Exhibit 99.1
Exhibit 99.1
October 2011
© 2004-2011 Chelsea Therapeutics, Inc.
Forward-Looking Statement
This presentation is being provided for informational and discussion purposes. This presentation is not intended to provide and should not be relied upon as investment advice or an opinion regarding the appropriateness or suitability of any investment. Nothing herein should be construed to be an offer to sell, or a solicitation of an offer to buy, any securities.
This presentation contains forward-looking statements regarding future events. These statements are just predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include failure to get regulatory approval for our product candidates, market acceptance for approved products, management of rapid growth, risks of regulatory review and clinical trials, intellectual property risks, and the need to acquire additional products. The reader is referred to the documents that Chelsea Therapeutics International, Ltd. files from time to time with the Securities and Exchange Commission.
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Overview
Chelsea Therapeutics is developing technologies that address important unmet medical needs or offer alternatives to current methods of treatment
Two Major Platforms Targeting Multiple, High Potential Markets
Norepinephrine Replacement Therapy
Northeratm (droxidopa)
Neurogenic Orthostatic Hypotension
(NOH)*
Intradialytic Hypotension* Fibromyalgia Adult ADHD
Freezing of Gait* Chronic Fatigue
Other norepinephrine related indications
Non-Metabolized Antifolates
CH-4051 & others
Rheumatoid Arthritis
Psoriasis Crohn’s Disease Ankylosing Spondylitis Uveitus Oncology Other Inflammatory Diseases
*Approved indication in Japan
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Robust Clinical Pipeline
PRECLINICAL PHASE I PHASE II PHASE III
Northera: Norepinephrine Replenishment Therapy
NOH
Study 302: PD, MSA, PAF Study 301: PD, MSA, PAF
Study 306A: PD Study 306B: PD
Fibromyalgia
Intradialytic Hypotension
Metabolically Inert Antifolates
Rheumatoid Arthritis
CH-4051: Study 202 CH-1504: Study 201
Other Autoimmune Diseases
CH-4051: Study 101
Data: Q3 09 Data: Q3 10 Data: Q1 11
Data: Q2 12 Data: Year End 2011 Data: Q1 09
Data: Q2 12
Data: Q1 09
Data: Q2 09
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Northera™: Norepinephrine Replacement Therapy
Oral “Prodrug” of Norepinephrine: Directly metabolized to form Norepinephrine
• Replenishes Diminished Level of Natural Hormone, Norepinephrine,
Within Autonomic Nervous System
• Unique Mechanism of Action Limits Side Effects Seen with Other Drugs
• Only Chronic Oral Therapy Treating Root Cause of Neurogenic Orthostatic Hypotension
Well Documented Safety and Efficacy
• Marketed Ex US (Japan) Since 1989
• Orthostatic Hypotension associated with Parkinson’s disease
• Freezing of Gait in Parkinson’s Disease
• Hypotension associated with dialysis
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Neurogenic Orthostatic Hypotension
Neurogenic Orthostatic Hypotension (NOH): Sudden, potentially dangerous, Fall in BP When Standing From a Sitting/Lying Position
Caused by diminished synthesis and/or release of the norepinephrine used by autonomic nerves to regulate vasoconstriction
• 500–1000 mL of blood shifts to the lower body upon standing
• Reduced ability to push blood back to the heart and brain from the lower body
Poor perfusion to the brain leads to dizziness, lightheadedness & syncope
• Some patients cannot stand unaided for more than a few minutes a day
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The NOH Patient
Symptomatic NOH affects patients with primary autonomic failure, a group of diseases that includes…
Parkinson’s Disease
• Prevalence of disease: 120 cases per 100,000 population
• Prevalence of NOH: 18% to 30%
Multiple Systems Atrophy
• Prevalence of disease: 5-15 cases per 100,000 population
• Prevalence of NOH: 75%
Pure Autonomic Failure
• Prevalence of disease: 10-30 per 100,000
• Prevalence of NOH: 100%
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NOH: Current Therapeutic Landscape
Midodrine (ProAmatine®)…alpha agonist
• Never satisfied FDA’s requirement to demonstrate symptomatic improvement
• Provides constant/undifferentiated pressor effect
• Black box warning for supine hypertension…22% at 10 mg. dose
• Alpha agonist side effects
• piloerection (goose bumps, hair standing on end) • paresthesia (tingling, pricking or numbness of skin (scalp)
• Poor patient persistence and compliance
• Poor penetration of PD Market
• $55-60M peak sales (priced at $30/day would generate $315 million annually)
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Northera: US Commercial Opportunity in NOH
Attractive US Pricing Model: US sales of $300-$375 million within 3-5 years of launch assuming:
• Chronic Treatment
• Price: $30/day
• Compliance: 70%
Limited Sales Force Requirements ~ 85 Sales Reps
• 10% of Midodrine Sales Generated by Only 232 Physicians
• ~4,000 Physicians Responsible for 50% of Midodrine Sales
• No Competing Sales Force
