A Phase 1b, Open-Label, Parallel Single-Dose Study to Evaluate the Pharmacokinetics and Pharmacodynamics of Tinlarebant in Healthy Volunteers Aged 50-85

This is a Phase 1b, parallel single-dose study to evaluate the Pharmacokinetics and Pharmacodynamics of tinlarebant when administered as a single oral dose to healthy volunteers aged 50-85. Tinlarebant also known as LBS-008 is being developed as an oral treatment to slow or halt progression of dry age-related macular degeneration (AMD) and juvenile onset macular degeneration, known as autosomal recessive Stargardt disease (STGD1). Both dry AMD and STGD1 are triggered by abnormalities in the retinal pigment epithelium (RPE) that induce secondary degeneration of photoreceptor cells. The ABCA4 gene encodes an ATP-dependent transporter (known as ABCA4, or Rim Protein). This protein resides at the rim of rod and cone photoreceptor disc membranes where it removes light-activated visual chromophore from the retina permitting vitamin A detoxification by a retinaldehyde dehydrogenase (AtRDH) which produces retinol. Retinol liberated from the retina is then taken up by the RPE and is enzymatically re-processed back to a light-sensitive visual chromophore. The RPE also converts dietary vitamin A (retinol) delivered from the blood circulation into visual chromophore and transfers it to the retina in order to maintain light sensitivity and function of the retina. It is important to note that the RPE shows a unique preference for uptake of retinol bound to RBP4. This is due to the unique expression of an RBP4 receptor, which is only expressed in the RPE and brain. In the absence of a functional ABCA4 protein, retinaldehyde accumulates within photoreceptor outer segments where it generates membrane-damaging reactive oxygen species and also spontaneously reacts with cellular lipids. These oxidized membranes and lipid-retinaldehyde species are gradually taken into the RPE through normal phagocytic processing where they form stable bisretinoid compounds, such as A2E. It is theorized that these compounds reach a critical mass within RPE phagolysosomes and cause dysfunction of the metabolic activities of the RPE leading to early accelerated accumulation of lipofuscin which fluoresces due to the high concentration of vitamin A byproducts. Clinically, the presence of autofluorescent lipofuscin precedes the appearance and growth of retinal lesions and VA loss in both GA in dry AMD and STGD1 patients. The LBS-008 drug product for the Phase 1b portion of the Phase 1b/2 study in adolescents with STGD1 is an extemporaneously prepared capsule intended for oral administration. A total of up to 16 healthy volunteers aged 50-85 are planned to be enrolled into 2 cohorts (8 participants per cohort). Participants will receive a single oral dose of tinlarebant, either 5 mg (Cohort 1) or 10 mg (Cohort 2). Tinlarebant will be administered in tablet form; a single tinlarebant tablet will contain 5 mg of IP. Participants in Cohort 1 will receive 1 tinlarebant tablet (5 mg dose) and participants in Cohort 2 will receive 2 tinlarebant tablets (10 mg dose). Enrolment and dosing of participants in Cohorts 1 and 2 may occur concurrently. Healthy volunteers aged 50-85, will be screened between Day -28 and Day -2, inclusive. Participants will be admitted to the clinical facility on Day -1 with tinlarebant dosing to occur on the following day (Day 1). All participants will be dosed under fasted conditions. Participants will be confined at the clinical facility from Day -1 through to Day 2 , with discharge following completion of all PK and PD blood sample collections and other scheduled assessments on Day 2. Participants will receive a single dose of tinlarebant tablet (s) in the morning of Day 1. Compliance will be monitored by site staff witnessing of dosing and will be documented in participant study files. If participants experience any clinically significant (CS) AEs during the confinement period, they may remain in the clinical facility for further observation at the discretion of the Principal Investigator (PI). Blood samples for PK and PD analysis will be collected pre-dose and at timepoints up to 24 hours (Day 2) post-dose during the confinement period. Participants will be required to attend the clinic as outpatients on Days 3, 4, 6 and 8 for further safety assessments, PK and PD blood sampling. Participants will then return to the clinical facility for final safety assessments at an EOS on Day 15. In the event of early study termination prior to the End Of Study (EOS) visit (Day 15), participants will be requested to attend the clinic for an early termination (ET) visit.