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| 8-K - FORM 8-K - DELCATH SYSTEMS, INC. | d463116d8k.htm |
 Investor Presentation
(NASDAQ: DCTH)
January 2013
Exhibit 99.1 |
 2
DELCATH SYSTEMS, INC
Forward-looking Statements
Private Securities Litigation Reform Act of 1995 provides a safe
harbor for forward-looking statements made by the
Company or on its behalf. This presentation contains forward-looking
statements, which are subject to certain risks and uncertainties that can
cause actual results to differ materially from those described. Factors that
may cause such differences include, but are not limited to, uncertainties
relating to: timing of completion of the FDA’s review of our NDA, the
extent to which the FDA may request additional information or data and our ability to provide the same in a timely
manner, acceptability of the Phase 1, 2 and 3 clinical trial data by the FDA, FDA
approval of the Company's NDA for the treatment of metastatic ocular
melanoma to the liver, adoption, use and resulting sales, if any, for the chemosaturation
system in the United States, adoption, use and resulting sales, if any, for the
Hepatic CHEMOSAT delivery system in the EEA, our ability to successfully
commercialize the chemosaturation system in various markets and the potential of the
chemosaturation system as a treatment for patients with cancers in the liver, the
timing and our ability to successfully enter into strategic partnership and
distribution arrangements in foreign markets including Australia and key Asian markets
and resulting sales, if any, from the same, patient outcomes using the Generation 2
system, approval of the current or future chemosaturation system for other
indications and/or for use with various chemotherapeutic agents, actions by the
FDA or other foreign regulatory agencies, our ability to obtain reimbursement for
the CHEMOSAT system in various markets, submission and
publication of the Phase II and III clinical trial data, the timing and results of
research and development projects, the timing and results of future clinical
trials including the initiation of clinical trials in key Asian markets with
the Hepatic CHEMOSAT Delivery System device for intra-hepatic arterial delivery and extracorporeal
filtration of doxorubicin, approval of the Hepatic CHEMOSAT Delivery System to
delver and filter doxorubicin in key Asian
markets and adoption, sales, if any, and patient outcomes using the same, the
timing, price and use, if any, of the committee equity financing facility
with Terrapin, the timing and use, if any, of the line of credit from SVB and our ability to
access this facility and uncertainties regarding our ability to obtain financial
and other resources for any research, development and commercialization
activities. These factors, and others, are discussed from time to time in
our filings with the Securities and Exchange Commission. You should not
place undue reliance on these forward-looking statements, which speak
only as of the date they are made. We undertake no obligation to publicly update or revise these forward-
looking statements to reflect events or circumstances after the date they are
made. |
 3
DELCATH SYSTEMS, INC
Investment Considerations
Concentrating the Power of Chemotherapy
•
Commercial stage company focused on oncology
•
Proprietary CHEMOSAT delivery systems allow unique whole organ
therapy for the liver
•
CHEMOSAT system has demonstrated extension of progression free
survival
•
Addressing large unmet market need for cancer patients who usually die
of liver failure
•
2013 estimated addressable market opportunity of $2.3 billion
•
Expanding clinical data expected to broaden clinical use and indication
•
On the cusp of realizing the potential:
o
EU commercial launch underway
o
Reimbursement in additional key EU markets expected in Q1
o
U.S.
NDA
under
review
–
PDUFA
date
June
15,
2013
•
Attractive financial model, $80 million in available resources and
experienced management team to execute plan |
 4
DELCATH SYSTEMS, INC
The Delcath CHEMOSAT System
Minimally Invasive, Repeatable Liver Procedure That Could Complement Systemic
Therapy 1.
ISOLATE
2.
SATURATE
3.
