2018 Investor Day PRESENTATION, HTL0018318 for DLB in Japan, by Dr Tim Tasker, CMO

INTRODUCTION TO SOSEI GROUP July 2017 Sosei Group Corporation HTL0018318 for Dementia with Lewy Bodies (Japan) Dr Tim Tasker, Chief Medical Officer 2018 Investor Day New Otani Hotel, Tokyo Disclaimer The material that follows is a presentation of general background information about Sosei Group Corporation and its subsidiaries (collectively, the “Company”) as of the date of this presentation. This material has been prepared solely for informational purposes and is not to be construed as a solicitation or an offer to buy or sell any securities and should not be treated as giving investment advice to recipients. It is not targeted to the specific investment objectives, financial situation or particular needs of any recipient. It is not intended to provide the basis for any third party evaluation of any securities or any offering of them and should not be considered as a recommendation that any recipient should subscribe for or purchase any securities. 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The important factors that could cause our actual results, performance or achievements to differ materially from those in the forward looking statements include, among others, risks associated with product discovery and development, uncertainties related to the outcome of clinical trials, slower than expected rates of patient recruitment, unforeseen safety issues resulting from the administration of our products in patients, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products obsolete, and other factors. These factors include, without limitation, those discussed in our public reports filed with the Tokyo Stock Exchange and the Financial Services Agency of Japan. Although the Company believes that the expectations and assumptions reflected in the forward-looking statements are reasonably based on information currently available to the Company's management, certain forward looking statements are based upon assumptions of future events which may not prove to be accurate. The forward looking statements in this document speak only as at the date of this presentation and the company does not assume any obligations to update or revise any of these forward statements, even if new information becomes available in the future. This presentation does not constitute an offer, or invitation, or solicitation of an offer, to subscribe for or purchase any securities. Neither this presentation nor anything contained herein shall form the basis of any contract or commitment whatsoever. 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The non‐GAAP financial measures contained in this presentation are not measures of financial performance calculated in accordance with IFRS and should not be considered as replacements or alternatives profit, or operating profit, as an indicator of operating performance or as replacements or alternatives to cash flow provided by operating activities or as a measure of liquidity (in each case, as determined in accordance with IFRS). Non-GAAP financial measures should be viewed in addition to, and not as a substitute for, analysis of the Company's results reported in accordance with IFRS. References to "FY" in this presentation are to the Company's fiscal years, namely the 12-month periods commencing in each case on April 1 of the year indicated and ending on March 31 of the following year, unless specifically otherwise indicated. 