Updated Phase 1 Data for IPI-549 Presented at AACR Annual Meeting 2017

WASHINGTON, April 1, 2017 /PRNewswire/ -- Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) today reported updated Phase 1 clinical data for IPI-549, an orally administered immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase gamma (PI3K-gamma). These Phase 1 clinical dose-escalation data demonstrated that IPI-549 was well tolerated both as a monotherapy and in combination with Opdivo^® (nivolumab), a PD-1 immune checkpoint inhibitor. Additionally, data from the more advanced monotherapy module of the study showed IPI-549 has a favorable pharmacokinetic (PK) and pharmacodynamic (PD) profile that supports once daily (QD) dosing. The data included 15 evaluable patients who received IPI-549 as a monotherapy and six evaluable patients who received IPI-549 in combination with Opdivo. The data were presented at the American Association for Cancer Research (AACR) Annual Meeting 2017 taking place in Washington, D.C., April 1 – 5. IPI-549 is believed to be the only selective PI3K-gamma inhibitor in clinical development.

"While tremendous progress has been made in the field of immuno-oncology, additional treatment options are needed for patients who relapse or do not respond to currently available therapies," stated Anthony Tolcher, M.D., FRCP(C), clinical director at South Texas Accelerated Research Therapeutics, an investigator for the Phase 1 study. "The emerging profile of IPI-549 is very encouraging and supports continued investigation as a monotherapy and in combination with other therapeutics, including Opdivo. I look forward to my continued participation in this study, particularly as we seek to explore the activity of IPI-549 in the planned expansion modules."

"Our preclinical research demonstrates that IPI-549 could offer a unique approach within immuno-oncology by reprogramming macrophages from a pro-tumor to an anti-tumor phenotype, thereby activating anti-tumor T cells," commented Jeffery Kutok, M.D., Ph.D., chief scientific officer at Infinity. "These data reported today are promising and represent a significant de-risking for our clinical program. We look forward to completing the dose-escalation modules of this study, and in the second half of 2017, we expect to initiate the expansion modules where we will continue to evaluate safety and also assess the activity of IPI-549 alone and in combination with Opdivo."

The Phase 1 study includes dose-escalation and expansion modules to evaluate IPI-549 as a monotherapy and in combination with Opdivo. Patient enrollment is complete in five monotherapy does-escalation cohorts with doses of IPI-549 ranging from 10 mg QD to 40 mg QD. Patient enrollment is also complete in two combination dose-escalation cohorts to evaluate IPI-549 20 mg and 30 mg QD in combination with Opdivo.

Infinity expects to complete the monotherapy dose-escalation phase of the study in the first half of 2017 and initiate the monotherapy expansion module in the second half of the year. The company also expects to complete the dose-escalation phase evaluating IPI-549 in combination with Opdivo and subsequently initiate a combination expansion module in the second half of 2017. The combination expansion module will include patients with non-small cell lung cancer (NSCLC), melanoma, and squamous cell carcinoma of the head and neck (SCCHN) whose tumors show initial resistance or subsequently develop resistance to immune checkpoint therapy. There is a great need for additional treatment options for the growing number of patients living with these cancers, which account for more than 17 percent of all new cancer cases in the U.S.^1,2

The updated Phase 1 clinical data presented in the educational session today will be further detailed in a poster being presented during a poster session taking place at the AACR Annual Meeting 2017 on Tuesday, April 4, from 8:00 a.m. – 12:00 p.m. ET. Details of the presentation are as follows:
Title: IPI-549-01 - A Phase 1/1b, First-in-Human Study of IPI-549, a PI3K-Gamma Inhibitor, as Monotherapy and in Combination with Nivolumab in Patients with Advanced Solid Tumors
Abstract number: CT089
Lead Author: Anthony Tolcher, M.D., FRCP(C), clinical director at South Texas Accelerated Research Therapeutics
Location: Convention Center, Halls A-C, Poster Section 33

Details of Today's Presentation
In a presentation entitled "Reprogramming Tumor-Associated Macrophages by Targeting PI3K-Gamma through a Small Molecule Approach," Jeffery Kutok, M.D., Ph.D., chief scientific officer at Infinity, discussed the preclinical rationale for targeting PI3K-gamma previously reported in two publications in Nature^3,4 and summarized updated clinical data from the Phase 1 study of IPI-549 in patients with advanced solid tumors. The clinical data reported today from a March 20, 2017, data cutoff included 15 evaluable patients who received monotherapy doses of IPI-549 ranging from 10 mg to 40 mg QD and six evaluable patients who received IPI-549 20 mg QD in combination with Opdivo.

Summary of Updated Phase 1 Data
The updated data from the monotherapy dose-escalation module demonstrated that IPI-549 treatment was well tolerated. Among the 15 evaluable patients, no dose limiting toxicities or serious drug-related side effects occurred, and no side effects led to treatment discontinuation or dose reduction. The PK and PD properties of IPI-549 appeared favorable, with near-complete and sustained inhibition of PI3K-gamma at doses at or above 20 mg QD, supporting once daily dosing of IPI-549. Of the 15 evaluable patients, six have remained on treatment for at least 24 weeks, and three patients have remained on treatment for more than 32 weeks. The monotherapy dose-escalation module is ongoing to determine the optimal dose for the monotherapy expansion cohort.

Preliminary data from the combination dose-escalation module evaluating 20 mg IPI-549 in combination with Opdivo demonstrated that the treatment regimen was well tolerated. Among the six evaluable patients, no dose limiting toxicities or serious drug-related side effects occurred and no side effects led to treatment discontinuation. Additionally, combination treatment did not result in new or unexpected side effects relative to the known safety profile of each treatment when administered as monotherapy. The PK profile of IPI-549 in combination with Opdivo appeared favorable and suggested that Opdivo does not affect the PK properties of IPI-549. The combination dose-escalation module is ongoing to determine the optimal dose for the combination expansion module.

