Revolutionizing the Fight Against Canine Cancer with Dr. Mark Mamula

When my senior dog was diagnosed with subcutaneous hemangiosarcoma, the weight of the fear and decision-making was immense. Now, imagine a world where innovative cancer treatments offer a glimmer of hope to pet parents.  In this episode Dr. Lindsey Wendt and I chat with immunologist, Dr. Mark Mamula  of Yale University about his  cutting-edge immunotherapy work for canine cancer.  Dr. Mamula's personal loss of a dog to cancer fuels his passion and research, making this conversation not only scientifically rich but also deeply personal.

Useful Links:
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Transcript

Speaker 1: 0:00

I want to thank both of you for jumping on and having this conversation with me, because it is a subject that's close to my heart. My 16-year-old pup recently was diagnosed with a subcutaneous hemangiocircoma and we were lucky that it was subcutaneous and we were able to take the lump out and they suggested doing some radiation just as a precaution. We opted not to do it right now. We opted, just because of his age, to just kind of do a wait and see. But I'm so curious as to how your work would really benefit pet parents, because you know it's really scary when this happens. I can tell you firsthand. So, dr Mamula, would you like to jump in and just kind of introduce yourself and tell us about the work that you do?

Speaker 2: 0:51

Oh, absolutely so. I'm Mark Mamula. I'm on the faculty at Yale University, I'm formally in the Department of Medicine in the section of rheumatology, but I am an immunologist by training and have studied immune system diseases for the better part of 35 years, and those include diseases like systemic lupus, erythematosis, type 1 diabetes. These are both fairly severe autoimmune diseases, as are diseases like multiple sclerosis and related syndromes. But that led to some of our more recent work in cancer therapies and I'm sure, as both of you know, immunotherapies have really changed the landscape of how we treat human diseases and, in a similar way, how we are thinking about treating canine cancers. Honestly, and as Lindsay can probably attest, is that therapy and treatment for canine cancers has there's been very little new out there in literally decades, and I think the field could benefit greatly from novel therapies that have been proven successful in the treatment of human cancers and they will find their way to the treatment of dog cancers. It's just taking a little time and of course, there are economic factors that come into play.

Speaker 2: 2:42

Certainly, treating human cancers is covered by insurance and treating canine cancers not necessarily so, but the important thing here is that I'm a dog lover. I have two golden retrievers. I am also a family that has lost a dog from cancer. I had a yellow Labrador retriever that passed away from a hemangiocercoma near her heart. Actually that was inoperable, and this is about 11 years ago now and I can pull up all of the thoughts and feelings that I had as a family person with a family member four-legged family member having cancer. So again, there's a lot to how I got to this place, this field, and what we're doing now and what we'll discuss today, and that's among it.

Speaker 3: 3:49

Thank you, dr Mamula. So for myself, the way that I found out about the work that you're doing is I actually so? I'm an integrative veterinarian, so I practice both conventionally and Eastern medicine, and a big part of my practice is cannabis medicine, and I do cannabis consultations for people all over the country, and I was actually working with a family on the East Coast who and it was a dog that had a hemangiocercoma that was removed. It was splenic and she had had spread to her liver, and so the pet parent is incredibly dedicated and she was looking for alternate options outside of standard chemotherapy, and so she was already pursuing a very Eastern support so herbs and mushrooms and wanted to bring in cannabis. But the other thing that she had actually been involved in is one of the clinical trials for the vaccine.

Speaker 3: 4:40

So that was the first time I had ever heard of it, and obviously I mean I'm lucky that I'm in Los Angeles and we have a very prolific oncology community here on the veterinary side, but even the oncologists I know here we're not aware of it either. So I'm so grateful that you are taking the time to share what you're doing with us so that we can share it with pet parents, and just the more exposure the better. But I'd love to start with just talking a little bit about the work that you're doing specifically with mangio sarcoma and what stage pet parents should know about it, should pursue it. I know I've heard that there's multiple clinical trials going on, but I'd love to just yeah, anything you can share about that that we can spread the knowledge we would love, sure.

