Tosk is developing a family of inexpensive, small molecule drugs designed to prevent the toxic side effects of common cancer treatments, resulting in significantly improved patient outcomes, enhanced dosing regimens, and reduced costs. Tosk also has a program to discover drugs that block cancer genes.
Q. Tosk’s TK-90, targeted at preventing mucositis, has been in human trials for a year. Could you provide an update on the latest developments?
We just completed a study of 25 head and neck cancer patients taking our CompanionTMdrug TK-90 alongside methotrexate to determine safety and optimum dosage. We met the first objective – safety – and, giving patients four different doses of methotrexate, found that the two highest doses were highly effective in preventing mucositis, a life-threatening side effect of many chemotherapies and radiation therapy. That far exceeds the 30% reduction needed for regulatory approval. Tosk is initiating a second phase of testing in 22 patients taking the optimal dose of TK-90. This study, which we anticipate will be completed in the first half of 2019, should fully establish TK-90 as an effective prophylaxis for mucositis. We call our drugs CompanionTM drugs because they are administered simultaneously with existing cancer therapies.
Is Tosk looking for partners to scale up and commercialize TK-90?
We have initiated a partner search to identify companies that would be a good fit with us on TK-90. We are considering big pharma, specialty pharma, and supportive care oncology companies. We are also raising money through a mezzanine private offering that we anticipate will be our last round prior to an IPO. We will pursue both avenues with the goal of completing both by the end of next year. The company has plans to grow and scale-up our operations, but we do not anticipate taking a product to market ourselves, which would require greater infrastructure and global reach than we can realistically put in place. Fortunately, larger pharmaceutical companies look to companies like Tosk to fill their pipelines and augment their own R&D efforts. There are a number of companies with established worldwide regulatory and distribution capabilities that could make good partners for us.
We expect that our products in addition to TK-90 and our proprietary drug discovery technologies will be a significant incentive for companies to work with us. We are not a one drug company and could help to fill the new product needs of a partner for many years to come.
Have you had previous experience partnering a small biotech with a big pharma?
I was first involved with pharmaceutical corporate partnering on the big pharma side when I served as director of corporate planning at Syntex Corporation, then the largest West Coast pharmaceutical company. I went on to co-found Genelabs Technologies, Adeza Biomedical, Vesta medical, and Centaur Pharmaceuticals. More recently, I served as an active Board member of SanBio. All in all, I have been involved with more than 20 large corporate deals and mergers, including selling one company to Pfizer.
Apart from TK-90, what is the current status of Tosk’s pipeline?
We have three other promising products in the pipeline. TK-39, Tosk’s second patented product, blocks the cardiotoxicity caused by a class of widely used cancer drugs known as anthracyclines. Their damage to heart tissue is permanent and limits the lifetime dose of these drugs. Anthracyclines are used to treat breast, bladder, and lung cancers, as well as lymphomas and leukemias. We plan to put TK-39 into human trials next year. Our third drug discovery initiative, TK-88, is designed to block the damage that widely used platinum-based drugs, such as cisplatin and carboplatin, can cause. These adverse effects can be permanent and include kidney damage, peripheral neuropathy, and hearing loss.
Tosk is partnering with Professor Jeff Thomas and the Texas Tech University Health Sciences Center on drugs to block the kRAS oncogene – a high priority for the National Cancer Institute (NCI). Could you tell us more about the background of this effort?
Professor Thomas has been a member of our scientific advisory board for more than five years. Texas Tech’s Health Sciences Center is the co-PI on our recent US$2 million Phase II SBIR kRAS grant. The U.S. National Institutes of Health’s National Cancer Institute has made this initiative a top priority because some 40% of all cancer patients are untreatable with an important class of cancer drugs – the EGFR inhibitors – due to the presence of a mutant kRAS gene. Using our approach, it may be possible to block the activity of this gene. This gene is also estimated to be present in 90% of pancreatic cancers, 45% of colon cancers, 35% of lung cancers, and a smaller percentage in most other cancers as well. Just looking at the EGFR application, if we could add the previously untreatable patients, sales of EGFR-inhibitors would increase by US$1 billion or more. Adding direct treatment of kRAS positive cancers would increase this number by several times or more.
What are the drivers behind Tosk’s diverse pipeline?
Tosk’s products are initially discovered using one of two different proprietary drug discovery technologies, both using the common fruit fly. These technology platforms use animals with a short life cycle to quickly and economically screen thousands of compounds to find hits. Hits are then optimized for safety and efficacy using more traditional medicinal chemistry techniques to improve performance and are then formulated to become IND candidates. One of our two technologies – the ‘side effect fly’ – is a proprietary screening method to identify candidate compounds that selectively block drug side effects. Our second technology platform – the ‘genetically modified fruit fly’ – involves implanting a human cancer gene into the genome of a fruit fly to screen for drugs to block the activity of that cancer gene. We have selected the mutated kRAS gene, which is important in driving the propagation of many cancers, as our first target for this technology.
Immuno-oncology is an area that has received a lot a press recently. How do Tosk’s areas of interest compare?
Though it was identified, along with immuno-oncology, as one of the 10 areas of emphasis by Vice President Biden’s Cancer Moonshot panel, side effect reduction is an under-appreciated field. Side effects not only adversely affect patients’ quality of life, but can be costly to treat and can limit the effectiveness of cancer therapy. Our small molecule drugs are inexpensive to produce and fit easily into existing treatment regimens. They are intended not only to reduce the cost of treatment but to improve outcomes for cancer patients. In some sense, our products are a distant competitor of immunotherapies and precision medicines, since we are trying to eliminate the need for those therapies.
What are Tosk’s key objectives moving forward?
We see our work as revolutionary, potentially positively impacting the lives of millions of patients suffering from cancer as well as their loved ones. This coming year, we intend to demonstrate clinical proof of concept for TK-90, have TK-39 cleared for clinical studies, have TK-kRAS ready for an IND, and continue to move TK-88 toward the clinic. We also look to enter into an agreement with a corporate partner and position the company for a liquidity event for investors. 2019 should be a pivotal year for Tosk.