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Boston Biomedical Presents New Preclinical Data At AACR 2017 Highlighting The Potential Role Of Cancer Stemness Inhibition

Published: Apr 05, 2017

CAMBRIDGE, Mass., April 4, 2017 /PRNewswire/ -- Boston Biomedical, an industry leader in the development of next-generation cancer therapeutics designed to inhibit cancer stemness pathways, presented preclinical data from its research and development portfolio at the 2017 American Association for Cancer Research (AACR) Annual Meeting held from April 1-5, in Washington, D.C.

Data from a preclinical study evaluating napabucasin in combination with an anti-PD-1 antibody, an immune checkpoint inhibitor, found that the combination was able to sensitize mice with colorectal cancer to checkpoint inhibitors. An additional preclinical study revealed napabucasin may overcome resistance to paclitaxel in stemness-high cells, further supporting that the compound can be effectively combined with this standard of care therapy. Napabucasin is an orally-administered investigational agent designed to inhibit cancer stemness pathways by targeting STAT3.

In addition, preclinical data of amcasertib was also presented. In preclinical models, amcasertib was shown to target Nanog via the STK33 pathway, and -catenin via the STK17A pathway. These data will provide important insights for advancing future research and development programs for these investigational compounds. 

Preclinical data of a new program, BBI-801, was shown for the first time. BBI-801 is a gene-silencing investigational agent designed to inhibit cancer stemness pathways and promote anti-cancer immunity by targeting -catenin and PD-L1 to enhance anti-cancer activity across multiple tumor types. BBI-801 was designed through Boston Biomedical's proprietary asymmetric interfering RNA (aiRNA) technology and is being investigated in preclinical studies.

"The preclinical data presented at this year's AACR annual meeting exemplifies our commitment to apply cutting-edge science to pioneer potential therapies for patients battling cancer," said Chiang J. Li, M.D. FACP, President, CEO, and Chief Medical Officer of Boston Biomedical, and the Head of Global Oncology for Sumitomo Dainippon Pharma Group. "We believe focusing on inhibiting cancer stemness pathways may lead to advancements in cancer therapies aiming to reduce recurrence, drug-resistance and metastases. We are looking forward to continuing to investigate our first-in-class compounds/programs in future studies."

Highlights of the Boston Biomedical poster presentations:

Abstract LB-023, Poster #9: STK17A, a novel serine threonine kinase, promotes cancer stemness phenotypes by phosphorylating -catenin

  • Taiki Kida, Harry A. Rogoff, Chiang J. Li.; Boston Biomedical Inc., Cambridge, MA
  • Results of this preclinical study suggest inhibition of Serine Threonine Kinase 17A (STK17A), a novel member of the death-associated protein family of serine/threonine kinases, promotes cancer stemness phenotypes via -catenin and up-regulation of its target genes. Amcasertib was found to potently inhibit STK17A, leading to inhibition of -catenin phosphorylation at ser675.

Abstract LB-069, Poster #8: In vivo delivery of asymmetric gene-silencing RNAs targeting CTNNB1 and PD-L1 show a broad spectrum of potent antitumor activities in preclinical cancer models

  • Youzhi Li, Yuan Gao, Yuxin Wang, Jie Su, Eric Hsu, Ewa Wybieralska, Janet Huang, Keyur Gada, Jun Oishi, Xiaoshu Dai, Erina Koga, Wei Li, Xiangao Sun, Emily Brooks, Chiang J. Li.; Boston Biomedical Inc., Cambridge, MA
  • This preclinical study investigated the in vivo delivery and anti-tumor activity of BBI-801 encapsulating asymmetric interfering RNA (aiRNAs) targeting CTNNB1 and PD-L1. The study demonstrated BBI-801 achieved significant tumor growth inhibition not only in -catenin over-expressed colorectal tumor models, SW480 and APCmin, but also in the rest of -catenin normal-expressed tumor models. BBI-801 was well-tolerated.

Abstract LB-140, Poster #12: Inhibition of cancer stemness sensitizes colorectal cancer to immune checkpoint inhibitors

  • Yuan Gao, Youzhi Li, Eric Hsu, Yuxin Wang, Janet Huang, Emily Brooks, Chiang J. Li.; Boston Biomedical Inc., Cambridge, MA
  • This preclinical study demonstrated napabucasin in combination with an anti-PD-1 antibody sensitized mice to checkpoint inhibitors in colorectal cancer xenograft model. The combination therapy led to tumor complete response (CR) in all treated CT26 tumors with 40% of the mice remaining tumor-free for 30 days following treatment termination. Additionally, this combination had a synergistic effect on the influx of tumor infiltrating CD8+T cells, which likely contributed to tumor regression.

