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). 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 ImprovedSM. Meaning, 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. 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.
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 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, and the market potential is huge. By making existing, frontline therapies more effective, we believe 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 patient shareholders.
3Are 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.
4It’s remarkable that 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.
5But isn't a lot of emphasis lately 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.
6In 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.
7I 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 way 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 new 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.
8So, what kind of progress are you making?
We already have one patented drug in human trials, TK-90, and another patented drug, TK-39, that we plan to put into clinical studies next year, both addressing very large markets. Assuming we have a positive outcome from our trials, we’ll be in a good position to license TK-90 to one or more pharmaceutical companies in return for milestone fees and royalties.
9TK-90 does what?
TK-90 targets the toxic side effects of front-line 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.
10And 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.
11Anything else of note you’re working on?
We have two other initiatives. One is a discovery effort for drugs that block the side effects of widely used platinum-based drugs, like cisplatin and carboplatin. Another 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. There are very few early stage biopharma companies with four drugs in the pipeline.
12How close are you to commercializing your drugs?
That depends on what you mean by commercialization. In the biopharma world, small discovery companies like Tosk often provide a return to investors long before their drugs are marketed. This is possible because large pharmaceutical companies typically acquire rights to the drugs midway through clinical studies or even earlier. Our goal is to provide investors a payoff within two years by taking this route.
13What would a payoff look like?
Could be one or more of a number of possibilities. We could partner with a large pharmaceutical company, we could license a drug, or the whole company could be acquired. This is common in the biopharma world. Or we could do an IPO.
14What is your anticipated timeframe on a liquidity event for investors?
As I just suggested, we anticipate a payoff in the relatively near future. However, it’s important to keep in mind that Tosk is not a one trick pony, so we don’t want to get ahead of ourselves. TK-39 could be partnerable at an earlier stage than TK-90, or together, they would make a very nice acquisition package for a company looking to bolster its oncology pipeline. Plus any or all of the other drugs we are developing. So, we think we will have more than one option for a liquidity event in the two to three-year timeframe.
15Do you have any idea what value you could put on one or more of the drugs you’re developing?
We really couldn’t do that at this point. But what we can say is that large pharmaceutical companies are paying more than ever before to acquire drugs that expand their product lines. Deals in the $500 million to $2 billion range are common for companies with clinical stage products. In fact, recently I saw an article that indicated Sanofi is in talks to purchase Flexion Therapeutics, a Boston area biotech with a lead product in clinical studies. The price? More than a billion dollars. That’s for a company with a single product with a relatively small market - knee injections for osteoarthritis - that hasn’t received approval as yet.
16That’s amazing.
Yes, but remember, companies like Pfizer, Merck, and other large drug companies are always on the lookout for new, high value drugs to fill their pipelines. Here’s an example, Cytomx Therapeutics, an early stage oncology company like ours, has a strategic collaboration with Bristol Myers Squibb that was signed in 2014. The pair just 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 themselves 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.
17You’ve obviously been through a similar process a number of times?
Yes, I have negotiated more than 15 corporate deals during my career. 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.
18You co-founded four companies?
I co-founded and led Centaur Pharmaceuticals, Adeza Biomedical, Vesta Medical and Genelabs Technologies. I was CEO of Vesta, Adeza and Centaur, and COO/CFO of Genelabs, my first startup.
19And they all did well?
Yes, two went public, one merged with another company to go public, and one was sold to Pfizer.
20You also worked for Big Pharma before becoming a biotech entrepreneur, didn’t you?
Yes, I was recruited by Syntex Corporation, then the largest West Coast pharmaceutical company with over 10,000 employees and over 100 operating divisions, to serve as Director of Corporate Planning, managing worldwide planning activities for the company. I also participated in their corporate partnering program, in that case from the big pharma side of the table.
21What else have you done professionally?
I was a principal at Booz Allen & Hamilton and a consultant at the Boston Consulting Group.
22And you were in the Navy, right?
Yes, when I came out of Stanford with a degree in physics, I joined Admiral Hyman Rickover’s Naval Nuclear Power Program. I retired as a Lieutenant USN and returned to Stanford to study in their MBA program.
23Are 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.
24What makes you think Tosk can succeed where others have failed?
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.
25Do you have plans to commercialize this proprietary technology?
We are in early discussions with one group to address new applications of our genetically modified fruit fly technology, the one we use for kRAS drug discovery. As for side effect reduction, we plan to keep that for ourselves.
26The 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 have a fabulous team, including our scientific and medical advisors. 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. Their advice has been invaluable.
27You also have well known research and development experts leading operations
Yes, Bill Garland and Steve Yanofsky, both distinguished PhDs, lead our R&D effort. Bill is an expert in drug development, from discovery through human clinical studies, and Steve is a cell biologist, pharmacologist, and project manager. Both have worked for start-ups as well as large pharmaceutical companies such as Hoffman-LaRoche and Affymax.
28How have you capitalized the company?
We have raised almost $15 million in equity financing, most of it from private investors, and $1.7 million in grants. We have several other grants under consideration at NIH. As I mentioned, the NCI has made eliminating the toxic effects of cancer drugs a priority, and discovering a kRAS blocking drug is NCI’s highest priority.
29I read that drug development normally costs hundreds of millions or billions of dollars. How have you made the progress you have spending such a relatively small sum?
Most of that spending is in later stage, worldwide clinical studies. Those investments become the responsibility of the large pharmaceutical partner once the research has been completed by a discovery company like ours. But, even so, we are very low cost compared to the great majority of pharmaceutical companies. We have a small, dedicated, highly skilled staff that we supplement with outside experts as needed. We run a lean, highly focused company by design. We’re extremely serious about our mission to alleviate the suffering of cancer patients across the globe. In fact, most of our team has been with us for the 10+ years we’ve been in business. At the same time, we’re excited about generating a large payoff for our investors and our dedicated staff. It’s rare in this business when you can do both.