Guannan Wang (00:01) Hello everybody. Welcome to another episode of the VetOmics podcast, genomic diagnostics and precision medicine in veterinary oncology. This is Dr. Guanan Wang. I'm a genomic scientist and the founder of VetOmics. VetOmics is dedicated to delivering high quality, clinically actionable genomic testing for pets with cancer. As we all know, precision medicine has transformed human oncology. Yet in veterinary medicine, there are still major gaps in genomic data, real-world drug usage information, and access to better targeted and immunotherapies. At VetOmics our mission is to help close these gaps by generating robust data, advancing education, and collaborating with key stakeholders to bring practical and effective precision oncology to the pets we love, we call our family. So I'm so excited today to be joined by Dr. Aarti Sabhlok a board certified veterinary oncologist whose career Aarti Sabhlok (01:06) Shh. Guannan Wang (01:17) reflects a deep commitment to advanced cancer care, clinical expertise, and a compassionate partnership with patients and families. Dr. Sablock was born in Columbus, Ohio, and after graduating from Cornell University in 1995, she has lived and trained in many places across the country before ultimately settling in in the Bay Area. Following extensive training in both medical and radiation oncology, Dr. Sablock brings a broad and thoughtful approach to the diagnosis. Aarti Sabhlok (01:38) Okay. you Guannan Wang (01:58) and treatment of cancer in pets. She works closely with primary care veterinarians and families to develop individualized treatment plans that integrate the latest advances in oncology. Dr. Sabhlok was also an early adopter of genomic testing and has great experiences using genomic guided therapies. and she has supported us through the early days ⁓ when we first launched VetOmics Dr. Sabhlok, thank you so much for being here today. Would you like to a few words before we dive into the topics? Aarti Sabhlok (02:40) Good morning. Well, thank you for having me. I appreciate it. It's been a pleasure to work with you. So thank you for reaching out. I still remember meeting you at the Northwest meeting. ⁓ Guannan Wang (02:58) Finally, Aarti Sabhlok (02:58) ⁓ So yeah, it's been Guannan Wang (03:00) from you, Aarti Sabhlok (03:00) a pleasure. You're just, I think what I appreciate most is you're always there to answer questions and I usually have a lot of them, so I appreciate that. Guannan Wang (03:13) Glad we can answer your questions. And we've also learned so much from you. So the feeling is mutual. So ⁓ to start our discussion, I would love to hear your overall perspective on genomic testing. You have ⁓ analyzed so many cases. You're probably like up there on the top. Aarti Sabhlok (03:16) Yeah. I appreciate it. I appreciate it. Yeah. Now, I started, I think when it was first available, just now many years ago. I think the hard thing is, I've been doing this for more years than I want to say out loud. I think the, yes, very experienced. At some point I realized that I was doing the same things. Guannan Wang (03:41) Yeah. That means experience. Aarti Sabhlok (04:09) and I was getting the same results. And as a private practice oncologist, I don't do a lot of clinical trials. And so I really, wanted more tools in my toolbox to help my patients, right? So whether that was, hey, we've completed traditional chemo and now we need something to maintain the patient or whether traditional therapy is not working or whether we can add it to what we're doing. the longer it's been around, more studies that are being done, the more we're extrapolating from what people are doing. I think there's more and more we can do with targeted therapy, just is, like I said, it's just, like having as many tools in my toolbox as I can when I'm talking to my clients and offering options. It's hard, you know, to go into a room and talk to a family about their family member, their pet, and say, well, this is all I have to offer And so I think that was one of the reasons I adopted it early was just to see and you know explaining to clients that at least in the beginning the data was very limited. We thankfully have more data now. ⁓ So yeah, and I said I do apologize. I have a little bit of a cold. So just bear with me this morning. Yeah, yeah. Guannan Wang (05:08) Thank you. Yes. Mm-hmm. Yeah. I appreciate that you are able to join us despite of the cold. Hope you feel better. So I hear that these tests offer more options now with the comprehensive genomic profiling. We are offering not only the conventional like Aarti Sabhlok (05:34) Yeah. Thank you. Yeah, thank you. Guannan Wang (05:57) targeted small molecular inhibitors, but also immunotherapies, right? So that's super, super exciting for all of us to be able to have our own immune checkpoint inhibitors for dogs, hopefully for other species as well. do you see clear measurable ⁓ benefit for ⁓ Aarti Sabhlok (06:01) Yep. Guannan Wang (06:20) your patients, is this something that can prolong survival? Do you see overall trend or more as meaningful benefit in selected individual cases? Aarti Sabhlok (06:31) Yeah, I mean, I think that is a part that we're still, at least I'm still figuring out, right? I do, I tend to offer it to a lot of my clients, osteosarcoma, hemangiosarcoma. We have standard of care, but I do feel, especially for hemangiosarcoma, that targeted therapy is becoming part of standard of care. Guannan Wang (06:41) Mm-hmm. Yeah. Aarti Sabhlok (06:54) And I do think that we'll see that as we have more cases, we'll see that in other cancers, because in human medicine, targeted therapy is becoming standard of care combined with in lymphoma cases, right? Where they're combining immunotherapy, chemotherapy, and now targeted therapy. So I feel like that path that we're heading that way. I have one case right now, because I just saw them a couple of weeks ago where Guannan Wang (07:10) Exactly. Exactly. Aarti Sabhlok (07:23) We did targeted therapy. The patient had hemangiosarcoma, had early metastasis less than six months on standard treatment. And we did chest x-rays. The metastatic lesions were small, but they were definitely