epicept corporation (epct)
DESCRIPTION
OneMedForum NY Company Presentation: EpiCept Corporation, a specialty pharmaceutical company, focuses on the development and commercialization of pharmaceutical products for the treatment of cancer . Learn More at: http://www.onemedplace.com/database/list/cid/13501TRANSCRIPT
1
Corporate Presentation
June 2010
2
Forward-Looking Statements
This presentation contains forward looking statements that involve risks and uncertainties regarding the operations and future results of EpiCept. You should review the company's filings with the Securities and Exchange Commission, including without limitation the company's Form 10-K and Forms 10-Q, which identify specific factors that may cause actual results or events to differ materially from those described in the forward looking statements. The content of this presentation contains time sensitive information that is accurate only as of the date of the presentation. The company undertakes no obligation to revise or update any statements to reflect events or circumstances after the date of this conference call.
3
A specialty pharmaceutical company focused on the development and
commercialization of pharmaceutical products for the treatment of cancer and
pain
Company Description
4
Investment Highlights
Ceplene approved in Europe and launched in UK, Germany and Austria
NDA filed in US, priority review requested
Ceplene is the first efficacious remission maintenance drug for AML
• Met primary endpoint in 320 patient pivotal Phase III trial
• 40% of Ceplene treated patients in first remission were leukemia free at 3 years vs. 26% of control patients (p=0.011)
Substantial upside retained in European partnership with Meda
Market exclusivity for 7 years in US and 10 years in EU
Potential for market expansion in MDS and CML
NP-1 completed Phase II for pain and Crolibulin in Phase I for solid tumors
Azixa partnered with Myriad Pharmaceuticals in Phase II for brain cancer
5
Action Dates
Ceplene
• US NDA filing 2Q 2010
• European commercial launch 2Q 2010
• Canadian NDS approval 3Q 2010
• FDA acceptance of Ceplene NDA / Announced PDUFA Date 3Q 2010
• ODAC meeting 4Q 2010
• US approval Q1 2011
Pipeline
• NP-1 partnership 2H 2010
• Azixa Phase II brain cancer results 2Q 2010
• Crolibulin Phase Ib combination trial initiation 2Q 2010
2010 Upcoming Milestones
6
Ceplene®
Reducing the Risk of Relapse in AML
7
Ceplene®: EU Approved Label
“Ceplene, administered in conjunction with interleukin-2, is indicated for maintenance of remission in adult patients with acute myeloid leukaemia in first remission to prolong the duration of leukaemia free survival.”
8
Meda Partnership
Leading international specialty pharmaceutical company
• Sales and marketing organization of about 1,200 people throughout Europe
• Established sales organizations in the US and more than 40 other countries
• Annual revenues of approximately $1.8 billion
• Oncology/hematology presence with several products, including OnsolisTM indicated for breakthrough pain in cancer patients
Up to $40 million in upfront payments and milestones, plus escalating double digit royalty
EpiCept is responsible for Ceplene's commercial supply
Territory includes Europe, Japan, China, Australia and selected Asian countries
Selective EU launches underway
9
Changing the AML Treatment Paradigm
Induction and Consolidation
Therapy
Complete Remission
(70%)
Bone Marrow Transplant
Remission Maintenance: Ceplene+IL-2
Remission Maintenance: Current SOC(no treatment)
(>80% Relapse)
• 90 – 95% mortality at 5 years
• Median survival 6 - 9 months
• 40% Ceplene+IL-2 patients reach LFS at 3 years vs. 26% of SOC patients
• Median improvement of 64 weeks in overall survival
• If successful it is a true cure
