Ribomic, Inc. · TSE:4591
Ribomic — J.P. Morgan Healthcare Conference 2022
41 slides from Ribomic's conference presentation, Jan 11, 2022
Slide 1: Therapeutic Aptamer Discovery and Clinical Development
Therapeutic Aptamer Discovery and Clinical Development JP Morgan Healthcare Conference (January 11, 2022) Yoshikazu Nakamura, Ph.D., President and CEO 1
Slide 2: Notice
Notice DISCLOSURE The presenter is an employee and shareholder of RIBOMIC Inc. DISCLAIMER The Materials in this presentation and any comments or information provided by the presenter are for scientific exchange purposes only and nothing conveyed or provided should be considered business promotion or
Slide 3: What is an Aptamer?
What is an Aptamer? Single-strand DNA/RNA can form diverse 3D structures, which often mimic or antagonize any target protein of interest. 3D printer model of 2.0 Å crystal structure of the autotaxin/aptamer Complex. (Nat. Str. Mol. Biol., 23: 395-401, 2016; collaboration with O. Nureki UTokyo) 3
Slide 4: Platform technology
Platform technology Experience and know-how based technology Repeat selection/ amplification cycle about ten times 4
Slide 5: Major pipelines in/towards clinical study
Major pipelines in/towards clinical study Compound Pre- Clinical phase Target Indication Discovery Name clinical 1 2a 2b 3 Age-related macular RBM-007 FGF2 degeneration (AMD) RBM-007 FGF2 Achondroplasia (ACH) Pulmonary Arterial RBM-011 IL-21 Hypertension (PAH) RBM-003 Chymase Heart Failure RBM-010 A
Slide 6: Fibroblast growth factor 2 (FGF2)
Fibroblast growth factor 2 (FGF2) Major player of 22 FGF family members. FGF2 Positive role in development and tissue FGFR1 remodeling and repair. However, FGF2 has never been investigated as a therapeutic target, because of the lack of FGF2 inhibitors. 6
Slide 7: Diverse therapeutic applications of RBM-007
Diverse therapeutic applications of RBM-007 7 * Yoshikazu Nakamura Cells 2021 Jun 28;10(7):1617.
Slide 8: RBM-007: Anti-FGF2 Aptamer
RBM-007: Anti-FGF2 Aptamer Targeting Wet Age-related Macular Degeneration (AMD) 8
Slide 9: Age-related macular degeneration (wet AMD)
Age-related macular degeneration (wet AMD) Disease Wet AMD is caused by choroidal neovascularization that blurs the sharp, central vision you need for “routine wet AMD or day to day” activities. Current Treatment Intravitreal injection of anti-VEGF drugs (Lucentis, Eylea, Avastin etc.) Unmet Needs V
Slide 10: FGF2 as a therapeutic new target in wet AMD
FGF2 as a therapeutic new target in wet AMD REASON 1 FGF2 is an inducer of neovascularization – stronger than VEGF. REASON 2 FGF2 is involved in fibrotic scar formation in retina. Anti-angiogenic and anti-scarring dual action of RBM-007 10
Slide 11: Phase 2 studies for wet AMD in the US
Phase 2 studies for wet AMD in the US 11
Slide 12: Phase 2 study design
Phase 2 study design AIM AIM Safety, tolerability and efficacy (vision Efficacy (vision acquisition and scar N=22 acquisition) of intravitreal RBM-007 in formation) of extended intravitreal anti-VEGF pretreated wet AMD RBM-007 in TOFU-rollover patients patients INJECTIONS INJECTIONS RBM-007 Monthly
Slide 13: TOFU study topline data on vision outcome
TOFU study topline data on vision outcome AIM Safety, tolerability and efficacy (vision acquisition) of intravitreal RBM-007 in anti-VEGF pretreated wet AMD Safety Good patients INJECTIONS with no unexpected AEs RBM-007 Monthly four times Eylea® Bimonthly two times RBM-007 monotherapy or RBM-007 in
Slide 14: TEMPURA study preliminary interim data on vision outcome
TEMPURA study preliminary interim data on vision outcome Investigator Sponsored Trial Dr. Raj Maturi Safety Good with no unexpected AEs (Midwest Eye Inst.) Improvement AIM Efficacy (visual acuity and central in vision and retinal thickness) and safety of intravitreal RBM-007 in naïve wet retinal ana
Slide 15: Questions behind three P2 programs
Questions behind three P2 programs Q2 Is RBM-007 effective in treatment-naïve wet AMD ? Q3 YES (interim data) Is RBM-007 effective to prevent retinal Q1 scar formation ? Is RBM-007 better than Eylea Under Investigation in anti-VEGF pretreated wet AMD ? NO Further study is necessary for elucidating t
