Dr. Khanna: I think the essence of practice in veterinary oncology is what I call communicative medicine, and communicative medicine to me is sort of thinking about what the family needs, thinking about what their goals are, through the lens of what they desire as an outcome, what they can tolerate in terms of risks and adverse events, and what is feasible financially. And by cobbling those three variables together, we as veterinary oncologists come up with individualized solutions for families one, two, and three, and that occurs through communication. It doesn't occur through an algorithm, which is the alternative.
Dr. Venable: Welcome to the Veterinary Cancer Pioneers Podcast, the show where we delve into the groundbreaking work of veterinary professionals who are dedicated to advancing the field of veterinary oncology. I'm your host, Dr. Rachel Venable, and I'm thrilled to embark on this journey with you.
Dr. Venable: Welcome to the Veterinary Cancer Pioneers Podcast, I'm your host, Dr. Rachel Venable, and I am so excited today to have our guest, Dr. Chand Khanna with us. His bio is quite impressive. Going through (it), Dr. Khanna is a founder and board chair of Ethos Discovery, a non-profit incubator of scientific innovation with a deep interest in solving complex medical problems and improving patient outcomes, which I definitely want to talk more about. I feel like, that's maybe even Dr. Khanna's mantra. We'll hear more, ask him some more questions about it. Dr. Khana is a veterinarian. He is a diplomate of internal medicine oncology. He also has a PhD in pathobiology. He also completed a postdoctoral fellowship in pediatric oncology branch of the the National Cancer Institute. He has worked at the National Cancer Institute as the head of the pediatric oncology branch, tumor and metastasis biology section. He is a founding director of the Center for Cancer Research Comparative Oncology Program.
He is full-tenure and senior investigator at the National Cancer Institute. He has published over 100 publications in cancer biology and therapy. He's also an editor of a recent textbook called Therapeutic Strategies in Veterinary Oncology. And he also worked in private practice in the Washington, D.C. area for several years up until 2021. He also had several leadership roles in veterinary and human oncology. So he was the president of the American College of Veterinary Internal Medicine. He has been a chair of the Children's Oncology Group Bone Biology subcommittee and the director of the Sarcoma Alliance for Research through collaboration. He's a founding member of the Canine Comparative Oncology and Genomics Consortium and he's a two-time recipient of the NCI Distinguished Mentor Award. So very fascinating resume and please help me in welcoming Dr. Khanna. Thank you so much for being with us today.
Dr. Khanna: Thank you, Rachel. It's really a great pleasure. I think that introduction is just a very polite way to say I'm a very old guy. But thank you.
Dr. Venable: Well, you know, to do all those things certainly does take time. And reading through it, I mean, I'll be honest, it's very inspiring, but it almost seems a little exhausting just going through it. Like how, I can't quite imagine how you did it. But also, to me, I feel like the big question isn't so much how, but why did you do all these things and are doing all these things?
Dr. Khanna: I'd love to be able to tell you that this was sort of a well-thought-out plan that was going to lead me here. But certainly, that's not the case. And when I talk to people early in their careers, I really advise them not to try to sort of find a beach to go sit on and figure out how their life is going to run. I'd say the short answer for me is I followed really good people. That was always what guided my decision-making. “So is this person someone I want to follow?” And if the answer was yes, I did that as well as I could. And I tried not to close any doors as I continued to follow people along the path.
Dr. Venable: I think that's great advice. Like you said, just not pigeonholing yourself, you know, be open to new ideas, but following good people, you know, following good mentors, people that can really move you forward and in directions you want to go. I also think it's fascinating how much you've been in the canine but also the human oncology world and you've certainly been a huge advocate of the One Health model and, you know, getting more awareness for dog cancer and how we can learn with people. What is it like being a veterinarian on a human oncology side, though? I'm sure (it's) very different to be a vet working with those people.
