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

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 chemotherapy.”

“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:

B-Cell Lymphoma

• 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 patients).
• Responses occurred early, with a median time to response of 1.8 months (range: 1.6 – 4.1 months).

CLL

• 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 responses.
• The median time to response was 1.9 months (range: 1.8 - 5.6 months).

T-Cell Lymphoma

• 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 expansion cohorts:

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
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.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.

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: 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 the Securities and Exchange Commission (SEC) on May 7, 2013, and other filings filed by Infinity with the SEC. 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.