Post on 01-Jun-2015
On a mission to provide quality of life to patients suffering from rare CNS diseases Proinvestor Life Science Seminar, 27th March 2012
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may be materially and adversely affected as compared the forward-looking statements
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that it will meet, the intentions or goals that may be described in this presentation.
Content
Introduction to NeuroSearch
Huntexil® - Clinical results
Huntexil® - Regulatory feedback
Huntexil® - The new phase III programme Prime-HD
Huntexil® - The commercial potential
Financials
March 20123
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
4 March 2012
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
5 March 2012
* TMS is the “golden standard” measure of motor function in HD
6
Content
Introduction to NeuroSearch
Huntexil® - Clinical results
Huntexil® - Regulatory feedback
Huntexil® - The new phase III programme Prime-HD
Huntexil® - The commercial potential
Financials
March 2012
What is Huntington’s disease?
Huntington’s disease has serious negative implications on quality of life for patients and their families
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
7 March 2012
Huntexil®
Belongs to the new class of dopidines
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
Unique therapeutic activityUnique therapeutic activity
Neuroleptic: Psychomotor activityNeuroleptic: Psychomotor activity Huntexil®: Psychomotor activityHuntexil®: Psychomotor activity
High
Low
Normal
High
Low
Normal
8 March 2012
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
9 March 2012
The Total Motor Score, TMS
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
TMS is part of the Unified Huntingtons Disease Rating scale (UHDRS)
*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.”
10 March 2012
Huntexil®
Effect on TMS
11
The HART studyThe MermaiHD study
The MermaiHD study
Phase III study with 437 patients in eight European countries
Statistically significant effects on TMS after 26 weeks (-3.0 points (p = 0.004))
The primary endpoint (mMS) was not met
The HART study
Phase IIb study with 227 patients in the United States and Canada
Statistically significant effect on TMS after 12 weeks (-2.8 points (p = 0.039))
The primary endpoint (mMS) was not met
March 2012
Huntexil® The HART study – TMS dose response
12 March 2012
Gait and balance
Huntexil®
Effect on hand movements, gait and balance
13
The HART study
The MermaiHD study
The HART study
The MermaiHD study
Hand movements
March 2012
March 201214
GaitInstruction video by courtesy of Ralf Reilmann, MD
Huntexil®
Safety profile is similar to placebo
Received Treatment*
Placebo
Huntexil® HART
10 mg BID
Huntexil® HART
22.5 mg BID
Huntexil® MermaiHD
45 mg once daily
Huntexil® HART &
MermaiHD45 mg BID
Total, active 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 Inter/Stop
18 (9%) 5 (9%) 2 (4%) 13 (9%) 25 (12%) 45 (10%) 63 (10%)
Any treatment emergent AEs Related
83 (41%) 18 (32%) 14 (26%) 56 (38%) 89 (44%) 177 (38%) 260 (39%)
15 March 2012
*BID = Twice daily
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
16 March 2012
17
Content
17
Introduction to NeuroSearch
Huntexil® - Clinical results
Huntexil® - Regulatory feedback
Huntexil® - The new phase III programme Prime-HD
Huntexil® - The commercial potential
Financials
March 2012
March 201218
Feedback from FDA and EMA following discussions regarding Huntexil® data package*
*Discussions in spring 2011; EMA advice on protocol assistance; FDA End-of-Phase II meeting **No formal requirement on statistical significance
Topic EMA FDA
Approvability on basis of HART, MermaiHD and earlier studies
• Additional confirmatory evidence is needed to support a MAA/NDA for Huntexil® in HD
• Additional confirmatory evidence is needed to support a MAA/NDA for Huntexil® in HD
Endpoint •TMS acceptable as primary endpoint • TMS acceptable as primary endpoint
Clinical relevance • Consistency** required between the TMS and other endpoints incl. responder rate
• Statistical significance required on global 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 appear to be sufficient (if no new safety signals emerges)
• Including Prime-HD, the safety database appear to be sufficient
• Potential higher dose require 50 patients exposure for 1 year
19
Content
19
Introduction to NeuroSearch
Huntexil® - Clinical results
Huntexil® - Regulatory feedback
Huntexil® - The new phase III programme Prime-HD
Huntexil® - The commercial potential
Financials
March 2012
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
20 March 2012
Huntexil®
Phase III programme overview
21 March 2012
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
MAD
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
CL
INIC
AL
ST
UD
IES
Content
Introduction to NeuroSearch
Huntexil® - Clinical results
Huntexil® - Regulatory feedback
Huntexil® - The new phase III programme Prime-HD
Huntexil® - The commercial potential
Financials
22 March 2012
Huntington’s DiseaseLarge unmet medical need
(1) Huntington Disease Society for America; European Huntington’s disease associations.(2) Prevalence sources: Rawlins M. Lancet 2010;376:1372–3.
