Infinity Presents Preclinical Data and Phase 1 Clinical Data on IPI-549 at PI3K Keystone Symposia Conference

CAMBRIDGE, Mass., Jan. 20, 2017 /PRNewswire/ -- Today, during a plenary session at the Keystone Symposia Conference, "PI3K Pathways in Immunology, Growth Disorders and Cancer," Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) presented preclinical data for IPI-549, an oral immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase-gamma (PI3K-gamma). Preclinical data showed that IPI-549 is able to help overcome resistance to checkpoint inhibition by remodeling the immune-suppressive tumor microenvironment primarily through its effects on myeloid cells, a type of cell considered to be involved in suppressing immune response against tumors. Initial Phase 1 monotherapy data from nine patients with advanced solid tumors were also summarized and showed that the safety, pharmacokinetics and pharmacodynamics of IPI-549 monotherapy treatment appeared favorable. IPI-549 is believed to be the only PI3K-gamma inhibitor in clinical development.

These preclinical data provide a compelling rationale for Infinity's ongoing Phase 1 clinical study designed to evaluate IPI-549 as a monotherapy and in combination with Opdivo^® (nivolumab), a PD-1 immune checkpoint inhibitor, in patients with advanced solid tumors. The combination portion of the Phase 1 study 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

"While new immunotherapies, such as T cell checkpoint inhibitors, are showing great promise in the treatment of various cancers, there are multiple mechanisms of immune tolerance in tumors. Additional treatment options are needed for patients who relapse or do not respond to currently available therapies," stated Jeffery Kutok, M.D., Ph.D., vice president of biology and translational science at Infinity Pharmaceuticals and a plenary speaker at the conference. "The data presented suggest that targeting PI3K-gamma by IPI-549 within immune-suppressive myeloid cells in the tumor microenvironment could offer a unique way to both enhance the activity of checkpoint inhibition in sensitive tumors, as well as to overcome tumor resistance to checkpoint inhibition. Infinity is excited to be at the forefront of developing a potentially transformative approach within immuno-oncology, and we look forward to reporting additional data from our Phase 1 study of IPI-549 later this year."

The tumor microenvironment, or TME, refers to the non-cancerous cells present in the tumor. Cells within the TME, including immune-suppressive myeloid cells, can provide growth signals to tumor cells, as well as signals that inhibit an anti-tumor immune response. The presence of the supportive TME is believed to be one reason why some cancer therapies do not provide durable or effective results. Targeting the immune-suppressive myeloid cells represents an emerging approach within the field of cancer immunotherapy, and inhibition of PI3K-gamma represents a novel approach to targeting the immune-suppressive microenvironment.

Summary of Today's Presentation
In a presentation entitled "The PI3K-gamma inhibitor, IPI-549, increases antitumor immunity by targeting tumor-associated myeloid cells and overcomes immune checkpoint blockade resistance in preclinical models," Dr. Kutok reviewed data previously published in two Nature articles^3,4 and presented at the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.^5,6

Preclinical data showed that macrophage PI3K-gamma signaling promotes immune suppression by inhibiting activation of anti-tumor T cells. Blocking PI3K-gamma activated the immune response and significantly suppressed growth of tumors in preclinical models. These data demonstrate that PI3K-gamma plays a key role in cancer growth and also help to further elucidate the mechanism of action for IPI-549.

Preclinical data also demonstrated that resistance to immune checkpoint blockade is directly mediated by the suppressive activity of tumor-infiltrating myeloid cells in a number of preclinical tumor models and confirmed that immune-suppressive myeloid cells play a critical role in resistance to checkpoint inhibitors. Furthermore, the data showed that inhibition of PI3K-gamma by IPI-549 switched the activation of myeloid cells from an immune-suppressive state to a pro-inflammatory state, leading to enhanced anti-tumor cytotoxic T cell activity, particularly when combined with checkpoint inhibitors. Thus, in preclinical models, IPI-549 treatment is able to overcome resistance to checkpoint inhibition. These findings provide further rationale for the ongoing Phase 1 study of IPI-549 in combination with checkpoint inhibitors.

Phase 1 clinical data from nine patients treated with IPI-549 administered as a monotherapy at doses ranging from 10 mg once daily (QD) to 20 mg QD were also summarized during the presentation. As of the September 2016 data cutoff, no dose limiting toxicities and no serious adverse events were observed. Pharmacokinetic and pharmacodynamic data supported once daily dosing of IPI-549 based on the observed half-life and inhibition of the PI3K-gamma pathway.

About the IPI-549 Phase 1 Study
The ongoing Phase 1 clinical study of IPI-549 is designed to explore the activity, safety, tolerability, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with Opdivo^® in patients with advanced solid tumors. The study includes monotherapy and combination dose-escalation phases, in addition to expansion cohorts, and is expected to enroll approximately 175 patients.

The IPI-549 monotherapy dose-escalation phase is expected to be completed in the first half of 2017, and the monotherapy expansion phase in patients with advanced solid tumors is anticipated to begin in the second half of the year. Once the dose-escalation phase evaluating IPI-549 plus Opdivo is completed, an expansion phase is planned to evaluate the combination in patients with select solid tumors, including non-small cell lung cancer (NSCLC), melanoma and squamous cell carcinoma of the head and neck (SCCHN). Patients enrolled in expansion cohorts evaluating IPI-549 plus Opdivo represent a difficult-to-treat population, as they must have demonstrated initial resistance or subsequently develop resistance to a PD-1 or PD-L1 therapy immediately prior to enrolling in the study.  

About IPI-549
IPI-549 is an investigational, orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 increases antitumor immunity by targeting tumor-associated myeloid cells and overcomes immune checkpoint blockade resistance in preclinical tumor models. 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.⁷

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, 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, 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 November 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.

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 September 29, 2016.
² Conquer Cancer Foundation, Head and Neck Cancer Statistics, http://www.cancer.net/cancer-types/head-and-neck-cancer/statistics, Last Accessed September 29, 2016.
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 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.
⁶ 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.
⁷ www.clinicaltrials.gov, NCT02637531.

SOURCE Infinity Pharmaceuticals, Inc.

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