copyright icagen, inc. 2004 – all rights reserved ion channel advances drug discovery &...

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.


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


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


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)


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


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


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


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.


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++


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


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


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


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


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)


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


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


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


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


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


www.ASSERTTRIAL.com www.ASSERTTRIAL.com

1-877-STUDY95


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


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


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


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


* 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


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


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


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


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


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


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


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 advances drug discovery &...

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