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| 8-K - FORM 8-K - INFINITY PHARMACEUTICALS, INC. | d230658d8k.htm |
 Building a Sustainable, Fully Integrated
Biotechnology Company
September 2011
Exhibit 99.1 |
 Forward Looking Statements
2
•
This presentation contains forward-looking statements within the meaning of The Private Securities
Litigation Reform Act of 1995.
•
These statements involve risks and uncertainties that could cause actual results to be materially
different from historical results or from any future results expressed or implied by such
forward-looking statements.
•
Such forward-looking statements include statements regarding: the therapeutic potential of
Infinity’s Hedgehog pathway, Hsp90, PI3K and FAAH inhibitors; the potential of IPI-926
and Hedgehog pathway inhibition in addressing chondrosarcoma, pancreatic cancer and
myelofibrosis; the completion of enrollment in the Phase 2 trial of IPI-926 in pancreatic cancer
by the end of 2011; the initiation a Phase 2 trial of IPI-926 in myelofibrosis in the third
quarter of 2011; the potential of combination therapy based on retaspimycin HCl in addressing
non-small cell lung cancer; the potential expansion of the Phase 2 trial of retaspimycin HCl in combination with docetaxel;
the commencement of Phase 1 clinical development of IPI-145 in the second half of 2011 and Phase 2
development of IPI-940 in pain by Purdue; 2011 financial guidance (including total
revenues, operating cash burn, and year-end cash and investments balance), and the
expectation that Infinity will have capital to support its current operating plan into 2014.
•
Such forward-looking statements are subject to numerous factors, risks and uncertainties that may
cause actual events or results to differ materially from the company's current expectations.
For example, there can be no guarantee that Infinity’s strategic alliance with
Purdue/Mundipharma will continue for its expected term or that these entities will fund
Infinity’s programs as agreed, or that any product candidate Infinity is developing will
successfully complete necessary preclinical and clinical development phases. Further, there can
be no guarantee that any positive developments in Infinity’s product portfolio will result in stock price appreciation. Infinity’s
expectations could also be affected by risks and uncertainties relating to: results of clinical trials
and preclinical studies, including subsequent analysis of existing data and new data received
from ongoing and future studies; the content and timing of decisions made by the U.S. Food and
Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites,
and publication review bodies; Infinity's ability to enroll patients in its clinical trials; unplanned
cash requirements and expenditures, including in connection with business development
activities; development of agents by Infinity’s competitors for diseases in which Infinity
is currently developing its product candidates; market acceptance of any products Infinity or its partners may successfully
develop; and, Infinity's ability to obtain, maintain and enforce patent and other intellectual
property protection for any product candidate it is developing. •
These and other risks which may impact management's expectations are described in greater detail under
the caption "Risk Factors" included in Infinity's quarterly report on Form 10-Q for
the quarter ended June 30, 2011 filed with the U.S. Securities and Exchange Commission on
August 9, 2011.
•
Further, any forward-looking statements contained in this presentation speak only as of the date
hereof, and Infinity expressly disclaims any obligation to update any forward-looking
statements, whether as a result of new information, future events or otherwise.
