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B E L I T E B I O / 1 Mission for Vision Nasdaq: BLTE Early Intervention with an Oral Treatment for Macular Degeneration
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B E L I T E B I O / 2 This presentation (including any oral briefing and any question-and-answer in connection with it) is not intended to, and does not constitute, represent or form part of any offer, invitation or solicitation of any offer to purchase, otherwise acquire, subscribe for, exchange, sell or otherwise dispose of, any securities of Belite Bio Inc (“Belite Bio”) from any investor or in any jurisdiction in which such an offer or solicitation is not authorized or would be unlawful. No shares or other securities of Belite Bio are being offered to the public by means of this presentation. No offering of securities shall be made in the United States except pursuant to registration under the U.S. Securities Act of 1933, as amended, or an exemption therefrom. This presentation is being given on the condition that it is for use by the recipient for information purposes and to evaluate Belite Bio and the proposed offering of securities of Belite Bio and for no other purpose. Any failure to comply with these restrictions may constitute a violation of applicable securities laws. Any statements in this presentation about Belite Bio’s future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements about the strategy, operations and future expectations and plans and prospects for the Company, and any other statements containing the words “expect,” “intend”, “plan,” “predict,” “target,” “will,” “could,” “should,” “continue,” and similar expressions. This presentation contains forward-looking statements, including statements regarding the potential implications of clinical data for patients, and Belite Bio's advancement of, and anticipated preclinical activities, clinical development, regulatory milestones, and commercialization of its product candidates. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including but not limited to Belite Bio's ability to demonstrate the safety and efficacy of its drug candidates; the clinical results for its drug candidates, which may not support further development or regulatory approval; the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approval of Belite Bio's drug candidates; Belite Bio's ability to achieve commercial success for its drug candidates, if approved; Belite Bio's ability to obtain and maintain protection of intellectual property for its technology and drugs; Belite Bio's reliance on third parties to conduct drug development, manufacturing and other services; Belite Bio's limited operating history and Belite Bio's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates; Belite Bio's ability to enter into additional collaboration agreements beyond its existing strategic partnerships or collaborations, and the impact of the COVID-19 pandemic on Belite Bio's clinical development, commercial and other operations, as well as those risks more fully discussed in the “Risk Factors” section in Belite Bio's filings with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Belite Bio, and Belite Bio undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law. Market data and industry information used throughout this presentation are based on the knowledge of the industry and the good faith estimates of Belite Bio’s management. The Company also relied, to the extent available, upon management’s review of independent industry surveys and publications and other publicly available information prepared by a number of third-party sources. All of the market data and industry information used in this presentation involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. Although the Company believes that these sources are reliable, it cannot guarantee the accuracy or completeness of, and has not independently conducted verification of the relevant market data and industry information used herein. While the Company believes the estimated market position, market opportunity and market size information included in this presentation are generally reliable, such information, which is derived in part from the management’s estimates and beliefs, is inherently uncertain and imprecise. No representations or warranties are made by the Company or any of its affiliates as to the accuracy of any such statements or projections. Projections, assumptions and estimates of our future performance and the future performance of the industry in which the Company operates are necessarily subject to a high degree of uncertainty and risk due to a variety of factors, including those described above. These and other factors could cause results to differ materially from those expressed in our estimates and beliefs and in the estimates prepared by independent parties. Forward-Looking Statements and Legal Disclaimer
