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January 2016

Overview of Acelex® (Polmacoxib),

a Novel NSAIDfor Osteoarthritis

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To become a fully integrated biopharmaceutical company in Korea and expand internationally through collaborations and partnerships

To become a fully integrated biopharmaceutical company in Korea and expand internationally through collaborations and partnerships VisionVision

2000.07 Founded2003.09 Publication in Nature (article and cover based on platform technology)2006.01 IPO on KOSDAQ 2006.10 Established US subsidiary, CG Pharmaceuticals, Inc. for clinical development2012.06 Designated by the Korean government as one of the ‘KIPC’ certified companies2014.07 Designated by the Korean government as one of the ‘K-BrainPower’ companies2015.02 Obtained the NDA approval from MFDS for Acelex® in Korea (osteoarthritis)2015.09 Launch of Acelex® in Korea

2000.07 Founded2003.09 Publication in Nature (article and cover based on platform technology)2006.01 IPO on KOSDAQ 2006.10 Established US subsidiary, CG Pharmaceuticals, Inc. for clinical development2012.06 Designated by the Korean government as one of the ‘KIPC’ certified companies2014.07 Designated by the Korean government as one of the ‘K-BrainPower’ companies2015.02 Obtained the NDA approval from MFDS for Acelex® in Korea (osteoarthritis)2015.09 Launch of Acelex® in Korea

HistoryHistory

Next generation NSAID, Acelex® for osteoarthritis (first-in-class) Novel antibiotic candidate for MRSA infection, CG400549 (first-in-class)Molecular-targeted cancer therapeutic, CG200745 (best-in-class)

Next generation NSAID, Acelex® for osteoarthritis (first-in-class) Novel antibiotic candidate for MRSA infection, CG400549 (first-in-class)Molecular-targeted cancer therapeutic, CG200745 (best-in-class)

Key ProgramsKey Programs

CrystalGenomics is a commercial stage biopharmaceutical company with innovative platform technologies dedicated in the discovery and development of novel pharmaceuticals in unmet medical need areas.

Corporate Overview

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Platform Technology : Overview

Integration of in vitro experiments and in silico technology enables the company to streamline

the drug discovery process from gene to drug.

Lead Discovery ( SCPTM )

SCPTM NMR

Virtual Screening

In vitro Assay

SCPTM LibrarySCPTM Screening

Synchrotron, NMR

Structure Determination ( SPSTM )

AGTCTCAG

TargetSelection

Lead Optimization and Candidate Selection ( SDFTM )

In vivo Evaluation

DMPKToxicologyPharmacology

BiologicalEvaluations

Target Assays Cellular AssaysIn vitro DMPK

Drug Design &MediChem

SDFTM X-raySDFTM InformaticsParallel Synthesis

Pre-clinicalCandidate

Lead / TargetComplex

OR2

R3

ON

R1

IND-enabling Tox(CRO in EU,USA)

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CG Has Global Standard Drug Discovery Capabilities

Viagra ®

(sildenafil)

Cialis ®

(tadalafil)

Levitra ®

(vardenafil)

CrystalGenomics was the first group to solve the complex crystal structure of PDE5 using SPS™ technology: Nature 425, 98-102 (2003).

5•5

•SBI BIOTECH CO., LTD.

Former & Current Alliance Partners

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R&D Pipeline

Disease TargetCandidat

eIndication Phase I Ph II Ph III

1Infectious Disease MRSA

2Cancer MDS

Area Product Indication Current Status Partners

2Cancer Pancreatic cancer

1Cancer AML

1CNS Alzheimer’s Disease

2Metabolic Anemia

1. First-in-class , 2. Best-in-class

Novel Therapeutics Pipeline

Inflammation 1Acelex® Osteoarthritis • Approved by the MFDS (Feb. 2015), • Launched in Korea (Sep. 2015) • Partnered with TR-Pharm for Turkey & MENA (Jan. 2016)

Area Indication Discovery Preclinical Ph I Ph II Ph III NDA

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Next Generation NSAID, Acelex® (polmacoxib)

(Novel NSAID with Tissue-Selective Activity)

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Acelex® 2mg Capsule Novel NSAID for the relief of signs and symptoms of osteoarthritis

▪ Global market for arthritis drugs was USD 50B, of which $17.5B consisted of COX-2 drugs & NSAIDs but existing therapies have CV and GI safety issues and there is a great unmet medical need for a safer drug1

