Ion Channel Advances
Drug Discovery & Development
Q12006
Copyright Icagen, Inc. 2004 – All Rights Reserved
Forward 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
2
Icagen 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
Copyright Icagen, Inc. 2004 – All Rights Reserved
3
Experienced 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
Copyright Icagen, Inc. 2004 – All Rights Reserved
4
Ion Channels
Proven Drug Targets
Cell
Membrane
Ions
Open
Ion Channels
Closed
Copyright Icagen, Inc. 2004 – All Rights Reserved
 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)
5
Discovery and Development Engine
Ion Channel
Chem-informatics
Lead
Optimization
Bioinformatics
Bioanalytics
Electrophysiology
Drug
Metabolism
50+ issued patents 150 patent applications
HTS
Ion Channel
Genomics
Pharmacology
Clinical and
Regulatory
Completed the cloning and characterization of entire
human ion channel genome
Copyright Icagen, Inc. 2004 – All Rights Reserved
6
Icagen Pipeline
Development
Discovery
Sickle Cell
Quality
Lead
Clinical
Candidate
IND
Ph I
Ph II
Ph III
Commercial
Rights
Icagen/McNeil
Atrial
Fibrillation
BMS
Pain/Epilepsy
Icagen
ADHD/memory
Icagen/Astellas
Icagen
Research
Pain
Glaucoma
Inflammation
Copyright Icagen, Inc. 2004 – All Rights Reserved
7
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 &Treatment
 Genetic abnormality in hemoglobin,
leading to dense, sickled red blood cells
(RBCs), hemolytic anemia and vasoocclusive 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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9
RBC Dehydration Leads to Hemolysis
Gardos
Potassium Ion
Channel
Deoxygenation
K+
K+
↑
Ca++
RBC
(with HbS)
Dehydrated
RBC
↑ Hemolysis
H2 O
Dense/Sickled
RBC
H2 O
↓ RBC Count
(Anemia)
 Dense / Sickled Cells
 Hemolytic Anemia
 Vaso-occlusive Crises
Copyright Icagen, Inc. 2004 – All Rights Reserved
10
ICA-17043 - Mechanism of Action
Gardos
Potassium
Channel
ICA-17043
(blocks Gardos
potassium channel)
↓ Hemolysis
K+
H2 O
H2 O
RBC
(with HbS)
Normal Density
RBC
↑ RBC Count
(Improvement in Anemia)
 Improved Function
Copyright Icagen, Inc. 2004 – All Rights Reserved
11
Phase II Study
Overview
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
10 mg/day 30 pts
6 mg/day
30 pts
Placebo
30 pts
Loading dose
 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
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12
Phase II Study
Summary of Key Findings
 Statistically significant improvement in all red blood cellrelated 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 ICA17043 group compared to the placebo group
Copyright Icagen, Inc. 2004 – All Rights Reserved
13
Phase II Study
Mean Change in Hemoglobin (g/dL)
Primary Endpoint – Change in Hemoglobin
10 mg QD
6 mg QD
Placebo
1.0
0.8
0.6
0.4
0.2
0.0
0
-0.2
Copyright Icagen, Inc. 2004 – All Rights Reserved
2
4
6
8
10
12
Time (Weeks)
14
Phase II Study
Effects on Hematologic Parameters
Placebo-adjusted difference in the 10 mg treatment arm (Intent to Treat)
Mean
Difference
%
P-Value of
Difference
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
Copyright Icagen, Inc. 2004 – All Rights Reserved
15
Phase 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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16
Phase III Study - ASSERT
A Stratified Sickle Events Randomized Trial
 Randomized, double-blind, placebo-controlled study in 300
SCD patients at ~65 sites
 Primary endpoint: reduction in crisis rate
10 mg/day 150 pts
 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
Placebo
150 pts
12 months
 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
Copyright Icagen, Inc. 2004 – All Rights Reserved
17
ICA-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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18
ICA-17043
Pulmonary Hypertension in SCD
 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
