UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
___________________
FORM 8-K
___________________
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): November 13, 2017
___________________
AVADEL PHARMACEUTICALS PLC
(Exact name of registrant as specified in its charter)
___________________
Ireland (State or Other Jurisdiction of Incorporation) | 001-37977 (Commission File Number) | 98-1341933 (I.R.S. Employer Identification No.) | ||||
Block 10-1 Blanchardstown Corporate Park, Ballycoolin Dublin 15, Ireland (Address of Principal Executive Offices) | Not Applicable (Zip Code) | |||||
Registrant's telephone number, including area code: +353 1 485 1200
___________________
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company o
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. o
Item 7.01 Regulation FD Disclosure.
On November 13, 2017, the Company posted to its website a set of presentation materials in conjunction with its investor and analyst update meeting for Noctiva™. A copy of this presentation is attached hereto as Exhibit 99.1.
The information responsive to this Item 7.01 of this Form 8-K, including Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as may be expressly set forth by specific reference in such a filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
* This information shall be deemed to be "furnished" and not filed herewith.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
AVADEL PHARMACEUTICALS PLC
By: /s/ Phillandas T. Thompson
Phillandas T. Thompson
Senior Vice President, General Counsel and Corporate Secretary
Date: November 13, 2017
Exhibit Index
1
Noctiva™
Analyst and Investor Presentation
Monday, November 13, 2017
2
Safe Harbor
This presentation may include forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section
21E of the Securities Exchange Act of 1934. The words “will,” “may,” “believe,” “expect,” “anticipate,” “estimate,” “project” and similar
expressions, and the negatives thereof, identify forward-looking statements, each of which speaks only as of the date the statement is
made. Although we believe that our forward-looking statements are based on reasonable assumptions within the bounds of our
knowledge of our business and operations, our business is subject to significant risks and as a result there can be no assurance that
actual results of our research, development and commercialization activities and our results of operations will not differ materially from
the results contemplated in such forward-looking statements. These risks include: (i) risks relating to our license agreement with Serenity
Pharmaceuticals, LLC including that our internal analyses may overstate the market opportunity in the United States for the drug
desmopressin acetate (the “Drug”) or we may not effectively exploit such market opportunity, that significant safety or drug
interaction problems could arise with respect to the Drug, that we may not successfully increase awareness of nocturia and the
potential benefits of the Drug, and that the need for management to focus attention on the development and commercialization of
the Drug could cause our ongoing business operations to suffer; and (ii) the other risks, uncertainties and contingencies described in
the Company's filings with the U.S. Securities and Exchange Commission, including our annual report on Form 10-K for the year ended
December 31, 2016, in particular under the captions “Forward-Looking Statements” and “Risk Factors,” including without limitation: our
dependence on a small number of products and customers for the majority of our revenues; the possibility that our
Bloxiverz®,Vazculep® and Akovaz® products, which are not patent protected, could face substantial competition resulting in a loss of
market share or forcing us to reduce the prices we charge for those products; the possibility that we could fail to successfully complete
the research and development for pipeline products we are evaluating for potential application to the FDA pursuant to our
"unapproved-to-approved" strategy, or that competitors could complete the development of such products and apply for FDA
approval of such products before us; the possibility that our products may not reach the commercial market or gain market
acceptance; our need to invest substantial sums in research and development in order to remain competitive; our dependence on
certain single providers for development of several of our drug delivery platforms and products; our dependence on a limited number
of suppliers to manufacture our products and to deliver certain raw materials used in our products; the possibility that our competitors
may develop and market technologies or products that are more effective or safer than ours, or obtain regulatory approval and
market such technologies or products before we do; the challenges in protecting the intellectual property underlying our drug delivery
platforms and other products; and our dependence on key personnel to execute our business plan. Except as may be required by
law, we disclaim any obligation to publicly update any forward-looking statements to reflect events after the date of this presentation.
3
Avadel: a new chapter
o Closing our history of solely focusing on
drug delivery
o Transitioning from dependence on
partners to self-funded innovation
o Welcoming long-term and sustainable
growth
o Committing to building shareholder
value through diversified specialty
product offerings
o Welcome and thanks to Avadel’s senior
team members here today:
– Greg Divis, EVP & CCO
– Mike Kanan, CFO
– Phil Thompson, GC
o Welcome to presenters:
– Alan J. Wein MD, PhD (Hon)
– Roger Dmochowski, MD, MMHC, FACS
– Samuel Herschkowtiz, MD, CEO, Serenity
– Seymour Fein, MD, CMO, Serenity
– Steve A. Kaplan, MD
– Greg Divis, EVP & CCO
4
Agenda
o Nocturia market overview
– Condition and its consequences; Alan Wein, MD, PhD(Hon) FACS
– Current treatment options; Roger Dmochowski, MD, MMHC, FACS
o Noctiva overview
– Innovation and the invention; Samuel Herschkowitz, MD, Chief Executive Officer,
Serenity Pharmaceuticals, LLC
– Clinical overview; Seymour Fein, MD, Chief Medical Officer, Serenity Pharmaceuticals, LLC
– Clinician’s perspective; Steven Kaplan, MD
– Commercial update; Greg Divis, Executive Vice President and Chief Commercial
Officer, Avadel
o Panel Q&A
o Closing remarks and company update; Mike Anderson, Avadel
5
Nocturia, the Condition and
Its Consequences
Alan J. Wein, MD, PhD(Hon), FACS
Founders Professor and Emeritus Chief of Urology
Director, Residency Program in Urology
University of Pennsylvania
Perelman School of Medicine
PENN Medicine
6
• Highly prevalent – impacts over 40 million Americans1
• Under-recognized as a distinct condition
• Associated with significant sleep disruption
• Increasingly bothersome based on number of voids per night
• Linked to health complications and a negative impact on
quality of life
Nocturia is
• Simply due to OAB or BPH
• Merely a normal part of aging
• A disease that only affects the elderly
• Something that should be ignored
Nocturia is
NOT
Nocturia: waking 2 or more times per night to urinate
1. Bosch JLH, Weiss JP. The prevalence and causes of nocturia. J Urol. 2010;184(2):440-446.
7
Prevalence, diagnosis, and treatment rates of nocturia1-7
1. Bosch JLH, Weiss JP. The prevalence and causes of nocturia. J Urol. 2010;184(2):440-446.
2. QuintilesIMS Secondary Research.
3. Lee LK, Goren A, Zou KH, et al. Potential benefits of diagnosis and treatment on health outcomes among elderly people with symptoms of overactive bladder. Int J Clin Pract. 2016;70(1):66-81.
4. Decision Resources, Treatment Algorithm in OAB.
5. Vuichoud C, Loughlin KR. Benign prostatic hyperplasia: epidemiology, economics and evaluation. J Urol. 2015;22(51):1-6.
6. Helfand BT, Evans RM, McVary KT. A comparison of the frequencies of medical therapies for overactive bladder in men and women: analysis of more than 7.2 million aging patients. Eur Urol. 2010;57(4):586-591.
7. Goldman HB, Anger JT, Esinduy CB, et al. Real-world patterns of care for the overactive bladder syndrome in the United States. Urology. 2016;87:64-69.
~40 million
~11 million
Prevalence rate: 16%1
Diagnosis rate: 27%2-5
Treatment rate: 27%6,7
~3 M
8
The prevalence and frequency of nocturia increase with age1
Popu
la
ti
o
n
-b
a
sed
P
re
v
a
le
n
ce
(
%
)
1. Markland AD, Richter HE, Fwu CW, Eggers P, Kusek JW. Prevalence and trends of urinary incontinence in adults in the United States, 2001 to 2008. J Urol. 2011;186(2):589-593.
