Boston Biomedical Announces Clinical Data Presentation Of Its Cancer Stem Cell Inhibitor Programs

CAMBRIDGE, Mass., June 16, 2014 /PRNewswire/ -- Boston Biomedical, a company focused on the research and development of novel cancer therapeutics targeting cancer stem cells (CSC), today provided a summary of the clinical data presented at the 2014 American Society of Clinical Oncology (ASCO) 50^th annual meeting, held from May 30 to June 3, 2014, in Chicago, IL. Clinical data were presented for BBI608 and BBI503, novel agents targeting cancer stem cells that have been developed by the company. BBI608 is a first-in-class cancer cell stemness inhibitor that blocks CSC self-renewal and induces cell death in CSC through blocking beta-catenin and Stat3 pathways. BBI503 is a first-in-class cancer stemness kinase inhibitor also targeting CSC self-renewal and survival. A Phase Ib study of BBI608 and a Phase I study of BBI503 were part of the Poster Highlights Session. The BBI503 study has also been selected to be one of the three presentations in the Developmental Therapeutics session at Best of ASCO 2014 in Japan, which will be held in Kobe, Japan, on July 5 and 6, 2014.

"Data showed encouraging signs of anticancer activity of BBI608 and BBI503 in multiple tumor types," said Dr. Chiang J. Li, M.D. FACP, the president, CEO and Chief Medical Officer of Boston Biomedical, and the Head of Global Oncology for Dainippon Sumitomo Pharma Group. "Based on the results of these and additional studies, we have initiated a global pivotal study of BBI608 plus weekly paclitaxel in patients with gastric/GEJ cancer. In addition, a Phase I study of BBI503 showed potent inhibition of cancer stemness biomarker in patient tumor tissues as well as a good safety profile without typical kinase inhibitor toxicities. Prolonged disease stabilization was observed in 45% of all evaluable patients. Phase II studies of BBI503 are ongoing or are being planned."

Clinical Data Summaries

1. A Phase I Extension Study of BBI608, a First-In-Class Cancer Stem Cell (CSC) Inhibitor, in Patients with Advanced Solid Tumors. (Abstract #2546)

Objectives of the study:
This Phase I/II extension study (BBI608-101) of BBI608 in patients with advanced solid tumors was conducted to determine the pharmacokinetics, safety, and tolerability of an optimized formulation of BBI608 (DP2A) designed for pivotal trials.

Highlights of the presentation:
DP2A was evaluated in 24 patients. In a crossover pharmacokinetics study, no significant difference in plasma exposure between DP1 (the original formulation of BBI608) and DP2A was observed. The dosing interval of twice daily administration (4 h apart vs. 12 h apart) of DP2A was further evaluated in this study. Despite equivalent plasma exposure to DP1, DP2A administered with doses 4 hours apart was associated with higher frequency of gastrointestinal adverse events, including diarrhea, abdominal cramps, nausea/vomiting, and anorexia, than observed in the dose-escalation study. When BBI608 DP2A was administered with doses separated by 12 hours, a reduction in gastrointestinal adverse events was observed, and the regimen was better tolerated compared with administration 4 hours apart. The recommended dosing regimen for BBI608 in pivotal trials was determined to be about 500 mg twice daily, with doses separated by 12 hours.

Among 15 patients receiving DP2A 12 hours apart, prolonged stable disease was observed in 2 of 7 non-colorectal cancer patients (ovarian cancer-16 wk and anal squamous cancer-32 wk). Among 8 colorectal cancer patients receiving DP2A 12 hours apart, disease control was observed in 67% evaluable for response (4/6), with progression free survival and overall survival at 17 weeks and 40 weeks, respectively. This data was consistent with that reported for CRC patients in the separate dose-escalation patient population reported at the 2013 ASCO Annual Meeting (Abstract #2542).

