Veterinary Industry Insiders: Dr. Andi Flory

How can genomics help with cancer?

It helps us by really understanding that there are these changes that can either be these very small changes where just a single letter is misspelled or changes in long stretches of DNA, where we've got insertions or deletions gains and losses of long stretches of DNA or even what's called translocations where DNA strands are kind of interchanged around and infused together. And so these changes are indicative of the presence of cancer. And so if we look and we find these changes in a patient’s sample, then that indicates that there are abnormalities in the genome and those changes really don't happen with any other condition except for cancer. So when you find these abnormalities, then it's an indication of cancer cells present in the body.

When you look at all of the different processes that are going on and how the epigenome is regulating so many different processes in the body by releasing different signals and causing this, everything's happened. And there are medicines that are infecting us in our environment. What kind of clinical conditions, other than cancer, impact the results of an OncoK9 test?

So they really shouldn't. So if you think about things like infection, inflammation, you know, those sorts of things, those are not conditions that will change your underlying DNA. They won't change your genome. And so they are not likely to confuse this test. Really the thing that causes those alterations in the genome, those mutations in DNA is really cancer. So when these changes are found, it's not likely to be one of those other conditions. So other conditions are not likely to cause these changes in the genome and these changes in DNA.

Being that this is new, this is pretty groundbreaking, and exciting new technology, how's it been validated? I know that having had, unfortunately, numerous family members go through cancer and battling that, it's one thing you come up with different things that they've might want to try, but I've seen so many doctors, over time, shut down possibilities and avenues just because saying, well, that hasn't been validated. So what sort of validation have you guys gone through today?

We performed a very large clinical study and we really wanted to make this a very large collection of dogs with and without cancer. And we needed it to be a large collection because we really wanted to be able to show the power of this test as a multi-cancer test. So we had to get a really big population of dogs. So we started a study that is still a little bit mind-boggling to me that we pulled this off, but we enrolled patients at over 40 sites around the world, they were enrolled into one of three protocols. The first was for dogs that were presumably cancer-free. And what that meant is that these were generally dogs that we're presenting to their general practitioner that had no history of cancer, and there was no suspicion of cancer based on a thorough history and physical exam by the enrolling veterinarian.

Importantly, those dogs were allowed to have acute and chronic medical conditions, so they could have diabetes and Cushings, arthritis, ear infections, and any sort of atopy and any kind of inflammatory diseases, infectious, autoimmune. They also were allowed to have very common skin tumors that are benign, like lipomas, sebaceous adenomas, skin tags, and things like that. So this was a real-world population of dogs. And the dogs in that study ranged from one year of age to 15 years of age. So a very wide range in terms of the ages of dogs in that study. The second and third cohorts in the study were for dogs that had cancer whether they were being managed with surgery or not. And so these dogs had a wide range of cancer types. And so we ended up enrolling 1700 dogs into the study, which is just still so mind-blowing to me. I mean, we're used to, in veterinary medicine, reading studies, even for commonly used diagnostics that we use in the clinic every single day that are like 16 dogs, 40 dogs, 50 dogs, we get really excited when we see a study of like a hundred dogs, right? So we enrolled 1700 dogs in the study. It was really a go bigger go home kind of moment.

And what we did with those 1700 dogs is that when we were ready to do the validation and, what validation really means, determining how well does it actually perform, how well does it detect cancer in dogs with cancer, and how well does it say this patient does not have cancer in a patient that does not have cancer? So we had the data available for over 1300 dogs when we were ready to do the validation and of those, some of those patients had to be excluded because of enrollment criteria or problems with the sample or problems with the data. So it left us still with 1100 dogs that were used in validation. So still just a huge number of dogs with and without cancer. So we performed this very rigorous process there than where we split these dogs into groups and one was used to really develop the algorithm. And one was to kind of teach the test what to call cancer and what not to. And then we had a group of around 900 dogs that were used to, I think I need to restate that cause I don't remember the total number of dogs, of around give me one second. Let me just look this up. So I don't get this wrong.

How many dogs were in that part of the study?

In the validation set, so after we used the training set to kind of help to determine the algorithm and to teach the test what to call cancer. Then we had about 900 dogs in the testing set, or the validation set to really determine how well did the test perform. So in a blinded fashion, test the sample and determine how well did the test say that the cancer dogs had cancer and how well did the tests say that the dogs without cancer did not have cancer.

What were those detection rates?

