MEDIA & PUBLICATION
MEDIA & PUBLICATION
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(Developed by subsidiary
Bringing Hope to Incurable Blindness
Age-Related Macular Degeneration
Patients with age-related macular degeneration in the US
Stargardt Disease prevalence rate
Case of AMD worldwide with global direct healthcare cost of USD 255B
Dry AMD estimated annual global market
Stargardt Disease estimated annual global market
First-in-Class Oral Therapy for Treatment of Dry Age-Related Macular Degeneration and Stargardt Disease
LBS-008, developed by
, a subsidiary of Lin BioScience, is a first-in-class oral therapy targeting Dry Age-Related Macular Degeneration (Dry AMD) and Stargardt Disease, which are eye diseases that cause vision loss in adults and children respectively and currently have no available treatment.
LBS-008 is a RBP4 (Retinol Binding Protein 4) inhibitor that prevents the buildup of toxins in the eye that cause Dry AMD and Stargardt. The toxins are byproduct of the eye's visual cycle, which is dependent on the presence of vitamin A (retinol). LBS-008 works by modulating the amount of vitamin A uptake into the eyes through inhibiting RBP4 which transports vitamin A into the eyes, and thus preventing the formation of the toxins associated with macular degeneration.
LBS-008 is the only Dry AMD drug candidate sponsored by and the first graduate drug candidate from the US National Institutes of Health’s (NIH) highly selective Blueprint Neurotherapeutics Network (BPN) which aims to accelerate the development of promising effective treatment for nervous system disorders with significant unmet medical needs. The BPN program leverages the resources of 15 NIH centers and provides US$10M non-dilutive funding to support the development of LBS-008 through completion of phase 1 clinical trials. In addition, UK National Institute for Health Research (NIHR) has published a systematic review of treatments for dry AMD and Stargardt disease in 2018 and recommended LBS-008’s mechanism of action in treating both diseases.
LBS-008 has obtained Orphan Drug Designation in the United States and Europe, as well as being awarded Rare Pediatric Disease (RPD) Designation in the US, for treating Stargardt disease. LBS-008 has completed its Phase I clinical trials in health volunteers and the data has demonstrated LBS-008’s superiority in safety and RBP4 lowering capability. LBS-008 is expected to initiate Stargardt phase 2 clinical trial in 2020, Stargardt phase 3 clinical trial in 2021, and dry AMD phase 2 in 2022.
Dry Age-Related Macular Degeneration (Dry AMD)
Age-related Macular Degeneration (AMD) is a leading cause of blindness in people over the age of 50 globally. This disease has two forms, dry form, which accounts for 90% of AMD cases, and wet form. Because no treatment currently exists, dry AMD is devastating for patients, affecting 170 million people worldwide (11 million in the US alone) with a global direct healthcare cost of 255 billion US dollars.
Stargardt disease is an inherited juvenile form of macular degeneration, which affects 1 in 8,000-10,000 children. Patients suffer from progressive vision loss often starting in childhood, with most patients becoming visually impaired by the age of 20. The disease is caused by a mutation in the ABCA4 gene, which leads to the accelerated formation and accumulation of A2E, a toxic by-product of the visual cycle. Accumulation of A2E in the retina causes progressive retinal cell death and permanent loss of vision. Currently, there is no treatment for Stargardt disease, which is an orphan indication.
Healthy photoreceptors and RPE cells
Dry AMD starts with insult to RPE cells
Age-dependent accumulation of lipofuscin
Rods Die Cones Spared
Formation of drusen (plaque-like sub-RPE deposits)
Complement activation (inflammation)
Progression to RPE atrophy and photoreceptor death
Several potential intervention points
How it Works (Mechanism of Action)：
Preventing the Accumulation of Toxic A2E
In order to see, light must pass through the eye and hit the light sensitive area at the back of the eye called the retina. Dry AMD and Stargardt occur when the center of retina, known as the macula, is damaged. The macula is made up of several layers of cells that work together to allow us to see clearly. The inside layer of the macula is made of photoreceptors (rods and cones) that react to light and send signals to the brain. Immediately behind the photoreceptors is a supportive layer of retinal pigment epithelium (RPE) cells. In addition to providing photoreceptors with structural support, RPE cells also supply them with nutrients and remove waste. It is believed that macular degeneration in AMD and Stargardt is caused by the abnormal buildup of A2E, a type of toxic by-products of the eye’s visual cycle, below RPE cells. Accumulation of A2E disrupts RPE cells, and subsequently causes rod and cone cells to die. Vision loss progresses with the death of photoreceptors. As RBP4 is the primary bloodstream transporter of retinol to the RPE, by modulating the amount of retinol entering the visual cycle, LBS-008 reduces the formation of A2E associated with macular degeneration and maintains the health of retinal tissues.
During the visual cycle, light is converted into electrical signals and sent to the brain for visual processing. This cycle of vision depends on the presence of vitamin A, which is transported from the blood into the RPE by circulating retinol binding protein 4 (RBP4). Once inside the RPE, retinol goes through several isomerizations until it reaches the photoreceptors as 11c-Ral. When light hits the photoreceptors, 11c-Ral is isomerized to at-Ral, which initiates the visual cycle. A natural and cytotoxic by-product of this process is a substance called A2E, which is normally processed and removed in a healthy person. However, accumulation of A2E due to aging or genetic mutations leads to AMD and Stargardt.