2011 bio international convention
TRANSCRIPT
1
Apricus Biosciences, Inc. Corporate presentation2011 Bio International Convention,
June 27 ‐30, Washington, DC
2
Safe‐Harbor Statement
Statements under the Private Securities Litigation Reform Act, as amended: With
the
exception
of
the
historical
information
contained
in
this
presentation,
the
matters
described
herein
contain
forward‐looking
statements
that
involve
risks
and
uncertainties
that
may
individually,
mutually,
or
materially
impact
the
matters
herein
described,
including,
but
not
limited
to,
the
Company’s
ability
to
execute
its
business
plan,
obtain
regulatory
approval
for
products
under
development,
enter
into
partnering
agreements,
realize
revenue
and
pursue
growth
opportunities,
some
of which
are
outside
the
control
of
the
Company.
Attendees
are
cautioned
not
to
place
undue
reliance
on
these
forward‐looking
statements
as
actual
results
could
differ
materially
from
the
forward‐looking
statements
contained
herein.
Attendees
are
urged
to
read
the
risk
factors
set
forth
in
the
Company’s
most
recent
annual
report
on
Form
10‐K,
subsequent
quarterly
reports
filed
on
Form
10‐Q
and
its
most
recent
SEC
filings. Company
disclaims any intention to update this presentation.
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Financial Snapshot
•
NASDAQ:
APRI
•
Shares Outstanding
19.6M*•
Shares Fully‐diluted
22M*•
Shares in the float
16M*
•
Cash‐position
$10.2M*
•
Share‐price
$5.26**
•
Marketcap
~$105M**
•
Average Daily volume
~320k**
•
Revenues 2010
~$5M*As of March 31, 2011**As of June 24, 2011
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Company Highlights
•
Specialty Biopharmaceuticals company with proprietary drug delivery platform
technology (NexACT®) to rapidly advance drug candidates through clinical
development
•
Mid‐to‐late staged pipeline with multiple, significant near‐term value drivers
•
Multiple Partnerships in place with additional significant partnerships expected
near term
•
Experienced management team, proven to deliver on milestones and
objectives
•
Solid financial position: Current cash position through H2 2012 with goal to be cash
flow positive exiting 2011
5
NexACT®: Multi‐Route Drug Delivery Technology
•
Patented:
NCE
patents
based
on
proprietary
permeation
enhancers
that
are
biodegradable, biocompatible, non‐toxic ingredients that mimic the composition of
human skin and tissues.
•
Effective: enables rapid absorption of high concentrations of drug directly to target
site or systemically into blood stream.
•
Safe: excellent pre‐clinical and clinical safety dossiers through thousands of patient
exposures
•
Versatile: effective with wide range of drugs classes and different routes •
Small molecules, peptides, proteins, SiRNA, anti‐sense, and antibodies•
Transdermal, Oral, Sub‐Q, Buccal, Rectal, Nasal, Ophthalmic
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NexACT®
(DDAIP) MOA‐Loosening Tight Junctions
7
Apricus Bio Product Pipeline
8
Vitaros®
(alprostadil/DDAIP) for the Treatment of Erectile Dysfunction
• PGE1, potent vasodilator, topical cream, high viscosity • Only approved ED drug for all patients• Rapid onset (generally 6‐30 minutes) • Significant efficacy, including difficult to treat populations
• Diabetics• Hypertensives• Patients with cardiac issues• Patients on nitrates and alpha blockers• Prostatectomy patients • Sildenafil (Viagra®) failures
• Side effects are generally mild, transient and topically related• Studied in over 3,300 patients
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Vitaros®
Global Assessment Question When using the study medication, did you feel your erections improved?
Phase 3 Pivotal Clinical StudiesIntegrated Efficacy Analysis – Intent to Treat Population
Vitaros®p<0.001
Vitaros®p<0.001
Viagra®50 mgs and 100 mgs
Source: Viagra PI; Patients were started on 50 mg and allowed to adjust the dose up to 100 mg or down to 25 mg of VIAGRA; all patients, however, were receiving 50 mg or 100 mg at the end of the study. On a global improvement question, 57% of VIAGRA patients reported improved erections versus 10% on placebo.
