Addressing the Need for New Drugs to Treat of Pediatric Cancers with Charles Keller, Scientific Director at the Children’s Cancer Therapy Development Institute: Audio automatically transcribed by Sonix
Addressing the Need for New Drugs to Treat of Pediatric Cancers with Charles Keller, Scientific Director at the Children’s Cancer Therapy Development Institute: this mp3 audio file was automatically transcribed by Sonix with the best speech-to-text algorithms. This transcript may contain errors.
Saul Marquez:
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Saul Marquez:
Welcome back to the Outcomes Rocket everyone, Saul Marquez is here and today I have the privilege of hosting the amazing Dr. Charles Keller. He’s a Scientific Director at the Children’s Cancer Therapy Development Institute. His research focuses on the development of more effective, less toxic therapies for childhood cancers. His special interest is advanced disease that has spread beyond the initial location of the cancer or which makes the tumor unresectable. Charles has co-chaired the Brain Tumor Development Therapeutics Committee of the Children’s Oncology Group and is a member of the Soft Tissue Sarcoma Committee of Children’s Oncology Group. He has also regularly been a standing ad hoc or ad hoc member of the NIH NCI study sections. He’s just an extraordinary person and leader. He’s got his biomedical engineering undergrad, then went to Baylor College of Medicine, where he received his M.D. degree. He is doing amazing things. And today we’re going to be covering the fantastic work that he does for four children, children specifically dealing with cancer. And so, Charles, such a pleasure to have you here with us.
Dr. Charles Keller:
Saul, I’m humbled to be here in Outcomes Rocket and I really appreciate you making childhood cancer a topic for the day.
Saul Marquez:
Absolutely. I’m looking forward to as well as all the listeners, we’re looking forward to learning from you, Charles, because there’s an opportunity to learn here. The work that you and your team does is is extraordinary for the kids that end up with cancer. And so before we dive into some of the specifics, I’d love to know more about what inspires your work and health care.
Dr. Charles Keller:
Well, I guess we all find that cause that that becomes our mission and drives us in life. Childhood cancer was that for me from the time of medical school. But that sort of in the more recent history, as we all sort of head towards midlife and re-evaluate our priorities, my four and a half year old daughter asked me if I’d ever done anything in my life, in my research life that had ever saved anyone’s life ever. And so answering a four and a half year old, that question I had to say no, which made me reevaluate the process of trying to develop childhood cancer cures and let some unusual but kind of fun non-profit biotech approach to getting basic science discoveries and certain clinical trials for children with cancer.
Saul Marquez:
Yeah, you know, it’s amazing. I was actually talking to another guest and these interactions, you never know where they’re going to come from. For you, Charles, it was that question from your four year old daughter. And for others, it’s other things, right? A conversation with a patient or one on one with an employee. But it’s a matter of being receptive to those messages when they come. And so for you, it was a hit you. And so now you’re doing something about it. Talk to us about your work and how you guys are adding value to the health care ecosystem.
Dr. Charles Keller:
Right. Well, so the Children’s Cancer Therapy Development Institute is a 501C3 non-profit biotech that tries to both understand how cancers work, but also test and evaluate thoroughly the drugs that might hit a particular target to stop the cancer from working. Then we deliver that preclinical data package to both the co-authors groups of Children’s Hospital to do the trials and the pharmaceutical companies that have the drugs. And we’re able to take a small four hundred thousand unit of research in petri dishes and test tubes and animals and bring that to de-risk the investment of pharmaceutical companies to make available six to seven hundred thousand dollars worth of drug and risk it for the cooperative group of children’s hospitals that run the trials to run a 10 and a half to 12 million dollar clinical trial.
Saul Marquez:
Well, so really, you’re providing such an incredible environment to facilitate the development of medications that work and that. So great for you to do that. And then on the pharma side, you’re helping them risk their investment. Where did you guys come up with the idea for CTI and tell us a little bit more about the spark there?
Dr. Charles Keller:
Ok, well, everything starts with the driving clinical problem. And the driving clinical problem is that in this era, there’s wonderful results for adult cancer. There are 12 or more drugs so effectively extending and saving the life of adults with cancer to earn FDA approval, but for kids, there have only been 11 instances of primary FDA approval for childhood cancer since nineteen seventy eight. So that’s eleven and forty three years for kids, but 12 every year for adults. So we had to ask, what’s the issue?
Dr. Charles Keller:
The issue is easy. It’s a really small market. There may be each year about sixteen thousand children who develop cancer, the most common form might represent slightly over a thousand patients. But for adult cancer, there’s more than one point seven million every year. And so if you have a market on average, a common childhood cancer may have four hundred patients. That’s not something that a pharmaceutical company can develop an R&D group on. It’s not necessarily something they’re going to spend their time testing drugs in hundreds of thousands of dollars worth of preclinical animal studies. But if you do the basic science research, find out what the target is delivering results of a drug, their drug that hits that target a clinically achieve levels, there are this wonderful internal champions of pharma that will say, of course, we’re very sympathetic, we have our own kids, we want to make that drug available to you, we’ll find a way. And so we’re solving what’s called the preclinical gap, the difference between universities studying the basic science of how cancer works, but then also the preclinical testing to make sure you’re picking the right drug at the right dose to get it into clinical trials so that children with cancer can have these hope filled clinical trial options.
