inf ash 2013
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ASH 2013
December 8, 2013
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Forward Looking Statement
2
This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995.
Such forward-looking statements include those regarding the Companys expectations about: its ability to execute on its strategic
plans; the therapeutic potential of PI3K inhibition and IPI-145; management of infectious complications; and the potential rationale
of investigating IPI-145 in additional indications and combinations therapies. Such statements are subject to numerous important
factors, risks and uncertainties that may cause actual events or results to differ materially from the companys current
expectations. For example, there can be no guarantee that Infinity will initial clinical trials or report data in the time frames it has
estimated, that any product candidate Infinity is developing will successfully complete necessary preclinical and clinical
development phases or that development of any of Infinitys product candidates will continue. Further, there can be no guarantee
that any positive developments in Infinitys product portfolio will result in stock price appreciation. Managements expectationsand, therefore, any forward-looking statements in this presentation could also be affected by risks and uncertainties relating to a
number of other factors, including the following: Infinitys 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. FDA and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies;
Infinitys ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash
requirements and expenditures; development of agents by Infinitys competitors for diseases in which Infinity is currently
developing, or intends to develop, its product candidates; and Infinitys ability to obtain, maintain and enforce patent and other
intellectual property protection for any product candidates it is developing. These and other risks which may impact
managements expectations are described in greater detail under the caption Risk Factors included in Infinitys quarterly reporton Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 7, 2013, and other filings filed by Infinity
with the SEC. 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. Infinitys website is http://www.infi.com. Infinity regularly uses its website to post information regarding its
business, product development programs and governance. Infinity encourages 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.
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Investigator Disclosures
Ian Flinn, M.D., Ph.D., Director, Hematologic Malignancies Research Program,
Sarah Cannon Research Institute Infinity Pharmaceuticals, Inc. (research funding)
Susan OBrien, M.D.,Ashbel Smith Professor and Chief, Section of Acute
Lymphocytic Leukemia, Department of Leukemia, University of Texas M.D.Anderson Cancer Center
Infinity Pharmaceuticals, Inc. (research funding, consultant)
Gilead Sciences (research funding, consultant)
Pharmacyclics, Inc. (research funding, consultant)
John Gribben, M.D., Hamilton Fairley Chair of Medical Oncology, Barts CancerInstitute, Queen Mary, University of London, UK Roche/Genentech (consultant),
Celgene Corporation (consultant, research funding)
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Agenda
Introduction: Julian Adams, Ph.D., President of R&D, Infinity Pharmaceuticals, Inc.
Overview of IPI-145 Phase 1 Data in Hematologic Malignancies: Dr. Julian Adams
IPI-145 Phase 1 Data in CLL: Ian Flinn, M.D., Ph.D., Sarah Cannon Research Institute
Panel Discussion/Q&A: Dr. Julian Adams (moderator)
Dr. Pedro Santabarbara, Chief Medical Officer, Infinity Pharmaceuticals
Dr. David Roth, SVP Clinical Development and Medical Affairs, Infinity Pharmaceuticals
Dr. Ian Flinn
Dr. John Gribben
Dr. Susan OBrien
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ASH 2013
December 8, 2013
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IPI-145: Potential to Transform the Standard of Care
in Hematologic Malignancies
6
Highly active in both B-cell and T-cell malignancies
Generally well tolerated
Most AEs are low-grade and/or asymptomatic
Consistent with co-morbidities in patients with advanced hematologicmalignancies
Others experience with BCR inhibitors and our own experience in
our trials has informed our strategies to optimize use of IPI-145
Phase 2 and Phase 3 registration trial under way
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IPI-145 Highly Active in R/R iNHL: 73% ORR
8Douglas et al., ASH 2013.