Dr. Khanna: Yeah, so that was really an exciting part of my career for a number of reasons. One is that it taught me how valued and different the veterinary perspective is, in clinical medicine and in science, and made me confident to believe that perspective was valued and worth contributing to the field. So I got to see that a lot in the research setting. MD researchers are used to knowing that veterinarians are in their institutions to care for laboratory animals, which is important work. So it was different for them to think of me as a person that wasn't there to do that, but I was there to do similar to the basic research they were doing. And I came to it asking clinical questions because I do view myself to be a clinician first. So I asked clinical questions using the same vocabulary that they had. And that I found gave them familiarity and comfort in who I was. And so when I could say, we can do this experiment with cell lines one, two, and three, and then we can move to a mouse. And I would talk to them about doing that work in the same way that they would. We were sort of on the same team, and then I'd get to sort of disrupt the world when I said, and then we can do a clinical trial in dogs. And that was really new. And because they trusted me in that discussion, mostly I think because of the vocabulary. And I think that's a really important theme for me to remember to come back to. All of this training and all these experiences are ultimately about gaining vocabulary. And by having that vocabulary, I could convince them that I was a peer, and by having them as a peer, then when I introduced this crazy idea of treating pet animals with cancer, in the context of a clinical trial, it didn't come across as such a crazy idea. because it's obviously not and we all know that. But I think if I didn't have the vocabulary that was brought to me by my training, I think I would have come across a little more crazy than I am.
Dr. Venable: I think it just cracks me up how you describe some of yourself, but I think you're being extremely modest, but that's really interesting. I've never thought about vocabulary and certainly, you have really paved the way for a lot of us. You know, I think it's fascinating using the dog and how much we can learn from each other. I really appreciate all that groundwork, you know, as you were one of the people (who) helped get that. I can't imagine the MDs and the researchers were just probably (looking) at you a little funny the first few times. I really appreciate you sticking to your guns and using that vocabulary. That's fascinating. I wouldn't have thought of that.
Dr. Khanna: Yeah, so let me just share something that I think I can put into words a little bit about how our veterinarian perspective is different and valued. And so the people I worked with at the NIH and SARC and the COG, (are) very, very smart MD scientists. And what they're really, really good at is how to ask questions that they already know how to answer. So they rarely ask a question of themselves, that they haven't got a well-resolved plan about how they're going to answer. And that's different than veterinary clinician-scientists. So what I did and what we do as a group is we think of what's an important question to ask in a specific clinical or research setting and whatever the question is, it is defined to us as a priority because of its importance, absent of our knowledge of how we're going to solve or answer that question and that is really different than how MD scientists for the most part are really good at it and it's asking only the question that they already know how they're going to answer and that it's a part of personality trait, which leads them to sort of working well within a set of guidelines and a set of rules. And to contrast ourselves, I think we work well in sort of a more open environment, a more entrepreneurial environment, where we are sort of thinking about good questions and then we figure out how we're going to possibly answer them. And I think when I thought about this, I think that comes back to our training. So, you know, the first day, you're in vet school or some point in vet school, you're sitting beside a woman who's studying respiratory diseases in feedlot cows. And on the other side, there's a guy who's studying feline asthma. And they're totally different things. But somewhere in our training, we're taught that we're going to figure this out using the same methodological approaches. And that's somehow programmed in us. So it makes us less fearful of asking questions we don't really know how to answer. And that's again, I think comes back to why we're valued in life sciences research. And I would argue not only value but necessary. These fields don't advance without that entrepreneurship. And I say that not by emphasizing a commercial or a business acumen. I think it's risk-taking. And that's what we're really good at. And we create things all the time that haven't been created. And our colleagues on the other side of the fence. And I'm not saying this to be. disrespectful of them, they're just trained in an environment where there are very established rules and you really don't ever get outside of those guardrails or those fences. And we do because we have to because there's not a lot of rules and structure around what we do professionally and otherwise.
Dr. Venable: And that's really true. I've never thought of that. But you're right, as veterinarians, you know, we have to be resourceful at times and think about, you know, there's so many species, especially when you start looking at exotic I know that was something that was always hard for me 'cause it's like, what is the dose of these drugs or what drugs can we even give? And that is interesting.I hadn't thought about that so much with contrasting with the human side. And, you know, you mentioned entrepreneurial, which certainly in your career, I would say you definitely done that, taken risk. And I wanted to learn a little bit more. So you're the founder and board chair of Ethos Discovery. Can you tell a little bit more about what that is, your mission and goals, and how you guys have been contributing to veterinary science?
