce the progressive photoreceptor loss associated with declining visual function. We designed bevemipretide as a next-generation approach to offer a broader range of potential therapeutic options to patients living with this devastating disease." The company is also advancing elamipretide, with the first patient enrolled in the ReNEW trial (NCT06373731), a Phase 3 clinical program for dry AMD.
Stealth BioTherapeutics plans to initiate clinical studies to support further development of topical bevemipretide as a potentially disease-modifying therapy in dry AMD.