I'm gonna share my screen again so that I can kind of show you. So we really wanted to look at what are the problems in veterinary medicine? Like what are the cancer types that veterinarians are seeing? And we wanted to start with the three cancers where really these are the biggest problems clinically, and those are the ones that are listed on the screen here. So lymphoma, hemangiosarcoma, and osteosarcoma are really three of the most aggressive cancers that we see in dogs. And they're very common, unfortunately. And the ability of the test, which is called OncoK9, to detect cancer in this group was 85%. So just really a phenomenal detection rate in these three most aggressive cancer types. Now, when we looked at the eight most common cancer, that I alluded to earlier that are listed on the screen here, so in addition to those top three mass cell tumor, soft tissue sarcoma, mammary gland carcinoma, anal sac adenocarcinoma, and malignant melanoma, the detection rate in this group was 62%.

So for the most common cancers that veterinarians see in practice, 62% detection or sensitivity. And then when we looked at the all-comers cohort because this was the study that allowed any cancer type to enroll. So it didn't exclude, for example, cancers that may not have as many biomarkers around, for example. The detection rate in this group was 55%. And across the study, the specificity was 98.5% meaning a false positive rate of only 1.5 percent. So really, really phenomenal detection rate and specificity as well. And I always like to kind of pause here and think about what's the current paradigm, what's our current ability to detect cancer early in our patients. And based on a study that we've done, the percentage of patients that are detected at a wellness exam, when they're feeling healthy was about 3% in our study. And the ability to detect cancer while incidentally being monitored for another disease was about 8%. So all in all that means that about 90% of pets are being diagnosed only because of the development of clinical signs when the cancer is pretty advanced. So these numbers and the ability to potentially diagnose our patients earlier are a huge improvement over the current standard of care.

Was there anything that you could kind of find, or point to any common factors for those that didn't get detected? Is there any, or is that just changed from one type to the next, in a variety of things?

That’s a great question. So some of it has to do with biology. Like if you think about the ability for a biomarker to be released into the blood into that liquid, there are some cancers that would preferentially shed their biomarker into a different liquid in the body. So if you think about tumors that are involving the urinary tract, for example, will preferentially shed more biomarkers into the urine rather than the blood. And so those are gonna be cancers where the ability to detect those would be a little bit less. In addition to that, in central nervous system tumors, you have something called the blood-brain barrier. That's really protecting the brain from the blood. And so it's not gonna be shedding a ton of biomarkers directly into the blood.

So, which patients is it best for?

So really the test is best for dogs that are at increased risk of cancer because of their age or because of their breed. So we know that cancer risk increases with age. And so there's a nine times higher risk of developing cancer for dogs that are over the age of seven. So it's really recommended as an annual screening test for dogs starting at the age of seven. However, we also know that there are some breeds that are predisposed to cancer. And so this is a list that shows breeds that are known to be predisposed to cancer. These are breeds that probably a lot of veterinarians could come and name in their sleep. Like everybody can kind of close their eyes and probably name a bunch of these, golden retrievers, boxers, German shepherds. As an oncologist, I see a lot of Bernese mountain dogs and flat-coated retrievers.

These are breeds that are known to be predisposed to cancer. And importantly, about this particular list, these are also the breeds that are the most common in the U.S. So this doesn't mean that this is an exclusive list of those predisposed breeds, but this is an example of the most common in the U.S. You also have your giant breed dogs. We know that those are predisposed to bone cancer. So dogs that are on this list, it may make sense to start screening at an age younger than seven. And that's really kind of a personal decision with the family and the veterinarian. There's kind of not a one size fits all recommendation for when cancer screening should start for all of these breeds. It kind of is a personal decision based on the family and the veterinarian's recommendation.

So when do you advise vets to use the test?

Usually, annually. So, annually is generally when most dogs are seeing their veterinarian, and that's kind of, it fits into that paradigm of care of that wellness exam. And so that's generally what's recommended is a once-a-year test. Now there are some families and some breeds that potentially doing a twice a year screening would be a good idea. We actually have a current clinical study called the cancer lifetime of screening in K9s or classic study that aims to answer the question, what sort of frequency is best. And it may be that frequency is kind of best determined by an individual. Like that there are some breeds or some ages or things like that that would benefit from a twice-yearly screen, but for most dogs we recommend annual. Now the other use of the test that I should mention is that it also can be used as an aid in diagnosis when cancer is suspected.

