Slide 1 : 2023 Symposium on Feline Health
Steve Dale: My name is Steve Dale, I’ve been on the board of directors of the EveryCat Health Foundation for 76 years or something like that. (Not really). It is one of the great joys. I’ll tell you, I’m on several boards and have been on several boards – this one in many ways is the one I’m most proud of being on because I’ve been able to see the difference that we’ve made and the difference that we’ve made in many areas including the one we are going to hear about today – feline infectious peritonitis is something that I wouldn’t have ever dreamed of.
How many of you have been doing what you do for, say, more than 10 years? Most of you have; would any of you have guessed that there would be, for a disease that has always been considered fatal, a change to the word treatable? No. You can applaud that, that’s fine. In 2019, at a symposium that we hosted at the University of California, Davis, it was officially determined that FIP should be changed to treatable. We brought in just about all of the researchers from all over the planet who have researched feline infectious peritonitis. Once again, I remind you if you have the opportunity in between things to go ahead and sign up at the raffle. You are more than welcome to do that. Right after the talks we are about to hear there will be a Q&A. There are cards at your table, and you can in handwriting that I hope I can read, you can write down what your questions are or comments. We will do that directly after which by the way we do have to finish at 7 o’clock. We have a hard stop.
Slide 2 : VIN Paul Pion
This talk, this event, is sponsored by the Veterinary Information Network. Dr. Paul Pion has helped us by sponsoring this event. Do we have that person here? We actually have a special call coming in. There we go. Hold on a second.
Slide 3 : Joan Miller
Hi Peter. I want to introduce you to someone. I mentioned that I’m in front of Peter. This is Peter Keys here. Peter, I’m in front of about 100 people, wave at Peter. Peter was married to Joan Miller. We are about to announce to all of you that the EveryCat Health Foundation, Peter, has now determined – we had our board meeting last night – the new investigator award that we have always had will from here on out be called the Joan Miller New Investigator Award. I’m not done, Peter. This event we are at right now where we are talking about FIP is being dedicated to Joan Miller.
I will tell you just a little bit. Joan Miller was the president of our board when we were the WINN Feline Foundation for I think it was 12 years. Joan Miller contributed to Dr. Peterson’s legendary book about feline Health. Joan Miller actually taught at the University of California, Davis, at one point with Dr. Niels Pedersen. If you have ever read a cat magazine ever, ever, ever, Joan Miller probably contributed stories to that magazine. For the Cat Fanciers Association, she was a world-class judge who judged all over the planet. If a country had a judging, Joan Miller was right there. In addition to that she was the legislative chair for many years.
Have you heard the term “Cats are not small dogs”? Where do you think that was first coined at? It was Joan Miller. I could go on and on with all of the influence and impact she has had on everyone in this room if you breed cats. Once again, please put your hands together so Peter can see you. Peter, you know I love you, and thank you so much for being here and for dropping in on this event. The thing is you didn’t even have to pay to get in. I think we’ve lost the connection now. It was the perfect time to lose connection I suppose.
Slide 4 : Funding
Finally, I want to say that our organization has funded – over 55 years we have funded about 9 million dollars in cat health research, over that actually. That is including nearly 1 million dollars for FIP studies through the Bria Fund, all of which is made possible by generous support from our donors and our sponsors. I will say that again, our donors. How many in this room have donated in one way shape or form? Many of you! Without those of you raising your hands we couldn’t do what we do. Please we are here for only one purpose and that is to help cats.
Slide 5 : Panel of speakers
I want to introduce our panel of speakers. I’ve got too many papers in front of me. I could do it without the papers, actually, and it turns out I might have to. Ah, there they are.
I’ll start with Dr. Drew Weigner, raise your hand so people know who I am talking about. He is the past president of the EveryCat Health Foundation. He has been on the board of directors since 2014 with over 35 years of veterinary experience in practice. Dr. Weigner was one of the first feline-only practitioners in the country. Dr. Weigner served as president of the Academy of Feline Medicine in 2022 and is a board member of the American Association of Feline Practitioners, for several terms. Dr. Weigner is now leaving the board of directors and I just want to say to Dr. Weigner on behalf of the board of directors – thank you. Let me say that again – thank you for everything you have done!
Dr. Brian Holub, raise your hand. Dr. Holub has been a member of the EveryCat Health Foundation Grant Review Committee since 1889. Oh, it’s 1989, I had no idea. Dr. Holub was the chief veterinary officer at VetCor—that’s a national network of veterinary hospitals from 2012 until 2022 when he dared to retire. Dr. Holub served as a clinical instructor at Cummings School of Veterinary Medicine, Tufts University from 1998 to 2014. He was in private practice for a very long time and that, he tells me, is still his favorite thing to do. He currently serves at the Ohio State University School of Veterinary Medicine Stanton Foundation Advisory Board. Round of applause please.
