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Copyright Icagen, Inc. 2004 – All Rights Reserved
Ion Channel AdvancesDrug Discovery & Development
Q12006
Copyright Icagen, Inc. 2004 – All Rights Reserved 2
Forward Looking StatementsForward Looking Statements
This presentation contains forward-looking statements that involve a number of risks and uncertainties. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words “believes,” “anticipates,” “plans,” “expects,” “intends,” and similar expressions are intended to identify forward-looking statements. Important factors that could cause actual results to differ materially from the expectations described in these forward-looking statements are set forth under the caption “Risk Factors” in the Company’s Annual Report on Form 10-K, which is on file with the Securities and Exchange Commission. These risk factors include risks as to whether the Company’s products will advance in the clinical trials process, the timing of such clinical trials, whether the results obtained in preliminary studies will be indicative of results obtained in clinical trials, whether the clinical trial results will warrant continued product development, whether and when, if at all, the Company’s products, including ICA-17043, will receive approval from the U.S. Food and Drug Administration or equivalent regulatory agencies, and for which indications, and if such products receive approval, whether they will be successfully marketed; the Company’s history of net losses and how long the Company will be able to operate on its existing capital resources; and the Company’s dependence on third parties, including manufacturers, suppliers and collaborators. We disclaim any intention or obligation to update any forward-looking statements as a result of developments occurring after the date of this presentation.
Copyright Icagen, Inc. 2004 – All Rights Reserved 3
Icagen at a GlanceIcagen at a Glance
Biopharmaceutical company with first-in-class orally active, small molecule drug candidates targeting ion channels and addressing large market needs
Phase III program in sickle cell disease
Orphan Drug and Fast Track
US 50/50 co-promotion, profit share with McNeil (J&J)
Three additional programs in Phase I or late-stage preclinical studies
Discovery engine generating broad pipeline of drug candidates
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Experienced Management TeamExperienced Management Team
Position Previous Affiliation
P. Kay Wagoner, Ph.D. President & CEO Glaxo US
Richard Katz, M.D. SVP Finance and Corporate Development, CFO Goldman Sachs
Edward Gray, J.D. SVP Intellectual Property,Chief Patent Counsel Eli Lilly
J. Heyward Hull, Pharm.D. SVP Development and Regulatory Affairs
Quintiles, Burroughs Wellcome
Douglas Krafte, Ph.D. VP Biology Aurora, Boehringer - Ingelheim
Gregory Rigdon, Ph.D. VP New Product Development Glaxo Wellcome
Mark Suto, Ph.D. VP Chemistry DuPont Pharmaceuticals
Greg Shotzberger, Ph.D. VP Business Development King Pharmaceuticals
Responsible for development plans for over 40 INDs and NDAs
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Ion ChannelsProven Drug TargetsIon ChannelsProven Drug Targets
Open
Closed
Ions
Ion Channels
CellMembrane
Critical role in functions of multiple organ systems Central and peripheral nervous
system, cardiovascular system, immune, ocular, others
Diversity provides therapeutic opportunity Selective expression Multiple subtypes and combinations Many binding sites on each channel
Proven drug targets Over 35 marketed drugs targeting
diverse indications, including Norvasc® (hypertension), Lamictal® (epilepsy) and Glipizide (diabetes)
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50+ issued patents -150 patent applications
Ion Channel Genomics
HTS
Electro-physiology
Ion Channel Chem-informatics
LeadOptimization
Bioanalytics
Pharmacology
Clinical andRegulatory
Bio-informatics
DrugMetabolism
Discovery and Development EngineDiscovery and Development Engine
Completed the cloning and characterization of entire human ion channel genome
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Icagen Pipeline Icagen Pipeline R
esea
rch
Dev
elo
pm
ent
Discovery Ph IIPh I Ph IIIINDClinical
CandidateQuality Lead
CommercialRights
Pain/Epilepsy
AtrialFibrillation
ADHD/memory
Inflammation
Glaucoma
Sickle Cell
Pain
Icagen/McNeil
Icagen
BMS
Icagen/Astellas
Icagen
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Sickle Cell Disease - Overview Sickle Cell Disease - Overview
Devastating illness Sickle cell crises leading to
hospitalizations
Anemia, pain, chronic organ damage, shortened lifespan
~100,000 patients in the United States, primarily of African descent
Current treatment options extremely limited Hydroxyurea (HU), a cancer
chemotherapeutic, currently the only approved drug
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Sickled Cells & Ion Channels Keys to Sickle Cell Disease &TreatmentSickled Cells & Ion Channels Keys to Sickle Cell Disease &Treatment
Genetic abnormality in hemoglobin, leading to dense, sickled red blood cells (RBCs), hemolytic anemia and vaso-occlusive crises
A prime factor in the sickling process is RBC dehydration primarily due to the loss of potassium salt and water
Blocking the loss of potassium salt and water from RBCs should decrease
- RBC dehydration,
- the formation of sickled cells,
- hemolytic anemia and
- vaso-occlusive crisis rate.