So let's say that a veterinarian is managing a case and they suspect cancer because of something they can see on the x-rays or something that they see on the blood work, but it could be cancer, it could be inflammatory, it could be autoimmune. And knowing which one it is could kind of help guide the decision pathway. This is a test that could be used in that situation to say are those underlying genomic alterations present in this patient that indicate that this is most likely cancer, and that could really kind of help to guide the further pathway. One thing one use that we see of it clinically is also for hesitant clients. For clients that you have suspected cancer, you've recommended a workup, they're not quite sure what they wanna do. They want a little bit more information to help make their decision, or they're not ready to schedule things or it's taking a while to get things scheduled. This is a test that can kind of help to guide that diagnostic pathway and provide some stepping stones to connect where you've recommended the case go and kind of where the client is.

I think in, in these cases where cancer is suspected, it becomes an easy path to recommend this test to the veterinarian, but when it comes to kind of the wellness screenings and introducing this maybe to a pet parent whose not sitting there suspecting their pet might have cancer yet. How would you introduce them to this idea? What would you say to veterinarians to kind of enable them and help them be able to broach the subject, make the recommendation, and actually get this as a test that's being recommended, get it on the table?

Great question. I think that one thing that can really help is to have families understand we go through this as people, right? We go through cancer screening ourselves, we get colonoscopies, mammograms, and PSA tests. And so these are tests that are all done with the intention of trying to find cancer as early as possible so that a real impact can be made. And it's known that early detection through those screening methods does improve outcomes. So I think likening it to the human experience of cancer screening is a good first step because I think that that really connects the dots and makes them realize that cancer screening is known to have true benefits in people and also in dogs. So kind of drawing that connection and helping them understand that even though your dog looks healthy now if cancer is developing if we detect it now, we're going to have a much better chance at fighting it and defeating it rather than waiting until your dog is sick.

How much does the test cost vets and what's your recommended cost to the pet owner?

The recommended cost to the pet owner is $499. And the cost to the vet can vary depending on where the test is coming from. So the test is available through our company through PetDx, but it's actually also available through IDEXX reference laboratories. So veterinarians can kind of pursue the route that is easiest for them or makes the most sense for them. But based on the research that we've done, that 499 price point is when the majority of dog owners really see the value and really will want to do this test.

What is the test? How do we get our hands on the test, or how does it, how does a veterinarian do it? And what's included, do they just take a blood draw and send it off? Or does it come as a kit? What's the test like?

So it does come as a kit. Great question. The way that it works is that veterinarians can order through IDEXX. They can request kits through IDEXX, or they can sign up with us. To sign up with us, they would send an email to [email protected]. And what happens when you send us an email at [email protected] is we send you kits that contain everything that you need to pull and package, and overnight the sample back to our lab here in San Diego. So what the kit contains are these special blood collection tubes. These are cell-free DNA optimized blood collection tubes because those fragments of DNA are very short-lived. They only really are around for minutes to hours. So they need to be stabilized with a special tube that will stabilize those delicate little fragments of DNA.

These tubes are so amazing. They do so for seven days at room temperature. So there’s no refrigeration, no freezing, there's no spinning. You don't have to send your tech to find the centrifusion, figure out how many minutes I need to do this for, and then get it on ice, and that sort of thing. You really just need to pull the blood into this tube. And the only handling is you have to kind of mix it to make sure that it adequately mixes with the preservative. And that's really it. In addition, the kit contains a vacutainer system. And this is just like, if you or I were to go to LabCorp and have our blood drawn, we would have our blood collected with the same system. It's a system that can pull the blood directly from the vein right into the tube. And it makes it super simple. And once you start using it, you kind of think why haven't we even been doing this all along in veterinary medicine, it makes things so easy.

We also provide two needles because every patient is different in terms of what your techs are gonna be comfortable with, and what's gonna be best for that patient. So we provide a straight needle and we provide a butterfly. And so these essentially just connect to this vacutainer system. And then this part, here you have your needle that's gonna go right into the patient and then your tube just clicks right in. And then you can click on and off the two different tubes. These tubes are a little bit larger than you would collect like a CBC chem. And you see there are these two lines here that are the minimum and the maximum fill line. The blood has got to be above that minimum fill line, otherwise, the test cannot be run. And that minimum fill line is seven milliliters. And the maximum fill line is eight and a half milliliters. So the minimum that we need from a patient is 14 ml of blood. So both tubes have got to be above that minimum fill line.

