Delaware
|
0-32353
|
84-1475642
|
(State
or other jurisdiction of incorporation)
|
(Commission
File Number)
|
(IRS
Employer Identification No.)
|
(d) |
Exhibits.
|
99.1 |
ZIOPHARM
Oncology, Inc. Shareholder Presentation dated April 23,
2008.
|
ZIOPHARM
Oncology, Inc.:
(Registrant)
|
||
|
|
|
Date:
April 23, 2008
|
By: |
/s/
Richard E. Bagley
|
RICHARD
E. BAGLEY,
|
||
President,
Chief Operating Officer and Chief Financial
Officer
|
Exhibit
No.
|
Description
|
99.1
|
ZIOPHARM
Oncology, Inc. Shareholder Presentation dated April 23, 2008
|
Jonathan Lewis, MD,
PhD
Chief Executive Officer
1
FORWARD-LOOKING STATEMENTS
Some of the statements made in this presentation are
forward-looking statements. These forward-looking
statements are based upon our current expectations and
projections about future
events and generally relate to our
plans, objectives and expectations for the development of
and commercialization of in-licensed cancer drugs. Although
management believes that the plans and objectives reflected
in or suggested by
these forward-looking statements are
reasonable, all forward-looking statements involve risks and
uncertainties and actual future results may be materially
different from the plans, objectives and expectations
expressed in this presentation.
2
ZIOPHARM Mission
Advance patient treatment in cancer
Apply new insights from molecular and cancer biology to
understand how to improve the efficacy and safety of
approved and developmental cancer therapies
Develop and commercialize a diverse, risk-sensitive
portfolio of cancer drugs to address unmet medical needs
3
2007 Year in Review
Three product portfolio in phase I/II trials; multiple
registration pathways for both niche and broad-based
indications
Multiple data points in all programs for phase II
randomized trials palifosfamide expected to initiate
Q3
2008
Significant portfolio sales potential remains validated
Intellectual property portfolio broadened
Leadership team strengthened
4
Leadership Team
Eli Lilly (Prozac®), Inflexxion,
PHARMetrics, PAREXEL
24
Steve Bloom
VP, Business Development
EPIX, Sandoz (Novartis)
17
John Amedio, PhD
VP, Manufacturing & Process Development
EPIX, Theseus, Dupont,
Genzyme, PAREXEL
22
Bob Morgan, JD
VP, Regulatory Affairs & Quality
Point Therapeutics, Procept
15
Barry Jones, PhD
SVP, Technical Operations
Biogen (Amevive®), ImmuLogic,
Point Therapeutics, BioTransplant
26
Barbara Wallner, PhD
Chief Technology Officer
Bayer (Nexavar®), Leo
14
Brian Schwartz, MD
Chief Medical Officer
Biotech CEO (Velcade®, OvaRex®)
President Squibb, US
SmithKline Beecham (Tagamet®)
40
Dick Bagley
President, Chief Operating Officer
Yale, Memorial Sloan Kettering
Antigenics (CMO)
17
Jon Lewis, MD, PhD
Chief Executive Officer
Industry Experience
Yrs. Exp
Executive
5
INDIBULIN (301)
PALIFOSFAMIDE (201)
DARINAPARSIN (101)
ZIOPHARM PIPELINE
PRE-CLINICAL
PHASE I
PHASE II
PHASE III
Oral Single Agent
Combination (erlotinib) Tarceva®
Second Combination Trial
Sarcoma
Combination (doxorubicin) Adriamycin®
Oral
RCT
Myeloma / Single Agent
Leukemia / Lymphoma
Hepatocellular Carcinoma
Oral
6
Product Status
Indibulin most commercial promise (major solid
tumors)
Palifosfamide most advanced (sarcoma)
Darinaparsin best tumor response (lymphoma)
7
Capital Markets / FDA
Strategy analysis results in 2008 adjustments
Palifosfamide most advanced program (sarcoma)
IV randomized phase II initiating Q3
Oral additional preclinical study
Indibulin most commercial promise (major solid tumors)
Tarceva® combination study in progress
Xeloda® combination trial in Q3
Darinaparsin best tumor response (lymphoma)
Phase II data in lymphoma, additional data in liver cancer will
guide partnering
8
INDIBULIN
ZIO-301
9
Indibulin
Novel, oral tubulin binding agent
Targets cancer cell mitosis and movement
Potent preclinical synergy with approved therapies
(Tarceva
®, 5-FU, Taxotere®
)
Low toxicity profile
Strong intellectual property
10
Indibulin Mechanism of Action
Tubulins are involved in cell migration seeding
Indibulin inhibits cell migration of MO4 cells in
concentration dependent manner
Anti-invasive and anti-metastatic activity
Indibulin is also anti-mitotic
Cell
Mitosis
Cell Migration
Seeding
11
Indibulin and Tarceva®
70.65
12
Indibulin Synergizes With 5-FU
Days post tumor implant
0
1000
2000
3000
4000
5000
6000
0
10
20
30
40
50
60
Vehicle
Indibulin, 30 mg/kg
75 mg/kg 5-FU
Combination
Human Breast Cancer, MX-1, Xenograft
Second Phase I/II Combination Trial To
Follow
13
Prostate
Rapidly rising PSA prior to starting study
NSCLC
Prior gem/cis
CRC
2 heavily pretreated patients
H & N
2 pretreated patients
Ovarian
Heavily pretreated patient with brain metastases
Reduction in abdominal tumor size and markers
Papillary thyroid
Reduction in tumor size
Reduction in thyroglobulin
Indibulin
Preliminary Efficacy Seen in Phase I Studies
Prolonged stable disease in multiple tumor types
AACR/ NCI/ EORTC 2007,
ASCO 2007
14
Indibulin Phase I Preliminary PET Data
Pt. 12: Periam-
pullary Ca
Pt. 8: Leiomyo-
sarcoma
Pt. 10: Ewings
Sarcoma
Pt. 13:
Neuro-
endrocrine
Pt. 11:
Osteo-
sarcoma
Pt. 6:
STS
Pt. 9:
Ovarian
Ca
Pt. 5:
Osteo-
sarcoma
Change In Maximum SUV Of Target Lesions From
Baseline*
Unverified data. Cutoff date: 20 FEB 2008
Ca=carcinoma; SUV=standardized uptake value (sum)
*Data represent maximum percent change in SUV of target lesions from
baseline as assessed by Investigator from PET
on Week 7 of treatment.