▪ 16,344 deaths and 545,452 hospital admissions from GI bleeding in 2006 and heavy NSAID usage partially to blame2

▪ Celebrex® (Pfizer) - 2012 global sales was USD 2.7B and USD 51M+ sales in Korea with double digit CAGR (2012)

▪ Approved by the MFDS of Korea (Feb. 5, 2015)

▪ Launched in September 2015 (marketed and sold by Dong-A ST)

▪ Partnered with TR-Pharm for commercialization of Acelex in Turkey & MENA region, covering 19 countries (Jan. 2016)

1IMS Top Line Industry Data (2009) 2Statistical Brief #65 Healthcare Cost and Utilization Project Jan. 2009 Agency for Healthcare Research & Quality, Rockville, MD

Acelex Target Market

Acelex®, A Novel NSAID for Osteoarthritis

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Acelex®, Tissue Selective NSAID for Osteoarthritis

Category Projected Advantages of Acelex

Efficacy• Quicker onset of relief from the signs and symptoms of OA over celecoxib.• Achieved superior PGA (Physicians Global Assessment) scores compared to celecoxib.

Dose • Only 2 mg/day dose, the lowest daily dose among all known NSAIDs.

Administration Frequency

• Convenient once-a-day dosing regimen unlike most other NSAIDs.

Gastrointestinal Side Effects

• Significantly improved GI safety in comparison with traditional NSAIDs on the market.

Cardiovascular Side Effects

• Acelex’s tissue-selective-COX2-inhibition mechanism is projected to provide a meaningful enhancement of cardiovascular safety over currently available NSAIDs.

< Acelex® 2mg Capsule > Tissue-Selective NSAID for the Relief of Signs Symptoms of Osteoarthritis (OA)

• Approved by the MFDS (Feb. 2015),

• Launched in Korea by Dong-A ST (Sep. 2015)

• Partnered with TR-Pharm for Turkey & MENA (Jan. 2016)

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OA Market Characteristics

Osteoarthritis (OA) is characterized by deterioration of cartilage tissue within joint and involves entire joint1

• Nearby muscles• Underlying bone• Ligaments• Joint lining (synovium)• Joint cover (capsule)

The cause is still not completely known and there is no cure Aging of population is driving growth of OA market

• Cartilage degradation is positively correlated with increasing age and is most common in people over 55 years of age

Obesity epidemic resulting in more wear and tear on joints is also contributing to growth of OA market

1 Business Insights © 2009; The Autoimmune Outlook to 2013

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Positioning of A Novel NSAID, Acelex® for Osteoarthritis

• Acelex would be the first, tissue-selective and once-a-day osteoarthritis drug with a novel mode of action that specifically targets affected joints to relieve pain and restores mobility• Acelex 2 mg once-a-day could provide more rapid onset of relief from the signs and symptoms of osteoarthritis in comparison with Celebrex 200 mg once-a-day without added safety risk.

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Product Profiles of Marketed NSAIDs and COX-2 Inhibitors

Classification Drug Products Characteristics GI Risk CV Risk

Traditional NSAIDs

Traditional NSAIDs: naproxen, ibuprofen, diclofenac

- Low selectivity- 2–4 times/day (75–2,400 mg/day)

Very high Moderate or high

Vimovo (Pozen, AstraZeneca)

- Naproxen + Esomeprazole-Twice/day- FDA warning for long-term use- Sales volume is small.

Moderate Moderate

COX-2Inhibitors

Celebrex®

(Celecoxib: Pfizer)

- Sales in 2010 was $2,374M- Once or twice/day (200–400 mg/day)

Low Moderate

Arcoxia®

(Etoricoxib: Merck)

- Sales in 2010 was $398M in EU- Not approved in the US - Once/day (30–120 mg/day)

Low High

Tissue Selective

COX-2 Inhibitor

Acelex®

(Polmacoxib: CG)- ‘Tissue selective’ COX-2 inhibitor- Once/day (2 mg/day)

LowNone

observedto date

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Whole Blood, Blood Vessels, CV Tissues

Inflamed Joints (OA, RA)

Limited side effects Good efficacy

Polmacoxib

COX-2

CA

CA >> COX-2 Preferred binding to CA

CA << COX-2 Preferred binding to COX-2

Polmacoxib, a dual inhibitor of COX-2 and human CA (carbonic anhydrase), does not inhibit COX-2 in CA-rich tissues (e.g. CV system), but it fully inhibits COX-2 in CA-deficient tissues (inflamed joints).

