Infinity Reports Updated Phase 1 Data Showing Encouraging Clinical Activity of IPI-145 in Chronic Lymphocytic Leukemia at ASCO

  Infinity Reports Updated Phase 1 Data Showing Encouraging Clinical Activity
  of IPI-145 in Chronic Lymphocytic Leukemia at ASCO Annual Meeting

 – Early Data Show that IPI-145 Is Well Tolerated, with a 55 Percent Partial
               Response Rate in Chronic Lymphocytic Leukemia –

– Rapid Onset of Clinical Activity Observed, with a Median Time to Response of
                                 1.9 Months –

   – Company Announces Initiation of New Phase 1 Expansion Cohort in Newly
             Diagnosed, High-Risk Chronic Lymphocytic Leukemia –

2013 ASCO Annual Meeting

Business Wire

CHICAGO -- June 2, 2013

Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) today announced updated Phase 1
data from an ongoing study of IPI-145, its potent, oral inhibitor of
phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma in patients with
relapsed/refractory chronic lymphocytic leukemia (CLL), a potentially fatal
hematologic malignancy, or blood cancer. Data from the study showed that
IPI-145 was well tolerated, with a rapid onset of clinical activity. These
findings were presented today at the 2013 American Society of Clinical
Oncology (ASCO) Annual Meeting. Based on the tolerability and activity profile
of IPI-145 observed to date, Infinity also today announced that it has
initiated a new expansion cohort within its ongoing Phase 1 study to evaluate
the safety, activity and pharmacokinetics (PK) of IPI-145 dosed at 25 mg twice
daily (BID) as treatment for patients with newly diagnosed, high-risk CLL.

“The early data from this Phase 1 study of IPI-145 continue to be encouraging.
IPI-145 was well tolerated and showed rapid clinical activity in patients with
CLL, with a median time to response of 1.9 months,” commented Ian Flinn, M.D.,
Ph.D., director, hematologic malignancies program, Sarah Cannon Research
Institute, and an investigator for the trial. “These data support continued
development of IPI-145, and I look forward to further evaluation of this
investigational drug in patients with both advanced and newly diagnosed CLL.”

“The data presented today reinforce Infinity’s enthusiasm for IPI-145. We
believe that the potency and activity of IPI-145 against both PI3K-delta and
PI3K-gamma contribute to its potential to become the best-in-class PI3K
inhibitor for the treatment of blood cancers,” stated Julian Adams, Ph.D.,
president of research and development at Infinity. “These data support the
initiation of an additional expansion cohort to evaluate the potential of
IPI-145 in newly diagnosed, high-risk patients with CLL. Beyond this Phase 1
study, Infinity is moving rapidly to advance the development of IPI-145 and is
planning to initiate at least two company-sponsored studies of IPI-145 in
hematologic malignancies this year.”

IPI-145 Data Presented at ASCO in Patients with CLL

The presentation, “Preliminary safety and efficacy of IPI-145, a potent
inhibitor of phosphoinositide-3-kinase-δ,γ, in patients with
relapsed/refractory CLL” (Abstract #7070), includes 117 patients in the total
safety population, of which 34 patients with CLL were evaluable for safety and
22 were evaluable for clinical activity.^1 All patients enrolled in the study
had advanced disease and had progressed during or were refractory to,
intolerant of, or ineligible for established therapy. CLL patients enrolled in
the study had a median of four prior systemic therapies (range: one - nine),
and 26 of the 34 patients (76 percent) had at least three prior systemic
therapies.

Safety and Pharmacokinetics

Data presented today showed that IPI-145 was well tolerated, with a safety
profile consistent with co-morbidities seen in patients with advanced
hematologic malignancies. There have been no dose-related trends in adverse
events at the doses evaluated from 8 mg BID to 75 mg BID in either the total
safety population or in patients with CLL. Adverse events were primarily
managed by dose interruptions and reductions. Among CLL patients enrolled in
the study, the most frequent Grade 3/4 adverse event was neutropenia. Grade 3
and Grade 4 neutropenia occurred in five (15 percent of) and eight (24 percent
of) patients, respectively. The majority of neutropenia observed did not
require dose reductions. Grade 3 elevations in transaminases (ALT/AST)
occurred in two (6 percent of) patients. Sixty-five percent of CLL patients
remain on study.

Data also showed that IPI-145 is rapidly absorbed and demonstrates a linear PK
profile through 75 mg BID, with complete inhibition of PI3K-delta and at least
50 percent inhibition of PI3K-gamma at doses ≥ 25 mg BID. IPI-145 also led to
profound and sustained inhibition of AKT phosphorylation, a marker of PI3K
activation, as well as reductions in several cytokines and chemokines that are
known to be important in lymphocyte trafficking and function.

Clinical Activity in CLL

IPI-145 is clinically active in patients with CLL, with a rapid onset of
response as defined by the International Workshop on Chronic Lymphocytic
Leukemia (IWCLL) IWC criteria^2 and a rapid resolution of lymphocytosis. Among
the 22 patients evaluable for response, there were 12 partial responses (55
percent IWCLL partial response rate) and an additional seven nodal responses.
The median time to response was 1.9 months (range: 1.8 - 5.6 months). Ten of
the 12 partial responses were at doses ≤ 25 mg BID.

The trial also included patients with a deletion of the short arm of
chromosome 17 (17p del) or with p53 mutations. Patients with CLL with a 17p
del or p53 mutations generally have a poor response to chemotherapy and worse
prognosis.^3 Among four patients evaluable with 17p del, there were two
partial responses, one stable disease, and one progression due to Richter’s
transformation. Among six patients evaluable with a p53 mutation, there were
four partial responses and two nodal responses.