Age (Years)
0
10
20
30
40
50
60
70
80
90
100
20-34 35-44 45-54 55-64 65-74 75+
3 or more episodes
2 episodes
1 episode
9
Nocturia impacts both men and women
1. Coyne KS, Zhou Z, Bhattacharyya SK, Thompson CL, Dhawan R, Versi E. The prevalence of nocturia and its effect on health-related quality of life and sleep in a community sample in the USA. BJU Int. 2003;92(9):948-954.
P
re
v
a
le
n
ce
(
%
)
Female
Age (Years)
Prevalence of Nocturia (≥2 Voids/Night) by Age in a US Community Study (N=5204)1
Male
0
5
10
15
20
25
30
35
40
18-24 25-34 35-44 45-54 55-64 65-74 75+
10
Multiple factors can cause nocturia1
1. Wein A, Lose GR, Fonda D. Nocturia in men, women and the elderly: a practical approach. Br J Urol. 2002;90(suppl 3):28-31.
Nocturia
Sleep
disturbances
Psychological
disturbances
Bladder-
storage
problems
Mixed
Nocturnal polyuria
• Overproduction of urine at
night
• >33% of daily urine volume
produced at night
24-hour polyuria
Polyuria
11
Nocturnal polyuria (NP) is present in the majority of
patients with nocturia
*Males only.
1. Avery K, Donovan J, Peters TJ, Shaw C, Gotoh M, Abrams P. ICIQ: a brief and robust measure for evaluating the symptoms and impact of urinary incontinence. Neurourol Urodyn. 2004;23(4):322-330.
2. Chang SC, Lin AT, Chen KK, Chang LS. Multifactorial nature of male nocturia. Urology. 2006;67(3):541-544.
3. Weiss JP. Prevalence of nocturnal polyuria in nocturia. J Urol. 2009;181(4):538.
Europe1
n=845
Japan2
n=41*
USA3
n=934
26%
74%
17%
83%
12%
88%
NP Without NP
12
0
10
20
30
40
50
60
1 2 3 4 or more
No bother
Small bother
Moderate bother
Major bother
N=3474
1. Tikkinen KA, Johnson TM, Tammela TL, et al. Nocturia frequency, bother, and quality of life: how often is too often? A population-based study in Finland. Eur Urol. 2010;57(3):488-496.
2. Chapple CR, Batista JE, Berges R, et al. The impact of nocturia in patients with LUTS/BPH: need for new recommendations. Eur Urol. 2006;5(1)(suppl):12-18.
Degree of bother increases with number of episodes per night1
Pe
rcen
tage
o
f
Pa
ti
e
n
ts
Nocturic episodes per night
“Nocturia is the most bothersome symptom in patients with
LUTS/BPH, having a significant impact on quality of life.”2
~Chapple, et al.
13
The first few hours of sleep are the most important1-3
o Deep, slow-wave, restorative sleep occurs during the first hours, while less
restorative, lighter sleep predominates later
o Waking during the first 3 to 4 hours is more likely to leave a person
groggy/tired the next day
1. Kerrebroeck PV, Drake M, Rees J. Nocturia: what do we need to know in 2017? Identify the cause and tailoring the treatment. Eur Med J Urol. 2017;5(1):32-37.
2. Stanley N. The underestimated impact of nocturia on quality of life. Eur Urol. 2005;4(7):17-19.
3. Akerstedt T, Nilsson PM. Sleep as restitution: an introduction. J Intern Med. 2003;254(1):6-12.
“A single episode of nocturia had greater adverse effects if
this occurred in the first 4 hours of sleep (where slow wave
restorative sleep occurs) as opposed to the second 4 hours.”1
~Van Kerrebroeck, et al.
14
Nocturia and sleep disruption have far-reaching health effects1-6
1. Kobelt G, Borgstrom F, Mattiassön A. Productivity, vitality and utility in a group of healthy professionally active individuals with nocturia. BJU Int. 2003;91(3):190-195.
2. Asplund R. Hip fractures, nocturia, and nocturnal polyuria in the elderly. Arch Gerontol Geriatr. 2006;43(3):319-326.
3. Van Dijk L, Kooij DG, Schellevis FG. Nocturia in the Dutch adult population. BJU Int. 2002;90(7):644-648.
4. Stewart RB, Moore MT, May FE, Marks RG, Hale WE. Nocturia: a risk factor for falls in the elderly. J Am Geriatr Soc. 1992;40(12):1217-1220.
5. Ponholzer A, Temml C, Wehrberger C, Marszalek M, Madersbacher S. The association between vascular risk factors and lower urinary tract symptoms in both sexes. Eur Urol. 2006;50(3):581-586.
6. Nakagawa H, Niu K, Hozawa A, et al. Impact of nocturia on bone fracture and mortality in older individuals: a Japanese longitudinal cohort study. J Urol. 2010;184(4):1413-1418.
Poorer overall health
Reduced health-related quality of life
Reduced work productivity
Increased falls and fractures
Increased mortality
A
B
C
D
E
15
Nocturia significantly impacts daily functioning of both
women and men1,2
0.7
0.8
0.9
1.0
0.9
0.8
0.7
***
***
***
***
***
***
***
***
***
***
***
***
** ***
*** ***
******
***
***
***
***
***
***
***
***
***
*
Men
Women
No nocturia 1 episode/night 2 episodes/night ≥3 episodes/night
L
e
v
e
l
V
a
lu
e
W
or
s
e
ning
→
Normal
←
W
or
s
e
ning
n=3597 Finnish women and men
*P<0.05; **P<0.01; ***P<0.001 (test for trend).
Worsening of nocturia is
associated with greater impact
1. Tikkinen KA, Johnson TM, Tammela TL, et al. Nocturia frequency, bother, and quality of life: how often is too often? A population-based study in Finland. Eur Urol. 2010;57(3):488-496.
2. Sintonen H. The 15D instrument of health-related quality of life: properties and applications. Ann Med. 2001;33(5):328-336.
16
Nocturia impacts daytime sleepiness, naps, and sick leave1
0
5
10
15
20
25
30
35
40
Moderate Severe 5 to 7 days/wk 3 to 4 days/wk Sick Leave
P
ropo
rtion
o
f
P
at
ient
s
Every night (n=2056) 5 to 6 nights (n=402) 3 to 4 nights (n=706) <3 nights (n=5773)
Daytime Sleepiness Naps
Nocturnal Awakening Frequency/Week
*
*
*
*
*
*
*
*
*
*P<0.001 vs awaking <3 nights/week.
1. Ohayon MM. Nocturnal awakenings and comorbid disorders in the American general population. J Psychiatr Res. 2008;43(1):48-54.
17
Nocturia affects daytime activity and work productivity1
1. Kobelt G, Borgstrom F, Mattiassön A. Productivity, vitality and utility in a group of healthy professionally active individuals with nocturia. BJU Int. 2003;91(3):190-195.
Increased
work
impairment
(assessed
using WPAI)
Increased
impairment
in non-work
activities
(WPAI)
Reduced
vitality
(SF-36)
Reduced
overall QoL
(utility; EQ-
5D)
Compared with controls, patients with nocturia had significantly (P<0.001):
Productivity, vitality, and QoL were assessed in 203 professionally active adults in Sweden with ≥1 void/night.
WPAI: Work Productivity and Activity Impairment Questionnaire
EQ-5D: Euro Quality of Life Questionnaire
Work impairment
increased with
nocturia severity
(P<0.05)
Vitality decreased with
nocturia severity
(P<0.01)
18
Nocturia: falls and hip fractures1,2,3
oNocturia increases risk of a fall 25% over 3 years
oOdds Ratio (OR) for a fall increases from 1.84 (Nx2) to 2.15 (Nx3)
oOR for hip fracture
– 1.36 in older men, N ≥ 2
– 1.8 in older men, N ≥ 3
1. Stewart et al. J Am Ger Soc, 1992
2. Bliwise et al. Sleep Medicine, 2009
3. Temml et al. NeuroUrol Urodyn, 2009
19
Nocturia is a strong predictor of mortality1
1. Kupelian V, Fitzgerald MP, Kaplan SA, Norgaard JP, Chiu GR, Rosen RC. Association of nocturia and mortality: results from the Third National Health and Nutrition Examination Survey. J Urol. 2011;185(2):571-577.
