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Dr. Tom Lin sat down for a feature length interview with Onyx.
Why did you found Belite Bio?
I’m trained in multidisciplinary medicine and since my PhD I’ve been particularly interested in neurodegenerative diseases. The central nervous system (CNS) is incredibly complex, and we still don’t fully understand many of the underlying causes of the diseases rooted there.
Working on my MBA at Columbia Business School, I came across an emerging drug candidate being developed at the medical school. This eventually became known as Tinlarebant, and to be honest getting the rights wasn’t easy.
There was interest from various Big Pharma companies, but being a student at Columbia University gave me an advantage. I made a business case to the university and Belite Bio was born. The name comes from the Bible: “Let there be light.”
What’s so special about Tinlarebant, how does it work?
The eye is a highly metabolically active organ. Vitamin A, which is continually used for regenerating visual chromophore, can also fuel the formation of toxic vitamin A byproducts, called bisretinoids. Bisretinoids have been observed in patients with dry age-related macular degeneration (AMD) and Stargardt disease (STGD1). In STGD1 patients, mutations in a key vitamin A processing enzyme within the retina (ABCA4) leads to an accelerated formation of bisretinoids and early loss of vision. Bisretinoids are also found in the eyes of healthy elderly subjects, however, the concentrations are very low. In patients with AMD and STGD1, these toxins are found in exceedingly high amounts and are believed to cause photoreceptor cell death leading to progressive loss of vision.
“Like managing cholesterol with statins—by controlling an essential substance within safe limits, you can prevent long-term damage.”
Tinlarebant targets a protein called retinol-binding protein 4 (RBP4). RBP4 is the sole carrier protein for delivery of vitamin A from the liver to the eye. By limiting the amount of RBP4 in the bloodstream, tinlarebant reduces the amount of vitamin A delivered to the eye, leading to reduced bisretinoid accumulation. Through various studies, we’ve found that RBP4 can be reduced to a significant extent without compromising normal vision function.
The conventional treatment for retinal diseases is an eye injection. Could a pill replace an injection?
Definitely. If you look at the current landscape of ophthalmology treatments, particularly for AMD, the standard of care usually involves regular intraocular injections—injections directly into the eye (and there is no treatment available for Stargardt disease). But most people don’t want a needle in their eye, right?
While these therapies represent a significant scientific step forward and have heightened hope among patients and ophthalmologists alike, injections have significant downsides, including invasiveness and discomfort. There are risks too: infection, inflammation, retinal detachment, and over the long term patients may find it hard to comply due to the treatment burden.
Stargardt disease and Geographic Atrophy progress over years, and thus frequent injections aren’t practical or sustainable. Oral therapies, on the other hand, provide a much more patient-friendly solution. Patients can take a pill daily, without the need for frequent clinic visits for invasive procedures.
You can read the latest research at belitebio.com