there, confirmed by a radiologist. And the owners had already elected to do targeted therapy when I first met with them. Kind of the plan had been do traditional. and then as maintenance maybe do targeted therapy. So we just shifted a little early on the plan and at their two month recheck, we did recheck x-rays and the pulmonary nodules, there were fewer of them. so, right, that's ⁓ that's measurable response. I think in a lot of patients I treat, I'm treating microscopic disease, not visible disease. Guannan Wang (08:06) Yeah, yeah. Aarti Sabhlok (08:13) And I can say, yes, those patients lived longer than the average patient, but I don't have something I can measure to show direct response. So this was a patient where truly there was a measurable response to the treatment that we did, which was, mean, the family is ecstatic, so that's why we do it. And I think for immunotherapy, ⁓ the checkpoint inhibitor, the Gilgatmab, was really, right, what they released it for was melanoma. Guannan Wang (08:32) Yes. Aarti Sabhlok (08:42) and mast cell, right? I've now used it for a variety of tumors based on genomic testing. And so I have another one I'm about to start. it's, you know, I reached out to Merck to talk to them about potentially doing a study because one of the tumors in human medicine that's treated with checkpoint inhibitors is transitional cell carcinoma. And so I think I've treated at least three of those at this point with gilvetmab Guannan Wang (08:42) I felt humor. Yeah, Okay. Aarti Sabhlok (09:11) ⁓ The responses have been mixed and I do think that ⁓ unfortunately in the first two cases it was one of the last therapies that we did. So I feel like the benefit was muted in that situation. Also in human medicine they show that checkpoint inhibitors are most effective when combined with chemotherapy. So I think using it earlier on would be more beneficial. So I'm still excited about it but. Guannan Wang (09:20) Yeah. Yeah. Aarti Sabhlok (09:40) Yeah, so that's. Guannan Wang (09:41) So mixed experience, right? Mixed experience. Aarti Sabhlok (09:44) mixed experience, but I think the fact that it comes up on their reports is exciting, right? I've gotten a number of reports where gilvetmab is one of the treatment options, and I never even would have thought about it because that's not what it's been marketed as. So that's been exciting as one, a world of drugs that we don't traditionally use, and then two, drugs that have been marketed for something else that Guannan Wang (09:49) Yeah. Mm-hmm. Aarti Sabhlok (10:13) that might, and especially if you look at human medicine, checkpoint inhibitors treat so many different cancers, right? And that's... ⁓ Guannan Wang (10:20) Yeah, across all solid tumor, think. Aarti Sabhlok (10:24) Correct, yeah, and I think that's what we're going to see in veterinary medicine over time as well, hopefully. Guannan Wang (10:31) Hopefully, and we actually have ⁓ genomic data to support that. We just need to actually test it in patients. We're here in that clinical data. we, ⁓ like the immunotherapy, so it's such good ⁓ area, right? Everybody is so excited, including myself. Aarti Sabhlok (10:40) Yeah, I'm here. I'm here to help. Guannan Wang (10:56) But we have to also bear in mind that even on the human side with biomarker stratification, immunotherapy, immune checkpoint inhibitors are ones that when they work, they work beautifully, but they only work in a small percentage of patients, like 30, 40%. And so that's what makes the biomarker stratification. Aarti Sabhlok (11:14) Yeah. Yeah. Guannan Wang (11:24) that much more important because you want to identify those patients to kind treat with these not inexpensive, therapies, right? as you mentioned, gilvetmab and others do come up on our report if we see like a high tumor mutation burden. ⁓ we've had Aarti Sabhlok (11:32) right. Yes. Mm-hmm. Guannan Wang (11:47) examples cases that respond beautifully to gilvetmab Like it's surprising. But we've also had patients that, gilvetmab was recommended, but the patient did not receive the benefit as we were hoping for, and which suggests that there might be Aarti Sabhlok (11:47) Okay. Guannan Wang (12:08) Other factors that play into the response, for example, you mentioned that, some of these patients, they receive gilvetmab as their last resolve, last treatment. At that point, are their, immune system still, fit or still good, to ⁓ boost that immune response? So that's also another. Aarti Sabhlok (12:17) Yeah. Okay. Guannan Wang (12:31) anotehr factor as Dr. Nicola Mason and I recently had an exchange about these immune therapies that you need to have everything perfect, right? You have the tumor that are, higher tumor mutation burden, which is the strongest biomarker for immune checkpoint inhibitors that allows the generation of more neo antigens that are being able to present on the tumor surface for T cells or B cells to recognize. But you also need to have a very, very functional fit immune system, right? The population Aarti Sabhlok (13:11) Right. Guannan Wang (13:13) to be able to launch that ⁓ immune response. That does make me wonder that instead of using gilvetmab as a last case, when the dog was not so sick, it might be more helpful, but we need to actually see what we find from the patients. Aarti Sabhlok (13:34) Is there a way in the genomic testing to see if you use something like gilvetmab whether there is an ideal targeted therapy or chemotherapy that should be used with it. Yeah. Guannan Wang (13:47) I can combine combined with yeah, as you know, we identify ⁓ multiple lines of treatment recommendations. which one is most likely potential driver and ⁓ the allele frequency, level of copy number changes, and the functional evidence of the mutations and evidence level of the association between the mutation and the drug. So multifactorial ⁓ decision-making process before we prioritize. And we prioritize gilbetmab sometimes if the evidence is strong But on the second line, there's always either another target therapy or immunotherapy. So some of our doctors, they start to ask the question, can we combine these drugs? Aarti Sabhlok (14:35) Yeah. Right. Right. Guannan