1. Overview of Acelex® (Polmacoxib), a Novel NSAID for Osteoarthritis
January 2016

2. Corporate Overview
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.
Vision
To become a fully integrated biopharmaceutical company in Korea and expand
internationally through collaborations and partnerships
History
Founded
Publication in Nature (article and cover based on platform technology)
IPO on KOSDAQ
Established US subsidiary, CG Pharmaceuticals, Inc. for clinical development
Designated by the Korean government as one of the ‘KIPC’ certified companies
Designated by the Korean government as one of the ‘K-BrainPower’ companies
Obtained the NDA approval from MFDS for Acelex® in Korea (osteoarthritis)
Launch of Acelex® in Korea
Key Programs
Next generation NSAID, Acelex® for osteoarthritis (first-in-class)
Novel antibiotic candidate for MRSA infection, CG (first-in-class)
Molecular-targeted cancer therapeutic, CG (best-in-class)

3. 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.
Structure Determination ( SPSTM )
Lead Discovery ( SCPTM )
SCPTM Library
SCPTM Screening
SCPTM NMR
AGTC
TCAG
Virtual Screening
In vitro Assay
Target
Selection
Synchrotron, NMR
Lead Optimization and Candidate Selection ( SDFTM )
Drug Design &
MediChem
SDFTM X-ray
SDFTM Informatics
Parallel Synthesis
Biological
Evaluations
Target Assays
Cellular Assays
In vitro DMPK
In vivo
Evaluation
DMPK
Toxicology
Pharmacology
IND-enabling Tox
(CRO in EU,USA) O R2 R3 N R1
Lead / Target
Complex
Pre-clinical
Candidate

4. CG Has Global Standard Drug Discovery Capabilities
CrystalGenomics was the first group to solve the complex crystal structure of PDE5 using SPS™ technology: Nature 425, (2003).
Viagra ®
(sildenafil)
Cialis ®
(tadalafil)
Levitra ®
(vardenafil)

5. Former & Current Alliance Partners
SBI BIOTECH CO., LTD. 5

6. Novel Therapeutics Pipeline
Area
Product
Indication
Current Status
Partners
R&D Pipeline
Inflammation
1Acelex®
Osteoarthritis
• Approved by the MFDS (Feb. 2015),
• Launched in Korea (Sep. 2015)
• Partnered with TR-Pharm for Turkey & MENA (Jan. 2016)
Disease Target
Candidate
Indication
Phase I
Ph II
Ph III
1Infectious Disease
MRSA
2Cancer
MDS
Area
Indication
Discovery
Preclinical
Ph I
Ph II
Ph III
NDA
2Cancer
Pancreatic cancer
1Cancer
AML
1CNS
Alzheimer’s Disease
2Metabolic
Anemia
1. First-in-class , 2. Best-in-class 6

7. (Novel NSAID with Tissue-Selective Activity)
Next Generation NSAID,
Acelex® (polmacoxib)
(Novel NSAID with Tissue-Selective Activity)

8. Novel NSAID for the relief of signs and symptoms of osteoarthritis
Acelex®, A Novel NSAID for Osteoarthritis
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) 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)
Acelex Target Market
1IMS Top Line Industry Data (2009)
2Statistical Brief #65 Healthcare Cost and Utilization Project Jan Agency for Healthcare Research & Quality, Rockville, MD 8

9. Acelex®, Tissue Selective NSAID for Osteoarthritis
< 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)
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. 9

10. 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

11. 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.

12. 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
COX-2
Inhibitors
Celebrex®
(Celecoxib: Pfizer)
Sales in 2010 was $2,374M
Once or twice/day (200–400 mg/day)
Low
Arcoxia®
(Etoricoxib: Merck)
- Sales in 2010 was $398M in EU
Not approved in the US
Once/day (30–120 mg/day)
High
Tissue Selective
COX-2 Inhibitor
Acelex®
(Polmacoxib: CG)
- ‘Tissue selective’ COX-2 inhibitor
Once/day (2 mg/day)
None
observed
to date 12

13. Mechanism of Polmacoxib
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).
Whole Blood, Blood Vessels, CV Tissues
Inflamed Joints (OA, RA)
CA >> COX-2 
Preferred binding to CA
CA << COX-2 
Preferred binding to COX-2
Polmacoxib
COX-2 CA
Limited side effects
Good efficacy

14. Summary of Clinical Studies for Acelex
Phase
Type
ClinicalTrials.gov
Identifier
Trial
Size
Status
Location 1
First-in-human study
Single ascending dose (SAD) study - 24
Completed UK
Multiple ascending dose (MAD) study
Safety and Pharmacokinetic (PK) Study 16
MAD study
Safety and pharmacokinetic study 48 US
Pilot biomarker study
NCT
US (Univ. of Penn)
Drug-drug interaction (DDI) study
NCT 26
Seoul, Korea
Supra-therapeutic MAD study
safety and PK study
NCT 2
Placebo controlled proof-of-concept study
NCT
248 EU
Celecoxib controlled dose finding study
NCT
125 3
Placebo and Celecoxib controlled pivotal
Ph 3 efficacy & safety for approval
and extended safety study
NCT
362 14

15. 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

16. 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.

17. Phase III Clinical Study
Summary

18. Study Title and the Objectives of the Study
Phase III Study: Study Title & The Objectives
Study Title and the Objectives of the Study
Study Title:
A Double-blind, Randomized, Multicenter, Active- and Placebo-Controlled Phase III
Study to Evaluate the Efficacy and Safety of CG 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.

19. Acelex®, Phase III Study Results
Acelex showed SUPERIOR EFFICACY over celecoxib with statistical significance (p = 0.005)
71.9% of subjects taking Acelex experienced improvement in
signs and symptoms of osteoarthritis
Overall improvement of signs and symptoms of osteoarthritis in terms of PGA* scores at week 3
*PGA (Physician’s Global Assessment ): Evaluation of the test subjects by the investigators (physicians)

20. 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

21. Safety Results from the 6-week Efficacy Study
Phase III Study: Safety (6-week Treatment Period)
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.

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

23. 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.

24. Projected Advantages of Acelex
Product Profile of Acelex
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.

25. Acelex®, Lifecycle Management Strategy
• 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.
Launch of 2 mg
Capsule 2015
Generic Entry Block
2026~2034
• Launch in Korea
• Export or Out-Licensing
Strengthening of the Acelex brand name through launch of multiple products

26. CG Pharmaceuticals, Inc.
CrystalGenomics, Inc.
5th F. Bldg.A, Korea Bio Park
700 Daewangpangyo-ro, Bundang-gu,
Seongnam-si, Gyeonggi-do
Korea
CG Pharmaceuticals, Inc.
5980 Horton Street, Suite 610
Emeryville, CA
U.S.A.