•
All trademarks used in this presentation are the property of their respective owners. •
Our Internet website is http://www.infi.com. We regularly use our website to post information
regarding our business, product development programs and governance. We encourage
investors to use www.infi.com, particularly the information in the section entitled
“Investors/Media,” as a source of information about Infinity. References to www.infi.com in this presentation are not intended
to, nor shall they be deemed to, incorporate information on www.infi.com into this presentation by
reference. |
       •
Clear registration paths
•
Multiple possible indications
•
Substantial market potential
•
Full U.S. commercial rights
in oncology/inflammation
INFI in 2011: Considerable Near-Term
Momentum
•
Well-financed, with capital into 2014
•
Purdue/Mundipharma alliance enables robust clinical development and approval
strategies; provides access to markets ex-US & those best served by a GP
sales force •
Compelling scientific rationale
•
Intriguing Phase 1b clinical data
•
Underserved markets
Novel
candidates in
development
•
Rigorous, adaptive trials
•
Companion biomarker strategy
Active
phase
2 trials
3 |
 Advancing Pipeline with Broad Commercial
Potential
4
Discovery
Phase 1
Phase 2
Phase 3
Preclinical
Hedgehog: IPI-926
Hsp90: Retaspimycin HCl
FAAH: IPI-940
PI3K: IPI-145
Pancreatic Cancer
Gemcitabine Combo
Chondrosarcoma
Solid Tumors
Docetaxel Combo
Non-Small Cell Lung Cancer
Discovery Programs
Myelofibrosis
Everolimus Combo
Non-Small Cell Lung Cancer |
 IPI-926:
Addressing Difficult-to-Treat Cancers by
Targeting the Hedgehog Pathway |
 IPI-926: Overview
6
•
Disrupts malignant activation of the Hedgehog pathway by inhibiting
Smoothened
–
Hedgehog pathway known to drive multiple difficult-to-treat cancers
•
Product strategy
–
Target areas of significant unmet need
–
Leverage strong scientific rationale
–
Pursue tractable clinical development path
–
Deliver commercially differentiated product |
 Large unmet need
•
~35,000 deaths /
year in the U.S. alone
•
Average survival
<6 months
•
5-year survival <5%
Resistant to therapy
•
Gemcitabine
approved Rx with
only a ~6 wk survival
benefit
•
Multiple failures in
Phase 2 and Phase 3
Treating Pancreatic Cancer Requires a
Fundamentally Novel Approach
7
Source: Xiong et. al, 2006. Drugs 66 (8): 1059-72.
Multiple Failures in Pancreatic Cancer
Single Agents
•
Topotecan
•
Irinotecan
•
Cisplatin
•
Oxaliplatin
•
Ifosfamide
•
Epirubicin
•
Docetaxel
•
Paclitaxel
•
Capeticabine
•
Pemetrexed
Combinations with Gemcitabine (Gem)
•
Gem + Fluorouracil
•
Gem + Cisplatin
•
Gem + Irinotecan
•
Gem + Oxaliplatin
•
Gem + Exatecan
•
Gem + Epirubicin
•
Gem + Carboplatin
•
Gem + Mitomycin
•
Gem + Docetaxel
•
Gem + Capeticabine
•
Gem + Pemetrexed
•
Gem + Tegafur/Uracil
•
Gem + Fluorouracil +
Leucovorin
•
Gem + Fluorouracil +
Cisplatin
•
Gem + Fluorouracil +
Tegafur/Uracil
•
Gem + Fluorouracil +
Cisplatin + Epirubicin |
 IPI-926 Enhances Delivery of Gemcitabine
to Tumor
8
Vehicle
Gemcitabine alone
IPI-926 +
gemcitabine
Current standard of care
in pancreatic cancer
Tumor cell nuclei
Fluorescent contrast agent
IPI-926 + gemcitabine doubles median survival in a mouse model of pancreatic
cancer (Olive et al. 2009, Science 324: 1457-61.)
|
 Strong Preclinical Rationale for IPI-926
in Pancreatic Cancer
9
Controls
IPI-926 + Gemzar®
Days
IPI-926 + Gemzar
®
doubles median survival
in pancreatic cancer model
0
10
20
30
40
50
60
70
80
90
0
20
40
60
80
100 |
 Rapid Translation of Preclinical Insights to
Randomized Phase 2 Clinical Trial
10
•
Primary endpoint is overall survival
–
Secondary endpoints include progression free survival, time to progression,
overall response rate
•
Rigorous design to mitigate Phase 3 risk
•
On track to complete enrollment by YE 2011
Dose
Escalation
MTD
IPI-926 (QD) + gemcitabine
(n = 60)
Placebo + gemcitabine
(n = 60)
Phase 1b
Phase 2
1:1
Randomization |
 Encouraging Activity and Tolerability Observed
in Phase 1b
•
IPI-926 + gemcitabine
led to a 31% response
rate
–
Overall response rate to
gemcitabine is historically
<10%*
•
Favorable PK and safety
profile
–
No interaction between IPI-
926 and gemcitabine
–
Most common AEs were
fatigue and nausea
–
Combination did not reveal
unique or more severe AEs
11
Stephenson et al., ASCO 2011.