Wang (14:47) at least based on what the clinical data either on the human side or on the dog side. the top recommended therapies, tend to respond better. Yeah. Aarti Sabhlok (15:00) Yeah, do. I will often when you give me multiple drugs, I will often look on the human side to see if there are studies where those drugs have been combined so that I can maximize what the information that you've provided to me. I do, you know, I do try to do my due diligence to see, you know, Guannan Wang (15:07) Yeah. Thank you. Bye. Yeah. Yeah. Aarti Sabhlok (15:23) Is there, are there studies, is there benefit, are there risks of combining various drugs together? You know, I know dogs aren't people, but I think at least we can extrapolate some information to see, yeah. At least to see if those drugs have been used together, right? Cause, yeah. Guannan Wang (15:27) Yeah. Mm-hmm. information from human. Yeah, exactly. Yeah, yeah, yeah, exactly. And we also have a growing body of canine data from doctors like you yourself, ⁓ very experienced, very comfortable with using these drugs. And when they see that these drugs are generally pretty well tolerated in most of their patients, so they start to combine with ⁓ Aarti Sabhlok (15:51) Yeah. Guannan Wang (16:09) conventional chemotherapy or combine with newer therapies. we have a spreadsheet where we list all the possibilities of combination. So that's definitely growing and based on real-world data, which is still limited, better than nothing, better than when we first started. Aarti Sabhlok (16:19) Yeah. Great. I have faith. have faith you're gonna get it. mean, you know, I think you can put together. Happens to you. Yeah, I think so. Guannan Wang (16:35) And you contribute to those data as well. Yes. That's exciting. I hear both ⁓ memorable cases where you see measurable success, but mostly these are immeasurable, in the maintenance setting. So they do live longer than you think they would live otherwise. Aarti Sabhlok (16:57) Yeah. Guannan Wang (17:03) Maybe that's something. ⁓ So, exciting to hear that. So, yeah. Yeah, yeah. Exactly. There are two types of emails I like to receive the best. So, ⁓ not that I dislike receiving some, but there are two that can really make my day, two types. One. Aarti Sabhlok (17:09) Yeah, for sure. I'm sure the clients are very excited, right? So then that that trickles down to all of us when they're excited. Yeah. Yeah Guannan Wang (17:33) is when you guys send me pictures of patients responding. we received many of those. a single agent, targeted therapy and, the dog has lived much, much longer than expected. That's definitely my favorite kind. There is another kind where doctors ⁓ send me an email. so Fluffy's disease progressed on this drug. Now, what do we do? Do we move on to the next one? Can we combine with something? although these types of email is more, disappointing and depressing, But disappointing. I know. disappointing. ⁓ from that point, so we can actually learn from that patient because, okay, Fluffy did not respond to this drug in this genomic context So what do we Aarti Sabhlok (18:14) disappointing, but as long as the patient's feeling well, yeah, it's disappointing. Guannan Wang (18:38) do now. This could be an isolated case, but this could suggest a trend, So that's something that, feedback to our recommendation protocols, where we can actually learn from that. So although it's, negative results, but we still consider helpful, valuable for developing Aarti Sabhlok (18:59) Yeah. Yeah. Guannan Wang (19:02) how we best recommend and prioritize drugs. So far, because of the breadth and depth of the test we offer, we are able to, most of the cases, ⁓ provide recommendations for more than three recommendations, which makes Aarti Sabhlok (19:20) Yeah. Guannan Wang (19:23) prioritization important, What do you start first to achieve that best response? we also have the next in line recommendations should the first line fail also, rational combination, right? Okay, if you want to combine instead of combine with anything else, maybe, combine with drugs that Aarti Sabhlok (19:26) Yeah. Yeah. Guannan Wang (19:45) we have a genomic indication on. So that's something that ⁓ we've heard some positive feedback on. So hopefully as we receive more real world data and we can showcase that these genomic guided therapy can prolong survival and have meaningful benefit. Yeah. Aarti Sabhlok (20:08) I mean, I'm a, you know, I'm a fan, right? So I'm a big fan. mean, it's, again, it's, ⁓ Guannan Wang (20:13) You are a big fan. I love it. It took us a while to reconnect, what you said. at last year's NW oncology meeting, you said, I'm going to send you so many cases. Don't worry. Because at that time, ⁓ Aarti Sabhlok (20:31) Yeah. Guannan Wang (20:35) we were just starting, So we, you That was last year. That was last year, just last year. It feels like you've been so wonderful. So that's why, you know, like sometime in my head I was like, okay, even though we don't have that much of a real world data. Aarti Sabhlok (20:37) That was a couple of years ago, right? Yeah. Was it really just last year? ⁓ goodness. Okay, seems like it's been a lot longer than that. Okay. Yeah. Guannan Wang (20:58) to justify the test or the benefit. At least our frequent users are still using us frequently. We're gaining more new users, I'm so grateful for the whole community. So it's word of mouth, a recommendation. But I hope deep down that this really help with your practice, help with your patients. Aarti Sabhlok (20:59) it. Yeah. For sure. Yeah. I mean, I wouldn't continue to use it if I hadn't seen benefit, right? I've definitely seen it. I think also there is a population of pet parents that don't want to do traditional chemo. whether it's been a personal experience, they've had that experience with the previous pet. And so going down the road of traditional chemo just does not feel right. And so I feel like this gives them another option, right? I mean, and again, Guannan Wang (21:28) Exactly. Yeah. Yeah, exactly. Yeah, yeah. Yeah, yeah. Mm-hmm. Yeah. Yeah. Aarti Sabhlok (21:53) the data of how much this is going to help targeted therapy without traditional therapy. We're