Does a dog need to be sedated? I know this can be a big deal for pet owners.

Generally not. Of the 1700 dogs in our study, I think it was very few of them that I don't think any of them actually had to be sedated. It's a blood collection and your teams are used to collecting blood. So just like you would experience, the vast majority of patients, you can collect blood without the need for sedation. So that's a benefit that it's a test that can help to understand whether cancer is present in your patient without the need for sedation.

You mentioned that the tube has a preservative in it, and that it's built to extend the, essentially, the usable life of that sample. Is this affected at all by things like temperature? So if we got a clinic that's in an extremely hot or cold place or something, are there any special precautions that they would need to take?

The tube can be affected by temperature. What I mean by that is that the tubes must not be, the samples must not be refrigerated or frozen intentionally, but we have had samples shipped from all over the world in all four seasons. And the temperature, those short excursions that happen during typical shipping have not affected the quality of the sample. So in general, the overnight shipping that occurs as part of this testing process generally is protective of the sample itself.

Do the kits expire? Is there any expiration on them?

Yeah, the component can expire, but if that occurs, then the hospital can just connect with us, and then we can send out additional components that are unexpired.

As you've rolled this out and you recommended your price point at $499, is this something that you've found could get covered by pet insurance?

In some cases, yes. We have talked to a lot of insurance companies that will cover it in that aid in diagnosis settings. So when a veterinarian has cancer on their differential list, they suspect cancer in this patient, and that's why they're doing the test. Generally, the insurance companies will cover it for that. In terms of the screening use case, I would say that most right now are not, but I would say stay tuned, cuz I think that that could change.

So how long does it take to get the results and how do veterinarians receive them?

Our turnaround time right now is between 10 and 12 days. And the way that veterinarians will receive the results will be generally through our veterinary portal. If they're connecting with us directly at PetDx or through IDEXX, depending on how they submitted the sample. So the turnaround time right now is like I said, between about 10 and 12 days.

Okay. And when it comes back, they're gonna see what? Cancer signal detected or undetected, like what are they gonna see? And what does it mean?

So this is what the test results look like. So it's really kind of a qualitative test result. It's really a yes, no answer. It’s a has cancer signal been detected or has cancer signal not been detected. And so it'll generally be one of these two results that you'll see that either we did detect those cancer-associated genomic alterations in the DNA, or we did not detect those cancer-associated genomic alterations. Now in the setting of a cancer signal not detected test, of course, it's important to know that if cancer is still clinically suspected in the patient, a full diagnostic evaluation should still be performed. In a cancer signal detected test result, as I mentioned before, the important thing here is that these results alone should not be used as the sole basis for making important decisions like treatment or euthanasia.

Okay. So what would they receive this, take me through for both of these things? I mean, what's the next step? What do you do if you get a cancer signal detected result?

Yeah. So in the case of a cancer signal detected result, it's gonna kind of depend on why did you do the test in the first place. Did you do the test because this is a patient that's predisposed to cancer as a screening test? So if that's the case, meaning you did not previously suspect cancer in this patient, what you're gonna wanna do is a confirmatory cancer evaluation or what we would kind of call the cancer hunt, right? So you're gonna do a thorough evaluation. You're gonna do a very thorough history. You're gonna do a thorough physical exam including an oral exam, a rectal exam, feeling the ventral neck, and filling the lymph nodes. You're gonna wanna do imaging. So you're gonna do thoracic radiographs and abdominal imaging that could involve an ultrasound and then aspirating anything that you find that's abnormal. So any lumps, bumps, enlarged lymph nodes, that sort of thing to look for, where could this cancer signal be coming from? If you've done this test because you already did suspect cancer, then this would be an indication for you to then go and perform those diagnostics to prove cancer in that patient.

So you gotta take the next step to prove it. Conversely, what if you get a cancer signal not detected result? What do you do next?

A cancer signal not detected result would kind of be a bit of peace of mind potentially. If you're dealing with a screening patient and you're looking to see if you have an indication of cancer present in this patient, then a negative result or a cancer signal not detected lowers the likelihood that that patient has cancer. It doesn't definitively say that this patient does not have cancer, but it really lowers that likelihood. But importantly, if cancer is still on the differential list, if cancer is still clinically suspected, then a full evaluation should still be performed.

OK. What if you get this in the situation that you get a cancer signal detected, so it comes back as a positive result and then they do a full workup and it doesn't find cancer. What do you say in those situations?