Vitaros®p<0.001
Placebo(Viagra®
study)
VitarosN=394
VitarosN=408
VitarosN=392
VitarosN=398
Placebo(Vitaros®
study)
Key Conclusion:Vitaros® 300 mcgs/100 ml dose strength is comparable to Viagra® 50 mgs dose strength
Vitaros® Studies
Viagra® Studies
10
Vitaros®
(alprostadil/DDAIP) for the Treatment of Erectile Dysfunction
11
Vitaros®
% of Patients
DrugDiscontinuation
Rate Headaches FlushingRhinitis/Nasal Congestions Back Pain Dyspepsia Abnormal Vision
Vitaros® 0 0 0 0 0 0 0
Viagra® 2 16 10 7 >2 7 11
Cialis® 3.1 15 3 3 6 10
Levitra® 3.4 15 11 3 2 5
Discontinuation Due to Serious Adverse Events: Orals vs. Vitaros®
Source: Vitaros PIII Clinical Trial; PDE5 Package Inserts
Key Conclusions:
•Vitaros® presents an excellent safety and tolerability profile• No serious side effects• Most adverse events were localized to the site of application
but were mild and short in duration
12
Vitaros®(alprostadil/DDAIP) for the Treatment of Erectile Dysfunction
13
Femprox®
(alprostadil/DDAIP) for the Treatment of Female Sexual Arousal Disorder (FSAD)
Premeasured unit dose225 mg of cream containing
0.4 % alprostadil (900 µg), DDAIP 0.5%
14
Femprox®
Phase 3 Study
•
A Randomized, Placebo‐Controlled, Double‐Blind, Parallel Design Study of the
Efficacy and Safety of Alprostadil Cream in Patients with Female
Sexual Arousal
Disorder (FSAD)o
n= 400 patients placebo, 500, 700 or 900 mcg alprostadil
cream groups, Application sites:
clitoris and G‐spot
o
Five (5) month study
Femprox®
Phase 3 Study
Safety and Tolerability
• The most frequently reported adverse events were mild to moderate local irritations, and were 14%, 22%, 18% and 31% observed for the placebo, 500mcg, 700 mcg and 900 mcg groups, respectively.
• No serious adverse events were reported.
• Overall, 5 patients (1.2%) were withdrawn from the study because of adverse events.
15
FemproxFemprox®®
Clinical/ Regulatory Strategy Next StepsClinical/ Regulatory Strategy Next Steps
16
1. Establishment of US and EU Clinical Advisory Board• Help design of confirmatory Phase 3 trial
required by FDA
2. Submission of briefing books for health authority interactions aimed at:• Approvability of successful single Phase 3 trial
in Europa, Canada and Switzerland• Type A FDA meeting to agree on regulatory path forward
for NDA.
3. Efforts to engage a pharmaceutical partner to continue clinical development
TasksTasks
√√
ScheduleSchedule
Q2, 2011
2 H, 2011
2 H, 2011
10 June‐8‐201117
MycoVa™
(Terbinafine/DDAIP) for the Treatment of Onychomycosis•Synthetic allylamine derivative which inhibits enzyme squalene epoxide in fungal
cell•DDAIP ‐
significant drug penetration through nail plate to bed and surrounding area•Formulations advantages
•
Drug availability•
Not trapped in lacquer matrix•
Easily treat adjacent skin and folds•
Patient convenience•
Ease of application, quick drying•
Wash off, no lacquer removal•Clinical Studies in ~900 patients
•
2 Phase 3 trials completed in US, EU and Canada•
1 EU comparator trial vs. Loceryl®
(amorolfine)
MycoVa™
MycoVaMycoVa™™
‐‐
Approval Path for EuropeApproval Path for Europe
EU Regulatory Strategy:
•
Switch from superiority claim to non‐inferiority claim based on N2303 data
and reanalysis.
• Obtain scientific advice from European health authorities.• Partnering attempts prior to market authorization.
Clinical Studies conducted in more than 2000 patients world‐wide:
• China Proof of Concept Study – High clinical and mycologucal cure rate • US Phase 1 (Safety and PK) –
Relevant concentrations in nail clippings• US, Canada and EU Phase 3 (N2301 and N2302) – Primary Endpoint not met• Phase 3 comparative trial (N2303) vs amorolfine (Loceryl) – no difference• Total patients treated > 2,000
18
EU TrialEU Trial‐‐NonNon‐‐Inferiority AnalysisInferiority Analysis TerbinafineTerbinafine
is nonis non‐‐inferior to inferior to amorolfineamorolfine
19
Mycological Cure Rate,n (%)
Difference
Chi-square 95% Confidence Interval
Terbinafine(N=507)
Amorolfine(N=522) Uncorrected
Continuity Corrected
82 (16.17) 82 (15.71) 0.46 -4.01, 4.94 -4.20, 5.13
Mycological Cure Rates at the End of Study (ITT Population, LOCF)
MycoVaMycoVa™™‐‐
Approval Path for US and RoWApproval Path for US and RoW
New Clinical Data Analysis•
Combined analysis of N2301 and N2302 show significant efficacy
vs. placebo
in mycological cure rate
•
Revised analysis of N2301 and N2302 without comorbid tinea pedis shows
statistically significant superiority vs. placebo, especially
at later stages of the study
US/ROW Regulatory Strategy:
•
Currently requesting guidance from Health Canada and FDA to achieve approval
as antifungal with “mycological cure rate”
as relevant endpoint
20
New Analyses: Combined Phase 3 studies N2301 and N2302
Revised analysis on mycological cure rate excluding patients with concomitant tinea pedis
21
Mycological cure in combined analysis= negative KOH microscopy & dermatophytes negative
culture
Treatment n Proportion(%)
Difference (95% CI)* p-value†
Terbinafine 24w(N=259)
33 12.746.54
( 1.52, 11.55) 0.0141Vehicle 24w(N=258)
16 6.20
Terbinafine 48w(N=271)
51 18.82
13.35( 7.93, 18.77) <0.0001
Vehicle 48w(N=256)
14 5.47
[*] Difference is terbinafine minus vehicle. Two-sided 95% CI of difference is based on the normal approximation to the binomial.[†] p-value given by the normal inverse combination test.Studies included: [Study N2301] and [Study N2302]ITT population, LOCF, at the end of the study (week 52) Source: Table 3.2-4 – CSFO327SCE – Combined data
Mycological Cure is significantly greater in patients without comorbid tinea pedis (TP) treated with MycoVa™ over 48 weeks than those receiving placebo at later stages of the study extending through to week 52.