2 Three Novel Phase 1 Candidates Phase 1b AZD4635 Immuno-oncology Phase 1b HTL0018318 Alzheimer’s Disease (AD) Phase 1 HTL0016878 Neurobehavioral Sx of AD Discovery and Preclinical Collaboration Partnerships A2a M1 M4 Ultibro® Breezhaler® COPD Seebri® Breezhaler® COPD Two Key Products Marketed HTL0018318 Muscarinic M1 Agonist Novel approach for symptomatic treatment of DLB 3 Emerging wholly-owned GPCR portfolio Denotes: Covered in this presentation Partnered GPCR portfolio Subject to approval, we are aiming for our lead M1 program for DLB to enter into a Phase 2 PoC study in Japan in 2018 SSTR Preclinical Code: Not disclosed Example indication: Cushing’s disease CGRP Phase 1 ready 2018 HTL0022562 Migraine & Other Severe Headache mGlu5 Phase 1 ready 2018 Code: Not disclosed Example indications: ALS or Dystonia Plus Examples of Selected Preclinical Pipeline Programs Including… GLP1 Preclinical Code: Not disclosed Example indication: Hypoglycaemia GLP2 Preclinical Code: Not disclosed Example indication: PN Short Bowel Syndrome Three Lead Programs M1 Phase 2 ready 2018 HTL0018318 Dementia with Lewy Bodies (Japan) 4 Agenda 4 1 2 3 Introduction to DLB Diagnosis/Treatment Approach for DLB HTL0018318 M1 Agonist for DLB in Japan 5 Introduction to DLB What is dementia? ➢ Dementia - a collection of symptoms including • Memory loss • Difficulties with thinking, problem-solving or language ➢ No specific disease called dementia ➢ Several diseases cause dementia ➢ 認知症は大脳の疾患の症状（群）をいう ➢ 認知症という病気があるのではない ➢ 多くの認知症を起こす病気がある Alzheimer’s disease Dementia with Lewy bodies (DLB) Parkinson’s disease dementia (PDD) Vascular dementia Frontotemporal dementia (Pick’s disease) Creutzfeldt-Jakob disease 5 6 Introduction to DLB Steady increase in dementia patients expected in Japan 0 5 10 15 20 25 30 0 100 200 300 400 500 600 700 800 900 2012 2015 2020 2025 2030 2040 2050 2060 人数（万人） 高齢者に占める割合（％） ➢ Approximately 5 million patients with dementia in Japan today ➢ Increased number of dementia patients expected with rapidly ageing population ➢ Real patient need ➢ Huge social and economical impact ➢ 現在の認知症の数 • 約500万人 Dementia has a physical, psychological, social, and economical impact, not only on people with dementia, but also on their carers, families and society at large 認知症患者は45年後まで増え続ける 6 7 Introduction to DLB Dementia is a social and political priority ➢ Dementia is a political priority in Japan, ➢ Government policies to ‘change the flow of dementia care’ • Early detection • More doctors and primary care givers • SOS networks’ to help find missing people and ‘dementia supporters’ to help within the community ➢ Pioneering approach to dementia care in Japan ➢ Could potentially facilitate the entry of new drugs Source: Alzheimer’s Disease International Presentation, 2014 Japan is leading the global fight in treating dementias like DLB 7 Government's 5-year Plan “Change the flow of dementia care” Long Term Hospitalization Post Crisis Intervention Community care services Home doctor Short term treatment in psychiatric hospitalization Integrated community care center Dementia medical center Initial Phase intensive care team Living in the community Early, proactive, preventive approach 8 Introduction to DLB Second most common type of progressive dementia ➢ Dementia with Lewy Bodies (DLB) • Dr. Kenji Kosaka of Japan instrumental in defining DLB ➢ Second most common type of progressive dementia after Alzheimer's disease ➢ DLB estimated to cause 10-20% of dementias ➢ Low level of recognition ➢ Difficult to diagnose due to complicated symptoms ➢ Central feature is progressive cognitive decline • Pronounced fluctuations in cognition • Recurrent visual hallucinations • Parkinsonism • REM sleep behaviour disorder (RBD) ➢ 84歳の女性 ➢ 主訴：ぼけてきた ➢ １年前から部屋の中に「大勢の子どもが見える」，「 犬や猿がいる」と訴える(幻視)．