Huntexil® is a potential treatment for Huntington's disease being developed by NeuroSearch. Two phase 3 clinical trials failed to meet their primary endpoints but showed statistically significant improvement in motor function. Based on feedback from regulators, NeuroSearch is conducting a new phase 3 trial called Prime-HD to further evaluate Huntexil®'s efficacy and safety. There is a large unmet medical need for new treatments for Huntington's disease given its prevalence and limitations of current therapies. NeuroSearch is also evaluating the potential commercial value and cost-effectiveness of Huntexil® to support regulatory approval and reimbursement.

1. On a mission to provide quality of life to patients
suffering from rare CNS diseases
Proinvestor Life Science Seminar, 27th March 2012

2. Forward looking disclaimer
This presentation contains certain “forward-looking Statements”, relating to NeuroSearch
activities and business, which can be identified by the use of forward-looking terminology such as
“estimates”, “believes”, “expects”, “may”, “are expected to”, “will”, “should” or other similar
expressions, or by discussions of strategy, plans or intentions. Such forward-looking statements
reflect the current views of the company with respect to future events and are based on data,
assumptions and estimates that the company considers to be reasonable. Many factors could
cause the actual results, performance or achievements of NeuroSearch to be materially different
from any future results, performances or achievements that may be expressed or implied by such
forward-looking statements. Such factors include, among others, risks associated with product
discovery and development, uncertainties related to the performance and outcome of clinical
trials, unforeseen product safety issues, issues relating to manufacturing, market approval or
acceptance of NeuroSearch products, competition, intellectual property issues, market conditions
and general economic conditions. Should one or more of these risks or uncertainties materialize,
or should other risks or uncertainties not foreseen or not identified materialize or should
underlying assumptions prove incorrect, the actual results of the company may be materially and
adversely affected as compared the forward-looking statements described in this presentation.
NeuroSearch does not undertake to meet, or give any guarantee that it will meet, the intentions
or goals that may be described in this presentation.

3. Content
 Introduction to NeuroSearch
 Huntexil® - Clinical results
 Huntexil® - Regulatory feedback
 Huntexil® - The new phase III programme Prime-HD
 Huntexil® - The commercial potential
 Financials
2 March 2012

4. Company introduction
 Established in 1989; went public in 1996
 Restructuring of the company announced in September 2011 to fully
focus on Huntexil® - reduction to 35 employees by mid 2013
 ~110 employees as of 1 March with headquarters in Denmark
 Huntexil® for treatment of motor symptoms associated with
Huntington‟s disease as main, fully owned drug candidate
 Cash position of DKK 221m (USD 39m) as of end December 2011
3 March 2012

5. Huntexil®
Highlights
 Two large clinical studies, HART and MermaiHD, failed to meet their primary
endpoints, but showed statistically significant improvement in motor function as
measured by Total Motor Score (TMS) which was the secondary/tertiary endpoint *
 The observed effect on TMS is calculated to correspond to approximately 6-8
months disease progression
 A statistically significant dose-response relationship observed in HART
 Safe and well-tolerated in the doses tested with no worsening of other disease
symptoms
 Designated orphan drug status with both the FDA and the EMA granting 7 and 10
years market exclusivity, respectively
 All rights for Huntexil® are retained
* TMS is the “golden standard” measure of motor function in HD
4 March 2012

6. Content
 Introduction to NeuroSearch
 Huntexil® - Clinical results
 Huntexil® - Regulatory feedback
 Huntexil® - The new phase III programme Prime-HD
 Huntexil® - The commercial potential
 Financials
5 March 2012

7. What is Huntington‟s disease?
 Fatal, autosomal dominant genetic disorder
− Mutant huntingtin gene with CAG expansion
− Neurodegeneration in several brain areas, especially in the striatum
− Glutamate and dopamine neurotransmissions are disrupted
 Symptom onset typically around 30–50 years of age
− Motor dysfunction
− Cognitive impairment
− Behavioural changes
 Continuous disease progression for 10–20 years after symptom onset
 HD has a marked impact on patients’ daily functioning and ultimately
leads to loss of independence and premature death
Huntington‟s disease has serious negative implications on quality of life for patients and their families
6 March 2012

