continuous therapy. because life goes on...nd0612l transforms levodopa pk in pd patients an average...
TRANSCRIPT
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Continuous therapy.Because life goes ON
Jefferies 2015 Global Healthcare Conference June, 2015
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Disclaimer
These slides and the accompanying oral presentation contain forward-looking statements concerning ourbusiness and financial performance and condition, as well as our plans, objectives and expectations for ourbusiness, operations and financial performance and condition. These forward-looking statements involveknown and unknown risks, uncertainties and other factors that may cause our actual results, performance orachievements to be materially different from any future results, performance or achievements expressed orimplied by the forward-looking statements. In some cases, you can identify forward-looking statements byterms including ‘‘anticipates,’’ ‘‘believes,’’ ‘‘could,’’ ‘‘estimates,’’ ‘‘expects,’’ ‘‘intends,’’ ‘‘may,’’ ‘‘plans,’’‘‘potential,’’ ‘‘predicts,’’ ‘‘projects,’’ ‘‘should,’’ ‘‘will,’’ ‘‘would,’’ and similar expressions intended to identifyforward-looking statements.Forward-looking statements reflect our current views with respect to future events and are based onassumptions and subject to risks and uncertainties. You should not unduly rely on any forward-lookingstatements. Although we believe that the expectations reflected in the forward-looking statements arereasonable, we cannot guarantee that future results, levels of activity, performance and events andcircumstances reflected in the forward-looking statements will be achieved or will occur. Except as required bylaw, we undertake no obligation to update publicly any forward-looking statements for any reason after thedate of this presentation, to conform these statements to actual results or to changes in our expectations.These forward-looking statements speak only as of the date of this presentation, and we assume no obligationto update or revise these forward-looking statements for any reason.For a description of the primary risks to which we are subject, please see the “Risk Factors” section of the finalprospectus for our initial public offering, which was filed with the U.S. Securities and Exchange Commission onNovember 17, 2014. The trademarks included herein are the property of the owners thereof and are used forreference purposes only. Such use should not be construed as an endorsement of the products or services ofthe Company.
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Who we are
Innovative formulations that significantly increase clinical efficacy in CNS diseases
New formulations of existing drugs allownew administration routes that overcome current limitations
> Oral drugs with short half life; low bioavailability and/or solubility
New drug has significant advantages:
> Higher efficacy
> Fewer side effects
> Improved quality of life and ease of use
High NCE-like barriers to entry grant de facto exclusivity
High price point
Accelerated lower risk regulatory pathway (505b2), short time to market
Generics
Ethical
Development Cost / Timeline / RiskLow High
Low
High
Pri
ce/I
P p
rote
ctio
n
Innovative Formulations
Few/ limitedalternatives
Unique indication
Strong patents
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Product Candidate
Indication Preclinical Phase I Phase II Phase III TTM
ND0612HSevere Parkinson’s Disease
H1-2/2018
ND0612LModerate Parkinson’s Disease
H2/2018
ND0680Severe Parkinson’s Disease
H2/2017 EU
ND0701Severe Parkinson’s Disease
H2/2017 EU
ND0801CNS disease Cognition disorders
LD/CD, Subcutaneous
LD/CD, Intra-Duodenal
Nicotine and Opipramol, Transdermal
Apomorphine,Subcutaneous
LD/CD, Subcutaneous
BE study, 2015
BE study, 2015
Ongoing Proof-of-concept study
Pipeline of products expected to launch by 2017-2018
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Blo
od
Lev
els
of
Levo
do
pa
Levodopa Administration
“Off” Time
“On” Time
Dyskinesia
Fluctu
ation
s
Mild
Delayed “on”Early “wearing off”
Moderate Severe
Narrowing therapeutic window with disease progression
ND0612
Levodopa, the Gold Standard, has a major drawback: short half life
(Bredberg et al. 1994)
“Oral route may not be the optimal method of delivering levodopa to patients who have a fluctuating response ”
Continuous delivery has been the greatest challenge of levodopa therapy
The brain needs steady levels of dopamine
Brain dopamine replaced by oral LD
Oral LD has a short half life
Instead of supplying steady LD levels – oral LD
creates sharp fluctuations, a “saw-tooth” graph
LD fluctuations lead to motor complications
OFF time (avg. of 6 hours) and dyskinesia
20% of patients develop after 6 months; 50% of patients develop after 18 months; almost all patients in 2-5 years
Constant LD levels may slow disease progression
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Attempts to achieve continuity
Controlled release tablets
Slow release tablets
Gastric retention devices
Dispensing devices
Because it was thought impossible;
previous attempts to formulate LD into
liquid forms have failed
Why a limited benefit?
