Tetraphase Pharmaceuticals Presents Preclinical Data on TP-2846, a Novel Drug Candidate for Acute Myeloid Leukemia
- Category: Small Molecules
- Published on Wednesday, 03 April 2019 14:18
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WATERTOWN, MA, USA I April 03, 2019 I Tetraphase Pharmaceuticals, Inc. (NASDAQ:TTPH), a biopharmaceutical company focused on developing and commercializing novel tetracyclines to treat serious and life-threatening conditions, today announced data from its preclinical program for TP-2846, the Company’s new pipeline candidate for acute myeloid leukemia (AML) discovered using Tetraphase’s proprietary total synthesis platform. The data were presented at the 2019 American Association for Cancer Research (AACR) Annual Meeting, held March 29-April 3 at the Georgia World Congress Center in Atlanta. The posters showed results from preclinical in vitro and in vivo studies demonstrating the activity, potency and unique mechanism of action (MOA) of TP-2846.
“Preclinical testing has characterized TP-2846 as a novel, potent, synthetic tetracycline with activity across multiple in vitro and in vivo cancer models,” said Guy Macdonald, President and Chief Executive Officer of Tetraphase. “We are very encouraged by these early data, which suggest that TP-2846 holds the potential to benefit AML patients regardless of their mutation status. Further, these data show that because of its unique MOA, TP-2846 may have antileukemic activity in patients whose cancer has progressed while on different treatment regimens.”
“TP-2846 has a new MOA that has never before been fully explored clinically as a viable approach to treating AML,” said Jacques Dumas, Chief Scientific Officer of Tetraphase. “Our preclinical data demonstrated high potency across multiple AML cell lines, along with in vivo tumor responses at well-tolerated doses. These early data are very encouraging and support the continued preclinical evaluation of TP-2846 as a potential new antileukemia agent.”
TP-2846 binds to the mitochondrial ribosome, inhibiting protein translation and inducing apoptosis. Mechanistic assays demonstrated changes in protein and gene expression – all consistent with disruption of mitochondrial translation.
TP-2846 showed antiproliferative activity against cultured AML cell lines in vitro, as well as bone marrow samples derived from AML patients in ex vivo assays. The data available to date also suggest that TP-2846’s activity is independent of p53 status. Because of its novel MOA, TP-2846 maintained antiproliferative activity in cell lines that are resistant to anthracyclines, cytarabine and venetoclax, which are currently approved treatments for AML.
In vivo efficacy studies were also performed, comparing TP-2846 to cytarabine and tigecycline, a tetracycline antibacterial, in two AML mouse xenograft models. In these studies, TP-2846 demonstrated potent, dose-dependent in vivo efficacy, including greater than 50 percent tumor shrinkage in 19 out of 20 animals treated with TP-2846, while none in the comparator treatment groups achieved a tumor response in the same studies. TP-2846 was well tolerated in both models.
About Tetraphase Pharmaceuticals, Inc.
Tetraphase Pharmaceuticals, Inc., is a biopharmaceutical company using its proprietary chemistry technology to create novel tetracyclines for serious and life-threatening conditions, including bacterial infections caused by many of the multidrug-resistant bacteria highlighted as urgent public health threats by the World Health Organization and the Centers for Disease Control and Prevention. The Company has created more than 3,000 novel tetracycline compounds using its proprietary technology platform. Tetraphase's lead product, XERAVATM (eravacycline), is approved for the treatment of complicated intra-abdominal infections by the U.S. Food and Drug Administration and the European Medicines Agency. The Company’s pipeline includes TP-271 and TP-6076, which are in Phase 1 clinical trials, and TP-2846, which is in preclinical testing for acute myeloid leukemia. Please visit www.tphase.com for more company information.
SOURCE: Tetraphase Pharmaceuticals