Belite Bio, Inc. (NASDAQ: BLTE) is set to present data from its completed Phase II trial of Tinlarebant (LBS-008) in adolescents with Stargardt disease at the American Academy of Ophthalmology (AAO) 2024 Annual Meeting in Chicago, IL. The presentation will highlight the potential of Tinlarebant, a novel oral therapy, to address the unmet medical needs of patients with this inherited retinal disease.
Tinlarebant's Mechanism of Action
Tinlarebant is designed to reduce the accumulation of bisretinoids, toxic by-products of the visual cycle that contribute to retinal cell death in Stargardt disease type 1 (STGD1) and geographic atrophy (GA). By reducing the levels of serum retinol binding protein 4 (RBP4), the protein responsible for transporting vitamin A (retinol) to the eye, Tinlarebant aims to modulate the amount of retinol entering the eye, thereby reducing bisretinoid formation.
Phase II Trial Results in Adolescent Stargardt Disease
The Phase II study enrolled thirteen subjects aged 12 to 18 years with Stargardt disease, confirmed by genetic testing for ABCA4 mutations. Patients were treated with 5mg/day of Tinlarebant for two years. The primary outcome measure focused on safety, tolerability, and optimal dosing, while secondary measures included assessments of fundus autofluorescence (FAF), visual acuity, optical coherence tomography (OCT), and microperimetry.
According to Quan Dong Nguyen, MD, MSc, presenting author and a key investigator in the trial, "Visual acuity was stabilised during the study with a mean loss of five letters in the cohort over 24 months. Many of our subjects who entered the programme have shown significant bilateral vision loss prior to enrollment. For example, in a subgroup of six subjects, they have shown a mean of a ten-letter loss per year prior to enrollment. Following 24 month treatment in the programme, the mean visual acuity loss in this group was just three letters a year."
Key Findings
- Lesion Growth: The study examined the transition from questionable autofluorescence (QDAF) to definite autofluorescence (DDAF) lesions and the growth of incident lesions. In five of twelve subjects, there was no incidence of lesion growth, and in seven of twelve subjects, no expansion of autofluorescence was observed.
- Visual Acuity: Visual acuity was stabilized during the study, with a mean loss of only five letters in the cohort over 24 months. A subgroup of six subjects who had previously experienced a mean loss of ten letters per year prior to enrollment showed a reduced mean visual acuity loss of just three letters per year during the 24-month treatment period.
- Safety and Tolerability: Adverse events such as sentopsia and chromatopsia were reported, but were generally mild and well-tolerated. Encouragingly, none of the thirteen subjects dropped out of the study due to adverse events.
Ongoing Phase 3 Trials
Belite Bio is currently conducting two Phase 3 trials (DRAGON and DRAGON II) in adolescent STGD1 subjects and a Phase 3 trial (PHOENIX) in GA patients to further evaluate the safety and efficacy of Tinlarebant.
Potential Impact
Stargardt disease is the most common inherited macular dystrophy, affecting both adults and children. Currently, there are no FDA-approved treatments for STGD1, highlighting the significant unmet medical need. The Phase II data presented by Belite Bio offers hope for a potential therapeutic intervention that could slow disease progression and preserve vision in affected individuals.
Additional Presentation
In addition to the podium presentation, Nathan L Mata, PHD, will present an e-poster on the investigation of an oral retinol binding protein 4 antagonist in the treatment of childhood-onset Stargardt disease.