テレビの中の登場人 物が実際に自分の家にいるように行動したり，災害が 自分のまわりで起こったように言う(誤認妄想) ．とり つかれたようになって，理解力が全くなくなってしまうこ とがよくある(認知機能の変動) ．数年前から夜間睡 眠中突然大声で叫ぶ(レム睡眠関連行動異常) ． 歩行が遅く，転倒しやすい(パーキンソニズム) ． 8 9 Introduction to DLB DLB is estimated to cause up to 20% of all dementias… Source: Management estimates; Eisai Press Release, April 2015 Up to 20% of dementia diagnosed as DLB, which represents a significant potential market for drug development activities …however may be underestimated due to ageing population, increased awareness and improvements in diagnosis Alzheimer's disease, 55% DLB, 20% Vascular dementia, 15% Other dementia, 10% 9 10 Introduction to DLB Pathology of DLB ➢ Lewy body dementia (LBD) includes: • DLB – Dementia with minimal Parkinson’s • Parkinson's disease dementia (PDD) – Parkinson’s disease with dementia ➢ LBD pathology includes Lewy bodies (abnormal deposits of a protein called alpha-synuclein) build up in areas of the brain that regulate behavior, cognition, and movement ➢ 広範かつ多数のレビー小体の中枢神経系への出現を 特徴とする変性性認知症疾患 ➢ DLBの臨床診断基準（1996) ➢ 認知症/認知障害の存在 ➢ パーキンソニズム発症から１年以内 ➢ ３主徴のうち２つ ➢ 特発性のパーキンソニズム ➢ 繰り返す構築され具体的な内容の幻視体験 ➢ 注意や明晰さの著明な変化を伴う認知機能の変動 ➢ 示唆的特徴（2005改訂版) ➢ RBD，抗精神病薬に対する過敏性，DATスキャン 10 11 Introduction to DLB Clinical features of DLB compared to AD ➢ Different disturbance of cognition with marked fluctuations in severity day to day ,hour to hour ➢ Faster progression ➢ Potentially associated with higher mortality rates ➢ Distressing Behavior and Psychotic Symptoms of Dementia (BPSD) • Hallucinations, delusions, REM sleep disorder, confusion, depression, anxiety ➢ BPSD affecting caregivers’ Quality of Life (QOL) ➢ Faster nursing home admission ➢ Frequent falls and fall-related injuries ➢ Dysautonomia ➢ Hypersensitivity to antipsychotics and anticholinergics prevents use of other drugs to control hallucinations ➢ 重症化が早い ➢ 死亡率が高い ➢ 精神症状・行動異常（BPSD）が特異的 • 幻視，誤認妄想，RBD，意識・認知の変動 ➢ BPSDが介護者QOLを決める ➢ 患者・介護者のQOLが低く，入所が早い ➢ パーキンソニズムによる運動障害が問題 ➢ 抗精神病薬でパーキンソニズムが生じる（過敏性） ➢ 転倒事故が多い ➢ 自律神経障害が強い Donepezil (AChE inhibitor) has provisional approval for DLB in Japan; no approved treatment worldwide 11 12 BPSD Introduction to DLB Features of Behavior and Psychotic Symptoms of Dementia (BPSD) ➢ Visual hallucinations • Recurrent well-formed visual hallucinations − People, children, animals, bugs • Memory +/-，insight+/- ➢ Passage hallucinations, sense of presence, visual illusions ➢ Delusional misidentifications ➢ Persecutory delusions ➢ Depression, anxiety pareidolia=para（疑似の,異常な）+ eidolon/eidos（像） 幻視 現実には存在しないものを視覚的 に知覚する 座敷わらし 心霊写真 パレイドリア 知覚対象を他のものとし て知覚する 12 13 Introduction to DLB Robin Williams’ Lewy body disease ➢ American actor and comedian Robin Williams died by suicide on August 11, 2014 ➢ Upon autopsy, he was found to have diffuse Lewy Body disease ➢ He had been diagnosed with Parkinson's disease prior to his death ➢ He also had depression, anxiety, and increasing paranoia ➢ 自宅で首つり自殺しているところを発見された．63 歳だった．うつ，不安，妄想，初期のパーキンソン 病に苦しんでいた(CNN 2014/8/11) ➢ レビー小体型認知症が自殺のキーファクターだった (CNN 2014/11/10) 13 14 Agenda 14 1 2 3 Introduction to DLB Diagnosis/Treatment Approach for DLB HTL0018318 M1 Agonist for DLB in Japan 15 Diagnosis/Treatment Approach for DLB Core features and indicative biomarkers exist for DLB – Japan the world leader ➢ Essential: dementia • Memory impairment may not be prominent • Deficits of attention, executive function and visuoperceptual ability may be prominent ➢ Core clinical features • Fluctuating cognition • Recurrent visual hallucinations • REM sleep behaviour disorder (RBD) • Parkinsonism ➢ Indicative biomarkers • DaTSCAN • MIBG myocardial scintigraphy • PSG confirmation of REM sleep w/out atonia 15 Improves ability to enroll homogenous