≥2 voids/night are associated with worse survival in a
population-based sample of 7455 men and 8533 women
Men
1
.9
.8
.7
.6
.5
Nocturia <2 Nocturia 2+
Months
0 12 24 36 48 60 72 84 96 108 120 132 144
Women
1
.9
.8
.7
.6
.5
Nocturia <2 Nocturia 2+
Months
0 12 24 36 48 60 72 84 96 108 120 132 144
US Data NHANES III
S
u
rv
iv
a
lP
ro
bab
ili
ty
Su
rv
iv
a
lP
ro
b
a
b
ili
ty
20
Nocturia, Current Treatment
Roger Dmochowski, MD, MMHC, FACS
Professor of Urology and Gynecology
Vanderbilt University Medical Center
21
“Improvements in nocturia contribute
considerably to overall improvements
in health-related quality of life.”1
1. Van Dijk MM, Debruyne WH, Rosette DL, Michel MC. The role of nocturia in the quality of life of men with lower urinary tract symptoms. BJU Int. 2010;105(8):1141-1146.
~Van Dijk, et al.
22
Simple logic to decrease nocturia
Decrease bladder
activation on motor
and/or sensory side of the
micturition cycle
(OAB, BPH, Combination)
Decrease significant
residual urine volume and
thereby improve
nocturnal storage
capacity
(BPH)
Decrease
nocturnal urine
production
23
Nocturia therapies: outcome indicators
Number of
nocturia
episodes
per night
Time to first
awakening
(FSUP)
QoL
indicators
Long-term
decrease in
adverse
events
(parallel
variation)
24
Nocturia treatment
• Preemptive voiding
• Nocturnal and late afternoon dehydration
• Dietary restrictions (eg, caffeine, alcohol)
• Medication timing (late afternoon diuretic)
• Compression stockings
• Afternoon and evening leg elevation
Behavior/lifestyle modifications
Target the most prominent symptoms or set of symptoms first
• Overactive bladder
• Prostatic enlargement/obstruction
• Nocturnal polyuria
Pharmacologic therapies
25
But current treatment options do not effectively treat nocturia
“Medications to treat LUTS
in men…were not
significantly better than
placebo in short-term
use.”1
EAU Guidelines Committee
“Data on OAB medications
generally had a female
predominant population
and were not significantly
better than placebo in
short-term use. It is an
assumption that this would
also apply in male only
populations…”1
EAU Guidelines Committee
“…little response has
been seen from
anticholinergic agents
and alpha-blockers.”2
Drake, et al.
1. Sakalis VI, Karavitakis M, Bedretdinova D, et al. Medical treatment of nocturia in men with lower urinary tract symptoms: systematic review by the European Association of Urology Guidelines Panel for Male
Lower Urinary Tract Symptoms. Eur Urol. 2017;72(5):757-769.
2. Kerrebroeck PV, Drake M, Rees J. Nocturia: what do we need to know in 2017? Identify the cause and tailoring the treatment. Eur Med J Urol. 2017;5(1):32-37.
26
OAB and BPH therapies do not address the true source of nocturia
Benign prostatic
hyperplasia (BPH)
Overactive
bladder (OAB)
Nocturia due to nocturnal
polyuria
1. Asseldonk BV, Barkin J, Elterman DS. Medical therapy for benign prostatic hyperplasia: a review. Can J Urol. 2015;22(suppl 1):7-17.
2. Jayarajan J, Radomski SB. Pharmacotherapy of overactive bladder in adults: a review of efficacy, tolerability, and quality of life. Res Rep Urol. 2013;6:1-16.
3. Fine ND, Weiss JP, Wein AJ. Nocturia: consequences, classification, and management. F1000Res. 2017;6:1627.
Alpha blockers relax the muscle of
the prostate and bladder neck,
allowing urine to flow more easily1
Nocturia due to nocturnal polyuria
results from overproduction of urine
by the kidneys at night3
Anticholinergics target receptors in
the bladder, improving capacity
and reducing involuntary
contractions, urgency, and
frequency2
27
BPH/OAB therapies have limited effect on nocturia
1. Noctiva Quantitative Market Research Assessment Patient Final Report. April 16, 2014.
2. Johnson TM, Jones K, Williford WO, Kutner MH, Issa MM, Lepor H. Changes in nocturia from medical treatment of benign prostatic hyperplasia: secondary analysis of the Department of Veterans Affairs
Cooperative Study Trial. J Urol. 2003;170(1):145-148.
3. Yamaguchi O, Marui E, Kakizaki H, Itoh N, Yokota T, Okada H. Randomized, double-blind, placebo- and propiverine-controlled trial of the once-daily antimuscarinic agent solifenacin in Japanese patients
with overactive bladder. BJU Int. 2007;100(3):579-587.
4. Buser N, Ivic S, Kessler TM, Kessels AG, Bachmann LM. Efficacy and adverse events of antimuscarinics for treating overactive bladder: network meta-analysis. Eur Urol. 2012;62(6):1040-1060.
Many patients are not satisfied with current treatment options1-4
Therapy Reduction in voids vs placebo
Doxazosin + Finasteride2 0.2 voids
Solifenacin3 0.16 voids
Fesoterodine4 0.14 voids
Oxybutynin4 0.11 voids
28
Nocturia treatment considerations
o BPH and OAB therapies do not adequately address the underlying
cause of nocturia in a majority of patients: nocturnal polyuria
o Improvement in nocturia is therefore often minimal with BPH/OAB
therapies
o Antidiuretic therapy with desmopressin targets nocturnal polyuria and is
endorsed with the highest level of recommendation by ICS and EAU1,2
1. Marshall SD, Raskolnikov D, Blanker MH, et al. Nocturia: current levels of evidence and recommendations from the International Consultation on Male Lower Urinary Tract Symptoms.
Urology. 2015;85(6):1291-1299.
2. Sakalis VI, Karavitakis M, Bedretdinova D, et al. Medical treatment of nocturia in men with lower urinary tract symptoms: systematic review by the European Association of Urology
Guidelines Panel for male lower urinary tract symptoms. Eur Urol. 2017;72(5):757-769.
29
Desmopressin is effective for the treatment of nocturia1
o Oral and sublingual formulations of desmopressin were associated with an increased
risk of hyponatremia
o Desmopressin works at the source of nocturia by increasing urea reabsorption in the
medullary collecting tubule
Study Effective dose
Route of
delivery
Clinical response
in treatment arm
(%)
Clinical response
in placebo arm
(%)
Incidence of
hyponatremia
(%)
Mattiasson 2002 0.1, 0.2, 0.4 mg Oral 34 3 8
Lose 2003 0.1, 0.2, 0.4 mg Oral 44 4 12
Lose 2004 0.1, 0.2, 0.4 mg Oral 67 NA 14
Van Kerrebroeck 2007 0.1, 0.2, 0.4 mg Oral 33 11 3
Rembratt 2003 0.2 mg Oral 82 NA 5
Kuo 2002 0.1 mg Oral 66.7 NA 3
Wang 2011 0.1 mg Oral 61.4 13.8 16
1. Friedman FM, Weiss JP. Desmopressin in the treatment of nocturia: clinical evidence and experience. Ther Adv Urol. 2013;5(6):310-317.
