Study finds OBI-3424 exerts profound in vivo efficacy and safety against patient-derived xenograft (PDX) models of T-cell acute lymphoblastic leukemia (T-ALL) expressing AKR1C3.
TAIPEI, Taiwan, Oct. 30, 2017 /PRNewswire/ -- OBI Pharma, Inc., a Taiwan biopharma company (TPEx: 4174), announced the results of a patient-derived xenograft (PDX) model study of OBI-3424 in T-cell acute lymphoblastic leukemia (T-ALL), presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Philadelphia, PA, USA.
The poster session, titled "The AKR1C3-Activated Prodrug OBI-3424 Exerts Profound In Vivo Efficacy Against Preclinical Models of T-Cell Acute Lymphoblastic Leukemia (T-ALL); a Pediatric Preclinical Testing Consortium Study", was presented by Professor Richard B. Lock, PhD, Head of the Children's Cancer Institute's Leukemia Biology Program at the Lowy Cancer Research Centre in Sydney, Australia.
The study was supported by National Cancer Institute (NCI) grants CA199222 & CA199000, and conducted by the NCI Pediatric Preclinical Testing Consortium.
Overall study results demonstrated that OBI-3424 was well-tolerated, with only a 2.8% toxicity rate in the drug-treated groups. OBI-3424 induced significant differences in EFS distribution compared to control in 9 of 9 (100%) of the evaluable patient-derived xenografts (PDXs). T-C values ranged from 17.1 to 65.2 days (T/C 2.3-14.0), and objective responses were observed in 8 of 9 PDXs (2 Complete responses, CRs; 6 Maintained CRs, MCRs). A significant reduction (P<0.0001) in bone marrow infiltration at Day 28 was observed in 4 of 6 evaluable T-ALL PDXs.
The importance of AKR1C3 in the in vivo responses of ALL PDXs to OBI-3424 was verified using a B-cell precursor ALL PDX (ALL-11) that had been lentivirally transduced to stably overexpress AKR1C3 (ALL-11/1C3) compared with empty vector controls (ALL-11/EV). Mice engrafted with ALL-11/1C3 exhibited an MCR (T-C >37.3 days, T/C >3) compared with a CR for ALL-11/EV (T-C 21.1 days, T/C 2.5). Infiltration of ALL-11/1C3 cells into the murine bone marrow was significantly reduced at Day 28 in OBI-3424-treated compared to vehicle-treated mice (P<0.0001), but not to mice engrafted with ALL-11/EV.
Professor Richard B. Lock, Head of the Leukemia Biology Program at the Children's Cancer Institute in Australia, stated, "OBI-3424 is one of the most effective drugs we have ever tested against T-ALL in over 12 years of evaluating drugs at the Children's Cancer Institute in Australia using preclinical models of aggressive childhood ALL. We are incredibly excited about the potential for OBI-3424 to improve the treatment and quality of life for patients with this aggressive type of cancer and look forward to having this potential evaluated in clinical trials."
"We are eager to advance the further development of OBI-3424 to fulfill the unmet needs for cancer patients who express the AKR1C3 enzyme. In addition, the IND filing for OBI-3424 with the U.S. Food and Drug Administration (FDA) is planned for early 2018," said Tony Yu, PhD, PharmD, Chief Scientific Officer, OBI Pharma, Inc.
OBI-3424 is a first-in-class novel small-molecule prodrug that selectively targets cancers overexpressing the enzyme aldo-keto reductase 1c3 (AKR1C3), and selectively releases a potent DNA alkylating agent in the presence of the AKR1C3 enzyme. This selective mode of activation distinguishes OBI-3424 from traditional alkylating agents, such as cyclophosphamide and ifosfamide, which are non-selective.
AKR1C3 overexpression has been documented in a number of treatment-resistant and difficult-to-treat cancers including: hepatocellular carcinomas (HCC), castrate-resistant prostate cancer (CRPC), and T-cell acute lymphoblastic leukemia (T-ALL).
Furthermore, individualized patient selection by staining for AKR1C3 overexpression by immunohistochemistry can be performed to identify patients with other tumor types most likely to respond to treatment with OBI-3424, and thus offering the possibility for a streamlined clinical development strategy.
OBI Pharma plans an Investigational New Drug (IND) application filing with the U.S. Food and Drug Administration (FDA) during early 2018 and Phase 1 clinical testing during 1H2018.
OBI Pharma holds worldwide rights for OBI-3424 with the exception of the following countries, whose rights are held by Ascenta Pharma: China, Hong Kong, Macao, Taiwan, Japan, South Korea, Singapore, Malaysia, Thailand, Turkey, and India.
About OBI Pharma
OBI Pharma, Inc. is a Taiwan biopharmaceutical company that was established in 2002. Its mission is to develop and license novel therapeutic agents for unmet medical needs against cancer targets such as Globo series, AKR1C3, and other promising targets. The company's flagship product is Adagloxad Simolenin (formerly OBI-822), a first-in-class active immunotherapy for metastatic breast cancer. OBI is also developing next generation immunotherapies for difficult to treat cancers, including lung, colorectal, pancreatic, gastric, and ovarian cancer. Additional information can be found at www.obipharma.com.
Statements included in this press release that are not a description of historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to, statements about future clinical trials, results and the timing of such trials and results. Such risk factors are identified and discussed from time to time in OBI Pharma's reports and presentations, including OBI Pharma's filings with the Taiwan Securities and Futures Bureau.
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