Investor Day Meeting

!une 27, 2013

1hls presenLauon conLalns forward-looklng sLaLemenLs, lncludlng, buL noL llmlLed Lo, sLaLemenLs relaLed Lo Lhe process and
umlng of anuclpaLed fuLure cllnlcal developmenL of our producL candldaLes, lncludlng Lhe release of Lhe Lop-llne cllnlcal daLa ln
Lhe nal plvoLal hase 3 sLudy of nano1ab SysLem, Lhe poLenual llng of an nuA for Lhe nano1ab SysLem and Lhe umlng Lhereof,
Lherapeuuc and commerclal poLenual of Lhe nanoLab SysLem and Lhe anuclpaLed umlng and Lherapeuuc and commerclal
poLenual of our oLher producL candldaLes, our poLenual commerclal markeL opporLunlLy, Lhe paLenL proLecuon for our producL
candldaLes, and our cash and use of proceeds esumaLes. lorward-looklng sLaLemenLs represenL our esumaLes and assumpuons
only as of Lhe daLe of Lhls presenLauon. AcLual resulLs may dler maLerlally due Lo Lhe rlsks and uncerLalnues lnherenL ln our
buslness, lncludlng Lhe ouLcome, cosL and umlng of our producL developmenL acuvlues and cllnlcal Lrlals, Lhe uncerLaln cllnlcal
developmenL process, lncludlng Lhe rlsk LhaL cllnlcal Lrlals may noL have an eecuve deslgn, our ablllLy Lo obLaln and malnLaln
regulaLory approval of our producL candldaLes, our ablllLy Lo obLaln fundlng for our operauons, our plans Lo research, develop
and commerclallze our producL candldaLes, our ablllLy Lo auracL collaboraLors wlLh developmenL, regulaLory and
commerclallzauon experuse, Lhe slze and growLh poLenual of Lhe markeLs for our producL candldaLes, our ablllLy Lo successfully
commerclallze our producL candldaLes and Lhe umlng of commerclallzauon acuvlues, Lhe raLe and degree of markeL accepLance
of our producL candldaLes, our ablllLy Lo develop sales and markeung capablllues, Lhe accuracy of our esumaLes regardlng
expenses, fuLure revenues, caplLal requlremenLs and needs for nanclng, our ablllLy Lo conunue obLalnlng and malnLalnlng
lnLellecLual properLy proLecuon for our producL candldaLes, and oLher rlsks deLalled ln our llngs and reporLs wlLh Lhe SLC
lncludlng our CuarLerly 8eporL on lorm 10-C led wlLh Lhe SLC on May 8, 2013. ?ou may obLaln Lhese documenLs for free by
vlslung LuCA8 on Lhe SLC's webslLe aL www.sec.gov. 1he sLaLemenLs presenLed ln Lhls presenLauon speak only as of May 21,
2013. We underLake no duLy or obllgauon Lo updaLe publlcly any forward-looklng sLaLemenLs conLalned ln Lhls presenLauon for
any reason.
Forward Looking Statements
Agenda
9:00am lnLroducuon
8lchard klng, CLC Acel8x harmaceuucals
9:03am 1he luLure of osL-Cperauve aln ManagemenL
ur 8lchard 8erkowlLz, CrLhopedlc Surgeon. Medlcal ulrecLor, 1oLal !olnL rogram,
Coral Sprlngs Medlcal CenLer, lL
9:20am SufenLanll - A lresh erspecuve
ur Lugene vlscusl, AnesLheslologlsL. rofessor of AnesLheslology, ulrecLor of
AcuLe aln ManagemenL, 1homas !eerson unlverslLy PosplLal
9:33am 1he SufenLanll nano1ab CA SysLem - hase 3 lnslghLs
ur amela almer, AnesLheslologlsL. Chlef Medlcal Cmcer, Acel8x
harmaceuucals
3
Agenda
9:33am C&A anel
ur 8lchard 8erkowlLz, ur Lugene vlscusl, ur amela almer,
am Llndley, 8n (SLudy nurse, Memorlal Permann Memorlal ClLy PosplLal,
PousLon, 1x)
10:13am PosplLal lormulary Adopuon
ur Mlke 8oyal, AnesLheslologlsL. Chlef Cllnlcal Aalrs, Acel8x harmaceuucals
10:30am Commerclallzauon
8lchard klng, CLC Acel8x harmaceuucals
10:43am Cpen Cuesuon Sesslon
4
Post-Operative Pain Management:
Looking to the Future
8lchard 8erkowlLz, Mu, lAACS
Medlcal ulrecLor, 1oLal !olnL rogram
Coral Sprlngs Medlcal CenLer

Optimizing the Patients Surgical Experience
LMNC Approach
Less lnvaslve surgery followed by Mulumodal, NCn-lnvaslve,
auenL-conLrolled analgeslc Lherapy:
- Less lnvaslve surgery resulLs ln less severe paln and early dlscharge
- Mulumodal approach slmulLaneously auacks muluple paln paLhways,
whlle also reduclng excesslve doslng of a slngle paLhway
- non-lnvaslve modallues allow ease of ambulauon and promoLes early
dlscharge
- auenL-conLrolled analgesla allows exlblllLy and enhances pauenL
sausfacuon

