TORONTO and SAN DIEGO, April 19, 2016 (GLOBE NEWSWIRE) -- Triphase Accelerator Corporation, a private drug development company dedicated to advancing novel compounds through Phase 2 proof-of-concept, today announced positive results from its ongoing Phase 1 proof-of-concept study evaluating marizomib in combination with bevacizumab in patients with WHO grade IV malignant glioma. These results were presented in a poster session during the American Association for Cancer Research (AACR) annual meeting in New Orleans, LA on April 19.
“These results are essential to our determining an appropriate and safe Phase 2 dose in order to continue the development of marizomib (MRZ) in glioma,” said Daniela Bota, M.D., medical director of Neuro-Oncology and associate professor of neurology at the University of California, Irvine, and lead investigator of the study. “The continuation of the study demonstrates tolerability of the combination therapy, and provides early indicators for potential slowing of disease progression.”
At this stage of the study, which followed 12 patients receiving an increasing dose of MRZ at day 1, day 8, and day 15, each with standard dose (10mg/kg) of BEV on days 1 and 15 of a 28 day cycle, patients demonstrated no concerning adverse events, and each infusion was well tolerated. Five patients demonstrated partial response to treatment, while another five showed stable disease. These results, when analyzed with results from the expansion cohort of the study, are expected to help investigators determine an optimal dose for Phase 2 efficacy studies.
Importantly, investigators also conducted pharmacodynamic analysis to determine the extent of proteasome subunit inhibition. The study indicated that MRZ resulted in complete and persistent inhibition of the chymotrypsin-like proteasome activity (CT-L), and the trypsin and caspase-like activity (T-L and C-L) were also inhibited. Preliminary data was also presented demonstrating a variable baseline proteasome activity in glioma leading the investigators to conclude that in addition to MRZ demonstrating therapeutic activity in glioma, proteasome activity may have the potential as a predictive biomarker.
“The interim results of the study are encouraging, as they demonstrate not only a wide inhibition of proteasome activity in glioma, but the potential to help select a more targeted patient population,” said Mohit Trikha, Ph.D., chief scientific officer and head of Triphase Accelerator R&D. “The safety and tolerability results we have seen thus far, combined with early indication of efficacy, confirm our resolve toward developing marizomib in glioma.”
About Marizomib
Marizomib is a novel, irreversible, potent and brain-penetrant proteasome inhibitor, which inhibits all three proteasome subunits, thus providing superior potency, specificity, and duration of proteasome inhibition, and potentially improved clinical activity.
Triphase Accelerator is developing marizomib in both intravenous (IV) and oral formulations as a potential best-in-class proteasome inhibitor for hematologic malignancies and solid tumors. The IV formulation has been evaluated in more than 300 patients in multiple clinical studies in patients with solid and hematologic malignancies, either as a single agent or in combination with dexamethasone, a histone deacetylase inhibitor, or an immunomodulatory drug.
The company is currently evaluating marizomib in a proof-of-concept clinical study in combination with bevacizumab (Avastin®) in patients with Grade IV malignant glioma (glioblastoma), and has received Orphan Drug designation for marizomib in glioblastoma in the United States from the FDA. In addition, Triphase Accelerator is currently developing marizomib in combination with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma, and has received Orphan Drug designation for marizomib in multiple myeloma in the United States and the European Union. Triphase Accelerator is also evaluating an oral formulation in preclinical studies.
About Triphase Accelerator
Triphase Accelerator is a private drug development company with a primary focus on oncology and with operations in Toronto and San Diego. Triphase Accelerator is dedicated to advancing novel compounds through Phase 2 proof-of-concept clinical studies using a unique, science-based, high-quality model that is faster and more cost-effective than traditional pharmaceutical and biotech industry drug development approaches. Triphase Accelerator was spun out of the Ontario Institute for Cancer Research (OICR), with support from the Fight Against Cancer Innovation Trust (FACIT), MaRS Innovation and MaRS. It has a strategic relationship with Celgene for marizomib. For more information, visit www.triphaseco.com or LinkedIn.