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ViroMed R&D IR Day Global Leader in DNA Gene Medicine #1

제품및 R&D 포트폴리오 바이오 천연물 유전자치료제 단백질 기능성소재 전문의약 DNA CAR T 항체사이토카인 piko ( 혈관 / 신경계질환 ) VM802 ( 혈액암 ) IE4 HX109 전립선비대증 HX210 ADHD 전임상연구 pmun ( 근육 / 신경계질환 ) VM803 ( 고형암 ) VM804 ( 고형암 ) 전임상연구 HX110 호흡기건강 HX111 불면증 임상개발 VM202 당뇨병성신경병증 ( 美임상 3 상 ) 당뇨병성족부궤양 ( 美임상 3 상 ) 루게릭병 ( 美임상 2 상 ) 심장병 ( 韓임상 2 상 ) VM501 항암보조요법 - 혈소판감소증 ( 中임상 3 상 ) 시장 PG102 HX106 유코믹스 레일라 VM206 유방암 ( 韓임상 1 상완료 ) HX111 #2

유전자치료제분류 유전자 직접주사 유전자전달체 세포이용 Cell/Gene Therapy - Naked plasmid DNA - Liposome - Electroporation AAV Adenovirus Retrovirus Vaccinia Herpesvirus 정상유전자 수정된유전자 새로운유전자 CAR-T CD34 기타세포 - Aptamer - RNAi Gene addition Gene replacement Gene editing #3

승인국가승인연도제품명회사명분류적응증 1 인당연간약가 미국 2017.12 Luxturna (AAV) Spark 유전질환 RPE65 변이관련망막형성장애치료제 $ 850,000 ( 약 9 억 652 만원 ) 미국 2017.10 Yescarta (CAR-T) Gilead (Kite) 암 B 세포비호지킨림프종 $ 373,000 ( 약 4 억 2 천만원 ) 미국 2017 Kymriah (CAR-T) Novartis 암 B- 세포유래급성림프구성백혈병 $ 475,000 ( 약 5 억 3,500 만원 ) 유럽 2016 Strimvelis (Retrovirus stem cell) GSK 유전질환 아데노신탈아미노효소결핍 (ADA-SCID) 600,000 ( 약 8 억원 ) 미국 2015 Imlygic (oncolytic virus) Amgen 암 절제불가능한악성흑색종 $ 65,000 ( 약 7,000 만원 ) 유럽 2012 Glybera UniQure 유전질환 지단백지질분해효소결핍증 (LPLD) 1,100,000 ( 약 15 억원 ) #4

총 21 개 암 (12 개 ), 유전질환 (4 개 ), 감염질환 (1 개 ), 만성질환 (4 개 ) 플라스미드 DNA 3 건 (2 건이바이로메드 ) 1 ViroMed 2 ViroMed 회사명적응증벡터 3 Vical & Astellas 만성질환 ( 당뇨병성신경병증 ) 만성질환 ( 당뇨병성궤양 ) 감염질환 (CMV 감염 ) 4 Advantagene 암 ( 전립선 ) DNA DNA DNA Vaccine HSV-TK/ Adenovirus 5 Advaxis 암 ( 자궁경부 ) HPV 6 Argos 암 ( 신장 ) RNA 7 Bluebird bio 8 Bluebird bio 9 BMS / Bavarian Nordic inc 유전질환 ( 대뇌부신백질이영양증 ) 유전질환 ( 베타지중해성빈혈 ) 암 ( 전립선 ) Lentivirus Lentivirus Poxvirus 10 FKD Therapies 암 ( 방광 ) Adenovirus 11 12 회사명적응증벡터 GenSight Biologics Guangzhou Double Bioproducts 유전질환 ( 레버시각신경병증 ) 암 ( 두경부 ) AAV Adenovirus 13 MolMed 암 ( 급성백혈병 ) Herpesvirus 14 Sillajen 암 ( 간 ) Vaccinia virus 15 Taxus Cardium 심장질환 ( 협심증 ) Adenovirus 16 Vascular Biogenics 암 ( 교모세포종 ) Adenovirus 17 TissueGene 퇴행성 ( 관절염 ) Retrovirus 18 Gilead / Kite 암 ( 외투세포림프종 ) CAR-T 19 Gilead / Kite 암 ( 비호지킨림프종 ) CAR-T 20 Celgene / bluebird bio 암 ( 다발성골수종 ) CAR-T 21 BioMarin 유전질환 ( 혈우병 ) AAV-factor VII #5

