Dr. Margaret K. Offermann, MD, PhD is a medical oncologist, tumor biologist, former Deputy National Vice President for Research at the American Cancer Society, and CEO of OncoSpherix, an early-stage cancer drug development company that is trying to significantly improve the lives of cancer patients. Join us to get to the inside scoop on how cancer treatments get discovered and tested, the challenges that are faced along the way, and why Dr. Offermann, a finalist for the 2020 Cade Prize, is so excited about her potential breakthrough.
Inventors and their inventions, welcome to Radio Cade a podcast from the Cade Museum for Creativity and Invention in Gainesville, Florida.The museum is named after James Robert Cade, who invented Gatorade in 1965. My name is Richard Miles. We'll introduce you to inventors and the things that motivate them, we'll learn about their personal stories, how their inventions work and how their ideas get from the laboratory to the marketplace.
James Di Virgilio: 0:39
Welcome to Radio Cade . I'm your host James Di Virgilio. Today we're visiting with one of our Cade prize finalists, the Cade prize rewards, inventors and entrepreneurs who demonstrate a creative approach to addressing problems in their field of expertise resulting in an innovative invention. Today, we have a special guest, both an MD and a PhD an oncologist, a tumor biologist, and an educator. Yet she is most excited about a new cancer treatment approach. So excited in fact that she is developing a company to launch this product. My guest today is Dr. Margaret Offermann. We're going to call her Kenny because she told me pre-show that that's what she likes to be addressed as. Kenny, it's a wonderful nickname. Welcome to the program. We're so excited to have you.
Dr. Offermann: 1:22
Thanks. It's a real pleasure to be here.
James Di Virgilio: 1:24
Now. Let's talk about you being the CEO of OncoSpherix and what you're developing. It's obviously a cancer drug. So many companies are working on these things. What is yours and why is it special?
Dr. Offermann: 1:35
Well, our drug development program is really focused on a common feature of nearly all solid tumors. And one of the problems with cancer is that it grows very rapidly and spreads to new places. And it's that spread that ends up being the problem with so many different patients who die of cancer. We now know that cancer cells grow faster than their blood supply. And then that creates low oxygen when they get far enough away from the blood vessels, it doesn't take very far. It's typically 10 to 15 cells away from a blood vessel. And rather than them being crippled by that low oxygen, they're actually very clever in how they fight back. What they do is respond with a master regulatory switch that allows them to bring in new blood vessels, allows them to move into those blood vessels and move to other places to set up shop in other tissues. And we have drugs that block that whole process by targeting the master regulatory proteins that not only allow but actively drive the process that allows these cancer cells to survive and spread.
James Di Virgilio: 2:59
Now, how many people per year have a type of cancer or a type of tumor that leads to the situation you just described?
Dr. Offermann: 3:05
Well if you're talking in the United States, it's roughly 600,000 people in the United States who die of cancer every year. And the vast majority of those are people who have solid tumors and the vast majority of those end up having tumors that outgrow their blood supply and express these proteins, which are called HIF 1 and HIF 2 which stands for hypoxia inducible factors one and two. And so this is where we have a lot of pre-clinical evidence, meaning in animal models, showing that we can end up preventing the growth of a variety of different types of tumors, including brain cancer, breast cancer, lung cancer, a rare eye melanoma, pancreatic cancer. So it's a wide variety that we already have data from some mouse studies. And we show not only that our drugs disrupt the growth of the primary tumor, but also prevent metastasis, which is the spread to new sites and also prolonged survival in the mice. And so we formed the company to be able to take these really encouraging results that were done by the scientific founders, from Emory and Georgia state Universities, and develop the compounds into drugs that can be used for treating human disease.
James Di Virgilio: 4:38
So let's look at this from a broad scope and I'm going to take my day to day investment manager, finance brain, and try to learn about this rather complicated, but what you are making to be accessible, medical issue, we have an aggressive growing tumor that tumor runs into a situation where it encounters low oxygen or it's hypoxic. This would normally kill regular cells I presume, or at least it would cause them problems. But in the case of this aggressive growing tumor, it's actually emboldening it. Is that a way to look at it? It's growing faster. It's basically not caring that it's in a low oxygen environment. Is that a somewhat accurate description?
Dr. Offermann: 5:12
I like your description of embolding cause that is exactly what happens. The cells in the hypoxic environment express this HIF 1 and HIF 2, it alters their energy source so that they can thrive in a hypoxic environment. Also brings in the new blood vessels and allows the cells to move into those blood vessels. And some of the genes that are induced in the scenario also contribute to the tumors, moving to new sites and thriving in new sites. So yes, it's very much is that it emboldens.
James Di Virgilio: 5:50
Do we have any treatment right now that attempts to stop this process?