FILTRATE
•
Improves disease
control in the liver
•
Treats entire liver
(macro and micro)
•
Controls systemic
toxicities
•
Allows for over 100x
effective dose
escalation at tumor
site
Chemosaturation |
 5
DELCATH SYSTEMS, INC
Melanoma Liver Metastases
A Great Demonstration of CHEMOSAT’s Potential
•
A challenging histology
•
Notoriously insensitive to
systemic chemotherapy and
focal interventions
•
CHEMOSAT has
demonstrated ability to extend
progression free survival
Our Opportunity
•
Ability to achieve ultra-high concentrations of chemotherapy that
are effective on a wide variety of cancers in the
liver •
Physicians are recognizing the broad applicability of CHEMOSAT, based
on early EU experience |
 6
DELCATH SYSTEMS, INC
Clinically Differentiated Results
•
Phase 1, 2 and 3 trials produced positive results in multiple histologies
•
Melanoma Liver Mets
o
Positive Phase 3 results in hepatic metastatic melanoma
o
n=93 (90% ocular melanoma, 10% cutaneous melanoma)
•
Neuroendocrine Tumor (NET) Liver Mets
o
mNET cohort in Phase 2 trial showed encouraging 42% objective response rate
(ORR) vs ~10% for approved targeted therapy
o
median overall survival of ~32 months on ITT basis
•
Hepatocellular Carcinoma (HCC)
o
Positive signal with high-dose melphalan in HCC cohort of Phase 2 trial (5/8
patients) is encouraging when approved systemic therapies have modest
efficacy and challenges with tolerability
•
Colorectal Cancer (CRC) Liver Mets
o
Data from surgical Isolated Hepatic Perfusion (IHP) with melphalan indicates
strong potential in well-defined patient population with earlier stage
CRC yielding ~50-60% median response rate and median OS of
17.4-24.8 mos •
Safety profiles consistent with pivotal US Phase 3 melanoma trial
|
 7
DELCATH SYSTEMS, INC
INDEPENDENT
REVIEW
COMMITTEE
(IRC)
ASSESSMENT
-
UPDATED
ANALYSIS
(4
June
2012)
Hepatic progression-free survival (IRC)
Hazard ratio = 0.50
(95%
CI
0.31
–
0.80)
P=0.0029
0
5
10 15
20
25
30
Months
7.0
1.7
1.0
0.8
0.6
0.4
0.2
Proportion of patients surviving
5.3 mo
Intent-to-treat population
Chemosaturation (CS-PHP)
Best alternative care (BAC)
Positive Phase 3 Results –
Primary Endpoint hPFS
CS-PHP Demonstrated 4x or 5.3 months Improvement in Primary Endpoint of
hPFS 0.0 |
 8
DELCATH SYSTEMS, INC
INVESTIGATOR
ASSESSMENT
-
UPDATED
ANALYSIS
(4
June
2012)
Overall progression-free survival (investigator)
Months
5.4
1.6
Proportion of patients surviving
Hazard ratio = 0.42
(95%
CI
0.27–
0.64)
P<0.0001
3.8 mo
Intent-to-treat population
Chemosaturation (CS-PHP)
Best alternative care (BAC)
Positive Phase 3 Results –
Overall PFS
CS-PHP also Demonstrated a Highly Statistically Significant Improvement in
Overall PFS 1.0
0.8
0.6
0.4
0.2
0.0
0
5 10 15
20
25
30 35 40
45
50 55 |
 9
DELCATH SYSTEMS, INC
TOTOL CS-PHP vs BAC ONLY
Proportion of subjects surviving
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
12
36
0
24
48
60
11.4
Total
CS-PHP
incl.
crossover
BAC only
Months
4.1
Intent-to-treat population
7.3 mo
Overall Survival –
Exploratory Subset Analysis
Overall
Survival
Tail
For
CS-PHP
Treated
Patients |
 10
DELCATH SYSTEMS, INC
Phase
2
Multi-Histology
NCI
Trial
–
Summary
•
Strong efficacy signals in mNET
o
42% objective Response Rate (ORR) vs ~10%
for approved targeted therapy
o
66% patients had hepatic tumor shrinkage and
durable disease stabilization
•
Positive Signal in primary hepatic malignancies
(HCC and Cholangiocarcinoma) in 5 of 8 patients
•
Similar safety profiles across tumor types |
 11
DELCATH SYSTEMS, INC
Phase 2 NCI Trial –
Metastatic Neuroendocrine Cohort
Pre-CS
(Baseline)
Post-CS #2
(+4 Months)
Post-CS #1
(+6 Weeks)
Compelling Clinical Data in Attractive mNET Market
Phase 2 mNET Tumor Cohort (n=24)*
Number (n)
Tumor Types
Pancreatic NET
13
Carcinoid tumor
3
Other NET
8
Response
Partial Response (PR)
10
Stable disease (SD)
6
Progressive disease
3
Not assessed or evaluable
5
Objective Response Rate
42%
Median Duration of Hepatic Response
Partial Response (n-10)
23.5 months
Partial Response/Stable Disease (n=16)
16.8 months
Hepatic Progression Free Survival (IIT n=24)
Median Hepatic PFS
16.8
Min/Max
2.1, 64.1
Overall Survival After CS
Median
31.9 months
Min/Max
2.4, 81.1
66%
disease
control |
 12
DELCATH SYSTEMS, INC
