Slide 1: R&D Briefing
R&D Briefing September 7, 2021
Slide 2: Cautionary Notes
Cautionary Notes Forecasts and other forward-looking statements included in this document are based on information currently available and certain assumptions that the Company deems reasonable. Actual performance and other results may differ significantly due to various factors. Such factors include
Slide 3: Compounds to be presented
Compounds to be presented Compound Mechanism Target indication Stage Schwann cell Diabetic ONO-2910 P2 differentiation promoter polyneuropathy Prostaglandin receptor ONO-2909 Narcolepsy P1 (DP1) antagonist Neurodegenerative ONO-2808 S1P5 receptor agonist P1 disease Prostaglandin receptor ONO-4578 So
Slide 4: ONO-2910
ONO-2910 Schwann cell differentiation promoter 3
Slide 5: ONO-2910
ONO-2910 Compound ONO-2910 Company Ono Mechanism Schwann cell differentiation promoter Formulation Tablet Indication Diabetic polyneuropathy Stage Phase 2 (Japan) 4
Slide 6: ONO-2910 Mechanism of Action
ONO-2910 Mechanism of Action Repair process of nerve fiber Myelin sheath Schwann cell Normal nerve fiber Demyelination・ Nucleus axon degeneration Hyperglycemia Differentiation Dedifferentiation (Myelination) (Injury) Nerve axon Enhancement ONO-2910 Suppression Myelin Axonal debris debris Prepared ba
Slide 7: ONO-2910 Pharmacological study result
ONO-2910 Pharmacological study result Rat streptozotocin (STZ)induced model Human Schwann cell Enhancement of Schwann cell differentiation Nociception threshold（g） N=8, MEAN±SE $ p<0.05 vs Normal（t-test） Orally, # p<0.05 vs vehicle（t-test） 70 once daily ＊ p<0.05 vs vehicle (Dunnett test) 12 * （MAG p
Slide 8: Diabetic Polyneuropathy
Diabetic Polyneuropathy Simplified Prerequisite conditions (the following two must be met) diagnostic 1. Diagnosed as diabetes 2. Neuropathies other than diabetic neuropathy can be excluded criteria Criteria (any two of the following three must be met) 1. Presence of symptoms considered to be due to
Slide 9: ONO-2909
ONO-2909 Prostaglandin receptor (DP1) antagonist 8
Slide 10: ONO-2909
ONO-2909 Compound ONO-2909 Company Ono Mechanism Prostaglandin receptor (DP1) antagonist Formulation Tablet Indication Narcolepsy Stage Phase 1 (Japan) 9
Slide 11: ONO-2909 Mechanism of Action
ONO-2909 Mechanism of Action Activation PGD2 of cerebral cortex ONO-2909 Dopamine Adrenaline Adenosine Histamine Sleep center Orexin Need for Wakefulness power sleep Decreased wakefulness due to orexin nerve depletion (narcolepsy) ONO-2909 suppresses sleep center activation and hypersomnia symptoms.
Slide 12: DP antagonist (Pharmacological study result 1)
DP antagonist (Pharmacological study result 1) Effect on wake time in normal rats DP antagonist was administered at 11:00 am, which corresponds to the sleep phase for rodents, and the wake time was measured by the EEG from 11:00 to 17:00 N=6～14, mean ± SD 250 *p<0.05 vs vehicle（Dunnett test） * * 6時間
Slide 13: DP antagonist (Pharmacological study result 2)
DP antagonist (Pharmacological study result 2) Effect on wake time in sleep deprivation rats Lighting-off 14:00＜Sleep＞20:00 ＜Arousal＞ EEG and EMG were analyzed for 3 8:00 hours after administration to Oral administration, Start of EEG measurement Lightning determine sleep stage Sleep deprivation （6
Slide 14: Narcolepsy
Narcolepsy 2 Major symptoms Major symptoms ①： Hypersomnia Falling asleep when unable First-line：Modafinil to remain awake Major symptoms ②：Cataplexy (Type 1 only) Orexin; hormones involved in maintaining awakening Feelings are high, and muscles throughout the body become weak Narcolepsy type1 patien
Slide 15: ONO-2808
ONO-2808 S1P5 receptor agonist 14
Slide 16: ONO-2808
ONO-2808 Compound ONO-2808 Company Ono Mechanism S1P5 receptor agonist Formulation Tablet Indication Neurodegenerative disease Stage Phase 1 (Europe/ Japan) 15
Slide 17: ONO-2808 Mechanism of Action
ONO-2808 Mechanism of Action Normal ⇒ Neurodegeneration Astrocyte Microglia Oligodendrocyte （OLG） OLG（Myelin sheath） ：p25α、OLG protein ：Monomer α-Syn Neuron ：Oligomer α-Syn Aberrant α-Syn Prepared based on N. Stefanova and G.K.Wenning. Neuropathol Appl Neurobiol. 2016 Feb;42(1):20-32 ：GCI ：Cytokine
