EXHIBIT 99.1
DOV Pharmaceutical, Inc.
[GRAPHIC]
2nd Annual Science Day
July 27, 2004
Millennium Broadway Hotel, NYC
Safe Harbor Statement DOV Pharmaceutical, Inc.
This document contains forward-looking statements that involve significant risks
and uncertainties, including those discussed below and described more fully in
our annual report on Form 10-K and our quarterly report on Form 10-Q/A as filed
with the Securities and Exchange Commission on March 15, 2004 and June 28, 2004,
respectively. These statements reflect our current expectations concerning
future events, and thus our actual results could differ materially from those
anticipated in these forward-looking statements as a result of many factors.
These factors include our ability to achieve and maintain profitability, the
extent to which we collaborate with third parties on drug discovery and
development activities, the ability of our collaborators and of DOV to meet drug
development objectives tied to milestones and royalties and our ability to
attract and retain experienced scientists and management. We undertake no duty
and have no intention to update any forward-looking statements to reflect the
occurrence of events or circumstances after the date of such statements or of
anticipated or unanticipated events that alter any assumptions underlying such
statements.
DOV Pharmaceutical, Inc.
GABA Receptor Modulator Program
July 2004
Phil Skolnick, Ph.D., D.Sc. (hon)
Senior Vice President, Research and
Chief Scientific Officer
GABA(A) Modulators: Potential DOV Pharmaceutical, Inc.
Therapeutic Applications
o Anxiety Disorders (GAD, Panic, Phobias)
o Epilepsy
o Tinnitus
o Muscle Spasticity
o Insomina
o Amnestic (Pre-Anesthesia)
GABA(A) Receptor Modulator Program DOV Pharmaceutical, Inc.
o Several distinct chemical genera have been targeted as novel,
GABA(A) receptor modulators
DOV 51,892 is the first of these molecules to reach clinical
candidate status
o Provisional patent applications encompassing two of these genera
were filed in 1Q04
- DOV 51,892 is exemplified in one of these patent applications
DOV 51,892: Salient Features DOV Pharmaceutical, Inc.
o Non-benzodiazepine
o Approximately twice as potent as Ocinaplon in both in vivo and in
vitro tests predictive of an anxioselective
o Orally active and more potent than Ocinaplon in anti-convulsant
testing
o Not metabolized in vitro
Ocinaplon: Active in Vogel and DOV Pharmaceutical, Inc.
Elevated Plus Maze
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DOV 51,892: Effects in TRC DOV Pharmaceutical, Inc.
(Vogel Test)
DOV 51,892: Active in Vogel Test
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DOV 51,892: Effects in DOV Pharmaceutical, Inc.
Elevated Plus Maze (EPM)
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DOV 51,892: "Side Effect DOV Pharmaceutical, Inc.
Profile"
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DOV 51,892 "Series" DOV Pharmaceutical, Inc.
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Binding: Anxiolytic Activity Side Effects
Relative (Conflict test, (Grip Strength,
DOV Affinity MED, mg/kg PO) MED, mg/kg, PO)
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273,547 1 6 >100
Ocinaplon
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51892 2.12 3 >100
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51897 1.22 >12 >24 IP
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51902 1.67 >12 >24
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51907 0.05 >24 IP
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51912 9.58 1 >12 (ongoing)
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51917 0.87 12 >24
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51922 0.35 6 >12
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51927 4.0 In progress In progress
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51932 0.18 N N
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51937 0.68 N N
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51942 0.06 N N
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51947 0.96 N N
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DOV Pharmaceutical, Inc.
DOV 102,677: A DAT Preferring
Reuptake Inhibitor
July 2004
Phil Skolnick, Ph.D., D.Sc. (hon)
Senior Vice President, Research and
Chief Scientific Officer
DOV 102,677 DOV Pharmaceutical, Inc.
[GRAPHIC]
(-)-1-(3,4-dichlorophenyl)-azabicyclo[3.1.0] hexane
DOV 102,677 DOV Pharmaceutical, Inc.
