Download Corporate Presentation

Company Update
May 2017
Forward-Looking Statements
This presentation contains "forward-looking statements" as defined by the Private Securities Litigation Reform Act
of 1995. We caution investors that forward-looking statements are based on management’s expectations and
assumptions as of the date of this presentation, and involve substantial risks and uncertainties that could cause our
clinical development programs, future results, performance or achievements to differ significantly from those
expressed or implied by the forward-looking statements. These risks and uncertainties include, but are not limited
to, those associated with: the potential market opportunity for SUSTOL®, CINVANTI™ and HTX-011, timing of
potential generic forms of palonosetron and the potential impact on sales of SUSTOL, the timing and outcome of
the End of Phase 2 meeting with the FDA for HTX-011, the timing of acceptance of the NDA for CINVANTI™, the
timing of the NDA filing for HTX-011, the timing of initiating Phase 3 studies for HTX-011, the projected sufficiency
of our capital position for future periods, our ability to repay any indebtedness, the progress in the research and
development of HTX-011 and our other programs, including the timing of preclinical, clinical, and manufacturing
activities, safety and efficacy results from our studies, and other risks and uncertainties identified in the Company's
filings with the Securities and Exchange Commission. Forward-looking statements reflect our analysis only on their
stated date, and we take no obligation to update or revise these statements except as may be required by law.
2
Status of Product Portfolio
CINV
Pain
Preclinical
Clinical
NDA
Approved
SUSTOL®
(granisetron) extendedrelease injection
CINVANTI™ (HTX019) aprepitant for
Now Approved by U.S. Food and Drug Administration
IV NK1 for CINV Prevention
PDUFA Date of November 12, 2017
injection
HTX-011 bupivacaine +
meloxicam ER
Local Administration
HTX-011 bupivacaine +
meloxicam ER
Nerve Block
3
Post-Op Pain in Local Administration
Post-Op Pain in Nerve
Block
Data from four positive Phase 2
studies in multiple surgical models
Phase 2 program in nerve block initiated
CINV PROGRAMS:
SUSTOL®
CINVANTI™ (aprepitant for injection)
SUSTOL® Performance
Launch Update
Date of first
commercial sale:
October 11, 2016
143 practices
have ordered
SUSTOL (91%
increase vs. Q4)
representing ~35%
of the 1.4M
targeted Aloxi
units
5
Q1 2017
performance:
~10,300 units
sold, $495 WAC,
~$3.6M net sales
(184% increase
from Q4 2016)
Positive payer
coverage: all 12
Medicare MACs
covering (44M lives)
and commercial
plans representing
139M
Market Research Insights
(Conducted eight weeks post-launch
and updated in March 2017)
•
Practices go through a “buying process”
to evaluate adoption of new drugs which
may last several quarters
–
Practices assess coverage, time to payment,
reimbursement rate in addition to clinical
experience and impact to practice operations
•
HCPs who have begun SUSTOL trial, report
positive experiences both clinically and
operationally
•
Most RNs with SUSTOL experience are
satisfied and have been able to
administer it successfully
46 Percent of MDs Evaluating SUSTOL® as Potential
Branded Agent of Choice (~6-9 Month Timeline)
Degree of MD Experience With SUSTOL
Practice’s Experience With SUSTOL Trial
100%
17%
I and other MDs in my
practice have used SUSTOL
23%
I have used SUSTOL but
other MDs have not
11%
I have not used SUSTOL
but other MDs have
5%
We will try SUSTOL and
are operationalizing it
80%
60%
40%
20%
7%
13%
31%
Safety 8%
38%
31%
Preparation and
administration 8%
46%
23%
15%
100%
6%
1-3 months
80%
27%
4-6 months
60%
13%
> 6 months
10%
SUSTOL will probably
be our brand of choice
but not sure when
39%
Not yet sure if
SUSTOL will become
our brand of choice
40%
SUSTOL is under
consideration
We have decided not to
use SUSTOL
No discussions regarding
SUSTOL to date
Which of the following best describes you / your
practice? Please select one.
- Putnam Physician Survey Nov 2016 (N=85)
6
38%
Payer coverage 8% 31%
23%
0%
Efficacy 8%
Timing for SUSTOL To Be Brand of Choice
Impact to
practice 15% 31% 8%
operations
Payer
reimbursement 8% 23% 8%
rate / time
Extremely
positive (6-7)
20%
Positive (5)
Negative (3)
Extremely
Negative (1-2)
What has been the experience with SUSTOL use in
your practice? Please rate 1-7.