#6

현재바이로메드에서임상중인 DNA 의약 프로모터 5 UTR pck 치료유전자 1 HGF-X7 4 5 18 Intron Her2/Neu Her2/Neu (Ex+Tr) CD (Ex+Tr)CD IRES GM-CSF HGF 728 HGF 723 Her2/Neu (Ex+Tr) CD GM-CSF VM202 당뇨병성신경병증 당뇨병성허혈성궤양 근위축성측삭경화증 ( 루게릭병 ) 허혈성심장질환 ( 임상 2 상, 3 상 ) VM206 Her2 양성암 유방암 위암 기타 ( 임상 1 상완료 ) #7

바이로메드 DNA 의약플랫폼 특수제작된발현플랫폼에유전자를넣어다양한유전자치료제개발 발현플랫폼 (pck, ptx, pqx) 치료유전자 HGF Her2/neu SNI RTS X + Y VM202 VM206 piko pmun 연구 Cancer Vaccines Allergy #8

플라스미드 DNA 신제품 유전자 SNI 유전자 RTS 1 2 3 4 5 6 1 2 3 4 최적화 최적화 근육개선신경재생통증완화 PMUN pqx PIKO 상처치료 혈관형성 조직개선 신경 - 외상에의한신경손상 (Traumatic nerve injury) - 말초신경병증 (Peripheral neuropathy) - 길랭 - 바레증후군 (Guillain-Barre syndrome) 근육 - 좌골신경통 (Sciatica) - 근이영양증 (Muscular dystrophy) - 근력저하 (Muscle weakness) - 근육병 (Myopathy) - 샤르코 - 마리 - 투스병 (Charcot-Marie-Tooth) - 관상동맥질환 (Coronary artery disease) - 심근증 (Cardiomyopathy) - 만성창상 (Chronic wound) - 신경병증성통증 (Neuropathic pain) - 척수손상 (Spinal Cord Injury) - 말초동맥질환 (Peripheral arterial disease) - 동맥허혈궤양 (Ischemic ulcer) 혈관 - 근육감소증 (Sarcopenia) - 파행 (Claudication) - 심부전 (Heart failure) ( 목표 : 2025 년임상 3 상 ) #9

종배양발효세포파쇄정제및농축 DS 제형및충진 DP ( 원료의약품 ) 완제 #10

근육주사를통해손상된혈관과신경을재생시킬수있는혁신적인 DNA 의약 두종류의 HGF 단백질 (HGF 723, HGF 728 ) 을고효율로동시에생산하도록설계된플라스미드 DNA 특징 유전자발현수준매우높음 치료유전자 : HGF 두개이형체동시발현 동결건조 : 안정성제고 대량생산용이 #11

심혈관질환 척수 신경계질환 허혈성심장질환 심근경색증 한국임상 2 상 ( 진행중 ) 운동신경세포 근위축성측삭경화증 ( 루게릭병 ) 미국임상 2 상 ( 준비중 ) 근육 허혈성지체질환 중증하지허혈 (CLI) 당뇨병성허혈성궤양 미국임상 3 상 ( 진행중 ) 당뇨병성신경병증 통증성당뇨병성신경병증 미국임상 3 상 ( 진행중 ) #12

- 임상 3 상에서성공한다면 - 세계첫번째당뇨병성신경병증유전자치료제 세계첫번째 disease-modifying 신경병증치료제 세계첫번째당뇨병성족부궤양유전자치료제 세계첫번째 DNA 의약 #13

Strategy of clinical development for VM202 Phase III William K. Schmidt, PhD

VM202 Innovative Medicine for Major Indications with High Unmet Medical Needs #15