Dr. Khanna: Yeah, so I'm really excited about this work of doing in this most recent phase of my career with Ethos Discovery. So Ethos Discovery is a standalone, not-for-profit incubator of scientific innovation. And it formed when the distinct commercial business launched called Ethos Vet Health. And when Ethos Vet Health formed. I was on the leadership team of Ethos Vet Health, and when that formed, we sought to differentiate that veterinary business through the optics of innovation in science and innovation in other areas, including education. And so to form an offer profit, to do de novo research within a private practice setting was right the way that we felt we could really differentiate the business, allure, attractive, and valued doctors to join the business, and then, therefore, grow the business, while doing the greater good, which is the mission of this not-for-profit, which is, as you said, to solve complex medical problems in both human and veterinary patients.
Dr. Venable: It sounds really interesting. What made you think more about private practice versus academia? Because traditionally, that's where we think of these incubators as more in an academic setting. So what made you go private?
Dr. Khanna: My professional life has been sort of a balance between practicing within veterinary oncology specialty practices, which in my case were practices that I founded, and in a different building, a short drive away, working as a research scientist within the National Institutes of Health. So I never had a reason to prioritize doing science in academia. I always had a reason and a mechanism to do science and clinical science within my own laboratory or within my own practices. So that was a natural connection to me. And again, I think the willingness to do, to take risks, and do new things was afforded by working in private practice. The caseload, which is an obvious differentiator, allowed me to quickly answer questions in clinical science that I would have had a difficult time answering in academia. And in my practice, as an oncology practice, being able to open a clinical trial, talk to owners after getting ACUC approval about the clinical trial, and then deliver them care within my practice was really a gratifying part of my professional life.
Dr. Venable: What would you say made the clinical trial so gratifying? What part of that?
Dr. Khanna: I think the essence of a practice in veterinary oncology is what I call communicative medicine and communicative medicine to me is sort of thinking about what the family needs, thinking about what their goals are, through the lens of what they desire as an outcome, what they can tolerate in terms of risks and adverse events, and what is feasible financially. And by cobbling those three variables together, we as veterinary oncologists come up with individualized solutions for family one, two, and three, and that occurs through communication. It doesn't occur through an algorithm, which is the alternative. So the algorithmic approach to medicine is what it's extreme MD orthopedic surgeons deliver algorithmic medicine. And they say this fracture by virtue of the length of this lesion and its impact on the cortex requires a screw of this size with this many grooves and a plate of this many holes. And that's defined by deep evidence and knowledge requires us doctors to deliver the care on that algorithm, but it's within very refined and constrained guardrails. Algorithmic approach to medicine is not by any means second tier. It's practice when there's deep, deep levels of evidence to underpin an algorithm and delivered by really smart people who can follow that algorithm and deliver the care to patient one, two, and three. But we, in veterinary oncology do what's quite different, which I describe as communicative medicine. So being able to distill an option in a clinical trial that solves the owner's desire for a distinct outcome, a distinct set of risks, and a distinct cost structure that just added to the number of options that I would offer an owner. When the owner said no to goals, risk, or cost of any option that I offered, then it was my job and communicative medicine to offer them something different. And ultimately, that would lead to a clinical trial as an alternative to a conventional approach.
Dr. Venable: I love that communicative medicine. I hadn't really thought of it that way, but that is great. And I love how you break it down because it really is such the big points that we have to cover in oncology. And I think we could do a whole podcast just on that. that. But today I kind of wanted to hear a little bit more about some of the research you're doing on Ethos. So we're going to shift a bit from the communication. I know you guys are doing a big program on hemangiosarcoma. And I was wondering if you could update us, kind of let us know what you guys are finding, anything exciting or unexpected with that?
Dr. Khanna: Yeah. thank you very much. So we're really excited about this work. And so hierarchies of evidence are really important to us. And unfortunately, in veterinary medicine and veterinary oncology, a lot of our opinions are formed by retrospective studies and anecdotes of other forms. And they are biased and they are flawed. And we know that, but we are convinced to forget that as we study for our board exams, and we memorize everything. And then at some point in the sort of maturation of yourself as a clinician, you realize that everything you memorize and have retold has some very fundamental inherent flaws. And there are flaws not of people trying to do good work, but flaws in the approach to take a retrospective and an anecdotal approach to delivering medicine. So we are fortunate within Ethos Discovery to have launched 400 dog randomized prospective clinical trial that's nationwide in splenic hemangiosarcoma, and specifically in splenic tumor rupture, so hemoabdomen in dogs. And although the intent of the research is to deliver curative outcomes for dogs with hemangiosarcoma, and although our preliminary assessment of our data says we are on the right track delivering those curative outcomes. Just by doing a prospective clinical trial, we've learned new things. And I'd like to summarize those because these are new things that doctors could take away and share with clients this afternoon and make a big difference in the care of patients.
