"Tosk’s proprietary drug discovery technologies are based on Drosophila melanogaster, the common fruit fly. Tosk believes that screening in a living animal is more effective than the cell-based, biochemical, and computer modeling methods used by most drug companies. We have developed and patented a technology to discover drugs that selectively block toxic side effects found in cancer therapies and to make certain therapies effective in patients who do not benefit from treatment."
Could you briefly introduce Tosk and outline the focus of the company’s pipeline?
Tosk has four cancer drugs in development. Three designed to selectively block the adverse effects of widely-used cancer therapies, and the fourth targets the kRAS oncogene. We call this approach Proven Solutions ImprovedSM and refer to our products as CompanionTM drugs, since they are administered alongside existing, widely-used cancer treatments to improve outcomes for patients. Tosk’s efforts address goals set forth in Vice President Biden’s 2016 Cancer Moonshot Blue Ribbon Report, which cited side effect management and precision medicine as two of 10 priority areas for US cancer research and product development.
What are the leading drivers of Tosk’s CompanionTM drug focus?
Tosk’s proprietary drug discovery technologies are based on Drosophila melanogaster, the common fruit fly. Tosk believes that screening in a living animal is more effective than the cell-based, biochemical, and computer modeling methods used by most drug companies. We have developed and patented a technology to discover drugs that selectively block toxic side effects found in cancer therapies and to make certain therapies effective in patients who do not benefit from treatment. The drugs currently available for side effects typically offer only limited, palliative relief. They treat side effect symptoms, but do not address their underlying causes. Tosk develops side effect preventative drugs that are intended to reduce or eliminate the need for palliative relief.
Recently, Tosk has expanded its fly-based technology platform to discover drugs that block the effects of cancer genes. This technology involves implanting human cancer genes into fruit flies and then screening for compounds that block the activity of these genes. We are harnessing this technology to address targets for which traditional drug discovery methods have failed and that are often referred to as “undruggable.”
Our efforts to develop and perfect these technologies have drawn on relationships with leading US academic institutions, including Texas Tech University, the University of California Santa Cruz, and the University of California Irvine.
What are Tosk’s most advanced products in the pipeline?
Our most advanced product is TK-90, which is in “proof of concept” clinical studies for mucositis side effect reduction. A second drug candidate, TK-39, selectively blocks cardiotoxicity, a life-threatening and permanent side effect of the anthracyclines, such as doxorubicin and Doxil®, and other cancer drugs. We expect TK-39 to enter clinical studies in breast cancer patients in 2019. The side effects we address not only impact the quality of patients’ lives but can be dose-limiting. Furthermore, side effects can be costly to treat, debilitating, and even life-threatening. For example, mucositis is not only painful and can result in weight loss in already frail patients, but it can also introduce a route of infection that is potentially fatal in immune-compromised patients. In the case of the anthracyclines, recent studies suggest that, even with a lifetime limit on dosing, 25% of patients suffer congestive heart failure within 10 years.
How does Tosk use its drug discovery platform technologies to find new drug candidates?
Tosk has two different drug discovery technologies, both using Drosophila melanogaster. The first is the “side effect fly”, which we use to screen candidate compounds for their ability to block drug toxicities. We select drugs with the most dose limiting, debilitating, and potentially life-threatening side effects. Then, we identify the lethal dose of the “parent” drug in a vial of 50 fruit fly eggs. We then test candidate compounds for their ability to block the lethal dose of the toxic drug. Those that block it and yield living larvae and flies are our “hits.” We then use cell culture to select the hits that do not also block the cancer-killing efficacy of the parent drug – these become “leads.” Leads are then optimized using traditional medicinal chemistry techniques for improvements in performance, formulation, and the like, to become “IND candidates.” Since we are trying to reduce drug toxicity, it is also important that our CompanionTM drugs do not have significant side effects of their own.
Our second drug discovery technology, the “genetically modified fruit fly”, is used to identify drugs that block the effects of cancer genes. We have selected mutated kRAS, which is important in the propagation of tumors, as our first target. We have recently received a US$2 million grant from the US National Cancer Institute to fund this research. The initial goal is to make certain cancer drugs work in patients who do not benefit from treatment. Those drugs include Erbitux® and other EGFR-inhibiting drugs, which are currently not effective in 40% of patients. A kRAS drug would also have the potential to be a direct cancer monotherapy in patients with mutated kRAS tumors, such as in many pancreatic, colon, and lung cancers.
Will demand for Tosk’s products be affected by new products for cancer currently in development?
Tosk’s markets are vast and will accommodate a number of new approaches. Cancer is now tied with heart disease as the leading cause of death in the US and most other industrialized countries. The market for effective cancer therapies in these countries is growing due to aging populations. And, since our drugs are low-cost, small molecules, they will be affordable in less wealthy countries as well.
Our approach is very much in line with the pattern of incremental improvement in outcomes for cancer patients that historically has come from better use of existing therapies and combining them with new therapies. The press has been full of articles recently on “breakthroughs” in cancer such as precision medicine, immunotherapies, and drug targeting. We applaud these efforts, but observers should keep in mind that these initiatives are really part of the long history of continuous, incremental improvements in cancer care.
Immunotherapy was one of the first types of cancer therapy used over 100 years ago, and it is an extension of the cancer vaccines and immune modulators first developed in the 1990’s. Drug targeting is part of the “magic bullet” approach which began in the 1970’s. Furthermore, newer therapies are typically used in combination with, or sequentially following, existing ones, rather than supplanting them. So, we see a very large market for Tosk’s technologies and products far into the future.
What are the next steps for Tosk’s four products in the pipeline?
We expect to establish clinical proof of concept for TK-90 for mucositis side effect reduction this year in a study of 60 head and neck cancer patients. TK-39 for cardiotoxicity side effect reduction is in the last stage of preclinical development, and we plan to initiate clinical studies for it next year. We have two other drugs in the pipeline, one for nephrotoxicity side effect reduction and, as previously mentioned, one to block the effects of the mutant kRAS oncogene, both of which are undergoing lead selection and optimization. We are very optimistic about the future benefits that each of these programs can deliver to cancer patients worldwide.