6
Current Post-Operative Analgesia Modalities
IV CA pump w|th op|o|d (usua||y morph|ne or hydromorphone)
keg|ona| anesthes|a techn|ques depend|ng on type]|ocanon of
surgery
Lpldural caLheLer wlLh local anesLheuc and oplold
nerve block: slngle-shoL or conunuous caLheLer lnfuslon
lleld/wound block wlLh local anesLheuc
Mu|n-moda| ora| ana|ges|cs: Comb|nanon of ora| extended- and
|mmed|ate-re|ease op|o|ds w|th ora| gabapennno|ds (Neuronnn
or Lyr|ca) and ora| ann-|nammatory agents
7
50-Year Old Technology
Wh||e panent-contro||ed moda||nes are
preferred, the comp|ex techno|ogy
used for IV]ep|dura| CA can |ead to
med|canon errors
- lrom 2003-2009:
- 36,000 reporLed adverse evenLs due Lo
lnfuslon pumps
- 87 pump recalls lnsuLuLed
1
- LsumaLed 407 errors per 10,000
lv CA pauenLs per year
2
- 80 of lv CA errors due Lo human
facLors (programmlng errors)
2,3
1
FDA / AAMI Summit Meeting held October 2010; http://www.aami.org/infusionsummit/AAMI_FDA_Summit_Report.pdf
2
Meissner, Hospital Pharmacy 44:312, 2009
3
ISMP: http://www.ismp.org/Newsletters/acutecare/articles/20070222.asp
8
Smart Pumps?
A var|ety of smart pump techno|og|es
have been |ntroduced
- Cver 3 years of observauon
(2000-2004, lncluslve) CA error
raLes remaln unchanged ln splLe of
Lechnologlcal lmprovemenLs
- umps may be smarL", buL..
humans remaln a weak llnk



Hankin CS, Zhang M: Abstract at: American Society of Health-System Pharmacists
Summer Meeting. June 11-15, 2005. Boston, Mass.
Institute for Safe Medication Practices. Available at: www.ismp.org. USP Quality Review,
No. 81. 2004.
Sikirica V et al. presented at The 41st American Society of Health-System Pharmacists
Midyear Clinical Meeting. December 3-7, 2006. Anaheim, Calif.
FDA / AAMI Summit Meeting held October 2010; http://www.aami.org/infusionsummit/
AAMI_FDA_Summit_Report.pdf
9
IV Drug Delivery Challenges
lv drug dellvery necesslLaLes
converslon Lo oral Lherapy Lo allow
dlscharge from hosplLal
Analgeslc gaps occur ln 12 of
pauenLs wlLh lv CA, mosLly due Lo
lv lnlLrauon
1
8lsk of phleblus wlLh perlpheral
caLheLers ls 7-9
2
8acLeremla due Lo a perlpheral
venous caLheLer occurs aL a raLe of
0.2-0.4
2
1
Panchal et al., Anesth Analg 105:143741, 2007
2
Webster et al., Cochrane Database Syst Rev 3:CD007798, 2010

10
Regional Anesthesia Challenges
Lp|dura| success rate |s on|y 70 and
can ohen cause |ower extrem|ty
weakness
1
Connnuous per|phera| nerve b|ocks
a|so ||m|t ambu|anon and have been
reported to have a 7 rate of panents
fa|||ng
2
- 8educlng rlsk of falls ls a !olnL Commlsslon
nauonal auenL SafeLy Coal
3
- 42 of lnpauenL falls resulL ln ln[ury,
4
cosung
hosplLals an average of $4,200 more per sLay
3

1
Ready : Reg Anesth Pain Med 24:499-505, 1999
2
Ilfeld et al., Anesth Analg 111:155254, 2010
3
http://www.jointcommission.org/assets/1/18/ 2011-2012_npsg_presentation_final_8-4-11.pdf
4
Hitcho et al., J Gen Intern Med 19:7329, 2004
5
Bates et al., Am J Med 99:13743, 1995



11
Current CAs requ|re IV po|e and pump
connecnon at a|| nmes, restr|cnng
mob|||ty, hamper|ng phys|ca| therapy
keg|ona| anesthes|a techn|ques cause
|ower extrem|ty weakness
8oth of these |ssues ||m|t mob|||ty
- Larly moblllzauon may decrease Lhe rlsk
of posLoperauve compllcauons, lncludlng
pneumonla, aLelecLasls, lleus and venous
Lhrombosls
1

Invasive Therapies Restrict
Mobility
1
Canavarro et al., Ann Surg 124:1801, 1946
12
Multi-Modal Oral Analgesics
13
Comb|nanon of ora| extended- and |mmed|ate-re|ease
op|o|ds w|th ora| gabapennno|ds (Neuronnn or Lyr|ca)
and ora| ann-|nammatory agents
Chen requ|res IV op|o|ds adm|n|stered by nurse for
breakthrough pa|n |n hrst 24 hours
Nurse nme-|ntens|ve reg|men
I|xed, one-s|ze-hts-a|| dos|ng |nterva|s of med|canons
Not panent-contro||ed

14
Can We Do Better?
Ma|nta|n panent contro| and prov|de
rap|d onset of ana|ges|a w|th beuer
aur|butes
Less tether|ng
Lnhanced mob|||ty
Improved phys|ca| therapy
Avo|d prescr|b|ng errors
L||m|nate programm|ng errors
Less nurs|ng nme w|th techno|ogy
Lnhanced panent sansfacnon