Our superstar guest, raise your hand, Dr. Brian Murphy. There he is. He is on a research group that has studied the development of feline coronaviruses, particularly FIP in cats, and immune response to the virus from 2013 on. In 2015, his team began collaborating with Gilead Sciences to identify antiviral therapies to treat FIPV-infected cats. By the way, he is going to give us some news. You can even use Twitter and tell everybody about it. It will be exciting. His research program has facilitated the identification of several effective antiviral therapies including the current work focused on creating a highly efficient combined antiviral therapy for FIPV-infected cats. Applause – I need one of those signs.
Peter Cohen at the far end of the table—there he is! Do you guys know who that is?
Just a cat lover – just this cat lover has raised a whole lot of money for the EveryCat Health Foundation to support the Bria Fund which supports FIP studies. He is the founder of Zen by Cat. This is a nonprofit organization dedicated to raising funds and providing education and awareness of FIP. He became active in funding FIP research after losing his own kitten, Ms. Bean, to the disease in 2016. His cat Smokey is one of the first cats that was declared cured of FIP when no one believed that could happen. Peter has been adopting cats for more than 30 years in his home. If you have not seen his website, you need to check it out. If for no other reason—it would be nice to give money—than to see the enrichment he has in a playground for cats. His home is the definition of enrichment. Peter, thank you for being here as well.
Now we move on to the science stuff, and the first person up here is Dr. Drew Weigner.
Slide 6 : Peritonitis
Drew Weigner: Thank you, Steve. It’s great to be here with all of you. It’s my first day of not being on the board in nine years, I’m not done yet as you’ll see.
My job here is to just give you a brief history of how we got here and then you’ll hear quite a bit more of what we are doing here and where we are going to be going in the future.
Slide 7 : FIP history
You’ve probably seen a picture similar to this before. This is actually the FIP virus, but it looks very similar, as you probably know, to COVID. Why? Well because they are coronaviruses. They have the same spikes which are used now for therapeutic targets and hopefully vaccine targets in the future.
This was first identified quite a long time ago; in 1963 in Boston. As soon as they discovered this, it was recognized around the world, so it didn’t spread at that point. It had already spread. They didn’t really know what it was. All they knew because they didn’t have this picture—and this was before electron microscopy was common. The way they knew this was because of something called ultrafiltration. They took fluid out of the abdomen of a cat with FIP and filtered it through an ultrafilter that filters out most infectious organisms so what is left is basically viruses. When they gave that to another cat it got FIP, so that is how they assumed at that point this was a virus. This was before medicine had advanced very far because you are talking about 1963.
Slide 8 : Wet form: effusions
You have seen pictures like this before. There are two forms, the wet form, which is much more common than the dry form. In the dry form, you see the granulomas.
Slide 9 : Dry form: granulomas
This was in the liver of a cat. It is commonly in the intestinal tract, but it can go to many other places as well, like the brain, the eye, and other places of the nervous system to form what is called dry FIP. It is much trickier to diagnose. This turns out it’s a little bit trickier to treat, as well as—you’ll see as we go on.
Slide 10 : How does it occur?
How does this occur?
This is just a common coronavirus that cats have. I wouldn’t say it’s ubiquitous because it’s not, but it is very common in cats, and most coronaviruses don’t cause much of any disease in cats. Occasionally, you see cats getting a short bout of diarrhea with feline coronaviruses—the common ones. I’ve seen cases like this in practice where one cat would get it and then all the cats would have diarrhea for a week or so, and then they are fine. But occasionally, one of these viruses will mutate within each infected cat, and when it does it causes a fatal disease which you are all very familiar with. It is common in young adults. It is a little bit more common in males and I think a good point to make is you can see this in groups of cats such as in shelters, and you have probably seen it in other catteries where it just pops up. Why does it just pop up? Well, that is because it is mutating in each cat. You don’t see this necessarily going through an entire cattery or an entire shelter. One of the keys to this, on the bottom, is the transmission. This fecal/oral route is key because cats use the litter box, it’s excreted in their stool and what do they do? They get out of the litter box and clean their feet to get the cat litter off and then they ingest the virus that way. Strict litter box hygiene is one way to limit the transmission of coronaviruses.
Slide 11 : Risk factors
These risk factors are important. There are many others, but these are the ones I think are going to be most commonly seen and most important to you, and that is, that you see this with other diseases. Feline leukemia and FIV are fairly common ones—the things that affect the immune system.