Phase 2 NCI Trial –
Hepatobilliary Carcinoma Cohort
•
Best hepatic tumor response by modified RECIST assessed by investigators
o
Partial response (PR)
1 patient
o
Stable disease (SD)
4 patients
o
Progressive disease
1 patient
o
Not assessed or evaluable
2 patients
•
Median duration of response
o
hPR (N=1)
6.42 months
o
hPR/SD (N=5)
8.12 months
•
Hepatic progression free survival (ITT N=8)
o
Median
5.60 months
o
Minimum, Maximum
2.7, 12.2 months
•
Overall survival (ITT N=8)
o
Median
9.12 months
o
Minimum, Maximum
3.4, 20.5 months
•
HCC is the most common primary cancer of the liver, with approximately 750,000* new
cases diagnosed worldwide annually
•
Intend
to
initiate
new
HCC
trials
with
CHEMOSAT
Encouraging Positive Signal for Primary Liver Cancer
*Source: GLOBOCAN |
 13
DELCATH SYSTEMS, INC
•
Substantial clinical evidence of benefit of using ultra-high dose
melphalan to treat mCRC via isolated hepatic perfusion (IHP)
procedure
o
Over 800 patients treated in 15 studies since 1998
o
Patients treated only once
o
Median response rate of ~50-60% and median OS of 17.4 –
24.8 mos1,2
•
Delcath
Phase
2
NCI
Chemosaturation
Trial
–
mCRC
Cohort
o
Challenges enrolling at NCI due to competing FOLFOX & FOLFIRI trials
o
17
patients treated since 2004
o
Safety profile –
expected and consistent with pivotal FDA Phase III
melanoma trial
•
Intend to invest in new mCRC trials with CHEMOSAT Melphalan
Strong Rationale for Using CHEMOSAT with Melphalan to Treat mCRC
1)
van Iersel LB, Gelderblom H, et al. Ann Oncol. 2008;19:1127-34
2)
Alexander, HR, Barlett DL, et al. Ann Surg Oncol, 16:1852-9, 2009
Phase 2 NCI Trial –
mCRC Cohort |
 14
DELCATH SYSTEMS, INC
Additional Clinical Data Generation
•
Goals:
Expand US (CS-PHP: MEL) label indications beyond the
initial indication we are seeking
Generate robust clinical data to support commercialization
•
FDA has accepted IND Amendment to include Gen 2 device in
Expanded Access Program (EAP), compassionate use (CU),
and all future clinical trials
•
On track to initiate EAP to treat first patient
•
Activate EU Registry to systematically collect data from
commercial experience
Establish CHEMOSAT as the Standard of Care (SOC) for Disease Control in the
Liver |
 15
DELCATH SYSTEMS, INC
2013 Clinical Development Plan
•
Planned 2013 studies, pending discussion with the FDA:
Hepatocellular carcinoma (HCC)
o
Global Phase 3 Randomized CHEMOSAT Melphalan vs. BSC for
Sorafenib Failure
Advanced colorectal cancer (CRC) with liver dominant metastasis
o
Global Phase 3 Randomized CHEMOSAT Melphalan vs.
Available Alternatives
Neuroendocrine tumor (NET) with liver dominant disease
o
Global Phase 3 Randomized CHEMOSAT Melphalan vs.
Available Alternatives
•
Phase 2 studies in multiple indications: HCC, NET, CRC, melanoma
•
Global
Investigator-initiated
trials
(IITs)
–
opportunity-driven
Establish CHEMOSAT as the Standard of Care (SOC) for Disease Control in the
Liver |
 16
DELCATH SYSTEMS, INC
CHEMOSAT -
Potential Multi-Billion Dollar Global Market
8,708
6,563
4,085
8,212
7,202
33,966
19,861
33,953
52,143
5,585
7,671
99,749
0
25,000
50,000
75,000
100,000
125,000
150,000
175,000
200,000
USA
EU
APAC
$2.3 Billion Market Opportunity in 2013 with Pharmaceutical-Like Gross
Margins Sources: LEK Consulting, GLOBOCAN, Company estimates.
EU: Initial target countries of Germany, UK, Italy, France, Spain, Netherlands,
Ireland. APAC: Initial target countries of China, Japan, S. Korea, Taiwan,
Australia. Assumes 2.5 treatments per patient.
Assumes EU ASP of $15K; US ASP of $25K; APAC ASP of $5K.
55,389
$2.2 B
42,367
$2.6 B
189,943
$2.2 B
HCC
CRC
Melanoma
NET
$2.3B Initial Opportunity
•
$100M Initial on-label
opportunity in Ocular
Melanoma in US*
•
$2.2B multi-histology
opportunity in EU |
 17
DELCATH SYSTEMS, INC
Approved (CE Mark Device)
NDA Filing Accepted by the FDA with PDUFA goal date of June 15, 2013
Application Submitted/ Planned –
Mutual Recognition of European CE Mark
Global Commercialization Status
Addressing A Multi-Billion Dollar Global Market |
 18
DELCATH SYSTEMS, INC
CHEMOSAT: EU Launch Underway
•
Marketing in target EU countries -
Italy, Germany, France,
UK, Ireland, NL, Spain
•
Training completed in key centers
o