- Putnam Practice Manager Survey Nov 2016 (N=40)
0%
5%
SUSTOL won’t be our
brand of choice
In what timeframe do you expect SUSTOL to
become the practice’s branded 5-HT3 of choice?
- Putnam Physician Survey Nov 2016 (N=85)
Most RNs with SUSTOL® Experience are Satisfied,
Have Administered Successfully
RN Overall Experience Administering SUSTOL
100%
RN View of SUSTOL vs. other oncology SC products
100%
14%
80%
60%
14%
SUSTOL is similar to other
subcutaneous injections in
oncology
81%
SUSTOL prep and admin are
unique, but we have been able
to administer it successfully
80%
Very satisfied (6-7)
57%
60%
Satisfied (5)
Neither satisfied nor dissatisfied (4)
Dissatisfied (3)
40%
Very dissatisfied(1-2)
20%
0%
24%
20%
5%
Please rate your overall experience administering SUSTOL
to patients. Please rate 1-7.
- Putnam Nurse Survey Nov 2016 (N=85, n=21)
7
40%
0%
5%
We have had significant
difficulty administering SUSTOL
Which of the following best describes your experience
preparing and administering SUSTOL to patients?
- Putnam Nurse Survey Nov 2016 (N=85, n=21)
CINV Prophylaxis Requires Two Complimentary
Mechanisms of Action
• EMEND IV® is currently the only
intravenous NK1 receptor
antagonist on the US market and
has >90% of the total NK1 market
• Infusion reactions (predominately
infusion site pain) and
hypersensitivity reactions
observed with EMEND IV® are
believed to be caused by the
surfactant polysorbate 80 in the
product
CINVANTI™ (HTX-019) (aprepitant for injection) is an investigational proprietary, surfactant-free intravenous
formulation of the NK1 receptor antagonist aprepitant
8
CINVANTI™ (HTX-019) for CINV
PDUFA Date of November 12, 2017
BE Study #104 Safety
Results
• CINVANTI™ is a proprietary,
surfactant-free intravenous (IV)
formulation of the NK1 receptor
antagonist aprepitant
– Bioequivalency study comparing
HTX-019 to EMEND IV®
(fosaprepitant) completed:
• Bioequivalence achieved for AUC
• Significantly fewer adverse events
with HTX-019
• Direct competitor to the >1 million units
of EMEND IV® used annually
• US 15/083,071 received a notice of
allowance and will provide exclusivity
to March 2036
9
HTX-019
EMEND IV
SAFETY
Events
Patients
Events
Patients
Total AEs
27
21%
54
28%
AEs considered related
18
15%
52
28%
SAEs
0
-
0
-
Moderate AEs
0
-
6
2%
AEs leading to
discontinuations
0
-
2
2%
Final dataset
100 subjects received HTX-019 and EMEND IV® in standard cross-over design
Conclusion:
HTX-019 was better tolerated than EMEND IV®, with 65%
fewer AEs at least possibly related to treatment, no AEs of
greater than mild severity, no premature discontinuations
2017 CINV Franchise Outlook
Heron expects steady but measured growth in
SUSTOL® trial and adoption
• Continue to anticipate $15M - $25M in SUSTOL net
sales in 2017
CINVANTI™ (HTX-019) program advancing
• PDUFA date November 12, 2017, launch Q1 2018
• If approved, Heron would be the first company to
address both mechanisms of action for the prophylaxis
of CINV with injectable products
• Offers strong strategic and operational fit with existing
commercial organization
10
Post-Operative Pain Program
HTX-011: Proprietary Extended-Release
Combination of Bupivacaine +
Meloxicam
Market Is Large and Local Anesthetic Use Is Common, but
Long-Acting Anesthetics Have Not Fulfilled the Promise
Procedures Requiring PostOperative Pain Relief, 2015-20201
Number of Procedures (Millions)
35
30
28
29
30
31
31
Local Anesthetic Usage Across
Key Surgeries, 20151*
3%
32
long-acting
anesthetics
25
20
74%
15
Generic local
anesthetics
10
Key Limiters of Current LongActing Anesthetics Penetration
• Perceived inability to achieve
marketed duration of efficacy2
• No large scale studies have shown
superiority versus bupivacaine
solution
23%
No local
anesthetics
5
• HCPs not persuaded that
incremental efficacy is worth the
cost