30
Current nocturia therapy has varying effectiveness
Has not shown
durable efficacy
in clinical
practice
Behavioral
modification
have marginal
efficacy for
treating nocturia
Drugs for OAB
and BPH
Effective for
nocturia, but use
limited by safety
concerns
Desmopressin
31
Conclusions
oNocturia is an important medical condition associated with significant
morbidity
oNocturia increases the risk of falls and is a strong predictor of mortality
oNocturia disrupts normal sleep, causes daytime fatigue and loss of
productivity, and impairs ability to perform daily activities
oBehavior modifications do little to address nocturia, and
pharmacologic options are limited by efficacy and safety concerns
32
Noctiva, the Invention
Samuel Herschkowtiz, MD
Chief Executive Officer, Serenity Pharmaceuticals, LLC
Noctiva is not yet available for prescription.
33
The challenge:
To limit the duration of antidiuretic action of
desmopressin to 4 to 6 hours at night in order to
achieve efficacy and improve the safety profile
(minimize risk of hyponatremia)
34
Noctiva (desmopressin acetate) product overview
First-in-class product1
For the treatment of nocturia due to nocturnal polyuria in adults who
awaken 2 or more times per night to void2
FDA-approved March 3, 20171
Avadel secured exclusive rights September 20177
Decreases the number
of nighttime voids2
No therapeutic equivalent3
Patented spray technology
to maximize drug delivery4
Very low-dose desmopressin
in a metered-dose nasal spray5
Works in the kidneys to
decrease urine production2
Rapid absorption and lasts for
~4 to 6 hours after administration2
1 spray 30 minutes before
bed2; works on first use4
Approval based on more stringent efficacy threshold
than other desmopressin studies (response defined
as 50% reduction in nocturic episodes [vs 33%])2,6
1. US Food and Drug Administration. FDA approves first treatment for frequent urination at night due to overproduction of urine. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm544877.htm. Published
March 3, 2017.
2. Noctiva [package insert]. Chesterfield, MO; Avadel Specialty Pharmaceuticals, LLC; 2017.
3. US Food and Drug Administration. Drugs@FDA: FDA-approved drug products. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=201656. 2017.
4. Data on file. Avadel Specialty Pharmaceuticals, LLC.
5. Kaminetsky J, Fein S, Dmochowski R, et al. Efficacy and safety of SER120 nasal spray in nocturia patients: pooled analysis of 2 randomized, double-blind, placebo-controlled phase 3 trials. J Urol. 2017 [in preparation].
6. US Food and Drug Administration. Nocdurna briefing document. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/
UCM429354.pdf. Published December 3, 2014.
7. Avadel Pharmaceuticals press release.
35
The solution: Noctiva
Very low dose of desmopressin1
Engineered to achieve highly consistent absorption from dose to dose and from
patient to patient1
Pharmacokinetic coefficient of variation is comparable to subcutaneous administration2
Patented permeation enhancer (CPD) results in higher bioavailability and rapid absorption,
resulting in peak blood levels within 20 to 45 minutes2,3
Almost no depot effect: all the desmopressin that will be absorbed into the blood is
absorbed quickly2
A
B
C
D
E
1. Kaminetsky J, Fein S, Dmochowski R, et al. Efficacy and safety of SER120 nasal spray in nocturia patients: pooled analysis of 2 randomized, double-blind, placebo-controlled phase 3 trials. J Urol. 2017 [in preparation].
2. Data on file. Avadel Specialty Pharmaceuticals, LLC.
3. Noctiva [package insert]. Chesterfield, MO; Avadel Specialty Pharmaceuticals, LLC; 2017.
36
Noctiva was designed specifically for the patient with nocturia*
o The novel and patented Noctiva formulation produces:
High
bioavailability1
(~8%)
Peak plasma
concentration <10 pg/mL2
Short duration
of action2
(4-6 hours)
Unique spray pattern3
(centrifugal, donut-shaped
droplet distribution, which
deposits more drug on
nasal turbinates)
These features optimize blood levels and duration of
action, which minimize the incidence of hyponatremia
*Due to nocturnal polyuria in adults who awaken at least 2 times per night to void.
1. Cohn JA, Kowalik CG, Reynolds WS, et al. Desmopressin acetate nasal spray for adults with nocturia. Exp Rev Clin Pharmacol. 2017. doi:10.1080/17512433.2017.1394185.
2. Noctiva [package insert]. Chesterfield, MO; Avadel Specialty Pharmaceuticals, LLC; 2017.
3. Data on file. Avadel Specialty Pharmaceuticals, LLC.
37
Noctiva vs aqueous-based nasal spray1
Aqueous base Noctiva
Plume geometry
Spray pattern
1. Data on file. Avadel Specialty Pharmaceuticals, LLC.
38
Overview of Clinical Data
Seymour Fein, MD
Chief Medical Officer, Serenity Pharmaceuticals, LLC
Noctiva is not yet available for prescription.
39
Noctiva has been studied in clinical trials in over 2300 patients
Open-label studies
ELD (N=32)
56-day study in elderly patients (75 to 85 years)
OL1 (N=376)
Long-term, 43 weeks
DB3-A2 (N=393)
126-week extension study
Pivotal Phase III studies
DB3 (N=745)
99 days
DB4 (N=797)
99 days
Initial Phase III studies
DB1 (N=301)
50 days
DB2 (N=326)
50 days
Phase I/IIA
NS 200801 (phase 1)
Single dose, crossover (N=12)
CRI 201002 (phase 1)
Single dose; impaired renal function (N=16)
NS 200802 (phase 2A)
12 days (N=43)
40
Overview of Pivotal Clinical Study Data
2 Phase III randomized, double-blind, placebo-controlled, parallel-group,
multicenter, clinical studies (DB3 and DB4)
Noctiva is not yet available for prescription.
41
Change in mean number of nocturic episodes per night1
-1.2
-1.4
-1.5
-1.6
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
LS
M
ean
Cha
n
ge
From
B
asel
in
e
DB3/DB4 combined results
NOCTIVA
1.66 mcg
N=342
NOCTIVA
0.83 mcg
N=354
Placebo
N=349
Baseline (LS mean) 3.3 3.4 3.3
Difference from placebo – -0.2 -0.3
P value vs placebo – <.0001 <.0001
ITT population with nocturia due to nocturnal polyuria.
Co-primary Efficacy Endpoint
1. Sussman D, Kaminetsky J, Efros M, et al. SER120 nasal spray is effective for the treatment of nocturia in patients regardless of etiology: A pooled analysis of two randomized, placebo-controlled phase 3 trials. Presented
at: Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU); February 28-March 4, 2017; Scottsdale, AZ.
42
Percentage of patients achieving ≥50% reduction in nocturic episodes1
27.5
37.3
48.0
0
10
20
30
40
50
Percen
ta
g
e
o
f
P
a
ti
en
ts
Difference from placebo (%) – 9.8 20.5
P value vs placebo .0055 <.0001
Co-primary Efficacy Endpoint
ITT population with nocturia due to nocturnal polyuria.
DB3/DB4 combined results
NOCTIVA
1.66 mcg
N=342
NOCTIVA
0.83 mcg
N=354
Placebo
N=349
1. Sussman D, Kaminetsky J, Efros M, et al. SER120 nasal spray is effective for the treatment of nocturia in patients regardless of etiology: a pooled analysis of two randomized, placebo-controlled phase 3 trials. Presented
at: Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU); February 28-March 4, 2017; Scottsdale, AZ.
43
1.66 mcg minus Placebo 0.83 mcg minus Placebo
Overall
Sex
Male
Female
Age
<65 years
≥65 years
Nocturia etiology
Nocturnal polyuria
No nocturnal polyuria
OAB by history
BPH by history
Favors SER120 Favors Placebo
Co-primary Efficacy Endpoint
Reduction in mean number of nocturic episodes per night by
gender, age, and nocturia etiology1
-1.0 -0.8 -0.6 -0.4 -0.2 0.0 0.2 0.4 0.6 0.8 1.0
ITT population-pooled analysis.