Eight EU Clinical Sites activated in 2012
•
EU clinicians using CHEMOSAT for a broad range of liver
metastases
o
Use includes: cutaneous melanoma, ocular melanoma, colorectal
cancer (CRC), gastric cancer, breast cancer, neuroendocrine tumor
(NET), hepatocellular carcinoma (HCC) and Cholangiocarcinoma
•
EU reimbursement gaining momentum
o
Italy
–
Reimbursement
pathway
established
o
Germany,
UK
–
Reimbursement
anticipated
Q1
2013
Rapid
expansion
of
EU
Clinical
and
Commercial
footprint
expected
for
2013 |
 19
DELCATH SYSTEMS, INC
U.S. NDA Under Review
•
PDUFA date: June 15, 2013
•
Initial indication: unresectable metastatic ocular melanoma
in the liver
o
Provides lowest risk pathway to FDA approval and fastest access
•
NDA filing included:
o
Comprehensive set of additional data in a new FDA compliant
CDISC database
o
Gen 2 filter as part of the Chemistry, Manufacturing and Control
(CMC) module
•
Oncology Drug Advisory Committee (ODAC) panel
expected May 2013
•
Three meetings scheduled with FDA to discuss clinical
programs for planned label expansions in each of NET,
HCC,CRC |
 20
DELCATH SYSTEMS, INC
U.S. Commercialization Strategy
•
Launch in Q4 2013 assuming approval on PDUFA date of June
15, 2013
•
Initial commercial focus on centers that are active in the EAP or
participated in the Phase 3 clinical trial
•
Utilize active EAP hospitals as Centers of Excellence for training
and support of new centers
•
Intend to seek chemosaturation specific CPT reimbursement
code, based upon value proposition relative to other cancer
therapies
•
Educate Medical Oncologists via Medical Science Liaison (MSL)
•
Direct strategy to sell to hospital based Interventional
Radiologists and Surgeons
Participating EAP Centers Provide Immediate Commercial Footprint
|
 21
DELCATH SYSTEMS, INC
Barriers to Entry
•
Patent Protection
o
6 U.S. patents in force and 6 U.S. patent applications pending
o
9 foreign patents in force (with patent validity in 25 countries) and 14 foreign
patent applications pending
o
Primary US device patent set to expire August 2016
o
Up to 5 years of patent extension post FDA approval
•
Trade Secret Protection
o
Developed improved filter media via proprietary manufacturing processes
•
FDA Protection
o
Orphan Drug Designation granted for melphalan in the treatment of ocular
melanoma, cutaneous melanoma and metastatic neuroendocrine tumors, as well as
for doxorubicin in the treatment of HCC
Provides 7 years of marketing exclusivity post FDA approval
o
Additional Orphan Drug applications to be filed for other drugs and indications,
including melphalan for HCC and CRC
Multiple Levels of Protection |
 22
DELCATH SYSTEMS, INC
Financial Summary
Cash & Cash Equivalents:
$28.3 million at September 30, 2012
ATM Program
$21.5 million remaining as of November 2012
Committed Equity Financing
Facility (CEFF)
Up to $35 million as of December 5, 2012
Working Capital Line of Credit:
$20.0 million credit facility
Debt:
None
Cash Spend:
$14.6 million in 3Q2012
Projected Q4 < $12 million
Shares Outstanding:
75.1
million
(85.5
million
fully
diluted
¹
)
as
of
November 2012
1) Fully diluted includes an additional 4.8 million options and 5.6 million
warrants $80 Million in Available Resources to Execute Plan
|
 23
DELCATH SYSTEMS, INC
Management: A Track Record of Success
Executive
Title
Prior Affiliation(s)
Years of
Experience
Eamonn Hobbs
President and CEO
AngioDynamics, E-Z-EM
32
Graham Miao, Ph.D.
EVP & CFO
D&B, Pagoda Pharma, Schering-Plough,
Pharmacia, JP Morgan
23
Krishna Kandarpa, M.D.,
Ph.D.
CSO and EVP, R&D
Harvard, MIT(HST), Cornell, UMass
33
Agustin Gago
EVP, Global Sales
AngioDynamics, E-Z-EM
31
Jennifer Simpson, Ph.D.
EVP, Global Marketing
Eli Lilly (ImClone), Johnson & Johnson
(Ortho Biotech)
23
Peter Graham, J.D.
EVP, General Counsel &
Global Human Resources
Bracco, E-Z-EM
18
David McDonald
EVP, Business Development
AngioDynamics, RBC Capital Markets
30
John Purpura
EVP, Regulatory Affairs & Quality
Assurance
E-Z-EM, Sanofi-Aventis
29
Harold Mapes
EVP, Global Operations
AngioDynamics, Mallinckrodt
27
Gloria Lee, M.D., PH.D.
EVP, Clinical & Medical Affairs
Hoffmann-La Roche, Syndax
Pharmaceuticals, Inc.
21
Bill Appling
SVP Medical Device R&D
AngioDynamics
27
Dan Johnston, Ph.D.