still getting there, we don't know. But I do feel like for some parents that this sits better. And so they're more comfortable doing medications at home or their pet gets too stressed coming into the vet's office more than once a month. And so it provides another avenue of treatment. Yeah, I have a new colleague that joined. Guannan Wang (21:57) . Yeah. Yeah. Yeah. Great, great. Aarti Sabhlok (22:21) in October, he's now using Vetomics as well. He didn't do that much of it or he didn't do any of it ⁓ in his residency. So I've got him on the bandwagon. Guannan Wang (22:22) huh. Yes. That's the next generation. Yeah, we have a few of them when they are still in residency program, they start to use us I remember leukemia case, after we reported out and like, Aarti Sabhlok (22:38) Yep, next generation, yeah. Guannan Wang (22:53) a few weeks after and then, you know, they reached back out. were like, he is responding, which is unbelievable that's really amazing to hear. we said, let's, follow up and, hopefully the response prolongs. ⁓ And then we can write a case highlight. My favorite Yeah. Aarti Sabhlok (23:00) Yeah Yeah, great. I mean, again, right, the more cases, the more data and good and bad, as you said earlier, I think even the cases that don't respond teach us something. Guannan Wang (23:17) Yeah. Exactly, exactly. Negative results are not bad at all. valuable to add into our data set. So you recommend genomic testing for a lot of your patients. Do you have a favorite cancer type that you always recommend, or this is a pretty Aarti Sabhlok (23:31) Right. Right. is by far the most common cancer I recommended for, but probably hemangiosarcoma, tumors where I don't have a lot of traditional options. ⁓ I mean, even for other cases, so things like lymphoma, I may not, I talk about it upfront, realizing that we, for a lot of the cancers that have standard of care, Guannan Wang (24:05) Mm-hmm. Aarti Sabhlok (24:11) People are overwhelmed at that first appointment when we talk about all of the options. So I do, I often with something like lymphoma, we'll bring it up in the beginning and then we will revisit it once the patient has started therapy, they're feeling better. It's like, okay, you know, let's re talk about this therapy. Do you have an interest? Where does it fit into what we're doing? And some of that again is extrapolating from people. And some of that is just what we've seen in veterinary medicine, talking to colleagues. Guannan Wang (24:15) Yeah. Mm-hmm. Hmm. Yeah. Yeah. Yes. Aarti Sabhlok (24:40) So, hemangiosarcoma by far, do, clients want to do it, I try to get them to do it upfront, because I do feel like that's an important one. ⁓ But I do recommend it for a lot of different, I have currently, ⁓ I think that I'm sending to you, I have a hemangiosarcoma, an osteosarcoma, and a poorly differentiated sarcoma that, I'm like, okay, great, I don't know what to do with this, you tell me, so. Guannan Wang (25:09) We might be able to, yeah, we might be able to even, provide some diagnostic clarity. we have diagnostic insights for around 30 % of our overall cases ⁓ and one third of those 30%. Aarti Sabhlok (25:11) Right, yeah. Guannan Wang (25:27) no definitive diagnosis before they came to us and we were able to pinpoint a diagnosis. like not all of them, a very small percentage, but as our data grows, I think we can really, leverage that as well. know, just last week we reported three cases where the first one had no... ⁓ okay let me make sure that I got that right. So the first one, two pathologists ⁓ think that ⁓ this is a gastric adenocarcinoma but they cannot rule out reactive process. And when we saw the data, it's ⁓ overwhelmingly quiet. quieter than all of our other cases, except for when this is a benign process. of course, we cannot definitively say that, OK, we don't think this is a gastric adenocarcinoma because we've sequenced the gastric adenocarcinoma and that they are always... No problem. Aarti Sabhlok (26:43) Sorry. Guannan Wang (26:55) Aww. ⁓ Aarti Sabhlok (26:57) ⁓ Sorry, he's guarding the house. I apologize. Guannan Wang (27:07) No problem. What's his name? Moose ⁓ okay. I love it. our cat Jessey is lying there ⁓ napping. Sometimes we do. Aarti Sabhlok (27:15) That's moose. Moose, yeah. Cats are much easier that way, yeah. Guannan Wang (27:30) I know, yeah. Depending on when we do the recording, he loves to be on on screen. Yeah. He's just too tired. Yeah, show himself, exactly, yeah. Aarti Sabhlok (27:39) Showing himself. Sorry about that. ⁓ Guannan Wang (27:50) Yeah, we've sequenced gastric adenocarcinoma before and very few cancer cases, definitive cancer cases that we sequenced have that quiet genome. So, although we cannot say definitively that this is a benign process, but with the differential, that this could still possibly be a benign process. Bless you. Aarti Sabhlok (28:00) Yeah. Thank you, it's okay. Guannan Wang (28:16) And so that just adds a little bit more information for the treating clinicians. And the other case, Aarti Sabhlok (28:21) Right. Guannan Wang (28:28) is a potential or suspect hemangiosarcoma case that did histopathology and also CD31 staining. They don't think this is a hemangiosarcoma, but then genomics shows that. So it's interesting that Aarti Sabhlok (28:30) Thanks Yeah. It is amazing. ⁓ Guannan Wang (28:52) or any encouraging to see ⁓ more cases like this. So I think ⁓ histopathology, cytology, are still definitely the gold standard. None of the genomics can make sense in the diagnostic scenario without histopathology. ⁓ Aarti Sabhlok (29:01) you Guannan Wang (29:13) But then I think we see more cases where genomics can actually add in additional layer of information where you can. So I think that's something that ⁓ we are pretty excited about. Yeah. Aarti Sabhlok (29:13) Okay. Right. Yeah. Yeah, and then sometimes prognostic information, shows up occasionally on some reports is helpful. I mean, I don't think a client ever wants to know that this is the worst of the worst, but I do think it is helpful to prepare them. And most clients, they do want to know what they're walking into or coming up against. So when that information is provided on a