Noctiva was
effective regardless
of sex, age, or
etiology
1. Data on file. Avadel Specialty Pharmaceuticals, LLC.
44
Time From Bedtime to 1st
Nocturic Episode
0 60 120 180 240 300
Change in Time From
Bedtime to 1st
Nocturic Episode
Minutes (SE)
P<0.0001
P<0.0001
Placebo (N=349) NOCTIVA 0.83 mcg (N=354) NOCTIVA 1.66 mcg (N=342)
Secondary Efficacy Endpoint
Change in time from bedtime to first nocturic episode1
ITT population with nocturia due to nocturnal polyuria.
Data reported as LSM (least squares mean) ± SE (standard error) unless otherwise indicated.
P<0.0001
P<0.0001252 minutes
234 minutes
210 minutes
108 minutes
96 minutes
66 minutes Patients using
Noctiva were
able to stay
asleep longer
1. Sussman D, Kaminetsky J, Efros M, et al. SER120 nasal spray is effective for the treatment of nocturia in patients regardless of etiology: a pooled analysis of two randomized, placebo-controlled phase 3 trials. Presented
at: Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU); February 28-March 4, 2017; Scottsdale, AZ.
45
Secondary Efficacy Endpoint
Change in percentage of nights with 0 or ≤1 nocturic episode1
0
5
10
15
20
25
30
35
40
45
50
Cha
n
ge
From
B
asel
ine
in
Percen
ta
g
e
o
f
N
ig
h
ts
0 nocturic episodes,
on a per-patient basis
NOCTIVA
1.66 mcg
N=342
NOCTIVA
0.83 mcg
N=354
Placebo
N=349
NOCTIVA
1.66 mcg
N=342
NOCTIVA
0.83 mcg
N=354
Placebo
N=349
ITT population with nocturia due to nocturnal polyuria.
P<0.0001
P=0.0166
P<0.0001
P=0.0099
≤1 nocturic episode,
on a per-patient basis
1. Sussman D, Kaminetsky J, Efros M, et al. SER120 nasal spray is effective for the treatment of nocturia in patients regardless of etiology: A pooled analysis of two randomized, placebo-controlled phase 3 trials. Presented
at: Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU); February 28-March 4, 2017; Scottsdale, AZ.
46
Reduction in nocturnal urine volume1
-350
-300
-250
-200
-150
-100
-50
0
mL
(S
E
)
DB3/DB4 combined results
NOCTIVA
1.66 mcg
N=342
NOCTIVA
0.83 mcg
N=354
Placebo
N=349
Secondary Efficacy Endpoint
Patients using
Noctiva produced
significantly less
urine at night
ITT population with nocturia due to nocturnal polyuria.
Data reported as LSM (least squares mean) ± SE (standard error) unless otherwise indicated.
P<0.0001
P=0.0395
1. Sussman D, Kaminetsky J, Efros M, et al. SER120 nasal spray is effective for the treatment of nocturia in patients regardless of etiology: a pooled analysis of two randomized, placebo-controlled phase 3 trials. Presented
at: Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU); February 28-March 4, 2017; Scottsdale, AZ.
47
Magnitude of change in responders for various efficacy variables1
2.9
5.3
0
1
2
3
4
5
6
Change in Time
to First Void
Time to First Void
Change in Time to First Episode
and Time to First Episode
-2.1
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
Mean Reduction in
Nocturic Episodes
20.08
76.20
0
10
20
30
40
50
60
70
80
90
0 ≤1
Reduction in Nocturnal Urine Volume
-329.6
-360
-310
-260
-210
-160
-110
-60
-10
Change in Percentage of Nights
with 0 or ≤1 Nocturic Episodes
1.5 mcg Treatment Group (N=214)
P
e
rc
e
n
t
In
c
re
a
se
Mean
Episode
Decrease
d
Time
in
Hour
s
Milliliters
Decrease
d
1. Data on file. Avadel Specialty Pharmaceuticals, LLC.
48
-1.3
-1.6
-1.7
-1.9
-1.8
-1.9
-1.8 -1.8
-1.9 -1.9
-2.0
-1.9
-2.1
-2.0
-1.9
-2.0 -2.0
-2.1
-2.5
-2
-1.5
-1
-0.5
0
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102 108 114 120 126
Time (weeks)
Noctiva 1.66 mcg long-term
Durability: reduction in mean nocturic episodes per night1
Open-Label, Long-Term Extension Trial—Up to 126 Weeks
Chan
g
e
in N
o
c
tur
ic
Ep
isodes/
N
ig
h
t
Time interval assessment (n) = Time of diary assessment (number of patients).
(n=10)
(n=39)(n=60)
(n=130)(n=194)
(n=222)(n=317)(n=346)
(n=358)
(n=375)
(n=388)
1. MacDiarmid S, Nicandro JP, Cheng M, et al. Long-term efficacy and safety of ser120 1.66 mcg in patients with nocturia: results from a 2-year open-label extension study. Poster presented at: Annual Meeting of the
American Urological Association (AUA); May 12-16, 2017; Boston, MA.
(n=330)
(n=184)
(n=223)
(n=166)
(n=60)
(n=48)
(n=21)
49
INTU items: placebo-subtracted mean change scores
ITT population1
1.66 mcg minus Placebo 0.83 mcg minus Placebo
Overall Impact Score
Daytime Impact Score
Item 1: Concentration
Item 2: Tiredness
Item 3: Completing Activities
Item 4: Irritability
Item 6: AM Restfulness
Item 10: AM Drowsiness
Nighttime Impact Score
Item 5: Nocturia Anxiety*
Item 7: Premature Waking*
Item 8: Insufficient Sleep
Item 9: Nocturia Bother*
-8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8
Favors Noctiva Favors PlaceboNoctiva 1.66-mg dose shows significant
improvement vs placebo.
INTU consists of
10 items and is
a reliable and
validated
patient-reported
outcome that
measures impact
of nocturia
1. Rovner E, Bennett J, Abrams S, et al. Improvement in patient-reported treatment benefit and health-related quality of life following treatment with ser-120 among patients with nocturia. Poster presented at: Society for
Urodynamics and Female Urology (SUFU); February 28-March 4, 2017; Scottsdale, AZ.
50
O’Brien multivariate rank analysis for INTU items: change from
screening to treatment1
Axis Length is Mean Rank. The highest rank represents the greatest reduction among all change
values of an outcome variable in the pooled set of 2 samples.
Concentration
Tiredness
Completing Activities
Irritability
Nocturia Anxiety
AM Restfulness
Premature Waking
Insufficient Sleep
Nocturia Bother
AM Drowsiness
268.0
225.0
NOCTIVA 1.66 mcgPlacebo
ITT population-pooled analysis.
1. Data on file. Avadel Specialty Pharmaceuticals, LLC.
51
Integrated Summary of Safety
Overview of hyponatremia data
52
5.2
0 0.3
9.3
2.3
0
12.3
2.1 1.5
0
5
10
15
20
25
130-134 mmol/L 126-129 mmol/L ≤125 mmol/L
Placebo Noctiva 0.83 mcg Noctiva 1.66 mcg
No. of
patients
18/349 33/354 42/341 1/349 8/354 7/341 1/349 0/354 5/341
Serum Sodium Concentration (mmol/L)
Pe
rc
en
ta
ge
o
f
P
a
tie
n
ts
Incidence of serum sodium concentration below normal range1
DB3/DB4 Studies
• Patients ≥65 had a higher
risk of hyponatremia
• Rate of hyponatremia
was similar in men and
women
1. Noctiva [package insert]. Chesterfield, MO; Avadel Specialty Pharmaceuticals, LLC; 2017.
53
Note: The N (%) from 0.75-mcg group is based on the number of patients from the ELD and OL1 studies.
