IDX21437

32nd Annual J.P. Morgan Healthcare Conference
January 2014
Ron Renaud
President and CEO
1
Safe Harbor Statement
This presentation includes forward-looking statements about our business, including
without limitation statements regarding drug discovery, research and clinical
development, regulatory approval processes and market opportunities. These
forward-looking statements are subject to important risks and uncertainties that may
cause actual events or results to differ materially from our current expectations for a
number of important reasons, including those detailed in our publicly-available
filings with the Securities and Exchange Commission. In particular, our expectations
could be affected by, among other things, unexpected regulatory actions or delays,
or government regulation generally. There can be no guarantee that development
of any of our drug candidates described herein will succeed or that any new
products will obtain necessary regulatory approvals required for commercialization
or otherwise be brought to market. All forward- looking statements speak only as of
the date of this presentation and, except as required by law, we undertake no
obligation to update such statements.
2
Building a Leading Antiviral Franchise
Idenix Strategy: Advancing All-Oral, Pan-Genotypic
Combination HCV Regimens
 Nucleotide Prodrug Program
-
IDX21437: phase I/II ongoing ex-US
IDX20963: ongoing preclinical work in response to FDA’s request
Additional candidates under evaluation
 NS5A inhibitor program : Samatasvir (IDX719)
-
Favorable safety and potent pan-genotypic activity demonstrated in
HCV-infected patients
-
Ongoing all-oral phase II 2-DAA HELIX-1 trial in combination with
Janssen’s simeprevir demonstrated favorable safety and 85% SVR4 in
50 mg group
-
Ongoing all-oral phase II 3-DAA HELIX-2 trial with Janssen’s simeprevir
and ritonavir-boosted non-nucleoside inhibitor (TMC647055)
 Idenix all-oral HCV combination: planned phase II pan-genotypic trial of
samatasvir and nucleotide in 2014
3
Building a Leading Antiviral Franchise
HCV Market: Significant Commercial Opportunity
Large Market
$200Bn+ cumulative
market anticipated
(2014-2030)
Significant
Commercial
Opportunity
Differentiated
Focused on attractive
profile (pan-genotypic,
convenient)
Long-Tail
Long-tail along with
differentiated positioning
anticipated
With a pan-genotypic all-oral HCV combination, Idenix will be wellpositioned to play a significant role in the future of HCV treatment
4
Building a Leading Antiviral Franchise
Long Tail Anticipated in HCV: Patient Pool and
Market Opportunity Anticipated To Last Until ~2030
 Disease Paradigm
– Because people infected with HCV are initially asymptomatic, it will take 15-20 years
for them to be diagnosed/treated
– New all-oral regimens will generate an increase in treated patients
– New patients will continue to become infected
 Restrictive Managed Care
– High cost of treatment may limit prescribing to specialists, especially outside the US
– Managed care may restrict treatment to more advanced, harder-to-treat patient
segments, particularly in the EU and emerging markets
 Capacity Constraints
– Currently, high-prescribing physicians limited to treating HCV ~25-30% of the time
Treatment of “already diagnosed” patients
at anticipated levels would take > 10 years
Source: Idenix market research ; >300 respondents (qual & quant), cross-geography (US, EU, Canada) & across
stakeholder groups
5
Building a Leading Antiviral Franchise
Significant Global Commercial Opportunity
15.0
16.6
17.1
$200 Billion+ Cumulative Potential
20.0
11.4
12.0
8.0
4.0
2.2
2.2
2.6
2.5
2.8
2.9
2.8
2.8
3.8
4.8
3.9
6.3
Estimated Global
HCV Sales ($Bn)
16.0
0.0
'03
4.5
'05
'07
'09
'11
'13
'15
'17
4.1
4.0
Prevalent
Diagnosed
HCV Patient
Population (M)
3.5
2.7
3.0
2.5
2.0
1.7
1.5
0.8
1.0
1.1
0.7
0.5
0.0
US
EU5
Source: EvaluatePharma, Analyst reports, Idenix market research
6
 Near-term projections
suggest a sustained $1520B annual global HCV
market (2016-2018)
Building a Leading Antiviral Franchise
JA
 Epidemiology suggests
currently only ~3M
diagnosed patients, ~5M
undiagnosed (US, EU5,
JA)
Differentiated Profile: Idenix Targeting High
Pan-Genotypic Efficacy for a Diverse Patient Population
 Market research indicates an effective pan-genotypic therapeutic is most
relevant differentiator for next-generation HCV therapeutics
 Market analysis indicates limited competition with nucleotide-based
regimens offering potential for high pan-genotypic efficacy
 Recent genotypic sub-typing indicates high regional variance – US/EU5
dominated by GT 1 but significant number (25-58%) of patients are nonGT 1 within these markets
Region
GT 1
GT 3
GT 4
42%
26%
17%
North Am/ Latin
Am/ Europe
↑↑
↓
↓
North Africa/
Middle East
↓
↓
↑↑
↑
↓
Global
Asia Pacific
Source: Idenix market research, Idenix, Razavi (AASLD 2013)
Base-case assumed 95% efficacy in difficult to treat patients, 8 weeks of treatment duration, 6 pills QD, limited (G1)
coverage, ribavirin back-bone, moderate tolerability concerns, and a simple prior authorization.
