Infinity Reports Phase 1 Data Showing Encouraging Clinical Activity of
IPI-145 Across a Broad Range of Blood Cancers at the 12th International
Conference on Malignant Lymphoma
– Early Data Show that IPI-145 Is Well Tolerated, with a Rapid Onset of
Clinical Activity –
12th International Conference on Malignant Lymphoma
CAMBRIDGE, Mass. -- June 24, 2013
Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) today announced 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
advanced hematologic malignancies, or potentially fatal blood cancers. Data
from the study showed that IPI-145 was well tolerated and clinically active
across a broad range of blood cancers, including indolent non-Hodgkin lymphoma
(iNHL), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL),
Hodgkin lymphoma (HL) and T-cell lymphomas. These findings were reported in
three presentations during the 12^th International Conference on Malignant
Lymphoma (ICML) held from June 19 – 22, 2013, in Lugano, Switzerland.
“These early data show that IPI-145 is well tolerated and clinically active in
patients with B-cell or T-cell malignancies, with a median time to response of
less than two months,” commented Ian Flinn, M.D., Ph.D., director, hematologic
malignancies program, Sarah Cannon Research Institute, and an investigator for
the trial. “Many of these hematologic malignancies are difficult to treat, and
new treatment options for patients are clearly needed. Investigational
medicines in development, such as IPI-145, are exciting because they offer a
targeted approach and have the potential to reduce or delay the need for
“We hope the rapid onset of activity observed with IPI-145 across a broad
range of hematologic malignancies will translate into a meaningful clinical
benefit for patients,” stated Pedro Santabarbara, M.D., chief medical officer
at Infinity. “Infinity is committed to rapidly advancing IPI-145 in the clinic
with a goal of developing the best-in-class PI3K inhibitor for the treatment
of hematologic malignancies. Earlier this month, we announced the initiation
of a Phase 2 trial of IPI-145 in patients with refractory iNHL, and we expect
to begin our next trial in patients with blood cancers later this year.”
On June 3, 2013, Infinity announced the initiation of a Phase 2, open-label,
single-arm study designed to evaluate the safety and efficacy of IPI-145 dosed
at 25 mg twice daily (BID) in approximately 120 patients with iNHL (follicular
lymphoma, marginal zone lymphoma or small lymphocytic lymphoma) whose disease
is refractory to both rituximab and chemotherapy or radioimmunotherapy. The
primary endpoint of the study is response rate according to the International
Working Group Criteria.^1 In June, Infinity reported data from its ongoing
Phase 1 study showing a 68 percent response rate in patients with iNHL, which
included three complete responses (CRs) and 10 partial responses (PRs) among
the 19 patients evaluable for response.
“The early Phase 1 data of IPI-145 in patients with iNHL are exciting, and we
believe IPI-145 has the potential to become the best-in-class PI3K inhibitor
in this indication,” stated Julian Adams, Ph.D., president of research and
development at Infinity. “Infinity has therefore moved quickly into Phase 2
development to evaluate IPI-145 dosed at 25 mg twice daily in patients with
refractory iNHL. In the Phase 1 study, this dose showed rapid, robust clinical
activity and demonstrated complete inhibition of PI3K-delta and at least 50
percent inhibition of PI3K-gamma.”
Summary of IPI-145 Data in Advanced Hematologic Malignancies Presented at ICML
In total, the Phase 1 data of IPI-145 reported in three separate presentations
at ICML included patients with B-cell lymphoma (51 patients evaluable for
safety and 38 for response), CLL (34 patients evaluable for safety and 22 for
response) and T-cell lymphoma (17 patients evaluable for safety and nine for
response).^2,3,4 These patients had advanced disease and had progressed during
or were refractory to, intolerant of, or ineligible for established therapy.
Patients had a median of four prior systemic therapies (range: 1 to 13), and
69 percent of patients had at least three prior systemic therapies.
Safety data presented in all three presentations 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.
Data also showed that IPI-145 is rapidly absorbed and demonstrates a linear
pharmacokinetic (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 rapidly decreased the levels of several cytokines and chemokines
known to be important in lymphocyte trafficking and function. Additionally,
rapid, sustained inhibition of AKT phosphorylation (a marker of PI3K
inhibition) was observed in CLL cells from patients treated with IPI-145, with
no difference observed between the 25 mg and 75 mg doses.
Data reported showed that IPI-145 is clinically active across a broad range of
patients with advanced hematologic malignancies, with responses observed in
patients with iNHL, CLL, T-cell lymphoma, MCL and HL. The onset of activity
was rapid, with a median time to response of less than two months (range: 1.6
– 5.6 months).