report, I do find it's disappointing as you said, it's disappointing, it's helpful information to give them to say, you know, hey, the tumor markers on this, they tend towards negative prognostics. And so just for us to be prepared as we go through. Guannan Wang (30:09) ⁓ Absolutely. So that being said, we do have to be very cautious about most of the prognostic biomarkers, except for a few come from the human data. And it's a two-edged sword. is that ⁓ one, we have that data, and they are oftentimes like a guideline recommended, level A, very, very high level. ⁓ Aarti Sabhlok (30:23) Right. Guannan Wang (30:38) that does not necessarily translate to dog patients directly. So I want to really make sure that we all understand that. Second of all, this is very different from the pathology report, because when I talked to a pathologist, they were like, there's never a good prognosis marker in Yeah. Aarti Sabhlok (30:38) Yeah. Right. Guannan Wang (31:01) So, but on the genomic side, there are actually many markers that indicate better prognosis So I think we should definitely need to bear in mind that ⁓ not all prognostic biomarkers indicate negative results. Some actually are associated with ⁓ better outcomes, Aarti Sabhlok (31:20) Yeah. Guannan Wang (31:25) And even with ⁓ the poor prognostic biomarker, when they are treated with ⁓ the appropriate genomic or other biomarker guided therapies, they actually perform better. We are only scratching the surface on the veterinary side in terms of prognostic markers. Yeah, but I. Aarti Sabhlok (31:46) Yeah. Yeah. Guannan Wang (31:49) over time, so we definitely can make a dent. do you have a lot of cases where you recommend ⁓ genomic testing, but the owner ⁓ decide not to do it. in those cases, what are the biggest barrier and how can we Aarti Sabhlok (32:06) I mean, honestly, it would be cost as a private practice clinician. Most of the things that I do are marked up, right? And so costs can be a barrier for some clients. I would say cost is one. I do think some people come in They come in to talk to me, but they come in with a bias against oncology and chemo in any form. ⁓ And yet they want the data, right? They want the information. And then there is probably the population that says that no matter what I do, I'm going to lose my pet to this cancer. I just, don't want to do it. I don't want to do it emotionally, physically to my pet. Guannan Wang (32:37) ⁓ okay. Yeah. Yeah. Aarti Sabhlok (32:59) financially, I mean, there's I think multiple factors that come into that. So I see the gambit. I see people who want to do everything, everything. And then I have clients that pick and choose. And then I have clients that, you know, they're not, they wouldn't touch chemo with a 10 foot pole, whether it's oral, IV, it doesn't matter. They're not doing it. And then there's those people that are just emotionally, they're, they're flattened by it and they just can't, right? So I, Guannan Wang (33:08) Yeah. Yeah. Hmm. Aarti Sabhlok (33:28) You know, it's my job is to meet a client where they are. And so it's to help them. And it's not my job to make them feel guilty for not doing something. My job is to make them comfortable with whatever decision they've made, even if that is to not treat their pet. OK, so then how are we going to keep your pet comfortable? What are the things that you need to look for that are going to help your pet as they go through this process? So, yeah, I mean, having done this, as I said, with experience. ⁓ Guannan Wang (33:48) Mm. Yes, a good experience. Aarti Sabhlok (33:57) I think it is just about meeting the clients where they are and helping. It's always about helping the pet. Guannan Wang (34:07) absolutely. to have that more individualized, not in terms of just based on their tumor genomics, but also based on their, whole situation, right? So it's critical. Aarti Sabhlok (34:19) Right. Yeah. Guannan Wang (34:23) This is not the first time that I heard about that. Previously, if you ask me, I would think it's crazy to not treat a dog with a perfect condition that we have a drug for and the dog will respond. But as I... Aarti Sabhlok (34:31) Yeah Guannan Wang (34:42) do this for not as long as you do, some time. So I began to understand, really, this is a very complicated ⁓ decision-making process. from our side, do you think Aarti Sabhlok (34:45) Yeah. ⁓ Yeah. Guannan Wang (35:03) more data, publications maybe, and more data to show that these tests or treatment, genomic guided treatment will help prolong the overall patient population would help. Aarti Sabhlok (35:20) I think, that's a good question. I think one, will get, I think you'll get more with publications data. I think you get more oncologists on board, right? Right, so those that are either sitting in the periphery, they use it a couple of times or those that Guannan Wang (35:26) Not even that. Mm-hmm. Mm. Mm. Aarti Sabhlok (35:41) haven't yet dipped their foot in this kind of world. I think that lends to getting more doctors involved and then that leads to more patients being involved. I think in my case, there's very few clients that ask me for publications when we talk about targeted therapy, right? Most of them understand that, and I explained to them, said, look, Guannan Wang (35:43) It's. Okay. Aarti Sabhlok (36:09) This is what they're doing in people. We are scratching the surface in veterinary medicine, but as we do it, as we accumulate data, and then if I have a case that goes along with their pet, I can say this was my experience. I don't know that the publications, there is a, I do see doctors in my practice and they want the publications for sure. Human physicians come in wanting the data. Guannan Wang (36:22) Mm-hmm. Yeah. Yes. Aarti Sabhlok (36:36) The average person doesn't necessarily need the data, but they want my general sense of whether the targeted therapy will help their pet. I think that's sometimes a little tricky because as you've said, every individual's tumor is different. so yes, this worked for this patient with this disease, but it may not work for the next patient with the same disease. So I do... Guannan Wang (36:46) Right, Aarti Sabhlok (37:04) I do have to