Copyright Icagen, Inc. 2004 – All Rights Reserved
19
SCD - Market Opportunity
Substantial Patient Population
Concentrated Physician Base
•Approximately 100,000 patients in the US
•Prevalent in Europe, Caribbean, Africa
•Small number of treatment centers
•Key thought leaders drive treatment approach
Attractive Market Opportunity
for Icagen's ICA-17043
Limited Therapeutic Options
Potential for Attractive Reimbursement
•Life threatening disease
•Hydroxyurea - cancer chemotherapeutic
prescribed for only ~10% of patients
•Orphan drug designation
•Majority of patients covered by third party payors
•Pricing in light of drugs for life-threatening conditions
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20
www.ASSERTTRIAL.com
1-877-STUDY95
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21
Lead 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 filing
Worldwide rights currently retained
Copyright Icagen, Inc. 2004 – All Rights Reserved
22
Leads Efficacious in Neuropathic
Pain Models
CCI Model - ICA-Lead (PO)
(1 hour pretreatment)
Paw withdrawal Threshold (grams)
•16.0
•14.0
•12.0
•10.0
Vehicle
•8.0
3 mg/kg
•6.0
10 mg/kg
•4.0
•2.0
•0.0
Right
Allodynia
Allodynia
Allodynia
Paw
Paw
Paw
Paw
Baseline
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1 Hour
2 Hour
23
Leads Efficacious in Inflammatory
Pain Models
Rat Carrageenan Model ICA- Lead (PO)
(2 hour pretreatment)
•20
Latency to lift paw (seconds)
•18
•16
•14
Vehicle
•12
Morphine 3mg/kg SC
•10
3 mg/kg
•8
10 mg/kg
•6
30 mg/kg
•4
•2
•0
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Inflamed paw
Normal paw
mean right
mean left
24
Leads Effective Against Capsaicininduced Pain
•22
Latency to lift paw (sec)
•17
Vehicle
3 mg/kg
10 mg/kg
•12
30 mg/kg
•7
•2
•-3
Copyright Icagen, Inc. 2004 – All Rights Reserved
inflamed
normal
25
Leads Effective in Epilepsy Models
Broad Spectrum of Activity
Epilepsy Animal Models
MES* Partial
Seizures
PTZ*
Generalized
Seizures
6 Hz*
TreatmentResistant
Drug
Mechanism
Lead
Compounds
Novel potassium
channel
++
++
++
Neurontin®
Unknown
Tegretol®
Sodium channel
Depakote®
Unknown
Lamictal®
Sodium channel
++
++
+
++
+
-
+
-
Topamax®
Sodium, GABA,
Kainate
++
-
-
Keppra®
Unknown
-
-
+
* MES - maximal electroshock; PTZ - pentylenetetrazol; 6 Hz - six hertz threshold
Copyright Icagen, Inc. 2004 – All Rights Reserved
26
Atrial Fibrillation
Icagen / BMS
Atria
Ventricles
Atrial
Myocytes
Ventricular
Myocytes
 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
Atrial Fibrillation
Copyright Icagen, Inc. 2004 – All Rights Reserved
 Icagen eligible to receive
milestones and royalties
27
Memory and ADHD
Icagen / Astellas
Hippocampal
Neurons
 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
++Drug
Drug
 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
Copyright Icagen, Inc. 2004 – All Rights Reserved
28
Chronic Pain: Targeting Ion Channels
Icagen
Pain
Brain
 Multiple validated ion
channel targets with
animal efficacy
Ascending
Pathway
Descending
Pathway
Dorsal Horn
Dorsal Root
Ganglion
Spinal cord
 Potent, selective, oral
compounds specific to
certain ion channels with
expression in key regions
of the pain pathway
 Animal efficacy
Injury
Peripheral nerve
 Lead optimization in
progress
Peripheral nociceptors
Copyright Icagen, Inc. 2004 – All Rights Reserved
29
Financial 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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30
2006 - 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
Copyright Icagen, Inc. 2004 – All Rights Reserved
31
World Class Board
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
Copyright Icagen, Inc. 2004 – All Rights Reserved
32
The 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
33
Ion Channel Advances
Drug Discovery & Development
www.icagen.com
Copyright Icagen, Inc. 2004 – All Rights Reserved