rbp4 technology for macular degeneration
TRANSCRIPT
BELITE BIO / 1
Mission for Vision2021
RBP4 Technologyfor Macular Degeneration
Tom Lin, CEOe / [email protected]
BELITE BIO / 2
First-in-ClassTreatment for Unmet Medical NeedBelite Bio is a clinical stage drug development company focused on First-in-Class therapeutics targeting untreatable inherited orphan diseases and age-related metabolic diseases, including atrophic Age-related Macular Degeneration (“dry AMD”), Stargardt disease (“STGD”, an inherited juvenile form of macular degeneration), and NASH (Nonalcoholic steatohepatitis).
Belite Bio holds the global exclusive / all indications license of Retinol Binding Protein 4 (“RBP4”) platform from Columbia University, which covers 453 structurally distinct RBP4 antagonists under patent protection in the major pharmaceutical markets, such as United States, European Union, China, Australia, Japan, Korea and so on. Current pipeline includes LBS-008 for dry AMD and STGD, and LBS-009 for NASH.
Our initial focus is on LBS-008, which is the only drug treating dry AMD selected by the NIH Blueprint Program (“BPN”), whose mission is to discover and develop therapies treating untreatable neurological disorders which cause huge impact to the US society. LBS-008’s mechanism of action has been recognized and recommended in a systematic review published by the UK National Institute for Health Research (“NIHR”) in 2018. BPN has provided 10mn funding on LBS-008.
LBS-008 has initiated its phase 3 for Stargardt disease and expects to initiate its phase 3 for dry age-related macular degeneration in 2022.
BELITE BIO / 3
The TeamTom Lin, MMED, PhD, MBA
(CEO)
• PhD in Medicine - University of Sydney; Specialization: Neurology & Immunology
o Treatment Strategies for Autoimmune Neuropathies
• Specialist Certificate in Clinical Neuroscience - University of Melbourne; Specialization: Neurology
o Neurological Disorders, Neuroimaging & Diagnostics
o Clinical Research & Design
• Master of Medicine - University of Sydney; Specialization: Multidisciplinary Medicine and Surgery
o Medicine: Cardiovascular & Renal Medicine, Neonatal Medicine
o Surgery: Vascular & Endovascular Surgery, Transplant Surgery
• Cancer Therapeutics & Research Certificate - Harvard Medical School
• Master of Business Administration - Columbia University, London Business School, HK University
• 10 years of executive management role in biotech, incl. 2 IPO
• Multidisciplinary Specialization Clinical Training & Research in Neuroscience, Cardiovascular & Renal Medicine, Oncology, Immunology & Immunotherapy
• Over 10 new drug developments in multiple therapeutic areas, including Ophthalmology, CNS, Cardiovascular, Oncology, Immuno-Oncology, Immunotherapies, Immunosuppressants
• Drug development experience from drug discovery to Phase 3
• Extensive Drug development from preclinical to global phase 3 trials
o Phase 1 – RBP4 Inhibitor for the Treatment of Atrophic Macular Degeneration & Stargardt Disease
o Phase 2 – Oubain Antagonist in the Treatment of Essential Hypertension
o Phase 2 – SERCA2a Inhibitor in the Treatment of Acute Heart Failure
o Phase 2 – Pan-HER Inhibitor in the Treatment of HER2+ Breast Cancer and Gastric Cancer
o Phase 3 – Anti-Glycan Active Immunotherapy in the Treatment of Metastatic Breast Cancer
o Phase 3 – Anti-α4 integrin Antibody in the Treatment of Resistant-Refractory Multiple Sclerosis
o Phase 2 – mTOR Immunosuppressant in the Treatment of Autoimmune Peripheral Neuropathies
o Co-invented and applied 63 patents
BELITE BIO / 4
The TeamIrene Wang, PhD, MBA
(COO)
• PhD in Biochemical Sciences, National Taiwan
University, Trained at Scripps Research (TSRI),
MBA from UCSD
• Co-invented and applied 132 patents and
published 6 papers
• Extensive Drug development from preclinical to
global phase 3 trials
Hao-Yuan Chuang, CFA, MBA, FRM
(CFO)
• MBA from Columbia University
• Served as Executive/Director positions, led
transactions: Suning – US$320M acquisition of
Inter-Milan; Wanda – US$10B property
acquisition, bond issue and IPO; CITIC Securities
International – Finance Advisor to Agricultural