n=174
n=175
P=0.0003
P=0.0058
P< 0.0001
MycoVa™
mycological cure rates in perspective with Penlac®
data
7/29/2011Apricus Bio (NexMed USA's NexACT Technology)22
Source: FDA Medical Review of ciclopirox Source: Nexmed Clinical Study Reports for terbinafine-DDAIP/HCl
In the ITT analyses of Phase 3 studies terbinafine-DDAIP/HCl shows statistically significant mycological cure compared with placebo, slightly higher than in pivotal ciclopirox studies.
Combined analysis excluding patients with tinea pedis increases the efficacy margin vs. placebo.
n.s. ** *
**
*
*
Mycological Cure = negative KOH microscopy & dermatophytes negative culture
n=110 n=223 n=237 n=264 n=263n=527
n=349
23
Market Opportunity
•
Multifunctional NexACT®
Small Molecule Platform Targets Over $10 Billion in approved and
Late‐Stage Product Opportunities
•
Vitaros®
For erectile dysfunction. Approved in Canada. NDA filed in US and Europe.
Worldwide market over $4 Billion
•
Femprox®
For FSAD. One successful Phase III. Awaiting guidance for filing
in Europe
and Canada. Preparing for US Phase III for NDA filing. Worldwide market
estimated to be up to $4 Billion
•
MycoVa™
For Onychomycosis. Europe Comparator Phase III trial competed. Awaiting
guidance for filing in Europe and Canada. Worldwide market over
$1 Billion
•
PrevOnco™
For liver cancer (HCC). In Phase II and heading to Phase III. Worldwide
market over $1 Billion
(Partial Pipeline)
24
Milestones Achieved
Had first drug Vitaros® for erectile dysfunction approved by Health Canada
Strengthened financial foundation of the company Cash into H2 2012
Completed first partnerships for Vitaros®Bracco‐Vitaros® (Italy)Elis‐Vitaros® (Middle East)Neopharm‐Vitaros® (Israel)
Unqualified audit opinion (Going Concern removed for the 1st time in 9 years)
Filed for European Approval for Vitaros® in Q2 2011
Last Financing October 2010 ~$9M at $1.83
Returned on shareholder valueUp over 50% YTD
25
Near Term Upcoming Milestones
Announce additional ex‐US commercial partnerships for Vitaros®: CanadaEuropeAfricaLatin America
Announce clinical development and regulatory milestones
Goal to be cash‐flow positive by the end of 2011through upfront payments from partnership agreements
Commence sales of Vitaros® in Canada
26
Upcoming Milestones
Announce first NexACT® technology licensing deal
File for marketing approval in Canada and Europe depending on regulatory guidance for
MycoVa™Femprox®
Out‐license other late‐stage clinical productsFemprox®MyCova™PrevOnco™
28
Proven & Experienced Management Team
•
President & CEO‐
Dr. Bassam Damaj •
Pfizer,
Genentech
(now
Roche),
Pharmacopeia
(now
Ligand),
Tanabe
Seiyaku
(now
Mitsubishi‐Tanabe), Bio‐Quant, Celltek, R&D Healthcare
•
Strong Finance, Operations, and Legal Team•
Steve Martin‐
Gen‐Probe, Stratagene
(now Agilent)•
Edward Cox‐
Bio‐Quant, NexMed•
Randy Berholtz‐
Nanogen, ACON Labs
•
Proven Senior Business Development Team •
Mark Wilson‐
Pfizer, Halozyme (Technology)•
Linda Smibert‐
BMS, AstraZeneca, Santarus (Products)
•
Experienced Research & Development and Medical/Regulatory Affairs Team•
Daniel Frank ‐
Wyeth, Pfizer•
Dr. Mohamed Hachicha
‐
Forest Labs, Purdue Pharma•
Dr. Richard Martin ‐
Exelixis•
Dr. Joachim P.H. Schupp
– Ciba‐Geigy, Novartis
29
In Summary
•
Approved drug (Vitaros®) and clinically validated drug delivery technology
•
Commercial partnerships in place and expanding
•
Efficacy and Safety of DDAIP as topical drug vehicle established
thousands
of patients
•
Clinical
and
Regulatory
Strategy
to
drive
projects
in
place
and developing
•
Unique,
patented and versatile
technology
that
can
be
partnered
multiple
times to multiple partners & used to develop multiple drugs
•
Revenue‐generating with current cash reserves into H2 2012