• High procedural mortality rate
No Remission
(30%)
10
Rationale for the Use of Ceplene with IL-2
IL-2
Activates and expands
T and NK cells
Ceplene (HDC)Protects T and NK cells against inactivation and apoptosis
Elimination of leukemic cells and protection against relapse
- T cells and NK cells can attack and eliminate AML blasts - T and NK cell functions determine relapse risk in AML
NK
NK
AML blast
11
Ceplene: Mechanism of Action in AML
NKp46
Activating Receptors
Myeloid Cell
NK Cell
H2 receptor
Cytotoxicity
O2
AML Blasts
NKG2D
NADPH oxidase
Response to IL-2
Apoptosis
12
Ceplene: Mechanism of Action in AML
Lysed
NKp46
Activating Receptors
Myeloid Cell
NK Cell
H2 receptor
Cytotoxicity
Ceplene (HDC)
NKG2D
NADPH oxidase
Response to IL-2
13
Pivotal Phase III Study Design, Trial Endpoints and Analyses
• Primary endpoint: Leukemia-free survival (LFS) after 3 years
• Secondary endpoints:
• Overall survival (OS)
• LFS in CR1 and CR>1 subgroups
• LFS rates at 6, 12, 18, 24 and 36 months
• Safety and quality-of-life (QLQ-C30)
AML Remissions(n=320)
18 Months 18 MonthsEndpointAnalysis
Ceplene+IL-2 (n=160)10 cycles over 18 months followed by 18 months of observation
Randomized
• Key prognostic variables tested by multivariate analyses
• Additional follow-up at 5 and 6 years
Standard of Care (No Treatment)(n=160)
14
Results of the Pivotal Phase III Study:Leukemia-Free Survival
Overall Population CR1 Population
15
Results of the Pivotal Phase III Study: Overall Survival
Months from Randomization
Ove
rall
Su
rviv
al (
%)
P = 0.118
CR1 Population
Ceplene/IL-2 (n=129) Control (n=132)
Ceplene/IL-2 (n=160) Control (n=160)
Overall Population
P = 0.161
100
80
60
40
20
0
100
80
60
40
20
00 12 24 36 48 7260 0 12 24 36 48 7260
Months from RandomizationMonths from Randomization
Ove
rall
Su
rviv
al (
%)
P = 0.118
CR1 Population
Ceplene/IL-2 (n=129) Control (n=132)
Ceplene/IL-2 (n=160) Control (n=160)
Overall Population
P = 0.161
100
80
60
40
20
0
100
80
60
40
20
00 12 24 36 48 7260 0 12 24 36 48 7260
Months from Randomization
Overall Population CR1 Population
16
Summary: Clinical Benefit of Ceplene+IL-2
• Phase III study met primary endpoint of LFS rate at 3 years
Overall Population CR1 Population
3 Year LFS
Log Rank
Treatment: 34%Control: 24%p = 0.008
Treatment: 40% Control: 26%p = 0.011
5 Year LFS
Log Rank
Treatment: 30%Control: 21%p = 0.017
Treatment: 34% Control: 22%p = 0.025
3 Year OS
Log Rank
Treatment: 48%Control: 44%p = 0.161Median Improvement: 24 weeks
Treatment: 55% Control: 46%p = 0.118Median Improvement: 64 weeks
17
Ceplene: US Regulatory Status
Pre-NDA meeting completed
NDA filed June, 2010
82% concurrence of FDA and EMEA approvals since 2006(1)
Key issues to be addressed:
1. Approval based on single pivotal trial
2. Acceptability of Leukemia Free Survival as primary endpoint
3. Trial design - Isolation of Ceplene’s contribution to efficacy vs. IL-2
(1) Source: FDA – Center for Drug Evaluation & Research, New Drug Review: 2009 (FDA/CMS Summit December 3, 2009), includes New Molecular Entities only
18
FDA Issue 1: Single Pivotal Trial
Robust statistical outcome of pivotal study (p<0.008)
Significant unmet medical need
Orphan indication
Numerous precedents for approval based on a single randomized pivotal trial for orphan indications and/or high unmet medical need if the data demonstrates substantial evidence of efficacy (Folotyn, Istodax, Velcade)
19
FDA Issue 2: Acceptability of LFS as Appropriate Primary Endpoint
Data supports LFS as a surrogate marker for survival
Median improvement of 64 weeks on overall survival
No adverse effect seen on survival
Numerous precedents in oncology for accelerated approval based on response rate, progression free survival, time to progression (Gleevec, etc.)