14
15 15
How About an Oral Opioid Delivery System
that is Patient-Controlled, Non-Invasive and
Preprogrammed?
13
Non-|nvas|ve (sub||ngua|) de||very
LllmlnaLes lv lnfecuon rlsk
Lnhances ease of ambulauon
re-programmed de||very
Slngle-sLrengLh 13 mcg nano1ab
wlLh xed 20-mlnuLe lockouL
LllmlnaLes medlcauon prescrlblng
errors
LllmlnaLes programmlng errors
NOT FDA APPROVED
Sufentanil A Fresh Perspective
Lugene vlscusl, Mu
rofessor of AnesLheslology
ulrecLor of AcuLe aln ManagemenL
1homas !eerson unlverslLy
Opioid Analgesia
Cplolds, such as morphlne,
hydromorphone, fenLanyl and
sufenLanll, are powerful
analgeslcs whlch blnd malnly Lo
mu-oplold recepLors ln Lhe
cenLral nervous sysLem (braln
and splnal cord)
Cplolds produce powerful
analgesla and are reserved for
LreaLmenL of moderaLe-Lo-severe
paln
17
History of Sufentanil
SufenLanll rsL synLheslzed by !anssen ln 1974
llrsL approved ln uS for lv dellvery ln 1984
Approved for lnducuon of anesLhesla
LaLer approved for epldural dellvery as an analgeslc ln comblnauon wlLh buplvacalne
hyslco-Chemlcal roperues
Llpophlllc -1300 umes more faL-soluble Lhan morphlne
20 non-lonlzed aL physlologlcal pP
laL-lovlng, non-lonlzed molecules can peneLraLe ussue membranes qulckly, allowlng a
non-lv rouLe of admlnlsLrauon and rapld braln peneLrauon
Plghly proLeln bound and falrly rapldly excreLed, wlLh a half-llfe of 2-4 hours
18
Why Sufentanil?
Anlmal sLudles have evaluaLed Lhe
1herapeuuc lndex =
medlan leLhal dose (Lu
30
)/
medlan eecuve dose (Lu
30
)
8apld L
1/2ke0
= 6 mlnuLes Lo
braln:plasma equlllbrauon
no acuve meLabollLes
1
Mather, Clin Exp Pharmacol Physiol 1995; 22:833.
2
Kumar, Eur J Pharmacol 2008; 597:39 (ED
50
) and Purdue Pharma MSDS, 2009 (LD
50
)
OPIOID THERAPEUTIC INDEX

Meperidine 5
1
Methadone 12
1

Morphine 71
1

Hydromorphone 232
2
Fentanyl 277
1

Sufentanil 26,716
1
19
Is the Differentiated Therapeutic Index Related
to MOR-1 Splice Variants?
1he slngle mu oplold recepLor (MC8)
gene has a serles of lnLrons and exons
Pow Lhese are auached LogeLher Lo
creaLe Lhe messenger 8nA LhaL makes
Lhe recepLor proLeln can vary
ulerenL oplolds blnd Lo Lhese MC8
spllce varlanLs ln a unlque way,
posslbly explalnlng Lhe dlerenual slde
eecL prole and Lherapeuuc lndex
value for Lhe varlous oplolds
8avlndranaLhan eL al, roc. naL. Acad. Scl, 106 :10811-16, 2009
20
Clinical Experience with
IV Sufentanil
When used lnLra-operauvely, sufenLanll demonsLraLed less posL-operauve
resplraLory depresslon and lmproved analgesla relauve Lo fenLanyl
1
SufenLanll-based lv CA demonsLraLed equal levels of analgesla, less sedauon and less oxygen
desaLurauon compared Lo lv CA groups LreaLed wlLh morphlne or alfenLanll
2
ln healLhy volunLeers, lv sufenLanll produced less resplraLory depresslon and more eecuve
analgesla compared Lo lv fenLanyl
3
lasma levels of sufenLanll LhaL produce sedauon and analgesla dld noL have any eecL on
elghL dlerenL parameLers of resplraLory or pulmonary funcuon ln an lCu semng
4
1
Clark n! eL al. Aoestbesloloqy 1987, 66:130-133
2
ved SA, eL al. cllo I lolo 1989, 3(S1):S63-S70
3
8alley L, eL al. Aoestb Aoolq 1990,70(1):8-13
4
Conu C, eL al. coo I Aoestb 2004, 31(3):494-499
21
22
Opioid Analgesia Results from a
Two-Stage Process
Ach|ev|ng a |asma Leve|
ulsLrlbuuon of drug Lo plasma, aecLed
prlmarlly by llpophlllclLy, lonlzauon of molecule
Lllmlnauon from plasma, aecLed by
meLabollsm Lo hydrophlllc acuve or lnacuve
meLabollLes
Gemng to the CNS Lector S|te
lnux across blood-braln barrler, aecLed by
llpophlllclLy, lonlzauon
CounLered by eMux vla -glycoproLeln (C)
LransporLer mechanlsms
unllke morphlne, sufenLanll ls noL a C
subsLraLe
Sufentanil Has a 6 Minute t
1/2ke0
Common|y used IV op|o|ds have a
de|ayed trans|t and equ|||branon
nme from p|asma to the CNS (t
xke0
)
Morphlne (L
xke0
) = 2.8 hours
1
Pydromorphone (L
xke0
) = 46 mlnuLes
2
lacLors LhaL lncrease L
xke0
:
low llpld solublllLy
hlgh degree of lonlzauon
drug acLs as a subsLraLe for CnS
eMux LransporLers


1
Lotsch et al., Anesthesiol 95:1329-38, 2001
2
Shafer et al., Geriatric Anesthesiology. 2
nd
ed. New York, NY: Springer; Chapter 15:20928, 2007 23
Active Metabolites Can Enhance Risk for AEs
Poor renal function enhances this risk
Meper|d|ne metabo||zed to normeper|d|ne can cause se|zures
1
Morph|ne's acnve metabo||tes M3G, M6G can rap|d|y accumu|ate
2,3
M6C has a L
xkeo
of 6.3 hours,
4
ls equlanalgeslc Lo morphlne and
ls presenL aL Lhe same concenLrauon as morphlne
M3C can reach levels hlgher Lhan morphlne and has been
llnked Lo neuroexclLaLory eecLs
nydromorphone metabo||te n3G ||nked to neuroexc|tanon, n6G
||nked to mu-op|o|d med|ated ana|ges|a
P3C and P6C can accumulaLe wlLh renal lnsumclency
followlng surgery
3,3
1
Clark et al., J Emerg Med 1995;13:797802
2
Smith et al., Clin J Pain 2011; 27:82438.
3
Smith et al., Clin Exp Pharmacol Physiol 2000; 27:5248.
4
Lotsch et al., Anesthesiol 2001; 95:132938.
5
Wright et al., Life Sci 2001; 69:40920.
24
Sufentanil NanoTab 15 mcg
novel, proprleLary subllngual dosage form LhaL ls
bloadheslve
8apld drug upLake from subllngual mucosa
Low sallvary response= mlnlmal drug swallowlng
Lhereby avoldlng errauc Cl upLake
non-lnvaslve rouLe wlLh no lnfuslon or pump requlred
Avolds lv peaks and Lroughs
ln hase 3 head-Lo-head sLudy, Lwo-fold longer
lnLerdoslng lnLerval Lhan lv CA morphlne
25
NOT FDA APPROVED
Sufentanil NanoTab PCA System
Preprogrammed, Non-Invasive Sublingual Delivery
26
NOT FDA APPROVED
Sufentanil NanoTab PCA System
Phase 3 Insights
amela almer, Mu, hu
rofessor of AnesLheslology,
Chlef Medlcal Cmcer,
Acel8x harmaceuucals, lnc.
Sufentanil NanoTab PK
Single-Dose and Multiple-Dose
28
kepeat Dose: anents dosed
1 Nano1ab every 20 m|nutes
1ota| 40 Nano1abs consumed
|n 13.3 hours