Speaker 2: 5:25

Well, I'm glad you did find us, find me. We have actually gotten a fair amount of social media attention, not through my own devices, because I'm not honestly I'm not social media savvy, but I did have a couple of very happy patients start a Facebook site and we can bring up some of those details along the way as well. And I've also started a company to manage the canine cancer therapy. It's called Therajancom T-H-E-R-A-J-A-Ncom. It describes the details of our ongoing clinical trial and there is also a lot of information on a website for the canine cancer alliance, and the canine cancer alliance is home-based in Seattle.

Speaker 2: 6:37

And they've been very supportive of our studies, both financially as well as social media-wise. I have done a few video interviews for the canine cancer alliance and, for those of you who may be more interested in some of the fine detail and the mechanistic and scientific basis for our therapies, I will bore you to tears if you pull up the canine cancer alliance with a video of me going through all of that and I can distill what we're doing for radio and podcasts, of course in a more simplistic form, and I think it is actually a very straightforward therapy for what we are doing. But, dr Lindsey, you asked about hemangiocercoma in particular, and yes, that is among the canine cancers, the dog cancers that are a target of our present clinical trials. In fact, three cancers are hemangiocercoma, osteocercoma and transitional cell carcinoma, and these three cancers in dogs are a share common features, notably that they have proteins stuck on their surface of the cancer cells. It's a family of cancer proteins that are found on all three of those types of cancers. The protein is called EGFR and another member of that family is called HER2, and many of the listeners here are probably already familiar with some of these proteins.

Speaker 2: 8:37

There are immune system therapies directed at these families of proteins in human cancer care, and you really don't have to look farther than your nightly news.

Speaker 2: 8:49

Drugs like Herceptin and Herbitux are literally on the TV almost on a daily basis and they happen to be very successful immune system therapies for human disease.

Speaker 2: 9:05

So that is really the central thesis, the central target of our own immune system therapies for treating dog cancers is this family of proteins. Why are they important? Well, these proteins, both in human and in dog cancers, activate tumor cells to grow, they activate tumor cells to cause mutations and they activate tumor cells to metastasize. So all three of these features are in part controlled by this family of proteins. So consequently, both in human disease and in treating dog cancers, the basis is to stop those signaling pathways through this family of proteins that sit on the surface of the tumor cell. So, really, simply put, our therapy arises or would be given to dogs after they have been diagnosed with one of these three cancers. There are actually many cancers that are in dogs and in humans that also express this family of proteins. Among them are things like anal sac carcinomas, some forms of lung cancer, adenocarcinomas, soft tissue carcinomas, a number of different cancers in dogs, our clinical trial at the moment, however, as I mentioned, is focused primarily on osteosarcomas, hemangiosarcomas and this transitional cell carcinoma Can.

Speaker 1: 10:57

I ask what the transitional cell carcinoma is. I think a lot of pet parents are familiar with osteosarcoma because that's like a bone cancer, correct? And then the meandiosarcoma I'm familiar with only purely because of my own dog. What was the third one and how does that present itself? Just so people might be able to make a connection.

Speaker 2: 11:16

Dr Lindsey, do you want to take that, or I can't.

Speaker 3: 11:19

I'd love to. So transitional cell carcinoma is typically found either in the bladder or in the prostate. So unfortunately and I'm actually I did not know that that was part of your work, but that's very exciting because I would say that that's one of the cancers where it tends to be diagnosed fairly moderately or late into disease, because the signs that a lot of dogs and cats will present with when they have transitional cell carcinoma, or TCC as we call it, are straining to urinate and things that will mimic a urinary tract infection. So I've known a lot of patients that they have not. The disease has not been found until it was very advanced because the signs are not specific enough or like things like blood in the urine. It tends to be something we see in older dogs and we aren't even necessarily really sure of what causes it either. There's some suspicion that there might be an aspect to it of like pesticides or things in grass because animals are squatting down. So yeah, transitional cell carcinoma tends to be the urinary tract and the prostate is an extension of that. That would be a male dog, of course.