8. Huntexil®
Belongs to the new class of dopidines
Unique therapeutic activity
 Huntexil® is able to enhance or inhibit dopamine-dependent functions
 Dopamine D2 competitive antagonist with fast off-rate kinetics
 Through its effects at D2 receptors and its downstream effects on glutamate transmission, Huntexil® can stabilise
dysregulated psychomotor functions
Neuroleptic: Psychomotor activity Huntexil®: Psychomotor activity
High High
Normal Normal
Low Low
7 March 2012

9. Huntexil®
Phase IIb/III trials
MermaiHD
 Randomised, double-blind and placebo-controlled phase III study
 Conducted in HD centres in Austria, Belgium, France, Germany, Italy, Portugal, Spain and United
Kingdom
 Objective: Evaluate efficacy and safety of Huntexil® (45 mg once or twice daily) after 26 weeks with
mMS as primary endpoint and TMS among other endpoints
 437 patients were randomised
HART
 Randomised, double-blind and placebo-controlled phase IIb study
 Conducted in HD centres in Canada and United States
 Objective: Evaluate efficacy and safety of Huntexil® (10, 22.5 or 45 mg, all twice daily) after 12
weeks + establish dose-response relationship with mMS as primary endpoint and TMS among other
endpoints
 227 patients were randomised
8 March 2012

10. The Total Motor Score, TMS
TMS is part of the Unified Huntingtons Disease Rating scale (UHDRS)
 Measures 15 items related to motor
symptoms
 Disease progression: ~4–5 points
increase p.a.*
 TMS is the most commonly used
scale to assess movement disorders
related to HD
 mMS is a sub-scale of TMS,
excluding eye and involuntary
movements
*Mahant N, McCusker EA, Byth K, Graham S. Huntington‟s disease: clinical correlates of disability and progression. Neurology
2003; 61: 1085–92: “Over a 12-month period, the natural progression in the UHDRS–TMS is approximately 4.6 points.”
9 March 2012

11. Huntexil®
Effect on TMS
The MermaiHD study The HART study
The MermaiHD study The HART study
 Phase III study with 437 patients in eight  Phase IIb study with 227 patients in the
European countries United States and Canada
 Statistically significant effects on TMS after  Statistically significant effect on TMS after
26 weeks (-3.0 points (p = 0.004)) 12 weeks (-2.8 points (p = 0.039))
 The primary endpoint (mMS) was not met  The primary endpoint (mMS) was not met
10 March 2012

12. Huntexil®
The HART study – TMS dose response
11 March 2012

13. Huntexil®
Effect on hand movements, gait and balance
Hand movements Gait and balance
The MermaiHD study The MermaiHD study
The HART study The HART study
12 March 2012

14. Gait
Instruction video by courtesy of Ralf Reilmann, MD
13 March 2012

15. Huntexil®
Safety profile is similar to placebo
Received Treatment*
Huntexil® Huntexil®
Huntexil® Huntexil® MermaiHD HART &
HART HART 45 mg once MermaiHD Total, active
Placebo 10 mg BID 22.5 mg BID daily 45 mg BID groups Total
Total Number of Patients 202 56 55 148 203 462 664
Any treatment emergent AEs 125 (62%) 30 (54%) 25 (46%) 91 (62%) 139 (69%) 285 (62%) 410 (62%)
Any treatment emergent SAEs 12 (6%) 0 2 (4%) 10 (7%) 12 (6%) 24 (5%) 36 (5%)
Deaths 2 (1%) 0 0 1 (0.7%) 1 (0.5%) 2 (0.4%) 4 (0.6%)
Any treatment emergent AEs
18 (9%) 5 (9%) 2 (4%) 13 (9%) 25 (12%) 45 (10%) 63 (10%)
Inter/Stop
Any treatment emergent AEs
83 (41%) 18 (32%) 14 (26%) 56 (38%) 89 (44%) 177 (38%) 260 (39%)
Related
*BID = Twice daily
14 March 2012