explain that to a client that yes, this has been my general experience, but there are patients on either end of that bell-shaped curve in terms of how they're going to do with it. Some are not going to respond, therapy is not going to work. And we may not yet understand the immunology of all of that in terms of that patient's immune system, markers that are expressed, how everything is activated, right? Guannan Wang (37:14) Hmm. interact. ⁓ Aarti Sabhlok (37:34) ⁓ what other medical issues that that patient have that are not cancer, but that might ultimately affect the way it responds to treatment. So I think these are all things that we're gonna learn the longer we do this, the more cases we accumulate. ⁓ But yeah, so I think the publications will be good because I think you'll get more doctors and more oncologists involved in what we're doing. And that was always going to be good because Guannan Wang (37:44) Okay. Mm-hmm. Aarti Sabhlok (38:03) The more cases we have, the more data we have, the more we can say that this is what we expect to happen in this case. Guannan Wang (38:12) exactly. To have more confidence, right? Honestly, that's so helpful for me to wrap my head around, some of these decision making and some of the, ins and outs we don't see patients as you guys do so we rely on you to provide you with the best data and tools to relay that information to the owners. Aarti Sabhlok (38:41) I think I had one client who wanted to speak with you directly that's... ⁓ Guannan Wang (38:46) You'd be surprised, you know, we are actually reached out by some owners. most of the cases, ⁓ it's from the oncologist or the clinicians to the owners. But in some cases, it's actually the other way around. The owner, ⁓ Aarti Sabhlok (38:51) Really? Guannan Wang (39:06) heard us first and then they reached out and they learned more and so they actually try to advocate doing this for their pets. we have not a insignificant number of cases that come to us that way. Yeah, which I recently I have a doctor from Australia I was like, how do you Aarti Sabhlok (39:22) okay. Guannan Wang (39:30) find out about us. they were like, ⁓ the owners, learned about you from a Facebook group. ⁓ And then they actually really pushed hard And then that doctor become a... Aarti Sabhlok (39:39) You Guannan Wang (39:47) frequent user now because what they did for that patient and now now they feel comfortable yeah but we don't even have a Facebook account ⁓ Aarti Sabhlok (39:48) That's great. So it may have been somebody else talking about it. Yeah. Guannan Wang (40:02) Probably, yeah, and I'm very eager to see what the Facebook group is about. but like I said, when I received those emails from you guys telling me this patient either respond or does not respond. So those always keep my gears turning. Okay, we need to do this. We need to do that. So which is so amazing. Do you always exhaust what's available standard of care therapy? Or you do so many cases, maybe for some of them, you actually prioritize the genomic guided treatment. what's your take on that? Aarti Sabhlok (40:42) I mean, I think it's a mixed bag. ⁓ I think, you know, again, the data of mixing targeted and traditional chemo is a little sparse, both on the human and veterinary side. But ⁓ so for instance, for hemangiosarcoma, the CHAMP study that was done by Ethos Discovery looked at targeted therapy combined with doxoruticin. And so based on that study, I'm more comfortable Guannan Wang (41:05) Yeah. Aarti Sabhlok (41:09) combining certain targeted therapies with IV chemo, but I'm a little bit more conservative with my dosing when I'm doing them together. ⁓ And then with some cancers, and again, with some cancers, it's the client. They didn't decide to do targeted therapy until we've exhausted. So I think my preference based on some of the studies of combining targeted and Guannan Wang (41:10) Mm-hmm. Yes. Aarti Sabhlok (41:38) traditional chemo, how it changes the immunologic environment of the cancer. Combining them is probably the better way to do it. ⁓ And so I think ultimately if I can get more clients to do it upfront, I would like to try combining them. Where I found, so I have a certain again population of clients that are willing to do that. And I have a certain population of clients that will only look at it after they've failed. Guannan Wang (41:56) Mm-hmm. Yes. Aarti Sabhlok (42:08) traditional therapy. yeah, but I think ultimately where we're going to find ourselves is that combining them just my and again, this is my little bit of experience over the last few years. I think ultimately combining them is going to be the way that we achieve maximum results. ⁓ But it's going to it's going to take some time to figure out the the precise dosing of the Guannan Wang (42:08) Every day. Mm-hmm. Mm-hmm. Mm-hmm. Mm-hmm. Aarti Sabhlok (42:34) the targeted therapies when you're using it in conjunction with traditional chemo. Because again, my main objective is that my patients have the best quality of life. And so I don't want to do anything that's going to interfere with that. It's not the right word, but that's going to compromise that quality. It's quality over quantity. that's mostly what I tell my clients is quality over quantity. Guannan Wang (42:55) Mm-hmm. Aarti Sabhlok (43:04) Quantity is our second goal, quality is our first goal, and so, yeah, I do think ultimately it's going to be combination therapy that's going to be the key. Guannan Wang (43:13) Mm hmm. And I would agree with you. So I did not think so a year ago, not even a year ago. You I remember when we had our first conversation, with Dr. MJ Hamilton When he said he is combining things, I was like, you're messing up. How are we going to ever collect clean data to show one way or another whether this helps or not. Very soon after, so as I talk to more clinicians, as we see more cases and the results, right? And then I think I had a 360 or 180 change, right? Aarti Sabhlok (43:59) Yeah. Guannan Wang (44:09) Looking back the history of our development of precision medicine and target therapy on the human side, at first all these target therapies were approved as like second line, third line, fourth line after