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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, 2-year treatment, completed (13 subjects) • Ph3, 2-year treatment, global trial (“DRAGON” Study) completed (104 subjects) • Ph2/3, 2-year treatment, global trial (“DRAGON II” Study) is ongoing (60 subjects)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 / 10Reference: 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 Tinlarebant
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B E L I T E B I O / 11 DRAGON Clinical Trial
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B E L I T E B I O / 12 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. Tinlarebant
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B E L I T E B I O / 13 Daily dosing of 5 mg/day Tinlarebant led to a sustained 80% reduction of RBP4 and RBP4 levels returned to 84 % of the baseline value at the End of Study (EOS) Biomarker: RBP4 - Percent Reduction from Baseline PD Set N=92 Efficacy Results 70% Reduction Target Tinlarebant Treatment Led to 80% Reduction in RBP4, Well Above Goal of 70%* * In a prior study of a surrogate RBP4 antagonist (fenretinide) in patients with Geographic Atrophy, an RBP4 reduction of ≥70% was associated with a statistically significant slowing of lesion growth [Mata et al., Retina. 2013; 33(3): 498-507.]
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B E L I T E B I O / 14 DDAF Represents Well-demarcated Areas of Complete RPE Loss & Grows Predictably, Making it an Approvable Primary Endpoint • DDAF (definitely decreased autofluorescence): level of darkness close to 100% (at least 90%) in reference to the ONH • QDAF (questionably decreased autofluorescence): between 50% and 90% darkness • DAF (decreased autofluorescence): the sum of DDAF and QDAF DDAF QDAF DDAF QDAF ONH Strauss RW, Ho A, Muñoz B, Cideciyan AV, Sahel JA, Sunness JS, Birch DG, Bernstein PS, Michaelides M, Traboulsi EI, Zrenner E, Sadda S, Ervin AM, West S, Scholl HPN; Progression of Stargardt Disease Study Group (2016) The Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Studies: Design and Baseline Characteristics: ProgStar Report No. 1. Ophthalmology. 123: 817-28. DAF DDAF+QDAF DAF DDAF+QDAF
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B E L I T E B I O / 15 DDAF Progression Rate in Stargardt Overall DDAF growth rate in the ProgStar cohort over 24 months: 0.74 mm2/year (confidence interval: 0.64 - 0.85 mm2/year) Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study Strauss RW, Ho A, Jha A, Fujinami K, Michaelides M, Cideciyan AV, Audo I, Birch DG, Sadda S, Ip M, West S, Schönbach EM, Kong X, Scholl HPN; ProgStar Study Group (2023) The progression of Stargardt Disease as determined by fundus autofluorescence over a 24-month period (ProgStar Report No. 17). Am J Ophthalmol. 250: 157-170.
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B E L I T E B I O / 16 Primary Endpoint: DDAF in the Study Eye (Change from Baseline) • Annualized rate of lesion growth in the aggregate area of atrophy (DDAF) from baseline as assessed by fundus autofluorescence imaging at Month 25. • Data is shown for the modified full analysis set (mFAS) which consists of all subjects who were randomly assigned to receive study drug and have received at least one dose of study medication. In addition, the mFAS subjects must have a defined DDAF lesion meeting the eligibility criteria at baseline and have at least one post baseline assessment. • Data analysis used a Mixed Model for Repeated Measures (MMRM) measuring change from baseline in DDAF in the study eye and including terms for treatment, visit, treatment*visit interaction, baseline focality of lesions, and baseline DDAF lesion size. • The Statistical Analysis Plan (SAP) specified an unstructured covariance matrix for the MMRM. The CRO also performed a post-hoc analysis using a first-order autoregressive covariance matrix to account for the longitudinal nature of the data while maintaining model stability in a relatively small sample such as in the DRAGON trial. Efficacy Results
