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© COPYRIGHT 2015 XENOPORT, INC. ALL RIGHTS RESERVED.
JEFFERIES 2015 GLOBAL HEALTHCARE CONFERENCE JUNE 4, 2015 VINCENT J. ANGOTTI, CHIEF OPERATING OFFICER
PAGE 2 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
SAFE HARBOR LANGUAGE
These slides and the accompanying oral presentation by XenoPort, Inc. contain forward-looking statements that involve risks and uncertainties, including statements relating to the commercial opportunity, promotional efforts and value proposition for HORIZANT® (gabapentin enacarbil) Extended-Release Tablets, including XenoPort’s planned sales force expansion and the timing thereof; potential future revenue, prescription growth and commercialization and partnering activities for HORIZANT; XenoPort’s 2015 revenue guidance and other 2015 goals; the planned clinical development of HORIZANT by the NIAAA, including the initiation, conduct and results of the NIAAA's proposed clinical trial and the timing thereof; XenoPort’s beliefs regarding the design of NIAAA’s proposed pivotal clinical trial and its potential to support a potential supplemental NDA for HORIZANT as a potential treatment for AUD; the planned development of AP by Indivior PLC (formerly Reckitt Benckiser Pharmaceuticals) and the timing thereof; the XP23829 clinical development program, including XenoPort’s development strategy as well as XenoPort's expectations to obtain top-line Phase 2 XP23829 study results by the end of the third quarter of 2015 and to accelerate and advance XP23829 into Phase 3 development; the initiation or conduct of current or potential future XP23829 clinical trials and related regulatory interactions and the timing thereof; partnering activities for XP23829; expected patent coverage; and the therapeutic and commercial potential of HORIZANT and XenoPort’s product candidates. XenoPort can give no assurance with respect to these statements, and we assume no obligation to update them. For detailed information about the risks and uncertainties that could cause actual results to differ materially from those implied by, or anticipated in, these forward-looking statements, please refer to the Risk Factors section of our Quarterly Report on Form 10-Q for the quarter ended March 31, 2015 and filed with the SEC.
PAGE 3 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
Growing, commercial business
Unique prodrug NCEs with long patent lives
Pipeline of product candidates
XENOPORT BUSINESS DRIVERS
PAGE 4 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
PRODUCT/INDICATION DEVELOPMENT STAGE PARTNER
GABAPENTIN ENACARBIL
Alcohol Use Disorder (AUD) – U.S. NIAAA Planning Pivotal Trial – 2Q’15
XP23829
Psoriasis Phase 2 Ongoing
Relapsing Forms of MS May Enter Phase 3 - Pending Psoriasis Data / Toxicology Studies
XP21279
Parkinson’s Disease Potential Phase 3 Development (Pending Resources)
ARBACLOFEN PLACARBIL (AP)
AUD Indivior Planning Phase 2 Development
POTENTIAL FOR SIGNIFICANT NEW OPPORTUNITIES FROM DEVELOPMENT PIPELINE
PAGE 5 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
XP23829 FOR POTENTIAL TREATMENT OF PSORIASIS AND RELAPSING FORMS OF MS
PAGE 6 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
APPROVED FUMARIC ACID ESTER PRODUCTS
FUMADERM • Mixture of fumaric acid esters • Available in Germany since 1994 for treatment of psoriasis
TECFIDERA (dimethyl fumarate) • A formulation of dimethyl fumarate (DMF) • Approved in March 2013 in the U.S. for the treatment of
relapsing forms of MS • Approved in February 2014 in the EU for relapsing-remitting MS • Shown effective in 2 clinical trials in psoriasis patients
PAGE 7 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
XP23829 A FUMARIC ACID ESTER COMPOUND
Releases the same active metabolite (MMF) in the body as TECFIDERA and FUMADERM
XP23829
DMF
MMF
MMF
Promoiety
Methanol
+
+
Esterases
PAGE 8 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
STATUS OF PRECLINICAL AND PHASE 1 TRIALS
Completed preclinical PK and safety studies • Including 13-week toxicology studies in 3 animal species with DMF
comparison arms • Demonstrated less skin and GI irritation compared to DMF • No adverse findings that were not observed with DMF
Completed three Phase 1 trials • Established human PK, metabolites and disposition • Compared PK/PD to TECFIDERA (dimethyl fumarate) • Confirmed total MMF exposure in blood similar to TECFIDERA • Demonstrated known pharmacodynamic effects on immune blood
cells with once-a-day dosing in humans
Ongoing chronic and reproductive toxicology studies • Studies Include DMF control arm • Data expected to be available in 2H 2015 in time for EOP2 meeting
with FDA
PAGE 9 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
POTENTIAL XP23829 ADVANTAGES
Lower incidence and/or less severe GI side effects and flushing Onset and/or magnitude of efficacy Dosing frequency • QD rather than BID (TECFIDERA) or TID (FUMADERM)
Indication • TECFIDERA and FUMADERM not approved for psoriasis in the U.S.