they exhaust all the standard care chemotherapies. Not only that, they were frequently approved in combination with chemotherapies. And only much much later, Aarti Sabhlok (44:41) Yeah. Yeah. Yeah. Guannan Wang (44:45) when we saw drugs that are approved like standalone, I think so we are still at the, on that early stage where we need to really show benefit, show results. I think combination is definitely, you know, the way to go pending tolerable safety and toxicity. Although there's not a lot of published ⁓ data on that front, we've actually accumulated quite some real world data where we keep this list of potential combinations and dosing and schedule. And that list is getting longer and longer based on oncologists' firsthand experience, of course, the data is anecdotal. it's a small cohort, right? It's real world. But at least we have a place to start, like a starting point where we can later test it in larger cohort or we design prospective studies, somewhere to start. Aarti Sabhlok (45:38) Yeah. There is, ⁓ my colleague was telling me, there's a paper that has either come out or is going to come out that actually shows that the tolerance of, and it's traditional chemo, not, and it's specific drugs, that depending on where you live in the country, the tolerance of those drugs is different. Guannan Wang (46:15) Great. Aarti Sabhlok (46:16) Yeah, and so the doses that are used of, say, let's say CCNU on the East Coast are generally much higher than, and I've not studied this in any way, but just anecdotally, the doses I used in Southern California were much higher than what I currently use in Northern California. So someone wrote a paper, I have to find the paper, and I do wonder, ⁓ Guannan Wang (46:24) I'm Thank haha Aarti Sabhlok (46:44) Because I, you know, in talking to some of the doctors, Carboplatin and Olaparib is a very common ⁓ combination of drugs that's used on human. And now in some of the reports I've gotten, and I've used it in some of my patients, I've not had the same side effects as some of my colleagues have had with the severe thrombocytopenia or severe neutropenia. I've not seen when I've used the combination. Guannan Wang (47:05) Yeah. Yeah. Yeah. Aarti Sabhlok (47:13) I wonder whether it's the patient, it's, yeah, is it the? Yeah, yeah. Guannan Wang (47:16) Dosing, right? Dosing schedule could be different. Exactly. know, perfect example of, you know, combination of olaparib and a carboplatin. in theory, this combo, have the maximal synergistic tumor killing effect. There are large-scale studies published on the human side. in general, our experience with a larger number of doctors is also that this combo is... ⁓ pretty well tolerated. I'm glad to hear your experience as well. that's another thing is do we have standard protocol for dosing, Sounds like there's a regional variation even for the conventional chemo, and that can make that tolerance or side effects, profile different. Aarti Sabhlok (48:17) Yeah, I generally will tend to lower my dose of traditional chemo if I'm combining it with targeted because I do think there's some cumulative bone marrow toxicity. Yeah, so I think the ideal dosing we don't yet know and like you've said, it varies by patient. Guannan Wang (48:26) Yeah, yeah, yeah. Yeah ⁓ Yeah, it's difficult because you want to find that balance between the minimal toxicity, but also efficacy, If we are only mindful of the safety, toxicity, minimal toxicity, that we might not reach a workable. Aarti Sabhlok (49:03) Right. Guannan Wang (49:06) concentration, for that to be effective. Yeah, so that's a fine balance, I think, for a lot of the ⁓ drugs and the combinations that we are still kind of in the middle of finding that perfect dose. But for most of the drugs that we recommend, we actually Aarti Sabhlok (49:28) Right. ⁓ Guannan Wang (49:36) have a ⁓ dose range and also a preferable starting point where you can start, but there is also very clearly listed. Okay, these are the side effects. These are from the data from the NDA for FDA approval. These are the anecdotal data in canine patients where we... Aarti Sabhlok (49:57) Right. Guannan Wang (49:59) the dog experienced this and that side effects. So to have that information, I think is critical so that you know what to kind of look for, right? Yeah. Like I said, this is a crowdsourcing effort. Aarti Sabhlok (50:09) Right. Guannan Wang (50:14) Seriously, you have a dog that has side effects. please let us know so that we can ⁓ make that available you also mentioned that oral targeted therapies. are in general like more easy to handle, right? So the owner can administer them at home. So do you have any safety concerns for the human and? Aarti Sabhlok (50:32) We're sure. Yeah, I mean, that's a good question. I think, you know, the things that I warn clients about is the same stuff. When we use palladia and we send palladia home and palladia is a targeted therapy. So I tend to use the same precautions, wear gloves, ⁓ you know, if they vomit or have feces or an accident in the house, pee, poop. Guannan Wang (50:54) Yeah. Yeah. Mm-hmm. Aarti Sabhlok (51:06) Clean it up wearing gloves. Practically speaking, don't touch it. My one story is I had a patient that was on targeted therapy and the dog pooped in the house. They had a young child who picked up the poop and then drew on the walls with it. And they called me in a panic and I said, you need to call your pediatrician. Like I am not the person to answer that question. Guannan Wang (51:11) Right, right, right. You ⁓ Aarti Sabhlok (51:35) And also, ew, like that's just gross. But okay, you call your pediatrician and they call, I called her back to see what the pediatrician had said and the pediatrician did not care at all. Because again, right, you know, the dosage is that, mean, just, it is an N equals one, but the pediatrician didn't seem that concerned that the child did handle the feces. ⁓ But yes, I mean, the general wear gloves, you know, Guannan Wang (51:36) wow. is minimal compared to... yeah. You Aarti Sabhlok (52:06) If you're pregnant, don't handle the medication. ⁓ Yes, mean, think it's with any recent. We sent home Cytoxin, we send home palliative. So it's the