This poster was presented in McCormick Place, S Hall A2, in Chicago, Illinois,
and may also be found in the Publications Archive on Infinity’s website
http://www.infi.com/product-candidates-publications.asp.

New Expansion Cohort in Phase 1 Study of IPI-145 in Advanced Hematologic
Malignancies

Based on the tolerability and activity observed in the ongoing Phase 1 study
of IPI-145 in patients with advanced hematologic malignancies, a new expansion
cohort within this study is open for enrollment. This cohort is designed to
evaluate the safety, activity and PK of IPI-145 dosed at 25 mg BID in
approximately 30 newly diagnosed patients who have high-risk CLL, defined as
patients over the age of 65 or with a 17p deletion or p53 mutations.

About the Phase 1 Trial of IPI-145 in Advanced Hematologic Malignancies

The Phase 1, open-label, dose-escalation trial of IPI-145 is designed to
evaluate the safety, PK and clinical activity of IPI-145 administered orally
BID in patients with advanced hematologic malignancies. The dose-escalation
portion of the study is complete, with the maximum tolerated dose defined at
75 mg BID. Infinity is continuing to evaluate IPI-145 in the following seven
expansion cohorts:

25 mg BID expansion cohorts

1. Relapsed/refractory CLL, indolent non-Hodgkin lymphoma (iNHL) and mantle
cell lymphoma (MCL)

2. Treatment-naïve CLL in high-risk patients (over age 65 or having a 17p del
or p53 mutations)

75 mg BID expansion cohorts

1. Relapsed/refractory CLL, iNHL and MCL

2. T-cell lymphomas

3. Aggressive B-cell lymphomas

4. Myeloid neoplasms

5. Acute lymphoblastic leukemia

About Infinity’s PI3K Program in Blood Cancers

Infinity is developing IPI-145, a potent, oral inhibitor of Class I
phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma. The PI3Ks are a family
of enzymes involved in multiple cellular functions, including cell
proliferation and survival, cell differentiation, cell migration and
immunity.^4 The PI3K-delta and PI3K-gamma isoforms are preferentially
expressed in leukocytes (white blood cells), where they have distinct and
mostly non-overlapping roles in immune cell development and function.
Targeting PI3K-delta and PI3K-gamma may provide multiple opportunities to
develop differentiated therapies for the treatment of hematologic malignancies
and inflammatory diseases.

IPI-145, Infinity’s lead product candidate, is currently progressing in a
Phase 1 study in patients with advanced hematologic malignancies. An
investigator-sponsored Phase 1b, open-label, dose-escalation study of IPI-145
in patients with B-cell NHL, CLL and T-cell lymphoma in combination with
rituximab (a monoclonal antibody therapy), bendamustine (a chemotherapy) or
both rituximab and bendamustine is also open for enrollment.

Additionally, Infinity is conducting preclinical studies of IPI-443, its
second oral PI3K-delta and PI3K-gamma inhibitor. IPI-443 has a distinct
biochemical profile from IPI-145 and also has the potential to treat
hematologic malignancies and inflammatory diseases.

About Infinity Pharmaceuticals, Inc.

Infinity is an innovative biopharmaceutical company dedicated to discovering,
developing and delivering best-in-class medicines to people with
difficult-to-treat diseases. Infinity combines proven scientific expertise
with a passion for developing novel small molecule drugs that target emerging
disease pathways. Infinity’s programs focused on the inhibition of
phosphoinositide-3-kinase and heat shock protein 90 are evidence of its
innovative approach to drug discovery and development. For more information on
Infinity, please refer to the company’s website at www.infi.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of
The Private Securities Litigation Reform Act of 1995. Such forward-looking
statements include those regarding the Company’s expectations about: its
ability to execute on its strategic plans; plans to initiate additional
clinical trials; and the therapeutic potential of PI3K inhibition, IPI-145 and
IPI-443. Such statements are subject to numerous important 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 will 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 Infinity’s product candidates will continue. Further, there can be no
guarantee that any positive developments in Infinity’s product portfolio will
result in stock price appreciation. Management’s expectations and, therefore,
any forward-looking statements in this press release could also be affected by
risks and uncertainties relating to a number of other factors, including the
following: Infinity’s 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; Infinity’s 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 Infinity’s competitors for diseases in which Infinity is
currently developing or intends to develop its product candidates; and
Infinity’s 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 management’s expectations are described
in greater detail under the caption “Risk Factors” included in Infinity’s
quarterly report on Form 10-Q filed with theSecurities and Exchange
Commission (SEC) onMay 7, 2013, and other filings filed by Infinity with
theSEC. Any forward-looking statements contained in this press release 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.

^1 Data reported as of the April 29, 2013, data cutoff.

^2 Halleck M et al. (2008) Guidelines for the diagnosis and treatment of
chronic lymphocytic leukemia: A report from the International Workshop on
Chronic Lymphocytic Leukemia updating the National Cancer Institute – Working
Group 1996 Guidelines. Blood 111: 5446-5456.

^3 Grever et al. (2007) Comprehensive assessment of genetic and molecular
features predicting outcome in patients with chronic lymphocytic leukemia:
Results from the US intergroup phase III trial E2997. J Clin Oncol 25:799-804.

^4 Weinberg RA (2007) Cytoplasmic signaling circuitry programs many of the
traits of cancer. In Jeffcock E, Zayatz E, and Mickey RK (Eds.) The biology of
cancer (pp. 179-183). New York, NY: Garland Science, Taylor & Francis Group.

Contact:

Infinity Pharmaceuticals, Inc.
Jaren Irene Madden, 617-286-6264 (mobile)
Jaren.Madden@infi.com
http://www.infi.com
 
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