• Formulary access restrictions2
0
2015
2016
2017
2018
2019
2020
Procedure growth driven by
aging population and more
active seniors
‒ Many institutions restrict
usage to certain departments,
procedures, or do not have a
long-acting local anesthetic on
formulary
‒ Very low penetration in ASC
and office settings1
Sources: 1- DRG claims analysis (2015), DRG Post-Operative Pain Pharmacor; 2- DRG physician and P&T member interviews
(2016; n=106); *Based on analysis of current post-operative pain management across 40 target procedures (~28M procedures)
12
HTX-011 Has the Potential to Transform PostOperative Pain Management
Product Attribute
13
Generic
Long-Acting
Local
Local
Anesthetics Anesthetics
HTX-011
Extended-release formulation
No
Yes
Yes
Synergistic MOA potentiates local
anesthetic efficacy by reducing
inflammation
No
No
Yes
Consistent 72 hour efficacy
No
No
Yes
Head-to-head superiority vs. bupivacaine
N/A
No
Yes
Applicable in large and small procedures
without admixture with bupivacaine
solution
N/A
No
Yes
Easy to learn, flexible administration with
potential safety advantages
No
No
Yes
Source: 1 – DRG physician and P&T member interviews (2016; n=106)
“I would love a product that is superior to Exparel® in that it
actually provided 72 hours of pain relief; this would
reduce rates of nausea, vomiting, and constipation and help
us discharge patients sooner.”
– General Surgeon1
“We’re looking for an injectable lasting 72 hours; this would
address the critical, most painful window of time
following surgery and could potentially eliminate the need
for additional pain treatments.”
– Plastic Surgeon1
“If a local anesthetic could provide significant pain relief for
48-72 hours, patients could be up and moving more quickly
and have significant reduction in length of stay as well
as opioid use post-operatively.”
– Orthopedic Surgeon1
“If we could numb the surgical area for three days,
we would have a lot of patient satisfaction and if a
patient is satisfied, they’re not going to be calling us for the
next three days.
– Anesthesiologist1
ACUTE PAIN AFTER SURGERY IS AN
IMPORTANT COMPONENT OF CHRONIC
OPIOID ABUSE
14
Risk of Chronic Opioid Use After Selected Surgeries
Adjusted Odds Ratio for Chronic Opioid Use
0
1
2
3
4
Total Knee Arthroplasty
6
5.1
Open Cholecystectomy
3.6
Simple Mastectomy
2.6
Total Hip Arthroplasty
2.5
Open Appendectomy
1.7
Laproscopic Cholecystectomy
Cesarean Delivery
5
1.6
1.3
Based on data from 641,941 opioid-naïve surgical patients compared to 18 million opioid-naïve non-surgical patients
(Sun, et al. JAMA Internal Med 2016; 176(9):1286-1293)
In Addition to Potential Addiction, Opioids Increase Healthcare
Costs Due to a High Rate of Side-Effects
Cost of Opioid-Related Adverse Drug Events1,2
Moderate to Severe OpioidInduced ADE
Cost per ADE Events in
2013 $
Ileus
$6,141
Pruritus
$502
Urinary Retention
$1,867
Respiratory Depression
$1,504
PONV
$1,225
Mental Status Change
$2,263
*All AE costs derived from Oderda 2003 with exception of ileus which is from Simons et al.
†Calculated from the half-year (January-June) data of the "Inpatient Hospital Services" component of the medical consumer price index in 1999-2013.
Source: US Bureau of Labor Statistics.
16
1. Oderda GM, Evans RS, Lloyd J, et al. Cost of opioid-related adverse drug events in surgical patients. J Pain Symptom Manage. 2003;25:276-283.
2. Simons R, Kim M, Chow W. Retrospective analyses of adverse events and economic costs [abstract taken from Reg Anesth Pain Med. 2009;PS3:17].
Reducing Pain Signals at the Site of the Incision
May Decrease the Development of Chronic Pain
Activing on opiate receptors in the brain, opioids can reduce the sensation
of pain, but do not block transmission of the pain signals. Occasionally, the
affected nerves become hyper-stimulated resulting in chronic pain.