16. Huntexil®
Post-study provision of drug
 EU
− After the open-label phase of MermaiHD, patients and physicians expressed an interest
in continuing treatment
− A compassionate use programme was initiated in 2009
− The programme has subsequently been locally adopted and approved in all eight
countries where MermaiHD was conducted
− 130 patients were enrolled by December 2011
− >40% of all completing patients are now included in the programme
 North America
− Post-study access to Huntexil® was not planned for after the 12-week HART study
(phase IIb)
− An open-label extension study was launched
− First patient was enrolled in March 2011 and when completed by December 2011, 118
patients were enrolled
− >50% of all eligible patients are thus included in the programme
15 March 2012

17. Content
 Introduction to NeuroSearch
 Huntexil® - Clinical results
 Huntexil® - Regulatory feedback
 Huntexil® - The new phase III programme Prime-HD
 Huntexil® - The commercial potential
 Financials
16 March 2012

18. Feedback from FDA and EMA following
discussions regarding Huntexil® data package*
Topic EMA FDA
Approvability on basis of • Additional confirmatory evidence is • Additional confirmatory evidence is
HART, MermaiHD and needed to support a MAA/NDA for needed to support a MAA/NDA for
earlier studies Huntexil® in HD Huntexil® in HD
Endpoint •TMS acceptable as primary endpoint • TMS acceptable as primary endpoint
Clinical relevance • Consistency** required between the TMS • Statistical significance required on global
and other endpoints incl. responder rate or functional scale (co-primary endpoint)
• Strong internal consistency between
secondary outcomes
Dosing • Recommended to explore higher doses
Safety • Including Prime-HD, the safety database • Including Prime-HD, the safety database
appear to be sufficient (if no new safety appear to be sufficient
signals emerges) • Potential higher dose require 50 patients
exposure for 1 year
*Discussions in spring 2011; EMA advice on protocol assistance; FDA End-of-Phase II meeting
**No formal requirement on statistical significance
17 March 2012

19. Content
 Introduction to NeuroSearch
 Huntexil® - Clinical results
 Huntexil® - Regulatory feedback
 Huntexil® - The new phase III programme Prime-HD
 Huntexil® - The commercial potential
 Financials
18 March 2012

20. Prime-HD for Huntexil®
Phase III efficacy study design
• Global study with 630 patients in three treatment arms
• Primary endpoint is TMS. The primary objective is to show efficacy of Huntexil ® 45 mg twice daily on TMS
• Other endpoints include Clinical Global Impression (CGI), activities of daily living (ADCS-ADL) and non-motor scales
from UHDRS
• A closed testing procedure will be applied for primary and key secondary endpoint (CGI)
• Prime-HD is powered (>90%) to detect a 3 points TMS difference with the 45 mg dose at a 5% confidence level
19 March 2012

21. Huntexil®
Phase III programme overview
MAD
CLINICAL STUDIES
TQT
Phase III: Prime-HD 45 mg or 67.5 mg both twice daily vs placebo, 26 weeks
Phase III extension: Open Prime-HD 67.5 mg twice daily, 26 weeks
Abuse liability
Bioequivalence
MAD has completed active phase and preliminary results support Prime-HD dosing regimen
TQT and bioEQ are performed in healthy volunteers
Abuse liability is performed in recreational drug abusers
20 March 2012

22. Content
 Introduction to NeuroSearch
 Huntexil® - Clinical results
 Huntexil® - Regulatory feedback
 Huntexil® - The new phase III programme Prime-HD
 Huntexil® - The commercial potential
 Financials
21 March 2012