Cooperative group studies use LFS as primary endpoint for AML
20
FDA Issue 3: Trial Design - Isolation of Ceplene’s Contribution to Efficacy vs. IL-2
Only Ceplene+IL-2 pivotal trial successful for remission maintenance
Six separate IL-2 monotherapy AML trials have failed to demonstrate IL-2 benefit
Meta and Bayesian analysis of background IL-2 monotherapy “contribution” concluded incremental contribution of Ceplene beyond IL-2 background at p<0.05
21
IL-2 Monotherapy Trials vs. Ceplene+IL-2
Trial NAge
(years)
Monthly IL-2 Dose
MIU/m2
P-values
Blaise et al. 78 <50 120 0.54
CALGB 9720 163 ≥60 81 0.47
CCG-2961 289 ≤21 52 0.49
CALGB 19808 214 <60 91 0.13
ALFA 9801 161 50-70 25 0.88
EORTC/GIMEMA 288 <61 12 - 24 0.57
Ceplene+IL-2
Phase III Study 320 18-84 15 0.01
22
IL-2 Monotherapy vs. Standard of Care
Dis
ease
-Fre
e S
urvi
val
Pro
babi
lity
No further treatment
P=0.47
Time (years)
Dis
ease
-Fre
e S
urvi
val
Pro
babi
lity
No further treatment
P=0.47
Time (years)
100
80
60
Standard of careIL-2
0 20 40 60
0.0
0.2
0.4
0.6
0.8
1.0
Months from 2nd randomization
P(E
ven
t Fre
e S
urv
iva
l)
Arm1Arm2
p= 0.88
IL-2No treatment
P=0.88
Months from IL-2 randomization
Dis
ea
se
-fre
e s
urv
iva
l
Ov
era
ll s
urv
iva
l
Blaise et al. CALGB 9720 ALFA 9801
Years from IL-2 randomization
CALGB 19808 CCG 2961
Note: Kaplan analysis curve for EORTC/GIMEMA trial not yet published
23
Ceplene: Market Opportunity
US
Prevalence 38,000
New Patients/Year 13,000(1)
Complete Remissions Achieved (70%) 9,100
Less Bone Marrow Transplants (20-25%) (2,275)
Annual New Patient Candidates 6,825
Median Annual Cost/Patient $ 35-40K
Ceplene Peak Market Potential $235-270 MM
(1) National Cancer Institute (2) European LeukemiaNet (ELN)
24
Ceplene US Commercialization Strategy
• Orphan protection granted, 7 years market exclusivity
• First and only product to prevent AML relapse
• No competing products in late stage development
• Continue targeting top KoLs through symposia, conferences, etc.
• Initiate pre-launch Ceplene experience program
• Outreach to patient advocate groups
• Planning self launch in US with 20-25 MSLs/sales representatives
• Target audience 1500 hematologists
• Target top 200 US hospitals
• Gain inclusion of Ceplene+IL-2 in AML treatment guidelines
25
Ceplene Summary
Ceplene+IL-2 is first and only therapeutic regimen to prevent relapse and prolong LFS in AML patients in remission
Ceplene+IL-2 LFS rate at 3 years of 40% vs. 26% for control (p=0.011) is clinically relevant for AML patients in first remission
Cycles of daily Ceplene+IL-2 s.c. injections at home are well-tolerated and are not an impediment to AML patients’ QoL or functional status
No competing therapy in Phase II or III clinical development
European partnership established, launches underway
Pursuing North American regulatory approvals
Orphan drug designation provides 7 years market exclusivity in US and 10 in EU
26
EpiCept™ NP-1: Product Profile
• Phase III ready topical cream for the relief of pain associated with post- herpetic neuropathy (PHN), diabetic neuropathy and chemotherapy
• 4% amitriptyline plus 2% ketamine combination provides pain relief equivalent to current therapies
• Over 1,300 patients treated in seven clinical trials
• Effective and well-tolerated in chronic use
• Better side effect profile than oral therapies
• Skin irritation is infrequent; fatigue and drowsiness are rare and mild
• NP-1 represents a large, low risk commercial opportunity