Why haven’t other drug forms been developed to enable alternative routes of administration?
NeuroDerm is the 1st to formulate LD into a liquid formulation
Because LD has only existed to date in solid
form that must be administered through the
GI tract, leading to erratic uptake and low
bioavailability
To date, efforts to improve continuous LD therapy have had limited success… NO GAME CHANGERS
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Treatment alternatives for advanced patients
Deep brain stimulation
Removal post infection ≤15%
Seizures 2.4%
Cognition impairments 41%
Device sales: ~$500M (excluding surgery)
Cost per patient: up to 100,000 1st yr, ~$25,000 yr/5yr
Intra-duodenal LD/CD pump (DuoDopa)
Peritonitis 3%
Complication of insertion 40%
Wound infection 21%
Europe sales: ~$200MCost per patient: $70,000/yr
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Lead candidates introduce a new paradigm in PD treatment
The first liquid LD/CD drug, replacing surgical treatments
Device CE approved in EU
>350,000 severe patients US and EU
Current segment treatment costs: ~$70,000 /yr/pt
H1-2/2018
2nd generation ND0612L,
delivered through a patch pump.
“One and done” operation
Device in development by a third party
The first liquid LD/CD drug, a new SOC in PD, significantly reducing OFF-time
Device CE approved (EU)
>900,000 patients US and EU
Current segment treatment costs: ~ $6,000/yr/pt
H2/2018
Severe Parkinson’s disease Moderate Parkinson’s disease Moderate Parkinson’s disease
ND0612H belt pump ND0612L belt pump ND0612L patch pump
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John Nutt, MD
Nir Giladi, MD
Peter A LeWitt, MD
Olivier Rascol, MD
Clinical guidance committee & scientific advisory board
Warren Olanow, MD
Karl Kieburtz, MD, MPH
Werner Poewe, MD
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n=30
0
100
200
300
400
500
600
15 16 17 18 19 20 21 22 23 24
Me
an P
lasm
a LD
Co
nce
ntr
atio
n (
ng/
ml)
80 µl/h 120 µl/h 160 µl/h 200 µl/h 240 µl/h
Time after infusion initiation
Phase I
Phase I and phase IIaND0612L achieves steady LD levels with linear dose proportionality
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ND0612L Phase II study design
Oral SOCND0612L+oral SOC
Placebo + oral SOC
Period 1: Randomized double blind 2 weeks
ND0612L
ND0612L+Ent
Period 2: Open, 1 week
Randomization
30 moderate to
severe patients
2:1
• Safety
• Tolerability
• PK
• OFF time
• ON time w/o troublesome dyskinesia
• AIMS
• Quality of sleep (PDSS)
• Quality of life (PDQ-39)
• Disease severity (CGI-C)
Primary end points Secondary end points Exploratory efficacy end points
• LD dose adjustment
• Pump usability
Pre-Randomized
16 patients
1:1
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10
100
1000
10000
-2 3 8
Baseline(Best Current Oral Therapy)
Pla
sma
LD (
ng/
ml)
Phase II – first period pharmacokineticsND0612L stabilizes LD plasma concentration above an average of ~800ng/ml
ND0612L transforms levodopa PK in PD patients
Peak to trough 53.7 59.4 4.8
Fluctuation index 2.4 2.9 1.4
ND0612L (Adjunct to Oral Therapy)
Best Current Oral Therapy(Placebo)
Time (h)n=30
Day 0 Day 14 Day 14
-2 3 8-2 3 8
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10
100
1000
10000
-2 0 2 4 6 8 10
n=6
ND0612L ND0612L+Entacapone
n=10
Time (h)
Baseline(Standard of care)
Pla
sma
LD (
ng
/ml)
-2 0 2 4 6 8 10 -2 0 2 4 6 8 10
n=4
Phase II – second period pharmacokineticsND0612L stabilizes LD plasma concentration
Day 0 Day 21 Day 21
ND0612L transforms levodopa PK in PD patients
An average steady plasma levodopa concentration of 550ng/ml was maintained with ND0612L alone, and 800ng/ml when combined with oral entacapone