Ior reference, s|ng|e IV dose
of 1S mcg resu|ts |n:
C
max
: 44S pg]m|
1
max
: 4 m|nutes
SufenLanll 13mcg Muluple uose
SufenLanll 13mcg Slngle uose
1lme osL-dose (hours)
S
u
f
e
n
L
a
n
l
l

l
a
s
m
a

C
o
n
c
e
n
L
r
a
u
o
n

(
p
g
/
m
l
)

1herapeuuc
8ange
ARX-01 Phase 3 Program
29
Surgery 1ype Study 1ype S|tes N Data
Abdomlnal &
CrLhopedlc Surgery
(lA309)
Cpen-label,
Acuve-comparaLor
1
o
L: anent G|oba|
Assessment of Method of a|n
Contro| over 48 hrs
26
339
1:1
nov 2012
Abdomlnal Surgery
(lA310)
uouble-bllnd, lacebo-
conLrolled
1
o
L:Sum of a|n Intens|ty
D|erence over 48 hrs
13
178
2:1
Mar 2013
CrLhopedlc Surgery
(lA311)
uouble-bllnd, lacebo-
conLrolled
1
o
L:Sum of a|n Intens|ty
D|erence over 48 hrs
34
426
3:1
May 2013
IAP309: Primary Endpoint
anent G|oba| Assessment - 48 hours (I11 opu|anon)
GA 48 demonstrates non-|nfer|or|ty and super|or|ty for Nano1ab (I11 opu|anon)
GA 48 among comp|eters demonstrates super|or|ty for Nano1ab
GA 24 and 72 hr (I11 popu|anon) a|so stansnca||y super|or |n favor of Nano1ab
30
78.S
6S.6
60
64
68
72
76
80
Sufentan|| Nano1ab
(n=177)
IV CA Morph|ne
(n=180)

o
f

a
n
e
n
t
s

|
n

e
a
c
h

G
r
o
u
p

Good]Lxce||ent kanng
22.1
3.7
12.9
-20
-10
0
10
20
30
p<0.001
p=0.007
r|mary Lndpo|nt Non-Infer|or|ty Compar|son

IAP309:
PGA-48 Completer Population
31
S0.7
39.7
42.S 41.9
6.8
17.6
0
0.7
0
10
20
30
40
S0
60
Sufentan|| Nano1ab (n=146) IV Morph|ne (n=136)

o
f

a
n
e
n
t
s

Lxce||ent Good Ia|r oor
Compar|son between two groups (p=0.03)
IAP309:
SPID-48 and TOTPAR-48 Scores
32
76.S
70.4
60
70
80
Sufentan|| Nano1ab
(n=177)
IV CA Morph|ne
(n=180)
S

I
D

o
v
e
r

4
8

h
o
u
r
s

LS Mean SID-48
98.3
90.2
80
90
100
Sufentan|| Nano1ab
(n=177)
IV CA Morph|ne
(n=180)
1
C
1

A
k

o
v
e
r

4
8

h
o
u
r
s

LS Mean 1C1Ak-48
=0.S46
=0.0S8
IAP309:
PGA-48 and SPID-48 by Surgery Type
33
81.1
83.3
69.6
66.7
66.7
63.3
S0
60
70
80
Abdom|na|
(n=79)
n|p
(n=162)
knee
(n=116)

t
s

S
c
o
r
|
n
g

G
o
o
d
]
L
x
c
e
|
|
e
n
t

GA-48
Sufentan|| Nano1ab Morph|ne IV CA
108
106
42
122
97
29
0
2S
S0
7S
100
12S
Abdom|na|
(n=79)
n|p
(n=162)
knee
(n=116)
4
8

h
o
u
r

S

I
D


SID-48
Sufentan|| Nano1ab Morph|ne IV CA
*
* p<0.0S
IAP309: Speed of Onset and
Drop-out due to Inadequate Analgesia
34
3
4
S
6
0

0
.
2
S

0
.
S

0
.
7
S

1

2

4

6

8

1
0

1
2

a
n
e
n
t

k
e
p
o
r
t
e
d

a
|
n

I
n
t
e
n
s
|
t
y


keducnon |n a|n Intens|ty
Sufentan|| Nano1ab Morph|ne IV CA
*
* *
1|me from hrst dose of study drug (hours)
0
2
4
6
8
10
4 8 12 16 20 24 28 32 36 40 44 48
k
-
M

L
s
n
m
a
t
e
d

L
v
e
n
t

k
a
t
e

(

)