17
HTX-011 directly blocks transmission of the pain signal,
potentially reducing the chance of chronic pain
Biochronomer® Bupivacaine Produced Significant
Reductions in Pain in Preclinical Models1
Pig Post-Operative Pain Model
Higher bar =
greater analgesia
18
Percentage of Maximal Force (60 gm) Tolerated
by Animal
Saline Control
Biochronomer Bupivacaine
Bupivacaine Liposome Injectable Suspension (2)
100.0
90.0
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
0.0
0
1. Post-operative pain model in pigs from Castle et al, 2013 EPJ
2. Human dose of bupivacaine liposome with 40% smaller incision
(n=4 pigs)
1
3
5
HOURS
24
48
72
96
120
Inflammation Plays a Key Role in Pain Management
(Current local anesthetics do not address this)
BUPH+
BUPN + H+
• Inflammation produces
an acidic environment
Outside membrane
Nerve Cell
Membrane
Inside membrane
BUPH+
• Shifts the balance to
ionized form, which is
unable to penetrate
nerve cell membrane
BUPN + H+
• Acidic environment associated with inflammation results in far less drug penetrating the nerve
membrane and reduced anesthetic effects1,2
• Bupivacaine is very sensitive to reduced pH
• Addition of meloxicam is designed to help reduce local inflammation and allow bupivacaine to work better in
the first several days after surgery
19
1. Ueno, et al. J of Inflammation Research 1:41-48 2008.
2. Local anesthetic nerve penetration model adapted from Becker and Reed, Anesth Prog 53:98–109 2006
Unique Combination of Bupivacaine & Meloxicam Produced
Complete Analgesia1
Higher bar =
Greater analgesia
Percentage of Maximal Force (60 gm) Tolerated
Pig Post-Operative Pain Model
Saline Control
Biochronomer Bupivacaine
Bupivacaine Liposome Injectable Suspension (2)
Biochronomer Bupivacaine + Meloxicam 6 Day Release
100.0
90.0
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
0.0
0
1
1. Post-operative pain model in pigs from Castle et al, 2013 EPJ
2. Human dose of bupivacaine liposome with 40% smaller incision
20
(n=4 pigs in each arm)
3
5
24
Hours
48
72
96
120
>72 Hour Duration of Action Seen as “Ideal”
Ideal Duration of Efficacy for LongActing Local Anesthetic
5 days
4%
Minimally Acceptable Duration of
Efficacy for Long-Acting Local
Anesthetic
>5 days
2%
4 days
9%
≤ 24
hours
12%
72 hours
11%
≤ 24
hours
44%
48 hours
27%
72 hours
46%
Source: Decision Resources Post-Operative Pain Physician Research
Initiative 2014 (N=30 qualitative interviews; N=184 quantitative survey)
21
48 hours
45%
HTX-011’s Unique Combination of Bupivacaine & Meloxicam
Produced Marked Analgesia Through 72 Hours1
Higher bar =
Greater analgesia
Percentage of Maximal Force (60 gm) Tolerated
Pig Post-Operative Pain Model
Saline Control
Biochronomer Bupivacaine
HTX-011
Bupivacaine Liposome Injectable Suspension (2)
Biochronomer Meloxicam
100.0
90.0
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
0.0
0
1
3
1. Post-operative pain model in pigs from Castle et al, 2013 EPJ
2. Human dose of bupivacaine liposome with 40% smaller incision
22
(n=4 pigs in each arm)
5 Hours 24
48
72
96
120
Activity of HTX-011 Cannot Be Replicated By Systemic
Administration of Meloxicam Along With ER Bupivacaine
Pig Post-Operative Pain Model
Saline Placebo
HTX-011 (Bupivacaine + Meloxicam)
Biochronomer Bupivacaine + Injectable Meloxicam*
100.0
90.0
Higher bar =
Greater analgesia
Percent of Maximum Force
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
0.0
0