Rehoming cats, shelters, breeding colonies, some of you have probably seen this where you have a cat that you adopt out and they go to a wonderful home and three weeks later they come down with FIV.
The stress of rehoming may affect their immune system. They don’t really know if that’s the only factor in this, but it is certainly one of them.
There is really very little information about how this occurs and whether this occurs more commonly in some breeds. There is a little bit of information that it may be more common in Persians and Birmans, but there is really not much to support this. It really doesn’t seem to be limited to certain breeds or any special breed.
Occasionally you will see this after queens have a litter of kittens, again, the stress of having the litter suppresses their immune system.
The most important thing by far is the last one, and that is the presence of feline coronavirus. I know this sounds stupid, but if you don’t have feline coronavirus around, you can’t have FIP. That is a major factor in whether these cats come down with the disease or not.
Slide 12 : Where you come in
I’m not going to go through all of this, but here is where you come in. You guys created us. Don’t think we don’t know this. We are here because of you because back in 1968, which is now 55 years ago, the CFA created what was then called the original CFA Foundation specifically to fund research. This was a game-changer in veterinary medicine. At that point, nobody was focusing on feline health studies. You were the ones that saw the need and created the foundation to do this.
Three years later the first grant was for studying FIP. At that point, it was called the Robert H. Winn Foundation in honor of Robert Winn who had just passed away.
A lot happened in between. If you jump down to 2013, right here, this is where we started funding Niels Pedersen and many others to study these novel antiviral drugs which Dr. Murphy will speak about. That started the ball rolling. It was not that long before the first paper was published in 2019 describing effective antiviral treatments for cats with FIP. We’re still working on an attempt for a vaccine because although treatment is very important and has been a game changer, prevention is going to be the big thing and we are still working toward that.
Slide 13 : EveryCat's FIP research
This is repetitive in that, yes, we funded really almost up to 1 million dollars now in FIP research. The Bria Fund was critical in facilitating this.
Slide 14 : Before 2002
You can see here two things; one is that all these studies that we have done for different things. The earliest ones go back to 2002 and there is a reason for this.
This is what was going on in 2002. This is one of our grant review committees back in 2002. You might recognize some of them. You might recognize the woman who is sitting in the middle of everything. That is Joan Miller. The other thing to note here is to look at these reams of papers. These are typewritten proposals. All of this is in our archives, but it is kind of hard to go back and find them as they are in storage, but they do exist. We funded way more studies than on the previous slide, and we have been doing this, as you know, for a long time. This brings us back to the very beginning and my last slide.
Slide 15 : Robert Winn
We owe this all to Robert Winn who came up with the idea of founding what has now become the EveryCat Health Foundation, and we wouldn’t be here without him. We have never forgotten that.
Thank you very much.
Slide 16 : Diagnosis guidelines
Let me introduce to you the next speaker. Thank you so much. Here is Brian.
Brian Holub: We are going to move on to a very wonderful, wonderful accomplishment. That is a consensus statement—a tremendous document that is now guiding veterinarians in the veterinary community on current diagnostic guidelines. I’m going to tell you right now that everything you see up here is going to come from that document. I feel in many ways like I have a backstage pass to a rock concert and our rock stars are sitting at this table over here and are the people that came up with these guidelines. I am just the messenger telling you what these superstars have come up with as a consensus. On many of the slides I’ll show you—I’m not going to describe in detail what is on them.
Slide 17 : Presented today
I want you to write down these websites. You are going to learn a lot about Zen by Cat, a hero to cats. Peter will be speaking a lot about current FIP treatment. I’m going to give you a little bit of my input on how it works, and I am going to tell you my experience. I’m currently still practicing on Mondays occasionally, maybe 25 days a year. I see Betsy, hi Betsy!
I’m going to tell you that I am currently treating three cats for FIP. I want you to know that veterinarians are treating cats now for FIP and we are following these guidelines, and we are using organizations to help us. Without these guidelines, we wouldn’t be able to get our diagnosis clearly defined. Without the help of Peter, particularly with Zen by Cat, and if we wouldn’t have had the ability to use the FIP Warriors® 5.0 Facebook Group, we wouldn’t have the treatment. We are going to talk about that a little bit, but veterinarians, myself included, are getting more and more comfortable in helping every one of our cat owners get this disease treated. We’re going to talk about a few things that I think you are going to want to know. We are going to be very brief on a lot of these slides. I don’t want you to learn a lot of details. I just want to show you the details that is out there for your veterinarian to be able to refer to.