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Building a Leading Antiviral Franchise
Relative
Prevalence
by Region
Despite a Competitive Market for All-Oral Combos,
Limited Regimens with Pan-genotypic Potential
Selected All-Oral HCV Combinations in Development with Launch Projected by 2018
Nuc Combo
One Pill, Once a Day
Pan-genotypic
sofosbuvir +
GS-5816 (Gilead)
Nuc Combo
One Pill, Once a Day
Only Selected Genotypes
Nuc Combo
More than One Pill, Once a Day
Only Selected Genotypes
DAA Combo Lacking a Nuc
More than One Pill, Once a Day
Only Selected Genotypes
[GT1] sofosbuvir +
ledipasvir (Gilead)
[GT2/3] sofosbuvir +
RBV (Gilead)
[GT1] ABT-450/ritonavir
[GT1] MK-5172 +
+ ABT-267 +
MK-8742 +/- RBV
ABT-333 + [GT1b] faldaprevir + [GT1] daclatasvir + (Merck)
RBV (AbbVie) deleobuvir + RBV
asunaprevir +
(Boehringer)
BMS-791325 (Bristol)
[GT1/4] simeprevir +
TMC647055/ritonavir +
samatasvir (Janssen / Idenix)
Collaborations between companies
More than One Pill, Once a Day
Only Selected Genotypes
Estimated
Launch
Timeline
2014
2015
2016
Note: Projected dates of major products assumes 100% probability of success. Pan-genotypic definition requires demonstrated class
pangenotypic activity (nucs) or clinical activity across genotypes 1 through 4.
Source: Company websites, analyst reports, clinicaltrials.gov, Idenix analysis
8
IDX21437 +
samatasvir (Idenix)
Building a Leading Antiviral Franchise
[GT1] simeprevir +
TMC647055/ritonavir +
JNJ-56914845 (Janssen)
[GT1] VX-135 +
daclatasvir
(Vertex / Bristol)
2017
[GT1/4] VX-135 +
simeprevir
(Vertex / Janssen)
2018
IDX21437: Next-Generation Uridine Nucleotide Prodrug
Phase I/II Clinical Trial Ongoing
 Favorable preclinical safety profile
‒ Preclinical toxicology profile provides good safety margins for anticipated
clinical doses
‒ Clean genotoxicity and cardiac safety assessments to date
 Potent, pan-genotypic activity in vitro
 High liver triphosphate levels generated in vivo
 Phase I/II clinical trial ongoing in multiple countries ex-US
‒ Phase I single- and multiple-dose portion complete
‒ 7-day proof-of-concept ongoing
9
Building a Leading Antiviral Franchise
IDX21437: Favorable In Vitro Cytotoxicity Profile
 Minimal cytotoxicity in a large panel of mammalian cell types
 No evidence of mitochondrial toxicity
Tissue/
Organ
Species
Cells/Cell Line
Liver
Human
HepG2
Liver
Human
Huh-7
Liver
Human,
Monkey,
Mouse, Rat
Heart
Cell
State
CC50 (µM)
Treatment
Duration
IDX21437
sofosbuvira
BMS-094a
ACH-3422d
P
3/11b/14c
58/345/ND
86/62b
3.2/ND/3.5
13.6/ND/ND
P
3/6
177/463
>100/160
2.5/ND
32/ND
Primary Hepatocytes
NP
2
30/67/>100
>100
38/33/47/3.2
88 (Monkey)
48 (Rat)
Human
iCell™ Cardiomyocytes
NP
12
>500
>500
1.1
-
Kidney
Human
CAKI-1
P
3/11b
>250/93
>50/112
1.3/7.1
-
Skeletal
muscle
Human
SJCRH30
P
3/11b
>250/196
>50/213
0.21/0.60
-
P = proliferating; NP = non-proliferating; ND = not done
ain-house data on non-IDX compounds
b11- or c14-day treatment was performed in galactose-containing media to increase potential drug-induced mitochondrial toxicity
d Company presentation, May 30, 2013
10
Building a Leading Antiviral Franchise
IDX21437: Phase I/II Clinical Trial Design
A phase I/II study assessing single and multiple doses of IDX21437 in healthy
volunteers and HCV-infected patients