*Same dose of meloxicam as in HTX-011 administered SQ
Post-operative pain model in pigs from Castle et al, 2013 EPJ
23
(n=4 pigs in each arm)
1
3
5
24
Hours
48
72
96
120
HTX-011 Clinical Experience Shows It Has the
Potential to Transform Post-Operative Pain Control
• Phase 2 data has demonstrated:
– Unprecedented statistically significant reductions in both pain and opioid use lasting up to
96 hours after surgery
– Utility in both small procedures (bunion), medium size procedures (hernia), and one of the
largest incisions (abdominoplasty)
– Up to 10-fold synergy of HTX-011 compared to extended-release bupivacaine and >20-fold
greater pain benefit through 72 hours than bupivacaine solution
• During Phase 2 we optimized all the attributes of HTX-011 needed to have a
successful Phase 3:
√ the formulation, where the product has shown the versatility to be used in a wide variety of
surgical procedures
√ the dose, where the lowest highly effective dose has been chosen for Phase 3
√ the route of administration, where instillation, a faster, easier and potentially safer route of
administration was demonstrated to be equally effective to standard injections
24
HTX-011 STUDY 203:
Phase 2 Abdominoplasty
25
Study 203: Abdominoplasty Study
Design & Demographics
HTX-011 200mg Inj
HTX-011 400mg Inj
HTX-011 600mg Inj
Saline Placebo Injection
HTX-011 400 mg
significantly reduced
pain (SPI0-24
p=0.012); no
additional benefit
seen with 600mg
Characteristic
Parameter
Saline
Placebo
HTX-011
400mg
Age (Years)
n
21
20
Mean
43.0
41.4
Minimum
29
27
Maximum
58
60
Male
0 (0)
0 (0)
Female
21 (100)
20 (100)
Caucasian
16 (76.2)
15 (75.0)
African
American
5 (23.8)
5 (25.0)
Asian
0 (0)
0 (0)
Other
0 (0)
0 (0)
Hispanic
5 (23.8)
7 (35.0)
Not Hispanic
16 (76.2)
13 (65.0)
Gender n (%)
Race n (%)
HTX-011 400mg Instillation*
Saline Placebo Instillation*
*Drug products predominantly instilled with a small
number of injections around the plication
26
Data from
instillation, the
optimal route of
administration,
presented
Ethnicity n (%)
HTX-011: Instillation Faster, Easier and Potentially Safer
Compared to injection, instillation
into the incision site is:
• Easier to administer and less invasive,
avoiding up to 50 or more injections
into the skin with large operations
• Safer, reducing the risk of venous
puncture
27
Study 203: Mean Pain Intensity Scores*
HTX-011 Is Significantly Better Than Placebo Through 96 Hours After
Abdominoplasty
HTX-011 400mg Instillation (n=20)
9
SPI48-72
p=0.038
SPI24-48
p=0.007
8
Saline Placebo (n=21)
• Results confirm
that HTX-011
can be
successfully
used in even the
largest
incisions
SPI72-96
p=0.016
Mean Pain Index
7
SPI0-72 would likely
be the Phase 3
endpoint
6
5
4
• 53 patients an
arm should be
sufficient to
achieve p<0.05
for SPI0-24
3
2
SPI0-24
p=0.086
1
SPI0-48
p=0.018
SPI0-72
p=0.016
SPI0-96
p=0.010
0
0
6
12
18
24
30
36
42
48
54
60
66
72
Hours
*LOCF method used to account for missing data, no adjustment for use of rescue medications
28
78
84
90
96
Study 203: HTX-011 Significantly Reduces Opioid Use
29
Mean Opioid Rescue
Over Time
Placebo (P)
(n=21)
HTX-011
400 mg
(n=20)
0 – 24 hours
25.9mg
16.1mg
p=0.014
0 – 48 hours
40.8mg
27.2mg
p=0.021
0 – 72 hours
51.3mg
32.7mg
p=0.011
0 – 96 hours
52.9mg
33.2mg
p=0.011
HTX-011
produced
significant
reductions in
opioid rescue
medication
through 96
hours after
abdominoplasty
Study 203: Treatment-Emergent Related Adverse
Reactions for All Cohorts*
Preferred Term