Slide 18 : Pathogenesis
We are going to learn a lot over and over again about the pathogenesis. This document—the guidelines—every word that is on here comes from that guideline. It is documented with these words and you just need to point your veterinarian toward those guidelines.
We know that it starts with this virus infection that we are calling FCoV or feline coronal viral infection. It is very important to know that only sometimes does it mutate to FIPV. That does not cause FIP yet. Only some FIPV cases will become capable of rapidly spreading. We still don’t have FIP yet. These rapidly spreading FIPVs then need to activate and only then do we get the severe inflammatory disease. That is pretty complex, and we are going to learn a lot more about that because I am not an expert in that. Brian, Dr. Murphy is an expert on that. You are going to see that all these steps have to happen, so to diagnose the disease it starts to become difficult. If you find feline coronavirus, does that mean the cats going to die of FIP? If you find FIPV, does that mean the cat is going to die of FIP? If you find that it has become capable of spreading, does that mean that the cat is going to die of FIPV? No. It is only when it starts to activate and we actually have symptoms. That is really difficult then for our veterinary community to be able to diagnose what is disease and what is all this other stuff going on that may never lead to disease? That is kind of the overview of what these guidelines are all about. I’m not going to go through all these details. I want to just show you the words that are in this document and come up with some concepts.
Slide 19 : FCoV infection
There are three outcomes. We get cats that are fairly resistant to infection with quick cessation of shedding or never shed at all so those cats in scenario one are 5% that will never get FIP and die.
The second group are cats that temporarily will have low levels of shedding for two or three months or longer and then will only shed intermittently. That is like 70 to 80% of the cats. Those aren’t our real worrisome cats but these are—these cats that develop long-term persistent shedding of high viral loads and so ideally with persistent shedders we want to get them out of the catteries.
We can do that. We can do that with testing. We are going to talk a little bit about testing. There are very difficult words that go with these letters so that is a quantitative or real-time reverse transcriptase, reverse transcriptase PCR. It is very confusing, RTRT – we use those same letters twice. Real-time just means it’s quantitative. It’s a lot or a little. That is very different than a non-real-time, a non-quantitative PCR. An RT-PCR and a quantitative real-time PCR, reverse transcriptase PCR test are very, very different. Don’t memorize this. It is very clearly in our document. I’m going to show you the document so you don’t try to write this down because there is no way you can write all this down, all these things that are going on here.
Slide 20 : Mutation and spread
All these words here are about mutations and about virulent FIP-associated coronavirus acquiring abilities to replicate and activate. All this stuff I talked about—I want your veterinarian to read that. It’s in a consensus statement that every veterinarian will absolutely trust. Those are those superstars, right? Those are those rock stars. We all have a backstage pass. That ticket is just giving them that website.
Slide 21 : Faces of FIP
Activation then leads to FIP. We have wet and dry, they are very different. Also, they are very different to diagnose, and we are not going to go too much into detail because it is overwhelming. I want you to know that the diagnostic guidelines have it all written down. How many times am I going to say that every word that you see up there is literally copied and pasted from the guidelines? You don’t need to write any of this down, just go to the guidelines.
Slide 22 : Diagnosis overview
FIP can be simple or challenging to diagnose, but very important. However, given the disease is fatal when untreated, the ability to obtain a diagnosis is pretty darn important. It is not that they have got a coronaviral titer which we are going to learn is meaningless, but that we get an accurate diagnosis; and how do we do that? These guidelines will help us. Diagnosing can be very, very straightforward, particularly when it’s wet or when there is an effusion. There are many ways to do it and I’ll show you one simple one, but there are many ways to do it. It can be incredibly challenging to diagnose it when it is dry. I want you to know that neurologic signs are reported in up to 30% of cats. Ocular FIP is in 16% of the cats that get the disease—the real disease—the one we are worried about and the one that we can treat.
Slide 23 : Brick by brick
I love this. It was put together by a past board member of EveryCat, Vicki Thayer, along with one of our long-term scientific advisors, Melissa Kennedy. It’s a bunch of building blocks and there is no simple way to get to a diagnosis, and none of these building blocks are in every single case. You have to build your case one brick at a time, and it is incredibly challenging to get the diagnosis, so we need some guidelines and that is what this is all about. I intentionally made this small so you don’t try to read it. I want your vet to go to the document and understand all these things that are in here. Basically, it says it’s either wet or it is dry, wet can be really easy, sometimes we just need a Rivalta test, and we have an answer. Other times they are going to want to run RT-PCR or they are going to want to run a quantitative. That is the really nice way to do it. A quantitative RT-PCR or they are actually going to want to stain for virus in the cells that are affected, particularly in a particular area we look for called macrophages. That may be one of the ways we diagnose it. I’ll talk briefly about that, but mostly I just want to point to the guidelines. No need to learn all this. You certainly don’t need to learn all this.