Large unmet medical need in HD
− Prevalence of symptomatic patients is estimated to be 1:10,000 in most Western countries (1)
− Approximately 110,000 symptomatic 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
Number of HD patientsNumber of HD patients(Patients: 1,000s)
c.34
c.42
c.35
North America Western Europe Eastern Europe and RoW
2323 March 2012
March 201224
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
Limited existing treatment
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
2525 March 2012
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 excl. Chorea
Chorea Behavioral symptoms*Cognitivesymptoms
Total cost to society**
Significant correlation(p < 0.01)
Not significant
Not significant
Not significant
Disease severity***Significant correlation
(p < 0.01)Not
significantNot
significantNot
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
2626 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
March 201227
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
March 2012
Interviews with 24 US based clinicians treating HD patients
Test of Huntexil® -like profile (Product Q) based on hypothetical PrimeHD results
Increase understanding of US HD market
Findings confirm attractiveness of Huntexil® hypothetical profile
Positive reaction to efficacy data and 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
29
US Clinician Market Research performed by external consultancy
HD MARKET ASSESSMENT AND PRIDOPIDINE PROFILE EVALUATION (USA)
Conducted for NeuroSearch September 2011
Optio Biopharma Solutions, LLC
901 Mission StreetSuite 105San Francisco, CA 94103www.OptioLLC.com
*) HD experts, movement disorder specialists, general neurologists and primary care physicians
March 2012
Huntexil®
Blockbuster potential
Population and patients (example)Population and patients (example)High rate of diagnosis
Clear disease markers
Severity of the disease
Hereditary nature of disease
High treatment rate
No worsening of other symptoms
High compliance ensured by caregivers, nurses and family members
Limited other treatment options
Patients eligible
Treatment relevant from first motor symptoms until ambulatory care is no longer possible
Population and patientsNorth
AmericaWestern Europe
Eastern Europe and
RoW Total
Population 342 420 876
HD prevalence 0,010% 0,010% 0,004%
HD patients 34.200 42.000 35.040 111.240
Rate of diagnosis 90% 90% 60%
Treatment rate 97% 97% 90%
Patients eligible 70% 70% 70%
61% 61% 38%
Patients (no.) for treatment 20.900 25.666 13.245 59.811
We estimate that ~60% of HD patients are potential for treatment with Huntexil®
March 201230
31
Content
Introduction to NeuroSearch
Huntexil® - Clinical results
Huntexil® - Regulatory feedback
Huntexil® - The new phase III programme Prime-HD
Huntexil® - The commercial potential
Financials
March 2012
Financial results – full year 2011
NeuroSearch Group (DKK million) 2011 2010
Revenue 0 0
Total costs *(383) (168)
Operating profit/(loss)
Net financial income/(expense)
Tax
(383)
34
0
(168)
22
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
March 201232
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.
March 201233
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
34 March 2012
* TMS is the “golden standard” measure of motor function in HD
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