Speaker 3: 12:27

Hemangio sarcoma, as we already kind of all mentioned together, is actually a really common cancer that we'll see on an emergency presentation. So when I was working in the emergency room it was a really unfortunate and common thing for people to say, oh, my dog just collapsed and they would come in, their bellies would be full of fluid and it would be because the spleen, which is a very blood-filled organ, is the I'm pretty sure that's the most common site of Hemangio sarcoma. I'm not an oncologist but I've done a lot of oncology work throughout my career in kind of the different facets. But it tends to be oftentimes a really emergent presentation and when that happens a lot of those dogs are rushed to surgery and you don't necessarily know whether it's a cancerous mass or a giant blood clot that caused it on the spleen. So it's nerve-wracking for pet parents.

Speaker 3: 13:16

And then the other sites that we can see it there are. The other one commonly that we see that Dr Amula already mentioned is the heart and that also tends to be a very emergent presentation collapse or difficulty breathing and there's a sac around the heart that will often fill with fluid because the mass itself it's a mass of blood vessels. So bleeding tends to be something we see a lot as a symptom of that, depending on where it is. And then, like you mentioned, charlotte, the under the skin, like subcutaneous area is another spot that will see it the least scary one, the least scary, the least scary one.

Speaker 3: 13:53

And then the third, osteosorcoma yes, unfortunately also very common. That will oftentimes present, just so pet parents know, because I think this is actually a really good tie-in limping. So if you have an older dog that's limping and is not responding to therapy, especially if you're doing like, okay, let's just try pain meds and rest, and if they're not improving, I highly recommend getting x-rays, because the sooner you find it, the more options that you have for treatment. And osteosorcoma in particular, many, many dogs, at the time that they're presented and diagnosed with it, already have microscopic spread to their lungs, and so you can. A lot of people will go forward with amputation of because it tends to be on a limb like a leg, so front or a back leg. But then you also have to think about okay, now I need to do something about the fact that these cells are already most likely spread throughout the body.

Speaker 2: 14:44

Dr Lindsey, that was a perfect explanation of those three cancers actually.

Speaker 3: 14:49

Thank you very much.

Speaker 2: 14:51

And, as I was actually listening, and this may not be apparent to all pet owners is that the cancers like osteosorcoma are frequent, a very high-frequency cancer in dogs and obviously in certain large breed dogs as well. Sometimes their symptoms may be more obvious to the owners than cancers like hemangiosorcoma or the transitional cell carcinomas for which, as you point out nicely that it may not be until really advanced disease arises that the owners observe any behavioral or functional deficits in their dogs. They may see if they see a lump on the leg. That's a bit of an obvious thing and sometimes the osteosorcomas can be caught earlier. Nonetheless, it's all.

Speaker 2: 15:55

Three of these cancers are very aggressive.

Speaker 2: 16:00

The hemangiosorcoma is probably more aggressive than the others but again, always depending on the stage and location of where the tumor exists and probably a lot of other factors that we don't yet fully appreciate, and it could be things like the gender of the dog, the breed of the dog, age, and then many things like the tumor itself, how many mutations, other features of the tumor that we don't really fully understand.

Speaker 2: 16:36

Human cancers, just like in dog cancers, the same cancer can be very different in two or three or five different dogs. Different mutations, different amount of these surface proteins are expressed. Again, this is true for things like human breast cancer that can also express HER2 and EGFR. Two different patients can express very different levels of these proteins and subsequently don't respond to the same cancer therapy. The same and the same is true for dogs. We honestly have done very well in some dogs and honestly not well in some dogs. In other dogs with the same cancer, with the same type of hemangiosorcoma or the same type of osteosorcoma, and again, that's probably due to features of the tumor itself and not actually the therapy.

Speaker 1: 17:40

So how? So moving forward? So you're creating a, you're creating a vaccine, right in, that is, it's a preventative vaccine.

Speaker 2: 17:50

This is not. No, this is a therapeutic immunization. I kind of refer to it as it's an immune system based therapy. So the dog is already diagnosed with cancer and our strategy is to get immunization. And it's really two very simple subcutaneous immunizations behind the neck of the individual animal and space three weeks apart. So in that manner it's not unlike how the original COVID vaccinations were designed.

Speaker 1: 18:26

Right, that's immediately what I thought of. Yeah.