Healthy Volunteers
10-300 mg IDX21437
Single
Dose
Treatment-naïve, GT 1
10-300 mg IDX21437
Treatment-naïve, GT 1, Cirrhotic
150 mg IDX21437
Healthy Volunteers
300 mg IDX21437
Multiple
Dose
(7-day)
Treatment-naïve, GT 1
50-300 mg IDX21437
Treatment-naïve, GT 2-6
50-300 mg IDX21437
Treatment-naïve, GT 1, Cirrhotic
150 mg IDX21437
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Building a Leading Antiviral Franchise
IDX21437: Phase I/II Study
7-day Proof-of-Concept Underway
 Single ascending dose portion of the phase I study in healthy volunteers
and HCV-infected patients completed
 Multiple dose (7-day) cohort in healthy volunteers completed
 IDX21437 was safe and well tolerated with no patterns in adverse events or
laboratory assessments observed
 Pharmacokinetics supports once-daily dosing and was similar between
healthy volunteers and HCV-infected patients
 Favorable safety and antiviral activity profile supported initiation of 7-day
proof-of-concept portion of the study which is underway
 Proof-of-concept study data expected 1H 2014
12
Building a Leading Antiviral Franchise
IDX21437: Co-formulated with Samatasvir
Commercially Attractive Formulation
 Developed co-formulated pill of IDX21437 and samatasvir
 Potential benefits of IDX21437 and samatasvir combination
‒ Only one other pan-genotypic combination of nucleotide/NS5A in
development
‒ All-oral, one pill, once-daily dosing
‒ High barrier to resistance
‒ Safe and potent
‒ Low potential for drug-drug interactions
Co-formulated IDX21437 + Samatasvir
13
Building a Leading Antiviral Franchise
Samatasvir: Best-in-Class Profile
Among HCV NS5A Inhibitors
 Strong preclinical profile
- Potent, pan-genotypic activity
- Favorable safety profile
300
EC50
vs
200
HCV
replicon
(pM) 100
- Low potential for drug-drug interactions
 Granted FDA fast track designation
0
1a
1b
2a
Samatasvir
2a
(virus)
3a
4a
5a
Daclatasvir
 3-Day proof-of-concept phase I/II clinical trial in 64 GT1-4 HCV-infected
patients demonstrated safety and pan-genotypic activity
 Two ongoing 12-week phase II all-oral DAA combination HELIX clinical trials
with Janssen Pharmaceuticals, Inc. through a non-exclusive collaboration
evaluating samatasvir, simeprevir and TMC647055
14
Building a Leading Antiviral Franchise
Part A
HELIX-1 Phase II Clinical Trial Design
n=~20
Treatment-naïve, GT 1b/4
50 mg samatasvir + 150 mg simeprevir + RBV
n=~20
Treatment-naïve, GT 1b/4
100 mg samatasvir + 150 mg simeprevir + RBV
n=~20
Treatment-naïve, GT 1b/4
150 mg samatasvir + 150 mg simeprevir + RBV
Study weeks
Week 12
(EOT)
Week 16
(SVR4)
Week 24
(SVR 12)
Week 48
(SVR 24)
 Part B is currently enrolling exploratory arms designed to evaluate safety and
antiviral activity of simeprevir and ribavirin combined with:
-
25 mg dose of samatasvir in GT 1b-infected patients
100 mg dose of samatasvir in GT 6-infected patients
100 mg dose of samatasvir in additional GT 1b-infected patients
 Objectives: safety and tolerability, efficacy (primary SVR4 with supportive SVR12
and SVR24), pharmacokinetics and pharmacodynamics, emergence of resistance
15
Building a Leading Antiviral Franchise
HELIX-1 Phase II Clinical Trial
Part A Results
 Safety: well-tolerated with no treatment-related serious adverse events in the
clinical trial to date