Flagship Product VM202 Innovative DNA medicine that induces formation of new blood vessels and repair damaged neurons following a simple series of IM injections Plasmid DNA designed to simultaneously express two isoforms of HGF Features High level gene expression in vivo Therapeutic gene: HGF Simultaneous expression of two isoforms of HGF Easy for bulk production Lyophilized: improved stability #16

#17 MOA of VM202 Spinal cord Sensory neuron Cell body 2. Pain Relief Degenerating axons Motor neuron Axon regeneration Reinnervation 3. Regeneration of peripheral nerve cells Muscle spindle HGF HGF NMJ 4. Amelioration of muscle atrophy I.M. injection (VM202) Skeletal muscle I.M. injection (VM202) 1. Angiogenesis

Clinical Development of VM202 Cardiovascular Coronary Artery Disease Acute Myocardial Infarction Phase II (Korea) ongoing Spinal Cord Neurological Amyotrophic Lateral Sclerosis Lou Gehrig s Disease Phase II (US) planned Motor neuron Spinal Cord Muscle Peripheral Artery Disease Chronic Non-Healing Foot Ulcer Phase III (US) ongoing Diabetic Peripheral Neuropathy Painful Diabetic Peripheral Neuropathy Phase III (US) ongoing #18

1 st Target Disease of VM202 Painful Diabetic Peripheral Neuropathy (PDPN) One of the most frequently observed neuropathies associated with 30% of all diabetes patients Patients suffer from sensory loss, dysesthesia, and night time pain. Hyperglycemia Painful diabetic peripheral neuropathy Blood vessel damage Nerves shrivel when blood vessels disappear Throbbing, Burning, Stabbing, Tingling Normal Blood vessel Nerve #19

Currently Used Medicines for Painful DPN There are 3 major drugs for DPN, generating $ 3-4 billion market. Anticonvulsant: Antidepressant: Opioid: NSAIDs Pregabalin (Lyrica, Pfizer) $ ~5.1 Billion (2014), Neuropathic pain market: 30-50% Duloxetine (Cymbalta, Eli Lilly) $ 5 Billion (2013), Neuropathic pain market: > $1 Billion Tapentadol (Nucynta ER, Depomed) Overall sales: $ 281 Million (US, 2016) FDA Approved for DPN Pain Treatment benefit modest Tolerability and side effects minimize compliance Several failed clinical trials in moderate to severe PDPN #20

Poor Tolerability of Current Medications for Painful DPN Outcome Efficacy outcomes Cumulative ranking for efficacy and tolerability Pregabalin (Lyrica) Gabapentin (Neurontin) Duloxetine (Cymbalta) 30% pain reduction 33.0 44.6 89.2 50% pain reduction 38.2 73.5 81.5 Tolerability outcomes Somnolence 40.2 48.1 6.1 Dizziness 35.0 36.3 74.7 Nausea 65.5 42.1 0.4 Headache 83.3 60.4 28.8 Fatigue 61.4 22.3 29.1 Constipation 41.1 49.9 86.9 Diarrhea 67.9 60.1 2.8 Discontinuation due to adverse events 46.2 34.3 19.5 Meta-analysis of 25 published studies, 1950-2014; van Nooten F, et al. Clin Ther. 2017 #21

Potential Advantages of VM202 Administered only 2x in Phase II clinical trials (Day 0 and Day 14) Minimal discomfort from patterned i.m. injections High efficacy observed at 3 months (primary endpoint) that continues for 9-12+ months without further treatment Very high tolerability (minimal treatment-related adverse effects) Very high patient acceptability (PGIC = patient global impression of change) Potential disease-modifying drug (first-ever!) #22

Study Outline of VM202-DPN Phase II A Double-Blind, Randomized, Placebo-Controlled, Multicenter Study (US, Korea) Principal Investigator JOHN (JACK) A. KESSLER, M.D. (Northwestern Medical School) 1. Indication: Painful Diabetic Peripheral Neuropathy 2. Total administered subjects: 103 3. Injection scheme Bilateral 2 injection cycles along the calf line (day 0 & 14) (~ 2cm deep) (~ 2cm distance) 4. Follow-up period: 9 months 5. Efficacy Pain score (Daily Pain and Sleep Interference Diary)* VAS*, BPI-DPN*, MNSI, PGIC* and histological findings on skin biopsy * These methods were used in Pfizer s clinical studies for Lyrica. 6. Safety #23