Speaker 2: 18:28

Yeah, a first vaccination and then three weeks later a second boost, and that's what we find raises immune responses against the tumor most effectively the therapy, the advantages of the therapy is that it's persistent and robust. The dog typically doesn't need another vaccination until eight to 12 months later. So an active immune response is ongoing and hopefully finding its way to tumors, whether they're metastatic sites or the primary tumor. And of course the goal of our therapy, just like other cancer therapies, is to slow cancer growth or, better yet, stop it. And of course the best of all outcomes is to eliminate tumors. And we have seen all three of those outcomes with our therapy. And so that's, you know, it's all in giving owners more months and hopefully more years with their pups.

Speaker 1: 19:41

And this would reduce the need to do treatments like chemotherapy and radiation, or is it something that would go in conjunction with or just depends on the dog?

Speaker 2: 19:50

Yeah, another great question. We're studying whether our immunotherapy is best when combined with other therapies, whether they be chemotherapies or even Eastern therapies. We don't yet have enough data. That's what the clinical trials are all about. I would guess, or I would surmise, that just like in human cancer care, where combination therapies tend to be most effective and give the best clinical outcomes, such will be the case in treating dog cancers that our immune therapy will likely end up being one component of a regiment of cancer care. Now, it's not to say that we haven't treated dogs. We have treated dogs just with our immune therapy and again, we've had some very good outcomes. But at the moment we're focusing on conventional chemotherapies combined with our immune system Therapy.

Speaker 1: 21:05

And would have you found any side effects with this yet? Or pretty.

Speaker 2: 21:10

With our therapy, with this immunization strategy, there are no systemic side effects. There will be no changes in your dog's behavior, appetite, levels of energy and other behaviors. The only one side effect, which I consider fairly minor, is about 20% of dogs one in five or two in 10, of course will get some inflammation at the site of the vaccination and that could be take the shape of a small marble-like mass underneath the site of the vaccination and in more rare cases it can get larger and it can leak a viscous fluid that is primarily immune cells. The vaccine doesn't leave the site, it doesn't travel systemically. It stays under the skin and immune cells come to the site and sample the immunization and travel back to the lymph nodes and begin to make an immune response to the tumor. This so over the course of about three weeks the dogs will end up making a very robust antibody response that hopefully starts to travel to the tumor and start blocking these growth factors right at the site of tumors and at the site of metastases to help prevent growth or even clear tumors.

Speaker 2: 22:51

We've published these studies. You can go to Google or Google Scholars and throw in a few keywords that may include my name and you'll see publications that we've done in this field and we're happy to report that we have had success in clearing metastases to the lung, in osteosarcoma at least, and Dr Lindsey can attest to the fact that one of the primary causes of morbidity and mortality in osteosarcoma, in this bone cancer, is from metastases to the lung. That's why dogs start to fail and that's what causes their eventual death from this type of cancer typically. So we've had success and we've got six cases that are documented by radiographs that have shown metastases to the lung that have cleared up within three to four, sometimes six months after our therapy. We have had long-term survivors in osteosarcoma and in hemangiosarcoma, some that have survived now as long as three years, sometimes more.

Speaker 3: 24:18

Which is amazing, I think. Oh sorry, charlotte, I was going to say. One thing to keep in mind is and, charlotte, I can go back and get the exact number for this, but typically at the time of diagnosis, if I remember correctly I want to say 90% of dogs have microscopic spread For osteosarcoma in particular, they have microscopic spread to their lungs, and so if you only do surgery, so if you only remove where the actual tumor is, still most of those dogs do not make it past three to six months, unless you are going and pursuing other therapies. So that sort of survival that he's describing is, it's miraculous. I mean that's absolutely amazing. And comparing that with the other options that you have, like radiation and chemotherapy, where there will be some degree of side effect, so that's, I mean that's, that's absolutely amazing.

Speaker 3: 25:11

And I did want to take one step back just for those that do our science and want a little bit of a breakdown. So the idea is, when we're giving this vaccine, it's a universal vaccine, so everyone's receiving the same type. There's no level of personalization to it, correct?

Speaker 2: 25:25

That's correct. Yes, okay.

Speaker 3: 25:27

So we're basically giving this. It's epithelial growth factor, so right, egf, so we're putting that under their skin and then their immune system, the dog's immune system, is going seeing that and then learning to attack it, and so that's how it goes to the cancer and knows that it's cancer. But I guess one other follow-up question I had is is there any concern? Because obviously any growth factor is present in the body for a reason, even outside of cancer cases. So is there any negative aspect for epithelial growth factor in other non-cancer areas being affected by the vaccine, or do we know?