So there are three points that are embedded in our message from this randomized prospective clinical trial and they're all points that relate to hope. So point number one on the message of hope in splenic hemangiosarcoma comes from our realization that the 2/3, 1/3 rule for all dogs with splenic tumor rupture or the belief that almost all older large-breed dogs with splenic tumor rupture have hemangiosarcoma, and in the retrospective literature, we know that is as low as 4% of dogs having benign tumors when they're old, large -breed dogs. And so if you look at the 2/3, 1/3 rule for all dogs of all breeds and all sizes, it becomes mostly a message shared by ER doctors, and I, as an oncologist, have... rarely have needed to use that 2/3, 1/3 rule because I'm talking about a golden retriever who is 12 years old and I know that rule doesn't apply to that dog. That dog from the retrospective literature has a very, very high risk of hemangiosarcoma, very low risk, as low as 4% having a benign tumor. But by doing this prospective clinical trial that we're doing, we've learned that that's really not true at all. And it's pretty close to 50/50 benign malignant. We're almost 300 dogs into this trial. We've published on the first 40. That was published in VCO a couple of years ago. And that same result from those first 40 continues to where we are with 300. And the number is around 40 % benign. And so you can imagine the family going to see their primary care vet or the ER vet and the ER vet relying on the retrospective data and telling them well your dog has probably got a splenic tumor rupture if it's malignant. It's the beginning of a long course of care. If it's benign, most likely cured with a surgical approach. But because you have a large older breed dog, it's almost certainly going to be malignant as they retrospect the literature would state. And that discussion eventually leading to sort of is this the best thing for your dog and what I call a misinformed euthanasia. And so that misinformed euthanasia continues to happen, although the evidence at the highest level of the pyramid would argue that that's not true. It's almost a 50/50 benign malignant. And we need, as veterinarians in general, primary care docs, ER docs and oncologists, change that discussion so that there are fewer misinformed euthanasias. That's hope number one. Benign tumors are much more common than you thought, and you should give the dog a chance by taking them to surgery.
Dr. Venable: When I think about the different rules, you know, splenic tumors, certainly we worry about hemangiosarcoma, the different sizes and things. But you're talking about non-traumatic hemoabdomen, and it's still 50/50. Because I feel like, like you said, the research, we all think non-traumatic hemoabdomen really high that it's malignant, right? Likely hemangiosarcoma. But you're saying what you guys are seeing, is it’s 50/50. Am I understanding that right?