DOV 102,677: Affinity for DATs
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Compound hDAT, Binding hSERT, Binding hNET, Binding
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DOV 216,303 186+/-40 188+/-28 378+/-43
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DOV 102,677 222+/-43 740+/-140 1030+/-76
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DOV 21,947 213+/-56 99+/-16 262+/-41
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Studies were performed in HEK 293 cells expressing the indicated human
transporter proteins. [(125)I]RTI-55 was used to label transport proteins.
DOV 102,677: DOV Pharmaceutical, Inc.
Antidepressant Profile
Effects of DOV 102,677
in the Rat Forced Swim Test
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DOV 102,677: DOV Pharmaceutical, Inc.
Antidepressant Profile
DOV 102,677 is Effective in the
Mouse Tail Suspension Test
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DOV 102,677: Comparison with DOV Pharmaceutical, Inc.
methylphenidate (35 d old mice)
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Potential Therapeutic DOV Pharmaceutical, Inc.
Indications for a DPRI
o Depression/Anxiety
o ADHD
o Parkinson's Disease
o Substance Abuse
o Restless Leg Syndrome
o Obesity
DOV Pharmaceutical, Inc.
Product Development Plans
July 2004
Warren Stern, Ph.D.
Senior Vice President, Drug Development
Status of Ocinaplon, a Nonsedating DOV Pharmaceutical, Inc.
Novel Anti-Anxiety Drug
o 473 Subjects received Ocinaplon (up to 270 mg/day) in 11 prior
trials
o Two Phase II placebo-controlled trials demonstrated marked efficacy
o Extensive animal toxicology testing has been completed
o Ocinaplon was placed on hold by the FDA in Oct. 2003
o On June 25, 2004 DOV reached agreement with the FDA concerning the
re-initiation of Phase III testing
Ocinaplon Study Design DOV Pharmaceutical, Inc.
Study 011. A Pivotal Efficacy and Safety Study of Ocinaplon in Outpatients
with Generalized Anxiety Disorder
o 373 Patients in 45 U.S. centers
o Comparison of 60 mg/day Ocinaplon (bid dosing), 60 mg/day Ocinaplon
(once daily) vs. placebo
o 7-Day placebo lead-in, 28-day randomized double-blind comparison to
placebo, 7-day placebo follow up
Ocinaplon Efficacy DOV Pharmaceutical, Inc.
Main Measures
o Hamilton Anxiety Rating Scale: Primary Endpoint
o Clinical Global, Patient Global, Patient-Self Rating Scale, HAMA
Subscales
Statistical Analyses
o Change from baseline at each week of dosing
Ocinaplon Safety DOV Pharmaceutical, Inc.
o Vital signs, physical exams, adverse events and clinical laboratory
tests
o Enhanced level of monitoring of liver function tests
> Twice weekly measures
> Daily follow up if values become abnormal
> Consultation with liver expert (if abnormal)
o Review of ongoing laboratory results by data monitoring committee
o Independent statistical analyses of safety
o Study stopping rules
Ocinaplon Timelines DOV Pharmaceutical, Inc.
2004 - 2005 Trials
Regulatory
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Meet with FDA to Review Ongoing Safety 2H05
Data and Discuss Scope of NDA Program
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Phase III Trials
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Initiate Study 011 (60 mg/day) 2H04
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Initiate Comparison of 3-dose Levels of 2H05
Ocinaplon
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Start Long-term Dosing 2H05
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Phase I Trials
Repeat Dose Pharmacokinetics
Drug Metabolism Study
Bicifadine Overview DOV Pharmaceutical, Inc.