Dr. Offermann: 5:55
There are some that try and deal with pieces of the process. For example, the blood vessels growing into a tumor or agents that can block that blood vessel formation. It's a process called Neoangiogenesis. So a big word that just basically means bringing new vessels into feed the growing tumor. And there are some antibodies, something called bevacizumab is one of the antibodies. And then there's, tyrosene kinase inhibitors that block the signaling that allows the blood vessels to grow. So there are treatments that address that piece of it. The problem is that there are many other pieces that aren't affected by those treatments. And not only that, but we now know that like with bevacizumab, when you block the blood vessels coming in the new ones, then you end up creating more hypoxia and you end up stimulating the hips . And so then while you may block that one small piece of the response, then the other ones are allowed to go unchecked . And so it's now known that HIF's are important in resistance to some of these treatments that specifically block the new blood vessel formation.
James Di Virgilio: 7:23
Yeah. It's a complicated system, right? I'm a big fan of chaos theory of the three body problem, which is really important and things like physics. And I think nowadays it's become something that anyone must be aware of. You can know factor A and factor B, which you're mentioning. And then you can say, okay, well, if I do this thing, if I do factor C, then this will solve the problem. Right? But in a complicated chaotic system, which the human body certainly is, that's not the way that it is. And you just kind of eloquently described what happens if you stop one thing. Well then here's these other things that happen . But so far in your pre-clinical trials, it seems that your solution is quite effective at actually stopping these variety of survival strategies.
Dr. Offermann: 8:04
It stops the variety of the survival strategies, but our treatment doesn't specifically kill all of the tumor cells. And so with you talking about blocking, one thing can end up triggering another. This is where we plan to layer our treatment on to other treatments. So that we're talking about preventing the compensatory response that occurs in these low oxygen areas, but you need to treat other parts of the tumor as well. And so we've been able to safely combine our treatment with chemotherapies that are designed to kill tumor cells and show that it's not only safely tolerated when you combine them. But also you get called synergy where you see the response with respect to tumor control. When you put agents together is superior to using them individually. And so we're quite excited about that. Once we could show that our drugs could be safely combined with other treatments, that we decided to form a company, to be able to take this forward for clinical testing and beyond in humans
James Di Virgilio: 9:25
And the year you formed the company was 2013, correct?
Dr. Offermann: 9:28
No, it was 2018.
James Di Virgilio: 9:30
You're brand new and the idea for this then came from what time period is this a two year old idea? Was this before this?
Dr. Offermann: 9:37
No, so I have the advantage of working with some outstanding academic scientists who have been working on this for more than 10 years, where they did drug screens to identify small molecules that end up inhibiting, not just HIF 1, cause there have been attempts to target HIF 1 before two major HIF's, HIF 1 and HIF 2, and some companies have tried to target either one or the other, our drug targets both. And so the scientific founders have worked on this for more than 10 years. That's where all of the animal studies with tumors has been done in their laboratories. And not only that, but they've really delved into mechanism of action so that we have a pretty good understanding on where the drugs are specifically blocking the ability of the HIF's to function.
James Di Virgilio: 10:37
So we're 10 years into this idea essentially, and we're still in a pre-clinical stage. What are the next steps look like for bringing us into not only a clinical stage, but then eventually actually bringing this to human use?
Dr. Offermann: 10:49
Well, so much of what's needed in transitioning from the academic research into clinical use is dealing with some bread and butter issues. Like how are you going to make the drug effectively? How is it going to be given? Is it going to be given orally? Is it going to be given intravenously? How often is it going to be given? If it's given orally, you have to deal with the taste and the frequency and the other issues and so we're working on that from a drug substance perspective, and then we're also working on what are the best tumors to begin with on testing it clinically and what are we going to combine it with for specific tumors? And so one of the things that we're particularly interested in testing clinically is glioblastoma multiforme, which is the most calm and aggressive brain tumor in adults. The last treatment that was approved for relapsed glioblastoma and nearly all people with glioblastoma end up relapsing, and then they become refractory to treatment. But bevacizumab the drug that inhibits new blood vessel formation through blocking something called VEGF, Dodd was approved many years ago for glioblastoma. It improves quality of life, but doesn't prolong survival. Our drug does everything that bevacizumab does plus a lot more. And we want to combine it with some other agents as an early clinical indication. So we have a lot of hoops. We have to jump through in taking our compound and making that deliverable to humans and making sure that we're safely combining it with other treatments and then testing it in a very structured way through clinical trials for treatment of humans. So, we're anticipating one of the things is that when you end up having people with relapsed cancer that have a very short survival after they relapsed , then it actually shortens the amount of time needed to show that your drug is having an impact on it. So we are anticipating that we'll be able to get into the clinic in two to three years and then have some answers pretty quickly thereafter. So Kenny, you're developing this drug, there's a long lead time. How do you fund the downtime? You're not making any revenue off this drug. You're just spending money researching and seeing if it works. So how do you survive and how do you fund it?