Personal Promotion: Top 5 Deciles: ~10,000 to 12,000 MDs
• Direct Sales Force Promotion to High Prescribers
• Promotional Support & Spending at Medical Meetings
• Sampling Program for New Patients
• Medical Science Liaison Outreach to KOLs and Patient Support Groups
• Accounts for ~80 % of Effort and Spending
Non-Personal Promotion: ~45,000 MDs
• Journal Advertising
• Direct Mail Educational and Promotional Programs
• Sampling Programs via Mail
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Northera NDA: Neurogenic Orthostatic Hypotension
•New Drug Application: Filed September 2011
• Fast Track Status
• Anticipating Priority Review, Estimated Approval Q1 12
Study 301: Pivotal Proof of Efficacy Study– Induction Design (conducted under SPA)
• Study 304: Long-Term Safety Extension to Study 301
• Study 305: 24 HR Blood Pressure Monitoring Study – Subgroup of 301 Patients
Study 302: Supporting Phase III Efficacy Study – Withdrawal Design
• Study 303: Long-Term Safety Extension to Study 302
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Study 301: Symptoms of NOH in PD, MSA & PAF
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Favors Northera
Favors Placebo
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Study 301: OHQ Composite
In Addition to Statistical Significance of Single Endpoint, FDA Examines the Cumulative Distribution Function Between Arms to Discern Treatment Effect
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Study 301: Dizziness and Standing SBP
Study 301: Change in OHSA #1 (Dizziness)
Study 301: Change in Standing SBP
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Pooled 301 &302 Analysis: OHQ composite
Meta-Analysis of 301 & 302 Data Support Treatment Effect Demonstrated in Study 301
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Pooled 301 &302 Analysis: Dizziness and Standing SBP
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Exhibit 99.1
Northera: Strong Safety & Tolerability Profile
Most common adverse events reported Study 301 & 302:
• Headache: 3.0 % placebo, 6.1 % Northera
• Falls: 6.8 % placebo, 0.8 % Northera
Efficacy studies (301, 302) highlight strong safety and tolerability profile
• Safety profile similar to placebo
• Associated with no serious adverse events
• 1% incidence (equal to placebo) of supine systolic blood pressure >200 mmHg
Clinical studies (303, 304, dedicated QTc study) continue to demonstrate the long-term safety of Droxidopa*
• Infrequent occurrence of treatment-emergent adverse events
• ECG study showed no cardiac safety concerns
Placebo NORTHERA
System Organ Class(N=132)(N=131)
Preferred Term n pts (% Eve n pts (% Eve
pts) nts pts) nts
Adverse Events 31 (23.5) 58 30 (22.9) 63
Nervous system disorders 10 (7.6) 13 18 (13.7) 22
Headache 4 (3.0) 4 8 (6.1) 9
Dizziness 2 (1.5) 2 5 (3.8) 5
Loss of consciousness 3 (2.3) 4 0 0
General disorders and 4 (3.0) 6 4 (3.1) 8
administration site conditions
Fatigue 3 (2.3) 3 2 (1.5) 2
Injury, poisoning, and 10 (7.6) 12 2 (1.5) 3
procedural complications
Fall 9 (6.8) 10 1 (0.8) 2
Infections and infestations 4 (3.0) 4 4 (3.1) 4
Urinary tract infection 2 (1.5) 2 4 (3.1) 4
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Expanding the Label in Parkinson’s Disease: Falls
Injuries sustained in falls are a common source of serious morbidity and mortality
• leading cause of death in the elderly population
#1 reason for patients being admitted to the hospital in PD
2nd most common reason for PD patients to be admitted to institutional care
• 1/3 of PD related nursing home admissions related to falls
Estimated 20% of patients with Parkinson’s disease have symptomatic NOH
• NOH (symptomatic & non-symptomatic) occurs in 43-58% of patients with PD
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Study 306A: Cumulative Falls
Northera (n=24) Placebo (n=27)
Number of Falls
Total falls = 197
Total falls = 79
Number of Days of Therapy
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Study 306A: Reducing Falls per patient/week
Falls per patient/week pre-specified as efficacy criteria in 306 statistical analysis plan
• Allows for distribution of falls to be standardized and compared by arm
• Detailed discussion of metric and analysis in SAP, previously reviewed and approved by FDA
2.3 Fold or 60% Reduction in Falls per Patient/Week
Mean Falls / Patient / Week
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Study 306A: Improving Hoehn & Yahr Scores
Commonly used 5-point rating scale characterizing the progression Parkinson’s disease
• Heavily weighted toward postural instability as the primary index of disease severity
Baseline to End-of-Treatment
Change in HY Score
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Study 306A: Response in Parkinson” s Disease
Assessing the severity of motor and non-motor symptoms of Parkinson’s disease
Part I Part II Part III Part IV
Change in Component Score
Part I: Non-Motor Experiences of Daily Living Part II: Motor Experiences of Daily Living Part III: Motor Examination Part IV: Motor Complications
