BRIAN FRENZEL, CEO


Brian Frenzel is a biotech veteran who co-founded four previous biomedical companies, Vesta Medical (acquired by Pfizer), Centaur Pharmaceutical (acquired by Renovis, leading to an IPO), Adeza Biomedical (IPO, subsequently acquired by Cytec) and Genelabs (IPO). Prior to becoming a biotech entreprenuer, he was Director of Corporate Planning for Syntex, at the time the West Coast's largest pharmaceutical company. Previously he was a principal at Booz Allen & Hamilton and a consultant at the Boston Consulting Group. He graduated from Stanford University with a degree in Physics and subsequently earned an MBA there. He also spent four years in Admiral Hyman Rickover's U. S. Navy's nuclear submarine service. He sat down recently to answer questions about Tosk.

1Brian, how does TOSK’s mission differ from other companies developing cancer drugs?
Tosk's motto is Proven Solutions Improved.SM. We take existing front line cancer drugs such as doxorubicin and methotrexate and make them dramatically better by stripping them of their toxic side effects. That’s what makes us unique — our complete focus on the design of a family of Companion™ drugs that eliminates the dose-limiting, painful, and potentially life threatening, adverse side effects of cancer treatments commonly prescribed today. Our Companion drugs are administered along side existing drugs using the same dosing method, intravenously or in pill form. Our first patented drug, TK-90, successfully completed human trials for Proof of Concept. A second patented drug, TK-39, will enter trials this year. Significantly, Tosk also has a program to develop Companion drugs that make certain widely used cancer drugs efficacious in millions of cancer patients who currently do not benefit from treatment. So our market potential is exceptionally large.
2Why have you chosen this particular avenue - improving existing therapies - as Tosk’s mission?
In spite of the attention generated by new cancer therapies, the “War on Cancer,” declared by President Richard Nixon in 1971, has only had a modest effect in improving outcomes for cancer patients. Today, some 1.7 million new cases of cancer occur annually in the U. S., and 600,000 patients die of cancer each year. Much of the incremental improvement in outcomes is due to 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 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 effective and less expensive, we can improve outcomes for cancer patients, worldwide. We also believe that our drugs will soon be of great interest to large pharmaceutical companies that are constantly looking to fill their pipelines or replace drugs coming off patent. That means a significant payoff to our shareholders.
3How close are you to providing a payoff to investors?
I can't say precisely of course, but our goal is to provide investors a payoff within two years by finding a partner or partners to work with. Large pharmaceutical companies are constantly looking to refill their pipelines, and they often look to small discovery companies like Tosk to work with. This can mean a return to investors long before the drugs are marketed, often midway through clinical studies or even earlier, based on milestones and licensing fees. The fact that we have four drugs in development, one of which has had success in human trials, as well as a proprietary technology, makes us particularly attractive.
4What would a deal look like?
It could range from a product licensing deal for one or more of Tosk's drugs, a sale of the entire company or an IPO. It's important to keep in mind that Tosk is not a one trick pony,. We have four drugs in development, with ideas for others. We have a proprietary discovery platform. So we have quite a few options in terms of liquidity events. Deals in our space have picked up significantly in the past couple of years, and at record breaking prices. Very recently, Bristol Myers acquired Celgene for $72 billion. Deals in the $200 million to $4 billion are not uncommon. Here’s an example, Cytomx Therapeutics, an early stage oncology company like ours, has a strategic collaboration with Bristol Myers that was signed in 2014. They recently announced an expansion of the collaboration, with Cytomx receiving an upfront payment of $200 million and an additional $448 million for each target drug under development based on certain milestones. The license is for early clinical and late preclinical stage drugs. And let me add, Cytomx has reserved for itself other drugs they’re working on. So, we, like them, could sell or license one or two drugs and keep the rest of our product development portfolio and our proprietary drug discovery technology. We have choices.
5How have you funded Tosk?
We have raised approximately $19 million in private equity, as well as $3.7 million in government research grants, which are highly competitive and awarded only to the most promising development projects. We recently received a two-year, $2 million Phase II SBIR grant from the National Cancer Institute to support our kRAS oncogene drug research and development program. This followed a Phase I SBIR grant that financed part of the original Tosk research in this field. The combination of equity and non-dilutive grant funding has funded Tosk’s research to date.
6You’ve obviously been through a similar process a number of times?
Yes, I have negotiated more than 15 corporate deals during my career, as well as negotiating liquidity events for the four companies I co-founded when I left the corporate world. 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. But it’s not a contradiction to also say we’re looking for a financial payoff.