When we have situations like that, there are a couple of reasons that could occur. The most common is that cancer is truly present in that pet, but it just hasn't been found yet. Maybe the diagnostics that have been done just haven't detected it yet. In some cases, it could be that the cancer is small and it hasn't progressed to the point, but most of the time it's gonna be that cancer is truly present, but it just has not been detected yet. And so one of the benefits of this test really is our veterinary support. We have a veterinarian that can walk the veterinarian through every case and help them to determine what should happen and what could happen with the workup in terms of helping define that. In those rare cases where we have not found cancer after a workup, after a positive test, then what's recommended is a little bit more close monitoring of that patient. So rather than only seeing them annually, for example, that's a patient that you probably would wanna be seeing every two months to watch for developing cancer, watch for new changes in their history, changes in their physical exam, enlarged lymph nodes, that sort of thing, or development of a mass or changes on any sort of physical parameters or lab work even.

It sounds like you have a lot of resources to support veterinarians in their use of the test that they can rely on. Just based on the results that you showed from your studies a little earlier, or I think that that scenario I painted if that comes up, it's probably because your results are just far more accurate in detecting things way earlier than like any other system out there. Let me ask you, we've talked a lot about dogs and I'm a dog guy. I love my dog, but we have a cat too. Is there a cancer onco-cat-9 test or something?

Yes, exactly. So we love cats and we certainly have cats on the horizon. This test, specifically, has to be matched to a species-specific genome. So this test won't work for cats. So don't send in your cat's blood sample just yet. But it is on the horizon and we hope to be testing cats soon.

Okay. That's fantastic. What about, for a clinic to get started, you said they can reach out to IDEXX, or if they're not already working with IDEXX, they can reach out to you directly.

Right. They can reach out to us at [email protected]. Now one of the veterinary support benefits that I should mention is that we recognize the challenges that come with starting to use a new diagnostic and veterinary medicine. You're not kind of sure, well, what am I gonna do with the results? How am I gonna talk to my client about it? How am I gonna talk to them about a workup if we need to do that? So one of the programs that we actually have is called the Advanced Cancer Evaluation Support Program or ACES program. And this is a program that when you get a report that says cancer signal detect, helps to support your process by providing a thousand dollars towards that patient's workup. And so what that really does is it helps to kind of take away that concern and stress that the veterinarian has and sort of understanding, well, what am I gonna recommend to my client and really helps to support them through that process so they can understand the real benefits of this test and they can see in their patient, the ability of this test to detect cancer.

I know you're still doing ongoing clinical studies in these things, and I know that we've got some vets in the audience right now that are just going like, wow, I'd really like to be part of their future studies and stuff. How can they participate?

Sure. We would love to. We currently have enrolling and certainly future plans for a variety of different clinical studies. And if you would like to investigate to be involved in our studies, you can send us an email at [email protected]. You can also access a portion of our website at petdx.com that details some of our current and upcoming clinical studies to see if those areas might be of interest.

You can go to pet dx.com to get more information on this. You can reach out to [email protected] with inquiries, and we've got a number of things, pages, and stuff about what you guys are doing on our website. Cause I'm just a huge fan. Having lost family members to cancer and loving my pets, I don't want to see that happen. It’s just the scourge of our lives here and you guys are doing incredible work, breakthrough medicine, to just get us to the next level here where we can really fight this, and early detection, we know, is just the key. So thank you. I'm blown away. You've shared so much really great information here today. Thank you so much. Do you have any parting words?

It's just so exciting to think about how this really could change things, right? I think that we have all, as veterinarians had a client say to us, isn't there a blood test for cancer, or can't you tell if my dog has cancer from the blood work. We have all heard pet owners say that, and so the ability to do that, it never seemed to be within reach. That always seemed like science fiction. So the fact that this is here now, and to just think about how this could really be paradigm-changing in terms of our ability to detect cancer early and what that can mean on outcomes and for our patients and for their families. It's really kind of exciting. It's a really exciting time to be part of veterinary medicine.

It really, really is for a million reasons. It really, really is. I absolutely love this industry and I'm so excited to know you, to be working with you guys to help you get some exposure to veterinarians around the country that can positively impact the lives of so many pets, so many pet owners, through this. So please, everybody reach out. Dr. Flory, thank you so much again for taking some time to come on and educate us today about these incredible breakthroughs. I encourage everybody to go on and check it out.