Patient has global MP for appearance
of new lesions
or for increase in size of target or non-target lesions
15
Indibulin: Development Strategy
Taxanes are standard of care
Lung, breast, prostate, ovarian and gastric cancer
Indibulin may garner significant market share
Oral dosing
Lack of neurotoxicity
Potential efficacy in MDR tumors
Potential initial indications
Lung, head & neck, breast, gastric, prostate, other
Label expansion following Fast Track development
program
16
Indibulin: Clinical Development Plan
Oral Single Agent
Preclinical Phase I Phase II Phase III
Phase I/II (erlotinib)
Tarceva®
combination
Second Combination
Trial
Q3
Potential Registration
Phase
09
Other POC Studies
Final
Composite
Data 1H08
17
PALIFOSFAMIDE
ZIO-201
18
Palifosfamide (ZIO-201)
Stabilized active metabolite of ifosfamide (IFOS); related to
cyclophosphamide - CPA
Novel IV alkylating agent; oral form developed
Niche and large market potential
Potent preclinical synergy with Adriamycin®
Activity, convenience and safety profile over ifosfamide
Patent applications filed in U.S. and internationally
Toxic Chloroacetaldehyde
Toxic Acrolein
Key IFOS metabolites
Active Metabolite (IPM)
Mesna
19
Ifosfamide (IFOS)
IFOS approved for testicular cancer; standard of care for
sarcoma; as part of ICE regimen for lymphoma
In Sarcoma:
5.5 8.4 % front-line response rate in multicenter,
randomized study (n=326)*
Response does not translate into survival benefit
Median PFS 2.16 3.0 months
Ifosfamide-based therapy associated with improved
survival in synovial sarcoma**
Drug is difficult to tolerate*:
Grade 3/4 febrile neutropenia 18-20%
Grade 3/4 encephalopathy 11%
*Lotigan et al, JCO, July 2007
**Eilber et al, Ann Surg, July 2007
20
Palifosfamide Advantages
Palifosfamide advantages over IFOS include:
Active, no pro-drug
No hemorrhagic cystitis or CNS toxicity
No Mesna
Active in IFOS and CPA resistant xenografts
IV and oral
21
Palifosfamide: Phase II Sarcoma
Phase II trial includes diverse sarcoma subtypes
50 patients, fully enrolled and treatment completed
Median number of prior chemotherapies was 5
As reported, SD or better in 48% of 44 evaluated patients
1 PR (liposarcoma) lasting 35 weeks
IFOS-naïve patients (n=11): 64% (7/11) SD or better
Adverse events primarily mild to moderate in severity and
gastrointestinal or renal related
No reports of CNS or bladder toxicities and no significant bone
marrow suppression or alopecia.
22
Palifosfamide: Phase II Sarcoma Trial
N
Median PFS
(weeks)
% Progression-free
at 3 months
All
44
10
40.1
IFOS-naïve
11
Not reached
52.1
Over age 65
11
17
53.0
Note: PFS was calculated using time interval of first study drug dose until date of documented disease
progression (clinical or radiological symptomatology or death). Patients were censored if
discontinued due to
toxicity or early withdrawal.