*Moore, et al. J Clin Oncol 25:1960-6.; Seitz et al. Oncology
18:43-7. |
 IPI-926 Leads to Stromal Pathway Activation
in Pancreatic Cancer Tumors
12
•
Nuclear localization of
Gli-1 is a molecular
marker of Hedgehog
pathway activation
•
Presence of Gli-1
consistent with paracrine
signaling in tumor
stroma
Stephenson et al., ASCO 2011. |
 Myelofibrosis: Phase 2 Trial
•
Hedgehog pathway plays a key role in pathogenic fibrosis
–
Significant need exists for novel treatment options that can directly target the
malignant fibrosis underlying this disease
•
No current treatments for underlying disease
–
Agents in development reduce spleen size, address symptoms
•
Phase 2 trial expected to start in Q3’11
–
Design:
Single-arm,
single-agent,
exploratory
trial
in
up
to
45 patients with myelofibrosis
–
Dose:
160
mg
IPI-926
administered
orally
once
daily
–
Primary
endpoint:
Hematologic
response
rate
13 |
 Chondrosarcoma: First and Only
Randomized Trial in this Patient Population
•
Significant unmet need
–
Chondrosarcoma is highly resistant to chemotherapy
and radiotherapy
–
Therapeutic standard is surgery
–
No effective treatments and no established standard of care for
patients with metastatic or locally advanced, inoperable disease
14
•
Preclinical data suggests inhibiting the Hedgehog pathway
reduces tumor volume and leads to calcification
•
IPI-926 granted Orphan Drug Designation by FDA and EMA in
this indication |
 Rigorous Phase 2 Trial Under Way
•
Global trial at approximately 40 sites
•
Randomized, double-blind, single-agent, placebo controlled study in
metastatic or locally advanced, inoperable chondrosarcoma
–
Trial design reviewed with FDA and EMA prior to study
•
Primary endpoint is progression free survival
–
Secondary endpoints include time to progression, overall survival, overall
response rate and response duration
~100
Patients
IPI-926 (QD)
Placebo
15
2:1
Randomization
Progression -
crossover to IPI-926 |
 Retaspimycin HCl (IPI-504)
Targeting Non-Small Cell Lung Cancer Through
Hsp90 Inhibition |
 Function of Hsp90
•
“Chaperone”
protein necessary for stability
and
function
of
certain
‘client’
proteins,
including oncoproteins
Retaspimycin HCl (IPI-504)
•
Highly potent, selective, water
soluble Hsp90 inhibitor
Program strategy; determine optimal:
Dose and schedule
Combination agents
Indications
Current status: Two clinical trials in NSCLC
17
Heat Shock Protein 90 (Hsp90):
An Important Cancer Target |
 •
Based on clinical data from
Phase 1b study
•
Adaptive, randomized Phase 2
•
Biomarker exploration
Combination with
Docetaxel in
Patients with a
Smoking History
•
Based on preclinical data in well-
defined patient population
•
Phase 1b/2 exploratory study
Combination with
Everolimus in
Patients with a
KRAS Mutation
Retaspimycin HCl: Potential Breakthrough
Approach to NSCLC
Pursuing multiple development paths as combination therapy
18 |
 Phase 1b Trial: Clinically Active in
Combination with Docetaxel
19
Compelling Phase 1b data
•
Partial response seen in 6
patients (ORR = 26%)
–
Docetaxel response rate is
~8%, and PFS is ~3 months
•
Stable disease seen in 7
patients
1
Riely et al., ASCO 2011.
2
Hanna, et al. J Clin Oncol 22:1589-97.
1
2 |
 Responses Observed in Patients with
Historically Poor Prognoses
•
In exploratory analyses, patients with the highest response rates fell into
overlapping categories:
–
Current or former smokers (ORR = 33%)
–
Those with squamous cell carcinoma (ORR = 43%)
20
Historical 2
Line
Docetaxel
NSCLC
Patients in
Trial
N=23
Smokers
N=18
Squamous
Cell
Carcinoma
N=7
Patient Populations
Retaspimycin HCl plus Docetaxel
Overall Response Rate
Riely et al., ASCO 2011.
nd |
 NSCLC Patients with Smoking History
Responded Favorably to Retaspimycin HCl
Janjigian et al. Cancer
2010. 116(3):670.