Bank of China’s US$22B IPO
Nathan L. Mata, PhD(CSO)
• PhD in Neurobiology, MS in Biochemistry,
University of Texas
• 15+ years of ophthalmic drug development
experience across numerous indications
including 2 NDAs for topical therapeutics
(Durezol® and Zirgan®)
• Led the clinical development efforts for first RBP
antagonist in advanced dry AMD and first visual
cycle modulator in advanced dry AMD and STGD
BELITE BIO / 5
Ophthalmology Clinical Advisory Board
• Dr. Frank Holz: Chairman of Ophthalmology,
University of Bonn
• Dr. Robyn Guymer: Professor of Ophthalmology, University of
Melbourne & Deputy Director of the Centre for Eye Research
Australia
• Dr. Michel Michaelides: Consultant
Ophthalmologist at Moorfields Eye Hospital
and Professor of Ophthalmology, UCL
Institute of Ophthalmology
• Dr. Janet Sunness: Medical Director of
Hoover Eye Center, Greater Baltimore
Medical Center
• Dr. Hendrik P.N. Scholl: Co-Director of the Institute of
Molecular and Clinical Ophthalmology, Basel & Professor and
Chairman of the Department of Ophthalmology, University of
Basel, and Adjunct Professor of Ophthalmology at the Wilmer
Eye Institute, Johns Hopkins University
• Dr. Quan Nguyen: Professor of
Ophthalmology, Stanford University
BELITE BIO / 6
Development Strategy• Focus on Stargardt Disease (“STGD”) then Dry AMDProblem of STGD: • Stargardt Disease, inherited form of macular degeneration, has no treatment• Loss of function of ABCA4 causes Vitamin A toxic byproducts (A2E) accumulation in the retina• More than 500 mutations on ABCA4 gene identified in STGD1 patients • Prevalence 1 in 9,000 in the US (30,000 STGD patients) with estimated US market size of $600M (Expected global
market size to be $1B)Proposed Solution:• Tinlarebant (LBS-008) as an oral daily treatment to target RBP4 (Retinol Binding Protein 4), disrupting Vitamin A
(retinol) binding to RBP4• Modulate the amount of retinol entering into visual cycleAchieved Milestones: • Completed - A Phase 1 Single Ascending Dose (SAD) in the US and Multiple Ascending Dose (MAD) in Australia• Ongoing – A Phase 3 for Stargardt disease• Received Rare Pediatric Designation in the US. Upon NDA, PRV can be eligible and sold (historical value $100M) • Received Orphan Drug Designation in the US and EU• One and only drug selected by the NIH Blueprint Program to treat Dry AMD with $10M funding• Recognized and recommended by UK National Institute for Health Research’s 2018 systematic review
Executive Summary
BELITE BIO / 7
Anti-RBP4 Platform for Aging Metabolic Diseases
MEET THE UNMET NEED
HOPE TO INCURABLE BLINDNESS
THE PATH TO METABOLIC DISEASE
Dry Age-Related Macular Degeneration & Stargardt Disease
Non-Alcoholic Fatty Liver Disease & Type 2 Diabetes
009LBS
PRE-CL IN ICAL
PHASE I I I
008LBS
BELITE BIO / 8
For Dry Age-Related Macular Degeneration & Stargardt DiseaseHOPE TO INCURABLE BLINDESS
11M
$1B+$20B+
Blind victims suffer from macular degeneration in the US
Estimated global market size Estimated global market size
1 in 10,000Stargardt Disease Juvenile onset macular degeneration (rare pediatric disease & orphan disease)
Dry AMD MARKETKEY OPPORTUNITY
Zero ApprovedTreatmentsMARKET
PHASE I
PRE-CLINICAL
DISCOVERY
LBS
008
RPD ODDfor Stargardt (US & EU)
Most Advanced Candidate
Reference: Globaldata, Lancet, Orphanet, STEM CELLS Translational Medicine
STGD MARKET
PHASE III
PHASE II
L B S
008
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Wet AMD: • 10% of AMD Cases• $6bn global sales in 2018
Dry AMD: • 90% of AMD Cases• 11mn patients in US alone• 170mn patients globally
Dry AMD number of patients: 9x to Wet AMDPRODUCT DISEASE PROFILE: 90% AMD ARE “DRY” AMD
L B S
008
BELITE BIO / 10
Accumulation of Cytotoxic A2E Due to Ageing, Frequently Exposing to 3C Products and Overuse of eyes
Normal Retina RPE Changes Rods Die, Cones Spared Cones Die
Vision Loss
Pathogenesis of Stargardt & Dry AMD
L B S
008
BELITE BIO / 1 1The ProgStar Study Group, Ophthalmology, 2016; 123
Case Study in the ProgStar study:• The FAF from this STGD patient showed lipofuscin (A2E) is the direct driver for the lesion growth, and can
predict the lesion growth location and rate.