Dr. Khanna: Yeah, so it's technically closer to 40/60. But yeah, so for me 50/50 pretty close to 50 /50. And so these are older large-breed dogs with splenic tumor ruptures. So when we look at splenic tumors that are not ruptured, it's even a higher rate of benign than what I've shared. But when they're ruptured, it's pretty close to 50/50. So I'll just transfer to hope number two. And hope number two is that greater than 95% of dogs, and these are older, large breed dogs that have entered the trial with splenic tumor rupture, walking out of the hospital in less than 40 hours. And although many younger and forward-thinking criticalists and surgeons probably know that, I trained at a time when I talked about the risks of splenectomy, reperfusion events, cardiac events, bleeding. And that also leads to the question of, do you want to put your older dog through this? And leads to this problem of misinformed euthanasia. And both of those messages, the 50/50 and the greater than 95% walking out of this, out of the hospital in 40 hours, both of these remind us that we should go ahead and recommend splenectomy. Euthanasia has a role for sure in every decision we make in veterinary medicine, but let's not let it be a misinformed euthanasia. And so having those dogs go through with splenectomy leads to better outcomes because they're more likely benign, and with the standards of care that are delivered in state of the art, especially hospitals, ER hospitals, it's almost a certainty that they're gonna get through surgery. And that wasn't maybe the case back in the day and certainly, it was not a message that I shared with clients as they contemplated this big problem on Friday night at 7:30 when they had to decide on splenectomy now, not even half an hour from now. Really tough problem. So I think we can take some pressure off and as we share this knowledge, hopefully have primary care vet doctors share that message at first presentation, reiterated by the ER doctors with the support of oncologists. But I know this is hard. So I know that we all plug our lymphoma talk into the cassette player when you're talking to the lymphoma family. And it starts and it ends almost interrupted with minor nuances as new knowledge comes forward. And to take that out and put in a new recording in this setting for the splenic tumor rupture is not easy. We've tried to do this by publishing the results and we're gonna publish on the experience at 300 dogs in. On this, again, this was not why we did the study. This was an unintended result of the study that we can share preliminarily and we shared it at the first 40. We're gonna share it again. And we can do that but it requires a doctor to either listen to this podcast or read an article and then record a new cassette for their discussion. With the owners and then even harder to get the ER vets and the primary care vets to change their message because we all sort of believe what we believe from back in the day and it's hard to imagine that not being true anymore. So it's hard, I understand that, but despite the long-term horizons for the third message of hope, which is that we actually believe we're on the right track towards delivering curative outcomes to dogs with splenic tumor rupture and hemangiosarcoma. And I can get into those details but hope number three is we believe we're on the right track there. We'll be publishing some of this data at the end of the year, and it'll still be preliminary data because, again, we're a little over two and a half years into a five-year study, and that data will mature over time. But so far, we know we're not on the wrong track. It's probably the most scientifically correct way to say what we've learned so far.
Dr. Venable: And that is really exciting, especially such a formidable cancer that honestly we haven't made much stride in a long time. You know we're still doing a lot of this same stuff. Some exciting stuff will come up and then die away. So yeah, definitely excited to learn more and hear what you guys have. I do want to touch on point number two though as far as, you know and I do think it is tragic to think about people euthanizing pets when maybe they didn't need to. And I think, like you said, it is hard to get people to learn a new message, say something else. I found some pushback originally about people wanting to do surgery, some of the different practices and places I've been. I was in the Midwest originally when I first started in private practice, and I feel like I got more of a pushback there, which I was kind of surprised, you know, my training at Colorado, we did surgery on everything. So splenectomy seemed pretty mild to me, you know. And so you're right, I think there are a lot of people out there that are still worried about all these complications. But to be honest, I know, maybe it's because I'm on the other end of the spectrum when I see the cases, but it seems honestly, fairly rare that dogs truly die or have just such severe complications post-op. Would you say that's what you guys are finding?
Dr. Khanna: It's extremely rare. We're interested to understand why that's the case. What was changed to deliver these exceptionally good outcomes, but it is almost the expectation. And so I would say that you should expect almost all dogs to walk out of the hospital in 40 hours of what we measured was the time that we measured. And that's probably a little bit of cases coming in to forecare to an ER earlier than they used to. Your cases getting cut by the primary care doctor while they're managing all of the other things that they're trying to manage in their day. And the delivery of criticalists to the care of animals, the delivery of cardiac monitoring, intra-op, post-operative, interoperative adjustments to cardiac events. Hepatonic saline before the dog goes in. I mean, you probably are gonna shudder at this, but when I trained, a dog like that came in, and you would take the largest bore catheter you could, and you'd put one in the front leg and one in the back leg, and you would get two technicians to squeeze both bags because you thought it was so important to re-perfuse them and expand their volume right away. And we now know that cautious volume expansion is better. And so maybe that's what's going on. We don't know why we're interested to figure it out, but what's undebatable is that they do exceptionally well, and all doctors along the chain need to communicate that. So people don't conclude that my old large breed dog has had a good life and this is only going to lead to hemangiosarcoma and I should probably euthanize them before surgery. That happens and for some families it's okay if there are other reasons for them to make that decision. I'm fully in support of them making that appropriate decision. And so when I think of 50/50 I mean as an oncologist that sounds like great odds to me and that's always yes. But for some people that's not good enough to go ahead. And I'm totally fine with that being the basis for them to say I'm not gonna go ahead towards a curative potential surgical approach.