23. Huntington‟s Disease
Large unmet medical need
 Large unmet medical need in HD Number of HD patients
(Patients: 1,000s)
− Prevalence of symptomatic patients is estimated to
be 1:10,000 in most Western countries (1) c.42
− Approximately 110,000 symptomatic c.35
c.34
patients worldwide
 Prevalence study published in The Lancet, 2010 (2)
− Minimum prevalence in England and Wales is 1.24:
10,000
− Earlier epidemiology studies are believed to have
underestimated prevalence due to the ‟stigma‟ of
the disease
North America Western Europe Eastern Europe and
RoW
(1) Huntington Disease Society for America; European Huntington‟s disease associations.
(2) Prevalence sources: Rawlins M. Lancet 2010;376:1372–3.
22 March 2012

24. Limited existing treatment
 Tetrabenazine (Xenazine®) is the only approved compound (only US)
− Indicated for chorea only
− Carries a premium price (~50,000 USD/pt/yr)
− „Black box‟ warning for increased risk of depression and suicidality
 Neuroleptics and antidepressants used off-label
23 March 2012

25. Health economy efforts
Cost-of-illness/Burden of disease (independent from NeuroSearch)
– To be included in the Core Value Dossier
– Includes data from all countries
Huntington Disease model (sponsored by NeuroSearch)
– To be included in the Core Value Dossier
Cost-effectiveness of Huntexil® (sponsored by NeuroSearch)
– To be included in the Local Value Dossier for HTA/P&R applications
– Includes data from country/countries relevant to local conditions
24 March 2012

26. Selected findings from cost-of-illness study
The direct medical costs (hospital visits, nursing home etc) associated with
Huntington's disease in France amount to approx. EUR 24,000 per patient per year
– Indirect costs (loss of productivity etc) are even greater
A survey in Poland and Italy reported an average time spent by caregivers caring
for a patient of more than 20 hours/day
Among caregivers surveyed in the United States, 43% reported overall
dissatisfaction with their quality of life
Motor symptoms excl. chorea are the main cost drivers
Motor symptoms Cognitive
Chorea Behavioral symptoms*
excl. Chorea symptoms
Total cost to Significant correlation Not Not Not
society** (p < 0.01) significant significant significant
Significant correlation Not Not Not
Disease severity***
(p < 0.01) significant significant significant
Preliminary results from France, adapted from Dorey et al 2010
*) None of the three symptoms depression, impulsivity, psychotic disorder tested individually were significantly correlated with total cost or
disease severity
**) Includes direct medical costs, loss of productivity etc
***) Measured on a self-reported version of the UHDRS Independence scale
25 March 2012

27. Huntexil®
Intellectual Property
 Orphan Drug status with the EMA
− Orphan drug data exclusivity 10 years from approval
 Orphan Drug status with the FDA
– Orphan drug data exclusivity 7 years from approval
 Strong intellectual property status
− Composition-of-matter patent expires in December 2020
− Patent term extension to be granted according to normal standards
− Patent term extension to 2024 / 2025 in US and 2025 in EU, respectively
26 March 2012

28. MermaiHD study published in The Lancet
Neurology
 The MermaiHD fase III study of Huntexil® has
been described in a scientific article accepted by
the well-reputed journal The Lancet Neurology
 Dr Andrew Feigin, The Feinstein Institute for
Medical Research, New York, USA, says*:
"A well tolerated drug that produces even small
benefits for patients with Huntington’s disease
would be a very welcome addition to the
currently available treatments for this debilitating
disorder… Analysis of individual items within the
UHDRS-TMS in the MermaiHD study also
suggests that pridopidine might benefit features
of HD for which there are currently no treatments
(eye movements, hand coordination, dystonia,
and gait or balance problems).“
*Press release from The Lancet Neurology
27 March 2012