73% ORR includes one Waldenstrm Macroglobulinemia patient with a minor response (MR)
without adenopathy (not shown above)
Maximum Change in Adenopathy: iNHL Patients Dosed 25 mg BID (n=15)
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IPI-145 Rapid Response in iNHL: Majority of
Responses Occur by the End of Cycle 2
9R/R iNHL patients, n=15 ( 25 mg BID)
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IPI-145 Early Evidence of Durable Responses in iNHL53% (8 of 15 Patients) Progression Free for Over One Year
R/R iNHL patients, n=15 ( 25 mg BID)
Douglas et al., ASH 201310
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R/R CLL
98% (42/43) achieved a reduction in adenopathy by CT assessment, all doses
89% (24/27) nodal response rate ( 50% reduction in adenopathy), 25 mg BID
Treatment-nave CLL
Nodal responses in 3/6 patients, including 2 patients with p53 mutation, 25 mg BID
Flinn et al., ASH 2013
IPI-145 Highly Active in R/R CLL: 89% Nodal Responses
at 25 mg BID Based on Objective CT Assessments
11
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IPI-145 Early Evidence of Activity in T-Cell Lymphomas
Flinn et al., ASH 201312
Population
Patients(n)
Best Responsen (%)
Evaluable ORR CR PR SD PD
TCL 26 10 (38) 1 (4) 9 (35) 7 (27) 9 (35)
C-TCL 14 4 (29) 0 4 (29) 7 (50) 3 (21)
P-TCL 12 6 (50) 1 (8) 5 (42) 0 6 (50)
C-TCL = cutaneous TCL; P-TCL = peripheral TCL
Early evidence of activity in C-TCL and P-TCL with IPI-145 up to 75 mg BID
Safety profile in line with comorbidities seen in patients with advanced hematologic
malignancies (Horwitz et al, ICML 2013; Douglas et al, ASH 2013)
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IPI-145 Early Evidence of Activity in
Aggressive B-cell NHL
13Campbell et al., ASH 2013
Doses up to 75 mg BID (n=14)
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IPI-145: Potential to Transform the Standard of Care
in Hematologic Malignancies
Most AEs are low-grade and/or asymptomatic
- Most common AEs were asymptomatic laboratory abnormalities
- Symptomatic Grade 3/4 AEs were uncommon
Others experience with BCR inhibitors and our own experience in
our trials has informed our strategies to optimize use of IPI-145
- Asymptomatic ALT/AST elevation, predominantly in lymphoma to date,
is managed with dose interruptions and re-treatment- Management of infectious complications has evolved to support
continued treatment
14
IPI-145 is generally well tolerated
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CLL: In This Disease Population, Infections Are
Common, Particularly in Heavily Pre-Treated Patients
Literature reports indicate that fludarabine treated patients have a
high incidence (89%) of infections that require hospitalization for IV
antibiotics*
In newly diagnosed patients treated with ibrutinib, the Grade 3
infection rate was ~10% in treatment-naive patients and ~40% inR/R and high-risk patients**
Consistent with the clinical recommendations in NCCN guidelines,
routine prophylaxis and other treatment recommendations were
introduced into ongoing studies of IPI-145
15*Perkins et al., Cancer2002**Byrd et al., ASH 2012
Following implementation of these recommendations, we have
observed no opportunistic infections and patients with infections
have been able to continue treatment with IPI-145
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IPI-145: Maintaining Patients on Study Going Forward
Adverse Event Expected Management in Phase 3 Study
Pneumonitis
Early intervention; drug interruption until resolution;
retreat with same dose
Steroids allowed
ALT/AST Dose interruption until resolution; retreat with same dose
Diarrhea Dose interruption until resolution; retreat with same dose
Steroids allowed
Infections
Drug interruption during active infection and antibiotics as
indicated and recommended for immunocompromised
patients; retreat with same dose
16
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DYNAMO: Phase 2 Study of IPI-145 in
Refractory iNHL Enrolling
Open-label, single-arm monotherapy study under way
Primary endpoint: Objective response rate
*Includes follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL)
Clinicaltrials.gov NCT01882803.
~120 iNHL patients*IPI-145
(25 mg BID)
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DUO: Phase 3 Study of IPI-145 in R/R CLL
Now Enrolling
Randomized, monotherapy study
Primary endpoint: Progression-free survival by
independent review
~300 patients R
IPI-145 (25 mg BID)(n = ~150)
Ofatumumab (IV)(n = ~150)
18
Clinicaltrials.gov NCT02004522.
