Metastasis of cancer cells from the primary tumor represents one of the most serious concerns for any cancer patient and can affect clinical decisions regarding treatment for the disease. The ability to predict the likelihood of metastasis is imperative, though existing solutions are limited in the scope of patients and types of cancer that can be screened. Changing this paradigm is MetaStat, a company developing a new way to predict the risk for tumor metastasis that could be used for any type of tumor cell and pave the way for clinicians to provide personalized cancer treatments based on the aggressiveness of the disease in each patient. We had a chance to speak with Dr. Oscar Bronsther, CEO of MetaStat, to learn more about the company’s breakthrough approach.
Michael Batista, Medgadget: What is your background and how did you become involved with MetaStat?
Dr. Oscar Bronsther: I have been an active surgeon for the majority of my career, conducting liver transplants at some of the leading universities in the US for the last 30 years. During that time I was involved in conducting biotechnology due diligence for angel investors as well as investing in companies myself. Over four years ago I did the due diligence on MetaStat and felt the science behind the company represented the most important breakthrough in understanding cancer biology since 1980. I originally invested in the company alongside other angel investors but for the first time in my career, I also asked for an opportunity to get more involved. When the company went public in 2012, I was originally asked to be the Chairman of the Board while I continued my clinical work. However, in December 2012, deciding a firmer hand was needed in dealing with the universities from whom the IP had been licensed, the Board approached me to become the CEO. In accepting the position, I terminated my surgical practice, which for me was an easy decision since a platform that can address 80 percent of all solid tumors has the potential to impact tens of thousands of lives each year.
Medgadget: What motivates MetaStat?
Bronsther: At MetaStat we’re concerned with the treatment and prevention of metastatic diseases. The key scientific breakthrough was the discovery of a pathway by which solid tumor cells acquire the ability to metastasize or leave the primary tumor to infiltrate other parts of the body. The reason this is so important is that 90 percent of deaths from metastasizing cancer result not from the primary tumor but from the tumors that occur as a result of metastasis from the primary tumor. To be clear, only some tumors are capable of metastasizing. Take breast cancer, for example. If left untreated, only 35 percent of patients would develop metastatic disease. If you did not treat it, the tumor would grow and expand in the breast but in only about one-third of patients would the tumor cells spread through the blood stream to other parts of the body. Another example is prostate cancer. If left untreated, only 20 percent of men would ever develop metastatic disease.
Let’s take a look at this from another point of view with breast cancer. Only 35 percent of women with breast cancer would develop metastatic disease if left untreated. However, today, 80-85 percent of women with newly diagnosed breast cancer are treated with chemotherapy up front in an attempt to prevent the development of metastatic disease. One hundred percent of women who get chemotherapy for breast cancer will get sick in some fashion and one percent will die from the treatment. It takes six months to deliver the complete course of chemotherapy with an average cost of $75,000 per woman. The point is that we are massively over treating patients unnecessarily because we previously did not have a good way to understand if a patient was going to have an aggressive versus an indolent tumor. Ideally, we could identify those who only need the tumor removed versus those who are at risk for metastatic cancer and require chemotherapy. This challenge is important to patients, physicians, and the healthcare system that bears the cost burden for these treatments.
Using a different product, not one from MetaStat, in one European study, roughly 200 women were down staged from a high to low risk for metastatic disease. Low risk here means they have less than a 10 percent chance of developing metastatic disease from their cancer over 10 years. Eighty-five percent of those who were recategorized as low-risk elected not to take chemotherapy while 15 percent took the treatment anyway. Clearly, this kind of insight results in changes to how patients make medical decision.
Medgadget: What is the science behind MetaStat and where did it come from?
Bronsther: Our two principal scientists, Dr. Frank Gertler, an MIT Koch Institute Professor, and Dr. John Condeelis, a professor and chairman at the Albert Einstein College of Medicine, have been collaborating on the science behind MetaStat for over a decade and represent as much as $50M in funding that has gone into bringing the science to the point where it can be leveraged in the clinical arena.
We currently have two breast cancer diagnostic products that rely on our understanding of the processes by which metastatic disease arises. It begins with Mena, a central and peripheral nervous system protein that influences the nucleation and polymerization of cellular actin networks. Post partum expression of Mena is suppressed with only trace amounts persisting. In all epithelial tumors, the gene that codes for Mena is turned back on causing the tumor state. There are two isoforms of Mena that we are particularly interested in, Mena-INV (Mena invasive) and Mena-11A. The difference between the two isoforms is just 19 amino acids but their effects are significantly different. Mena-INV changes the cytoskeletal structure of cancer cells by preventing actin capping causing actin filaments to continue growing and create elongated cancer cells that can easily break away and metastasize. Mena-INV also upregulates the sensitivity of epithelial growth factors. Mena-11A, on the other hand, reduces the ability of cancer cells to break away from the tumor. The relative levels of Mena-INV and Mena-11A can directly predict metastatic potential.
Medgadget: What are MetaStat’s products?
Bronsther: We currently have two diagnostic tools: MetaSite Breast and MenaCalc.
The MenaCalc Platform is an assay that looks at the relative abundance of the two key Mena isoforms as predictive indicators of cellular phenotype and migration potential. MenaCalc has been used in some interesting studies and has shown to be highly prognostic in non-small-cell lung cancer and prostate cancer. What’s great about the platform is the evidence showing that it can be broadly applicable to any metastatic tumor. Compared to using gene signatures, this is a huge step forward since gene signatures vary amongst different cancers and require significant research to identify. It costs roughly $125-150M to develop an algorithm for prostate cancer screening based on gene signatures. MenaCalc is currently being used for breast cancer but will be expanded to prostate cancer and adenocarcinoma of the lung.
MetaSite Breast is an immunohistochemistry-based test used to identify and quantify active metastasis sites on fixed breast tissue samples. The test works by triple staining for an indicative three-cell structure composed of an endothelial cell, perivascular macrophage, and a tumor cell expressing the Mena protein. Results published in the August 2014 edition of the Journal of the National Cancer Institute showed that MetaSite was able to outperform the validated IHC4 test control and proved that the number of three-cell structure sites corresponded to increased metastatic risk.
Medgadget: What is MetaStat’s competitive advantage?
Bronsther: Today, MetaStat can screen 100 percent of women for breast cancer. There are other products in the market but they are limited in scope. After ours, the next leading product only covers 60 percent of women. Limitations in these other products are due to only being applicable to the most common subtype of breast cancer. These competitors use a gene signature rather than exploiting the biological pathway by which metastatic disease arises. We want to be clear, and this is true for any product in this space, that we can never say a patient has a zero percent chance of having metastatic cancer, what we can provide are estimates based on an understanding of the patient’s individual biology.
Medgadget: What’s next for MetaStat?
Bronsther: With some initial successful outcomes, we’re beginning to take steps toward commercializing MetaStat’s products. To that end we’ll soon be starting two new clinical trials that will have fully automated tasks for both products within the next four to six months as well as building out our CLIA laboratory.