29. US Clinician Market Research performed by
external consultancy
 Interviews with 24 US based clinicians treating
HD patients
 Test of Huntexil® -like profile (Product Q)
based on hypothetical PrimeHD results
HD MARKET ASSESSMENT AND PRIDOPIDINE
PROFILE EVALUATION (USA)
 Increase understanding of US HD market
Conducted for NeuroSearch
September 2011
 Findings confirm attractiveness of Huntexil®
hypothetical profile
Optio Biopharma Solutions, LLC
901 Mission Street
Suite 105
 Positive reaction to efficacy data and
San Francisco, CA 94103
www.OptioLLC.com
appreciation of clinical relevance
 Safety profile was a key benefit
 Very high intention to prescribe
 Clinician segments* rated Product Q from
5.5 to 6.3 on a scale to 7 being the most
appealing profile
*) HD experts, movement disorder specialists, general
neurologists and primary care physicians
28 March 2012

30. Huntexil®
Blockbuster potential
Population and patients (example)
High rate of diagnosis
Eastern
 Clear disease markers North Western Europe and
Population and patients America Europe RoW Total
 Severity of the disease Population 342 420 876
HD prevalence 0,010% 0,010% 0,004%
 Hereditary nature of disease HD patients 34.200 42.000 35.040 111.240
Rate of diagnosis 90% 90% 60%
High treatment rate Treatment rate 97% 97% 90%
Patients eligible 70% 70% 70%
 No worsening of other symptoms 61% 61% 38%
Patients (no.) for treatment 20.900 25.666 13.245 59.811
 High compliance ensured by caregivers,
nurses and family members
We estimate that ~60% of HD patients are
 Limited other treatment options potential for treatment with Huntexil®
Patients eligible
 Treatment relevant from first motor symptoms
until ambulatory care is no longer possible
29 March 2012

31. Content
 Introduction to NeuroSearch
 Huntexil® - Clinical results
 Huntexil® - Regulatory feedback
 Huntexil® - The new phase III programme Prime-HD
 Huntexil® - The commercial potential
 Financials
30 March 2012

32. Financial results – full year 2011
NeuroSearch Group (DKK million) 2011 2010
Revenue 0 0
Total costs *(383) (168)
Operating profit/(loss) (383) (168)
Net financial income/(expense) 34 22
Tax 0 47
Net result of continuing activities (349) (99)
Net result of discontinuing activities (329) (160)
Net result for Group (678) (259)
*Include DKK 170 million one-off costs regarding an impairment write-down of intangible assets
and a provision for changed milestone payments to the sellers of Carlsson Research and
additional DKK 99 million related to impairment charges on property and other assets
Liquidity and capital resources on 31 December 2011
• Cash and cash equivalents including securities totalled DKK 221 million
• Expected total payments for staff working on projects under the alliance
with Janssen, DKK 38 million
• Remaining payments from the sale of Sophion Bioscience DKK 9 million
31 March 2012

33. Financial expectations for 2012
Financial expectations for 2012
● Operating loss on continuing operations of approximately DKK 75 million excluding
any possible costs related to the phase III programme on Huntexil®
● The Prime-HD study will not be initiated before financing is secured to finalise the
study. So far, no decision on preferred route of financing has been taken
● No further costs related to the discontinued operations are expected in 2012. The cash
flow effect in 2012 is expected to be in the region of DKK 70 million.
32 March 2012

34. Huntexil®
Highlights
 Two large clinical studies, HART and MermaiHD, failed to meet their primary
endpoints, but showed statistically significant improvement in motor function as
measured by Total Motor Score (TMS) which was the secondary/tertiary endpoint*
 The observed effect on TMS is calculated to correspond to approximately 6-8
months disease progression
 A statistically significant dose-response relationship observed in HART
 Safe and well-tolerated in the doses tested with no worsening of other disease
symptoms
 Designated orphan drug status with both the FDA and the EMA granting 7 and 10
years market exclusivity, respectively
 All rights for Huntexil® are retained
* TMS is the “golden standard” measure of motor function in HD
33 March 2012

35. For more information, please visit; www.neurosearch.com
or write to; investor@neurosearch.com