Treatment period for the ELD study was 8 weeks while the treatment period for the OL1 study was 43 weeks.
Incidence of patients with nadir serum sodium post baseline by
serum sodium range1
ISS ELD/OL1/DB3-A2 Studies, Safety Population
Serum Sodium Range
(mmol/L)
Noctiva
1.66 mcg
N=358
n (%)
Noctiva
0.83 mcg
N=238
n (%)
130-134 43 (12.0) 13 (5.5)
126-129 1 (0.3) 0
≤125 0 0
• In a 2-year, open-label
extension study, no
patient using 1.66 mcg
Noctiva reported an
occurrence of
hyponatremia
1. Data on file. Avadel Specialty Pharmaceuticals, LLC.
54
NoctivaTM (desmopressin acetate) Indication and Boxed
Warning
o INDICATIONS AND USAGE: Noctiva is a vasopressin analog indicated for the treatment of nocturia due to nocturnal
polyuria in adults who awaken at least 2 times per night to void.
– Limitation of Use: Not studied in patients younger than 50 years of age.
WARNING: HYPONATREMIA
Noctiva can cause hyponatremia. Severe hyponatremia can be life-threatening, leading to seizures, coma,
respiratory arrest or death.
Noctiva is contraindicated in patients at increased risk of severe hyponatremia, such as patients with excessive
fluid intake, illnesses that can cause fluid or electrolyte imbalances, and in those using loop diuretics or
systemic or inhaled glucocorticoids.
Ensure serum sodium concentrations are normal before starting or resuming Noctiva. Measure serum sodium
within seven days and approximately one month after initiating therapy or increasing the dose, and
periodically during treatment. More frequently monitor serum sodium in patients 65 years of age and older and
in patients at increased risk of hyponatremia.
If hyponatremia occurs, Noctiva may need to be temporarily or permanently discontinued.
Please see the full Prescribing Information for Noctiva at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201656lbl.pdf
55
Noctiva Important Safety Information (continued)
o CONTRAINDICATIONS: Hyponatremia or a history of hyponatremia, polydipsia, primary nocturnal enuresis, concomitant
use with loop diuretics or systemic or inhaled glucocorticoids, estimated glomerular filtration rate below 50 mL/min/1.73
m2, Syndrome of inappropriate antidiuretic hormone secretion (SIADH, during illnesses that can cause fluid or electrolyte
imbalance, New York Heart Association (NYHA) Class II-IV congestive heart failure, uncontrolled hypertension
o WARNINGS AND PRECAUTIONS
– Fluid retention: Not recommended in patients at risk of increased intracranial pressure or history of urinary retention.
Monitor volume status in patients with NYHA Class I congestive heart failure.
– Nasal conditions: Discontinue in patients with concurrent nasal conditions that may increase absorption, until
resolved.
o ADVERSE REACTIONS: Common adverse reactions in clinical trials (incidence >2%) included nasal discomfort,
nasopharyngitis, nasal congestion, sneezing, hypertension / blood pressure increased, back pain, epistaxis, bronchitis and
dizziness.
o DRUG INTERACTIONS: Monitor serum sodium more frequently when Noctiva is concomitantly used with drugs that may
cause water retention and increase the risk for hyponatremia (e.g., tricyclic antidepressants, selective serotonin re-uptake
inhibitors, chlorpromazine, opiate analgesics, nonsteroidal anti-inflammatories, lamotrigine and carbamazepine).
o USE IN SPECIFIC POPULATIONS
– Pregnancy: Use of Noctiva is not recommended.
– Pediatric: Do not use Noctiva for primary nocturnal enuresis in children.
Please see the full Prescribing Information for Noctiva at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201656lbl.pdf
56
A Clinician’s Perspective
Steve A. Kaplan, MD
Professor of Urology, Icahn School of Medicine at Mount Sinai
Director, Benign Urologic Diseases and The Men’s Health Program,
Mount Sinai Health System
Noctiva is not yet available for prescription.
57
Summary point 1
o Out of an estimated 40 million Americans with nocturia, only approximately
11 million have been diagnosed1-4
o Prevalence increases with age5
o Nocturnal polyuria impacts 4 out of 5 people with nocturia6-8
Nocturia is an under-recognized condition
1. QuintilesIMS Secondary Research.
2. Lee LK, Goren A, Zou KH, et al. Potential benefits of diagnosis and treatment on health outcomes among elderly people with symptoms of overactive bladder. Int J Clin Pract. 2016;70(1):66-81.
3. Decision Resources, Treatment Algorithm in OAB.
4. Vuichoud C, Loughlin KR. Benign prostatic hyperplasia: epidemiology, economics and evaluation. J Urol. 2015;22(51):1-6.
5. Markland AD, Richter HE, Fwu CW, Eggers P, Kusek JW. Prevalence and trends of urinary incontinence in adults in the United States, 2001 to 2008. J Urol. 2011;186(2):589-593.
6. Avery K, Donovan J, Peters TJ, Shaw C, Gotoh M, Abrams P. ICIQ: a brief and robust measure for evaluating the symptoms and impact of urinary incontinence. Neurourol Urodyn. 2004;23(4):322-330.
7. Chang SC, Lin AT, Chen KK, Chang LS. Multifactorial nature of male nocturia. Urology. 2006;67(3):541-544.
8. Weiss JP. Prevalence of nocturnal polyuria in nocturia. J Urol. 2009;181(4):538.
58
Summary point 2
Nocturia has important consequences for
health, lifestyle, and work
o Nocturia sufferers may have an elevated risk of diabetes, hypertension,
coronary heart disease, and death1
o Nocturia significantly impacts daily functioning2,3
o Those who awoke at least 3 nights per week to void had a statistically
significant increase of daytime sleepiness, naps, and sick leave4
o Nocturia is a strong predictor of falls and mortality5-9
1. Lightner DJ, Krambeck AE, Jacobson DJ, et al. Nocturia is associated with an increased risk of coronary heart disease and death. BJU Int. 2012;110(6):848-853.
2. Tikkinen KA, Johnson TM, Tammela TL, et al. Nocturia frequency, bother, and quality of life: how often is too often? A population-based study in Finland. Eur Urol. 2010;57(3):488-496.
3. Sintonen H. The 15D instrument of health-related quality of life: properties and applications. Ann Med. 2001;33(5):328-336.
4. Ohayon MM. Nocturnal awakenings and comorbid disorders in the American general population. J Psychiatr Res. 2008;43(1):48-54.
5. Stewart RB, Moore MT, May FE, Marks RG, Hale WE. Nocturia: a risk factor for falls in the elderly. J Am Geriatr Soc. 1992;40(12):1217-1220.
6. Bliwise DL, Foley DJ, Vitiello MV, Ansari FP, Ancoli-Israel S, Walsh JK. Nocturia and disturbed sleep in the elderly. Sleep Med. 2009;10(5):540-548.
7. Ponholzer A, Temml C, Wehrberger C, Marszalek M, Madersbacher S. The association between vascular risk factors and lower urinary tract symptoms in both sexes. Eur Urol. 2006;50(3):581-586.
8. Parsons JK, Mougey J, Lambert L, et al. Lower urinary tract symptoms increase the risk of falls in older men. BJU Int. 2009;104(1):63-68.
9. Kupelian V, Fitzgerald MP, Kaplan SA, Norgaard JP, Chiu GR, Rosen RC. Association of nocturia and mortality: results from the Third National Health and Nutrition Examination Survey. J Urol. 2011;185(2):571-577.