Photoreceptors
RPEA2E
Pathogenesis of Stargardt & Dry AMDAccumulation of Cytotoxic A2E Due to Ageing, Frequently Exposing to 3C Products and Overuse of eyes
L B S
008
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MOA: Stargardt & Dry AMD RBP4 Transports Retinol (Precursor to Cytotoxic A2E) into Retina by Way of Visual Cycle
PHOTORECEPTORS(PR)
RETINAL PIGMENT EPITHELIUM (RPE)
BLOODSTREAM
LBS-008 RBP4Inhibits RBP4 from delivering retinol into RPE, reducing A2E accumulation
Primary transporter of retinol into RPE
A2E
RPE65 LRAT
11c-RDHat-RDH
at-Ral
at-RE at-Rol11c-Rol
Retinal isomers are required by normal visual function. They are also precursors to the cytotoxic
A2E, which causes dry AMD and Stargardt.
Rhodopsin
LBS-008 Induced Down-Regulation
Retinal Isomers
Enzymes
Pigments
ABCA4Gene mutation causes loss of
ABCA4 transporter
function
STARGARDT11c-Ral
at-Rol
RBPReceptor
RBP4
L B S
008
BELITE BIO / 13
Reduces A2E Accumulation by 80%IN ABCA4-/-RDH8-/- MICE, COMPARED TO LBS-008-TREATED
5.7
25.9
1.6
• Daily dosing of 25mg/kg of LBS-008 for 12 weeks.• Significant 94.3% and 93.4% serum RBP4 reduction in LBS-008 treated
mice at 1- and 12-week time points, respectively. • ~80% A2E reduction in treated mice compared to DKO mice at 12-
week timepoints.
LBS-008
L B S
008
BELITE BIO / 14
Photoreceptor Degeneration in Abca4-/-Rdh8-/- Mice
IN ABCA4-/-RDH8-/- MICE, COMPARED TO LBS-008-TREATED
LBS-008- treated
• Histological cross-section of retina near optic nerve, Outer Nuclear Layer (ONL) is the cell layer consisted of photoreceptor cell bodies (rods and cones).
Fawzi et al, Investigative ophthalmology & visual science 55(4) · March 2014
• Dry AMD or STGD is associated with thinning of the ONL and the loss of
photoreceptor cells, indicating macular degeneration.
• ONL thickness was significantly decreased in the diseased group (abcd4/rdh8
knockout mice), as compared to the diseased group treated with LBS-008, ONL
were preserved.
12 week timepoint
L B S
008
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US NIH Endorsement
L B S
008
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UK NIHR Endorsement
▪ 7,948 articles were screened for this Systematic Review on Treatments for dry AMD
and Stargardt Disease. Principal findings include:
o Research focus should be at earlier stages in both diseases, before vision is
impaired.
o Most promising treatments for dry AMD and STGD appear to be prevention of
lipofuscin A2E accumulation.
o Recommends LBS-008’s RBP4 inhibition as a promising treatment in dry AMD
and STGD.
BELITE BIO / 17
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