Infinity Reports Phase 1 Data for IPI-145 at ACR/ARHP Supporting Development in Inflammatory Conditions
Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) today announced new data from its completed Phase 1 study of IPI-145, the company's potent, oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma. The data showed that IPI-145 was well tolerated and demonstrated favorable pharmacokinetics following administration of single and multiple doses in healthy adult subjects. Infinity also presented data demonstrating the activity of IPI-145 in preclinical models of rheumatoid arthritis (RA). These findings were presented at the American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) 2012 Annual Meeting held in Washington, DC.
“These data show that IPI-145 is well tolerated in healthy subjects and inhibits immune cell activation even at low doses,” stated Vito J. Palombella, chief scientific officer at Infinity. “The profile of IPI-145 observed in this Phase 1 trial, combined with our preclinical studies in inflammation, support Phase 2 clinical development in patients with asthma and RA as well as other potential inflammatory indications.”
The PI3Ks are a family of enzymes involved in multiple cellular functions, such as cell proliferation and survival, metabolism, cell differentiation and cellular trafficking.1 PI3K-delta and -gamma, two isoforms of PI3K, are necessary for adaptive and innate immunity, and the role of these enzymes in various immune cells supports the development of IPI-145 for the treatment of inflammatory disorders as well as hematologic malignancies.2 Infinity believes that IPI-145 is the only PI3K-delta and -gamma inhibitor currently in clinical development.
Data Presented at ACR/ARHP
The Phase 1, double-blind, randomized, placebo-controlled trial of IPI-145 in healthy adult subjects evaluated single doses of IPI-145 ranging from 1 mg to 30 mg. Multiple doses of IPI-145 ranging from 1 mg twice daily (BID) to 5 mg BID for 14 days and 10 mg once daily (QD) for 14 days were also evaluated. In addition, the effect of food on the pharmacokinetics of IPI-145 was studied. One hundred six patients were enrolled in the Phase 1 trial.
New data presented at ACR/ARHP showed that IPI-145 was well tolerated at all doses studied, with a favorable pharmacokinetic and pharmacodynamic profile. Among subjects who received multiple doses of IPI-145 BID (N=36) or placebo (N=12) for 14 days, the most common adverse events were related to blood draws and protocol-associated procedures. The most common non-procedural adverse events occurring in ≥2 subjects were headache (8% vs. 25% placebo), myalgia (6% vs. 8% placebo) and nasopharyngitis (6% vs. 0% placebo). There were no dose-related trends in adverse events. Additionally, there were no significant findings in safety lab studies including standard hematological parameters (e.g., hemoglobin, white blood cells, platelets), as well as chemistry parameters (e.g., transaminases, bilirubin, alkaline phosphatase, glucose, creatinine) or electrocardiograms.
Pharmacokinetic data showed that IPI-145 was rapidly absorbed, with a dose-proportional increase in exposure. The half-life of IPI-145 following 14 days of dosing ranged from approximately seven to 12 hours, supporting BID dosing in ongoing trials. The pharmacokinetics were not significantly altered by the consumption of a high-fat, high-calorie meal, suggesting that IPI-145 can be administered with or without food. In addition, an ex vivo pharmacodynamic assay demonstrated rapid, dose dependent and durable inhibition of basophil activation at all dose levels.
Infinity also presented preclinical data with IPI-145 in two models of RA. In both models, IPI-145 showed dose-dependent activity, inhibiting ankle swelling and protecting bone and cartilage in the joints of diseased animals.
The poster, “The Potent Phosphoinositide-3-Kinase(δ,γ) Inhibitor IPI-145 Is Active in Preclinical Models of Arthritis and Well-Tolerated in Healthy Adult Subjects,” may be found in the Publications Archive on Infinity's website http://www.infi.com/product-candidates-publications.asp.
About Infinity's PI3K Program
IPI-145 is a potent, oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma. IPI-145 is the only PI3K-delta and -gamma inhibitor in clinical development. Targeting PI3K-delta and -gamma may provide multiple opportunities to develop differentiated therapies against inflammatory diseases as well as hematologic malignancies. A Phase 2a, randomized, double-blind, placebo-controlled, multi-dose, cross-over study of IPI-145 in patients with asthma is under way, and Infinity is planning a Phase 2 trial of IPI-145 in RA. Infinity is also conducting a Phase 1 open-label, dose-escalation study of IPI-145 in patients with advanced hematologic malignancies. On December 10, 2012, researchers will present initial data from the Phase 1 trial of IPI-145 in hematologic malignancies at the 54th American Society of Hematology (ASH) Annual Meeting and Exhibition being held in Atlanta, Georgia. Infinity also has an active discovery effort under way to identify next-generation, isoform-specific PI3K inhibitors.
About Infinity Pharmaceuticals, Inc.
Infinity is an innovative drug discovery and development company seeking to discover, develop and deliver to patients best-in-class medicines for diseases with significant unmet need. 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.
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 therapeutic potential of and potential clinical development plans for IPI-145. 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 timeframes 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 could also be affected by risks and uncertainties relating to: 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 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 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 for the year ended December 31, 2011 and subsequent filings filed by Infinity with the Securities and Exchange Commission. 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 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.
2 Rommel C (2011) Taking PI3Kδ and PI3Kγ one step ahead: dual active PI3Kδ/γ inhibitors for the treatment of immune-mediated inflammatory diseases. In Rommel C, Vanhaesebroeck B, and Vogt PK, (Eds.) Phosphoinositide 3-kinase in Health and Disease (pp. 279-299). Springer Berlin Heidelberg.