Dr. Venable: Yeah, I think that does sound fair, right? But I agree as oncologist that sounds like great numbers. I think we always have to be a little bit of the internal optimist If you're an oncologist, I don't think he would last otherwise. You know, I also wanted to hear a little bit more. You said you're seeing some positive results with treatment Can you share any a little bit more specifics? Like Is it certain chemo combinations? Is it immunotherapy? Can you share anything?
Dr. Khanna: Yeah, so I can tell you about the arms in the study. I can't share really any of the data because we haven't done a formal analysis and I can tell you why I'm optimistic. But let me take a step back and tell you where the roadmap for this curative outcome comes from. So the roadmap follows the roadmap for curative outcomes in childhood leukemia. So in the '60s and '70s, cure rates for childhood leukemia, which we understand to be a mixed bag of diagnoses, was pretty poor, but generally summarized as less than 25% actually cure rate in the '60s and '70s. And the children's oncology group has sort of raised that plateau from 25% to 50% to the most recent reports being cure rates over 90%. So that's spectacular success. And if you look at the survival curves by decade, there's not like one drug that took the big jump. It's stepwise improvements. It's every child in North America being on a clinical trial that's answering an iterative clinical question to deliver that survivorship rate that's there now. And it's the children's oncology group being agnostic to the source of good ideas. So, not every new trial idea had to emerge from a specific investigator or a specific institution.The COG sort of was a clearinghouse of good ideas and they just picked the winner that was faced with them on this date and they picked that winner, they did that trial, they looked at the result, they did the next trial. So that approach is what we've used as a roadmap within Ethos Discovery. So the ideas for the arms in the trial come from any source. We have collaborators from all over the world and all forms of collaboration, biopharma, academia, human health, animal health. And so we just are picking the best bats that we think we're faced with when we start. We have a breakpoint in the study where we'll switch to a new set of drugs. But the first iteration of the trial has Dr. Rubison after splenectomy for localized. So all of these are dogs with localized splenic hemangiosarcoma. So no mets found at surgery or on chest rads, localized disease, adjuvant dox is the control. That's number one. Doxorubicin combined with sorafenib, the multi-targeted kinase inhibitor, which is different than palladia in some important ways. I just want to highlight and it's different than palladia because it simultaneously blocks VEGF and MAP kinase and that advantage reduces the risk of accelerating metastasis which has been observed in human cancers and many mouse models when you only block VEGF like you do with palladia and that acceleration is called evasive resistance and that accelerating metastatic disease even though you may shrink a measurable tumor so you avoid that with sorafenib. That was part of the biological rationale to use it. We had done the dose-finding studies, the PK studies with sorafenib prior to this study opening up. So that was another part of the rationale. Arm three is a novel formulation of rapamycin that we call RapaBoil combined with doxorubicin. And RapaBoil recognized the radiation oncologist and my business partner Ira Gordon. And for anything that I say, that sounds like an acronym, Ira Gordon is a savant of acronyms and I would just sort of say this is what we're doing. It's an oil blend of rapamycin and he would like in a second say call it RapaBoil, just somehow these things come to his mind. He's a brilliant guy and brilliant in many ways but evidenced by his ability to come up with acronyms. So RapaBoil was developed because we learned that the clean, active pharmaceutical ingredient of rapamycin when it's compounded and delivered without alteration is a pretty bad drug for dogs and we know that it doesn't work in dog osteosarcoma and I believe it doesn't work because of its poor biodistribution after being given orally and its requirement to have interrupted schedules of delivery because of toxicity so an oil blend gives a constant low rate of exposure and allows you to give it constantly in the adjuvant period, and we're able to safely do that with doxorubicin in this clinical trial. And that's the rationale for us to bring this drug forward. And as I said, like in the last instance, we've done the PK, we've done the tolerability with this new formulation of rapamycin called RapaBoil. And then the last drug in the study, the fourth arm in the study, is a drug called the Oraxol, and Oraxol is an oral formulation of taxol that's safely administered to dogs, and we've published on that data as well. I can just say that since we follow long-term adverse events in these forearms, and we've been doing that as part of our diligence in the study, too many of these dogs are doing well beyond a year for these drugs not to be working. We haven't done, as I said, any formal interim analysis that I can present, but we have done a test of futility, and I can summarize that there's no futility in what we're doing. Now, that doesn't allow me to say that what we're doing is working, it's just not futile. There's a subtle nuance of logic there, so it's not futile, but that doesn't mean that it's working, but it gives us the encouragement to stick with this and we'll expect to report the preliminary data in about 10 months.