Saul Marquez:
That’s really great. And you you called out something really, really important, Dr. Kessler, is that you have these very small populations. So the market’s small and the motivation to commercialize is not there. Right? I mean, ultimately for profit companies with the need for ROI. Unfortunately, these kids fall through the cracks. And 11 in the last 40 some years versus 12 a year is startling.
Dr. Charles Keller:
Thanks for summarizing that so well. And I think it’s hardest, of course, for the families who say that we’ve known about this cancer now for 70 years. What progress do we have? More effective treatments do we have? But if you just want to take brain tumors, for example, there have been no childhood cancer, brain tumor therapies that have received primary FDA approval in all of history. It’s just the beginning of –. There have been two secondary approvals. One was in the early 2000s for — for a very rare form of inheritable sangoma tumor for children with tuberous sclerosis. And the other drug that was developed was acnu, which is a derivative of mustard gas in nineteen seventy eight.
Saul Marquez:
And that’s it. That’s it. Crazy. I mean, it’s amazing. So then through the work that you and your team do, you’re creating this opportunity to access some potential solutions. And so I love to hear if you have any stories you’d like to tell around how you and your team have helped improve outcomes or to your daughter’s question, have you saved the life, Dad?
Dr. Charles Keller:
Well, if you’ll allow me, I’ll tell you a story of my friend David. So my friend David Glass is a muscle expert at Novartis, and his mother passed away of cancer and he realized that, no, he couldn’t do anything to help her to honor her memory for her kind of cancer. But he was a muscle expert. I studied childhood muscle cancers. And so we said, why don’t we do something together that would honor my mother by studying childhood cancer? And he said, we’ll test a few drugs. And so I said, OK, great. He said, how about 640? And I said, well, 640 sounds super because there have only been six hundred studied for childhood cancer since nineteen fifty. And he said, Charles, you really misunderstand me, I mean six hundred and forty thousand. So that’s a thousand times more than have been studied in all of our time. But Novartis did this Novartis GMF did this in a weekend. Mind you, the breast cancer research going on during the week. So they couldn’t take the robots off line, but they have enough robots to fill a football enzyme. And so there was one badly behaving robot and technician had to go in at nine forty five p.m. on a Saturday night to sort of set it back in motion. But from a Friday to a Monday, they screen six hundred and forty thousand compounds to give me an Excel file with the names of all drugs and their chemical structures and said there are thirty thousand hits, twenty four hundred super hits and four hundred and forty six super duper hits. Of those, the top 13 compounds all fall in the same cardiovascular drug class that’s been approved and safe since 1992 and extended release capsules. Why don’t you pursue that.
Saul Marquez:
Fascinating. That is fascinating. So have you pursued it?
Dr. Charles Keller:
We have.
Saul Marquez:
Tell us about that. I’d love to learn more.
Dr. Charles Keller:
Well, sure. So to make a long story short, the cell lines that we set them for the screen were from a genetically engineered mouse model that I developed back when it was trained with Nobel laureate Mario Capecchi. They’re very robust, growing cells that resemble the human disease very well. We took the compounds from Novartis, double checked them against two dozen human cells with muscle cancer. They all had activity. We did a series of compounds in the same class structure, activity, relationship that the longer the side got, the better the activity.
Dr. Charles Keller:
What we’ve done, subsequent studies to look at the different mechanisms underlying that and continue to work with Novartis on moving our lead compound to a revised lead that would not only have great cancer properties, but not affect blood pressure. And so one of those examples, there was something no one ever expected to be the right kind of drug for Charleton muscle cancer. But through simple application of existing technology and some internal champions, we now have a drug in motion.
Saul Marquez:
Wow, that’s awesome. Dr. Keller, congratulations on that. That’s amazing. Right. From a weekend of analysis, you get this. I mean, gosh, I can’t even imagine how many rows and columns were in that spreadsheet,
Dr. Charles Keller:
It’s monstrous. 80 megabytes, actually.
Saul Marquez:
So 80 megabytes worth of rows and columns. You narrow it down to about 12 and now you have a drug that is potentially beneficial to a muscle cancer and kids could potentially benefit from. As you think about different angles to provide access to this type of medicine. Obviously, the work that you guys are doing, your organization is making a difference. But what would you say is is one of the biggest setbacks you’ve experienced and maybe that other people experience in trying to make what you’ve done possible?
