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:

How does TOSK’s mission differ from other companies developing cancer drugs?

Our overriding mission, to improve outcomes for cancer patients, is not different from 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 immuno oncology (I-O), CRISPR, 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.

Why have you chosen this particular avenue — improving existing therapies — as one of Tosk’s missions?

Today, some 1.8 million new cases of cancer occur annually in the US, and over 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 therapies 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 need for a very broad market. By making existing, frontline therapies more efficacious and cost effective, we can improve outcomes for cancer patients, worldwide. Furthermore, since side effects can be costly to treat, we believe our drugs have the potential to reduce the overall cost of care, which is very important in an environment of increasing healthcare costs.

It’s remarkable that frontline drugs decades old are still a critical component of cancer therapy.

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.

Are your drugs expensive?

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 of administering our drugs. Healthcare payers around the world are looking for ways to reduce the cost of medical care. We believe we can help.

I imagine the US government is interested in what you are doing.

Yes. We got a 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 President Biden’s new cancer research initiatives translate into expanded grant support.

But isn’t emphasis being put on immunotherapy rather than chemotherapy?

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.

In addition to eliminating toxicity, which of course is quite an achievement, are there other benefits to your work?

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 does what?

TK-90 targets the toxic side effects of frontline cancer therapeutics like methotrexate, 5-FU, and radiation therapy. Their primary, dose limiting side effect is mucositis, which is inflammation and ulceration of the inner lining of the digestive tract. It’s painful and can force physicians to cut back or eliminate the very treatments that keep the cancer in check. We had 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. Recently, TK-90 has proven to be highly safe and effective in proof of concept studies in cancer patients.

And TK-39?

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.

You mentioned you are working on an exciting project in which the NCI is particularly interested?

Yes, that is our most scientifically challenging effort — to find drugs to block mutant KRAS genes. 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. 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 a very competitive field, but we feel we have an advantage with our Genetically Modified Fly discovery technology.

Are others working to address the adverse effects of cancer therapy?

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 successful. 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 much 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 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.

I understand that developing a drug typically costs many millions, sometimes even billions, of dollars. How have you accomplished what you have done while spending such a relatively small sum?

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 discovery 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 tight budget. We’re looking to both improve 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.

What makes you think Tosk can succeed given the challenges you face?

We have patented drug discovery tools that others do not. Our 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 sizable company. Of course, we think all four will be successful.