Speaker 2: 26:07

Yeah, that's a great question. Human therapies that have been focused at epidermal growth factor receptor EGFR have a few side effects and the therapies in humans include a drug called herbitux, also known as satuximab. In humans the side effects are can, in rare, very rare cases, can be significant, but typically not. We have looked for off-target sort of other tissue effects with our immune therapy in our own patients and in fact they were done here at Yale University medical school we had taken local patients that have received our therapy and have done necropsies, postmortem studies, of virtually every tissue in the dog, from heart, liver, brain, pancreas, skin, virtually all tissues. We don't see any gross observed side effects to our therapy and the fact that dogs are, you know, surviving now two, three or four years also support the observation that there are very few or no other off-target side effects to our therapy. Just to amplify a little bit of Dr Lindsay's comments about how aggressive and fatal these cancers can be In osteosarcoma only about 30 to 35 percent of dogs will survive one year after diagnosis, which means that 65 percent, for example, will not survive even 12 months. In our published studies we find that our 12 month survival with this therapy, in addition to chemotherapy used at the same time is about 65 percent. So it nearly doubles the survivability of osteosarcoma in a wide array of dogs that have gotten this type of cancer. We're still calculating survival for hemangiosarcoma and that's part of our ongoing studies. And as you know, dr Lindsay, hemangiosarcoma is survival is measured literally in weeks, sometimes months, not years for hemangiosarcoma. So it's a significantly more aggressive cancer that has to be dealt with quickly.

Speaker 2: 29:04

Which takes me to the next point, which is early therapy is obviously the best and we try and get immune therapy going even prior to surgery for these cancers in dogs. There are no contraindications for getting immunized with our therapy before surgery. Oftentimes in osteosarcoma, dogs will be immunized at the time of amputation, which is one of the first line therapies for this bone cancer in dogs. So establishing a good, strong, anti-tumor attacking immune response is always best, the earliest you can get it going. Dogs can get chemotherapies, typically carboplatin and or doxorubicin, at the same time as being immunized with our therapy. They're not contraindicated. It doesn't dampen the immune response to these tumor proteins. So that at the moment is our strategy of our present clinical trials is to get immunotherapy going as early as possible.

Speaker 1: 30:23

So how does one become part of your clinical trials? Because I have two clients with cancer and my own dog right now, so he's looking good. We looked all over, he had all sorts of tests and he doesn't seem like it's anywhere else in his body, just in his skin. But we'd like to do everything we possibly could.

Speaker 2: 30:43

Yeah, that's terrific. You're a good mom.

Speaker 1: 30:47

Thanks, he's my guy.

Speaker 2: 30:51

So we have clinical trials going on at the moment and these are all hopefully to support eventual USDA licensing which we have applied for and we hope to be in almost any vet clinic that would want to use this therapy in the coming, hopefully three or four months from now, from December 2023. So these present clinical trials again are to support eventual USDA licensing. The present trials are supported by the USDA. They have approved all of the clinics that we are now in, which are 11 different clinics one in Canada, the other 10 in the United States. Originally the sites were Seattle, two clinics in Washington State, washington State University and Seattle the Bridge Animal Referral Center, bark as it's called, in Seattle.

Speaker 2: 31:59

We found that the need and the demand and the interest in participating in this clinical trial far exceeded the ability of those two sites to accommodate. And then we had people driving from Chicago and a couple from Florida drove to Seattle for this therapy and I honestly couldn't sleep at night knowing people were driving sick they're dogs with cancer across country just to get our therapy. So we tried to include geographically distinct sites that could accommodate people so they would have less travel time to get our therapy. So are there 10 sites, if I can remember all of them, seattle Washington State University. We had one in Santa Cruz, california, but they lost their veterinary oncologist, so they are no longer a site, unfortunately. There is a site in Phoenix, there is a site in Cincinnati, cleveland, chicago, two sites in Northern Virginia and one outside.

Speaker 1: 33:13

Toronto.

Speaker 2: 33:14

So I think I've covered all of them. We're missing sites geographically in.