Status of Bicifadine, a Novel Non-Opiate Analgesic
o Initial NDA indications:
Acute post-surgical pain and chronic lower back pain
o Novel mechanism of action:
Non-opiate and not anti-inflammatory
o Completed 8 Phase I studies, 15 Phase II studies and 1 Phase III
study with over 1500 subjects receiving Bicifadine
o Animal safety program, largely completed; carcinogenicity studies
(ongoing)
o Two single-dose, placebo-controlled dental-pain model studies
completed; significant dose-dependent effects at 200-600 mg
Bicifadine relative to placebo
Bicifadine Regulatory DOV Pharmaceutical, Inc.
End of Phase II Meeting with FDA
o Provided direction in absence of guidelines
o No concerns with preclinical and clinical safety data
o Acute pain: pivotal trials in 3 pain additional models, one
replication
o Chronic back pain: two 90-day, double-blind, placebo-controlled,
dose-response studies
o Safety
> 100 patients for 1 year, 300 patients for 6 months
> 2-year animal carcinogenicity (ongoing)
Bicifadine Development Timelines DOV Pharmaceutical, Inc.
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Bicifadine Bunionectomy DOV Pharmaceutical, Inc.
Study
Design of Pivotal Study 008-Post Surgical
Bunionectomy Pain Model
o Double-blind, randomized comparison of Bicifadine vs. placebo w/
tramadol as active control
o Bicifadine dosing: loading dose of 400 mg, 8 hours later patients
are randomized to 200, 300 or 400 mg tid of Bicifadine
o N=90 per treatment group (5 x 90=450 patients), 3 U.S. centers
o Main efficacy measure: Visual Analog Scale ratings of pain intensity
o Safety measures: adverse events, vital signs, ECG, clinical labs,
discontinuation effects
Bicifadine Back Pain Study DOV Pharmaceutical, Inc.
Design of Pivotal Study 020-Chronic Lower Back Pain
o Double-blind, randomized comparison of 3 months of dosing with 3
dose levels of Bicifadine vs. placebo
o Bicifadine dosing at 200, 300 and 400 mg bid
o 600 patients to be enrolled (4 x 150=600), 40-50 U.S. centers
o Efficacy: pain on study visit dates
o Safety measures: adverse events, vital signs, ECG, physical,
clinical labs, drug discontinuation events
o Eligible to rollover to long-term treatment with Bicifadine (up to
12 months)
Bicifadine Long-Term Dosing DOV Pharmaceutical, Inc.
Design of Long-Term Safety
Study 022-Chronic Lower Back Pain
o Partially blinded evaluation of up to 1000 patients treated with
Bicifadine at doses from 200 mg bid to 400 mg bid for up to 1 year
o Safety-control group of patients who receive treadle
o Patients who rollover from either of 2 pivotal Phase III studies or
new patients receiving Bicifadine 400 mg bid
o Efficacy: Visual Analog Scale ratings of pain
o Safety: adverse events, vital signs, ECG and clinical laboratory
tests, drug discontinuation
Bicifadine Phase I Studies DOV Pharmaceutical, Inc.
Phase I Studies To Be Conducted
2004
o Bioequivalence for new manufacturer and dosage strength
o Drug interactions
o Elderly pharmacokinetics
2005
o Hepatic and renally-impaired subjects
o Abuse liability assessment in drug abusers
o Morphine interaction
o NSAID interaction
o Metabolism
2006
o Effects on cognition/driving
o Other drug interaction studies
DOV 21,947 Antidepressant DOV Pharmaceutical, Inc.
Status of DOV 21,947: Triple Reuptake Inhibitor
Antidepressant
4 Phase I studies completed
o Single rising dose
o 10-day repeat dose
o Food effect
o Gender effect
IND Active in June 2004
DOV 21,947 Antidepressant DOV Pharmaceutical, Inc.
Phase II Placebo-Controlled, Double-Blind Efficacy Study 006
In 356 Depressed Outpatients To Be Initiated in 4Q2004
o 10, 25, or 50 mg bid/day of DOV 21,947 or placebo for 8 weeks;
15-20 U.S. centers
o Efficacy: HAMD supplemented by CGI, Patient Self-Rating
Scales, MADRS, Pain Measures and QOL Scales
o Safety: adverse events, sexual side effects, vital signs,
physical, ECG, clinical labs
DOV 216,303 Antidepressant DOV Pharmaceutical, Inc.