Reported Preliminary Progression-free Survival
Because of limited efficacy of post-surgical standard care, 40%
progression-free rate is indicative of a highly active experimental
therapy warranting further study
23
Retroperitoneal Sarcoma: Multiple Prior
Recurrences
13.9 × 11.2 cm
Baseline
12 weeks
9.0 × 7.0 cm
24
Palifosfamide : Clinical Development Plan
Sarcoma
Preclinical Phase I Phase II Phase III
Sarcoma Combination
(doxorubicin) Adriamycin®
Phase I/II
RCT
Oral
Final Data
2H08
Q3
IND 08
25
Palifosfamide : Synergistic With
Adriamycin®
(MX-1 Xenograft Model)
Time since tumor implantation, days
26
Palifosfamide Registration Options
Registration strategy
Data and expert opinion suggest: palifosfamide /
Adriamycin
® vs. Adriamycin®
in front and second-line
patients;
PFS as primary endpoint
Do single study for approval
Window of opportunity for studies in sarcoma
27
DARINAPARSIN
ZIO-101
28
Darinaparsin (ZIO-101) Organic Arsenic
Organic Arsenic: first in a new class of molecules
Novel IV multifunctional agent; phase I oral accelerated
Potentially safer and more active for cancer treatment than
approved inorganic arsenic
Early activity in NHL and liver; Active in myeloma, other heme
indications
Issued U.S. patents, applications internationally
O
H
H
N
O
N
H
N
H
2
O
S
A
s
C
H
3
H
3
C
O
H
O
O
29
Darinaparsin: Mechanism of Action
Darinaparsin
Death
receptor
NADPH
oxidase
Active
NADPH
oxidase
ROS
Cytochrome C
Apoptosome
Caspase 9
Caspase 3
Caspase 8
Bax
Bcl2
Bclxl
Nucleus
PARP
Cell cycle
arrest
Apoptosis
Anti-angiogenesis
Mitochondrial
perturbation
30
Darinaparsin: Phase I/II Trials
Hematological Cancers
Results reported in hematology phase II trial
In 6 of 14 leukemia patients SD
In 3 of 7 evaluable lymphoma patients: CR in heavily pretreated NHL (PTCL),
prolonged SD in B-cell lymphoma; and interval response in HL (NS)
Solid Tumors
Phase I solid tumor results reported (37/40 patients)
2/3 renal with stable disease; 4/18 colorectal with stable disease; one pancreas,
H&N, spinal tumor
Multiple Myeloma
Phase I myeloma patients (14 evaluable reported) heavily pretreated (failed median 8
prior therapies)
6/14 stable disease, > 4 months duration
Two phase II trials, best response stable disease (one > year); registration strategy
not viable in current market
Liver Cancer
Patients with multiple treatment courses; reports of Q0L
AACR 2008, ECCO 2007, ASCO 2007,
AACR/ EORTC/ NCI 2006
31
Darinaparsin: NH Lymphoma CR
Baseline
12 weeks
32
Darinaparsin:
Early Activity Results
Pancreas Cancer Liver Metastases
Baseline
Post treatment
33
Well tolerated
No clinically relevant QTc prolongation, bone marrow
suppression or peripheral neuropathy
DLT of transient confusion, ataxia
All toxicities reversible
Darinaparsin: Safety Summary
34
Darinaparsin: Clinical Development Plan
Preclinical Phase I Phase II Phase III
Myeloma/Single Agent
Oral
Hepatocellular Carcinoma
Final Data
1H08
Interim
Data 1H08
Preliminary
Data 1H08
Additional IV phase II data and oral results
form basis for future study
Leukemia/Lymphoma
Final Data
1H08
35
Head & Neck
(3rd)
Oral Single
Agent IV
Breast(3rd)
Colorectal(3rd)
Prostate (3rd)
NSCL(2nd)
Ovarian (3
rd)
Oral Combination
Secondary Indications
Target Indications
INDIBULIN
Breast (3rd)
Colorectal (3
rd)
Prostate (3rd)
Ovarian
(3rd)
Oral Combination
Lymphoma (ICE, RICE)
Ovarian (3rd)
Pediatric Sarcoma
Sarcoma (1st, 2 nd)
IV Combination
Secondary Indications
Target Indications
PALIFOSFAMIDE
Business Strategy: Progressive Label Expansion
Other Hodgkins/Non-Hodgkins (3rd)
Other Solid Tumors
PTCL (front)
Liver
APL
MM (3rd)
Liver
IV Single Agent
IV Combination
Oral Single Agent
Oral Combination
Secondary Indications
Target Indications
DARINAPARSIN
36
Upcoming Milestones
2H
Ph II
Compound
Goal
Target
INDIBULIN (301)
Initiate ph Ib/IIa combination Tarceva® trial
Q1
Initiate second ph II combination trial
Q3
Final composite data from three ph I trials
1H
Potential registration phase
09
PALIFOSFAMIDE (201)
Initiate IV ph I/II combination Adriamycin® trial
Q1
Initiate oral ph I solid tumors
09
Final ph II sarcoma data
2H
Randomized front & second line worldwide sarcoma
trial
Q3
DARINAPARSIN (101)
Final ph II myeloma
1H
Final ph II heme
1H
Interim ph II liver
1H
Preliminary oral ph I
1H
37
Financial Highlights
Cash at 12/31/07: $35.0 MM
Current Cash Burn: $2.1 MM / mth
Primary Shares: ~ 21 MM
Cash financial guidance: Strategy review decisions impact
cash burn by extending into Q3 09 (update of 10KSB)
38
NASDAQ:ZIOP
39