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B E L I T E B I O / 3 Belite Management Team Experienced Leadership Team Tom Lin, MMED, PhD, MBA (Chairman, CEO) • 10+ years of executive management roles in biotech • Over 10 new drug developments in multiple therapeutic areas including ophthalmology • University of Sydney, University of Melbourne, Harvard Medical School, Columbia University, London Business School, Hong Kong University Nathan Mata, PhD (CSO) • 15+ years of ophthalmic drug development experience across numerous indications, including two NDAs (Durezol and Zirgan) • Led clinical development efforts for the first RBP antagonist in advanced dry AMD and the first visual cycle modulator in dry AMD and STGD1 • Introduced the industry’s first STGD1 ABCA4 knockout mice model • University of Texas Hao-Yuan Chuang, CFA, MBA, FRM (CFO) • 13+ years of capital market experience; closed more than US$32 billion of transactions • Wanda, Suning, CITIC Securities • Columbia University, London Business School, Hong Kong University Hendrik Scholl, MD, MA (CMO) • 25+ years of expertise in treating retinal diseases, including Stargardt disease and AMD • Coordinating principal investigator of the largest natural history study of Stargardt disease (ProgStar Study) • Participated in over 10 clinical studies both in Stargardt disease and AMD, over 280 publications in peer-reviewed journals • University Eye Hospital Tübingen, University Eye Hospital Bonn, Wilmer Eye Institute at Johns Hopkins, University Eye Hospital Basel, Medical University of Vienna
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B E L I T E B I O / 4 Belite Bio Pipeline Overview PRECLINICAL PHASE 1 PHASE 2 NDA • A Ph3, 2-year treatment, global trial (“PHOENIX” Study) is ongoing (completed enrollment, 530 subjects) Stargardt Disease (STGD1) • Ph2 24-month final data continues to show slowing of lesion growth • Ph3, 2-year treatment, global trial (“DRAGON” Study) completed (104 subjects, age 12-20, topline data expected Q4 2025) • Ph2/3, 2-year treatment, global trial (“DRAGON II” Study) is ongoing (60 subjects, age 12-20)Tinlarebant PHASE 3 Geographic Atrophy (GA) • Tinlarebant is a novel, once daily oral tablet designed to bind to serum retinol binding protein 4 (RBP4) as a means to specifically reduce retinol delivery to the eye. This approach is intended to slow or halt the formation of the toxic retinol-derived by-products that are generated in the visual cycle and are implicated in progression of STGD1 and GA. • Belite Bio believes that early intervention directed at emerging retinal pathology, which is not mediated by inflammation, would be the best approach to potentially slow disease progression in STGD1 & GA. • Unmet Market Opportunity: • No FDA approved treatments for STGD1 • No FDA approved orally administered treatments for GA • Breakthrough Therapy, Fast Track, and Rare Pediatric Disease Designation in US and Orphan Drug designation in US / EU / JP , Pioneer Drug designation in JP , for STGD1 • 14 active patent families; composition of matter patent until at least 2040 without patent term extension
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B E L I T E B I O / 5 Tinlarebant Overview
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B E L I T E B I O / 6 MARKET PHASE I PRE -CLINICAL DISCOVERY PHASE III PHASE II 1 in 8,800 (3) The most common inherited retinal dystrophy 109k (3) 53k (3) US China Patient population with Stargardt Disease: Market Opportunity STARGARDT ADVANCED AMD • AMD patient population is expected to grow from 196M in 2020 to 288M in 2040 Reference: (1) Wan LingWong et al. Global prevalence of AMD and disease burden projection for 2020 and 2040. 2014; (2) Prevalence Estimates Vision and Eye Health Surveillance System Vision Health Initiative (VHI) CDC, 2022 (3) HananyM, RivoltaC, Sharon D (2020) Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases. ProcNatl AcadSci U S A. 117: 2710- 2716/Cornelis SS, RunhartEH, Bauwens M, Corradi Z, De BaereE, RoosingS, Haer-WigmanL, DhaenensCM, Vulto-van SilfhoutAT, CremersFPM (2022) Personalized genetic counseling for Stargardt disease: Offspring risk estimates based on variant severity. Am J Hum Genet. 109: 498-507./Mata N, QuinodozM, RivoltaC, Scholl HPN (2025) in preparation. “a promising first-in-class oral medication intended to slow or halt the progression of dry AMD” Columbia University + NIH Blueprint Tinlarebant (1) All AMD Prevalence Global 196M(1) U.S. 20M(2) % Prevalence of Advanced AMD