Dr. Venable: Wow, that is really exciting. And it's a lot of different drugs, a lot of drugs that we don't use regularly. So it'll be really neat to see how everything pans out. And you mentioned a lot about PK data and that kind of thing. Cause I do think, especially with a lot of these new targeted therapies that we're hearing about, I know for me, I'm always kind of wondering, well, how do I dose it? Where do I find? So how do you recommend finding that information? Cause I personally struggle when I try to look up PubMed or just anywhere, what do you recommend when you're trying to look up that data?
Dr. Khanna: Well, so that's a great question and the answer is you can't. So there is a misbelief that you could open a Freedom of Information Act and let's say let's pick a drug, vemurafenib because of the interest that people may have in using vemurafenib to target BRAF mutation and in TCC. It's a good reason to believe that. That is a target, no evidence to know in the context TCC that it's a wise thing to do. But let's say you got over that question of context, and you said I wanna give this drug to dogs. So you could misunderstand and read articles about the development of vemurafenib in Beagle Dogs, which is available to us through freedom of information, and come up with a dose of vemurafenib that's given to beagle dogs safely. You could falsely conclude that that's a safe drug to use in dogs with cancer. It's false because beagle dogs are not 12-year-old golden retrievers with a syndrome of cancer. It's also false because the drug you're probably going to give is a compounded formulation of the API of vemurafenib, not the human vemurafenib drug, which is hard for you to get as a veterinarian and probably in the order of $6,000 a week to dose a dog. So you're probably not doing that for a variety of reasons. And so you're probably giving the API for a compounder. And now you're giving something that's never been tested, never had any PK on. And although you've read this stuff about vemuraphanib, you've read about something that's totally different, because the drug is the combination of the API plus the recipient. Pharmacologists make their livelihood by manipulating the excipient to change the drug, and we all know about this really well, because we know that doxyl is not the same as doxorubicin, because they're different formulations. And nobody would give doxyl knowing everything about doxorubicin and believing they knew how to give doxyl until you did a clinical trial with doxyl, which is a different formulation. So you have to do a clinical trial with the formulation that you're going to use to have the answer to the question you're asking. It's not available anywhere for you to look up and figure out. There's a misunderstanding that you can do that. It's just a matter of fact, you cannot do that.
Dr. Venable: Well, that explains my negative searches then. I guess.
Dr. Khanna: It is, I mean if you were to say, "Can I read about vemurafenib?" Yes. But then the conclusion is that you have to get the family to agree to, you have to find a specialty pharmacy to get the branded vemurafinib drug and pay the cost for that drug for your patient. And since that's not really what we're talking about, learning a lot about vemurafinib doesn't help you at all.
Dr. Venable: Yeah, that is really interesting. And so with your studies, like you said, you did the PK data and things. So I'm guessing when you guys go to publish, you'll probably have that cited or at least other sources where we can. Cause even some of the stuff you were saying about rapamycin, I mean, I knew, like with osteosarcoma, I saw that study, but I didn't, the bioavailability part that you're talking about, I hadn't realized. So I either missed the studies or something. So that is really interesting. And I hope you guys will add some of that into your study, just so another resource for oncologists like me where we're trying to figure out, okay, like you said, can we find the data, or does my search need to say like, okay, no, this is apples and oranges. We can't really compare it.
Dr. Khanna: Yeah. And so I can say that for sorafenib, we have published that data. For rapamycin, we've published part of it and we have not yet published the studies on oraxol. But yes, we will publish them and we'll publish them well in advance of the conclusion of this study. But all of those studies were necessary to begin to ask the question about whether the drugs work. So we have published on the PK of the variety of formulations of rapamycin, including the clean API, which was used in that osteosarcoma study. And what I conclude from those papers that I was on those publications, is the PK is highly variable. And if you were to dose the drug like an immunosuppressive drug, you seek to exceed a threshold that is defined in the human. And we do that. But when you're using it as an anti-metastatic drug, which is different, it has a different PK requirement. And that is what we modeled when we developed RapaBoil. The failure of the clean API, I hypothesize that's what was going on. There are many other possible explanations, but that is why we developed RapaBoil. But those data are published, and they're published in a variety of formulations of rapamycin. I now conclude that the clean API is the reason that the drug failed in osteosarcoma.