Tumor Response to Retaspimycin HCl plus Docetaxel
by Smoking History
NSCLC Patient Survival
by Smoking Status
Log rank p=0.03
21
Tumor response increased with
increase in smoking pack years
In general, smokers with NSCLC have
lower survival rates than non-smokers
Never (331)
15 pack years (270)
> 15 pack years (1409)
Median
17.8 mo
14.6 mo
10.8 mo |
 Phase 1b Trial: Favorable Safety Profile
•
All toxicities were manageable
•
No unexpected or overlapping toxicities seen
•
GI toxicities were primarily Grade 1 or Grade 2
•
No significant ocular toxicities were observed
•
No dose reductions or discontinuations in response to liver
function tests
22
Riely et al., ASCO 2011. |
 Adaptive Phase 2 Trial Ongoing in NSCLC
23
~100 smokers w/
2
nd
-
or 3
rd
-line
NSCLC
(docetaxel naïve)
•
1°
Endpoint:
•
2°
Endpoints:
•
Exploratory:
Biomarkers, PG markers
Sub-population expansion
up to 45 additional patients
Sub-population expansion
up to 45 additional patients
Docetaxel (q3w) +
Retaspimycin HCl (weekly)
(N=50)
Docetaxel (q3w) +
placebo(weekly)
(N=50)
•
Dosing Schedule
–
retaspimycin
HCl: 450
mg/m
2
IV
QW
–
docetaxel:
75 mg/m
2
IV Q3W
Interim Analysis
OS
PFS, ORR, Safety
R |
 Phase 1b/2 Trial Ongoing in NSCLC Patients
with mKRAS
•
Encouraging preclinical rationale
–
Retaspimycin HCl plus an mTOR inhibitor resulted in synergistic
activity
and
substantial
tumor
regression
in
a
mouse
model
1
•
Exploratory Phase 1b/2 trial underway in up to 45 patients with a
KRAS mutation
–
Phase 1b: Dose-escalation study to determined recommended dose
combination
–
Phase 2: Will evaluate safety and clinical activity; may be expanded
based on overall response rate
24
1
Research conducted in collaboration with Karen Cichowski at Harvard Medical School.
|
 Hypothesis: In combination, these agents may synergize by promoting ER stress. This
process may be fueled by excessive oxidative stress, caused by Hsp90 dependent ROS
production and mTOR inhibition dependent suppression of antioxidant pathways.
G6PD suppression
25
Preclinical Model:
Potential MOA for Synergy of Retaspimycin HCl
with Everolimus in RAS Mutant Tumors
ER Swelling
control
Rapa / 504
Massive accumulation of
autophagosomes
Decrease in Cellular
antioxydants
ROS generation
Hsp90 inhibition
mTOR inhibition |
 %
NSCLC Patients by Cell Type (2009)
% Stage IIIb/IV NSCLC Patients
by Smoking Status (2009)
NSCLC: Significant Commercial Opportunity
% NSCLC Patients
by Mutation Status (2009)
26
Squamous
Cell
Carcinoma
35%
Adenocarcinoma
47%
Large Cell
Carcinoma
18%
> 15 pack years
70%
KRAS
30%
Non-KRAS
70%
Sources:
Decision
Resources
NSCLC
Pharmacor
Report,
June
2009;
Cancer.
2010
February
1;
116(3):
670–675.
doi:
10.1002/cncr.24813.