Effect on Pain Severity (Daily Pain Diary) 2 Rounds of IM injection of VM202 2 Rounds of IM injection of VM202 Changes in severity from baseline 0.0-1.0-2.0-3.0-4.0 * -1.53-1.59-1.95-3.03 (Δ=-1.5) All Subjects (n=84) -2.78-2.98 0 3 6 9 Months after first injection [*p<0.05, vs. placebo, p<0.05, vs. baseline, Δ VM202 16mg Placebo] (Δ=-1.19) (Δ=-1.03) Placebo VM202 16 mg (8 mg/leg) High long-term pain-relieving effects Data on other pain killers taken from public sources Changes in severity from baseline 0.0-1.0-2.0-3.0-4.0-1.30-1.17-3.67 Subjects NOT on Lyrica and/or Neurontin (n=49) -3.46-2.08 * -3.55 (Δ=-2.37) (Δ=-2.29) (Δ=-1.47) 0 3 6 9 Months after first injection [*p<0.05, vs. placebo, p<0.05, vs. baseline, Δ VM202 16mg Placebo] * Placebo VM202 16 mg (8 mg/leg) : Higher pain-relieving effects in subjects not on gabapentin and/or pregabalin #24

Data Suggesting VM202 s Potential to Become a Disease-Modifying Drug Effect of VM202 in Monofilament Test All Subjects (n=84) NOM = patients NOT taking Lyrica and/or Neurontin in the present study *p<0.05, vs. placebo group 9 months Placebo VM202 Left 13.3% 44.4% Right 25.0% 38.5% Both 19.4% 41.5% * NOM (n=49) Left 0% 56.3% Right 18.2% 57.2% Both 9.1% 56.7% Simplified from Kessler et al. Annals of Clinical and Translational Neurology, 2: 465-478 (2015) The 16 mg group showed improvement in sensory threshold at 9 months. Again, patients not on Lyrica and/or Neurontin responded far better to VM202, for up to 9 months. * * #25

Key Discoveries of DPN Phase II Trial 1. VM202 has shown an excellent safety profile compared to current prescription drugs. (No antibody to HGF, No change in HGF serum level). 2. The 16 mg dose of VM202 (8 mg/leg) gave significant improvements in all pain measurements for a long period of time. (Daily pain diary, BPI-DPN, VAS, PGIC) 3. Pain relieving effects were more pronounced in patients who are not taking Lyrica and/or Neurontin. 4. Data from monofilament tests suggests that VM202 may aid recovery of sensory functions and has the potential to be a disease-modifying drug. #26

Study Outline of VM202-DPN Phase IIIs Double-Blind, Randomized, Placebo-Controlled, Multicenter Center Phase III-1 1. Target indication PDPN 2. Treatment arms 477 * (Placebo: 159, VM202: 318) Phase III-2 PDPN (not on gabapentin and/or pregabalin) 333 (Placebo: 111, VM202: 222) 3. Injection scheme 2 cycles 16 mg + 16 mg (Days 0, 14) (Days 90, 104) 4 cycles 16mg + 16mg + 16mg + 16mg (Days 0,14) (Days 90,104) (Days 180, 194) (Days 270, 284) 4. Follow-up 9 months 12 months 5. Primary endpoint Daily pain diary at 3 months, 50% responder at 3 months 6. Secondary endpoint Daily pain diary at 6 months 50% responder at 6 months 50% responder at 12 months Monofilament test at 12 months * 321 administered as of Jan 5, 2018 #27

VM202 Painful Diabetic Peripheral Neuropathy Current Phase III Clinical Trial Protocol VMDN-003 initiated November 10, 2016 Double-blind, randomized, placebo-controlled, multicenter, 9-month study Safety and efficacy of bilateral IM injection of VM202 in the calves of subjects with painful diabetic peripheral neuropathy (DPN) 16 mg of VM202 administered in divided doses at Day 0 and Day 14; second treatment of 16 mg VM202 at 3 months administered as divided doses at Day 90 and Day 104 Final total dose of 32 mg VM202 administered per subject Treatment - VM202-318 subjects Control - Placebo (VM202 vehicle) - 159 subjects Study Objectives: To evaluate the efficacy (relief of pain) and safety of IM administration of VM202 vs. placebo in subjects with painful DPN in the lower extremities #28