VP, Pharmaceutical R&D
Pfizer, Wyeth
12 |
 24
DELCATH SYSTEMS, INC
2012 Accomplishments
•
First patients treated with CHEMOSAT Melphalan in
Europe in January
•
Obtained CE Mark for Gen 2 CHEMOSAT Melphalan filter
in April
•
Executed contract for MSL services in EU in 1Q 2012
(Quintiles was selected to support EU launch of
CHEMOSAT)
•
Secured agreements with 14 leading cancer centers in EU
•
8 EU Clinical Sites Activated for commercial use
•
US NDA submitted in August 2012
•
US NDA accepted with PDUFA date of June 15, 2013
•
Obtained CE Mark for CHEMOSAT Doxorubicin in October
•
Interim reimbursement established in Italy in December
|
 25
DELCATH SYSTEMS, INC
2013 Anticipated
Milestones
•
First
patient
enrolled
in
EAP
-
Q1
2013
•
Secure
interim
reimbursement
in
Germany
and
UK
-
Q1
2013
•
Submission for publications of Phase 3 data and mNET arm of Phase 2 data in
Q1 2013
•
Initiate EU Registry -
Q1 2013
•
First commercial sale in APLA –
Q2 2013
•
ODAC Panel Meeting May 2013
•
Receive NDA approval of Delcath’s chemosaturation system by PDUFA date of
June 15, 2013
•
Commence Company’s first investigator initiated trial (IIT) –
Q2 2013
•
First patient enrolled in Company sponsored trial (CST) to expand indications
– Q4 2013
•
US commercial launch of Delcath’s chemosaturation system –
Q4 2013
•
First patient enrolled in Taiwan HCC pivotal trial –
Q4 2013
•
Execute strategic partnership for China |
 26
DELCATH SYSTEMS, INC
A Compelling Investment Opportunity
•
Commercial stage company focused on oncology
•
CHEMOSAT provides a unique whole organ therapy for the liver
•
CHEMOSAT system has demonstrated extension of progression
free survival (PFS)
•
Addressing large unmet market need for cancer patients who
usually die of liver failure
•
EU commercial launch underway
•
2013 estimated addressable market opportunity of $2.3 billion
•
Reimbursement in additional key EU markets expected in Q1
•
U.S. NDA under review
•
Expanding clinical data expected to broaden clinical use and US
labeling
•
Attractive financial model, $80 million in available resources
and experienced management team to execute plan
. |
 ©
2011 DELCATH SYSTEMS, INC. ALL RIGHTS RESERVED |
 28
DELCATH SYSTEMS, INC
Appendices |
 29
DELCATH SYSTEMS, INC
LIVER CANCER TREATMENT
OPTIONS
Appendix 1 |
 30
DELCATH SYSTEMS, INC
Existing Liver Cancer Treatments Have Significant Limitations
The Problem
•
Metastatic disease to the liver, brain or lungs is often the life-
limiting location of solid tumors
o
Often life-limiting or leads to withdrawal of systemic treatments in
favor of palliative care
•
Effective treatment for patients with liver-limited or dominant
cancers remains a clinical challenge
o
Can be diffuse
o
Often not responsive to chemotherapy and radiation therapy
•
Whole organ therapy creates a new option for patients in the
management of liver dominant disease |
 31
DELCATH SYSTEMS, INC
Existing Liver Cancer Treatments Have Limitations
Unmet Medical Need Exists for More Effective Liver Cancer Treatments
Treatment
Advantages
Disadvantages
Systemic
–
Non-invasive
–
Repeatable
–
Systemic toxicities
–
Limited efficacy in liver
Regional
(e.g., Isolated Hepatic Perfusion)
–
Therapeutic effect
–
Targeted
–
Invasive/limited repeatability
–
Multiple treatments are
required but not possible
Focal
(e.g. surgery, radioembolization,
chemoembolization, radio
frequency ablation)
–
Partial removal or
treatment of tumors
–
Only 10% to 20% resectable
–
Invasive and/or limited
repeatability
–
Treatment is limited by tumor
size, number of lesions and
location
–
Tumor revascularization
–
Cannot treat diffuse disease |
 32
DELCATH SYSTEMS, INC
Diffuse Hepatic Metastases from Melanoma
•
Diffuse disease in the liver is prevalent
•
Effective treatment for patients with liver-limited or dominant cancers
remains a clinical challenge
•
Whole organ therapy creates a new option for patients in the management
of liver dominant disease |
 33
DELCATH SYSTEMS, INC
Concentrating the Power of Chemotherapy for Disease Control in the Liver
Our Solution –
Whole Organ-Focus Disease Control
•
Our proprietary CHEMOSAT system isolates the liver
circulation, delivers an ultra-high concentration of
chemotherapy (melphalan) to the liver and filters most of the
chemotherapy out of the blood prior to returning it to the patient
•
The procedure typically takes approximately two hours to
complete and involves a team including the interventional
radiologist and perfusionist
•
CHEMOSAT (Gen 2) has demonstrated minimal systemic
toxicities and impact to blood components in initial commercial
use and may complement systemic therapy
•
CHEMOSAT has been used on approximately 200
patients to
date through clinical development and early commercial launch
|
 34
DELCATH SYSTEMS, INC
CHEMOSAT MARKET OPPORTUNITY
BY DISEASE & TARGET COUNTRIES
Appendix 2 |
 35
DELCATH SYSTEMS, INC
•
Europe –
Largest near-term opportunity
•
CRC –
Largest opportunity worldwide
•
Melanoma –
Largest opportunity is in the US
•
China –
Largest opportunity for HCC
Market Opportunity by Disease (patients)
Market Opportunity defined as Total Potential
Market
(TPM)
for
CHEMOSAT
®
1.Primary cancer incidence
2.Adjusted for predominant disease in the liver (primary
or metastatic cancer)
3.Adjusted
for
addressable
patients
via
Delcath
CHEMOSAT
® |
 36
DELCATH SYSTEMS, INC
Europe Market by Disease –
Device Only
Germany
(Direct)
UK
(Direct)
France
(Indirect)
Italy
(Indirect)
Spain
(Indirect)
Netherlands
(Direct)
Ireland
(Direct)
Total
Potential
(patients)
Potential
Market
($ MM)
1,2,3
Total Potential Market #Patients
Ocular
Melanoma
404
297
295
285
197
79
19
1,576
$ 62
Cutaneous
Melanoma
1,625
994
753
801
360
379
73
4,987
$ 206
CRC
9,902
5,300
5,475
7,281
4,016
1,644
335
33,953
$1,339
HCC
(Primary)
1,637
720
1,514
2,597
1,087
82
35
7,671
$277
NET
1,783
1,336
1,353
1,299
974
360
98
7,202
$ 281
TOTAL
15,351
8,647
9,389
12,263
6,634
2,545
560
55,389
$ 2,166
Europe Presents Significant Potential Market Opportunity
Sources: LEK Consulting, GLOBOCAN, Company estimates.