PAGE 10 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
XP23829 DEVELOPMENT STRATEGY
Conduct a Phase 2 psoriasis study to gain valuable knowledge for XP23829 product profile • Efficacy • Safety and Tolerability (including effects on lymphocytes) • Dose and dose regimen (QD vs. BID)
Plan to advance into Phase 3 psoriasis development, pending Phase 2 results Psoriasis study results may be used to justify dose-selection and support development strategy in MS Recently gained FDA agreement on key aspects of Phase 3 MS development program • Proceed upon obtaining supportive data from chronic and reproductive
toxicology studies and Phase 2 psoriasis results • A single Phase 3 trial could support potential NDA submission
Continuing to seek development strategy input from potential partners
PAGE 11 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
PSORIASIS RESULTS RELEVANT TO DEVELOPMENT FOR RELAPSING FORMS OF MS
11
TECFIDERA Phase 2 Psoriasis Study
6%
31%
52%
71%
0%
10%
20%
30%
40%
50%
60%
70%
80%
Placebo 120 mg/Day 360 mg/Day 720 mg/Day
MEDIAN PERCENT REDUCTIONS FROM BASELINE PASI
(n=36) (n=36) (n=36) (n=36)
Biogen Press Release 2004 Langner, J Am Acad Dermatol 2005
WEEK 12
TECFIDERA Phase 2 Relapsing Forms of MS Study
4.5
3.3 3.1
1.4
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
Placebo(N=65)
120 mg/day(N=64)
360 mg/day(N=64)
720 mg/day(N=64)
NUMBER OF NEW GDE LESIONS (WEEK 12-24)
Kappos, Lancet 2008
PAGE 12 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
Study Design Randomized, double-blind, multicenter, parallel group, placebo-controlled, dose-finding efficacy and safety study in subjects with moderate-to-severe chronic plaque-type psoriasis
Number of Sites ~35 sites in United States
Number of Subjects ~200 randomized 1:1:1:1
Primary Endpoint The percent change in Psoriasis Area and Severity Index (PASI) score from Baseline (12 weeks)
XP23829 PHASE 2 CLINICAL TRIAL IN PSORIASIS PATIENTS
400 mg BID
Placebo
800 mg QD
400 mg QD
Screening/ Washout
Week -4 Week 0 Week 3 Week 12 Week 16
Post-Treatment Follow-up
Titration Maintenance Phase
Top-line results expected by end of 3Q’15
PAGE 13 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
PLAQUE PSORIASIS MARKET IS UNDERSERVED
Chronic, systemic, inflammatory disease Most prevalent autoimmune disease • Afflicts 7.5 million Americans*
• 1.5 million with moderate-to-severe psoriasis**
Treatment options not optimal • Topicals
• Useful in mild cases • Oral options have limited efficacy and/or
potentially concerning side effects • Acitreten, cyclosporine, methotrexate and OTEZLA
• Injectable biologics are efficacious but come with safety warnings
• ENBREL, HUMIRA, REMICADE, STELARA
52% of patients are dissatisfied with current treatment*
* National Psoriasis Foundation Fact Sheet, as posted 2/23/15 ** The Psoriasis and Psoriatic Arthritis Pocket Guide, National Psoriasis Foundation, 2009