 Antiviral activity:
n
Rapid Virologic Response (RVR);
Measured after 4 weeks of treatment (LOQ)
End Of Treatment Response (EOT);
Measured at end of 12-week treatment period (LOD)
Sustained Virologic Response (SVR4);
Measured 4 weeks after end of treatment (LOD)
Samatasvir/Simeprevir Treatment Groups
50 mg/150 mg
100 mg/150 mg
150 mg/150 mg
20
21
22*
20/20 (100%)
20/21 (95%)
18/19 (95%)
18/20 (90%)
19/21 (90%)
11/19 (58%)
17/20 (85%)
16/21 (76%)
10/19 (53%)
•Three subjects prematurely discontinued treatment within the first 3 weeks (1 lost to follow-up, 2 non-compliance)
•LOQ = limit of quantitation (< 25 IU/mL); LOD=limit of detection (<10 IU/mL)
16
Building a Leading Antiviral Franchise
HELIX-2 Phase II Clinical Trial Design
All-oral 12-week 3-DAA Combination Regimen
n=~20
Treatment-naïve or relapsers, GT 1
50 mg samatasvir + 75 mg simeprevir + 450 mg
TMC647055/r + RBV
n=~20
Treatment-naïve or relapsers, GT 1
50 mg samatasvir + 75 mg simeprevir + 450 mg
TMC647055/r
Study weeks
Week 12
(EOT)
Week 16
(SVR4)
Week 24
(SVR 12)
Week 36
(SVR 24)
 Ongoing clinical trial initiated in December 2013
 Objectives: safety and tolerability, efficacy (primary SVR4 with supportive
SVR12 and SVR24), pharmacokinetics and pharmacodynamics,
emergence of resistance
 SVR4 data anticipated 2H 2014
 Additional exploratory arms may be included
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Building a Leading Antiviral Franchise
Focus on Nucleotides as Cornerstone of HCV Treatment
 Intense development efforts of novel nucleotide prodrugs for > last 2 years
‒ Nucleotide chemistry and prodrug expertise
‒ Strong intellectual property position
Nucleotide
Chemistry
 Raised the bar for nucleotide discovery
‒ Novel bases, prodrugs and sugar moieties
‒ Improved characteristics of nucleotide prodrugs
Prodrug
Expertise
 Over 2,000 nucleotide prodrugs discovered
‒ IDX21437 phase I/II clinical trial ongoing
Innovative and
Focused Efforts
‒ Additional candidates under evaluation


Follow-on nucleotides
“Nuc-nuc” strategy
 Combination of nucleotide/NS5A is preferred pan-genotypic approach
‒ Idenix has assets for 2-DAA combination regimen in-house
‒ Suitable for safe, potent, once-daily fixed-dose combination
 Potential for application in non-HCV therapeutic areas
18
Building a Leading Antiviral Franchise
Idenix - Beyond HCV
Using Chemistry Expertise to Target New Therapeutic Areas
 Concerted effort underway on indications beyond HCV
‒ Leveraging our existing areas of expertise and library into new indications
‒ Exploring applications of 1) nucleotides and 2) prodrug technology
‒ Pursuing future indications while maintaining primary focus on HCV
Infectious Diseases: Idenix
chemical library screened
‒ Wide variety of viruses screened:
flaviviruses, other RNA viruses,
DNA viruses
‒ As an example, >160 compounds
with non-HCV flavivirus inhibitory
activity
‒ Significant antibacterial hits
identified, antifungal screening
ongoing
19
Building a Leading Antiviral Franchise
Oncology: Exploring cytotoxic
nucleotide prodrugs
‒ Prodrug approach to provide tissue specificity
and overcome resistance mechanisms
‒ Ex vivo patient screening identified multiple
active cytotoxic nucleotide prodrugs
‒ Further preclinical efficacy and tissue
selectivity evaluation underway in vivo