Status of DOV 216,303:
Triple Reuptake Inhibitor Antidepressant
o Two Phase I studies completed
> S0ingle Dose
> 10-day Repeat Dose
o One Phase II trial completed in 67 depressed patients in Germany
> 2-week double-blind comparison of 50 mg bid vs. citalopram
(Celexa) 20 mg bid
> Results to be unblinded by the end of 3Q04
DOV Diltiazem Product DOV Pharmaceutical, Inc.
Concept
PK Profile of 240mg DOV Diltiazem vs. 240mg Tiazac
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4 Phase I Pharmacokinetic Studies Conducted
DOV Diltiazem Regulatory DOV Pharmaceutical, Inc.
DOV Diltiazem Activities in 2004/2005
o July 2004 End of Phase II meeting with FDA to discuss NDA
development plan
o Reached agreement with FDA on the following:
> No new preclinical safety studies
> Clinical program consisting of several trials that DOV can
accomplish by end of 2005
DOV Diltiazem Timelines DOV Pharmaceutical, Inc.
2004 2005
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Activities Q3 Q4 Q1 Q2 Q3 Q4
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Select Final Formulation from
Contract Manufacturer X
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Initiate Scale Up Mnufacture
of Product Dosage Strengths X
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File IND X
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Conduct Pharmacokinetic Studies X X X
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Conduct Phase III Program X X X X
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DOV Pharmaceutical, Inc.
Overview of DOV's Strategy for Market
Exclusivity
July 2004
Arnold Lippa, Ph.D.
President and Chief Executive Officer
The Art of Market Protection DOV Pharmaceutical, Inc.
Maintaining Market Exclusivity
o Government Approved Monopoly
o Patents
o Trade Secrets
The Art of Market Protection DOV Pharmaceutical, Inc.
Maintaining Market Exclusivity
o Government Approved Monopoly
U.S. - Waxman-Hatch Act - up to 5 years of market
exclusivity for new chemical entity and 3 years for new
formulation
EU - up to 10 years of market exclusivity for new
chemical entity
Japan - up to 15 years of market exclusivity for new
chemical entity
The Art of Market Protection DOV Pharmaceutical, Inc.
Maintaining Market Exclusivity
o Government Approved Monopoly
o Patents
Composition of Matter
Process
Method of Use
DOV Pharmaceutical, Inc.
Jeffrey J. King
Partner
Graybeal Jackson Haley LLP
Overview of Presentation DOV Pharmaceutical, Inc.
o FDA rule changes/Hatch-Waxman developments
o Strength/enforceability of "later-listed" patents
o Assessment of DOV patent strategy
Provisions of Hatch-Waxman Act DOV Pharmaceutical, Inc.
o 5 yrs. Market Exclusivity for NCEs
o Patent Term Extensions
o Automatic 30-Month Stay of ANDA Approvals
Remedies for Drug Innovators DOV Pharmaceutical, Inc.
o Patent term extension (not covered here)
o ANDA triggers 271(e)(2) infringement right of action
o Automatic 30 month stay of ANDA approval
Particulars of Orange Book Listing DOV Pharmaceutical, Inc.
o NDA applicant or holder must submit patents covering drug,
formulations and approved uses
o Must submit declaration attesting that patent covers drug,
formulation or approved use
Details of New FDA Regulations DOV Pharmaceutical, Inc.
o Only one 30-month stay of generic drug application
o No listing for patents on intermediates, metabolites, packaging
o No supplemental notice required for later-listed patents
o Requires more detailed Orange Book listing (type of patent/product
novelty/approved use)
o Requires listing for polymorphs of active ingredients (supported by
test data showing bioequivalence)
Implications For Off-Patent DOV Pharmaceutical, Inc.