1|me aher hrst study drug dos|ng (hrs)
Drop-out - Inadequate Ana|ges|a
Sufentan|| Nano1ab Morph|ne IV CA
* p<0.01
3
4
S
6
7
0 0.S 1 4 8 12
Abdom|na|
(n=37 Suf, 42 Mor)
*
IAP309: Speed of Onset in Each Population
35
1|me from hrst dose of study drug (hours)
3
4
S
6
7
0 0.S 1 4 8 12
n|p
(n=84 Suf, 78 Mor)
Sufentan|| Nano1ab
Morph|ne IV CA
*
3
4
S
6
7
0 0.S 1 4 8 12
knee
(n=S6 Suf, 60 Mor)
*
*
* p<0.0S * p<0.0S * p<0.0S
IAP309: Doses Used by Time Period
36
28.2
36.2
28.2
7.3
0
10
20
30
40
S0
<24 24-<48 48-72 >72

o
f

a
n
e
n
t
s

Sufentan|| (Doses |n 48 hours)
1S.6
22.2
21.1
41.1
0
10
20
30
40
S0
<24 24-<48 48-72 >72

o
f

p
a
n
e
n
t
s

Morph|ne (Doses |n 48 hours)
13
9
12
0
S
10
1S
20
2S
30
0-12 hr 12-24 hr 24-48 hr
M
e
d
|
a
n

D
o
s
e
s

U
s
e
d

Sufentan|| (Doses]Study er|od)
2S
17
19
0
S
10
1S
20
2S
30
0-12 hr 12-24 hr 24-48 hr
M
e
d
|
a
n

D
o
s
e
s

U
s
e
d

Morph|ne (Doses]Study er|od)
IAP309: Sufentanil Doses by Time Period/Surgery
37
17
1S
17.S
0
S
10
1S
20
0-12 hr 12-24 hr 24-48 hr
knees (Med|an S1)
11
9
12
0
S
10
1S
20
0-12 hr 12-24 hr 24-48 hr
n|ps (Med|an 31)
11 11
16
0
S
10
1S
20
0-12 hr 12-24 hr 24-48 hr
Abdom|na| (Med|an 40)
12
10
1S
0
S
10
1S
20
0-12 hr 12-24 hr 24-48 hr
Cvera|| (Med|an 39.S)
IAP309: Patient and Nurse Ease of Care
38
4.4S
4.07
3.6
3.8
4
4.2
4.4
4.6
Sufentan|| Nano1ab IV CA Morph|ne
anent Lase of Care
4.27
3.82
3.6
3.8
4
4.2
4.4
4.6
Sufentan|| Nano1ab IV CA Morph|ne
Nurse Lase of Care
4.1S
3.84
3.2
3.4
3.6
3.8
4
4.2
Sufentan|| Nano1ab IV CA Morph|ne
anent Sansfacnon
3.92
3.3S
3.2
3.4
3.6
3.8
4
4.2
Sufentan|| Nano1ab IV CA Morph|ne
Nurse Sansfacnon
<0.001
=0.017
=0.004 <0.001
IAP310 & IAP311 Primary Endpoint:
SPID-48 ITT Population
39
0
20
40
60
80
100
120
0.23 0.73 2 6 10 16 24 32 40 48
1
|
m
e
-
W
e
|
g
h
t
e
d

S

I
D

IA 310 - Abdom|na|
SufenLanll nano1ab lacebo
-20
0
20
40
60
80
100
0.23 0.73 2 6 10 16 24 32 40 48
1
|
m
e
-
W
e
|
g
h
t
e
d

S

I
D

1|me aher hrst study drug dos|ng
(hrs)
IA 311 - Crthoped|c
SufenLanll nano1ab lacebo
p=0.001
<0.001
AE Profile vs Meta Analysis of IV PCA opioid
40
Study
Sufentan|| -
310 & 311
|acebo -
310 & 311
Cashman & Do||n,
'94 &'9S (9S CI)
Abdom|na|:n|p:knee () 27:38:33
Nausea 46.9 36 26.8-37.6
Vom|nng 11.7 6.1 17.1-24.8
Consnpanon S.1 2.4
Cxygen Desaturanon 7.7 3 S.6-22
Itch|ng 6.8 0 10.7-17.S
Ur|nary ketennon 1.2 0 6.6-2S
Confus|ona| State 2.1 1.2
Sedanon]Somno|ence 2.3 0.6 4.6-6.4
IAP309: Rate of Oxygen Desaturation Events
41
19.7
12.4
9.6
30
20
16.1
0
S
10
1S
20
2S
30
3S