Any Adverse Event
Saline Placebo
(n=84)
25.0%
HTX-011
(n=68)
25.0%
Nausea
7.1%
7.4%
Vomiting
1.2%
2.9%
Headache
3.6%
7.4%
Dizziness
3.6%
0
Hypoesthesia
1.2%
2.9%
Wound dehiscence
2.4%
1.5%
Pruritus
8.3%
2.9%
Hypotension
2.4%
4.4%
Decreased appetite
0
2.9%
*Adverse events considered at least possibly related with an incidence of >2%
30
HTX-011 STUDY 208:
Phase 2 Bunionectomy
31
Study 208: Bunionectomy Study Design &
Demographics
HTX-011 200mg
HTX-011 120mg
Characteristic
Age (Years)
HTX-011 60mg
Bupivacaine 50mg
Gender n (%)
Parameter
Saline
Bupivacaine
HTX-011
200mg
HTX-011
120mg
HTX-011
60mg
n
86
15
30
56
35
Mean
49.9
52.7
52
49.6
54.2
Minimum
21
36
20
24
24
Maximum
76
84
71
75
76
Male
12 (14.0)
2 (13.3)
5 (16.7))
11 (19.6)
4 (11.4)
Female
74 (86.0)
13 (86.7)
25 (83.3)
45 (80.4)
31 (88.6)
Caucasian
50 (58.1)
8 (53.3)
24 (80.0)
38 (67.9)
21(60.0)
African
American
30 (34.9)
6 (40.0)
4 (13.3)
17 (30.4)
13 (37.1)
Other
6 (7.0)
1 (6.7)
2 (6.7)
1 (1.8)
1 (2.9)
Hispanic
21 (24.4)
2 (13.3)
5 (16.7)
18 (32.1)
7 (20.0)
Not Hispanic
65 (75.6)
13 (86.7)
25 (83.3)
38 (67.9)
28 (80.0)
Saline Placebo
Race n (%)
HTX-002 120mg
HTX-009 120mg
Ethnicity n (%)
HTX-011 30mg on-going
Open wound and closed wound injections combined
32
Study 208: Mean Pain Intensity Scores*
HTX-011 Is Significantly Better Than Placebo For All Doses Tested
8
SPI24-48
200mg v B: p=0.0025
120mg v B: p=0.0169
60mg v B: p=0.170
7
Mean Pain Intensity
6
5
4
3
2
1
0
0
SPI0-24
200mg v P: p<0.0001
6
18
24
120mg
v 12
P: p<0.0001
60mg v P: p<0.0001
HTX-011 200mg
33
SPI0-72
would likely
be the
Phase 3
endpoint
SPI0-48
200mg v P: p<0.0001
120mg v P: p<0.0001
60mg v P: p=0.0063
30
36
HTX-011 120mg
42
SPI0-72
200mg v P: p<0.0001
120mg v P: p=0.0009
60mg v P: p=0.0353
48
54
60
66
SPI0-96
200mg v P: p<0.0001
120mg v P: p=0.0018
60mg v P: p=0.061
72
78
84
90
Hours
HTX-011 60mg
Bupivacaine 50mg
*LOCF method used to account for missing data, no adjustment for use of rescue medications
Saline Placebo
96
Study 208: Mean Pain Intensity Scores*
HTX-011 Is Significantly Better Than Bupivacaine For All Doses Tested
SPI24-48
200mg v P: p=0.0029
120mg v P: p=0.0201
60mg v P: p=0.127
8
7
60mg of
bupivacaine
combined with
meloxicam in
HTX-011 is
significantly
better than
50mg of
bupivacaine
solution
through 48
hours
Mean Pain Intensity
6
5
4
3
SPI0-48
SPI0-96
SPI0-72
200mg v B: p<0.0001
120mg v B: p=0.0009 200mg v B: p=0.0001 200mg v B: p=0.002
60mg v B: p=0.0206 120mg v B: p=0.0103 120mg v B: p=0.034
60mg v B: p=0.0849 60mg v B: p=0.196
2
1
0
SPI0-24
200mg
v B:
p<0.0001
0
6
12
18
24
120mg v B: p=0.0002
60mg v B: p=0.0031
HTX-011 200mg
30
36
HTX-011 120mg
42
48
54
60
66
78
84
90
Hours
HTX-011 60mg
Bupivacaine 50mg
*LOCF method used to account for missing data, no adjustment for use of rescue medications
34
72
Saline Placebo
96
Bupivacaine 50 mg (n=25)
26-fold Greater
Reduction in Pain
100
80
60
40
20
p=0.002
p=0.002
p=0.017
0
0 - 24 hr
35
HTX-011 60 mg (n=52)
120
AUC LSMD(−) vs Placebo
Greater Pain Reduction vs Placebo
HTX-011 60 mg Produces 26-Fold Greater Reduction in
Pain Compared to Bupivacaine 50 mg Through 72 Hours
0 - 48 hr
*p-values are from ANOVA using AUC0-72 of Pain Intensity with wWOCF for HTX-011 vs bupivacaine
0 - 72 hr
Study 208: HTX-011 Significantly Reduces Opioid Use
Mean Opioid
Rescue Over
Time
0 – 24 hours
0 – 48 hours
0 – 72 hours
0 – 96 hours
36
Placebo (P)
(n=86)
16.5mg
26.6mg
33.2mg
33.8mg
Bupivacaine