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ND0612L reduces OFF time w/o increasing dyskinesia (in clinic)
Improves motor fluctuations without “paying the penalty” of troublesome dyskinesia
-0.09 -0.47
-3.5
-3
-2.5
-2
-1.5
-1
-0.5
0
Ch
ange
fro
m b
ase
line
(h
r)
Placebo (n=11) ND0612L (n=18)
Troublesome dyskinesia
2 Hours reduction in OFF time 41% vs. 9% in the placebo
Reduction in troublesome dyskinesia
-0.41
-2.42
-3.5
-3
-2.5
-2
-1.5
-1
-0.5
0
Ch
ange
fro
m b
ase
line
(h
r)
Placebo (n=11) ND0612L (n=18)
OFF time
• Early onset of treatment effect observed
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ND0612L improves quality of sleep, quality of life and global clinical disease severity
90% improvement in disease severity 90% vs. 36% compared to placebo
36%
90%
0%
20%
40%
60%
80%
100%
% o
f p
atie
nts
imp
rove
d (
CG
I-C
sco
re)
Placebo (n=11) ND0612 (n=19)
Global clinical improvement
-1.78
-6.6
-10
-8
-6
-4
-2
0
Me
an c
han
ge in
PD
Q-3
9 s
core
Placebo (n=11) ND0612 (n=19)
Quality of life
17% improvement in quality of life 17% vs. 5% compared to placebo
30% improvement in quality of sleep 30% vs. 0.9% compared to placebo
-0.5
-17.13
-20
-16
-12
-8
-4
0
Me
an c
han
ge in
PD
SS s
core
Placebo (n=11) ND0612 (n=19)
Quality of sleep
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No systemic or local irritation , all patients elected to continue to the open label extension phase
Skin local safety in healthy volunteers - no local irritation
Good safety profile
In volunteers and PD patients so far:
• Draize score slightly elevated, slight pruritus, similar in both groups, normalized at week 3
• SC nodules (0.5-1cm) resolving spontaneously
• No particular systemic AE
• No patient discontinued early
• Local safety – similar to Phase I in healthy subjects
Transient and reversible local minor reaction
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Alone With entacapone
ND0612L ND0612H
Summary of preliminary results to date of phase IIa of ND0612H
Pla
sma
LD (
ng
/ml)
Steady ND0612H levels alone and with oral entacapone (1x/5h)
ND0612H should be suitable for the majority of severe (incl. Duodopa) patients
1807
1,436
596477
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42%
42%
16%
~$70,000Severe
Moderate~$6,000
Mild
Breakdown by severity and cost (2011) Affects one in one hundred people over age 60 (> 6 million WW)
Moderate to severe patients - ~60 % of all PD
PD treatment market $3.8B
‒ Drugs: ~$3.3B; many are generic
‒ Devices: <1% of PD patients are treated by DBS but consume approx. $500M excluding surgery costs
‒ Duodopa sales exclude US sales and cost of surgery
‒ Most moderate and severe patients are inadequately controlled
Historical peak sales of leading treatments
Mirapex DBS Duodopa
Target population Moderate Severe Severe
Annual peak sales $0.7B WW $0.5B WW* ~ $0.2B EU
*Excluding surgical costs ($30K-$50K/pt)
Advanced PD patients –a hidden segment with the largest unmet need
Parkinson’s disease is the second largest neurodegenerative disease
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ND0612L/H serve moderate and severe PD patients –the segments with the largest unmet need
US EU Global
Total PD patients 1,000,000 1,200,000 6,300,000
Moderate PD patients 420,000 504,000 2,646,000
Severe PD patients 160,000 192,000 1,008,000
Severe PD patients treated with advanced treatments (2014)
DBS new patients/yr ~13,000** ~9,000** ~22,000**
Duodopa patient base 0 ~3,500 ~4,000
Duodopa new patients/yr 0 ~700 ~800
Apomorphine patient base*** 0 ~4,000 ~6,000
Severe patients not treated with advanced treatments
~>100,000 ~>120,000 ~>700,000
*DBS, Duodopa and continuous apomorphine** 10,261 & 6,986 net yearly patient base growth plus estimated replacement of deletions from the patient base***Continuous apomorphine treatment