1) Assumes 2.5 treatments per patient.
2) Assumes ASP of ~$15K USD.
3) Assumes mix of direct sales and distributors. |
 37
DELCATH SYSTEMS, INC
US Market by Disease –
Device and Drug Combination
Sources: LEK Consulting, GLOBOCAN, Company estimates.
1) Assume 2.5 treatments per patient.
2) Estimated ASP of $25K.
Liver Metastasis
Potential Market
# Patients
Potential Market
# Procedures
Potential Market
($MM)
1,2
Ocular
Melanoma
1,685
4,213
$ 105
Cutaneous
Melanoma
7,023
17,557
$ 439
CRC
19,861
49,653
$ 1,241
HCC (Primary)
5,586
13,964
$ 349
NET
8,212
20,530
$ 513
TOTAL
42,367
105,917
$ 2,648 |
 38
DELCATH SYSTEMS, INC
APAC Market by Disease
China
(Device)
S. Korea
(Device)
Japan
(Device)
Taiwan
(Device)
Australia
(Device)
Total
Potential
(patients)
Potential
Market
($MM)
1,2
Total Potential Market #Patients
HCC
(Primary)
85,780
3,258
8,296
2,152
263
99,749
$ 1,156
Other
CRC
31,127
3,245
14,298
1,441
2,031
52,143
$ 642
NET
29,197
1,048
2,759
500
462
33,966
$ 393
Ocular
Melanoma
1,765
66
175
31
96
2,134
$ 25
Cutaneous
Melanoma
382
43
136
246
1,144
1,951
$ 23
OTHER
TOTAL
62,472
4,403
17,368
2,218
3,733
90,194
$ 1,083
TOTAL
148,104
7,661
25,665
4,370
3,996
189,943
$ 2,239
APAC Target Markets Represent Over $2 Billion Potential Market Opportunity
Sources: LEK Consulting, GLOBOCAN, Company estimates.
1) Assume 2.5 treatments per patient.
2) Estimated ASP of ~$5K. |
 39
DELCATH SYSTEMS, INC
HIGH-DOSE MELPHALAN
HISTORY AND RATIONALE
Appendix 3 |
 40
DELCATH SYSTEMS, INC
The Evidence for Melphalan
Melphalan, an established chemotherapy agent, is proven active at
high doses with broad antitumor activity
8. Verhoef C, et al. Ann Surg Oncol 15:1367-74
7. Van Iersel LB, et al. Ann Oncol 2010;21:1662-7
6. Van Iersel LB, et al. Ann Oncol 2008;19:1127-34
5. Alexander HR Jr, et al. Ann Surg Oncol 2009;16:1852-9
4. Alexander HR Jr, et al. Clin Cancer Res 2003;9:6343-9
3. Alexander HR Jr, et al. Clin Cancer Res 2000;6:3062-70
2. Noter SL, et al. Melanoma Res 2004;14:67-72
1. Grover AC, et al. Surgery 2004;136:1176-82 |
 41
DELCATH SYSTEMS, INC
Melphalan Dosing & Background
•
Well understood, dose dependent, tumor preferential, alkylating cytotoxic agent
that demonstrates little to no hepatic toxicity
•
Manageable systemic toxicities associated with Neutropenia and
Thrombocytopenia
•
Drug dosing 12x higher than FDA-approved dose via systemic IV
chemotherapy •
Dose delivered to tumor is over 100x higher than that of systemic IV
chemotherapy
Type
Dosing (mg/kg)
Multiple Myeloma (label)
0.25
Chemoembolization
0.62
Surgical Isolated Hepatic Perfusion (IHP)
1.50
Myeloablation
2.50-3.50
Chemosaturation (PHP)
3.00
An Established Drug for Liver Cancer Therapy |
 42
DELCATH SYSTEMS, INC
Melphalan Sensitivity: In Vitro Tumor Cell Lines Study
We Believe CHEMOSAT Will Be Effective On a Wide Range of Solid Tumors
192 uM |
 43
DELCATH SYSTEMS, INC
PHASE 3 TRIAL
Appendix 4 |
 44
DELCATH SYSTEMS, INC
Phase III Clinical Trial Design
Randomized to CS
93 patients: ocular
or cutaneous melanoma
Best Alternative Care (BAC)
Investigator and patient decision
(any and all treatments)
CS/Melphalan
Treat every 4 weeks x 4 rounds
(responders
can receive up to 6 rounds)
Cross-over
Primary Trial Endpoint
•
Statistically significant difference in Hepatic Progression
Free Survival (“hPFS”): p < 0.05
(IRC) •
Over 80% of Oncologic drugs approved by FDA between
2005
–
2007
on
endpoints
other
than
overall
survival
Modeled hPFS for Trial Success:
7.73 months (CS)
vs.