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Study 306A: Efficacy in Repeat Fallers
>40% of patients in Study 306A experienced 2 or more falls in 10 weeks
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Northera sNDA: Reduction in Falls in PD with NOH
Study 306A: Phase III
Preliminary Data Reported January 2011
• Preliminary, unblinded data from 51 patients that completed treatment
• Data safety monitoring committee recommends trial continue to evaluate the reduction in falls associated with Northera treatment in Parkinson’ s disease patients with NOH
Study 306B: Supporting Phase III Efficacy Study
Data: Q2 2012
• FDA Confirmed Suitability of Primary Endpoint: Falls per patient/week
• Powering for approximately 45 % reduction in the number of falls per patient/week
• Target Enrollment: 160 patients
• Anticipate top line data during Q2 2012
Future Studies to Support 306B Findings
• To be initiated post-approval, following 306B results
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Norepinephrine Replacement Therapy: Label Expansion
Norepinephrine Related Disorders
Intradialytic Hypotension
Droxidopa
Fibromyalgia
Droxidopa + Carbidopa
Adult Attention Deficit Disorder
Droxidopa + Carbidopa
Chronic Fatigue Syndrome
Droxidopa
15-25% of all hemodialysis patients suffer from IDH
Chronic Pain Disorder that Affects 5.8 million Americans
2nd Most Common Neuropsychiatric Disorder Affecting
4.4% of US adults
Debilitating Fatigue Disorder Affecting 1—4 million Americans
CHTP: Phase II
Completed
CHTP: Phase II
Data: YE 11
Investigator: Phase II
Completed
Investigator: Phase II
Data: 2011
Future Growth Opportunities
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Non-Metabolized Antifolates
Novel Antifolate with Blockbuster Potential
• Non-metabolized Oral Antifolate Engineered for Improved Efficacy, Safety & Tolerability
• Potential First Line and Combination Treatment for Rheumatoid Arthritis
• Additional High Potential Global Markets: Psoriasis, Crohn’ s Disease, Other Immunological Disorders and Cancer
Methotrexate (MTX) remains most widely prescribed RA treatment:
• Limitations are AEs and long-term safety concerns
• Nausea and Diarrhea
• Kidney and Liver Toxicity
• Undergoes significant metabolism
• Est. 1/3 of MTX Patients Only Achieve a Partial Efficacy Response Likely Associated with Variation in Metabolism of MTX
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Developing a Better, Safer Methotrexate
MTX
7-OH MTX
Polyglutamylated MTX and/or
7-OH MTX
CH-4051
CH-4051
(no change!)
(no change!)
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CH-4051: Greater Efficacy, Better Safety
Phase II Proof-of-Concept Study with Racemic Mixture, CH-1504:
Demonstrated Comparable ACR 20 Response Rates To MTX Improved Safety Profile & Tolerability
Key preclinical findings show:
Superior Efficacy: Superior to both CH-1504 and MTX
2-fold Improvement in Signs and Symptoms in Rat Model
2-fold Improvement in Enzymatic Activity (DHFR inhibition)
8-fold Improvement in Cellular Uptake (Reduced Folate Carrier)
Superior Safety/toxicity:
Improved Tolerability in Rat Model
Key findings from phase 1 (SAD/MAD) study show:
Demonstrated safety :
20-fold Higher Doses Than Those Tested with CH-1504 No Serious Adverse Events
Improved pharmacokinetics:
2-fold Improvement in Bioavailability vs. CH-1504
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CH-4051 Phase II: MTX Partial Responders RA
Staggered start:
• Enroll 10 Patients in MTX and 0.3 mg & 1.0 mg CH-4051 Arms
• Open All Arms After Blinded Safety Analysis of Initial Patients in Low Dose Arms
Un-blinded Interim Efficacy Analysis: Q4 11 Full data set: Mid 2012
Screening
Randomization Visit (1:1)
N= 50
N= 50 N= 50 N= 50
N= 50
Baseline Visit
0.3 mg CH-4051/daily 1.0 mg CH-4051/daily 3.0 mg CH-4051/daily
3.0 mg CH-4051/daily + FOLATE
20 mg/wk MTX + FOLATE
Hybrid ACR Score
Up to 2 weeks
2 weeks
+ Follow Up
12 weeks
4 weeks
MTX Washout Double-Blind Treatment
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Financial Summary
Capitalization (as of 7/26/11)
Common Stock 61,847,700
Warrants 3,241,550 Options 5,697,430
Fully Diluted 70,786,680
Cash and Short-Term Investments ( as of 6/30/11) $67.1 million
Warrants Expiring (cash exercise):
March 2012 – Exercise price $5.66—Anticipated $4.5 million
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Looking Ahead
Operational Focus
• Drive Northera Registration Program/NDA
• Advance CH-4051 in RA and Droxidopa in Additional Indications
• Execute Strategic, Cash Generating Licensing/Partnership Opportunities
Upcoming Milestones
Top-line Results Northera PIII: NOH Study 301 Q3 10
Initiate CH-4051 PII: RA Q4 10
Interim Analysis: NOH Study 306 Q1 11
Top-line Results Droxidopa Investigator PII: ADHD July 11
File Northera NDA: NOH Sept. 11
Un-blinded Interim Efficacy Analysis: CH-4051 PII Q4 11
Top-line Results Droxidopa PII: Fibromyalgia Q4 11
Anticipated US Approval of Northera in NOH Q1 12
Top-line Results Northera PIII: NOH Study 306b Q2 12
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