2. A Phase Ib Study of the Cancer Stem Cell Inhibitor BBI608 Administered with Paclitaxel in Patients with Advanced Malignancies. (Abstract #2530)

Objectives of the study:
This Phase Ib study in patients with advanced cancer was conducted to determine the safety, tolerability, recommended Phase II dose, and preliminary anti-cancer activity of BBI608 plus paclitaxel (BBI608-201 study).

Highlights of the presentation:
BBI608 was administered to 3-patient cohorts in escalating doses (200 mg twice daily, 400 mg twice daily, and 500 mg twice daily) in combination with paclitaxel (80 mg/m² by intravenous injection, once weekly, for 3 of every 4 weeks). A total of 24 patients with advanced solid tumors including gastric/GEJ adenocarcinoma, ovarian cancer, melanoma, bladder cancer and non-small cell lung cancer (NSCLC) were enrolled.

The full dose of BBI608 could be safely combined with the full dose of weekly paclitaxel, and the combination regimen was well tolerated. No significant pharmacokinetic interactions were observed.

Preliminary anti-tumor activity in the heavily pre-treated population included objective response, prolonged stable disease, and/or disease control in 10 of 15 (67%) of evaluable patients. Of note, of the 5 patients with chemo-refractory gastric/GEJ adenocarcinoma, two patients had received prior taxane, and four of the five patients had received 2 or more prior lines (2, 3, 3, and 4 prior lines, respectively). All 5 of these patients experienced objective clinical benefit from the study regimen; 3 with tumor regression (48%, 45%, 25%) and the remaining 2 with prolonged stable disease for more than 6 months. Tumor regression, prolonged stable disease, or disease control was also observed in patients with platinum-resistant ovarian cancer (1 of 2), melanoma (2 of 3), bladder cancer (1 of 3) and NSCLC (1 of 1).

3. A Phase I Dose Escalation Study of BBI503, a First-In-Class Cancer Stemness Kinase Inhibitor in Adult Patients with Advanced Solid Tumors. (Abstract #2527)

Objectives of the study:
A first-in-human Phase I dose escalation study in patients with advanced solid tumors was conducted to determine the safety, tolerability, pharmacokinetics, recommended Phase II dose, and preliminary anti-tumor activity of BBI503 (BBI503-101 study).

Highlights of the presentation:
BBI503 was administered in escalating doses from 10 mg to 450 mg once daily to 26 patients with advanced, heavily-pretreated solid tumors including colorectal cancer, head and neck cancer, renal cell carcinoma and hepatocellular carcinoma.

BBI503 was well tolerated, with mild gastrointestinal adverse events observed. No typical kinase inhibitor toxicities were observed. BBI503 showed a dose-dependent increase in plasma concentration up to 300 mg once daily.

Potent inhibition of stemness marker (Nanog) was observed in patient tumor tissue. Of 20 evaluable patients, 9 (45%) had prolonged stable disease for 16 weeks or longer.

About Boston Biomedical
Boston Biomedical, Inc. (Founder, President, CEO and CMO: Chiang J. Li, M.D. FACP) was founded in November, 2006 and is wholly owned by Dainippon Sumitomo Pharma Co., Ltd. Boston Biomedical is focused on the research and development of novel cancer therapeutics, and has developed a world-leading product pipeline targeting cancer stem cells. Boston Biomedical's innovation in drug discovery has received a number of recognitions and awards in the United States, including the Frost & Sullivan 2010 North American Drug Discovery Technology Innovation of the Year Award, the National Cancer Institute (NCI) cancer stem cell initiative grant award in 2010, and the 2011 Biotech Pioneer Award at the Alexandria Oncology Summit. The company also received the "Company To Watch" award in the 10th Annual Team Massachusetts Economic Impact Awards in 2013. Boston Biomedical is headquartered in Cambridge, Massachusetts, USA. Additional information about the company and its product pipeline can be found at http://www.bostonbiomedical.com.

Disclaimer Regarding Forward-Looking Statements

The forward-looking statements in this document are based on management's assumptions and beliefs in light of information presently available, and involve both known and unknown risks and uncertainties. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice.

SOURCE Boston Biomedical