VM202 Painful Diabetic Peripheral Neuropathy Current Phase III Clinical Trial 25 geographically-distributed sites in the USA #29

VM202 Painful Diabetic Peripheral Neuropathy Current Phase III Clinical Trial Dosing: All subjects will receive sixteen (16) 0.5 ml injections of VM202 or placebo evenly distributed over each calf at each visit. VM202 vehicle is indistinguishable from reconstituted VM202. Neither subject nor clinician will be able to distinguish placebo from VM202. #30

2 nd Target Disease of VM202 Chronic, Non-Healing, Ischemic Foot Ulcers in Diabetes Patients Ischemic foot ulcers result from narrowing or blockage of peripheral arteries in the legs. Many diabetes patients suffer from chronic, non-healing foot ulcer. Blocked / Occluded Peripheral Artery Vessels Claudication Rest Pain Ulcer (Chronic) Gangrene Amputation Hyperglycemia Atherosclerosis Diabetes 26 million Peripheral Neuropathy 15 million Chronic Foot Ulcer 4.5 million CLI 0.85 million Peripheral Artery Disease 8.5 million Chronic Foot Ulcer CLI Critical Limb Ischemia Total Number ~ 4.5 Million ~ 0.85 Million Amputation 82,000 200,000 Medical Costs $ 9-13 Billion ~ $ 8 Billion #33

Phase II Trial for CLI as a POC model A Double-Blind, Randomized, Placebo-Controlled, Multicenter Study (US, Korea) Principal Investigator EMERSON C. PERIN, M.D. (Stem Cell Center Texas Heart Institute) 1. Indication: Critical Limb Ischemia (Rutherford class 4 and 5) 2. Total administered subjects: 52 Placebo (0.9% normal saline): 11 subjects Low dose of VM202 (2 mg/visit): 21 subjects High dose of VM202 (4 mg/visit): 20 subjects 30/52 (57.6%) subjects had diabetes. 3. Injection scheme: 4 injection cycles along the calf line (days 0, 14, 28, & 42), unilateral IM injection 4. Follow-up period: 12 months 5. Efficacy 6. Safety #34

Substantial Healing Effects Observed in Ulcers Placebo (Screening) Placebo (Day 90) Group (Number of ulcers) Completely healed Improved 1) Low dose (Screening) Low dose (Day 365) Placebo (n = 9) 11% (1/9) 11% (1/9) Low dose (n = 27) 52% (14/27) * 70% (19/27) High dose (Screening) High dose (Day 365) High dose (n = 13) 62% (8/13) * 69% (9/13) * (Kibbe et al., Gene Therapy (2016) 1-7) 1) Reduction of ulcer area > 50% [* p < 0.05, vs. placebo (Fischer Exact Test)] A higher % of completely healed ulcers was observed in the high dose group during 12-month follow-up period. #35

Study Outline of VM202-PAD Phase III Double-Blind, Randomized, Placebo-Controlled, Multicenter 1. Indication: Chronic Non-Healing Ischemic Diabetic Foot Ulcers - Ulcer(s) on or around the foot area that are unresponsive to standard therapies and persist despite 4 weeks of appropriate care 2. Total administered subjects: 300 16 mg VM202 + Standard Care: Placebo (VM202 vehicle) + Standard Care: 200 subjects 100 subjects 3. Injection scheme: 4 unilateral injection cycles in the ipsilateral calf of the affected foot (day 0, 14, 28, and 42) 4. Follow-up: 7 months 5. Efficacy endpoints: Primary: Complete wound closure, 4 months 6. Safety endpoints SilhouetteStar Ulcer size is measured using 3D camera to determine ulcer depth or volume #36

