The biOasis Brain Cancer Program

Rationale

In the past decade, significant advancements in cancer therapies occured. As a result, life expectancy of cancer patients has been greatly extended. However, because most cancer therapeutics are unable to cross the blood-brain barrier, brain cancer remains largely untreatable. Depending on the type of cancer, about 30% to 50% of patients develop brain cancer. Because of increased life expectancy in cancer patients, these rates of brain cancer incidence are increasing because patients are living long enough for cancer to metastasize to the brain.

Therapeutics that are effective in the treatment of cancer throughout the body may also be effective in the treatment of brain cancer if a means of transporting the therapeutics across the BBB could be discovered.

The biOasis Transcend Platform is a group of proprietary technologies designed for the transport of a wide array of therapeutic agents across the blood-brain barrier for the treatment of many types of CNS disorders, including brain cancer.

Two significant animal studies showed that Transcend (MTf) is able to transport all three of the tested cancer drugs across the BBB. In these studies, two of the three Transcend therapeutics (chemical conjugates) were also tested for efficacy, both with significant success.

Based on these results, biOasis has chosen brain cancer as a primary therapeutic program to be advanced in-house. The in-house brain cancer program was selected by biOasis using several criteria, including potential commercial value, unmet medical needs and the anticipated speed and cost of development of advancing the therapeutics to clinical trials.

Background Studies

Study: Texas Tech University Health Sciences Centre 

Disease: Metastatic HER2+ Breast Cancer

Treatment: Trastuzumab, a humanized monoclonal antibody used in the clinic to treat HER2+ breast cancer.

Medical Problem: Trastuzumab is highly effective in treating HER2+ breast cancer throughout most of the body. However, up to 40% of patients will develop brain metastases that are largely untreatable because Herceptin® cannot cross the BBB in efficacious quantities. The prognosis is often fatal.

Transcend Therapeutic: Transcend (MTf) + Trastuzumab chemical conjugate.

Activities, Partners and Contributors

  • Texas Tech University Health Sciences Center (TTUHSC) pharmacokinetics studies
  • National Research Council: imaging Study
  • BC Cancer Research Centre: confocal imaging at the James Hogg Research Centre
  • ADCC (antibody dependent cell-mediated cytotoxicity) assay
  • Human tumor xenograft model & histopathological evaluation study
  • Image analysis and quantitative autoradiography in this animal study

Results

  • In Vivo Efficacy in Breast Cancer Model
  • Reduced the number of HER2+ breast cancer tumors in the brain by 68% compared to Trastuzumab alone
  • Reduced total tumor volume by 86%
  • Transcend + Trastuzumab not only crosses the blood-brain barrier but also penetrates the blood-TUMOR barrier up to 10 times better than Trastuzumab alone

Opportunity: When Transcend was conjugated with Trastuzumab, it was shown, in vivo, to delivery Trastuzumab across the BBB and into the brain tissues at efficacious levels, both killing cancer cells and reducing the volume of the remaining tumours.

 

Study: MTf Proof of Concept

Scientific Paper: “A Unique Carrier for the Delivery of Therapeutic Compounds Beyond the Blood-Brain Barrier,” published in PLoS ONE, June 25th 2008.

Study Led by: Professor Wilfred A. Jefferies at the Biomedical Research Centre at The University of British Columbia in Michael Smith Laboratories

Background: Ten years of research by Professor Jefferies provides the initial proof of concept for melanotransferrin (MTf or Transcend) as a carrier capable of delivering therapeutics from the blood to the brain in levels that are efficacious for the treatment of neurological disorders, including classes of resident and metastatic brain tumors.

Disease: Variety of cancers

Treatment: Adriamycin 1 (doxorubicin) is a anthracycline antibiotic and is used to treat cancers of the breast, bladder, lung, ovaries, stomach, thyroid, multiple myeloma as well as some leukemias and Hodgkin’s lymphoma.

Paclitaxel is a mitotic inhibitor and is used to treat solid tumour cancers of the breast, ovaries, lungs, bladder, prostate, etc.

These chemotherapeutic drugs have been used historically to treat a wide range of cancers.

Medical Problem: These chemotherapeutic drugs do not cross the BBB to treat cancers that metastasize in the brain. Adriamycin 1 (doxorubicin) most serious adverse effect is life threatening heart damage.

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Results:

  • Transcend (MTf) can shuttle therapeutic agents such as anti-cancer drugs, Adriamycin 1 (doxorubicin) & Paclitaxel, through the BBB to tumours found within the brain.
  • Significant increase in brain uptake with the Transcend + Doxorubicin conjugate VS Doxorubicin alone.
  • Significant increase in brain uptake with the Transcend + Paclitaxel conjugate VS Paclitaxel alone.
  • Transcend + Doxorubicin VS Doxorubicin on its own showed a significant DECREASE in uptake in the heart. (Paclitaxel not tested for efficacy)

Opportunity: Transcend (MTf) + Adriamycin 1 could be used to treat brain cancers and decrease heart-uptake side effect, offering increased global usage of Adriamycin 1 (doxorubicin).

Plan of Action

Based on these two studies, biOasis has chosen brain cancer as a primary program for the advancement of the company’s Transcend Platform. Specifically, biOasis has chosen to place the Transcend (MTfp) and Trastuzumab proprietary fusion protein within the company’s developmental pipeline with the objective of advancing the therapeutic to clinical trials.

Herceptin’s commercial market was $6.6 billion in 2013. Herceptin® is a registered trademark of Genentech/Roche and faces patent expiration by 2016. The MTfp-Trastuzumab fusion protein patent would extend for another 20 years.

biOasis’ plans for the Transcend (MTfp)-Trastuzumab fusion protein, as well as the biOasis name for the protein, are to be announced at a later date.