Only <1% of severe PD patients in the US and EU are treated by advanced treatments but spend approx. $800M* (excluding surgery)
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505(2)(b) pathway for both products
ND0612L development plan agreed with the FDA
End of phase II meeting expected in 2015
Clinical development plan
Hybrid pathway is anticipated for both products
A PK similarity program for ND0612H (vs. Duodopa) was agreed with the EMA
EMA agreed to only 1 pivotal trial with no active comparator for ND0612L
H2/2014 2015 2016 2017 2018
ND0612HEU – HybridPhase IIa - 004, PK (16 patients)
Phase II – BE, 005 (12 patients)
Phase II – BE, 009 (40 patients)
Long term safety (50-100 patients)
MAA
US – 505(b)(2) / EU – HybridPhase IIb - 006, PK (30 patients)
Phase III - 010 (120 patients)
Long term safety (50-100 patients)
NDA
ND0612LPhase II – 003 (30 patients)
End of phase II meeting
Phase III – pivotal (240 patients)
Phase III – pivotal (360 patients)
Long term safety (50-100 patients)
NDA, MAA
EU approval
US approval
US /EU approval
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Expected milestones
ND0612H ND0612L
2014 • Completion of a PK study (004)
2015
• FDA clinical hold lift• Completion of a PK study vs. Duodopa (005)• Initiation of a BE study vs. Duodopa, EU (009)• Initiation of a phase II study, US (006)• Initiation of a long term safety study (011/12)
• FDA clinical hold lift• End of phase II meeting • Initiation of 2 pivotal studies (007,008)
2016
• Completion of BE study, Europe (009)• Completion of phase II study ,US (006)• End of phase II meeting • Initiation of phase III, US (010)
2017 • Completion of long term safety study (011/12)• Completion of phase III, US (010)
• Completion of pivotal studies (007,008)• Completion of long term safety studies (011/012)
2018 • EU and US approval • EU and US approval
2019/20 • Bridging study and approval of a patch pump version
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Experienced and cohesive management team
Alon Yaar, DVM MBAChief Operating Officer
Oron Yacoby-Zeevi, PhD DVMVice President R&D
Sharon Cohen Vered, PhDHead of CMC
Sheila Oren, MD MBAVice President Clinical and Regulatory Affairs
Roy Golan, CPA LLMVice President Finance
Oded S. Lieberman, PhD MBAChief Executive Officer
Robert Taub, MBAChairman
Revlon Health Care
Group (RHCG)
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NeuroDerm (NASDAQ: NDRM )
Cash: $38.9 million – March 31, 2015
Lock-up: 180 days (Expired in Mid May 2015)
Analyst Coverage & Price Target: Jefferies ($21.00), Cowen and Company ($30.00), Oppenheimer & Co. ($19.00)
& Roth Capital Partners ($17.50)
Shares Outstanding: 17 million (18.7 million on a fully diluted basis)
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Enabling a paradigm shift in the treatment of PD
Low risks, short timelines high value premium products
Positive clinical results
Numerous near term value driving milestones
• Significant reduction in LD plasma fluctuations: >800 ng/ml
• Reduction in OFF-time compared to SOC: >2 hours
• No increase in dyskinesia
• Increase in quality of life and sleep quality
• Safe and well tolerated
• First ever liquid formulation of LD/CD enables continuous administration, transforms PD therapy, replaces surgery
• $2M granted from the Michael J. Fox Foundation for Parkinson’s Research
• Formulations with low risks, cost and short time to market (2017/18)
• Innovative technology - high barriers to entry, effective exclusivity
• NCE-like value proposition and pricing
• 2014: 2 phase II study results
• 2015: 1 phase II study results; 3 pivotal studies initiation
Investment highlights