59
Summary point 3
We finally have a safe and effective
nocturia* therapy for both men and women
o Noctiva is the first and only FDA-approved treatment for nocturia1*
o Noctiva effectively treats nocturia using 1/100th of the desmopressin
dosage of other formulations2,3
o Noctiva decreased nocturic episodes, lengthened the time to first void,
and decreased nighttime urine volume4
o Noctiva significantly improved quality of life in patients with nocturia2
o Risk of hyponatremia was low, with a similar incidence in men and women2
*Due to nocturnal polyuria in adults who awaken at least 2 times per night to void.
1. US Food and Drug Administration. FDA approves first treatment for frequent urination at night due to overproduction of urine. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm544877.htm.
Published March 3, 2017.
2. Noctiva [package insert]. Chesterfield, MO; Avadel Specialty Pharmaceuticals, LLC; 2017.
3. DDAVP nasal spray [package insert]. Bridgewater, NJ: sanofi-aventis U.S. LLC.
4. Cohn JA, Kowalik CG, Reynolds WS, et al. Desmopressin acetate nasal spray for adults with nocturia. Exp Rev Clin Pharmacol. 2017. doi:10.1080/17512433.2017.1394185
60
Commercial Strategy and
Launch Update
Greg Divis, Executive Vice President and
Chief Commercial Officer
Avadel
61
Highlights
o Market overview
o Situation analysis—recent key learnings
– Prescriber
– Patient
– Payer
o Brand strategic plan
o Launch update and timing
o Physician segmentation and field force update
o Key financial highlights
o Summary
62
Nocturia market overview
~3
M
Attractive existing market with significant upside for market expansion
~50% Dx nocturia alone
~50% Dx nocturia with
other (OAB/BPH)
6 to 12 million8 annual TRxs
$2B+8 current annual
market value
1. Bosch JLH, Weiss JP. The prevalence and causes of nocturia. J Urol. 2010;184(2):440-446.
2. QuintilesIMS Secondary Research.
3. Lee LK, Goren A, Zou KH, et al. Potential benefits of diagnosis and treatment on health outcomes among elderly people with symptoms of overactive bladder. Int J Clin Pract. 2016;70(1):66-81.
4. Decision Resources, Treatment Algorithm in OAB.
5. Vuichoud C, Loughlin KR. Benign prostatic hyperplasia: epidemiology, economics and evaluation. J Urol. 2015;22(51):1-6.
6. Helfand BT, Evans RM, McVary KT. A comparison of the frequencies of medical therapies for overactive bladder in men and women: analysis of more than 7.2 million aging patients. Eur Urol. 2010;57(4):586-591.
7. Goldman HB, Anger JT, Esinduy CB, et al. Real-world patterns of care for the overactive bladder syndrome in the United States. Urology. 2016;87:64-69.
8. Data on file.
63
At a state level, the highest nocturia prevalence rates tend to occur in the
Midwest and South Central states
2.95 6.83 10.70
Patients With Nocturia
per 1000 Population
Source: QI Nocturia Predictive Modeling October 2017 based on Xponent and Claims Databases, MAT July 2017. US Census projected
population data 2016.
64
Anticholinergics and alpha-blockers are the most common
treatments for nocturia due to OAB and BPH overlap
Sources: Physician interviews, physician survey. July 2017.
Physicians will treat patients based upon
the presentation and etiology of nocturia
• Patients with other comorbidities, such as
diabetes, hypertension, or infections, will
be treated for those conditions first unless
nocturia is a primary patient complaint
• Older desmopressin formulations currently
used primarily when no other underlying
conditions appear with nocturia
65
Current branded treatments and price points
Product WAC Package Size
VESIcare Oral Tablet 10 mg or 5 mg
(same price)
$314.77 30 tablets
Detrol LA Oral Capsule Extended Release 24 Hour 2 mg $365.00 30 capsules
Ditropan XL – Ditropan XL Oral Tablet Extended Release
24 Hour 10 mg
$636.12 100 tablets
Myrbetriq Oral Tablet Extended Release
24 Hour 25 mg
$323.45 30 tablets
Flomax Oral Capsule 0.4 mg $731.45 100 capsules
DDAVP Nasal Solution 0.01% $439.36 5 mL
Average daily costs range between ~$10-$15/day
Source: PriceRx database query conducted by IQVIA on 11/9/2017.
66
Situation and insights
400+ 400+ 40+
interviews with
urologists, OB/GYNs,
UroGYNs, PCPs, NPs,
and PAs
patients included in
qualitative and
quantitative studies
interviews with P&T
committee members
within large national
and regional MCOs
Comprehensive, ongoing market research with HCPs, patients, and payers
67
HCPs’ ability to offer patients symptomatic relief from nocturia
is variable
Most doctors acknowledge that current treatments don’t work well on nighttime symptoms
• Nocturia is typically
discovered during routine
H&P or “review of systems”
and tends to be more
frequently talked about
directly with patients by
urologists and OB/GYNs
• HCPs look at nocturia as a
symptom and do their best
to identify and address the
underlying cause, whether it
is (1) a medical condition
like BPH, (2) behavioral/
lifestyle choices, or
(3) medication-related (eg,
loop diuretics)
• While their results vary in
addressing patients’
nocturia, depending upon
the cause, it is generally
understood that medical
treatments (eg, anti-
cholinergics) do not work
well on nighttime symptoms1
1. Van Kerrebroeck P, et al. Nocturia research: current status and future perspectives. Neurourol Urodyn. 2010;29(4):623-628.
Source: Physician interviews. October 2017.
68
HCPs believe the way to highlight the importance of addressing
nocturia is to point out that it can substantially impact QoL
They recommend emphasizing individual QoL benefits
• Rather than focus on one particular effect of nocturia, HCPs told us that improving
the patient’s QoL is the paramount goal in addressing nocturia: helping the
patient to enjoy an uninterrupted night’s sleep will yield multiple QoL and
health-related dividends
• While not a sleep story, per se, HCPs feel that the value of addressing nocturia is
promoting a more “sustained, restorative” sleep, which in turn yields differential
benefits, depending upon the patient type (eg, more productivity for those who
are working, safety for older patients) and expected associated benefits of
improved sleep
• In seeking to encourage a greater focus on nocturia, HCPs emphasize that while
offering symptomatic relief is an important goal, looking for the underlying cause of
the nocturia remains their medical responsibility
Source: Physician interviews. October 2017.
69
Impact of nocturia on patients is variable: for most, it is
frustrating but viewed as a natural consequence of aging
Most people experiencing nocturia are unaware that this condition even has a name
Variability is driven by:
o Frequency of sleep disruptions
o Ease of falling back to sleep
o Ability to accommodate sleep
disruptions
– Impacts working patients
more
o Other comorbid health issues
o Impact on partner sleep
Nocturia is seen by most as a
natural consequence of aging:
o Onset is gradual
o It is often not discussed with the
HCP
o May be associated with other
urinary conditions (eg, BPH, OAB)
o Not seen as treatable
There are different segments of
patients experiencing nocturia
o Variation is driven by
– Bother
– Ability to fall back to sleep
– Age
– Work status
– Comorbidity
Source: Patient interviews. October 2017.
70
Patients face barriers in talking to doctors about their
nocturia—they don’t (yet) have a name for it
Why It Gets Raised Why It Does Not Get Raised or Addressed
• Patient has other urinary symptoms,
particularly daytime symptoms (OAB, BPH)
• The patient’s nocturia is very bothersome
(multiple voids a night, inability to fall
back to sleep)
o It is significantly impacting the
patient’s ability to function during
the day, esp. function on the job
• A natural part of the aging process
• Lack of awareness of potential treatment options
• The onset is gradual that it’s often hard to notice that there is a problem
• Symptoms are often forgotten about during the day
• Belief that a “weak bladder” is a natural condition after having children
• Belief that symptoms are not (or are) a “red flag” of a potentially serious
underlying medical condition
Physician and patient education early and often is key
Source: Patient interviews. October 2017.