Additional Phase 1 data reported included the following:
*Among the 51 patients with B-cell lymphoma evaluable for safety, the most
common Grade ≥ 3 adverse events were neutropenia (22 percent Grade 3;
eight percent Grade 4), which was transient and rarely required dose
modification, and Grade ≥ 3 ALT/AST elevations (16 percent Grade 3; two
percent Grade 4), the majority of which were managed by dose interruptions
and reductions. IPI-145 did not cause a clinically significant effect on
hematologic parameters. Six (12 percent of) patients discontinued
treatment due to an adverse event.
*The adverse events observed in patients with iNHL were consistent with
those reported in patients with B-cell lymphoma.
*There was a 68 percent response rate in patients with iNHL, which included
three CRs and 10 PRs among 19 patients evaluable for response. Stable
disease was reported in three patients. Additionally, there was a minor
response in a patient with Waldenström’s macroglobulinemia.
*Responses were also observed in patients with MCL (one CR and three PRs
among six evaluable patients) and HL (one CR among three evaluable
*Responses occurred early, with a median time to response of 1.8 months
(range: 1.6 – 4.1 months).
*Among the 34 patients with CLL evaluable for safety, the most common Grade
≥ 3 adverse events were neutropenia (15 percent Grade 3; 12 percent Grade
4), the majority of which did not require dose reduction, and ALT/AST
elevations (six percent Grade 3; no Grade 4). The majority of all ALT/AST
elevations were managed by dose interruptions and reductions. IPI-145 did
not cause a clinically significant effect on hematologic parameters. Seven
(21 percent of) patients discontinued treatment due to an adverse event.
*There was a 55 percent response rate in patients with CLL, which included
12 PRs among 22 patients evaluable for response. PRs were defined by the
International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria.^5
Stable disease was reported in nine patients, of which seven had nodal
*The median time to response was 1.9 months (range: 1.8 - 5.6 months).
*Among the 17 patients with T-cell lymphoma, the most common Grade ≥ 3
adverse event was ALT/AST elevation (24 percent), the majority of which
were managed by dose interruptions and dose reductions. Clinically
significant neutropenia was not observed. Two (12 percent of) patients
discontinued treatment due to an adverse event.
*There was a 33 percent response rate in patients with T-cell lymphoma,
which included one CR and one PR in patients with peripheral T-cell
lymphoma (PTCL) and a PR in a patient with cutaneous T-cell lymphoma
(CTCL). Stable disease was reported in two patients with CTCL. The median
time to response was 1.9 months (range: 1.7 – 2.7 months).
The data reported at ICML may also be found in the Publications Archive on
Infinity’s website http://www.infi.com/product-candidates-publications.asp.
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
25 mg BID expansion cohorts
1.Relapsed/refractory CLL, iNHL and MCL
2.Treatment-naïve CLL in high-risk patients (over age 65 or having a 17p
deletion or a p53 mutation)
75 mg BID expansion cohorts
1.Relapsed/refractory CLL, iNHL and MCL
3.Aggressive B-cell lymphomas
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.^6 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 2 study in patients with indolent non-Hodgkin lymphoma (iNHL) and 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.
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: the
therapeutic potential of PI3K inhibition, IPI-145 and IPI-443; progress in and
plans for the development of IPI-145; plans to initiate additional clinical
trials of IPI-145; and the Company’s ability to execute on its strategic
plans. 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 Cheson BD et al. (2007) Revised response criteria for malignant lymphoma.
J. Clin Oncol 25:579-586.
^2 Kahl, B. et al. (2013) Preliminary Safety and efficacy of IPI-145, a potent
inhibitor of phosphoinositide-3-kinase-δ,γ in patients with
relapsed/refractory B-cell lymphoma. Presented at the 12^th International
Conference on Malignant Lymphoma, Lugano, Switzerland.
^3 Flinn, I et al. (2013) Preliminary Safety and efficacy of IPI-145, a potent
inhibitor of phosphoinositide-3-kinase-δ,γ in patients with
relapsed/refractory CLL/SLL. Presented at the 12^th International Conference
on Malignant Lymphoma, Lugano, Switzerland.
^4 Horwitz, S et al. (2013) Preliminary Safety and efficacy of IPI-145, a
potent inhibitor of phosphoinositide-3-kinase-δ,γ in patients with
relapsed/refractory. Presented at the 12^th International Conference on
Malignant Lymphoma, Lugano, Switzerland.
^5 Hallek 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.
^6 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.
Infinity Pharmaceuticals, Inc.
Jaren Irene Madden, 617-453-1336
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