EX-99.1 2 dex991.htm SLIDE PRESENTATION Slide presentation
©
2004-2010 Chelsea Therapeutics, Inc.
Northera™
(droxidopa)
Preliminary Findings From Study 301 in
Symptomatic Neurogenic Orthostatic
Hypotension
September 2010

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Forward-Looking Statement
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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Northera  Phase III Program: NOH
Northera  Phase III Program: NOH
Study
302:
Pivotal
Proof
of
Efficacy
–
Withdrawal
Design
Study
303:
Long-Term
Safety
Extension
to
Study
302
–
includes
long-term 
efficacy
assessment
after
3
months
Study
301:
Pivotal
Proof
of
Efficacy
–
Induction
Design
Study 304: Long-Term Safety Extension to Study 301
Study
305:
24
HR
Blood
Pressure
Monitoring
Study
–
subgroup
of
301
patients
Study
306:
Pivotal
Proof
of
Efficacy
–
Induction
Design

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Key Symptomatic Efficacy Outcome Measures
Key Symptomatic Efficacy Outcome Measures
Orthostatic Hypotension Questionnaire: OHQ
•
Orthostatic Hypotension Symptom Assessment: OHSA
Please circle the number on the scale (0-10) that best rates how severe your symptoms
from low blood pressure have been on average over the past week Please respond to
every
symptom.
If
you
do
not
experience
the
symptom,
circle
zero
(0).
PLEASE
RATE
THE
SYMPTOMS THAT ARE DUE ONLY TO YOUR LOW BLOOD PRESSURE PROBLEM.
1.Dizziness, lightheadedness, feeling faint, or feeling like you might blackout
2.Problems with vision (blurring, seeing spots, tunnel vision, etc.)
3.Weakness
4.Fatigue
5.Trouble concentrating
6.Head/neck discomfort
•
Orthostatic Hypotension Daily Activities Scale: OHDAS
We are interested in how the low blood pressure symptoms you experience affect your
daily life. Please rate each item by circling the number that best represents how much the
activity has been interfered with on average over the past week by the low blood pressure
symptoms you experienced.
1.
Standing short time
2.
Standing long time
3.
Walking short time
4.
Walking long time

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Study 301: Baseline Diagnoses
Study 301: Baseline Diagnoses
Symptomatic, Neurogenic Orthostatic Hypotension Associated with Primary
Autonomic Failure, Dopamine
-hydroxylase Deficiency & Non-diabetic Autonomic
Neuropathies
•
Diverse patient population with varied & distinct primary diseases
•
Common feature: 
20 mm Hg drop in SBP upon Standing

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Study 301: Demographic Data
Study 301: Demographic Data
Double Blind Phase
Placebo
Northera
(N=80)
(N=82)
Gender [N(%)]
  Male
42 ( 52.5)
42 ( 51.2)
  Female
38 ( 47.5)
40 ( 48.8)
Ethnicity
  White
75 ( 93.8)
82 (100.0)
  Black/African-American
1 (  1.3)
0
  Asian
1 (  1.3)
0
  Hispanic/Latino
3 (  3.8)
0
Age (years) at Screening
  n
80
82
  Mean (SD)
55.7 (20)
57.4 (17)
  Median
61.5
60.0

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Study 301: Trial Design
Study 301: Trial Design
Titration Stopping Rules:
1.Asymptomatic
and
>10
mmHG
in
Standing
SBP
2.Sustained SBP
180 mmHg or DBP
110 mmHg
3.Intolerable AEs
4.Maximum Dose of 600mg TID reached
Responder Criteria:
1.
1
unit
improvement
on
OHSA
item
#1
(dizziness);
AND
2.
10
mmHg
in
Standing
SBP

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Study 301: Optimal Dose Post-Titration
Study 301: Optimal Dose Post-Titration
100
200
300
400
500
600
0
10
20
30
40
50
Dose of Northera (mg TID)

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Study 301: Broad Symptomatic Benefits
Study 301: Broad Symptomatic Benefits
Favors
Northera
Favors
Placebo
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
OHSA
OHDAS
***
*
p
0.05
**
p
0.01
***
p
0.001
**
*
*
**
***
**
**
**
**
**

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Study 301: Change in OHSA Scores
Study 301: Change in OHSA Scores
0
1
2
3
Placebo
*
p
0.05
**
p
0.01
***
p
0.001
***
**
*
*
Northera

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Study 301: Change in OHDAS Scores
Study 301: Change in OHDAS Scores
0
1
2
3
Placebo
***
**
**
**
Northera

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Study 301: Change in Composite Scores
Study 301: Change in Composite Scores
OHQ
OHSA
OHDAS
0.0
0.5
1.0
1.5
2.0
2.5
Placebo
*
p
0.05
**
p
0.01
***
p
0.001
**
**
**
Northera

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Study 301: Effect of Northera on Standing SBP
Study 301: Effect of Northera on Standing SBP
Washout
R
Placebo
70
80
90
100
110
120
Northera
No Drug
Placebo
*
p
0.05
**
p
0.01
***
p
0.001
***

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Study 301: Effect of Northera on Supine SBP
Study 301: Effect of Northera on Supine SBP
Washout
R
Placebo
70
80
90
100
110
120
130
140
Northera
No Drug
Placebo
*
p
0.05
**
p
0.01
***
p
0.001
***

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Study 301: Effect of Northera
Study 301: Effect of Northera
on Standing SBP
on Standing SBP
SBP from randomization
Supine
Standing
0
2
4
6
8
10
12
Placebo
Northera
***
p
0.001
***
***