VM202 5-Year Timeline Partnership with global pharmaceuticals Two phase IIIs DPN, PAD BLA Current approval 1 st treatment DPN Phase III-1 Completion expected DPN Phase III-2 Completion expected approval 1 st treatment approval 1 st treatment PAD Phase III-1 Completion expected 2015 2016 2017 2018 2019 2020 2021 #37

Market estimation for PDPN Cathryn A. Carroll, PhD

ViroMed s Goal through 2025 Global Leader in DNA-Based Gene Therapy To be the only biotech company with world s largest revenue from gene therapies by 2025 Targeting major human diseases with high unmet medical needs Skills and expertise in clinical development Market competitiveness Cardiovascular diseases Neurovascular and neuromuscular diseases Muscular diseases Running two phase IIIs in the US for DPN* and NHU* Extensive clinical experience High safety of DNA drug Advanced technology * DPN: diabetic peripheral neuropathy * NHU: non-healing ischemic diabetic foot ulcer Highly prevalent diseases Current treatment methods: - Highly limited in efficacy & safety Disease modifying potential #39

Key Considerations to Be Competitive Differentiating VM202 (EASY) VM202 s Position in PDPN Market Drug Pricing Analysis To Date Target Patient Population & Peak Sales Estimates to Date 2018 Market Shaping Needs & Priorities #40

Differentiating VM202 Is Easy Overview of various pathogenetic components contributing to DPN. Kevin L. Farmer et al. Pharmacol Rev 2012;64:880-900 2012 by The American Society for Pharmacology and Experimental Therapeutics #41

Know Competition Strengths & Weakness Anticonvulsants: Antidepressants: NSAIDs Opioids: Pregabalin (Lyrica, Pfizer) $ ~5.1 Billion (2014), Neuropathic pain market: 30-50% Gabapentin (Neurontin, Pfizer) $ ~ 210 Million (2014) Duloxetine (Cymbalta, Eli Lilly) $ 5 Billion (2013), Neuropathic pain market: > $1 Billion Tapentadol (Nucynta ER, Depomed) Overall sales: $ 281 Million (US, 2016) Treatment benefit (pain control) is modest No disease modifying potential, neuroregeneration or angiogenesis Act centrally with significant adverse effects including increased risk of suicidal thoughts or behavior, dizziness, sleepiness Several failed clinical trials in moderate to severe PDPN #42

Know VM202 s Expected Place In Therapy #43

Price Appropriately (Completed by Viewpoint Health November 2017) Key Attributes Results Indication & region PDPN in the USA Price Net of Discounts/Rebates $50,000 No. of treated patients (2021-2032) for 10-12 years Estimation period Peak revenue ($ Billion) Probability of Successful Commercialization 1,363,150 10 years $14.0 100% Discount rate 15% VM202-DPN risk-adjusted NPV ($ Billion) $14.1-$15.5 #44

Proactively Prepare the Market for Launch Differentiating VM202 Through An Innovative Linguistic Platform (Lexicon) Insight Gathering Telling the ViroMed & VM202 Story #45

Proactively Prepare the Market for Launch Shining The Light on Patient & Caregiver Needs Activating KOLs Surveillance on Distribution and Physician Adoption of Like Technologies #46

Key Considerations to Be Competitive It s Easy to Differentiate VM202 VM202 s Greatest Differentiation is in Individuals with Moderate to Severe PDPN Drug Pricing Analysis Will Continue Target Patient Population and Peak Sales Estimates to Date are Exciting Market Shaping Activities Are Under Way #47

ViroMed s Goal through 2025 Global Leader in DNA-Based Gene Therapy To be the only biotech company with world s largest revenue from gene therapies by 2025 Targeting major human diseases with high unmet medical needs Skills and expertise in clinical development Market competitiveness Cardiovascular diseases Neurovascular and neuromuscular diseases Muscular diseases Running two phase IIIs in the US for DPN* and NHU* Extensive clinical experience High safety of DNA drug Advanced technology * DPN: diabetic peripheral neuropathy * NHU: non-healing ischemic diabetic foot ulcer Highly prevalent diseases Current treatment methods: - Highly limited in efficacy & safety Disease modifying potential #48