IPI-549 Alters the Immune-Suppressive Microenvironment and Enhances the Activity of Checkpoint Inhibitors in Preclinical Models

CAMBRIDGE, Mass., April 18, 2016 /PRNewswire/ -- Infinity Pharmaceuticals, Inc.  (NASDAQ: INFI) today announced new preclinical data for IPI-549, an orally administered immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase gamma (PI3K-gamma). Preclinical data in multiple solid tumor models demonstrate that IPI-549 targets immune cells and alters the immune-suppressive microenvironment, promoting an anti-tumor immune response that leads to tumor growth inhibition. Data also demonstrate that IPI-549 enhances the effects of checkpoint inhibitors, resulting in improved survival in murine models. These data were presented at the American Association for Cancer Research (AACR) Annual Meeting 2016 in New Orleans, Louisiana. A Phase 1 clinical study is under way to explore the safety and activity of IPI-549 both as a monotherapy and in combination with anti-PD-1 antibody therapy, a type of checkpoint inhibitor.   

"While advances in our understanding of the immune response to cancer have resulted in new therapies for patients, additional treatments are needed that can offer even more patients the chance for prolonged survival," stated Jedd Wolchok, M.D., Ph.D., chief of Melanoma and Immunotherapeutics Service, Lloyd J. Old/Ludwig Chair in Clinical Investigation Department of Medicine and Ludwig Center, at Memorial Sloan Kettering Cancer Center and lead investigator for the Phase 1 clinical study of IPI-549. "Emerging data from our collaboration with Infinity's discovery team provide additional rationale for combining IPI-549 with checkpoint inhibitors, and I am pleased to be leading the Phase 1 study for this program."

Preclinical Data for IPI-549 Presented at the AACR Annual Meeting 2016 (Abstract #554)
Infinity researchers, in collaboration with researchers at Memorial Sloan Kettering Cancer Center, presented preclinical data for IPI-549 in a poster entitled, "Checkpoint blockade therapy is improved by altering the immune suppressive microenvironment with IPI-549, a potent and selective inhibitor of PI3K-gamma, in preclinical models."

In preclinical models, treatment with IPI-549 leads to a decrease in tumor-associated immune suppressive myeloid cells.  IPI-549 treatment also leads to a decrease in FOXP3 T-regulatory cells, which have immune-suppressive effects, and an increase in intratumoral CD8+ T-cells, which are known to play a role in inhibiting tumor growth. Taken together, these data suggest that through its effect on myeloid cells and T-cells, IPI-549 has the potential to disrupt the immune-suppressive microenvironment and enable a heightened anti-tumor immune response.

Preclinical data in murine models show that treatment with IPI-549 in combination with anti-CTLA4 or anti-PD-L1, two types of checkpoint inhibitors, results in greater tumor growth inhibition compared to monotherapy treatment. Additionally, IPI-549 in combination with anti-PD-1 increased the number of complete responses and improves survival. Re-implantation of tumor cell lines into mice that had achieved complete responses revealed low or no tumor engraftment, suggesting sustained tumor-specific immune protection. 

These data provide additional preclinical rationale for the ongoing Phase 1 clinical study designed to explore the safety and activity of IPI-549 as a monotherapy and in combination with anti–PD-1 antibody therapy in patients with selected solid tumors, including non-small cell lung cancer and melanoma (ClinicalTrials.gov identifier NCT02637531).          

Infinity is also developing duvelisib, an investigational, oral, dual inhibitor of PI3K-delta and PI3K-gamma. The PI3K pathway is also known to play a critical role in regulating the growth and survival of certain types of blood cancers. Duvelisib is being evaluated in registration-focused studies, including DYNAMO^TM, a Phase 2 study in patients with refractory indolent non-Hodgkin lymphoma (iNHL), BRAVURA, a Phase 3 study in patients with relapsed iNHL, and DUO^TM, a Phase 3 study in patients with relapsed/refractory chronic lymphocytic leukemia. For additional information about clinical studies of duvelisib, please visit www.infi.com or www.clinicaltrials.gov.

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.

Duvelisib and IPI-549 are investigational compounds and their safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

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. 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-gamma selective inhibition and IPI-549, including in combination with other potential therapies; the therapeutic potential of PI3K-delta, gamma inhibition and duvelisib; plans to investigate IPI-549 in patients with solid tumors; and its 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, complete enrollment, initiate clinical studies, or submit regulatory filings 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 Infinity's strategic collaboration with AbbVie will continue or 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; a failure of Infinity and/or AbbVie to fully perform under the strategic collaboration and/or an early termination of the collaboration and license agreement; 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 annual report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 23, 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.

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

Christi Waarich
Senior Manager, Investor Relations
617-453-1363 or [email protected]

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SOURCE Infinity Pharmaceuticals, Inc.

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