PAGE 14 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
Safety/Tolerability
Effic
acy
UN
FAVO
RAB
LE
FAVO
RAB
LE
UNFAVORABLE FAVORABLE
Qualitative Positioning
XP23829
DESIRED PRODUCT POSITIONING FOR XP23829 AS ORAL TREATMENT FOR PSORIASIS
PAGE 15 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
0
10,000
20,000
30,000
40,000
50,000M
ar-0
9Ap
r-09
May
-09
Jun-
09Ju
l-09
Aug-
09Se
p-09
Oct
-09
Nov
-09
Dec
-09
Jan-
10Fe
b-10
Mar
-10
Apr-1
0M
ay-1
0Ju
n-10
Jul-1
0Au
g-10
Sep-
10O
ct-1
0N
ov-1
0D
ec-1
0Ja
n-11
Feb-
11M
ar-1
1Ap
r-11
AUBAGIO GILENYA TECFIDERA
ORAL TREATMENTS FOR RELAPSING FORMS OF MS
U.S
. TR
x
2014 SALES U.S. Ex-U.S.
$2.4 B $0.5 B
$0.3 B $0.5 B
$1.2 B $1.3 B
Source: Symphony Health Solutions, PHAST Prescription Monthly, April 2013 – April 2015
1% market share is ~$100M in annual U.S. product sales at current prices
PAGE 16 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
XENOPORT’S BROAD INTELLECTUAL PROPERTY
Three issued U.S. patents • Claims covering composition-of-matter of XP23829 (expiration date in 2029)
48 patents issued worldwide, covering: • XP23829 and other MMF prodrug compositions and their uses • Crystalline forms of XP23829 • Oral dosage forms of MMF prodrugs* • Methods of treatment with MMF prodrugs* • Methods of selecting and/or administering MMF prodrugs* to
reduce side effects
Applications filed broadly in major pharmaceutical markets *May include XP23829, DMF and certain other MMF prodrug molecules
PAGE 17 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
HORIZANT OUR FIRST APPROVED PRODUCT
PAGE 18 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
Approved in U.S. for moderate-to-severe primary RLS in adults in April 2011
Approved in U.S. for the management of PHN in adults in June 2012
XenoPort promotional efforts began in June 2013
6 Orange Book listed patents with expiry dates from 2022 – 2029
Please review the full prescribing and safety information for HORIZANT. The most common adverse reactions of HORIZANT in RLS patients: somnolence/sedation and dizziness, and in PHN patients: somnolence, dizziness and headache.
HORIZANT® (GABAPENTIN ENACARBIL) EXTENDED- RELEASE TABLETS
PAGE 19 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
*In two 12-week clinical trials, patients taking HORIZANT showed no evidence of symptom augmentation. The duration of these trials may not have been sufficient to adequately assess symptom augmentation.
HORIZANT ATTRIBUTES: MODERATE-TO-SEVERE PRIMARY RLS
Proven effective Convenient once-a-day dosing No titration Only non-dopamine agonist approved by FDA No evidence of augmentation, rebound or impulse control disorders* Recommended as a first-line treatment in recently published treatment guidelines
PAGE 20 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
Please review the full prescribing and safety information for HORIZANT. The most common adverse reactions of HORIZANT in RLS patients: somnolence/sedation and dizziness, and in PHN patients: somnolence, dizziness and headache.