7The team you’ve put together, both operating and advisory, is quite remarkable. Donald Kennedy, to name just one of your Scientific Advisors, was Commissioner of the FDA, president of Stanford University, editor of Science, and professor of biology at Stanford. It’s clearly an all-star group.
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 world class group of 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. Our scientific and medical advisors are world renowned and provide us with extremely helpful perspectives and advice.
8It’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. 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 violently ill, 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 fundamental to cancer 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.
9Are your drugs expensive?
No. These are small molecule drugs that are relatively easy and inexpensive to produce. In fact, we project that our Companion drugs will actually reduce the cost of cancer care because the side effects that they reduce or eliminate are costly to treat. If you eliminate that cost, you more than cover the cost of our Companion drugs. The U. S. Government, and others, is looking for ways to reduce the cost of medical care. We believe we can help.
10I imagine the US government is interested in what you are doing.
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. In the past Tosk has received funding from competitive federal grant programs and we hope that the emphasis on the Cancer Moonshot translates into expanded grant support. An additional $2 billion of federal funding has already been budgeted for the Cancer Moonshot.
11But isn't emphasis being put on immune therapy rather than chemotherapy?
Immunotherapy will be one part of the picture, but the most important immune therapies are being tested as candidates to combine with existing chemotherapies. They don't eliminate the need for chemo, and they have side effects of their own. And, they are very expensive and require specialized hospitals not available to most patients around the world. Looking forward, reducing the side effects of chemotherapy will be just as important as ever, maybe even more important.
12In 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 side effects, cancer drugs could be administered at higher doses over longer periods of time, giving them a better chance to work. Also, as I mentioned earlier, 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.
13TK-90 does what?
TK-90 targets the toxic side effects of frontline cancer therapeutics like methotrexate and radiation therapy. Their primary side effect is mucositis, which is inflammation and ulceration of the lining of the digestive tract. It’s very 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) designation to go into human studies from the FDA in the minimum review time of 30 days. That first trial was successfully completed in the last quarter of 2018, and a second trial, looking to confirm results of the first, will begin in the first quarter of 2019. We anticipate FDA approval once this trial is completed.
14And 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 successfully 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 are now ready to enter the final preclinical toxicology studies needed to file for an IND with the FDA to enter human clinical trials for TK-39. We expect to begin the human trials this year.
15You mentioned you are working on an exciting project that the NCI is paryticularly intereted in??
We have two other initiatives. The one you are talking about is our most scientifically challenging effort - to find drugs to block the mutated kRAS gene. This is a genetic characteristic found in up to 40 percent of cancer patients that renders certain cancer drugs ineffective. Drugs emerging from this effort have the potential to become cancer therapies in all kRAS positive cancers, including 90% of pancreatic cancers, 45% of colon cancers, and 35% of lung cancers. The global market for this is very large. We are collaborating in the effort with the National Cancer Institute and Dr. Jeffrey Thomas’ laboratory at Texas Tech University. Dr. Thomas is a member of our Scientific Advisory Board. A drug to block oncogenic kRAS is considered the National Cancer Institute's number one priority, and our compound screening technology has yielded several promising drug candidates. Our other effort is TK-88, a discovery effort for drugs that block the side effects of widely used platinum-based drugs, like cisplatin and carboplatin.
16Are others working to address the adverse effects of cancer therapy?
Yes, with different approaches. Historically, most pharma companies have either tried to design out the 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, there has not been much success using these approaches with front-line cancer therapies. 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 and pain killers. But these usually offer limited relief after most of the damage has been done.
Finally, in some cases, antidote to the chemotherapy can be administered if the side effects become too severe. But of course, this shuts down the efficacy of the 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 prevent side effects using drugs that selectively target 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-blocking agents.
17I understand that drug development normally 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 later 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 lots of 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 proprietary technology platforms, patent two new drugs, put one of these into human trials, and also advance two other important drug discovery programs. 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.
18What makes you think Tosk can succeed given the challenges you face?
We have a patented drug discovery tool that others do not. We call it Optimizing Marketed Drugs™ (OMD™). OMD uses the common fruit fly as a discovery tool to rapidly and inexpensively screen thousands of compounds in order to identify those with the potential to reduce or eliminate toxicity. Texas Tech’s Dr. Thomas, who I mentioned earlier, is a recognized expert in fruit fly biology and has been instrumental in this effort. We move “hits” from this screen into more traditional animal models to confirm safety, adverse effect reduction, and non-interference with the chemotherapeutic effect 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 genetically modified strain of fruit flies with a human cancer gene integrated into its genome. In other respects, it is similar to the OMD technology. And we've have had a recent success, as I mentioned -- our drug TK-90 proved successful in human trials. So it's full speed ahead, as we used to say in the Navy!