Speaker 1: 33:21

Los Angeles.

Speaker 2: 33:22

Los Angeles.

Speaker 2: 33:24

And I'm a UCLA grad, so I'm remiss in not including an LA based site. So if either of you have ideas or interest in, we could potentially add a site in Los Angeles, and that is as simple as getting the USDA to agree. And there has to be a veterinary oncologist at the site because at the moment the trial is run with a staff person that can give a patient the wide array of potential cancer therapies not just our own so that can counsel them in a complete program of caring for their dog. But the clinical trial criteria are listed again on therajancom or on the Canine Cancer Alliance site and it will provide significantly more detail. It will require a referral from your general practice veterinarian and a diagnosis of one of the cancers that are in our clinical trial and then you will get seen by a board certified veterinary oncologist and you'll get terrific care at any of these sites.

Speaker 1: 34:53

Fantastic, and I'll of course put those links in the show notes so people can have easy referral to them and find them quickly if need be. Dr Lindsey, did you have a question?

Speaker 3: 35:02

I did. How challenging is it to get the USDA? I guess I'm surprised that there's not more oncologists banging down your door to want to participate in this. Is it difficult to get the USDA approval or is there some other barrier for wider the?

Speaker 2: 35:19

one barrier is that we're providing the vaccine at no cost to patients.

Speaker 2: 35:29

In full disclosure. The patients will get charged for an office visit for a professional consultation and if other therapies are included, like chemotherapy, they will have to support the cost of chemotherapy and potentially radiographs or other diagnostic elements that go along with cancer care. But our therapy itself we are not charging for. So you can now understand the economics here, which is we couldn't keep up with all of the need or the interest if we were sending out free vaccine to 300 offices. So we're a bit overwhelmed, as in just keeping up with patients at 10, 11 different sites and we're trying to collect carefully articulated clinical data that we can provide to the USDA. That will hopefully allow us to get licensing and hopefully allow us to show up in your local vet office.

Speaker 3: 36:38

Yeah, yeah, it's very exciting. And then I mean, the other thing that came to mind very quickly when you were talking is the future potential for this to be a preventative approach for the breeds that are, because there's certain breeds so just to bring everyone to the same page there are certain breeds that are very predisposed to Homanjio sarcoma and osteosarcoma in particular, and so, knowing that, so, for example, homanjio sarcoma, it's unfortunately very common in golden retrievers and German shepherds those are the two first breeds that just come to mind without me going and looking through my research and paperwork. And for osteosarcoma, as we had mentioned, it tends to be a large breed dog issue. So there's a lot of people with Rottweilers and certain breeds that, unfortunately, you have to almost be prepared for this to be something that you might encounter if you are a breed lover of one of those kiddos. So is there the potential for this in the future? If you have one of those breeds, that's a high likelihood to use this preventatively.

Speaker 2: 37:42

That is a terrific question, dr Lindsey, and really gets to the potential future of this therapy. We are considering doing preventative immunization in large breed dogs. In collaboration with a couple of the veterinary oncologists, we're trying to get some foundations to support this study because, of course, immunizing a newborn or six or eight month old Leonberger or a golden retriever or other large breed dog and then measuring the incidence of cancer in our populations versus the general population are potentially a very long term study. I would be thrilled, obviously, if it did turn out to be a preventative therapy. At the moment, however, is that we do see the need and we do see actually success in the therapeutic applications of our therapy. But in total general information, there are 60 million families with dogs in this country. There are about 90 million dogs in total. I'm adding to that group. I have two of my own, of course, so most households maybe just have one. I found that too often work better than one, so it's a bit like having siblings. Right, you'd give them siblings if hopefully, two are good playmates together.

Speaker 1: 39:26

Sometimes it goes the opposite direction. That's correct too. Then you just have two anxious dogs waiting for you to come home.

Speaker 2: 39:33

That's true too. But the unfortunate statistics among that number are that generally speaking it's accepted that one in four dogs will get some type of cancer, and if your dog is lucky enough to survive 10 years of life, the chances of your dog getting cancer are nearly one in two. And, Dr Lindsey, I'm sure amongst your practice you realize these statistics in the older dog population that you see as well. They just obviously more frequently show up with cancers. And of course similar things can be said for human cancer as well, as over time and over age the incidence of cancer goes up in the human population as well.