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B E L I T E B I O / 17 Applying an unstructured covariance matrix, the treatment effect size was 35.7% compared to placebo and yielded a p-value of P = 0.0033 With a first-order autoregressive covariance matrix, the treatment effect size remained consistent (35.4%) with P <0.0001 DDAF lesion growth was slowed to 0.38 mm2/year vs. 0.59 mm2/year for placebo and 0.74 mm2/year observed in ProgStar Primary Endpoint: DDAF Change from Baseline (Study Eye) mFAS N = 96 Efficacy Results Primary Endpoint Showed a Statistically Significant & Clinically Meaningful Outcome
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B E L I T E B I O / 18 Tinlarebant slowed DDAF lesion growth in the fellow eye by 33.6% compared to placebo (P = 0.041) Primary Endpoint: DDAF Change from Baseline (Fellow Eye) mFAS N = 95 Efficacy Results A Statistically Significant Treatment Effect Was Also Observed in the Fellow Eye for the Primary Endpoint
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B E L I T E B I O / 19 Tinlarebant slowed DAF lesion growth by 33.7% compared to placebo (P = 0.027) Key Secondary Endpoint: DAF Change from Baseline (Study Eye) mFAS N = 96 Efficacy Results Tinlarebant Slowed DAF Lesion Growth, the Key Secondary Endpoint, in the Study Eye by 33.7%
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B E L I T E B I O / 20 Tinlarebant slowed DAF lesion growth in the fellow eye by 32.7% compared to placebo (P = 0.017) Key Secondary Endpoint: DAF Change from Baseline (Fellow Eye) mFAS N = 94 Efficacy Results Tinlarebant Slowed DAF Lesion Growth, the Key Secondary Endpoint, also in the Fellow Eye by 32.7%
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B E L I T E B I O / 21 As Expected, BCVA in Study Eye Did Not Show Any Significant Change Tinlarebant Placebo BCVA at Baseline 39.9 39.4 BCVA at EOS 39.7 40.0 • The overall change of visual acuity was minimal over the period of 24 months in both treatment groups • Test–retest variability for ETDRS change scores in Stargardt disease are known to yield a repeatability coefficient ≈ 8 letters (1) • Such minor changes in average visual acuity over two years are in line with the natural history of Stargardt disease and were observed in the ProgStar Study (1) Parker MA, Choi D, Erker LR, Pennesi ME, Yang P, Chegarnov EN, Steinkamp PN, Schlechter CL, Dhaenens CM, Mohand-Said S, Audo I, Sahel J, Weleber RG, Wilson DJ. Test-Retest Variability of Functional and Structural Parameters in Patients with Stargardt Disease Participating in the SAR422459 Gene Therapy Trial. Transl Vis Sci Technol. 2016 Oct 1;5(5):10. Efficacy Results
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B E L I T E B I O / 22 ProgStar: Visual Acuity Change over 24 Months Prospective Cohort (N=434) • Overall rate of BCVA loss was 0.55 letters/year over two years • BCVA of eyes with baseline BCVA between 20/70 and 20/200 declined at a rate of 0.6 letters/year Kong X, Fujinami K, Strauss RW, Munoz B, West SK, Cideciyan AV, Michaelides M, Sahel JA, Ahmed M, Ervin AM, Schönbach EM, Cheetham JK, Scholl HPN; ProgStar Study Group (2018) Visual Acuity Change over 24 Months and its Association With Foveal Phenotype and Genotype in Individuals With Stargardt Disease: ProgStar Report Number 10. JAMA Ophthalmol. 136: 920-928.