Slide 16: RBM-007: Anti-FGF2 Aptamer
RBM-007: Anti-FGF2 Aptamer Targeting Achondroplasia (ACH) 16
Slide 17: Achondroplasia (ACH)
Achondroplasia（ACH） Overview Achondroplasia is a form of short-limbed dwarfism, meaning "without cartilage formation,” caused by mutations in the FGFR3 gene. The disorder occurs in approximately one in 25,000 live births. FGFR3 The mutant FGFR3 receptor is overactive and interferes with normal skele
Slide 18: RBM-007 restores defective skeletal growth in ACH mouse
RBM-007 restores defective skeletal growth in ACH mouse WT ACH Vehicle RBM-007 Vehicle RBM-007 Vehicle RBM-007 Vehicle RBM-007 Wall thickness [μm] Overall appearance of the wildtype (WT) and ACH mice Micro-CT imaging of the femurs in 3D; sections in treated with RMB-007 or vehicle for 18 days. front
Slide 19: RBM-007 restores in vitro differentiation of ACH-derived iPS cells
RBM-007 restores in vitro differentiation of ACH-derived iPS cells into matured chondrocyte Staining of chondrocytic bodies with safranin O Expression of chondrocyte maturation (8-week old) markers by RT-PCR ACH1 ACH2 ACH3 SOX9 COL2A1 ACAN 4 Vehicle 1000 1000 Relative mRNA levels Relative mRNA level
Slide 20: RBM-007 restores in vivo differentiation of ACH-derived iPS cells
RBM-007 restores in vivo differentiation of ACH-derived iPS cells into matured chondrocyte Scheme of transplantation into scid mice Chondrocyte cell diameter In vitro In vivo *** n.s. R-v RBM-007 Vehicle 50 n=3 R-R RBM-007 RBM-007 Hypertrophic cell diameter (µm) v-v Vehicle Vehicle 40 v-R Vehicle RB
Slide 21: Evidence for potency of RBM-007 in ACH published in Sci. Transl. Med.
In vitro / in vivo evidence for potency of RBM-007 in ACH treatment published in Sci.Transl. Med. Restored Bone Growth in ACH Animal Models Regeneration of Patient- derived iPS Cells *Sci Transl Med. 2021 May 5;13(592):eaba4226. doi: 10.1126/scitranslmed.aba4226. 21
Slide 22: Phase 1 study design and result
Phase 1 study design and result A single dose of 1.0 mg/kg caused SAE (acute anaphylactic reaction), which disappeared with appropriate treatment. The study was continued by reducing the dose to 0.6 mg/kg. Good safety and tolerability with no unexpected AEs when injected subcutaneously at 0.1-0.6 mg
Slide 23: Summary of Phase 1 study for Achondroplasia
Summary of Phase 1 study for Achondroplasia ▷ Good safety and tolerability of RBM-007 in the range between 0.1 and 0.6 mg/kg when administered subcutaneously. ▷ Pharmacokinetic (PK) profiles of RBM-007 after single or two-time subcutaneous injections are clarified. ▷ We plan to send IND application
Slide 24: Clinical study design for Achondroplasia
Clinical study design for Achondroplasia 24
Slide 25: Other programs: RBM-011 Anti-IL-21 Aptamer
Other programs RBM-011: Anti-IL-21 Aptamer In collaboration with Dr. Nakaoka, National Cerebral and Cardiovascular Center (Osaka) 25
Slide 26: Pulmonary Arterial Hypertension (PAH) and IL-21
Pulmonary Arterial Hypertension (PAH) and IL-21 Disease A life-threatening disease which shows high blood pressure in Patients Worldwide the lungs. Unmet Needs There is no radical drug developed for PAH. Cause 76,600 IL-21 induces proliferation of smooth muscle cells in lung arteries leading to hype
Slide 27: Anti-mIL-21 aptamer effects on blood vessel remodeling in PAH mouse model
Pharmacological effects of anti-mIL-21 aptamer on blood vessel remodeling in PAH mouse model Osmotic pump on day -1 Medial Wall Thickness (%) Aptamer or vehicle 8 12wk of age Analysis 0 4wks Hypoxia (10% O2) ia le ox ehic Ap L or m v Hx g/m Hx Elastica van Gieson stain N 2m Anti-mIL-21 aptamer signi
Slide 28: Anti-rIL-21 aptamer effects on hemodynamics in severe PAH rat model
Pharmacological effects of anti-rIL-21 aptamer on hemodynamics in severe PAH rat model Aptamer Su5416 i.p. RVSP (mmHg) once/3day 6 9 11 14wk of age Analysis 0 8wks Hypoxia Normoxia (10% O2) NOR Vehicle 0.1 1 10 mg/kg Apt Apt Apt Anti-mIL-21 aptamer significantly improved elevated right ventricular s