27
EpiCept™ NP-1: PHN Clinical Data
NP-1 (n=32)
Placebo(n=46)
Baseline (mean)
6.47+1.65 6.5+1.60
Day 21(mean) 3.28+ 2.1 4.35+2.2
Mean Change 3.19 + 2.0
p=0.026
2.15+1.8
Efficacy vs. placebo tested in 150 PHN patients in dose response trial
Dose-response trial met primary endpoint; p=0.026
Strong analgesic effect
Additive to or can replace standard of care
Effective in persistent pain
Supports advancement to Phase III
28
EpiCept™ NP-1: PHN Clinical Data Phase II, Non-inferiority design, vs. gabapentin and placebo in PHN for 4 weeks
Met primary endpoint: • Efficacy superior to placebo, p =.044• Not inferior to gabapentin, p =.84
Results indicate at least equivalent efficacy to unit market leader
Better side effect profile
Supports advancement to Phase III
Primary Endpoint: Mean pain score
NP-1n=135
Placebon=76
Gabapentinn=138
Baseline 6.04 ± 1.25 6.37 ± 1.32 6.32 ± 1.17
At the end of week 4 3.54 ± 1.98 4.22 ± 2.30 3.55 ± 1.93
Mean difference in pain score
2.42 ± 0.18
p =.044
1.88 ± 0.23 2.47 ± 0.18
ITT Population
29
2008 US market size: 4.7 million patients, $2.6 billion in sales
2018 est. US market size: 6.1 million patients; $5.1 billion in sales
Key market drivers: aging population and unmet medical need due to ineffective therapy
Competing products: gabapentin (generic), Lyrica (Pfizer), Cymbalta (Eli Lilly), Lidoderm (Endo)
• No current therapy effective in more than 50% of patients• Oral therapies have CNS side effects• Lidoderm patch not convenient for many areas prone to pain
May be used in combination with other therapies
Patent protection to 2021 plus US orphan drug designation in PHN
EpiCept™ NP-1: Market Opportunity
30
Crolibulin
• Small molecule, vascular disruption agent (VDA), disrupts newly formed vascular cells and blood flow to tumor
• Superior anti-tumor (apoptotic) activity compared to other VDAs
• Enhanced efficacy in combination with Cisplatin or other chemotherapeutics
• Active on multi-drug resistant cells
• DLT/MTD identified
• Activity in resistant hepatocellular carcinoma
• Objective evidence of anti-tumor response by CT perfusion
• Combination trial to be initiated Q2 2010
• Strong intellectual property position
31
Azixa™ (MPC-6827): Myriad Pharmaceuticals
Small molecule, apoptosis inducer with VDA activity, concentrates in the CNS
Two Phase I studies completed in brain cancer: primary and metastatic
Treatment schedule: Once a week for 3 weeks on 28 day cycle
Reported Phase I results
- Reached Maximum Tolerated Dose (MTD)
- Signs of efficacy: measurable reduction in tumor size in primary glioblastoma and patients with secondary metastases
Myriad Pharmaceuticals conducting Phase II trials dosing in primary and metastatic brain cancer
32
Investment Highlights
Ceplene approved in Europe and launched in UK, Germany and Austria
NDA filed in US, priority review requested
Ceplene is the first efficacious remission maintenance drug for AML
• Met primary endpoint in 320 patient pivotal Phase III trial
• 40% of Ceplene treated patients in first remission were leukemia free at 3 years vs. 26% of control patients (p=0.011)
Substantial upside retained in European partnership with Meda
Market exclusivity for 7 years in US and 10 years in EU
Potential for market expansion in MDS and CML
NP-1 completed Phase II for pain and Crolibulin in Phase I for solid tumors
Azixa partnered with Myriad Pharmaceuticals in Phase II for brain cancer
33