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Phase 1 Exploration OngoingTBD
DUO Phase 3
Phase 1b/2 (+Rit, +Bend, +Rit/Bend)*
Mono Rx
Combo
DYNAMO Phase 2
Phase 1b/2 (+Rit, +Bend, +Rit/Bend)*
Mono Rx
Combo
Realizing Potential of IPI-145 in
Hematologic Malignancies
19
R/R iNHL
R/R
CLL
Phase 1b/2 (+Rit, +Bend, +Rit/Bend)*Combo
Other(T-cell , aNHL)
*Investigator sponsored trial
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Agenda
Introduction: Julian Adams, Ph.D., President of R&D, Infinity Pharmaceuticals, Inc.
Overview of IPI-145 Phase 1 Data in Hematologic Malignancies: Dr. Julian Adams
IPI-145 Phase 1 Data in CLL: Ian Flinn, M.D., Ph.D., Sarah Cannon Research Institute
Panel Discussion/Q&A: Dr. Julian Adams (moderator)
Dr. Pedro Santabarbara, Chief Medical Officer, Infinity Pharmaceuticals
Dr. David Roth, SVP Clinical Development and Medical Affairs, Infinity Pharmaceuticals
Dr. Ian Flinn
Dr. John Gribben
Dr. Susan OBrien
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CLL Cohort 1 (n = 28)R/R 25 mg BID
Phase 1 Trial of IPI-145 in Hematologic MalignanciesPreliminary Outcomes in CLL
Flinn et al., ASH 2013.21
CLL Cohort 2 (n = 24)R/R 75 mg BID
CLL Cohort 3 (n = 15)
Tx-Nave 25 mg BID( 65 years or 17p(del) / p53 mutation)
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R/R CLLn=52
Tx-Nave CLLn=15
Age (years), median (range) 66 (51-82) 74 (49-83)
Females, n (%) 11 (21) 4 (27)
ECOG Status 0 / 1 / 2, n 11 / 37 / 3 5 / 9 / 1
Prior Systemic Therapies, median (range) 4.5 (1-12) n/a 3 Prior Systemic Therapies 81% n/a
< 6 Months Since Last Therapy 61% n/a
Stage 3 (High-Risk) 73% 53%
Extent of CLL
Bulky Lymphadenopathy (> 5 cm lesion) 49% (23/47) 0Organomegaly 30% (13/43) 50% (7/14)
ALC (x103cells/L), median (range) 13 (0.6-280) 68 (10-204)
17p(del) or p53 mutation 53% (21/40) 54% (7/13)
Prior BTK-inhibitor Therapy, n 4 n/a
CLL Patient Characteristics Representative of the
Populations Under Study
Flinn et al., ASH 2013.22
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Relapsed/Refractory (n=52) Treatment-Nave (n=15)
All Grades
%
Grade 3
%
Grade 4
%
All Grades
%
Grade 3
%
Grade 4
%
Neutropenia 46 17 13 7 0 7
Rash (combined) 33 2 2 0 0 0
Diarrhea 29 6 0 20 0 0
Fatigue 29 4 0 7 7 0
Cough 25 4 0 13 0 0
Pyrexia 25 2 0 0 0 0
Nausea 21 0 0 7 0 0
ALT / AST 19 6 0 7 7 0
Anemia 19 12 0 7 0 0
Arthralgia 15 0 0 0 0 0
Peripheral edema 15 0 0 13 0 0
R/R CLL: Median time on treatment = 5.1 months
Treatment-nave: Median time on treatment = 2.7 months
CLL AEs*: Majority of AEs Are Manageable,
Asymptomatic and/or Low Grade
Flinn et al., ASH 2013.24
* All Causality 15% in R/R CLL
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Stability of Mean Peripheral Blood Counts During
IPI-145 Therapy in CLL Patients
C1D1(32)
C2D1(25)
Screening(n) patients
C3D1(22)
C4D1(18)
C5D1(14)
C6D1(13)
ANC
Platelets
Hemoglobin
g/dL
10
11
12
40
120
240
103/ L
103/ L
13
80
200
14
15
160
Mean SD
0
2
1
54
3
6
25Flinn et al., ICML 2013
AE G d 3 i CLL P ti t 25 BID
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AEs Grade 3 in CLL Patients 25 mg BID (All Causality 5%)Hematologic and Infectious AEs More Common in Heavily Pretreated
R/R CLL Patients
Flinn et al., ASH 201326
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R/R CLL
98% (42/43) achieved a reduction in adenopathy by CT assessment, all doses
89% (24/27) nodal response rate ( 50% reduction in adenopathy), 25 mg BID
Treatment-nave CLL
Nodal responses in 3/6 patients, including 2 patients with p53 mutation, 25 mg BID
Flinn et al., ASH 2013
IPI-145 Highly Active in R/R CLL: 89% Nodal Responses
at 25 mg BID Based on Objective CT Assessments
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Population
Patients(n)
Best Response(n)
ORR by IWCLL
(CR + PR)
(%)Evaluable CR PR SD PD
Overall R/R CLL 47 1 21 24 1 47
