Infinity Presents Initial Clinical And New Preclinical Data On IPI-549 At Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference

CAMBRIDGE, Mass., Sept. 26, 2016 /PRNewswire/ -- Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) today announced initial clinical and new preclinical data for IPI-549, an orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. Preliminary Phase 1 results from nine patients with advanced solid tumors show that the safety, pharmacokinetics and pharmacodynamics of IPI-549 monotherapy treatment appear favorable. Additionally, new preclinical data demonstrate that IPI-549 can reverse tumor resistance to checkpoint inhibitors, providing additional rationale for the planned evaluation of IPI-549 in combination with a checkpoint inhibitor in the ongoing Phase 1 study. These data are being presented in a poster session at the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival taking place in New York City.

"While there have been recent advancements in therapies as a result of our understanding of the immune response to cancer, additional treatments are needed that can improve survival for more patients," stated Anthony Tolcher, M.D., FRCP(C), clinical director at South Texas Accelerated Research Therapeutics and an investigator for the IPI-549 Phase 1 clinical study. "The initial Phase 1 monotherapy data for IPI-549 are encouraging, and I look forward to the upcoming initiation of the first cohort evaluating IPI-549 in combination with a checkpoint inhibitor."

"As the only PI3K-gamma inhibitor in clinical development, IPI-549 offers a unique approach to enhancing the anti-tumor immune response. Our preclinical findings suggest that IPI-549 remodels the immune-suppressive tumor microenvironment, primarily through its effects on myeloid cells, leading to enhanced anti-tumor T cell activity and cytokine production, all of which play critical roles in immune response," stated Jedd Wolchok, M.D., Ph.D., Chief of the Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center (MSK), as well as Associate Director of the Ludwig Center for Cancer Immunotherapy and Director of the Parker Institute for Cancer Immunotherapy, both at MSK. Dr. Wolchok is also a scientific collaborator on the IPI-549 program and lead investigator for the Phase 1 clinical study. "Data also demonstrate that the effects of IPI-549 on the tumor microenvironment reverse resistance to checkpoint inhibition in multiple preclinical models, providing further rationale for evaluating this combination therapy in patients."

The ongoing Phase 1 clinical study of IPI-549 is designed to explore safety, tolerability, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with an anti-PD-1 antibody, a checkpoint inhibitor, in approximately 175 patients with advanced solid tumors, including non-small cell lung cancer (NSCLC), melanoma and squamous cell carcinoma of the head and neck (SCCHN).¹ The monotherapy dose-escalation portion of the study is continuing, and Infinity expects to initiate cohorts studying IPI-549 in combination with an anti-PD-1 antibody this fall.

Although there has been great progress in the treatment of cancer, there remains a need for additional treatment options. NSCLC, melanoma and SCCHN account for more than 17 percent of all new cancer cases in the U.S.^2,3

Summary of Early Phase 1 Clinical Data Presented for IPI-549
The poster, "IPI-549-01: A Phase 1/1b first-in-human study of IPI-549, a PI3K-gamma inhibitor, as monotherapy and in combination with an anti-PD1 antibody in subjects with advanced solid tumors,"⁴ included data from nine patients with advanced solid tumors who received monotherapy treatment with IPI-549, with doses ranging from 10 mg once daily (QD) to 20 mg QD.

No dose limiting toxicities and no serious adverse events have occurred. Six of nine patients remain on study, with a maximum exposure of 24 weeks at the time of analysis. Pharmacokinetic and pharmacodynamic data support once daily dosing of IPI-549 based on the observed half-life and inhibition of the PI3K-gamma pathway.

Summary of New Preclinical Data Presented for IPI-549
The poster, "The PI3K-gamma inhibitor, IPI-549, increases antitumor immunity by targeting tumor-associated myeloid cells and remodeling the immune-suppressive tumor microenvironment,"⁵ includes new data further elucidating the mechanism of action for IPI-549 and demonstrating the synergy between IPI-549 and checkpoint inhibitors in multiple preclinical models.

Preclinical studies show that resistance to checkpoint inhibition is associated with increased numbers of myeloid cells, and that IPI-549 treatment is able to reverse the lack of response in tumor models that are insensitive to checkpoint inhibitors. These findings provide further rationale for studying IPI-549 in combination with an anti-PD-1 antibody (a type of checkpoint inhibitor) in the clinic.

Preclinical data also demonstrate that treatment with IPI-549 leads to a shift in tumor-associated myeloid cells from the immunosuppressive phenotype (M2 phenotype) to the proinflammatory phenotype (M1). Additionally, treatment with IPI-549 also increases the frequency of tumor-specific T cells and increases the production of proinflammatory cytokines. These findings lend support to the hypothesis that inhibition of PI3K-gamma by IPI-549 leads to an activated and more efficient anti-tumor immune response through its effects on the immune-suppressive tumor microenvironment.

About IPI-549
IPI-549 is an orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 inhibits immune-suppressive macrophages within the tumor microenvironment, whereas other immunotherapies such as checkpoint modulators more directly target immune effector cell function. 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.

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.

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, initiation of cohorts studying IPI-549 in combination with an anti-PD-1 antibody this fall, and the safety, pharmacokinetics and pharmacodynamics of IPI-549 monotherapy treatment. 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 and other risks 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 August 9, 2016, 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.

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

¹ www.clinicaltrials.gov, NCT02637531

² 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 September 14, 2016.

³ Conquer Cancer Foundation, Head and Neck Cancer Statistics, http://www.cancer.net/cancer-types/head-and-neck-cancer/statistics, Last Accessed September 14, 2016.

⁴ Tochler, A., Hong D., Sullivan R, et al. IPI-549-01: A Phase 1/1b first-in-human study of IPI-549, a PI3K-gamma inhibitor, as monotherapy and in combination with an anti-PD1 antibody in subjects with advanced solid tumors. Presented at Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival (Poster B070), 2016.

⁵ Rausch, M., Tchaicha, Tibbitts, T. et al. The PI3K-gamma inhibitor, IPI-549, increases antitumor immunity by targeting tumor-associated myeloid cells and remodeling the immune-suppressive tumor microenvironment. Presented at Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival (Poster B032), 2016.

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SOURCE Infinity Pharmaceuticals, Inc.

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