4 months (BAC)
Secondary Trial Endpoints
•
Investigator hPFS
•
Hepatic objective response rate
•
Overall objective response rate
•
Overall
Survival
–
Diluted
by
Cross
Over
•
SAP calls for analysis of various patient subsets
Pre-CS (Baseline)
Post-CS (22+ Months)
Hepatic
Response
–
Metastatic
Melanoma
Fully Powered, 93 Patient, Randomized, Multi-Center NCI Led Study
CS = Chemosaturation (CHEMOSAT) |
 45
DELCATH SYSTEMS, INC
Positive Phase 3 Results
•
Primary endpoint (hPFS by IRC) exceeded, p value =
0.0029, hazard ratio of 0.50 as of June,
2012 o
CS/PHP
median
hepatic
progression
free
survival
(hPFS)
was
4-fold
of
control,
or
5.3
months
improvement
o
CS/PHP
achieved
a
median
hPFS
of
7.0
months
vs
1.7
months
for
BAC
control
o
75% overall clinical benefit (CR + PR + SD)
•
Secondary endpoints consistent with primary endpoints
o
CS/PHP achieved a median overall PFS of 5.4 months vs. 1.6 months for BAC
o
OS –
No difference demonstrated due to heavy crossover from BAC to CS/PHP
o
Median OS 10.6 months vs. 10.0 months for CS/PHP and BAC
respectively •
OS exploratory analyses supportive of key observations
o
Median overall survival of 11.4 months for all patients treated with melphalan,
including crossover o
BAC patients did not cross-over to CS/PHP had a median survival of 4.1
months o
7 CS/PHP-treated and 3 BAC-only patients still alive as of 6/2012
•
Gen 1 Safety profile –
consistent with currently approved labeling for melphalan
o
30-day deaths on PHP: 3/44 patients (6.8%)
1 Neutropenic Sepsis (2.3%); 1 Hepatic Failure 2.5% (95% tumor burden); 1 gastric
perforation o
30-day deaths on BAC: 3/49 patients (6.1%)
Trial Outcomes Favorable and Consistent with Special Protocol Assessment
|
 46
DELCATH SYSTEMS, INC
PUBLISHED PHASE 1 / 2 STUDIES OF
DOXORUBICIN WITH CS-PHP
Appendix 5 |
 47
DELCATH SYSTEMS, INC
Phase 1 & 2 Studies of PHP-Doxorubicin For HCC
Delivered Safely in Multiple Studies with Promising Response Rates
No. of
pts
No. of
PHP/
pt
Disease stage
(tumor diameter)
Treatment
Median survival
(mo)
Response
Rates
Reference
HCC
(n=79)
CHM
(n=23)
1–4
1–2
IV A: n=66
IV B: n=13
All multiple
bilobar
Extrahepatic disease in 52%
Doxorubicin 60
–150 mg/m
Cisplatin
50–150 mg/m
2
Mitomycin C 50–200 mg/m
2
16
13
HCC pts
RR 64.5%
5-year
survival 20.3%
Kobe
1
Phase I/II
HCC
(n=11)
1–3
Mean
9.5 cm
Doxorubicin 60
–120 mg/m
2
6.5
13 (responders)
2 (non-responders)
RR 20%
MDACC
Phase I
HCC
(n=5)
CHM
(n=8)
Other
(n=8)
2–4
Extrahepatic disease in 17%
Doxorubicin 50
–120 mg/m
5-FU 1000–5000 mg/m
2
NR
RR 22%
Yale
Phase I
HCC
(n=7)
Other
(n=11)
1–10
NR
Doxorubicin 90
–120 mg/m
23 (responders)
8 (non-responders)
RR 58%
Yale
4
Phase I
1) Ku Y et al. Chir Gastroenterol 2003;19:370–376.
2) Curley SA et al. Ann Surg Oncol 1994;1:389–99.
3) Ravikumar TS et al. J Clin Oncol 1994;12:2723–36.
4) Hwu WJ et al. Oncol Res 1999;11:529–37.
