Stealth BioTherapeutics presents preclinical data on bevemipretide's retinal delivery in AMD models

(Image Credit: AdobeStock/Lili.Q)

Stealth BioTherapeutics Inc. presented new bevemipretide (SBT-272) preclinical data from a study demonstrating topical ocular delivery to the retina with protective effects observed in models of age-related macular degeneration (AMD).

The data were presented at the Keystone Symposium Targeting Dry Age-related Macular Degeneration: Pathophysiology and Emerging Therapies held September 17-19, 2024, in Pacific Grove, CA. The aim of the study was to evaluate ocular and systemic distribution of topical bevemipretide and its potential protective effects in models of AMD.¹

The study looked at bevemipretide, which targets the inner mitochondrial membrane where it reversibly binds to cardiolipin. This improves mitochondrial function and reduces the production of reactive oxygen species (ROS), according to the company.¹

In the study, New Zealand white rabbits and Yucatan minipigs were administered bevemipretide eyedrops (concentrations up to 5%, 2 times a day in both eyes) for 28 days to look at the tissue and plasma concentrations of bevemipretide after 28 days of dosing. Twenty-four hours after the final dose, animals were euthanized and blood samples were collected and both eyes were harvested.²

Additionally, rats were treated twice daily with topical bevemipretide (2%) to study retinal thickness following bright light-induced retinal degeneration. Rats were treated 2 days before light exposure and for an additional 2 weeks following exposure. On day 3, rats were exposed to 10,000 lux bright light for 1 hour to induce retinal damage, while on day 17, total retinal thickness was measured by OCT imaging.²

The protective effects of bevemipretide were also investigated using iPSC-derived retinal pigment epithelial (RPE) cells from patients with AMD.^1,2

According to the data, in both rabbits and minipigs, “bevemipretide eyedrops were well-tolerated and demonstrated desirable ocular posterior segment and systemic exposure profiles with optimized delivery to the retina and low plasma concentrations.”²

In light exposure, the bright light significantly reduced total retinal thickness in rats, which was partially mitigated by treatment with topical bevemipretide.^1,2

The viability of patient-derived RPE cells cultured on a nitrite-modified extracellular matrix was also significantly improved by treatment with bevemipretide, according to the data.²

Mitochondrial ROS production by ARPE-19 cells treated with hydroquinone was also significantly reduced by treatment with bevemipretide. This is a model used to mimic cigarette smoke-induced oxidative stress in AMD.²

Reenie McCarthy, CEO of Stealth BioTherapeutics commented on the study results in a press release from the company¹ 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.”

Stealth BioTherapeutics recently enrolled and dosed its first patient in the ReNEW trial (NCT06373731) as part of its Phase 3 clinical program for elamipretide in patients with dry AMD.

According to McCarthy, the company plans on initiating clinical studies to support further development of topical bevemipretide as a potentially disease-modifying therapy in dry AMD.

References:

1. Stealth BioTherapeutics Presents New Bevemipretide (SBT-272) Data at Keystone Symposium Targeting Dry Age-Related Macular Degeneration. Press Release; September 17, 2024. Accessed September 19, 2024. https://www.prnewswire.com/news-releases/stealth-biotherapeutics-presents-new-bevemipretide-sbt-272-data-at-keystone-symposium-targeting-dry-age-related-macular-degeneration-302251010.html

2. Targeting Mitochondria with Bevemipretide: Retinal Exposure and Protective Effects in Models of AMD. Accessed September 19, 2024. https://stealthbt.com/wp-content/uploads/Keystone2024_Targeting-Mitocondria-with-Bevemipretide.pdf