clinical trial population DaTSCAN MIBG Myocardial Scintigraphy ➢ Meta-analysis ➢ 対AD (病理): • 感度=87% • 特異度=92% Brigo F, et al. J Neurol Sci 2015 Healthy Parkinson’s Alzheimer’s DLB ➢ Multicenter clinical study • 対AD: − 感度=68.9%（早期/遅延） − 特異度=89.1%（早期/遅延） Yoshita M, et al. PLoS One 2015 ➢ Multicenter pathology study • 感度: 90.9%(早期)，95.7%(遅延) Takahashi M, et al. JNNP 2015 Healthy DLB 16 Diagnosis/Treatment Approach for DLB Core features and indicative biomarkers exist for DLB 16 Japan arguably leads the world in the differential diagnosis of DLB ➢ RBD is a parasomnia manifested by vivid, often frightening dreams ➢ Patients act out their dreams with simple or complex motor behavior during REM sleep ➢ Loss of atonia during REM sleep ➢ Patient or bed partner have sustained injuries from limb movements ➢ Sleep EEG features characteristic REM sleep behavior disorder (RBD) Polysomnography (PSG) ➢ PSG confirmation of REM sleep without atonia ➢ PSGはRBDの確診に必須 ➢ PSGは認知症患者，メモリークリニックでは困難 17 Diagnosis/Treatment Approach for DLB Global regulators recognise the real patient need for new treatments Source: Alzheimer’s Disease International Presentation, 2014 With no new dementia treatments in 15 years, globally regulators are looking at ways to fast track and/or improve the chances of success for new drugs ➢ “U.S. regulators have proposed lowering the bar for clinical trial success for experimental Alzheimer’s drugs” - Reuters,15 Feb 2018 ➢ “European regulators are following in the footsteps of the U.S. FDA with plans to help pharmaceutical companies win approval for novel Alzheimer’s drugs” - Reuters, 28 Feb 2018 Several dementia drug failures over the past five years… Regulatory environment is adapting quickly to the high unmet need for new treatment… ➢ Axovant Sciences (DLB) - nelotanserin ➢ Merck (AD) - verubecestat ➢ Lundbeck (AD) - idalopirdine ➢ Axovant Sciences (AD) - interpirdine ➢ Eli Lilly (AD) - solanezumab ➢ Prana Biotech (AD) - hydroxyquinoline ➢ Pfizer (AD) – bapineuzumab O O O O O O O 17 18 Diagnosis/Treatment Approach for DLB A muscarinic M1 agonists is likely to have a superior profile – Lewy Body disease affects the origin of the cholinergic fibres – different from Alzheimer’s disease ➢ MRI of 72 DLB patients with 72 age matched AD and 72 controls ➢ Marked loss of cortical GM in AD (red) ➢ Loss in dorsal midbrain, SI and hypothalamus in DLB ➢ Loss in cortex in AD Source: Whitwell et al ,Brain 2007 Focal atrophy in DLB differs from AD Brain atrophy in DLB is different to that in AD and is more centred on cholinergic system 18 19 Diagnosis/Treatment Approach for DLB A muscarinic M1 agonist is likely to have a superior profile – much greater reduction in cholinergic system in DLB than in Alzheimer’s disease Source: Shimada H, et al. Int J Geriatr Psychiatry (2015) Greater reduction of AChE activity in DLB patients relative to AD patients N-[11C]-methyl-4-piperidyl acetate (MP4A) PET 19 20 Diagnosis/Treatment Approach for DLB Donepezil (AChE inhibitor) is the Standard of Care for DLB in Japan ➢ Donepezil (AChE inhibitor) inhibits cholinesterase enzymes (AChE) that break down acetylcholine (ACh) ➢ ACh is the neurochemical that stimulates the M1 receptor, which in turn mediates cognition ➢ Enhancement of ACh by donepezil provides benefit in patients ➢ Benefits limited due to low/declining levels of ACh as disease progresses, plus adverse side-effects1 20 Postsynaptic Neuron M1 R M1 R M1 R Acetylcholine (ACh) AChE AcCoA + choline ChAT Choline + acetate ACh M2 (–) N (+) donepezil (AChE inhibitor) Presynaptic cholinergic Neuron Donepezil is the standard of care for DLB patients in Japan… but clinical efficacy