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Acelex capsule 2mg - tissue selective cox-2 inhibitor crystal genomics acelex nc jan2016

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ACELEX capsule 2mg - Tissue Selective COX-2 inhibitor CrystalGenomics Acelex NC Jan2016. Acelex® (polmacoxib) is a non-steroidal anti-inflammatory drug (NSAID), specifically a COX-2 inhibitor, for the treatment of symptoms associated with arthritis. Suffering from joints pain which might have been due to age or other reason. Acelex capsule 2 mg is one of new drug in the market for joints pain relief. – PowerPoint PPT presentation

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Title: Acelex capsule 2mg - tissue selective cox-2 inhibitor crystal genomics acelex nc jan2016


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.
To become a fully integrated biopharmaceutical
company in Korea and expand internationally
through collaborations and partnerships
Vision
2000.07 Founded 2003.09 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
development 2012.06 Designated by the Korean
government as one of the KIPC certified
companies 2014.07 Designated by the Korean
government as one of the K-BrainPower
companies 2015.02 Obtained the NDA approval from
MFDS for Acelex in Korea (osteoarthritis) 2015.09
Launch of Acelex in Korea
History
Next generation NSAID, Acelex for osteoarthritis
(first-in-class) Novel antibiotic candidate for
MRSA infection, CG400549 (first-in-class) Molecula
r-targeted cancer therapeutic, CG200745
(best-in-class)
Key Programs
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.
Lead Discovery ( SCPTM )

Structure Determination ( SPSTM )
SCPTM Library SCPTM Screening
SCPTM NMR
Virtual Screening
In vitro Assay
Target Selection
Synchrotron, NMR
Lead Optimization and Candidate Selection ( SDFTM
)
In vivo Evaluation DMPK Toxicology Pharmacology
Drug Design MediChem SDFTM X-ray SDFTM
Informatics Parallel Synthesis
Biological Evaluations Target Assays Cellular
Assays In vitro DMPK
IND-enabling Tox (CRO in EU,USA)
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, 98-102 (2003).
5
Former Current Alliance Partners
  • SBI BIOTECH CO., LTD.
  • 5

6
Novel Therapeutics Pipeline
Area Product Indication Current Status Partners
RD 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 II Ph III
1Infectious Disease 1Infectious Disease MRSA MRSA
2Cancer 2Cancer MDS MDS
Area Indication Discovery Preclinical Ph I Ph II Ph III NDA
2Cancer Pancreatic cancer
1Cancer AML
1CNS Alzheimers Disease
2Metabolic Anemia
1. First-in-class , 2. Best-in-class


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

8
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) - 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)
Acelex Target Market
1IMS Top Line Industry Data (2009) 2Statistical
Brief 65 Healthcare Cost and Utilization Project
Jan. 2009 Agency for Healthcare Research
Quality, Rockville, MD
9
Acelex, Tissue Selective NSAID for Osteoarthritis
lt Acelex 2mg Capsule gt
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  Acelexs tissue-selective-COX2-inhibition mechanism is projected to provide a meaningful enhancement of cardiovascular safety over currently available NSAIDs.
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 24 times/day (752,400 mg/day) Very high Moderate or high
Traditional NSAIDs Vimovo (Pozen, AstraZeneca) Naproxen Esomeprazole Twice/day FDA warning for long-term use Sales volume is small. Moderate Moderate
COX-2 Inhibitors Celebrex (Celecoxib Pfizer) Sales in 2010 was 2,374M Once or twice/day (200400 mg/day) Low Moderate
COX-2 Inhibitors Arcoxia (Etoricoxib Merck) - Sales in 2010 was 398M in EU Not approved in the US Once/day (30120 mg/day) Low High
Tissue Selective COX-2 Inhibitor Acelex (Polmacoxib CG) - Tissue selective COX-2 inhibitor Once/day (2 mg/day) Low None observed to date
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 ltlt COX-2 ? Preferred binding to COX-2
CA gtgt COX-2 ? Preferred binding to 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
1 Multiple ascending dose (MAD) study Safety and Pharmacokinetic (PK) Study - 16 Completed UK
1 MAD study Safety and pharmacokinetic study - 48 Completed US
1 Pilot biomarker study NCT00780325 24 Completed US (Univ. of Penn)
1 Drug-drug interaction (DDI) study NCT01154764 26 Completed Seoul, Korea
1 Supra-therapeutic MAD study safety and PK study NCT01154790 48 Completed Seoul, Korea
2 Placebo controlled proof-of-concept study NCT00530452 248 Completed EU
2 Celecoxib controlled dose finding study NCT01341405 125 Completed Seoul, Korea
3 Placebo and Celecoxib controlled pivotal Ph 3 efficacy safety for approval and extended safety study NCT01765296 362 Completed Seoul, Korea
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 (7580x 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
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
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.
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 (Physicians 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 (p0.003), but
celecoxib did NOT show statistically significant
differentiation from placebo at Week 3 (p0.069)

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
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)
Conclusions
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
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  Acelexs 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 20262034 and
maximize revenues.
Launch of 2 mg Capsule 2015
Generic Entry Block 20262034
Launch in Korea Export or Out-Licensing
Strengthening of the Acelex brand name through
launch of multiple products
26
CrystalGenomics, Inc. 5th F. Bldg.A, Korea Bio
Park 700 Daewangpangyo-ro, Bundang-gu, Seongnam-si
, Gyeonggi-do 463-400 Korea
CG Pharmaceuticals, Inc. 5980 Horton Street,
Suite 610 Emeryville, CA 94608 U.S.A.
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