71
Payers do not actively manage or monitor nocturia as it is a
low-cost area for plans and lower priority overall
Source: Payer interviews. July 2017.
Current Market Access Environment
Management
• Low priority is placed on nocturia because it
is a low-cost, low-burden lifestyle disease
• Coverage is mostly dependent on cost of
the product and generic availability
Formulary
Positioning
• At launch, majority of branded products will
be placed on tier 3 for both commercial
and Medicare plans
• Contracting and rebates are needed for
preferred tiering (especially Part D)
Restrictions • “Me too” products run the risk of restrictions
and non-coverage, particularly on
Medicare plans
• Step edits are common for high-cost
products or branded products with generic
availability
“We don't have any case
management [for nocturia]; it’s
really not on our radar screen. If
you think about what we call
basically urinary incontinence,
that borders on a lifestyle-type
disease state and therefore we
don’t put a lot of emphasis on
that. Health plans are dealing
with expensive orphan or
oncology drugs, so this is really
way down the line for us.”
- MCO Payer
“Tiering is based on price, cost,
and contracting. For new agents
where contracting isn't good, we
put them on tier 3. For example,
Myrbetriq is currently non-
preferred with step edits.”
- MCO Payer
72
Today
No specific treatment
for nocturia;
payers are focused
elsewhere; HCPs
and patients
are frustrated
Future
Noctiva – a treatment
of choice for nocturia
for payers, HCPs,
and patients
73
Today
No specific
treatment
for nocturia;
payers are focused
elsewhere; HCPs
and patients
are frustrated
Future
Noctiva - a
treatment of
choice for
nocturia for
payers, HCPs,
and patients
Our approach
Market Expansion
Expand
to drive broad
market adoption
Specialist-Focused
Establish
leading market
position among
specialists quickly
Pre-Launch
Energize
the market
early and
often
74
Overarching launch plan
Expand
to drive broad
market adoption
Establish
leading market
position among
specialists quickly
Energize
the market
early and
often
• Shape market by educating
high-value HCPs and payers
• Ensure positive first experiences
for target HCPs and their patients
to drive early adoption
• Integrate and educate patients
to self-identify and “get in line”
for new treatment
• Target key prescribers of currently
treated patients and create
advocates to drive rapid uptake
• Drive patients with unresolved
symptoms to demand the first and
only FDA-approved treatment
• Expand prescriber base to
diagnose and treat with Noctiva
as their first-line choice
• Build broad consumer awareness
to drive diagnosis and treatment
with Noctiva
75
Launch update and timing
Q4’17 Q1’18 Q2’18 Q3’18 Q4’18
Phase 1:
Foundation building
Phase 2:
Disease-state education and early experience
Phase 3:
Full commercial specialty-focused launch
Objectives:
o Secure top talent for
key positions
o Prepare Noctiva for
specialty-focused
launch, including full
campaign
o Develop relationships
with key opinion leaders
and professional
organizations
o Develop economic
and clinical value
proposition for Noctiva,
and begin payer
outreach to prioritized
accounts
Objectives:
o Raise awareness
with HCPs with a
focused disease-state
educational campaign
o Ensure positive early
experiences with a
targeted patient access
and assistance program
o Implement early access
program(s) through “soft
launch” with controlled
distribution
o Payer and market
access engagement
Objectives:
o Maximize the value of Noctiva with high
nocturia-treating specialists
o Partner with large group practices to drive
efficiencies while ensuring broad reach
through sales team
o Employ disruptive patient identification and
engagement programs
o Execute coordinated medical publication
strategy to ensure a continuous flow of
clinical data
o Expand payer coverage reach and Part D
contracting
76
Organizational build update
All teams (except sales reps) to be on board by December 2017.
Sales team by January 2018
Market Access
4 National Account Managers
+ contracted team
1 Patient Access and
Reimbursement Lead
8 MSLs, contracted
1 Medical Lead, contracted
part-time
Medical & Clinical
Sales Management
1 Head of Sales
8 District Managers
80 Reps covering ~10,000
high-volume prescribers
Contracted through
leading CSO
Sales Team
1 Head of Urology
2 Brand Team Members
Marketing
77
Sales force size and structure
Source: Avadel/QI - Sales Force Design for Noctiva – HCP Segmentation.
HCP Specialty
Does an HCP specialty/
practice make them more
apt to adopt our therapy?
6
• HCP specialty and practice affiliation
4
• NBRx in the Noctiva market
Dynamic Market Volume
How likely is the HCP to initiate
new therapy or switch?
Nocturia Diagnoses
How often does the HCP
Dx patients with nocturia?
2
• Nocturia diagnoses
3 Market Potential
How big an opportunity
does the customer present?
• TRx for patients aged 50+
Early Adoption
How likely is an HCP willing
to try new therapies?
5
• Adoption analog activity
Patients With Nocturia
How many patients with
nocturia does the HCP
treat (modeled)?
1
• Noctiva patient volume at HCP level
HCP segmentation and valuation framework is primarily
based on 6 key dimensions
78
As might be expected, top nocturia market writers tend to cluster in
metropolitan areas
Source: QI Nocturia Segmentation and Predictive Modeling October 2017 based on Xponent
and Claims Databases, MAT July 2017.
Top Nocturia Writers
1 Dot = 5
79
80 optimized territories cover ~81% of targeted HCPs and ~90% of all current
nocturia diagnosis claims
Source: QI Nocturia Segmentation and Predictive Modeling October 2017 based on Xponent
and Claims Databases, MAT July 2017.00.
Top Nocturia Writers (1 Dot = 5)
In Noctiva footprint
In Noctiva whitespace
• 10,000+ specialty targets for year 1
• 80 Reps making up 8 total districts
• 8 MSLs aligned against districts
• 7 NAMs against prioritized payers
80
Key financial updates
Transformational opportunity requires significant and disciplined investment
•~50% on new teams
•~20% on promotional campaign
•~20% on educational campaign
•~10% on other (data, research, PMR, etc)
2018 launch
investment
of $50M+
•Expected to be impacted in the first couple of years due to
market education and activation investments coupled with
time to secure Part D preferred access
Market uptake
•Competitive to most commonly used branded agents
currently prescribedPricing assumption
81
Revenue opportunity
$250M-400M peak revenue opportunity
Assumes 6% to 10% penetration
of currently treated pool at peak
Maximizing the specialist opportunity will
lead to expanding our treater base and building
broader condition and Noctiva awareness.
$500M-750M+ revenue opportunity
Assumes 11% to 15+% penetration and
a 20% growth in the treated patient pool
at peak
Specialist-focused
launch
Expanded launch
opportunity
82
Summary
Noctiva provides significant growth catalyst and potential value creation opportunity for our shareholders
Transformational opportunity for AvadelA
Innovative and differentiated productB
First and only FDA-approved medication in highly
prevalent conditionC
Documented serious health-related consequences of
no or ineffective treatments D
Strong IP position (2030) with exclusive state-of-the-art
manufacturing facilityE
83
Q&A
84
Closing remarks
Future
2018 and beyond…
Present
2012-2017
Past
1990-2012
• Focused on drug delivery
and life-cycle plays for large
pharma with no internal
pipeline or long-term growth
strategy
• Unprofitable with only one
product approval. No
organizational direction
or growth plan
• Profitable with internal pipeline
development: enabling growth
organically and through
business development
• 5-year plan: Growing specialty
pharma company
• $500+ million in sales
• >$1B market cap
• Distinctive product offerings
for patients and providers
85
Thank You