limited Donepezil in DLB patients provides some benefit – however effects are limited 1 Adverse side-effects of AChE inhibitors could be mediated at other sub -types of muscarinic receptors (M2, M3, M4), some located peripherally, at which enhanced ACh activity does not differentiate 21 Diagnosis/Treatment Approach for DLB Donepezil (AChE inhibitor) the SoC for DLB in Japan – shows the type of benefits that cholinergic enhancement by M1 agonists may produce Source: Mori E, et al. Ann Neurol, 2012 ChEIs improve cognition and show a greater degree of efficacy in DLB than in Alzheimer’s disease ➢ Clinical studies of DLB patients receiving donepezil demonstrated improvements in several neuropsychiatric domains affected by DLB ➢ Delusions, hallucinations and cognitive fluctuations ➢ Patients receiving 5 or 10 mg donepezil showed greatest improvement ➢ MMSE score improved by 2.0 to 3.8 points in those receiving donepezil over placebo ➢ Larger difference than that reported in other studies of ChEIs in DLB, Alzheimer’s and Parkinson’s disease dementia ➢ Shown in 12 week studies shorter than 6 months needed in Alzheimer’s disease Change from baseline Response rate (Improved MMSE≥3) 8 6 4 2 0 -2 -4 0 4 8 12 LOCF Mean MMSE changes (weeks） placebo （ n=32） 3mg （ n=35） 5mg （ n=32） 10mg （ n=36） • Significance level p<0.016 (Bonferroni correction) * Placebo 3mg 5mg 10mg 0 10 20 30 40 50 60 70 12.9 42.9 65.6 44.4 P=0.013 P<0.001 P=0.007 * 21 22 Treatment Approach for DLB – a disease affecting the cholinergic system A muscarinic M1 agonist is likely to have a superior profile 22 ➢ Greater cholinergic deficit in DLB patients relative to Alzheimer’s disease (AD) patients ➢ Loss of presynaptic cholinergic system reduces treatment potential of AChE inhibitors ➢ Post synaptic receptors more intact in DLB patients, potential for greater response to muscarinic M1 agonists Real opportunity for M1 agonist to have superior profile relative to donepezil in DLB patients The cholinergic channel is well understood… Acetylcholine (ACh) Postsynaptic Neuron AChE AcCoA + choline ChAT M1 R Choline + acetate ACh M2 (–) N (+) donepezil (AChE inhibitor) M1 R M1 R Presynaptic cholinergic Neuron DLB patients: postsynaptic neuron more preserved than AD patients DLB patients: presynaptic cholinergic system less preserved than AD patients P 23 Agenda 23 1 2 3 Introduction to DLB Diagnosis/Treatment Approach for DLB HTL0018318 M1 Agonist for DLB in Japan 24 HTL0018318 is a potential first-in-class therapy for DLB Highly selective M1 receptor agonist derived from StaR® & SBDD Selectivity is crucial. HTL0018318 has a differentiated mechanism with the potential to optimise symptomatic benefits in DLB patients Source: Internal analysis 1 Bodick et. al. “Effects of Xanomeline, a Selective Muscarinic Receptor Agonist, on Cognitive Function and Behavioural Symptoms in Al zheimer’s Disease” Arch Neurol. 1997;54@465-473 ➢ Cognitive benefits of M1 receptor agonism supported by Lilly’s clinical studies of Xanomeline1 ➢ Xanomeline’s development stopped due to unacceptable CV and GI side effects linked to stimulation of M2 & M3 ➢ HTL0018318 – a potent muscarinic M1 agonist with negligible M2/M3 agonism ➢ StaR® & SBDD “designed out” unwanted selectivity over the M2 & M3 receptors % activation -11 -10 -9 -8 -7 -6 -5 Log [Xanomeline] (M) M1 M2 M3 M4 Cognition CV side-effects GI side-effects Behavioural M1 Cognition O O 24 P P P HTL0018318 is a selective M1 receptor agonist with potential to benefit cognition and neuropsychiatric symptoms with negligible agonist activity at M2 or M3 receptors Rationale Behind Muscarinic M1 Agonism Xanomeline1 25 HTL0018318 