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B E L I T E B I O / 23 Safety Results
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B E L I T E B I O / 24 Tinlarebant Demonstrated a Well Tolerated Safety Profile Safety Set N = 104 Category Tinlarebant 5mg (N=69) Placebo (N=35) TEAE 59 (85.5%) 27 (77.1%) Severe TEAE 2 (2.9%) 1 (2.9%) Serious TEAE 2 (2.9%) 4 (11.4%) Study Drug-Related TEAE 14 (20.3%) 4 (11.4%) Study Drug-Related Serious TEAE 0 (0.0%) 0 (0.0%) TEAE Leading to Study Drug Discontinuation 0 (0.0%) 0 (0.0%) TEAE Leading to Study Discontinuation 0 (0.0%) 0 (0.0%) TEAE Leading to Death 0 (0.0%) 0 (0.0%) • Total of 6 serious adverse events (SAEs) reported in the study – all events were non-ocular, with 4 assessed as unrelated and 2 assessed as unlikely related to the study treatment • Most reported Non-Ocular adverse events (AEs): Nasopharyngitis (all cases were assessed as unrelated/unlikely related to treatment), Headache, and Acne – most events were mild and resolved during the study period Subjects Who Experienced at Least One Non-Ocular Treatment-Emergent Adverse Events (TEAE), N / (%) Safety Results
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B E L I T E B I O / 25 The Majority of Ocular Adverse Events was Mild Safety Set N = 104 Category Tinlarebant 5mg (N=69) Placebo (N=35) TEAE 53 (76.8%) 8 (22.9%) Severe TEAE 2 (2.9%) 0 (0.0%) Serious TEAE 0 (0.0%) 0 (0.0%) Study Drug-Related TEAE 49 (71.0%) 8 (22.9%) Study Drug-Related Serious TEAE 0 (0.0%) 0 (0.0%) TEAE Leading to Study Drug Discontinuation 4 (5.8%) 0 (0.0%) TEAE Leading to Study Discontinuation 2 (2.9%) 0 (0.0%) TEAE Leading to Death 0 (0.0%) 0 (0.0%) • Most reported Ocular AEs: Xanthopsia, Delayed dark adaptation, and Night Vision Impairment • The majority of the events were mild, and most resolved while on study • There were no serious ocular TEAEs – 4 TEAEs lead to study drug discontinuation and 2 TEAEs lead to study discontinuation Subjects Who Experience at Least One Ocular TEAE, N / (%) Safety Results
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B E L I T E B I O / 26 Phase 3 PHOENIX Trial in Geographic Atrophy
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B E L I T E B I O / 27 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 RBP4Tinlarebant
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B E L I T E B I O / 28 GA Phase 3 “PHOENIX” (1) Enrollment 530 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 Tinlarebant
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B E L I T E B I O / 29 Summary
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B E L I T E B I O / 30 Summary of Results of the DRAGON Trial • The DRAGON trial met its primary endpoint: A highly statistically significant slowing in DDAF lesion growth was observed in subjects treated with 5 mg/day oral Tinlarebant as compared to placebo • The treatment effect was 36% and must be considered clinically meaningful • The observed treatment effect was supported by the fellow eye data and the key secondary endpoint: a reduction of DAF area growth • The change in best-corrected visual acuity was minimal in both the treatment and the placebo group – and is in-line with natural history data • The biomarker of tinlarebant treatment, RBP4 reduction, showed a sustained 80% reduction with very little variability • Tinlarebant (5 mg p.o., daily) was well tolerated in adolescent STGD1 patients Summary
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B E L I T E B I O / 31 Tinlarebant has the Potential to be the First-Ever Approved Treatment for Stargardt Disease • First-ever oral therapy in a retinal degenerative disease to demonstrate a clinically meaningful slowdown of neurodegeneration • 36% reduction in DDAF lesion growth rate, representing a robust and reproducible treatment effect in Stargardt disease • Excellent safety and tolerability profile across two years of treatment • Addresses the root pathogenic mechanism (bisretinoid accumulation), offering a rational, disease-modifying approach where no approved therapies currently exist • Broad applicability across disease stages, from early ABCA4-mediated changes to more advanced atrophy • Personal clinical impact: After >20 years caring for these patients, this represents a true game changer – a therapy I would confidently offer to all my Stargardt patients* Conclusions * Quoted from Dr. Hendrik Scholl, Chief Medical Officer of Belite Bio, based on his personal experience as an ophthalmologist tr eating STGD1 patients.
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