Q&A

Outcomes for cancer patients have shown steady, slow, improvement during our lifetimes. Most of this progress has come from incremental improvements to existing therapies, not dramatic breakthroughs. Tosk believes that it can accelerate improvements in patient outcomes with two new approaches to cancer therapy: (i) selective blocking of treatment adverse side effects and (ii) selective blocking of the activity of cancer genes. Unlike most companies that are developing expensive, end-of-life therapies, Tosk’s drugs are designed to be frontline and relatively inexpensive to administer, reducing the overall cost of care, and making them available to a worldwide market.

Tosk’s new drug discovery and development strategy is different from most pharmaceutical companies. We think that this gives us an advantage, but it sometimes leads to confusion and misinterpretation. Brian Frenzel, Tosk’s CEO, recently fielded questions frequently asked about Tosk during an interview with Global Business Reports:

Our overriding mission, to improve outcomes for cancer patients, is not different than most. However, our approach is quite different. Most early stage cancer drug companies and the research divisions of large companies, the ones you read about in the newspaper, focus their attention on what we call heroic, expensive, end-of-life therapies (HEELTs for short). These go by names like immunooncology (I-O), CRISPER, CAR-T, PD-1, and PD-L1. They tend to be used only after other drugs have failed because they are usually very expensive to administer and require
sophisticated medical center support. They harness biologicals like proteins, antibodies, and cells as the treatment modality.
Tosk is different – we use transformative, proprietary methods to discover new small molecule drugs. Our objective is to fill in the gaps in existing therapies, thereby improving them. We have used our technology to discover drugs that prevent the adverse side effects of existing, frontline therapies and to block the activity of cancer genes, starving them of their ability to promote tumor growth. We think this approach has inherent advantages, but cancer is a huge unmet medical need, so there is ample room for many companies to succeed.

Today, some 1.7 million new cases of cancer occur annually in the US, and 600,000 patients die of cancer each year. Though there has been steady improvement in outcomes since US President Richard Nixon declared a “War on Cancer” in 1971, much of the incremental improvement in outcomes has come from more effective use of drugs developed decades ago, improvements such as better dosing regimens and combinations of existing drugs. We use the term “parent” to describe the older drugs, and “Companion™  to describe ours. Together, they’re a one-two punch. We’ve also chosen this mission because it addresses a serious, unmet medical needs for a very broad market. By making existing, frontline therapies more efficatious and cost effective, we can improve outcomes for cancer patients, worldwide. We also believe that our drugs will soon be of interest to large pharmaceutical companies that are looking to fill their pipelines or replace drugs coming off patent. That means a significant payoff to our shareholders.

Yes, I have co-founded and been the CEO of three and the COO of another biomedical product companies that achieved a successful exit through IPO or M&A. I was also an active member of the Board of Directors and continue as a senior advisor to SanBio Ltd., a cell therapy company that recently went public. I have also advised and invested in a number of other biomedical companies in which I was not a member of the management team.

But I’m not the only one. All our senior team members and several of our advisors have done so as well. We’re all devoted to helping in the fight against cancer and believe our drugs can make a significant contribution to the longevity and quality of life of cancer patients.

Yes, we are quite fortunate to have three distinguished PhD scientists leading our R&D initiatives: Bill Garland, Steve Yanofsky, and Solomon Ungashe, as well as a great group of scientific and medical advisors. Bill is an expert in drug development, from discovery through human clinical studies. Steve is a highly accomplished cell biologist, pharmacologist, and project manager. Solomon is a medicinal chemist with tremendous background in drug discovery, formulation, and lead optimization. All have worked for startups as well as large companies, such as Hoffman-LaRoche, Bell Labs, and Affymax. They know how to get things done. Our Chairman, Harold Crow, a pharmaceutical industry veteran, has founded several start-ups, while director Charles Garvin is well known in the venture world and has seeded start-ups in a variety of industries, including biotechnology.

That’s the reality. methotrexate, for example, is effective against a range of cancers, including leukemia. It was introduced in 1947. Doxorubicin, widely used against lung, breast, and bladder cancer, as well as lymphoma, was launched in 1949. Unfortunately, Their adverse effects often force oncologists and their patients, to ask, “is the cure worse than the disease?” Not only can cancer therapies make a patient very sick, they can damage the heart, kidneys, liver, and other organs. The adverse effects can be permanent and reduce the patient’s lifespan, even if the cancer is cured. The question we asked ourselves at Tosk is, “how can we make these drugs, which we believe will be used for treatment for many decades to come, better?” Our answer — two patented drugs that target adverse side effects that damage the heart and the GI tract, and two research-stage drug candidates following in the pipeline.

No, they are small molecule drugs that are relatively easy and inexpensive to produce. In fact, we project that our drugs will actually reduce the cost of cancer care because the side effects that they prevent are costly to treat. If you eliminate that cost, you more than cover the cost administering of our drugs. Healthcare payors around the world are looking for ways to reduce the cost of medical care. We believe we can help.

Yes. We got a recent boost from Joe Biden’s “Cancer Moonshot” initiative. Symptom Management Research was identified as one of 10 areas of focus needed for future cancer research. Included in this area was the need to find ways to ameliorate the adverse side effects of cancer therapy. Tosk has received funding from competitive state and federal grant programs, and we hope that the Cancer Moonshot translates into expanded grant support.