James Di Virgilio: 13:42
For us to get through a clinical trial for the first clinical indication, which is the glioblastoma multiforme to brain tumors, we've estimated it's going to take about $12 million and that's actually just to get through the first phase of it. And then once we end up getting through that phase, then we would expect a big valuation point and then needing many millions more to complete the clinical testing. So we're working on getting that funding and developing a strategy to be able to get it in bits and pieces. Since with us being early stage, we're concerned, we may not be able to get all 12 million in one fundraising. Now, what is it like for you Kenny, to be the CEO? You've been the Deputy National Vice President for research at the American Cancer Society. You did residency and your fellowship at U Chicago and Harvard. So you've certainly been at the top on the academic side. You've practiced as an oncologist for years, and now you're dealing with this situation. You're a CEO, you're raising funds. You're having to generate investor interest. What has that been like for you?
Dr. Offermann: 14:55
Well, one of the things that I've learned over the years is that the best way to do a good job is to surround yourself with really first rate people, because I can't know and do everything. And if I can end up having people who are at the top of their game, who can help guide me, then it's a win, win situation. And so we're working on building our team. We are in the early stages of the company we've brought on board, some fabulous people. We started with outstanding scientist who made the basic discoveries. I have the advantage of being both a tumor biologist, where I can look at the science and know that it's first rate. And I can also look at the clinical need as an oncologist and recognize where there are unmet needs, but it's the pieces in between that I really need to build the team to get us where we need to go. And that's what we're in the process of doing right now.
James Di Virgilio: 16:04
And this is going to be one of the easiest questions I've ever asked anyone on this podcast, because yours is health-related and it's cancer related, and everybody wants to fight cancer and beat cancer. But your motivations for doing this, I imagine, are not the money, not the prestige, not taking a company, potentially private to public or staying private and being fabulously wealthy, but attempting to advance the defense or the offense, if you will, against cancer, correct? That's the motivation, that's the seed idea. And now you've got something that you think may help humans.
Dr. Offermann: 16:38
That's exactly right. I've seen the pain and suffering up close and personal for all too many people who have had uncurable cancer. And the number of tools that we have to offer are growing dramatically because of the investment in research that has been made, we've learned so much about what goes wrong when cancer develops and some of the Achilles heels that can be attacked. And some of the things involve very specific tumors and very specific pathways. There's a lot of work going on with targeted therapies that are specific to specific pathways. And there's a lot going on in immunotherapy where one can harness the power of the immune system to be able to attack cancer. But despite those advances, there's still over 600,000 people per year in the United States alone who are dying of advanced cancer. And so those things aren't enough. And so this is where I'm excited about the drugs that we are developing that inhibit HIF's because they should benefit a lot of different people, improve quality of life, improve survival, and take advantage of some of the other discoveries that have been made by combining our drugs with their drugs, where it's a win, win situation. So yes, my motivation is really to help the hundreds of thousands of people in the United States and then the millions of people around the world who unfortunately have to find out that they're battling cancer.
James Di Virgilio: 18:23
Now, Kenny, let's talk about what happens here with this drug. And we'll talk about maybe the better end of variance statistically with how well it treats patients. Are we talking about adding years to their life? Are we talking about adding months to their life? What does this look like? If I have advanced cancer and it had a tumor that's growing quickly and this drug actually works as we hope it to work, how much extra time are we potentially adding?
Dr. Offermann: 18:45
Well, it really depends on the tumor and what you're combining it with. And so that's where until we end up getting into the clinical trials, I really can't answer that question. I know that's an unsatisfactory answer. I can tell you that with some of our mouse models with lung cancer and breast cancer where just using our lead clinical candidate as a single agent, without combining it with anything else in these mouse models of human cancer, we were a hundred percent blocking metastasis, and that was with several different tumor models. Now, whether that is going to occur in humans or not time will tell, but the pre-clinical data is quite exciting.
James Di Virgilio: 19:33
And if you a hundred percent block that in those mice, does that give them duration of life? That is just back to normal? What are we looking at and the animal trials?
Dr. Offermann: 19:42
So in the animal trials, it's not eliminating the primary tumor. And so that's where, when we end up combining with some other drugs, then the data, it again, depends on which particular tumor model we're looking at. And we've only recently started doing our studies with combination therapy and we have only done the combinations when testing against lung cancer. So it's really premature for me to answer exactly how long things are being prolonged. So stay tuned cause we're working on it and hope to have more detailed answers in the not too distant future.
James Di Virgilio: 20:25
Fair enough. Those are tough things to evaluate. It also illustrates why so many drug companies, it's so difficult to develop a treatment that actually works. Now, let's talk about something. That's been a narrative here recently in the public, this idea that drug companies make so much money and that drugs cost so much money once they come out. And why can't we make more affordable treatments for a variety of things. Can you speak a little bit about given all of your experience what's going on, why it's maybe difficult to create cancer or expensive R and D drug therapies for a cheap price or a treatment price?