Source: Pivotal trial data
HORIZANT ATTRIBUTES: MANAGEMENT OF PHN
Simple 4-day titration Efficacy as early as one week Pharmacokinetic differentiation • High bioavailability (75%) • Sustained 24-hour gabapentin blood levels
42% of patients experienced ≥50% pain score reduction
Pain relief over 24 hours
TIME (HR)
0
5
10
0.00 12.10 24.00
Predicted Plasma Concentration of Gabapentin After HORIZANT 600 mg BID
for PHN1
1. Adapted from Lal R, et al. J Clin Pharmacol. 2013;53(1):29-40
STEA
DY-
STR
EAM
G
ABAP
ENTI
N C
ON
CEN
TRAT
IO
(µg/
ml)
Peak to Trough Ratio = 1.5
PAGE 21 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
HORIZANT COMMERCIALIZATION STRATEGY
JUNE 2013 Objective: Demonstrate promotional responsiveness quickly and efficiently • Personal promotion and marketing efforts focused in ~ 40 territories
Focus on specialists and high prescribing PCPs of RLS and PHN drugs
OCTOBER 2014
Expanded to ~65 territories Observed 74% increase in prescribed tablets in new territories in 4Q’14 versus 4Q’13
2015
Planned expansion to up to 120 territories by mid-2015 Maintaining focus on specialists and high prescribing PCPs of RLS and PHN drugs
PAGE 22 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
$1.6 $2.0
$2.7 $3.0
$4.9
$5.6
$6.6 $6.6
$0.00
$1.00
$2.00
$3.00
$4.00
$5.00
$6.00
$7.00
2Q'13 3Q'13 4Q'13 1Q'14 2Q'14 3Q'14 4Q'14 1Q'15
GROWING HORIZANT SALES
Regions with NO XenoPort Promotion
Prescribed Tablets HORIZANT Quarterly Net Sales
*Reflects XenoPort net sales of HORIZANT following its reacquisition on May 1, 2013.
*
*Source: Healthcare Analytics, a Symphony Health Solutions Company: The information attributed to Source Healthcare Analytics herein is provided as is, and Source Healthcare Analytics, LLC makes no representation and/or warranty of any kind, including but not limited to the accuracy and/or completeness of such information. Source Healthcare Analytics is credited as a source of certain data only. The attribution of Source Healthcare Analytics as the source of such data shall not be construed as an endorsement by Source Healthcare Analytics of the views, opinions or findings expressed, shared or otherwise published herein.
-
50
100
150
200
250
300
350
400
450
500
2011
-06
2011
-08
2011
-10
2011
-12
2012
-02
2012
-04
2012
-06
2012
-08
2012
-10
2012
-12
2013
-02
2013
-04
2013
-06
2013
-08
2013
-10
2013
-12
2014
-02
2014
-04
2014
-06
2014
-08
2014
-10
2014
-12
2015
-02
2015
-04
In T
hous
ands
Pre- XP Launch
Post- XP Launch
PAGE 23 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
GROWING HORIZANT SALES
1,311
2,290
979
0
400
800
1200
1600
2000
2400
R4W
Rxs
Horizant R4 NRx, RRx, TRx
Horizant Rolling 4 NRx Horizant Rolling 4 TRx Horizant Rolling 4 RRxs
PAGE 24 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
GROWING HORIZANT SALES
-
20,000
40,000
60,000
80,000
100,000
120,000 Horizant Rolling Average 4 Week Tabs
116,526
PAGE 25 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
EXPANDING HORIZANT OPPORTUNITY
HORIZANT clinical trial in patients who have AUD • Six-month treatment duration • NIAAA plans to enroll ~350 patients • Initiation planned for 2Q’15. Results may be available by end of 2016
XenoPort to supply clinical trial material NIAAA plans to conduct trial and pay all other expenses FDA meeting outcome • Accepted trial design • XenoPort believes trial results may support filing of potential sNDA for HORIZANT
if results are robust and compelling • Additional confirmatory evidence from literature or other sources should support the clinical trial
findings
CLINICAL TRIAL AGREEMENT
PAGE 26 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
PROOF OF CONCEPT: GABAPENTIN / ALCOHOL DEPENDENCE
PAGE 27 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
2015 GOALS
HORIZANT net sales of $39 to $43 million
Initiation of HORIZANT AUD clinical trial by NIAAA in 2Q’15 Top-line data for XP23829 Phase 2 psoriasis clinical trial by the end of 3Q’15 Complete chronic and reproductive toxicology studies for XP23829 and initiate carcinogenicity studies Scale-up manufacturing of XP23829 to support potential Phase 3 Potential End-of-Phase 2 meeting with FDA for XP23829
PAGE 28 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
FINANCIALS
$191.6 million of cash, cash equivalents and short- and long-term investments at March 31, 2015 • Includes $111.4 million net proceeds secured through recent
convertible senior debt financing
62.8 million shares outstanding at April 15, 2015
© COPYRIGHT 2015 XENOPORT, INC. ALL RIGHTS RESERVED.