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B E L I T E B I O / 7 Tinlarebant PHOTORECEPTORS (PR) RETINAL PIGMENT EPITHELIUM (RPE) BLOODSTREAM RPE65 LRAT 11c-RDH at-RDH at-Ral at-RE at-Rol11c-Rol Rhodopsin ABCA4 RBP4 TTR at-Rol RBP Receptor 11c-Ral Normal Processing of Vitamin A in the Visual Cycle Retinoids Visual Pigment Tinlarebant Induced Down-Regulation Enzymes Visual Chromophore
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B E L I T E B I O / 8 Tinlarebant RPE65 LRAT 11c-RDH at-RDH at-Ral at-RE at-Rol11c-Rol Rhodopsin ABCA4 RBP4 TTR at-Rol RBP Receptor Gene mutation causes loss of ABCA4 transporter function STARGARDT A2E Mutation of ABCA4 causes accumulation of vitamin A aldehydes (Ral), which are precursors for biosynthesis of cytotoxic A2E 11c-Ral Formation of Toxic Vitamin A Byproducts in Stargardt Disease 1 (STGD1) Retinoids Visual Pigment Tinlarebant Induced Down-Regulation Enzymes Visual Chromophore PHOTORECEPTORS (PR) RETINAL PIGMENT EPITHELIUM (RPE) BLOODSTREAM
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B E L I T E B I O / 9 Tinlarebant RPE65 LRAT 11c-RDH at-RDH at-Ral at-RE at-Rol11c-Rol Rhodopsin Retinoids Visual Pigment Tinlarebant Induced Down-Regulation Enzymes ABCA4 RBP Receptor A2E Mutation of ABCA4 causes accumulation of vitamin A aldehydes (Ral), which are precursors for biosynthesis of cytotoxic A2E 11c-Ral Visual Chromophore Mechanism of Tinlarebant Action RBP4 TTR at-Rol RBP4Tinlarebant Bisretinoids are derived from vitamin A (retinol). Therefore, reducing the delivery of retinol to the eye is expected to reduce bisretinoid levels in the eye leading to preservation of the retina PHOTORECEPTORS (PR) RETINAL PIGMENT EPITHELIUM (RPE) BLOODSTREAM
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B E L I T E B I O / 10 Tinlarebant Reference: Lindner et al. Differential Disease Progression in Atrophic Age-Related Macular Degeneration and Late-Onset Stargardt Disease. Invest Ophthalmol Vis Sci. 2017;58(2):1001-1007. Similar Pathophysiology in STGD1 & GA • STGD1 and GA share a similar pathophysiology characterized by excessive accumulation of cytotoxic bisretinoids, retinal cell death, and loss of vision • Vision loss occurs slowly, despite peripheral expansion of ‘dead retina’, until the disease reaches the center of the eye (the macula) • Slowing or halting the spread of ‘dead retina’ is the intended effect of Tinlarebant treatment GA: 73-YEAR-OLD FEMALE STGD1: 61-YEAR-OLD FEMALE
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B E L I T E B I O / 11 Fenretinide Proof-of-Concept Study
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B E L I T E B I O / 12 Reduction of RBP4 Slows Lesion Growth in GA Subjects Sirion’s Ph 2 Proof-of-Concept Fenretinide Study in GA Reinforces Tinlarebant Potential 1-line gain in visual acuity at end of study ~25% statistically significant slowing of lesion growth vs placebo Tinlarebant is designed to overcome the lower potency and limited bioavailability of fenretinide Agent Ki RBP4 Tinlarebant 2 nM Fenretinide 200 nM ≥ 70% RBP4 reduction Only 1 out of 3 subjects treated with 300 mg of fenretinide achieved RBP4 reduction ≥ 70% relative to baseline Baseline 1-M 6-M 12-M 18-M 24-M3-M Reference: Mata et al. Investigation of oral fenretinide for treatment of geographic atrophy in age-related macular degeneration. Retina. 2013 Mar;33(3):498-507. N values shown for subjects with RBP4 and lesion data Fenretinide is an orally administered synthetic retinoid • Developed as an anti-cancer drug • Competes with retinol for binding to RBP4 as a side effect
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B E L I T E B I O / 13 Phase 2 STGD1 Trial
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B E L I T E B I O / 14 Tinlarebant Clinical Trial Design Overview in STGD1 Phase 2 STGD1 Phase 2 “LBS-008-CT02” (Preliminary 24-Month Interim Data Available) Enrollment 13 subjects* (QDAF, no DDAF)** Sites Australia & Taiwan Masking Open Label Placebo N/A Treatment duration 2 years Primary measures Safety & tolerability, optimal dose Other measures DDAF, QDAF, BCVA, SD-OCT, microperimetry Interim analysis Yes Key inclusion criteria 12-18 years old, diagnosed STGD1 with at least one mutation identified in the ABCA4 gene Reduction in Lesion Growth Rate (DDAF) as Measured by Retinal Imaging is the FDA Accepted Primary Endpoint in STGD1 and GA *LBS-008-CT02 initially enrolled 13 subjects in Australia and Taiwan. One subject in Australia was lost to follow up, therefore 12 subjects with complete 24-month data were evaluated. **DDAF = definitely decreased autofluorescence; QDAF = questionably decreased autofluorescence.