Mechanism of Polmacoxib

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Summary of Clinical Studies for Acelex

Phase TypeClinicalTrials.gov

IdentifierTrialSize

Status Location

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First-in-human studySingle ascending dose (SAD) study - 24 Completed UK

Multiple ascending dose (MAD) studySafety and Pharmacokinetic (PK) Study - 16 Completed UK

MAD studySafety and pharmacokinetic study - 48 Completed US

Pilot biomarker study NCT00780325 24 Completed US (Univ. of Penn)Drug-drug interaction (DDI) study NCT01154764 26 Completed Seoul, Korea

Supra-therapeutic MAD studysafety and PK study NCT01154790 48 Completed Seoul, Korea

2Placebo controlled proof-of-concept study NCT00530452 248 Completed EU

Celecoxib controlled dose finding study NCT01341405 125 Completed Seoul, Korea

3Placebo and Celecoxib controlled pivotal

Ph 3 efficacy & safety for approval and extended safety study

NCT01765296 362 Completed Seoul, Korea

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Compiled Summary of Completed Studies

Clinical Studies Summary

Phase 1 studies

• Dose dependent exposure observed.• No significant PK differences among different ethnic and gender groups.• Clearly differentiated whole blood vs. plasma distribution of polmacoxib – Proof of

polmacoxib-CA binding (75 80x higher conc. in whole blood vs. plasma).∼

• No drug-drug interaction observed.• Stable blood pressure maintained throughout entire duration of clinical studies• Absence of significant side effects even in the supra-therapeutic MAD Study • Cardiovascular safety – Various measurements including ECG, Holter monitoring, vital

signs, and blood chemistry lab tests did not indicate signs of CV adverse events.• Gastrointestinal safety – Absence of significant GI adverse events

Phase 2a study• Clinically significant efficacious dose = 1.2 mg per day• No drop outs due to lack of efficacy• Maintenance of stable blood pressure throughout entire study

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Compiled Summary of Completed Studies

Clinical Studies Summary

Phase 2b study

• Non-inferiority tests: polmacoxib 2 mg/day and 4 mg/day vs. celecoxib 200 mg/day• Uniform dosing on Days 1-28 (no loading dose)• Very high study drug compliance rates (81-85% in all groups)• Few dropouts (93-95% completion rate among all 3 treatment arms)• Polmacoxib 2 mg and 4 mg were non-inferior to celecoxib 200 mg for all efficacy

measures• Polmacoxib 2 mg dose produced higher efficacy than celecoxib 200 mg, though not

statistically significant (study was not powered for superiority)• No drop outs due to lack of efficacy• Polmacoxib 2 mg has a favorable adverse effect profile (comparable to celecoxib 200 mg)• Polmacoxib 2 mg dose selected for Phase 3 clinical studies

Phase 3 study

• Effficacy (6 week study) Superiority of polmacoxib 2 mg once-daily vs. placebo Non-inferiority of polmacoxib 2 mg once-daily vs. celecoxib 200 mg once-daily• Long Term Safety (6 month study) No drug-related serious adverse events in either of the polmacoxib or celecoxib groups. Most of the adverse events were mild to moderate and were expected to happen in this type of trial.

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Phase III Clinical Study

Summary

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Phase III Study: Study Title & The Objectives

Study Title:A Double-blind, Randomized, Multicenter, Active- and Placebo-Controlled Phase III Study to Evaluate the Efficacy and Safety of CG100649 in Osteoarthritis Patients

Objectives: The objective of the 6-week Efficacy Study was to evaluate the safety and non-inferiority of the analgesic efficacy of polmacoxib (formerly CG100649) 2 mg vs. celecoxib 200 mg, and the analgesic superiority of polmacoxib 2 mg vs. placebo, when administered once daily in subjects with osteoarthritis of the hip or knee over the 6 week treatment period.

The objective of the Extension Study was to collect a total of 24 weeks of safety data for those subjects who agreed to continue into the extension.