Solution (B)
(n=15)
HTX-011
120 mg
(n=56)
HTX-011
60 mg
(n=35)
16.3mg
8.0mg
p<0.0001 v P
p=0.0008 v B
8.2mg
p<0.0001 v P
p=0.002 v B
28.6mg
17.8mg
p=0.0008 v P
p=0.0117 v B
15.2mg
p=0.0009 v P
p=0.0103 v B
35.8mg
23.8mg
p=0.0122 v P
p=0.0457 v B
20.5mg
p=0.0053 v P
p=0.0226 v B
35.8mg
24.6mg
p=0.0181 v P
p=0.0727 v B
20.7mg
p=0.005 v P
p=0.0255 v B
Doses down to
60mg HTX-011
produced
significant
reductions in opioid
rescue medication
and significant
increases in median
time to first opioid
(increased by 300%)
and the percent of
opioid-free patients
through 96 hours
(increased by 240%)
Study 208: Treatment-Emergent Related
Adverse Reactions for All Cohorts*
Preferred Term
Saline Placebo
(n=86)
Bupivacaine
(n=15)
HTX-011
(n=121)
Any Adverse Event
20.9%
20.0%
27.3%
Nausea
9.3%
13.3%
14.0%
Vomiting
11.6%
6.7%
3.3%
Erythema
1.2%
0
5.0%
Headache
1.2%
0
5.8%
Swelling
0
0
2.5%
*Adverse events considered at least possibly related with an incidence of >2%
37
HTX-011 STUDY 202:
Phase 2 Hernia Repair
Data Presented at 2016 Pain Week
38
HTX-011 Study 202: Herniorrhaphy Study Design
Injection
HTX-011 200mg
Part B
Instillation
Injection
HTX-011 400mg
Instillation
Saline
39
Injection
Instillation and Injection Reduced Pain Equally Well
140
121.6
120
Mean SPI0-24
100
86.2
85.2
HTX-011B 400mg Injection (N=14)
HTX-011B 400mg Instillation (N=16)
80
60
40
20
0
40
Saline Placebo (N=31)
Study 202: Mean Pain Intensity Scores
HTX-011 400mg Significantly Better than Placebo Through 48 hours
8
SPI24-48
p=0.138
7
Mean Pain Intensity
6
5
4
3
2
1
SPI0-24
p=0.0035
0
0
6
12
SPI0-48
p=0.025
18
24
HTX-011 200mg
41
30
36
SPI0-72
p=0.082
42
HTX-011 400mg
*LOCF method used to account for missing data, no adjustment for use of rescue medications
P-values are for the 400 mg dose
48
54
Saline Placebo
60
66
72
Study 202: Opioid Use Substantially Reduced
Consistent with the significant reductions in pain observed with HTX-011,
opiate use was also reduced:
• Percent of patients who required no opioid rescue medication for the 96
hour study period substantially increased (24.1% versus 6.5%)
• Mean total opioid consumption decreased by 22.4% through 96 hours
post-surgery
42
Summary of Treatment-Emergent Adverse Events
(TEAEs) in Study 202*
Preferred Term
HTX-011B 200 mg (N=31)
HTX-011B 400 mg (N=30)
Saline Placebo (N=31)
12 (38.7%)
10 (33.3%)
16 (51.6%)
Nausea
2 (6.5%)
5 (16.7%)
4 (12.9%)
Headache
3 (9.7%)
3 (10.0%)
0
Constipation
3 (9.7%)
1 (3.3%)
5 (16.1%)
0
0
2 (6.5%)
Any TEAE
>1 TEAE in any treatment arm
Hypersensitivity
43
SYNERGY BETWEEN BUPIVACAINE AND
MELOXICAM HAS BEEN CONFIRMED IN
TWO PAIN CLINICAL MODELS
HTX-011 SIGNIFICANTLY BETTER THAN
EITHER COMPONENT ALONE
44
HTX-011 Has Demonstrated Significantly Greater Pain
Reduction Than Either Bupivacaine or Meloxicam Alone
Comparison of AUC0-72
HTX-002 (Bupivacaine)
HTX-009 (Meloxicam)
HTX-002 + HTX-009
HTX-011 (Bupivacaine + Meloxicam)
~7-fold Synergy
AUC LSMD(-) vs Placebo
140
120
100
~9-fold Synergy
80
60
40
20
p=0.043
p=0.002
p=0.035
p=0.034
0
-20
-40
Bunion (120 mg)
45
*p-values are from ANOVA using AUC0-72 of Pain Intensity with wWOCF
Hernia (200 mg)
No Extended Release Bupivacaine Has Demonstrated a PK–
PD Relationship
EXPAREL®
(ER Bupivacaine)
HTX-002
(ER Bupivacaine)
•
•
No PK-PD Relationship
3
No PK-PD Relationship
140
∆ Pain Score
Plasma Conc
80
1.5
60
1
40
0.5
20
0
0
0
24
48
72
Hours
PK – PD data from Exparel® Bunionectomy Study; Golf, et. al.