2
2
2
2
3 |
 48
DELCATH SYSTEMS, INC
PRODUCT DEVELOPMENT PIPELINE
Appendix 6 |
 49
DELCATH SYSTEMS, INC
Product Development Pipeline
•
Orphan
Drug
-
Ocular
Melanoma liver mets
•
Proprietary drug-melphalan &
CHEMOSAT System
•
All
liver
cancers
–
melphalan
•
Classified as Medical Device
•
3
rd
party melphalan
•
Gen 2 melphalan CE Mark
•
Doxorubicin system CE Mark
•
CHEMOSAT for additional drugs
•
CHEMOSAT for other organs (lung
and brain)
•
mNET, mCRC and HCC
indications
Initial Opportunity
Near Term (< 5 years)
Intermediate Term (> 5 years)
•
mCRC and HCC clinical trials
•
CHEMOSAT for additional drugs
•
CHEMOSAT for other organs (lung
and brain)
•
CHEMOSAT Melphalan in
Taiwan and Japan
•
CHEMOSAT Doxorubicin in
China and South Korea
•
3
rd
party doxorubicin
•
CHEMOSAT for additional drugs
•
CHEMOSAT for other organs (lung
and brain)
•
CHEMOSAT Melphalan in
Australia, New Zealand, and
Hong Kong
•
3
rd
party melphalan
Development Aligned to Address Significant Market Opportunity
|
 50
DELCATH SYSTEMS, INC
CHEMOSAT System for Doxorubicin –
CE Mark
•
Satisfied all of the requirements to affix the CE Mark to Hepatic
CHEMOSAT Delivery System device for intra-hepatic arterial delivery
and extracorporeal filtration of doxorubicin in October, 2012
o
Provides a pathway for regulatory approval in China and S. Korea
•
Provides basis for partnership opportunities in China and S. Korea
where doxorubicin has a broad label for multiple tumor types
•
Multiple published Phase I/II studies from MD Anderson Cancer Center
and Yale with percutaneous hepatic perfusion (PHP) and Kobe
University using doxorubicin show promising response rates for HCC*
•
Plan
to
use
CHEMOSAT
Doxorubicin
in
Asia
Phase
III
2L
HCC
trials
Addressing the Large HCC Market Opportunity in China |
 51
DELCATH SYSTEMS, INC
NON US/EU
REGULATORY UPDATE
Appendix 7 |
 52
DELCATH SYSTEMS, INC
International Strategy beyond EU and US
•
Leverage CE Mark to obtain reciprocal regulatory approvals for CHEMOSAT
System in other international markets
o
Obtained approval for Gen 2 CHEMOSAT System with melphalan in Australia
•
International regulatory submissions status:
Application submitted and expected approvals in
Hong Kong
-
2013
Canada
-
2013
Singapore
-
2013
Argentina
-
2013
Brazil
-
2014
Intend to submit applications
S. Korea
(CHEMOSAT Doxorubicin)
Mexico
China
(CHEMOSAT Doxorubicin)
Taiwan
Russia
India
Japan
Israel
•
Utilize
3
rd
party
melphalan
and
doxorubicin
available
to
physicians
Combination of Strategic Partnerships and Specialty Distributors
|
 53
DELCATH SYSTEMS, INC
CHEMOSAT CENTERS
Appendix 8 |
 •
Entered training and marketing agreements with leading cancer centers in
Europe o
Milan, Italy –
European Institute of Oncology (IEO)
o
Frankfurt, Germany –
Johann Wolfgang Goethe-Universität (JWG)
o
Kiel, Germany –
Universitätsklinikum Schleswig-Holstein
o
Villejuif, France –
Cancer Institute Gustave Roussy (IGR)
o
Barcelona, Spain –
El Hospital Quiron
o
Naples,
Italy
–
Instituto
Nazionale
Tumori
Fondazione
"G.
Pascale"
o
Amsterdam,
The
Netherlands
–
Netherlands
Cancer
Institute-Antoni
van
Leeuwenhoek
Hospital
o
Erlangen,
Germany
–
University
Hospital
of
Erlangen
o
Pamplona,
Spain
–
Clinica
Universidad
de
Navarra
o
Bordeaux, France –
Hôpital Saint-André
(St Andre)
o
Galway, Ireland –
University Hospital Galway (UHG)
o
Leiden,
The
Netherlands
–
Leiden
University
Medical
Center
o
Southampton, United Kingdom –
Southampton University Hospital (SUH)
o
Göttingen, Germany -
University Medical Center Göttingen (UMG)
o
Varese, Italy –
Varese University Hospital (VUH)
•
Training completed and patients treated at IEO, JWG, IGR, St Andre, UHG, SUH, UMG,
VUH CHEMOSAT Centers in Europe
54
DELCATH SYSTEMS, INC
•
Liver
metastases
from
cutaneous
melanoma,
ocular
melanoma,
gastric
cancer,
breast
cancer,
neuroendocrine tumor (NET), hepatocellular carcinoma (HCC) and
Cholangiocarcinoma |