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B E L I T E B I O / 15 Tinlarebant • The 5 mg daily dose was effective to reduce RBP4 level by a mean of approximately 80% relative to baseline • RPB4 levels returned to 87% of the baseline value at End of Study (28-days following drug cessation) • Recovery of RBP4 concentration correlated well with the decreased tinlarebant exposure Ph2 24-month: Reduction of Plasma RBP4 Levels Note: Preliminary data and is subject to data verification and clean-up Target Threshold (≥70% RBP4 reduction)
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B E L I T E B I O / 16 Tinlarebant Note: * Only 50 patients from ProgStar Cohort (aged ≤18 ) were included in the analysis due to one subject having ungradable screening FAF data 1. Strauss RW, Ho A, Muñoz B, et al. ProgStar Report No. 1. Ophthalmology. 2016;123(4):817-28. 2. Strauss RW, Muñoz B, Ho A, et al. ProgStar Report No. 9. JAMA Ophthalmol. 2017; 135(11):1232- 1241. • No development of DDAF in 5 of 12 subjects at the 24-month timepoint • A comparison of the 24-month DDAF lesion growth between Tinlarebant-treated subjects and ProgStar participants possessing similar baseline characteristics (aged ≤18 years) showed a sustained lower DDAF lesion growth in Tinlarebant-treated subjects over the 24-month treatment period (p<0.001) Ph2 24-month: Sustained Lower Lesion Growth Compared to ProgStar LBS-008-CT02 ProgStar Cohort 1, 2 Patient Pool N=12 N=51* (aged ≤18 years) Mean change in incident DDAF lesion size at Month 24 0.51± 0.4 mm2 1.00 ± 1.3 mm2 Note: Preliminary data and is subject to data verification and clean-up Growth of Incident DDAF Retinal Lesions Change in incident DDAF lesion size (mm2) ProgStar Cohort (linear regression) Tinlarebant Subjects (linear regression) p<0.001 • A comparison of incident DDAF lesion growth among ProgStar subjects with similar baseline characteristics as subjects in LBS- 008-CT02 (i.e, ≤ 18 years old) was performed
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B E L I T E B I O / 17 DRAGON Clinical Trial Interim Analysis
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B E L I T E B I O / 18 Tinlarebant DRAGON & DRAGON II Clinical Trial Design in STGD1 STGD1 “DRAGON” Phase 3(1) STGD1 “DRAGON II” Phase 1b/2/3 Enrollment 104 subjects (have DDAF) 60 subjects (have DDAF) Sites Global Japan, US, UK Randomization 2:1 ratio (Tinlarebant : Placebo) 1:1 ratio (Tinlarebant : Placebo) Masking Double Blind Treatment duration 2 years Primary measures Efficacy as measured through DDAF lesion growth rate, safety & tolerability Other measures QDAF, BCVA, SD-OCT, microperimetry Interim analysis Yes Key inclusion criteria 12-20 years old, diagnosed STGD1 with at least 1 mutation identified in the ABCA4 gene, atrophic lesion size within 3 disc areas (7.62 mm2), a BCVA of 20/200 or better Reduction in lesion growth rate (DDAF) as measured by retinal imaging is the FDA accepted primary endpoint in STGD1 and GA (1) FDA may require another clinical trial depending on the data from the ongoing Phase 3 study.