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RBC Dehydration Leads to HemolysisRBC Dehydration Leads to Hemolysis
RBC(with HbS)
GardosPotassium Ion Channel
↑ Hemolysis
↓ RBC Count (Anemia)
Dense / Sickled Cells Hemolytic Anemia Vaso-occlusive Crises
H2OK+
Dense/Sickled RBC
K+
H2O
Dehydrated RBC
Deoxygenation
↑Ca++
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RBC(with HbS)
H2O
KK++
HH22OO
Normal Density RBC
ICA-17043(blocks Gardos
potassium channel)
GardosPotassiumChannel ↓ Hemolysis
↑ RBC Count (Improvement in Anemia)
Improved Function
ICA-17043 - Mechanism of ActionICA-17043 - Mechanism of Action
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Goal: Study designed as proof of concept to determine whether ICA-17043 would improve the hematologic profile of patients with sickle cell anemia
Randomized, double-blind, placebo controlled, dose-range finding 12 week study in 90 patients
Primary endpoint: improvement in anemia as measured by change in hemoglobin
24 patients on concurrent hydroxyurea therapy were randomized into the three arms
19 academic medical centers across the US
Completed in 2004
Placebo
30 pts
30 pts
30 pts
10 mg/day
6 mg/day
Phase II StudyOverviewPhase II StudyOverview
Loading dose
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Phase II Study Summary of Key FindingsPhase II Study Summary of Key Findings
Statistically significant improvement in all red blood cell-related measures in 10 mg arm
Medically meaningful increase in hemoglobin and decrease in hemolysis
Dose dependent responses
All effects present in both 6 mg and 10 mg treatment arms, with magnitude of effect greater in the 10 mg arm
Response seen in both monotherapy and hydroxyurea groups
Favorable safety and tolerability profile
In patients reporting 2 or more crises in the year prior to the Phase II, found trend towards lower crisis rate in ICA-17043 group compared to the placebo group
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0 2 4 6 8 10 12
-0.2
0.0
0.2
0.4
0.6
0.8
1.0
Mea
n C
han
ge
in H
emo
glo
bin
(g
/dL
) 10 mg QD 6 mg QD Placebo
Time (Weeks)
Phase II StudyPrimary Endpoint – Change in HemoglobinPhase II StudyPrimary Endpoint – Change in Hemoglobin
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Phase II StudyEffects on Hematologic ParametersPhase II StudyEffects on Hematologic Parameters
Mean Difference
% Difference
P-Value of Mean
Hemoglobin ↑ 0.67 ↑ 8 <0.001
Red blood cell count ↑ 0.31 ↑ 12 <0.001
Hematocrit ↑ 1.89 ↑ 8 0.002
Reticulocytes ↓ 0.06 ↓ 18 <0.001
Dense red blood cells ↓ 0.04 ↓ 22 0.008
Indirect bilirubin ↓ 1.30 ↓ 43 <0.001
LDH ↓ 106 ↓ 21 0.002
Placebo-adjusted difference in the 10 mg treatment arm (Intent to Treat)
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Phase II Open Label Extension (OLE) Summary of Key FindingsPhase II Open Label Extension (OLE) Summary of Key Findings
OLE designed to gain long-term safety in patients completing Phase II All patients received 10 mg daily dose of ICA-17043
Study treatment duration - 48 weeks
Favorable safety and tolerability profile observed
No serious adverse events attributed to ICA-17043
Pattern of beneficial hematologic effects maintained
In patients reporting 2 or more crises in the year prior to the Phase II, observed fewer per protocol crises while receiving ICA-17043, as compared to patient-reported histories
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Randomized, double-blind, placebo-controlled study in 300 SCD patients at ~65 sites
Primary endpoint: reduction in crisis rate
Secondary endpoints include hematologic parameters
Patients are being enrolled with a history of ≥ 2 sickle cell crises per year
As many as 50% of patients may also be taking hydroxyurea and will be stratified by treatment arm
Over 150 patients enrolled with completion of enrollment targeted for H2 06
Data Safety Monitoring Committee (DSMC) reviewed safety data in January and recommended continuation of trial as planned with no changes in protocol
Interim DSMC safety and efficacy analysis in 2006 when ~50% of patients have been on study drug for three months