Speaker 1: 40:31

Wow, but one in two for dogs.

Speaker 2: 40:34

That's the estimate yep.

Speaker 1: 40:36

Yeah, you're very lucky chance. You're 16, buddy still moving and grooving. Wow, wow. You sound asleep right now you can't hear. But well, have any more questions, dr Lindsey.

Speaker 3: 40:55

I do.

Speaker 1: 40:56

Okay, good, yeah, do it, Do it. Do you have any idea?

Speaker 3: 40:59

what the price point of this will be, and I'm sure this is probably too early on to ask this, but do you think that pet insurances would cover this? I mean, I would imagine they would and I would hope that they would, but has that discussion happened with any of the big companies yet?

Speaker 2: 41:14

Yeah, those are great questions. We are not part of a big company yet. We are a mom and pop company. The Therogencom group is a group of three advisors and three scientists, at the moment keeping up with clinical trials going on at 11 sites. My rationale in developing this therapy was in hopefully making it affordable to almost anyone with a dog with cancer, with a dog that's suffering from this terrible disease. Remember, I'm a family member of a dog that suffered with this disease. I think we all appreciate how expensive veterinary care can be, depending on where you live in the country, of course. One round of chemotherapy can cost anywhere from three to $600. Am I in the right ballpark, dr Lindsey?

Speaker 3: 42:22

You are. I'll give an example At least yeah, I was gonna say in Los Angeles a full, what we call a CHOP protocol for lymphoma, because that's the one I'm most aware of financially is between eight to $12,000, going through a full series. So it is incredibly cost prohibitive for many, many families.

Speaker 2: 42:42

So add to that cost surgical fees.

Speaker 1: 42:46

Yeah, mm-hmm.

Speaker 2: 42:47

Having a hemangiocircoma excised, surgically removed or amputation in a dog with bone cancer. Add another four to six to $8,000, potentially.

Speaker 3: 43:03

Easily, Easily. And all the monitoring as well. Yeah, and all the monitoring as well the chest x-rays, all of the blood work, everything else that happens. You're right, it's easily $20,000 to $30,000 in Los Angeles. A lot of times when people are going through.

Speaker 2: 43:20

This may come back to haunt me, but I would like to be under $1,000 total for the rounds of immunization that are required of our therapy.

Speaker 3: 43:30

So that's amazing.

Speaker 2: 43:32

So hopefully we would be only a small fraction of the total cost of a patient, a dog patient's cancer care.

Speaker 3: 43:42

Yeah, and especially for families that can't afford that larger price point. I mean, yeah, something around $1,000. I mean, of course it's still a lot of money for many people, but it's, it's a great option for people that otherwise often don't even have the option to pursue chemotherapy or radiation. So that is amazing. Are you going to? This is a little bit of an aside, but are you going to look for investors or what is the plan for the expansion? Because I mean, it sounds like with the advocacy it seems like it would be something that I'm sure a lot of companies are going to come up and approach you, and I'm sure some of those are the bigger, the bigger corporations that we already know are dominating that Maryfield.

Speaker 2: 44:25

Dr Lindsey, you yet bring up another great point, which is and it is apropos to our conversations about cost and price points for therapies for dogs is that, owning the property myself and with those around me that are interested in the therapy, I can control the price.

Speaker 2: 44:53

It's not my goal to license this to a big pharmaceutical company where I no longer have control over either the product, its use or it's more important, most importantly its price. I don't want this. I am really business naive, but I'm being forced to learn some of the business of veterinary biologics. I'm a scientist and interested in the medicine and the mechanisms of treating cancer, first and foremost, and making this affordable to as many of those that need it, and the best way for me to control all of those things is by having the company that will ultimately distribute the product. Now, I do realize that I can't control what a vet in Los Angeles or in Montana or in Chicago or in New Haven, connecticut, where I am, what they will ultimately charge for it, but I do believe I can provide economic pressure. Is that a polite?

Speaker 2: 46:13

way of describing this For example, if every veterinarian knows the wholesale cost of what my immunotherapy is, it doesn't take much to figure out how much profit a practitioner is making off of it. And again, it's all in making it affordable and accessible to those that want it.