THANK YOU VINCENT J. ANGOTTI, CHIEF OPERATING OFFICER
PAGE 30 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
BACK UP SLIDES
PAGE 31 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
XP23829 IS DIFFERENT BY DESIGN
XP23829 has reduced local GI irritation compared to DMF based on XenoPort preclinical studies A pH-independent delayed- and extended-release tablet
• Avoids high local concentrations particularly in stomach/duodenum
• Potential to increase drug exposure to immune cells found throughout the intestine
• Reduces Cmax and extends blood levels of MMF
IN VITRO DISSOLUTION*
0 HOURS 2 HOURS 8 HOURS 4 HOURS 12 HOURS
*XenoPort data on file
pH=1.2 pH=6.8
PAGE 32 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
XP23829 POTENTIAL MS DEVELOPMENT PLAN
Gained FDA agreement on key aspects of Phase 3 development program • Proceed upon obtaining supportive data from chronic and reproductive
toxicology studies and Phase 2 psoriasis results • A single Phase 3 trial could support potential NDA submission
Phase 2 psoriasis study results (efficacy, safety, tolerability) may be used to justify dose-selection and support development strategy Continuing to seek development strategy input from potential partners
PAGE 33 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
-
50
100
150
200
250
300
350
400
450
500
2011
-06
2011
-07
2011
-08
2011
-09
2011
-10
2011
-11
2011
-12
2012
-01
2012
-02
2012
-03
2012
-04
2012
-05
2012
-06
2012
-07
2012
-08
2012
-09
2012
-10
2012
-11
2012
-12
2013
-01
2013
-02
2013
-03
2013
-04
2013
-05
2013
-06
2013
-07
2013
-08
2013
-09
2013
-10
2013
-11
2013
-12
2014
-01
2014
-02
2014
-03
2014
-04
2014
-05
2014
-06
2014
-07
2014
-08
2014
-09
2014
-10
2014
-11
2014
-12
2015
-01
2015
-02
2015
-03
2015
-04
GROWING HORIZANT TABLET GROWTH POST-LAUNCH OF HORIZANT BY XENOPORT
Prescribed Tablets
*Source: Healthcare Analytics, a Symphony Health Solutions Company: The information attributed to Source Healthcare Analytics herein is provided as is, and Source Healthcare Analytics, LLC makes no representation and/or warranty of any kind, including but not limited to the accuracy and/or completeness of such information. Source Healthcare Analytics is credited as a source of certain data only. The attribution of Source Healthcare Analytics as the source of such data shall not be construed as an endorsement by Source Healthcare Analytics of the views, opinions or findings expressed, shared or otherwise published herein.
In T
hous
ands
Pre- XenoPort Launch
Post- XenoPort Launch
PAGE 34 | JEFFERIES GLOBAL HEALTHCARE CONFERENCE | JUNE 2015
GROWING HORIZANT SALES
1,311
2,290
979
0
400
800
1200
1600
2000
2400
24-J
an24
-Feb
24-M
ar24
-Apr
24-M
ay24
-Jun
24-J
ul24
-Aug
24-S
ep24
-Oct
24-N
ov24
-Dec
24-J
an24
-Feb
24-M
ar24
-Apr
24-M
ay24
-Jun
24-J
ul24
-Aug
24-S
ep24
-Oct
24-N
ov24
-Dec
24-J
an24
-Feb
24-M
ar24
-Apr
R4W
Rxs
Horizant R4 NRx, RRx, TRx
Horizant Rolling 4 NRxHorizant Rolling 4 TRxHorizant Rolling 4 RRxs
-
20,000
40,000
60,000
80,000
100,000
120,000
3-M
ay3-
Jun
3-Ju
l3-
Aug
3-Se
p3-
Oct
3-N
ov3-
Dec
3-Ja
n3-
Feb
3-M
ar3-
Apr
3-M
ay3-
Jun
3-Ju
l3-
Aug
3-Se
p3-
Oct
3-N
ov3-
Dec
3-Ja
n3-
Feb
3-M
ar3-
Apr
3-M
ay
Horizant Rolling Average 4 Week Tabs
116,526