Company: BLTE
Filing Date: 2025-12-02
Form Type: 424B5
Source: 0001104659-25-117702
Chunk: 42

Company: BELITE BIO, INC
Filing Date: 2025-12-02
Form: 424B5
Chunk 42
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 large molecular size complex which resists elimination in the kidney. Upon entry into the RPE, retinol undergoes a series of enzymatic reactions resulting in generation of the visual chromophore, 11-cis retinal. The visual chromophore is delivered to the retina where it combines with opsin to form the light-sensitive visual pigment, rhodopsin. Photoactivation of rhodopsin liberates all-trans retinal which is transported out of the retina by the ABCA4 protein.

<div align='center'>S-27</div>

TABLE OF CONTENTS

In the absence of a functional ABCA4 protein, retinal accumulates within photoreceptor outer segments where it generates membrane-damaging reactive oxygen species, and also spontaneously reacts with cellular lipids and other retinaldehyde molecules. These retinal-retinal species, known as bisretinoids, and oxidized membranes are taken into the RPE through normal diurnal phagocytic processing where they gradually accumulate. 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 severely compromises the ability of the RPE to nourish the retina.

#### Symptoms of STGD1
<div align='center'>Source: https://makariwellness.com/stargardt-disease/</div>

#### Preclinical Proof of Concept
Abca4 – / – / Rdh8 – / – STGD1 mouse model

In the Abca4 – / – / Rdh8 – / – double knockout STGD1 mouse model, daily dosing at approximately 25 mg/kg of Tinlarebant was given for 12 weeks. A mean RBP4 reduction of approximately 90% in Tinlarebant treated double knockout mice was achieved and led to an approximately 80% reduction of A2E, that are known to cause STGD1 and have been implicated in progression of dry AMD, compared to the untreated double knockout mice.

Importantly, Outer Nuclear Layer, or ONL, thickness was significantly decreased in untreated ABCA4 – / – / RDH8 – / – mice, compared to the double knockout mice treated with Tinlarebant. Macular degeneration in dry AMD and STGD1 is associated with thinning of the ONL which indicates loss of photoreceptor cells, which is believed to be caused by excessive levels of bisretin