Slide 18: S1P5 agonist (Pharmacological study result)
S1P5 agonist (Pharmacological study result) Effect in mouse experimental autoimmune encephalomyelitis (EAE) model Day -1 0 2 5 29 Vehicle, S1P5 agonist administration Measurement of EAE clinical score MOG+PTX PTX MOG：Myelin oligodendrocyte glycoprotein PTX：Pertussis Toxin N=10, mean ±SD, *p<0.05 vs
Slide 19: Main neurodegenerative disease and number of patients in the US
Main neurodegenerative disease and number of patients in the US 1) 1 mil patients Parkinson disease Alzheimer's Lewy body 5.2 mil1) dementia dementia 1.4 mil2) Neuro- degenerative disease Amyo- Multiple trophic 20K1) lateral system 7-16K3) sclerosis atrophy Multiple sclerosis 400K1) 1)：Thermo Fisher
Slide 20: ONO-4578
ONO-4578 Prostaglandin receptor (EP4) antagonist 19
Slide 21: ONO-4578
ONO-4578 Compound ONO-4578 Company Ono Mechanism Prostaglandin receptor (EP4) antagonist Formulation Tablet Indication Solid Cancer Phase 1 (Japan) Stage Colorectal cancer, pancreatic cancer, Non-small cell lung cancer, gastric cancer 20
Slide 22: ONO-4578 Mechanism of Action
ONO-4578 Mechanism of Action Prostaglandin E2 (PGE2) is produced from arachidonic acid through cyclooxygenase-2 (COX-2) COX-2 is overexpressed in solid cancer1). PGE2 has been reported to induce myeloid-derived suppressor cells (MDSC) and M2 macrophages in the tumor microenvironment through one
Slide 23: ONO-4578 Non-clinical data
ONO-4578 Non-clinical data Fig 1. Time course of median tumor volume in syngeneic mouse colorectal cancer MC38 tumor-bearing model In syngeneic mouse tumor-bearing model, Vehicle αPD-1 ONO-4578 improved immunosuppressive αPD-1+4578（0.1 mg/kg） αPD-1+4578（0.3 mg/kg） tumor microenvironment and showed
Slide 24: ONO-4578 Clinical data
ONO-4578 Clinical data 60 mg + 240 mg Part B（Dose escalation） In the ONO-4578-01 study in Japanese 40 mg + 240 mg ・ONO-4578, once daily, po patients with solid tumors, the tolerability 20 mg + 240 mg 10 mg + 240 mg ・Opdivo 240 mg, every 2 and safety of ONO-4578 alone (Part A) 5 mg + 240 mg weeks,
Slide 25: ONO-4578 Development stage
ONO-4578 Development stage Clinical stage Type of cancer Phase 1 (FIH) Phase 1 b Phase 2 Mono or combination with Solid tumor Opdivo Dose escalation Gastric Combination with Opdivo cancer Colorectal Combination with Opdivo cancer Pancreatic Combination with Opdivo cancer Non-small cell Combination w
Slide 26: ONO-2017 (cenobamate)
ONO-2017 （cenobamate） Voltage-gated sodium currents inhibition/ GABAA modulation 25
Slide 27: ONO-2017
ONO-2017 Compound ONO-2017（Cenobamate） Company SK Biopharmaceuticals Co., Ltd. Voltage-gated sodium currents inhibition/GABAA Mechanism modulation Formulation Tablet Indication Epilepsy (Partial seizure, tonic-clonic seizure) US: Launched by SK Life Science Stage Europe: Launched by Angelini Pharma
Slide 28: ONO-2017 Mechanism of Action
ONO-2017 Mechanism of Action ONO-2017 Cenobamate Lamictal® Vimpat® Fycompa® Normal Epileptic seizure Mechanism of action of antiepileptic drugs Upper figure：Web https://www.credentials.jp/2019-02/expert-1902/ Lower figure： https://epilepsy-support.net/about.html 27
Slide 29: ONO-2017 Clinical Results
ONO-2017 Clinical Results Partial seizure, Patients with poor seizure control, Combined use with existing drugs Treatment period: Dose-escalation period + 12 or 13 weeks maintenance period Patients: Adult epilepsy patients with partial seizures for which existing antiepileptic drugs are not fully ef
Slide 30: Epilepsy
Epilepsy ・Lennox-Gastaut syndrome ・West Syndrome Patients refractory to existing treatments: 20-30% ● Partial (Focal) seizures: 130-190 K ● Tonic-clonic seizures: 20-30 K • Prepared based on materials for training of epilepsy for school. • Epidemiology of epilepsy. Epilepsy 2020.; 14: 7-10. • JAMA N
Slide 31: Dedicated to the Fight against Disease and Pain
Dedicated to the Fight against Disease and Pain