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B E L I T E B I O / 19 Tinlarebant DRAGON Clinical Trial Demographics and Baseline Characteristics Mean (SD), Total N=104 Age (Years) 15.4 (2.47) Baseline Height (cm) 168.12 (10.349) Baseline Weight (kg) 61.75 (16.891) Baseline BMI (kg/m2) 21.62 (4.578) N (%), Total N=104 Sex Male 65 (62.5%) Female 39 (37.5%) Race White 38 (36.5%) Asian 58 (55.8%) Multiple 1 ( 1.0%) Other 7 ( 6.7%)
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B E L I T E B I O / 20 Tinlarebant DRAGON Interim Analysis Conclusions • Additional DSMB comments: • It is recommended to submit the data for further regulatory review for drug approval • No modification of the study is required • Continue the study without sample size increase • Tinlarebant (5 mg p.o., daily) continues to be safe and well tolerated in adolescent STGD1 patients • At the time of the Interim Analysis, the overall withdrawal rate is 9.6% (10 of 104 Subjects); the withdrawal rate due to ocular adverse events is 3.8 % (4 of 104 Subjects) • Visual acuity was stabilized in the majority of subjects, with mean change from baseline of less than three letter scores under both standard and low luminance, throughout the two-year study
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B E L I T E B I O / 21 Tinlarebant Adverse Events Severity Frequency N=104 (# and % of patients) Xanthopsia Mild 28 (26.9%) Delayed Dark Adaptation Mild 27 (26.0%) Night Vision Impairment Mild 15 (14.4%) Headache Mild 8 (7.7%) DRAGON Interim Safety Data Treatment-Emergent Adverse Events • Tinlarebant (5 mg p.o., daily) continues to be safe and well tolerated in adolescent STGD1 patients • Xanthopsia and Delayed Dark Adaptation are the most common drug related ophthalmic AEs • Majority of Xanthopsia, Delayed Dark Adaptation and Night Vision Impairment were mild; some resolved while on treatment • Headache is the most common treatment-related non-ocular AE • No severe or serious treatment-related AEs reported • No clinically significant findings in relation to vital signs, physical exams, cardiac health, or organ functions Note: Data Extraction Date as of 11Feb2025; for ocular AE, only frequency > 10% is listed and for non-ocular AE, only frequency > 7% is listed
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B E L I T E B I O / 22 Tinlarebant DRAGON Interim Visual Acuity Data Change from Baseline (ETDRS Letter Score, Mean) Visual Acuity Was Stabilized
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B E L I T E B I O / 23 Phase 3 PHOENIX Trial in Geographic Atrophy
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B E L I T E B I O / 24 Tinlarebant Dosing Period Final dose 70% Reduction Phase 1, 5mg Daily Dosing in Healthy Adults: Mean Percent Reduction of RBP4 (excludes placebo) Tinlarebant: ≥ 70% Reduction of RBP4
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B E L I T E B I O / 25 Tinlarebant GA Phase 3 “PHOENIX” (1) Enrollment 529 subjects Sites Global Masking Double Blind Placebo 2:1 ratio (Tinlarebant : Placebo) Treatment duration 2 years Primary measures Slowing of atrophic lesion growth, safety & tolerability Other measures BCVA, SD-OCT, microperimetry Interim analysis Yes Clinical Trial Design Overview in GA • Established Efficacy Endpoint – Reduction in atrophic lesion growth rate as measured by retinal imaging is the FDA accepted primary endpoint • Early Intervention – Targeting patients with small lesion size to potentially slow disease progress at an early stage • Oral Once a Day Treatment – well suited for long-term treatment for chronic diseases • Broad Potential – Primary focus on GA; potential to treat earlier stages (e.g., intermediate AMD) (1) Additional Phase 3 study expected to be required prior to NDA filing
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