is a potential first-in-class therapy for DLB Novel approach for symptomatic treatment ➢ Same thesis as donepezil – stimulate the M1 receptor, mediate cognition and neuropsychiatric effects ➢ HTL0018318 bypasses presynaptic activity, and does not rely on ACh levels in the brain ➢ Acts directly to stimulate the M1 receptor as an analogue of ACh post the synapse ➢ Designed to replace the underlying neurochemical deficit in DLB patients ➢ HTL0018318 offers first-in-class therapy 25 Selective muscarinic M1 receptor agonism offers first-in- class therapy for DLB patients HTL0018318 represents a novel approach to stimulation of the M1 receptor Presynaptic cholinergic Neuron Acetylcholine (ACh) AcCoA + choline ChAT Choline + acetate ACh M2 (–) N (+) Postsynaptic Neuron M1 R M1 R M1 R HTL0018318 Muscarinic M1 receptor agonist P P P 26 HTL0018318 for DLB in Japan Great potential for M1 agonist treatment for DLB in Japan 26 ➢ DLB is the second most common form of dementia and highly relevant in Japan ➢ Real patient need in Japan – ageing population ➢ Recognition and diagnosis of DLB symptoms significantly more advanced in Japan ➢ M1 agonist will show activity more rapidly and easily in DLB than in Alzheimer’s due greater cholinergic defect ➢ Potential to have a superior profile to donepezil as HTL0018318 acts independently of presynaptic system ➢ Potentially favourable environment – regulators in US/EU adapting dementia guidelines to meet increased disease understanding ➢ HTL0018318 represents a new treatment approach with potential to show meaningful patient benefits P P P P P P P Postsynaptic Neuron Acetylcholine (ACh) AcCoA + choline ChAT M1 R Choline + acetate ACh M2 (–) N (+) M1 R M1 R HTL0018318 Muscarinic M1 receptor agonist P P P Presynaptic cholinergic Neuron 27 HTL0018318 for DLB in Japan Summary of clinical program to date ➢ HTL0018318 derived from Heptares’ StaR® technology and SBDD ➢ HTL0018318 - same compound being investigated in AD trials with our partner Allergan • Allergan paid $125 million upfront for a portfolio of muscarinic compounds, including HTL0018318 ➢ In Phase 1a studies, HTL0018318 demonstrated to be safe and well tolerated, including in elderly people ➢ Ethnic bridging studies were completed by Heptares - safe and well tolerated in Japanese subjects ➢ HTL0018318 currently in a Phase 1b trial in patients with AD in Europe1 ➢ Agreed with Allergan that Sosei has rights for approval and commercialization of HTL0018318 for DLB in Japan Clinical progress to date encouraging. Subject to approval, we hope to move into a Phase 2 PoC study in DLB in Japan in 2018 1 EU study of HTL0018318 in AD https://www.clinicaltrials.gov/ct2/show/NCT03456349 27 28 HTL0018318 for DLB in Japan Target Product Profile for a Muscarinic M1 agonist to treat DLB ➢ Monotherapy Treatment of DLB ➢ Enhances cognitive function • Particularly executive dysfunction and visuospatial impairment (early MAD data supports this) ➢ Reduced frequency of cognitive fluctuations ➢ Reduced visual hallucinations in DLB ➢ Better tolerated than donepezil with less side effects on gut (GI) and postural hypotension (cardiac) ➢ Reduced caregiver burden from the DLB patient with economic benefits on cost of care ➢ Greater magnitude of cognitive enhancement and effects upon hallucination and delusions than donepezil ➢ Reduced autonomic disturbance and reduced postural hypotension Working towards a novel drug for DLB in Japan with the potential to significantly improve symptomatic treatment for patients, and ease the burden on Japanese society 28 Best Case Base Case 29 29 Thank you!

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