Speaker 3: 46:39

Thank you so much for taking that approach to that. I know that at your heart you're a scientist and a dog lover, but I also know that we live in a capitalist society and that there are probably many people that would be seeing dollar signs, to be very frank. So I from the dog community, I am thanking you on all of our behalf because that's so honorable to keep the ethos of why you're doing it through the whole aspect of how you're going to bring it.

Speaker 2: 47:13

Well, as I mentioned, I may have mentioned earlier, this is the most fun and rewarding program that I've had in a long professional career here at Yale University, and I'll tell you why with a couple of very simple stories. Is that, over the course of doing clinical trials and we our first round of clinical trials now date back about five years, when we were distributing our therapy to a number of other different veterinary practices I would get emails from families that would find me, and many of them would come from elderly individuals, men or women, that had lost their spouses and their dogs are either their service animals or their only companion left. And now the pup has cancer and can we help? And they're on fixed incomes and can they afford our help? Well, the way the early trials were set up was all I said was email me the address of your veterinarian and it will show up tomorrow, and it did so.

Speaker 2: 48:32

Those that could afford and donate to our program in keeping the clinical trial going were essentially subsidizing, to a point, those that couldn't afford it. And I'll tell you that's how I sleep, well, at night. And then the backside of the story is getting another email from the same family a year later saying you know, my pup is doing great thanks, and the vet said he was not going to make it another three or four or six months. And now we're a year, year and a half or two years out, and so there is no price that is worth that kind of reward to me. So that's why we're doing it.

Speaker 3: 49:25

It's beautiful.

Speaker 1: 49:26

It really is.

Speaker 3: 49:28

Are there any other kind of targets that you would want to work on, want to work on next or any other types of cancer Like, I'm just thinking, lymphoma, because we see that so commonly? Is there any kind of targeted therapy for lymphoma or any other dog or cat cancers that you're thinking of looking into?

Speaker 2: 49:47

Yeah, another terrific question. Unfortunately, lymphomas and leukemias the so-called liquid tumors because they circulate right and they originate from bone marrow typically and there are blood cancers they do not have this particular tumor surface cell surface protein. They do not have EGFR or HER2 on their surface. So we are not yet we are not a therapy for the liquid tumors, lymphomas or leukemias. We would like to understand better how certain types of lung cancer respond to our therapy. You probably see some nasopharyngeal cancers. We have a number of patients that have had cancers that affect the nasal passages, possibly bone or eye socket things like that. Cranial brain cancers. We've had success with anal sac carcinomas, the transitional cell. We're seeing good outcomes. So I think we have our hands full with a number of the solid tumors that many dogs get because, again, most of them do express this family of proteins.

Speaker 3: 51:16

Would you consider doing a trial? Because, especially for nasal adenocarcinomas so nasal cancer just again, to kind of bring everyone together is very challenging in terms of treatment. So it's usually radiation and it's very stressful as a pet parent to have a dog that has nasal cancer. They're having nosebleeds constantly. It's very challenging to manage their quality of life. So would that be a potential future study?

Speaker 2: 51:44

Absolutely yes. You bring up the challenges of treating that kind of cancer. They are frequently not eligible for surgical removal of these cancers, in part because of where they are. Honestly, they tend or can be very aggressive in moving to the eye socket or to the structures of the head, for example. So, yeah, those are particularly challenging and that is again another group of cancers that we would love to know how effective this therapy works.

Speaker 1: 52:29

Well, thank you so much. I think this was a really lovely conversation and so useful, and I can't wait to edit this and put this out into the world and give some pet parents a little bit of hope, right, so? Thank you, dr Lindsay, for joining me and asking all of the questions that I have to Google all those words now and see what some of those things mean.

Speaker 3: 52:52

I don't know. I'm happy to help and just thank you for giving the opportunity for this, charlotte. Thank you so much, and thank you so much, mark, for everything that you're doing. I'm excited to see what the future holds.

Speaker 2: 53:00

It's a pleasure to be here. Thank you for having me and would love to come back and give you results of our clinical trial and where you can find us in the future. I would love that, thanks.

Speaker 1: 53:10

Dr Lindsay.