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Study 301: No Serious Adverse Events
Study 301: No Serious Adverse Events
•
Most common adverse events reported:
•
Headache:
0.0 % placebo,   7.4 % Northera
•
Falls:
4.3 % placebo,   0.0 % Northera

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Study 301: Response in Parkinson’s  Disease
Study 301: Response in Parkinson’s  Disease
0.00
0.25
0.50
0.75
1.00
1.25
1.50
1.75
2.00
2.25
Placebo
Northera

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0
2
4
6
8
10
12
0
1
2
3
4
5
6
7
8
9
302
301
303
Weeks of Treatment
Study 302: Parkinson’s Response Over Time
Study 302: Parkinson’s Response Over Time

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Study 306: NOH in Parkinson’s Disease
Study 306: NOH in Parkinson’s Disease
Randomization
Visit 2
Up to 2 weeks
8 weeks
Visit 1
Visit 3a, 3b, 3c….
Visit 7
2 weeks
•
Enriched Homogeneous population: 84 PD Patients with NOH
•
Longer Treatment duration allows active arm to improve and placebo to fail
•
Primary efficacy measure: OHQ composite
•
Top-line data Q2 2011
Double-Blind Titration
Double-Blind Treatment

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Next Steps: NOH Registration Program
Next Steps: NOH Registration Program
Complete Study 301 Data Analysis
Present full data set: American Autonomic Society Annual Meeting, Nov. 2010
Continue
Preparations
for
Rolling
NDA
Submission
to
be
initiated
first
half
2011
Request Pre-NDA Meeting
Complete Study 306
Estimated Completion of Enrollment: Year End 2010
Top-line Data: Q2 11
Complete Data Analysis for NDA
Complete NDA Submission: Q3 11
Anticipating Robust Filing Package
Supportive Data from Study 302
Highly Significant Outcome in Study 301
Confirmatory Data from Study 306
Strong Safety Data from Studies 303, 304 & 305
Meaningful Data from Japanese registration program
Fast-Track status should expedite NDA review process

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Study 301: Broad Symptomatic Benefits
Study 301: Broad Symptomatic Benefits
-0.50
-0.25
0.00
0.25
0.50
0.75
1.00
1.25
1.50
OHSA
OHDAS
302
301
*
p
0.05
**
p
0.01
***
p
0.001
*
**
***
**
**
*
**
**
***
**
**
*
*
*
*

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Positioning Northera
Positioning Northera
Target Profile: Northera™
is used as first line chronic oral therapy in NOH because it
is the only drug proven to reduce the physical symptoms of dizziness,
lightheadedness, and falling sensations associated with neurogenic orthostatic
hypotension by safely replenishing low levels of the natural neurotransmitter,
norepinephrine.
Pharmacoeconomic
Rationale: Reduction of Falls
•
Of the estimated 1.7 million nursing home residents in the US, approximately half fall annually,
twice the rate for persons dwelling in the community; 11% sustain a serious fall-related injury.
•
The mean incidence of falls in nursing homes is 1.5 falls per bed per year.  The most common
precipitating causes include gait and balance disorders, weakness, dizziness, environmental
hazards, confusion, visual impairment, and postural hypotension.
•
$10B for  hip fractures (1996)*
•
Does not include cost for head trauma, soft tissue injury, dislocations, etc.
•
$20B for all fall related costs (1998)**

•
Poor Surrogate at Best: Midodrine (ProAmatine®)…alpha agonist: 52,000
patients*
•
Not approved for symptomatic benefit
•
Provides constant/undifferentiated pressor effect: equal effect supine vs. standing
•
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 sales (priced at $30/day would generate $315 million annually)
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Current Therapeutic Landscape
Current Therapeutic Landscape
*Verispan

•
Attractive US Pricing Model: US sales of $300-$375 million within 3-5 years of
launch assuming:
•
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: ~20,000 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: US Commercial Opportunity
Northera: US Commercial Opportunity

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Study 301: Summary Findings
Study 301: Summary Findings
•
Broad Symptomatic & Functional Benefits
•
Statistically
Significant
Improvement
in
Composite
OHQ
Score
vs.
Placebo
(p=0.003)
•
Mean decrease of 1.83 units in composite OHQ score
•
Statistically Significant Improvement in composite OHSA (p=0.01) and composite
OHDAS (p=0.003)
•
Statistically Significant Improvement in 8 out of 10 Individual OHQ Items
•
Clear Mechanistic Rational for Symptomatic & Functional Improvements
•
Statistically Significant Improvement in Standing SBP vs. Placebo (p<0.001)
•
Mean improvement of 11.2 mmHg in standing SBP
•
Preferential Effect on Standing SBP vs. Supine SBP
•
Safe and Well Tolerated
•
No Serious or Severe Adverse Events
•
Headache (7.4%): all cases reported mild
•
Treatment associated with fewer falls
•
No patients on Northera reported falling vs. 3 patients on Placebo

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Looking Ahead….
Looking Ahead….
Top-line Results Northera: Study 303
Q2 10
Initiate Northera PIII: NOH Study 306
Q2 10
Interim Analysis Droxidopa PII: Fibromyalgia
H2 10
Top-line Results Northera PIII: NOH Study 301
Q3 10
Initiate CH-4051 PII: RA
Q4 10
Top-line Results Droxidopa Investigator PII: ADHD
Q1 11
Top-line Results Northera PIII: NOH Study 306
Q2 11
Un-blinded Interim Data CH-4051: RA
Q3 11
Top-line Results Droxidopa PII: Fibromyalgia
YE 11
•
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