10 mg/day
Placebo
150 pts
150 pts
12 months
Phase III Study - ASSERTA Stratified Sickle Events Randomized TrialPhase III Study - ASSERTA Stratified Sickle Events Randomized Trial
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ICA-17043 Pediatric PatientsICA-17043 Pediatric Patients
Approximately 50% of SCD patients are under 18 years of age
Improving hematological profile, i.e, improving anemia, decreasing hemolysis and dense, sickle cell formation may reduce chronic organ damage
ASSERT trial enrolling 16 and 17 year olds
Initiating pediatric studies - 6 to 16 year olds
First study: pediatric safety, pharmacokinetics / pharmacodynamics beginning in first half of 2006
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Pulmonary arterial hypertension (PAH) is a common complication of sickle cell disease, with about 30% of patients affected
Following diagnosis, two-year survival is approximately 50%, with limited therapeutic options
Anemia and hemolysis are believed to be key to the pathogenesis of secondary PAH in patients with SCD
ICA-17043 Phase II demonstrated an improvement in anemia and reduction in hemolysis
Plan to initiate study in SCD patients with secondary PAH in late 2006
ICA-17043 Pulmonary Hypertension in SCD
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Attractive Market Opportunity Attractive Market Opportunity for Icagen's ICA-17043for Icagen's ICA-17043
SCD - Market OpportunitySCD - Market Opportunity
Potential for Attractive Reimbursement•Orphan drug designation
•Majority of patients covered by third party payors
•Pricing in light of drugs for life-threatening conditions
Substantial Patient Population
•Approximately 100,000 patients in the US
•Prevalent in Europe, Caribbean, Africa
Concentrated Physician Base•Small number of treatment centers
•Key thought leaders drive treatment approach
Limited Therapeutic Options•Life threatening disease
•Hydroxyurea - cancer chemotherapeutic prescribed for only ~10% of patients
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www.ASSERTTRIAL.com www.ASSERTTRIAL.com
1-877-STUDY95
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Lead Candidates for Epilepsy / Neuropathic Pain - IcagenLead Candidates for Epilepsy / Neuropathic Pain - Icagen
First-in-class, oral drug candidates for the treatment of epilepsy and neuropathic pain
Genetically validated potassium channel target
Broad spectrum activity in preclinical models of both epilepsy and neuropathic pain
Completing preclinical studies for IND filingWorldwide rights currently retained
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Leads Efficacious in Neuropathic Pain ModelsLeads Efficacious in Neuropathic Pain Models
CCI Model - ICA-Lead (PO)
(1 hour pretreatment)
•0.0
•2.0
•4.0
•6.0
•8.0
•10.0
•12.0
•14.0
•16.0
Right Allodynia Allodynia Allodynia
Paw Paw Paw Paw
Baseline 1 Hour 2 Hour
Pa
w w
ith
dra
wa
l T
hre
sh
old
(g
ram
s)
Vehicle
3 mg/kg
10 mg/kg
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Leads Efficacious in Inflammatory Pain ModelsLeads Efficacious in Inflammatory Pain Models
Rat Carrageenan Model ICA- Lead (PO) (2 hour pretreatment)
•0
•2
•4
•6
•8
•10
•12
•14
•16
•18
•20
Inflamed paw Normal paw
mean right mean left
La
ten
cy
to
lif
t p
aw
(s
ec
on
ds
)
Vehicle
Morphine 3mg/kg SC
3 mg/kg
10 mg/kg
30 mg/kg
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Leads Effective Against Capsaicin-induced PainLeads Effective Against Capsaicin-induced Pain
•-3
•2
•7
•12
•17
•22
inflamed normal
La
ten
cy
to
lif
t p
aw
(s
ec
)
Vehicle
3 mg/kg
10 mg/kg
30 mg/kg
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* MES - maximal electroshock; PTZ - pentylenetetrazol; 6 Hz - six hertz threshold
Epilepsy Animal Models
Drug MechanismMES* Partial
Seizures
PTZ* Generalized
Seizures
6 Hz* Treatment- Resistant
Lead Compounds
Novel potassium channel ++ ++ ++
Neurontin® Unknown ++ - -
Tegretol® Sodium channel ++ - -
Depakote® Unknown + + +
Lamictal® Sodium channel ++ - -
Topamax® Sodium, GABA, Kainate ++ - -
Keppra® Unknown - - +