same. I don't think I do anything different than than those precautions. But I also, you know, I do tell clients that the metabolites are generally much lower than what we see in people. So ⁓ just I think common sense prevails, but I do. Guannan Wang (52:06) you Like everything else, right? you're pregnant, you even handle the litter box. Cat litter box. Okay. Aarti Sabhlok (52:35) I do list it out because again, you run into a case like the baby picking up poop. Guannan Wang (52:40) Yeah, I know. Yeah, yeah, yeah. Yeah. I recently got asked about like dog peeing in the house after taking, taking targeted small molecules. Yeah, I said, you know, we'll connect you with more experienced oncologists because I'm not the best person to answer that question. But from what I hear and the common sense. Always wear gloves, always clean it up, don't touch it with your bare hand. So that seems to work for most patients. So yeah, that's good to hear. I hope we don't have a lot of cases where the baby is picking up. But you never know, these things happen, right? Aarti Sabhlok (53:06) Yeah. Yeah. was not anywhere on my radar of things that was gonna happen, was that. I was just like, ⁓ yes, please call your pediatrician. Yeah, the pediatrician really wasn't worried. Yeah, it was, you you learn. You learn by all these experiences. Guannan Wang (53:29) Yeah. No. Exactly. playing. what changes or advances would you like to see in our in this field in the short term or in long term that you want to see happen Aarti Sabhlok (53:59) I'd love to see universities get on board with doing more clinical trials with small molecule inhibitors, ⁓ with DNA sequencing and small molecule inhibitors, because a lot of the trials that happen in veterinary medicine start at the university level. And so I think having multi-institutional trials only benefits those of us that are working in private practice and to advance the Guannan Wang (54:15) Yeah. Aarti Sabhlok (54:26) the science and the data. So that would be lovely to see. Yeah, I think in the longer term, it's repetition. The more cases we have, I think the more confidently we can walk in and say, you know, we really need to do this upfront for this cancer and be able to say that this is going to be of benefit. But that, think, is a few years away. Guannan Wang (54:28) Absolutely. Yeah. Mm-hmm. few years away. Yeah, but we are working on that. We're on that with you guys. yeah, yeah, yeah, collecting data. Yeah. And any like a practical ⁓ tips that you would like to share with your colleagues who are maybe new to the field? I know you already kind of make your new colleague do a genomic test even though he just started. Okay. Aarti Sabhlok (54:57) Yes, which I appreciate. ⁓ I didn't make him. He had just seen me doing them. He was like, what are you doing? And I said, well, these are the things that I tried. But I'm also learning from him, is because I've been out for a while and he's newly out and it's good. We talk about a lot of cases and I think that's good. ⁓ Tips. Tips would be, that's a tough one. ⁓ Guannan Wang (55:25) Yeah. Yeah. Yeah. Yeah. Aarti Sabhlok (55:48) I think just embrace what genomic testing has given us thus far. Understand that there are limitations, but that we grow by doing more. And so if you're hesitant, then yeah, stick with the cases where we've seen a lot of benefit. Hemangiocerecoma to me being the prime one that I can always think of, because there are studies that were done that show its potential benefit. I think if you had to start with one cancer, for me it would be hemangiocercoma. And then once you get your foot in and you're feeling more comfortable, then you can extrapolate to or move on to others. we're not gonna hurt our patients by offering more things to help them. And so I think anything that we can do that does not negatively impact a patient's quality of life, but has the potential to improve their quantity of life is a good thing. Everyone wins. The clients win, we win, the patient wins. So I just, yeah. Guannan Wang (57:04) I love it. I think that's really very emotionally summarize ⁓ why we do what we do and to offer more options that does not hurt. Even though we are still ⁓ early and we've seen some early promising signs and we will gain more knowledge and experience when we have more, do more. Aarti Sabhlok (57:33) I also think that people need to understand that you are very willing to talk about cases, right? It's not you're not sending this sample to a unknown void where there's no one to talk to. ⁓ You are so responsive via email, text message, phone call, just, you know, questions. And I think that but I think, again, for someone who's coming new into this, that's important that they have someone that they can talk to or that you could say, hey, here's my experience, but why don't you talk to this oncologist in your area who's used the test and then you can collaborate because I don't mind talking to people in my area. It's not a competition, we're colleagues. just, but yes, you are so helpful and responsive. I think that's a ⁓ huge part of working with your group has been just the communication. Guannan Wang (58:10) Yeah. Thank you. Thank you for saying. we try really hard. Aarti Sabhlok (58:32) You're welcome. but very important, yes. Guannan Wang (58:41) Yeah, we definitely prioritize talking cases above everything else. we always have our projects in the background, right? But anything clinical cases related is a top priority. So thank you for those words. Yeah. This has been ⁓ so tremendously helpful. Aarti Sabhlok (59:01) Absolutely. Guannan Wang (59:07) to learn how you practice and all your practical tips for someone who is new to the space or who is hesitating to get into the space. ⁓ I think ⁓ your experience ⁓ goes a long way. Aarti Sabhlok (59:27) Yep, I'm just now that's what I mean to say. I'm very experienced. I'm not gonna talk about age. ⁓ Thank you for having me. It's been a pleasure chatting with you. Guannan Wang (59:30) Good experience, good experience. Yeah. Yeah, thank you. Yeah, we'll stay in touch. Aarti Sabhlok (59:43) I will. Thanks, Guannan Have a good day. Bye. Guannan Wang (59:45) Bye you too. Bye.