Slide 29: Summary of RBM-011 preclinical study for PAH
Summary of RBM-011 (anti-IL-21) preclinical study for PAH ▷ The RBM-011 is a highly potent inhibitor on IL-21 biological activities in pM range using in vitro cell based assay. ▷ RBM-011 showed excellent therapeu-c effect in PAH models of mice and rats. ▷ Currently the cGMP production of RBM-011 is u
Slide 30: Other programs: RBM-010 Anti-ADAMTS5 Aptamer
Other programs RBM-010: Anti-ADAMTS5 Aptamer 30
Slide 31: Osteoarthritis and ADAMTS5
Osteoarthritis and ADAMTS5 Disease Osteoarthritis (OA) is a debilitating degenerative disease of articular joints Patients Worldwide characterized by articular cartilage degradation and alterations. Unmet Needs There is no radical drug developed for OA. 320M Cause ADAMTS5 is a major cartilage-degrad
Slide 32: Anti-ADAMTS5 aptamer in antigen-induced arthritis mouse model
Pharmacological effects of anti-ADAMTS5 aptamer in antigen-induced arthritis (AIA) mouse model ***︓p<0.001 Ct vs AIA_saline t-test ###︓p<0.001, ##︓p<0.01, #︓p<0.05 ) *** AIA_saline vs AIA_Apt Dunnett test ( sGAG(μg/mL) ' & # ## % $ # ### RBM-010 inhibits sGAG 43% 54% " 100% production in a dose-depe
Slide 33: Anti-ADAMTS5 aptamer in DMM OA mouse model
Pharmacological effects of anti-ADAMTS5 aptamer in destabilization of the medial meniscus (DMM) OA mouse model n Total proteoglycan loss n Total cartilage structural damage *: P<0.05 v.s. Saline, *: P<0.05 v.s. Saline, Dunn’s rank sum analysis Dunn’s rank sum analysis 25 30 20 25 15 * 20 * Score Sco
Slide 34: Summary of RBM-010 preclinical study for OA
Summary of RBM-010 (anti-ADAMTS5) preclinical study for OA ▷ The RBM-010 is a highly potent inhibitor on ADAMTS5 biological activities in pM range using in vitro cell based assay. ▷ RBM-010 showed excellent therapeutic effect in OA models of mice and rats. ▷ Currently the development of formulation
Slide 35: Other programs: RBM-003 Anti-Chymase Aptamer
Other programs RBM-003: Anti-Chymase Aptamer In collaboration with Drs. Jin and Takai, Osaka Medical College 35
Slide 36: Acute heart failure and chymase
Acute heart failure and chymase Disease Acute Heart failure (AHF) is life-threatening cardiac dysfunction with the Patients Worldwide most frequent cause of unplanned hospital admission. Unmet Needs AHF is still associated with poor outcomes and there is no radical drug developed for AHF. 1.3M Cause
Slide 37: Anti-chymase aptamer in MI hamster model
Pharmacological effects of anti-chymase aptamer in MI (myocardial infarction) hamster model n Preventive effects Mean ± S.E. (n=4-5) n Curative effects (14 days after surgery) Mean ± S.E. (n=14-24) *p < 0.05, **p < 0.01, ***p < 0.001 versus sham, ***p < 0.001 versus sham, ##p < 0.01, ###p < 0.001 ve
Slide 38: Summary of RBM-003 preclinical study for AHF
Summary of RBM-003 (anti-chymase) preclinical study for acute heart failure (AHF) ▷ The RBM-003 is a highly potent inhibitor on chymase biological activities in pM range using in vitro cell based assay. ▷ RBM-003 showed excellent therapeutic effect in MI (myocardial infarction) hamster model. ▷ Curr
Slide 39: VISION 2025: Five clinical stage pipelines
VISION 2025: Five clinical stage pipelines RBM-007 Exudative Age-related Macular Degeneration 2022 Complete Phase 2 (wet AMD) RBM-007 Achondroplasia 2022 Initiate Phase 2a (ACH) RBM-011 RBM-010 RBM-003 Pulmonary Arterial Heart Failure Osteoarthritis Hypertension (PAH) before 2025 Initiate Phase 1 39
Slide 40: ESG
RIBOMIC ongoing sustainability initiatives Environment Unmet medical needs: ESG Social RIBOMIC’s MISSION “We try our best to develop novel Governance medicine for unmet medical needs. ” 40
Slide 41: Thank you!
Thank you ! Prof. Pavel Krejci and his team members Masaryk University, Czech Prof. Keiichi Ozono Thank ou ! and his team members Osaka University, Pediatrics Dr. Yoshikazu Nakaoka and his team members National Cerebral and Healthcare Workers Cardiovascular Center Prof. Shinji Takai and his team mem