Leads Effective in Epilepsy ModelsBroad Spectrum of ActivityLeads Effective in Epilepsy ModelsBroad Spectrum of Activity
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Atrial FibrillationIcagen / BMSAtrial FibrillationIcagen / BMS
Potent, selective oral drug candidate prolongs atrial refractory period in human tissues without affecting ventricular refractory period
Lack of selectivity of currently available agents results in potential to cause ventricular arrhythmias
BMS has completed an initial Phase I safety study
Icagen eligible to receive milestones and royalties
AtrialMyocytes
VentricularMyocytes
Atrial Fibrillation
Atria
Ventricles
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Memory and ADHDIcagen / AstellasMemory and ADHDIcagen / Astellas
Potent, selective, oral compounds specific to an ion channel in brain regions important for memory and attention
Compounds increase electrical firing and neurotransmitter release, and are efficacious in animal studies
Astellas conducting preclinical studies to select a clinical candidate for memory disorders
Icagen conducting preclinical studies to select a clinical candidate for attention deficit / hyperactivity disorder+ Drug+ Drug
HippocampalNeurons
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Multiple validated ion channel targets with animal efficacy
Potent, selective, oral compounds specific to certain ion channels with expression in key regions of the pain pathway
Animal efficacy
Lead optimization in progress
Pain
Injury
Peripheral nociceptors
Peripheral nerve
Ascending Pathway
Descending Pathway
Dorsal HornDorsal Root
GanglionSpinal cord
Brain
Chronic Pain: Targeting Ion Channels IcagenChronic Pain: Targeting Ion Channels Icagen
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Financial HighlightsFinancial Highlights
Solid Cash Position
Cash balance at year-end 2005 of ~$48 million
Existing cash balance and committed funding projected to support near-term clinical and preclinical plans
Conservative financial management
Projected operating loss of $27 - $31 million during 2006, including approximately $2 million in stock-based compensation expense
Risk Diversification
Risk mitigated through (i) pipeline breadth, (ii) strategic partnerships, (iii) validated target class, and (iv) strong intellectual property position
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2006 - Key Milestones2006 - Key Milestones
Complete enrollment in our SCD Pivotal Phase III - ASSERT
Complete interim analysis of ASSERT Phase III data
Initiate ICA-17043 clinical trials in pediatric patients
Initiate ICA-17043 clinical trials in PAH
Select clinical candidate for neuropathic pain / epilepsy program
Select clinical candidates from preclinical programs
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Board Member Affiliation
Charles Sanders, M.D., Chair Glaxo US - Former Chairman & CEO
Anthony Evnin, Ph.D. Venrock Associates - General Partner
Dennis Gillings, Ph.D. Quintiles Transnational - Chairman & CEO
Andre Lamotte, Sc.D. NMT/HBM – Former Venture Partner
Richard Morrison, Ph.D. Eli Lilly - Former President, Lilly Brazil
Martin Simonetti CEO – VLST Corp.
P. Kay Wagoner, Ph.D. Icagen - President & CEO
World Class BoardWorld Class Board
Copyright Icagen, Inc. 2004 – All Rights Reserved 33
The Icagen OpportunityThe Icagen Opportunity
Leading biopharmaceutical company focused on ion channel targets Novel small molecule therapeutics Multiple and diverse therapeutic areas Programs focused on areas of significant unmet medical need
Phase III program for sickle cell disease Once-daily oral therapeutic for chronic preventive treatment Orphan Drug Status and Fast Track Designation Pivotal Phase III study underway 50:50 U.S. co-promote / profit-share with McNeil (Johnson & Johnson)
Three programs in Phase I or late preclinical stage Neuropathic pain / Epilepsy– Clinical candidate stage Atrial fibrillation - Phase I Memory, ADHD - preclinical testing
Broad research pipeline / proven technology platform
Copyright Icagen, Inc. 2004 – All Rights Reserved
Ion Channel AdvancesDrug Discovery & Development
www.icagen.com