Immunotherapy will be one part of the picture, but most immune therapies are being tested in combination with existing chemotherapies. They don’t eliminate the need for chemo, and they have side effects of their own. Also, they are very expensive and require specialized hospitals not available to most patients around the world. Looking forward, reducing the side effects of cancer therapy will be just as important for the foreseeable future as it is today.

Yes. The dose of most cancer therapies is limited by side effects. If we can reduce or eliminate their side effects, cancer drugs could be administered at higher doses over longer periods of time, giving them a better chance to work. Also, the cost of treating adverse effects can be as high or higher than treating the cancer itself. If we can eliminate this added cost, we can reduce the overall cost of cancer care.

TK-90 targets the toxic side effects of frontline cancer therapeutics like methotrexate, 5-FU, and radiation therapy. Their primary side effect is mucositis, which is inflammation and ulceration of the lining of the digestive tract. It’s painful and can force a patient’s physician to cut back or eliminate the very treatments that keep the cancer in check. We experienced good results in our lab using highly predictive rodent models, and we received an IND (Investigational New Drug) cleanance to go into human studies from the FDA in the minimum review time of 30 days.

TK-39 is designed to selectively block the damage that commonly used cancer drugs such as doxorubicin do to the heart. This cardiotoxicity is permanent and severely limits the lifetime dose of these drugs. TK-39 continues to demonstrate excellent results in cell culture and animal studies. We have recently completed a rodent study demonstrating that TK-39 protects the heart’s function from damage caused by doxorubicin and also completed another animal study which shows that TK-39 does not interfere with the cancer killing ability of doxorubicin. Unlike some rodent studies, these are very predictive of what will happen in humans. We have initiated final preclinical toxicology studies needed to file an application with the FDA to enter human clinical trials for TK-39.

Yes, that is our most scientifically challenging effort — to find drugs to block the mutant kRAS gene. A drug that can do this has the potential to treat kRAS positive cancers, including 90% of pancreatic cancers, 45% of colon cancers, and 35% of lung cancers. The global market for these is very large. We are collaborating in this effort with the National Cancer Institute and Dr. Jeffrey Thomas’ laboratory at the Texas Tech University Health Science Center. Dr. Thomas is a member of our Scientific Advisory Board. A drug to block oncogenic kRAS is considered the National Cancer Institute’s highest priority, and our compound screening technology has yielded several promising drug candidates.This is very competitive field, but we feel we have an advantage with our Genetically Modified Fly discovery technology.

Yes, for the most part with different approaches. Historically, most pharma companies have either tried to engineer out drug side effects by changing the chemical structure of existing drugs or to develop new formulations of drugs in order to target the drug more selectively to the cancer, often called the “magic bullet” approach. Unfortunately, in many cases these approaches have not proven successfull. Physicians have generally attacked the problem using trial and error to develop better dosing regimens and combinations of drugs that provide better efficacy with lower side effects. Many of the advances in cancer treatment over the years have come from these efforts. Even so, physicians are often faced with a Hobson’s choice — either limit dosing and reduce the efficacy of a drug or take the chance that side effects will kill the patient before the cancer does.

Yet another approach is to treat the side effects after they occur. For example, there are many palliative relief medications for mucositis, such as anti-ulcer medications, antibiotics, and pain killers. But these usually offer limited relief after most of the damage has been done.

Finally, in some cases, an antidote to the chemotherapy can be administered if the side effects become too severe. But of course, this shuts down the efficacy of the cancer drug along with the side effects, so this approach suffers from the same problem as limiting the dosing.

There have been a few other efforts to develop drugs that selectively block side effects. Most have failed. We know of two competing efforts underway in other companies which are using repurposed, or failed, older drugs to prevent mucositis in patients receiving radiation therapy. Another company is attempting to succeed where others have failed by trying to engineer out the side effects of doxorubicin. Over all, there are not many companies attempting to develop side-effect-reducing agents.

Most of the costs of pharmaceutical development occur in late stage, worldwide clinical studies. These costs are generally borne by larger pharmaceutical companies that partner with drug development companies such as ours. Even so, we have made considerable progress at lower costs than most companies would incur. We take pride in running a very lean, focused operation that has allowed us to develop two proprietary technology platforms, patent two new drugs, put one of these into human trials, and also advance two other important drug discovery programs on a very low budget. We’re looking to both transform the lives of cancer patients as well as generate a venture capital return for our investors. It’s rare in business when you can do both.

We have patented drug discovery tools that others do not. The Side Effect Fly uses the common fruit fly as a discovery tool to rapidly and inexpensively screen tens of thousands of compounds in order to identify those with the potential to block drug toxicity. We move “hits” from this screen into more traditional animal models to confirm safety, adverse effect prevention, and non-interference with the therapeutic efficacy of the parent compound. Other screening efforts have typically used either cell culture methods, which are low cost, but not as specific as whole animals, or an initial screen using rodents, which is time consuming and prohibitively expensive for screening large numbers of compounds.

Our kRAS screening technology uses a different method that we call the Genetically Modified Fly. This involves integrating a human cancer gene into the genome of the fly. In other respects, it is similar to the Side Effect Fly technology. These game changing technologies have begun to bear fruit leading to four products in the pipeline, the most advanced of which has yielded positive results in human clinical studies.
We have four shots on goal with these projects and any one of them could be the basis for a sizeable company. Of course, we think all four will be successful.