t
s

w
|
t
h

C
2

D
e
s
a
t

L
v
e
n
t
s

SufenLanll
Morphlne
C
2
<93 C
2
<94 C
2
<93
p=0.028
Conclusions
42
Subllngual sufenLanll provldes ldeal k prole for 8n dosed oplold
Plgh llpophlllclLy allows non-lv dellvery, rapld LranslL Lo braln
Subllngual depoL enables 90-mlnuLe re-doslng vs 40-mlnuLe for lv
no acuve meLabollLes, rapld L
1/2ke0
ellmlnaLes dose-sLacklng rlsk
SLrong SufenLanll nano1ab CA SysLem Cllnlcal role Lmerglng
LxcellenL acuLe paln conLrol, early paln conLrol superlor Lo lv morphlne
Auracuve AL prole wlLh low raLe of oxygen desaLurauon evenLs
Superlor auenL Sausfacuon and nurse Lase of Care Lo lv morphlne
uevlce ellmlnaLes programmlng errors, faclllLaLes pauenL ambulauon
Panel Q&A
ur 8lchard 8erkowlLz
ur Lugene vlscusl
ur amela almer
am Llndley, 8n
43
Formulary Adoption
Mlke A. 8oyal, Mu, !u, M8A
Chlef Cllnlcal Aalrs,
Acel8x harmaceuucals, lnc.
45
lrom lnvenLory conLrol Lo rauonal use
Lnsure LhaL safe and eecuve drugs are avallable
ldenufy preferred drugs and avold Lherapeuuc dupllcauon
CosL conLrol: aggresslve conLracung and conLrol mechanlsms
lormulary managemenL wlLh sLrlcL &1 conLrols
urug use pollcy maklng
urug use monlLorlng
Hospital Formularies and the Modern P&T Process
46
The Old Days: Formulary Review
New Request by any MD
Fill out application
Approved
Formulary Inclusion
harmacy open Lo see sales reps/MSLs
1urnaround ume: days Lo a few weeks
use o formulary slmple and frequenL
Lnd user Lralnlng could occur before
approval
Cost Focus has Shifted Power to Pharmacy in
P&T Process
47
AdvanLage Lo new producLs whlch sausfy unmeL needs or have
pharmacoeconomlc beneLs
Several physlclans may need Lo advocaLe for new addluon
rocess ls more dellberaLe
Amerlcan College of Cllnlcal harmacy
Resulting in Todays Multilayered Process
48
New Drug Requests by multiple
MD; Department Chiefs helpful
Fill out applications; write letters
Get on P&T schedule
Formal Pharmacy Review
Not Approved
To Med/Exec Cmte Review
Final
Approval
Formulary Inclusion
Decision by Med/Exec Cmte
Pharmacy Preparation of Monograph
Without Pharma input
Approved
Key Influencers of Speed of P&T Approvals
49
ChaL rooms Lo share lnfo abouL new producLs
CounLer-deLalllng
8esLrlcLed access Lo &1 members/process
Lack of publlshed acuve comparaLor and pharmacoeconomlc daLa
MandaLory walung perlods posL luA approval
erlodlc &1 schedullng wlLh llmlLed # of producLs revlewed
harmacy conLrol of presenLers aL &1 meeungs
uevlce analysls may requlre anoLher commluee lnpuL
Sufentanil NanoTab Formulary Expectations
50
lv CA cosLs and challenges already well undersLood
non-lnvaslve, pre-programmed CA SysLem auLomaucally auracuve
Acuve comparaLor daLa Lo currenL SLandard of Care wlLh comparable emcacy
expecLed by &1 Commluees ln research, buL exceedlng expecLauons are:
uemonsLrauon of superlorlLy Lo lv CA morphlne
lasLer onseL and reduced percenLage of oxygen desaLurauon evenLs
CosL as a facLor ls manageable
LxpecL comparable prlclng Lo currenL lv CA
ulerenuauon based on pauenL sausfacuon, cllnlcal beneLs, and
overall cosL reducuon expecLed Lo encourage adopuon
Cverall, expecL formulary adopuon Lo be rapld
Publication Strategy Supporting Formulary
Assessment
51
2013
creaLe awareness of lv CA llmlLauons and problems
beneLs of sufenLanll, especlally when glven subllngually
sophlsucauon and lnherenL conLrols of Lhe SysLem
posluve resulLs from Lrlals (posLer and saLelllLe presenLauons)
2014
shl Lo publlcauons ln pharmacy [ournals wlLh a focus on cosL
savlngs, pauenL sausfacuon, and poLenual reducuon ln error raLes
and ALs wlLh a swlLch from lv CA
2013
reLurn focus on posluve resulLs from Lhe SysLem
messaglng Lo end users
Medical Affairs Strategy
52
CoordlnaLe wlLh commerclal Lo opumlze reach/frequency and ldenufy
early LargeLs
locus on pharmacoeconomlc value wlLh pharmacy dlrecLors, lead wlLh 309
acuve comparaLor (lv CA) daLa ln uossler and presenLauons
use a blended Leam of harmus (for dlmculL &1s) and 8n LducaLors (for
educauon, asslsLance wlLh pull Lhrough) Lo sLarL early on
CaplLallze on lnvesugauonal slLes as cenLers of excellence" for reglonal
rlpple eecL - early posluve Lrlal experlence predlcLs &1 approval
locus phase 4 acuvlues on developlng besL pracuces" for speclc
surgerles LhaL lnclude Lhe SysLem as parL of mulumodal approaches
laclllLaLe developmenL of sLandlng orders
AsslsL pharmacy depLs ln MuL/uuL deslgns LhaL augmenL
pharmacoeconomlc daLa
Commercialization
8lchard klng
Chlef Lxecuuve Cmcer,
Acel8x harmaceuucals, lnc.
The Post-Operative Pain Market is Dynamic
1rends
o||nca|
Lconom|c
Soc|o|og|ca|
1echno|og|ca|
Macro Inuences
Length of Stay]Semng
1ypes of rocedures
a|n Management
Stakeho|ders
ke|mbursement and Cost
otenna| Dr|vers of Adopnon for Any roduct |n th|s Area

Cost-eecnveness (re|anve to current standard of care)
anent sansfacnon, |ead|ng to |nsntunona| focus on pa|n management
54
Source: 8oseua CuallLauve lnLervlews, lall 2011.
Pain Management Focus and Trends in US
55
Length of Stay
CpporLunlLy for producL LhaL helps Lo reduce lengLh of sLay ls hlgh
ush for shorLer lengLh of sLay lmplles paln belng pushed Lo home semng
rocedure M|x and Invas|veness
CpporLunlLy for producLs wlLh eecuve paln rellef for 6-23 hr posL-op sLay
Mu|nmoda| Ana|ges|a
CpporLunlLy for non-lnvaslve, pauenL-conLrolled analgesla dellvery as componenL
of oLherwlse xed doslng reglme
Lmergence of Insntunona| a|n 1eams
ln addluon Lo surgeons, supporL from anesLheslologlsLs/paln speclallsLs crlucal
auenLs emerglng as sLakeholder, as pauenL sausfacuon more lmporLanL
Cost
23-hour sLay supporL and cosL eecuveness key focl
Sources: 8oseua Mlnl-quanL Survey elded Lo 29 physlclans (13 hosplLallsLs and 14 anesLheslologlsLs) ln WlnLer 2011.
8oseua CuallLauve lnLervlews, lall 2011.
Introducing..
56
(sufentanil sublingual
microtablet system)
For use in hospitals only.
For use only with ZALVISO

Sufentanil sublingual microtablet system
N
D
C

X
X
X
X
-
Y
Y
Y
Y
-
P
P



L
O
T

N
O
.