Drug Patent Strategies
o 30-Month stay remains effective administrative tool
o Preserves most types of later-listed patents for Orange Book
o Increases emphasis on post-ANDA patent enforcement (civil)
o Moderately increases Orange Book listing burden (patent
characterization; test data showing polymorph equivalence; listing
required to preserve treble damages)
Types of Later-Listed Patents DOV Pharmaceutical, Inc.
o Formulations
o Structural Variants/Polymorphs
o Therapeutic/Prophylactic Uses
o Delivery (Route/Mode/Pharmacology)
o Process/Product-By-Process
Formulation Claims DOV Pharmaceutical, Inc.
o Enhance stability/shelf-life
o Improve bioavailability/in vivo stability
o Modify pharmacokinetics/pharmacodynamics (Tmax, clearance, extended
release)
o Target delivery (e.g., to CNS)
o Combine with other active agents for indicated use
o Combine with proprietary carrier, vehicle, active agent
Claims Directed to Structural Variants DOV Pharmaceutical, Inc.
o New, related compounds (e.g., protein isoforms)
o Modified or derivative compounds (e.g., stable complexes)
o Polymorphs (crystal variants, hydrates, solvates, amorphous forms)
Claims Directed to New DOV Pharmaceutical, Inc.
Uses/Methods
o New therapeutic or prophylactic indication
o New delivery route (e.g., IN, IP, TD)
o New delivery mode (e.g., targeted, PK or PD profile)
o Diagnostic methods
o Drug screening/Rational drug design (e.g., using 3D coordinates, IR
spectra)
Process and Product-By Process Claims DOV Pharmaceutical, Inc.
o Economy of manufacturing
o Use of novel reagents/intermediates
o Predictability of process/product
o Yield/purity/form of end-product
Requirements for Patentability DOV Pharmaceutical, Inc.
o Utility
o Novelty
o Nonobviousness/Unexpected Results
o Description/Enablement
Overview of DOV Patent Landscape DOV Pharmaceutical, Inc.
o Ocinaplon
o Uptake Inhibitors (e.g., DOV 216,303)
o Bicifadine
Bicifadine - Patent Status DOV Pharmaceutical, Inc.
Summary of DOV's Patent Landscape
Ocinaplon Bicifadine DOV 216,303 DOV 21,947
Composition of Matter DOV 102,677
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Chemical Expired Expired Expired Issued (2021)
Composition
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3 Dimensional In Preparation Filed/Pending --- ---
Structure
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Complex Filed/Pending Filed/Pending
Mixture/Formulation In Preparation --- ---
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Process Issued (2007) In Preparation --- Issued (2021)
Filed
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Use Filed/Pending Expired Expired Issued (2021)
In Preparation Issued (2018)
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3 Dimensional Structure DOV Pharmaceutical, Inc.
[PICTURE] [PICTURE] [PICTURE]
Form A Form B Form C
3 Dimensional Structure DOV Pharmaceutical, Inc.
POLYMORPHS OF BICIFADINE
INTERCONVERSION
[PICTURE] ---------------> [PICTURE]
Form A Form B
Plates Blades
Thermodynamically more stable
form
U.S. Patent Application 10/702,397 DOV Pharmaceutical, Inc.
for Bicifadine Polymorph B
o Filed November 5, 2003
o Claim 1: Bicifadine polymorph B, with dependent claims to IR
spectrum/X-ray diffraction
o Claim 6: Method of producing polymorph B
o Claim 14: Pharmaceutical composition (poly-B)
o Claim 18: Method for reducing pain (poly-B)
Overview of SmithKline v. Apotex Case DOV Pharmaceutical, Inc.
o Patent on anhydrous form of Paxil expired
o Apotex filed Paragraph IV cert. on anhydrous form
o SmithKline asserted patent on hemihydrous form (argued hemi-form
inherently present by conversion)
o District court relied on "detectable" "commercial" levels
o Fed. Cir. reversed, but held patent invalid by on-sale bar
(experimental use not exemption for product claimed only in
structural terms)