Dr. Offermann: 21:02
Well , it really depends on the specific disease that you're going after and the specific clinical approach that you're taking. There are some treatments that are outrageously expensive to develop an example, being the cart T treatments, where you're harvesting an individual's T cells, which are an important part of the immune system, genetically engineering them, and then giving them back to the patient. So those treatments are outrageously expensive to make because you have to make it from each patient's individual cells. And the steps involved are quite labor intensive. And right now the number of patients who are benefiting from that is relatively small, so that when you factor in how one can recoup the cost of the clinical development, it gets kind of buried into the cost of treatment as well. There are a number of treatments that are kind of like still expensive to make, but not quite so expensive, like monoclonal antibodies. And then there are some treatments that are inexpensive to make some small molecules, chemical compounds like ours. So making the compounds themselves are relatively inexpensive, which is an advantage when you're looking at what contributes to cost . But the other thing that contributes to cost is how many patients you can give it to and for how long so that you can actually recover some of the cost of the clinical trials, because somebody has to ultimately pay for the treatments that are out there. And so I, as an oncologist, certainly would love to see the cost of treatments come down and access go up. And one of the things I'm excited about this particular treatment is that by having a wide spectrum of cancer types that could be treated with it. And then the fact that the underlying chemistry is relatively inexpensive. I'm certainly hoping that this is going to be something that is more affordable.
James Di Virgilio: 23:19
Well, I certainly hope so as well. And you did a great job laying out what it looks like to develop a drug. And of course the question is too reductive to say, well, everyone faces this hurdle, but oftentimes it's society to be one thing is to be cheap in an idea marketplace where everyone is able to freely work on improving things. You can rest assured that you'll get to the most efficient price. But as you mentioned, oftentimes, things are just very expensive to develop, and if you want to be able to have a treatment accessible to you, sometimes the only way to have it is for it to be very expensive in the beginning. And then eventually more people needed It becomes affordable for everyone, but that is in fact how the process works. Of course, you're on the early end of this process. Now with OncoSpherix, we like to spark wonder at the Cade or much more than a museum. In fact, really the museum is a conduit for delivering innovation and creativity. You of course are an innovator and you are creative. Do you view yourself that way?
Dr. Offermann: 24:16
I think so. Yes I do.
James Di Virgilio: 24:18
And that's fun because I like to ask that question because on paper, right, you're a scientist, you're a researcher, you're a doctor, everything about it says this person is a scientist, but in reality, you're a problem solver and creativity is problem solving. And that's exactly what we're seeing on display with what you're doing. What advice or wisdom would you give to aspiring problem solvers? No matter what field they're in to engage with the ideas they have to make the world around them better.
Dr. Offermann: 24:44
Well, part of it is having a vision and in my particular case, being an oncologist, and I've been a tumor biologist for many years where I've been trying to answer some fundamental questions initially, not really looking at how they're going to be applied, but to get a basic understanding of how things work. That is the beginning of innovation. So not answering, what's already known, but trying to delve into the unknown, then being able to apply some of that new knowledge to problems. Part of it is being part of a team and looking at the world around you and being aware of what's going on in different fields. And so how can you tap into things that are happening in other fields? And then bring them back to the questions that you're trying to address and surrounding yourself with really smart, innovative thinkers, being curious and not doing the same thing every day, being willing to take risks . So I know that's kind of meandering, so I don't see any one thing that ends up being like the magic bullet by being willing to take risks, having a vision, being curious, going into the unknown and surrounding yourself with really smart people who also are explorers .
James Di Virgilio: 26:21
Yeah, there's a lot of good wisdom in there . Cast off the fear of failure. Anyone who invents anything, does anything worth, anything will fail. That's part of the journey to progress, but failure brings learning. And as you mentioned, the more people you have around you that are smart, that are willing to fail the higher heights you can reach. And that really is how humans achieve things. It's been great to have you on the program, Dr. Offerman, better known as Kenny. I like, again, that nickname, middle name Kennedy, in case you're wondering you can find her on LinkedIn. You can also find OncoSpherix on the web, or they'll tell you a little more about what they're doing and how they're trying to solve these advanced cancer tumors with quite the innovative solution. Thank you so much for being on the program today Kenny
Dr. Offermann: 27:04
Pleasure. Thank you for having me.
Radio Cade is produced by the Cade Museum for Creativity and Invention located in Gainesville, Florida. This podcast episode's host was James Di Virgilio and Ellie Thom coordinates inventor interviews, podcasts are recorded at Hardwood Soundstage and edited and mixed by Bob McPeak . The Radio Cade theme song was produced and performed by Tracy Columns and features violinist, Jacob Lawson.