46
Δ Pain Score
(Saline – HTX-002)
∆ Pain Score
(Saline minus Exparel)
100
2
Plasma Bupivacaine (ng/mL)
120
2.5
Unique Combination of Bupivacaine & Meloxicam
Demonstrates Clear PK–PD Relationship
•
For the first time an extended release local anesthetic has shown a clinical PK – PD
relationship
Study 208
Similar PK – PD
relationship
observed with
HTX-011 in
Study 202
Hernia Repair
47
PHASE 2 STUDIES IN TKA AND NERVE
BLOCK HAVE STARTED
48
Study 209: Total Knee Arthroplasty Study Design
(n=120)
Saline Placebo
Injection
Bupivacaine 150 mg
Injection
49
HTX-011 400 mg
Instillation ± Injection
Cohort 2
Cohort 1
HTX-011 200 mg
Instillation ± Injection
Saline Placebo
Injection
Bupivacaine 150 mg
Injection
Study 211: Pectoral Pocket Nerve Block in Breast
Augmentation Study Design (n=72)
Saline Placebo
Nerve Block
Bupivacaine 50 mg
Nerve Block
50
HTX-011 60 to 120 mg
Nerve Block
Cohort 2
Cohort 1
HTX-011 60 mg
Nerve Block
Saline Placebo
Nerve Block
Bupivacaine 50 mg
Nerve Block
HTX-011 Shows Durable Response in Sciatic Nerve
Block Model in Pigs
Saline
Bupivacaine 25 mg
Exparel 106 mg
HTX-011 100 mg
300
Force in Grams
250
200
150
100
50
0
0.5H
51
1H
2H
4H
6H
8H
HOURS
9H
10H
24H
28H
48H
Summary: HTX-011 Is Poised to Fulfill the Promise
of Long-Acting Local Anesthetics in Post-Op Pain
52
Large, growing market opportunity

Differentiated, synergistic mechanism addresses inflammation – a key inhibitor of both
generic and long-acting local anesthetics

Demonstrated superiority vs. generic bupivacaine solution supports value story

Consistent 72-hour efficacy
- Pain reduction
- Opioid reduction

Applicable in large and small procedures without admixture with bupivacaine solution –
reducing chance of dosing errors and systemic toxicity

Flexible administration with potential safety advantages

Potential to address most pressing unmet needs cited by key stakeholders – patients,
surgeons, anesthesiologists & formulary decision makers

De-risked Phase 3 development program and extensive patent protection through 2035

Key Catalysts in Pain & CINV Franchises
HTX-011 for Post-Operative
Pain
 Early Q1 Top-line
abdominoplasty data
 Early Q1 Phase 2 program in
nerve block initiated
 Initiated TKA study
(local administration)
End-of-Phase 2 (scheduled)
Initiation of Phase 3 studies
NDA filing 2018
53
CINVANTI™ (HTX-019) for CINV
 Q1 (Jan.) – NDA submission
Q4 – PDUFA goal date of 11/12/17
SUSTOL® for CINV
2017 net sales guidance:
$15M - $25M
Financial Update (May 10, 2017)
•
Current cash, cash equivalents and short-term investments are
sufficient for at least one year.
Summary Statement of Operations
(In thousands, except per share data)
Net product sales
$
3,632
Operating expenses1
52,931
Other expenses, net
(1,030)
Net loss1
$ (50,329)
Net loss per share2
$
Condensed Balance Sheet Data
(In thousands)
54
Three Months Ended
March 31, 2017
(1.00)
March 31, 2017
Cash, cash equivalents and short-term investments 3
$ 165,216
Total assets
$ 189,558
Promissory note payable
$
Total stockholders’ equity
$ 102,160
1
Includes $8.0 million of non-cash, stock-based compensation expense.
2
Based on 50.5 million weighted-average common shares outstanding for the three months ended March 31, 2017.
3
First quarter 2017 net cash used in operations totaled $50.6 million and included $14 million related to changes in accounts receivable, accounts
payable and accrued expenses. Net cash used in operations expected to be less over remaining quarters of 2017.
50,000