‒ Potential for clinical evaluation of nucleotide
prodrugs within 12 to 18 months
Idenix - Beyond HCV
Selected Data from Pilot Programs
Infectious Diseases
Oncology
Virus
>50%
inhib at
10 μM
100%
inhib at
10 μM
>50%
inhib at
1 μM
Dengue
116
34
25
JEV
55
15
17
Yellow fever
13
5
2
West Nile
4
1
0
Rhinovirus
39
19
13
RSV
21
7
0
Influenza
13
3
0
SARS
9
2
0
HSV-1
34
13
4
Viable
Hits
Flaviviruses
(includes
pan-flavi hits)
Other RNA
viruses
DNA virus
Hits with Increasing Activity
 9.9% hit rate – 281 unique compound hits from
2,848 selected representative compounds
20
Building a Leading Antiviral Franchise
Emax (% of tumor cells remaining)
Compound Library Virus Screening
Ex Vivo Screening of Leukemia
Cells from Patients
Idenix
Prodrug 1
Additional
Idenix
Prodrugs
EC50 (µM)
Currently marketed cytotoxic nuc
(parent molecule of prodrugs)
 Active cytotoxic prodrugs identified against
patient tumor cells
Ongoing Intellectual Property Matters with Gilead
Patent Infringement
Litigation
Patent Interference
(Initiated by Idenix)
Patent Interference
(Declared by
USPTO)
Other
2 patent infringement
lawsuits brought by
Idenix (December 2013):
1 patent interference
brought by Idenix (part of
Delaware infringement
lawsuit filed December
2013):
USPTO has declared 2
patent interferences
between:
Gilead has filed 3
invalidity lawsuits
against Idenix in
various jurisdictions
outside the US
1) Idenix v. Gilead, 1:13-cv13052; Idenix co-owned
patents, 6,914,054 and
7,608,597; US District
Court of Massachusetts
2) Idenix v. Gilead, 1:13-cv01987; Idenix co-owned
patent, 7,608,600; US
District Court of Delaware
Idenix v. Gilead, 1:13-cv01987; asserts a claim for
interfering patents between
Idenix '600 patent and
Gilead’s patent 8,415,322;
US District Court of Delaware
1) Idenix’s US Patent
Application 12/131,868
and Gilead’s US Patent
7,429,572; USPTO
assigned Idenix junior
party status for second
phase (initiated Feb 2012)
1) Canada (June 2012)
2) Norway (Sept 2012)
3) Australia (Jan 2013)
2) Idenix's US Patent
7,608,600 and Gilead's
US Patent Application
11/854,218; Idenix initially
declared as senior party
(initiated December 2013)
Idenix will diligently and vigorously protect our investment in
nucleoside drug discovery and our overall IP portfolio
21
Building a Leading Antiviral Franchise
Financial Highlights
$ Millions (unaudited)
FYE
Q1
Q2
Q3
2012
2013
2013
2013
Total Revenue
$69.7
$0.8
$0.1
$0.02
R&D Expense
$70.2
$24.0
$19.8
$21.7
G&A Expense
$24.2
$7.5
$9.1
$8.6
($32.4)
($30.7)
($28.9)
($34.0)
Net Loss
$ Millions
As of December 31, 2013
Cash Balance
22
$122.0
Building a Leading Antiviral Franchise
Significant 2014 Milestones
Milestone
Timeline
IDX21437 phase I/II
 7-day proofof-concept data
1H 2014
IDX21437 + samatasvir phase II
 Initiate
phase II trial
2H 2014
IDX21437 + samatasvir phase II
 SVR4
2H 2014
HELIX-1: samatasvir+simeprevir
 SVR4
Q1 2014
HELIX-2: samatasvir+simeprevir+TMC647055/r
 SVR4
2H 2014
Idenix internal pan-genotypic combination
Janssen collaboration (phase II programs)
Goal: To be prepared for all-oral late-stage
HCV fixed-dose combination studies by year-end 2014
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Building a Leading Antiviral Franchise
24

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