25 mg BID 27 1 12 13 1 48
17p(del) or p53mut 12 0 6 5 1 50
75 mg BID 20 0 9 11 0 45
17p(del) or p53mut 7 0 2 5 0 29
Median time to response was < 2 months
Flinn et al., ASH 2013
IPI-145 Highly Active in R/R CLL: IWCLL Responses
28
Ti St d R/R CLL P ti t t 25 BID
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Time on Study: R/R CLL Patients at 25 mg BIDEarly Patient Experiences Inform Potential to Optimize Future Patient
Management
29Flinn et al., ASH 2013
Long-term
progression free
Patients enrolled in 2013,Progression free, data maturing
Discontinued
All discontinuationsfrom patients enrolled
before 2013
75% (6/8) patients treated for 1 year remain progression-free on treatment
8 recently enrolled patients (< 6 months) in early follow-up for PFS
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IPI-145: Potential to Transform the Standard of Care
in Hematologic Malignancies
30
Highly active in both B-cell and T-cell malignancies
Generally well tolerated
Most AEs are low-grade and/or asymptomatic
Consistent with co-morbidities in patients with advanced hematologicmalignancies
Others experience with BCR inhibitors and our own experience in
our trials has informed our strategies to optimize use of IPI-145
Phase 2 and Phase 3 registration trial under way
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Agenda
Introduction: Julian Adams, Ph.D., President of R&D, Infinity Pharmaceuticals, Inc.
Overview of IPI-145 Phase 1 Data in Hematologic Malignancies: Dr. Julian Adams
IPI-145 Phase 1 Data in CLL: Ian Flinn, M.D., Ph.D., Sarah Cannon Research Institute
Panel Discussion/Q&A: Dr. Julian Adams (moderator)
Dr. Pedro Santabarbara, Chief Medical Officer, Infinity Pharmaceuticals
Dr. David Roth, SVP Clinical Development and Medical Affairs, Infinity Pharmaceuticals
Dr. Ian Flinn
Dr. John Gribben
Dr. Susan OBrien
31
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ASH 2013
December 8, 2013
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Back-ups
33
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Phase 1 Study of IPI-145 in Hematologic Malignancies
Dose Escalation
8 100 mg BID
75 mg BID
MTD Expansion Cohorts
R/R CLL/SLL, iNHL, MCL
T-cell lymphomas
Aggressive B-cell lymphoma
Myeloid neoplasms
Acute lymphoblastic leukemia
25 mg BID
Expansion Cohorts
R/R CLL/SLL, iNHL, MCL
High-risk / Tx-nave CLL
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Non-Infinity References Included in This Presentation
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Ibrutinib Infections in CLLASH 2012
36Byrd et al., ASH 2012.
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Ibrutinib Infections in CLLNew England Journal of Medicine 2013
37Byrd et al., NEJM2013.
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Ibrutinib Infections in CLLNew England Journal of Medicine 2013
38Byrd et al., NEJM2013.
Fludarabine Refractory CLL
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Fludarabine-Refractory CLL89% of refractory CLL patients reported to have disease
(non drug) related serious infections
39Perkins et al., Cancer 2002.
Fludarabine Refractory CLL
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Fludarabine-Refractory CLL89% of refractory CLL patients reported to have disease
(non drug) related serious infections
40P ki t l C 2002
CONCLUSIONS
The current data show that the frequency of infections serious enough to require
hospitalization for intravenous antibiotics in patients with fludarabine-refractory CLL/SLL
is extremely high. These infections occurred frequently even in the setting of
conventional chemotherapy. As a result of this propensity for infection, caution should be
exercised in interpreting the frequency of infections seen during development of
promising new treatment modalities
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