Abstract LB-142, Poster #14: Identification of STK33 as a cancer stemness kinase and regulator of Nanog function

  • Susan L. Tran, Yudai Furuta, Chen Zhu, Ao Yang, Xiangao Sun, Harry A. Rogoff, Chiang J. Li.; Boston Biomedical Inc., Cambridge, MA
  • Results of this preclinical study demonstrated STK33, a pathway that directly interacts with Nanog and appears to promote its stabilization through phosphorylation, is a critical element in the signaling network that governs the stemness of cancer cells. The study suggests amcasertib may suppress Nanog by inhibiting STK33 and therefore, may be a potential therapeutic target for cancer.

Abstract LB-143, Poster #15: Identification of STAT3-NRF2-hypoxia as a novel reinforcing mechanism for promoting cancer stemness

  • Luz Elisa Tavera, Karen Simon, Juying Li, Katherine Geromini, Zhuo Zhang, Sarah Keates, Harry A. Rogoff, Chiang J. Li.; Boston Biomedical, Inc., Cambridge, MA
  • This preclinical study revealed STAT3-NRF2-Hypoxia as a novel reinforcing regulatory mechanism for promoting cancer stemness and chemotherapy resistance. These findings suggest hypoxia is associated with STAT3, which promotes stemness and chemotherapy resistance, and napabucasin inhibits STAT3. Data demonstrated that in response to STAT3 pathway activators, NRF2 is up-regulated at both mRNA and protein levels under hypoxia and this up-regulation is STAT3 dependent.

Abstract 4777, Poster #15: Cancer stemness and resistance: Napabucasin (BBI-608) sensitizes stemness-high cancer cells to paclitaxel by inhibiting the STAT3-MUC1 pathway

  • Harry A. Rogoff, Juying Li, Chiang J. Li.; Boston Biomedical, Inc., Cambridge, MA
  • This preclinical study showed that the MUC1 pathway may cause paclitaxel resistance based on a stemness-high culture system generated through the reporter activity of a SOX2-regulatory region constructed in MKN28 gastric cancer cells. The results demonstrated that napabucasin may overcome resistance to paclitaxel by decreasing MUC1.

About Cancer Stem Cells
Cancer stem cells (CSCs) possess the property of stemness the ability to self-renew and differentiate into heterogeneous cancer cells. This allows the CSCs to act like seeds, causing a patient's cancer to relapse or spread within the body.i,ii Evidence suggests that these cells possess resistance to chemotherapy, radiation and targeted therapy as well as immunotherapies, so while such treatments can successfully shrink tumors, a population of CSCs may still survive.ii,iii

Boston Biomedical is leading the biopharmaceutical industry in the development of novel compounds designed to target cancer stemness pathways, with the goal of addressing ongoing challenges in cancer treatment.

About Boston Biomedical
Boston Biomedical was founded in November 2006 and is wholly owned by Sumitomo Dainippon Pharma Co., Ltd. Boston Biomedical's mission is to develop the next generation of cancer therapeutics by creating drugs designed to target cancer stemness pathways. 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 www.BostonBiomedical.com.

Disclaimer Regarding Forward-Looking Statements
The forward-looking statements in this press release are based on management's assumptions and beliefs in light of information presently available, and involve both known and unknown risks and uncertainties. Any forward looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice.

For general inquiries:
Boston Biomedical 
617-674-6800

For media inquiries:  
Sara Baker
CHAMBERLAIN PR
212- 849-9474
sara.baker@inventivhealth.com 

RELATED LINKS
http://www.bostonbiomedical.com

i Gupta PB, Chaffer CL, Weinberg RA. Cancer stem cells: mirage or reality? Nat Med. 2009;15(9):1010-1012. 
ii Ajani JA, Song S, Hochster HS, Steinberg IB. Cancer stem cells: the promise and the potential. Semin Oncol. 2015;42(suppl 1):S3-S17. 
iii Jordan CT, Guzman ML, Noble M. Cancer stem cells. N Engl J Med. 2006;355(12):1253-1261.

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SOURCE Boston Biomedical, Inc.

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