Study Title and the Objectives of the Study

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Acelex®, Phase III Study Results

71.9% of subjects taking Acelex experienced improvement in signs and symptoms of osteoarthritis

*PGA (Physician’s Global Assessment ): Evaluation of the test subjects by the investigators (physicians)

Acelex showed SUPERIOR EFFICACY over celecoxib with statistical significance (p = 0.005)

Overall improvement of signs and symptoms of osteoarthritis in terms of PGA* scores at week 3

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Acelex®, Phase III Study Results

Acelex showed QUICKER ONSET OF RELIEF from osteoarthritis symptoms over celecoxib

Acelex showed statistically significant superiority over placebo at Week 3 (p=0.003), but celecoxib did NOT show statistically significant differentiation from placebo at Week 3 (p=0.069)

WOMAC Physical Function scores at Week 3

Acelex demonstrated non-inferior or better efficacy against celecoxib in all other efficacy endpoints including WOMAC-pain and –stiffness subscales at week-3 and week-6

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Safety Results from the 6-week Efficacy Study

There were no drug-related serious adverse events in either of the polmacoxib or celecoxib treatment groups.

Most of the adverse events were mild to moderate and were expected to happen in this type of trial.

There were no statistically significant differences in all three groups.

Phase III Study: Safety (6-week Treatment Period)

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Polmacoxib has successfully met the clinical study endpoints as the 2 mg dose of polmacoxib was tolerated well and based on the results of the 6‑week treatment period, polmacoxib 2 mg demonstrated analgesic efficacy and safety similar to that of celecoxib 200 mg, and analgesic superiority over that of placebo.

However, based on the secondary endpoints of WOMAC-Physical function at Week 3 and PGA at Week 3, the efficacy profile of polmacoxib was superior in comparison with celecoxib. This suggests that polmacoxib 2 mg achieves a quicker onset of relief from the signs and symptoms of osteoarthritis compared to celecoxib 200 mg.

The Treatment Emergent Adverse Events (TEAEs) were reported in this study were generally mild and of the type expected for COX-2 inhibitor drugs.

There were no clinically meaningful or statistically significant differences in the number of TEAEs among the groups treated with polmacoxib 2 mg, celecoxib 200 mg or placebo.

Phase III Study: Conclusions (6-week Treatment Period)

Conclusions

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Phase III Study: Extended Safety Study

Safety Conclusions from Safety Extension Study (24 weeks)

• Only polmacoxib 2mg administered (open-label, single arm)

There were no drug-related serious adverse events.

During the safety extension study, the 2mg dose of polmacoxib was tolerated well and TEAEs were generally mild.

There were no notable increases in the incidence of any TEAEs during the 18-week safety extension period, or the combined 24-week extended safety period.

There were no clinically relevant findings in the analysis of clinical laboratory tests, vital signs, ECGs, or physical examination results.

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Category Projected Advantages of Acelex

Efficacy

• Demonstrated quicker onset of relief from the signs and symptoms of OA over Celebrex.• Achieved superior PGA (Physicians Global Assessment) scores, than Celebrex with statistically significance, an efficacy endpoint for measuring the physicians’ perception of patient improvement in terms of the OA signs and symptoms.

Dose • Able to achieve therapeutic efficacy (OA) with only 2 mg/day dose, the lowest dose among all known NSAIDs (both non-selective and selective COX-2 inhibitors).

Administration Frequency

• Convenient once-a-day dosing regimen → The administration frequencies of most commercially available traditional NSAIDs and incrementally modified NSAID containing products for OA range between b.i.d (twice daily) through t.i.d (three times daily).

Gastrointestinal Side Effects

• Acelex has significantly improved GI safety profile in comparison with other commercially available NSAIDs.

• The GI safety profile of Acelex eliminates the need for concomitant administration of GI protectant agents.

Cardiovascular Side Effects

• Acelex’s unique mode of action is projected to provide a meaningful enhancement of cardiovascular safety from currently available NSAID products.

Product Profile of Acelex

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Launch of 2 mgCapsule 2015

Generic Entry Block2026~2034

• Launch in Korea• Export or Out-Licensing

• Expansion of Acelex portfolio through development of combination products, incrementally modified products, new dosage forms, and additional indications.• Goal is to maintain exclusive position up to 2026~2034 and maximize revenues.

Acelex®, Lifecycle Management Strategy

Strengthening of the Acelex brand name through launch of multiple products

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CrystalGenomics, Inc.5th F. Bldg.A, Korea Bio Park700 Daewangpangyo-ro, Bundang-gu,Seongnam-si, Gyeonggi-do 463-400Korea

CG Pharmaceuticals, Inc.5980 Horton Street, Suite 610Emeryville, CA 94608U.S.A.