Summary of Preclinical Research
Preclinical research has demonstrated that PI3K-gamma is highly expressed in tumor-associated macrophages and that blockade of PI3K-gamma signaling by treatment with IPI-549 results in reprogramming macrophages. This reprogramming shifted macrophages in the tumor microenvironment from the M2, or pro-tumor phenotype, to the M1, or anti-tumor phenotype and increased the number and activity of anti-tumor T cells that attack the tumor and also increased the production of pro-inflammatory cytokines.

Preclinical data from multiple solid tumor models demonstrated that IPI-549 was active as a monotherapy and that IPI-549 administered in combination with checkpoint inhibition led to enhanced activity compared to either treatment alone. Additionally, preclinical data demonstrated that M2, pro-tumor macrophages are associated with resistance to checkpoint inhibitor monotherapy and treatment with IPI-549 in combination with checkpoint inhibitors is able to overcome this resistance by reprogramming macrophages from the M2, pro-tumor phenotype to the M1, anti-tumor phenotype. Taken together, these preclinical data demonstrate that PI3K-gamma plays a key role in the immuno-suppressive tumor microenvironment, help to further elucidate the mechanism of action for IPI-549 and provide a strong rationale for the ongoing Phase 1 study of IPI-549.

Additional Discussion on PI3K-Gamma at AACR Annual Meeting 2017
Judith A. Varner, Ph.D., professor in the departments of Pathology and Medicine at UC San Diego School of Medicine and the senior author of one of the two articles on PI3K-gamma published in Nature³ in November 2016, will discuss the importance of targeting PI3K-gamma to control cancer immune suppression during a scientific session at the AACR Annual Meeting 2017 on Monday, April 3, from 6:15 p.m. – 6:45 p.m. ET.

• Session: Joint Cancer Immunology (CIMM)/Tumor Microenvironment (TME) Working Groups Evening Scientific Session at the AACR Annual Meeting 2017 on.
• Presentation Title: Targeting the molecular switch controlling immune suppression for cancer therapy.
• Location: Independence Ballroom A-D, Meeting Level 4, Marriott Marquis

About the IPI-549 and the Ongoing Phase 1 Study
IPI-549 is an investigational, orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 reprograms macrophages from a pro-tumor to an anti-tumor phenotype and is able to overcome resistance to checkpoint inhibition.^3,4 As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.

A Phase 1 study of IPI-549 in patients with advanced solid tumors is ongoing to explore the activity, safety, tolerability, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with Opdivo^® (nivolumab), a PD-1 immune checkpoint inhibitor, in patients with advanced solid tumors.⁵ The study includes monotherapy and combination dose-escalation phases, in addition to a monotherapy expansion module and a combination expansion module. The expansion module evaluating IPI-549 plus Opdivo will include patients with non-small cell lung cancer (NSCLC), melanoma and squamous cell carcinoma of the head and neck (SCCHN). Patients enrolled in the combination expansion module represent a difficult-to-treat population, as they must have demonstrated initial resistance or subsequently develop resistance to an anti-PD-1 or anti-PD-L1 therapy immediately prior to enrolling in the study. Overall, the study is expected to enroll approximately 175 patients.

IPI-549 is an investigational compound and its safety and efficacy has not been evaluated by the U.S. Food and Drug Administration or any other health authority.

About Infinity
Infinity is an innovative biopharmaceutical company dedicated to advancing novel medicines for people with cancer. Infinity is developing IPI-549, an oral immuno-oncology development candidate that selectively inhibits PI3K-gamma. A Phase 1 study in patients with advanced solid tumors is ongoing. For more information on Infinity, please refer to Infinity's website at www.infi.com.

Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 including those regarding the company's expectations about the timing and type of data presentations, the therapeutic potential of PI3K-gamma inhibition and of IPI-549, alone or in combination with other agents including Opdivo (nivolumab), and clinical trial plans regarding IPI-549. 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, including, for example, that there is no guarantee that IPI-549 will successfully complete necessary preclinical and clinical development phases, or gain regulatory approval. Further, there can be no guarantee that any positive developments regarding IPI-549 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 content and timing of decisions made by the U.S. FDA and other regulatory authorities; Infinity's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; Infinity's ability to obtain, maintain and enforce patent and other intellectual property protection for IPI-549; and other risks described in greater detail under the caption "Risk Factors" included in Infinity's Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on March 14, 2017, 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.

OPDIVO^® is a registered trademark of Bristol-Myers Squibb.

Contact:
Jaren Irene Madden, Senior Director, Investor Relations and Corporate Communications
617-453-1336 or [email protected]

¹ American Cancer Society, Cancer Facts and Statistics 2016, http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2016/index and http://www.cancer.org/cancer/skincancer-melanoma/detailedguide/melanoma-skin-cancer-key-statistics, Last Accessed March 2, 2017.
² Conquer Cancer Foundation, Head and Neck Cancer Statistics, http://www.cancer.net/cancer-types/head-and-neck-cancer/statistics, Last Accessed March 2, 2017.
³ Kaneda, M., Messer, K., Ralainirina, N., Li, H., et al. PI3Kγ is a molecular switch that controls immune suppression. Nature, 2016 Nov;539:437–442.  
⁴ De Henau, O., Rausch, M., Winkler, D., Campesato, L., et al. Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells. Nature, 2016 Nov;539:443-447.
⁵ www.clinicaltrials.gov, NCT02637531.

SOURCE Infinity Pharmaceuticals, Inc.

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