Dr. Charles Keller:
Right.. Well, I think it’s the same thing that we faced with those other drugs in clinical trials. So if a drug has an adult market, it has what we would call in a sort of vernacular. If a drug has an adult market to make money for it, it will be around. It can be used, it can be repurposed or have secondary purpose for children with cancer. When drugs don’t meet their endpoints for adult cancer, adult disease, they get shelved and getting it off the shelf is the absolute hardest part. Sometimes you would think it might be the easiest part, but just take a drug off the shelf and hand it over to the banker’s box worth of paperwork, because we’re double checking that the amount of drug that’s stored is still good, that it’s not since become perishable, that costs about seven hundred fifty thousand to a million dollars.
Saul Marquez:
So just to take a failed drug off of the shelf like a drug that didn’t meet its intended goal, it’s going to cost seven hundred and fifty to a million dollars.
Dr. Charles Keller:
Well, not only that Saul, but everyone heard about that drug generally moved on from that pharma company at that point. And so you have a pharmaceutical company that said from a business point of view, that drug is no longer of interest. There’s nobody who has been familiar with it anymore. You have to spin a whole new set of employees to look at all the stored information to double check the science, refamiliarize themselves with that. It’s not insignificant. There’s a lot of work to it. But sometimes, remarkably, you find internal champions that will go to bat and make this available for you. So we at CCTDI nonprofit research lab, we realized one thing very quickly. You can’t file for FDA approval for a registration trial unless you’re a for profit entity. So we did what every non-profit figures they would. We went ahead and started it paid Oregon Public Benefit Corporation for profit, pediatric cancer, biopharma, biopharma, wholly owned entirely by the non-profit 501C3. And so we have a team of people that are biopharma that have turned out on drugs to analyze them. And sort of the next natural step is to to get the investors, really the venture philanthropists, to bring forth funds to invest so that we can fulfill those term sheets.
Saul Marquez:
Well, that’s certainly noble work, Charles, and very admirable that that you guys are working to bring these things to market, just considering a lot of the obstacles and challenges that come with it. Who cares? It’s not about, hey, the market’s only a thousand. It’s every life matters. And so your your work is so meaningful. And really, I’m sure, folks, you’re listening to this today, like, wow, what a guy. Well, it’s him. It’s his team. Dr. Keller’s just providing a phenomenal opportunity for kids around the world. Kudos to you, Charles. And so as we think about what you’re most excited about today, what would you say that is and how are you approaching it?
Dr. Charles Keller:
It’s a great question. At the top of my head is the opportunities to think world first for children with cancer around the world. I think you made that point there really just in the last sentence. So one of the most interesting drugs that we have, as would help children with sarcomas, is called intensive step. It did not meet its endpoints for breast cancer. And so it’s being evaluated elsewhere in the world, particularly by a company called Edding Pharma out of Shanghai. So with one of my other collaborations I have with IBM to use the world community grid to to drug design for childhood cancers, I happen to know the head of pediatric cancer treatment, pediatric hematology oncology at Hong Kong University. And so we’re looking at a way to bring in 10 to provide in pharna to a clinical trial in Hong Kong and Shenzhen to benefit the children in Hong Kong and Shenzhen who have sarcomas. But then that information came from a Phase 2 trial we to bring it back to US for a Phase three trial.
Saul Marquez:
Well, I think that’s awesome. So now you are working globally.
Dr. Charles Keller:
It’s all about it’s all about friends and internal champions. And there’s some really amazing internal champions at Edding Pharma.
Saul Marquez:
Wow. Well, great, great call out there. And kudos to the Edding Pharma team for the work that you’re doing in collaboration with Charles and his team. There’s opportunities all around us. And I think, Dr. Kelly, you’ve mentioned find those internal champions in there. There’s other people that care. It’s just a matter of taking that first step as the first one to care and do something about it, because you will find somebody to to help support what you’re working toward. And and so I love what you guys are up to. And I’m really looking forward to seeing the work just compound. Dr. Keller, you continue doing what you do. There’s going to be solutions for a lot of these kids. And so what closing thought would you leave us all with and then work in the listeners, learn more about you and and the work that your team does?
Dr. Charles Keller:
Well, thank you for that. So the closing thought is that you can do a tremendous amount when you do this community and for a mission based cost. And then the places to reach us are on our website. So we’re at cc-tdi.org. We’re also on Facebook at cctdilab. We love to hear from people. And it’s really the opportunity to meet people who have outside expertise different from ours that generally make the difference.
Saul Marquez:
I love it. Well, folks, just a great opportunity to learn more about what Charles and his team are up to. cc-tdi.org. There’s an opportunity for you to donate to the podcast will be donating as well here. On behalf of all of our listeners, I encourage you all to do the same. We’ll leave the link there in the in the show notes. Ten dollars. Twenty five dollars. Fifty bucks, you name it. But the work that Dr. Keller and his team are doing is just incredible. We want to support him and what he’s doing. And again, I just want to thank you, Charles, for just sharing what you do with all of us. It’s inspiring and it’s certainly making a difference. So we really appreciate what you do.
Dr. Charles Keller:
Saul, thank you. We appreciate what you do a tremendous amount. Look forward to checking back with you as things progress.
Saul Marquez:
We look forward to having you back. Thanks, Charles.
Saul Marquez:
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