Estimates based upon G7 regions (US, UK, IT, DE, ES, FR, JP)
Phase 1b/2 trial of
retaspimycin HCl +
everolimus
Phase 2 trial of retaspimycin HCl + docetaxel
~145,000
~182,000
~125,000
Non-smokers &
15 pack years
30% |
 IPI-926 and Retaspimycin HCl:
Development Summary
IPI-926
•
Opportunity to deliver commercially differentiated product for broad
range of difficult-to-treat cancers
•
Phase 2 clinical trial program underway
–
Pancreatic cancer: On track to complete enrollment by YE 2011
–
Myelofibrosis: Trial expected to begin in Q3’11
–
Chondrosarcoma: Enrollment ongoing
Retaspimycin HCl
•
Combination therapy based on retaspimycin HCl may provide important
therapeutic benefit in NSCLC
•
Two trials underway
–
Phase 2 trial in combination with docetaxel in smokers
–
Phase 1b/2 trial in combination with everolimus in patients
with KRAS mutation
27 |
 Additional Pipeline Opportunities |
 IPI-145: Novel PI3K Inhibitor Rapidly
Advancing to the Clinic
29
•
IPI-145 is a potent, oral inhibitor of PI3K
and
PI3K
–
PI3K plays a role in hematologic
malignancies and inflammatory conditions
•
Compelling human proof-of-concept of PI3K
inhibition in heme malignancies
–
IPI-145 is 10-
to 30-fold more potent inhibitor of
PI3K
than PI3K
inhibitor with reported data
•
Data suggest inhibition of PI3K
is important,
particularly in inflammation
–
IPI-145 has shown compelling preclinical activity in
several models of inflammation
•
Phase 1 development expected to begin in 2H
2011 |
 •
IPI-940 inhibits FAAH and is designed to potentiate the effect
of anandamide
Constitutively active FAAH degrades anandamide, the body’s natural
source of pain relief
•
Encouraging data from Phase 1 trial in healthy volunteers
Marked FAAH inhibition and increased anandamide levels
No observed dose-limiting toxicities
•
Purdue and Mundipharma exercised rights for
worldwide development and commercialization
Purdue expected to begin Phase 2 development in pain
IPI-940: Phase 2-Ready FAAH Inhibitor
30 |
 Strong Financial Foundation to
Reach Key Inflection Points |
 Strategic Alliances Provide Funding and
Access to Global Markets
32
Hedgehog, PI3K and early discovery
•
R&D funding from Mundipharma
•
INFI to develop and register product candidates globally
•
INFI to commercialize products in the U.S.
•
Access to ex-US markets: Mundipharma to commercialize
products ex-U.S.
•
INFI entitled to royalty of 10% to 20% on ex-U.S. sales
FAAH
•
Purdue and Mundipharma responsible for global development
and commercialization
•
Access to GP sales force: Purdue and Mundipharma
responsible for global commercialization
•
INFI entitled to royalty of 10% to 20% on global sales
|
 Financial Strength to Drive Value Creation
33
$152.5M
Committed R&D Funding
Remaining in 2011 and 2012
$50M
Line of Credit
(Balloon note at prime, matures 2019)
Cash and Investments
(as of 6/30/10)
Current and Committed Capital
$285 Million
1
Line of credit may be drawn for any corporate purpose.
~$82M
0
50
100
150
200
250
300
1
(as
of
6/30/11) |
 2011 Financial Guidance:
Cash Runway into 2014
•
Projected
2011
revenue
of
$90M
-
$95M
•
Projected
2011
operating
cash
burn
of
$30M
-
$40M
•
Anticipate year-end cash and investments balance of
$110M -
$120M
–
Based on current operating plan; excludes $110M R&D funding
commitment from Mundipharma for 2012
•
Approximately 26.6 million shares outstanding
34 |
       •
Clear registration paths
•
Multiple possible indications
•
Substantial market potential
•
Full U.S. commercial rights
in oncology/inflammation
INFI in 2011: Considerable Near-Term
Momentum
•
Compelling scientific rationale
•
Intriguing Phase 1b clinical data
•
Underserved markets
Novel
candidates in
development
•
Rigorous, adaptive trials
•
Companion biomarker strategy
Active
phase
2 trials
•
Well-financed, with capital into 2014
•
Purdue/Mundipharma alliance enables robust clinical development and approval
strategies; provides access to markets ex-US & those best served by a GP
sales force 35 |
 Building a Sustainable, Fully Integrated
Biotechnology Company
September 2011 |