X
X
X
X
X




E
X
P

D
A
T
E

D
D
M
M
Y
Y

P ONLY
CONTENTS cartridge
1 40*equals 22.5 mcg sufentanil citrate
For management of moderate to severe acute pain.
! " # $ % & ' ( ) *
(sufentanil sublingual
microtablet system)
15mcg* sufentanil/microtablets
376 170 431
1 inch
BLACK
(sufentanil sublingual
microtablet system)
CONTROLLER
(sufentanil sublingual
microtablet system)
CONTROLLER
1 inch
(sufentanil sublingual
microtablet system)
CONTROLLER
(sufentanil sublingual
microtablet system)
CONTROLLER
Pouched Cartridge Label
Label on Controller Packaging
Product Logo
Regulatory Pathways
57
NDA athway
SubmlL nuA (C3 2013)
luA llles nuA (C4 2013)
uAAA ulvlslon revlew
CuL8 Leads (urug)
Cu8P ConsulLauon (uevlce)
Approval (C3 2014) for slngle label
for use of drug and devlce for
moderaLe Lo severe acuLe paln
managemenL ln hosplLal semng
no AdComm LxpecLed (PosplLal use
producL, noL Lo go home)
MAA athway
Acel8x Lo deLermlne CenLral vs
MuLual 8ecognluon aLhway
MAA submlsslon wlll be for drug
producL (C2 2014)
uevlce wlll be presenLed Lo noued
8ody Lo pursue CL mark (C2 2014)
Approval (C2 2013) for drug producL
and CL mark for devlce granLed
Acel8x can LranslaLe Cul / llu
languages Lo Lu speclc
requlremenLs
US Surgical Procedures Evolving Settings
58
Strateg|c Importance

ost-operanve Length of Stay
lnapproprlaLe
auenL 1ypes
ApproprlaLe auenL 1ypes (# rocedures wlLh ModeraLe Lo Severe
aln)
6-12 hours 23 hours 1-2 days 2+ days
1
r
e
a
t
m
e
n
t

S
e
m
n
g

lnpauenL
osL-op
Surglcal
rocedures
(31,680k)
C
o
g
n
l
u
v
e

o
r

p
h
y
s
l
c
a
l

l
m
p
a
l
r
m
e
n
L

L
h
a
L

p
r
e
v
e
n
L
s

p
a
u
e
n
L
s

f
r
o
m

u
s
l
n
g

a

p
a
u
e
n
L
-
c
o
n
L
r
o
l
l
e
d

d
e
v
l
c
e

Low
(1,679k)
Medlum/Plgh
(3,071)
Plgh
(8,047)
PosplLal
AmbulaLory
Surgery
(PCu)
(24,890k)
Low
(933k)
Medlum
(930k)
n/A n/A
ASC
(18,813k)
Low
(1,367k)
Low
(212k)
n/A n/A
Low
Cpportun|ty
Plgh
CpporLunlLy
Sources: 8oseua Mlnl-quanL Survey elded Lo 29 physlclans (13 hosplLallsLs and 14 anesLheslologlsLs) ln WlnLer 2011.
Moderate-to-Severe Pain in US Hospital Settings
59
nosp|ta| |n-panent, moderate-to-severe acute pa|n, post-operanve
12M procedures per annum, alvlso poLenually usable ln 93 cases
nosp|ta| |n-panent, moderate-to-severe acute pa|n, not post-operanve
7.4M pauenLs per annum, alvlso poLenually usable 66-80 cases
lndlcauon llkely Lo cover Lhls pauenL populauon
lv push oplold medlcauon ls sLandard for acuLe non-posL-operauve paln, noL lv CA
hyslclans reporLed alvlso may be supplemenLary Lo lv push, raLher Lhan a replacemenL
nosp|ta| am||ated hosp|ce, moderate-to-severe acute pa|n
LsL. 300k pauenLs per annum, alvlso usable ln 40 cases
lndlcauon llkely Lo cover Lhls pauenL populauon
A8x-01 ls poLenual replacemenL for llquld morphlne, measured by nurse when dosed
Sources: 8oseua Mlnl-quanL Survey elded Lo 29 physlclans (13 hosplLallsLs and 14 anesLheslologlsLs) ln WlnLer 2011.
8oseua CuallLauve lnLervlews, lall 2011.
8.3
9.2
8.3
7.9
0.0
1.0
2.0
3.0
4.0
3.0
6.0
7.0
8.0
9.0
10.0
Ortho OBGYN Gen Surgeon Anes
Auracnveness kanng of Akk-01
2
Crtho C8GN Gen Surgeon Anesth
8.8
8.1
7.8
7.8
8.8
7.4
0.0
1.0
2.0
3.0
4.0
3.0
6.0
7.0
8.0
9.0
10.0
Gastro OBGYN Gen Surgeon
Auracnveness kanng of Akk-01
1
Gastro Crtho C8GN Card|o Gen Surg Anesth
Physician Reaction to Acute Pain Product Profile
60
uS hyslclans
1
Lu hyslclans
2
1. 8oseua: Mlnl-quanL Survey of 29 uS physlclans (13 hosplLallsLs and 14 anesLheslologlsLs) ln WlnLer 2011.
2: 8oseua: CuallLauve lnLervlews wlLh 33 Lu physlclans (9 anesLheusLs/22 surgeons/4 kCLs) ln Sprlng 2013
Physician Reaction to Product Profile

61
1bls ls o blq lmptovemeot becoose tbe
poueot coo qet oot of beJ polcket.
- C8/C?n
1
lts o 10 lf lm osloq lcAs ooJ woot to
swltcb. lts oo 8 becoose lts sull o ootcouc
meJlcouoo. lo oo lJeol wotlJ, lm lookloq
fot sometbloq otbet tboo o ootcouc. -
CrLhopedlc Surgeon
1
lt qlves o poueot posslblllty to move
otoooJ, be ot sbe Joesot bove to be ueJ
op to tbelt beJ.
- AnesLheusL, oland
2
lts vety outocuve. Aoytbloq tbot
woolJ qlve poueots powet to coottol
tbelt polo, ooJ less wotk fot ootses ls
blqbly outocuve. AnesLheslologlsL
1