Dr. Venable: Interesting. So it'll be interesting to see if later on, if you can do, you know, if an RapaBoil works, like in the hemangiosarcoma, if you could then go back to osteosarcoma and see does this formulation now work like we suspected, you know, because we were hoping it would have worked in the first study.
Dr. Khanna: Yeah. So that's a great idea. And in fact, we're partly doing that now. And so we have, in addition to the interest that I've shared about hemangiosarcoma, we have a study where we're able to do pulmonary metastasectomy using a video thoracoscopic procedure, which delivers a very short, near the hemangiosarcoma, like recovery for these deep chested older dogs with mets to the lungs from osteo.
They're walking out of the clinic in very short periods of time with these three-pencil-hole incisions. This study is called MIMIC, for Minimally Invasive Metastectomy in Canines. Thanks again to Ira. That study is proving that we can deliver a short surgical recovery for these older, deep-chested dogs. And we've done that. Haven't published that yet, but we're working on those publications. Chris Thompson is the surgical oncologist leading that work. And so once we get understanding how dogs do with metastectomy after minimally invasive procedures, we'll add RapaBoil to that question and see if we can, in a shorter period of time, answer the question that was asked in the Rapamycin API clinical trial.
Dr. Venable: Yeah, that sounds really interesting. And I love all the stuff you guys are doing at Ethos. And so how can people find out more information about your clinical trials or just Ethos in general?
Dr. Khanna: Yeah, so I'd love for people to find us on social media, all channels, we have an Ethos Discovery presence, our website, Ethos Discovery website lists our clinical trials, where they're open and always happy to have people just call and say, you know, how can this client participate and we can direct them to that. So that's as simple as my email or contacting us through the website.
Dr. Venable: Well, perfect. That certainly sounds easy enough. And another exciting thing to add, you guys are going to be presenting about this hemangiosarcoma project at ACVIM. You're going to have a panel discussion with four other members of Ethos Discovery. So for people that want to learn more about this trial and just more details, ask questions live. That's a great place to do it. And it also looks like you guys are going to be at ACVS with a similar discussion. And you're also going to be talking about the osteosarcoma metastasis study. So that will all be really interesting, especially that minimally invasive surgery. I think that surgery conference, they will really want to learn more about that. So great places to hear more about your research. And I really enjoyed this conversation, learned a lot. I will definitely find those rapamycin and papers. And as we're starting to wrap this up, just the question I always ask everybody, is there someone that you would recommend to be a guest on this podcast?
Dr. Khanna: I do have someone I'd recommend. There's two people for the same reasons are Joelle Fenger, a veterinary oncologist from Ohio State originally, and Heather Wilson-Robles from Texas A&M. Both are on my Ethos Discovery team. And I think as some clinician scientists, both of them experiencing clinical science within private practice with us as team members within Ethos Discovery. I think would be interesting to hear from somebody who may have been interested in academia and wants to sort of explore a role in science while in private practice. And they're different things. And I think both of them would have interesting insights. And both of them are excellent clinician-scientists and examples of forward-thinking women clinician scientists leaders. So I think they'd be great.
Dr. Venable: That's fantastic. Yeah, they do definitely sound like great guests so we will have to reach out to them. And Dr. Khanna, again, thank you so much for being on our podcast. I learned so much, and I think all our listeners will as well. So thank you again.
Dr. Khanna: Thank you, Rachel, very much. Thank you for the opportunity, and thanks for what you're doing. I think this is really important and happy to follow-up ever I can.
Dr. Venable: Well, that's it for this episode of the Veterinary Cancer Pioneers podcast. If you enjoyed this episode and gained valuable insight, we would be so grateful if you could share our podcast with your friends and colleagues. And it would be even more wonderful if you want to give us a five-star rating, positive review, or any kind of feedback on Apple Podcasts or wherever you listen. The Veterinary Cancer Pioneers Podcast is presented to you by ImpriMed.