5ofeotooll ls tbe petfect Jtoq, l ose
lt oll tbe ume. - CardloLhoraclc
Surgeon
1
1bete ote mooy oJvootoqes bete
combloeJ. oo wlll bove o qteot
compllooce bete. l tblok tbot
poueots wlll occept lt vety well, l
qoess mocb mote os tbe lv lcA.
- CrLhopedlc Surgeon, Cermany
2
1. 8oseua: Mlnl-quanL Survey of 29 uS physlclans (13 hosplLallsLs and 14 anesLheslologlsLs) ln WlnLer 2011.
2: 8oseua: CuallLauve lnLervlews wlLh 33 Lu physlclans (9 anesLheusLs/22 surgeons/4 kCLs) ln Sprlng 2013
62
Segmentation
All physlclans lnLervlewed have sLrong lnLeresL ln alvlso
llrsL segmenLauon lLer wlll be formulary approval
MarkeL segmenLauon wlll focus on llkely sequence of adopuon
CrLhopedlc surgerles rsL (1.3M per annum
1
)
23-hour sLay surgerles also early (4M p.a
2
)
Cl and C?n surgerles, supporLed by abdomlnal daLa seL (4.3M p.a
1
)
C1 (1M p.a
1
), C8 (2M p.a
1
), fuslon/fracLure surgerles (1M p.a
1
) as
famlllarlLy wlLh alvlso grows
8urns, oLher acuLe ln-hosplLal paln (7M p.a
2
) opporLunlsucally
1. nauonal PosplLal ulscharge Survey, 2010
2. 8oseua Mlnl-quanL Survey elded Lo 29 physlclans (13 hosplLallsLs and 14 anesLheslologlsLs) ln WlnLer 2011.
Building Commercial Infrastructure
63
P2 2013: Markeung Leam esLabllshed (2 Senlor, 2 Mld-managemenL)
P1 2014: MSL Leam esLabllshed / deployed (6-8 MSLs), Sales SLrucLure
llnallzed
C3 2014: Sales ManagemenL 1eam Lmployed (6-8 8eglonal ulrecLors)
C4 2014: MSL's, Sales ManagemenL, ConLracung Leam push for lormulary
8evlew and Approval
C1 2013: Sales 8eps deployed (up Lo 63, dependenL on formulary
adopuons), roducL Sale lnluaLed, hase 3 publlcauons appearlng

Pricing and Pharmacoeconomics
64
0
30
100
130
200
230
300
330
Lo lv CA Pl lv CA alvlso
8ange C
o
s
t

p
e
r

p
a
n
e
n
t

f
o
r

2

d
a
y
s

(
5
)

urug 1ublng uevlce
harmacoeconomlc value creaLed by:
Lllmlnauon of programmlng errors
Lllmlnauon of excess doslng due pump fallure
Lllmlnauon of lv slLe lnfecuon rlsk for lv CA
Larller and easler ambulauon poLenually
acceleraLes hosplLal release
Larly onseL paln rellef resulLs ln lower oplold
doslng, less overshooL
8educed SALs (parucularly oxygen
desaLurauon) resulLs ln lower lCu vlslLs/cosLs
Lnhanced auenL Sausfacuon resulLs ln
lmproved CMS relmbursemenL, hlgher
hosplLal markeL share
Cost of Managing IV PCA - 2 days of therapy
Cost Per Patient
Staff Time and Labor
1,2,3,4
$85.82
Medical Cost of Adverse Events Caused by IV PCA Errors
5,6
$50.05
Administrative Costs due to Adverse Events Caused by IV PCA Errors
7,8
$96.85
TOTALS $230
Pharmacoeconomics
Literature identifies cost of managing IV PCA
uoes noL accounL for:
oLenual beneL of early ambulauon resulung ln hlgher bed Lurnover
lmproved auenL Sausfacuon lmpacL on relmbursemenL or pauenL volume
CosL of pump malnLenance ln 8lomedlcal Lnglneerlng
65
1. Average of nurses ume esumaLes by Lvans eL al 2007, 8onneL eL al 2009, Mordln eL al 2007 and Chonlere eL al 1998
2. LxperL oplnlon by Alex Macarlo Mu from dlscusslons wlLh PosplLal harmaclsLs
3. Medlan 8ase Salary + 8onus + 8eneLs obLalned from SalaryCenLer.com, P8 Salary Wlzard
4. A Comparlson of nurse 1asks and 1lme assoclaLed wlLh Lwo pauenL-conLrolled analgesla modallues uslng delphl panels, Lvans C, eL al aln Man nurs 2007, 8,2, 86-93
3. Melssner 8, eL al. Posp harm 2009,44:312-324.
6. Campbell Alllance MarkeL 8esearch SLudy - 2003 esumaLe of uS pauenLs LhaL use lv CA umps
7. Source.: 1oby Cordon Sc u - LxperL oplnlon lnLervlews and llLeraLure revlew - uec 2009
8. 8lomedLcon Analysls of Pankln eL al 2007 reporLs of lv CA Lrrors
Conclusion
66
SLrong alvlso Cllnlcal role Lmerglng
LxcellenL acuLe paln conLrol, early paln conLrol superlor Lo lv morphlne
Auracuve AL prole wlLh low raLe of oxygen desaLurauon evenLs
Superlor auenL Sausfacuon and nurse Lase of Care Lo lv morphlne
uevlce ellmlnaLes programmlng errors, faclllLaLes pauenL ambulauon
Worklng Lowards C3 2013 nuA Submlsslon
Commenclng Commerclal reparauon
lans ln hand Lo bulld commerclal lnfrasLrucLure
SlgnlcanL amounL of markeL undersLandlng work compleLed
uenluve posluonlng and brandlng work underway
Closing Q&A
Mlke 8oyal
8lchard klng
am almer
67