Slide 24 : The two paths
I wanted to show you the depth that we have gone into to understand effusions and absence of effusion. All these words come down here to the little test we are going to run.
Slide 25 : Use the guidelines
Many of these words are going to be exactly the same on all of these documents. Those that were positive for feline coronavirus or reverse transcriptase PCRs, you’re going to find out that is very confusing because there are lots of different RT-PCRs that are out there. That is where your vet gets confused. Which ones can we trust, and which ones can we not? One lab will say my test is more accurate in diagnosing. Well, we have now a consensus statement that says that is baloney. There is not one version of the reverse transcriptase PCR that is more accurate.
Slide 26 : Rivalta's test
Sometimes you don’t need anything fancy. There is this thing called a Rivalta test where you take a little bit of distilled water and acetic acid, so vinegar, and you put a drop in there. The way the drop drops we could figure out the spot pretty much if your cat has FIP. Wet often needs more than that, but it often needs nothing more than that to be able to diagnose the disease and then encourage you to get treatment.
Slide 27 : Detecting viral RNA
Other times it takes other tests. Other times we need to actually find the viral antigen. Here we can actually detect the viral antigen by using these real-time reverse transcriptase PCR and we are going to be able to get the diagnosis. Beware, since less virulent coronavirus can spread systemically it will never activate and cause inflammation, but it can spread systemically. Our real-time PCR test will become positive. Is that test a gold standard? Does that test mean I need to treat my cat? No. We do not have a test that can tell you that—I’m very sorry. It is not necessarily specific for a diagnosis of FIP. That is what we want you to get out of the guidelines. Additionally, it has been shown, and is very important to know that it did not differ significantly between little, tiny fine needle aspirates and incisional big open them up biopsies.
This is very important because years ago I used to think maybe I had to go in and take a bigger sample to get a diagnosis. Well, you don’t. We do not need to be more invasive. In fact, this is very important, the more invasive the biopsy technique is not mandatory for obtaining a sample. We need your veterinarian to read that, and they can go to this guideline and they can read that.
Slide 28 : RT-PCR vs real-time
We’ve talked about this. We’ve got the reverse transcriptase PCR and then we also have this real-time reverse transcriptase PCR. There is a whole bunch of versions of this which I’ll talk about in a second, but not in depth. What is nice about this is it is diagnostically more accurate because the real-time RT-PCR, that’s a little cue, we’ll say real-time when we see that, or we’ll use the word quantitative. The quantitative RT-PCR is a scale. The higher that number, the more the viral load, the higher the viral load, the more likely that they really have FIP. That is quantitative so the RT-qPCR can indicate the amount of virus in the sample, and cats with FIP generally have higher viral loads than healthy cats that we may get a positive RT-PCR on.
We need your vet to know that they need to ask for the right test. We don’t want you to be telling them what that test is, we want you to just be sending them to that website and having them read these guidelines which are industry standards so we can actually have the right test run. Don’t believe labs that say “My, RT-PCR two step nPCR is the one they need to run.”
Slide 29 : RT-PCR types
Don’t believe them when they say “My test (another lab) says the one for the M gene is the one to run. It is much more correlated with disease.” No, this was a big one we thought for a while. No, the 7b RT-PCR is not any more accurate in diagnosing which cats are the fakers or the real ones. None of them, not the S gene RT-PCR. This clearly says in the guidelines that these have been shown to just as often give you false positive results as other methodologies.
I’m not going to mention a lab, but if lab A says I’ve got a special version of this test we now have documentation to say that is maybe not so. Don’t encourage your vet to send it to this lab or that lab because they have a 7b or an S. We now have documentation that says that’s not true.
Slide 30 : RT-PCR testing
The other thing—it’s all in the guidelines. I’m not going to go to this slide again. I just want to show you all the stuff that is in the slides about all the different ones in there—the RT-nPCR and the RT quantitative 7b. All of these M genes, all of these are very clearly documented in our guidelines. This is a day’s worth of lectures if you really want to get into that depth.
Slide 31 : Detection-viral antigen
Another thing, and this can really be reliable, is the actual detection of the viral antigens. The antigens can be detected by the staining of the antigen within the target cell fluid or particularly the tissue macrophages. They use different immunostaining methods that are beyond my understanding that Dr. Murphy will be able to understand without thinking about it. The vet will send it to the lab. The brilliant rockstars at the lab will be able to tell us that we have detection of a viral antigen. Then we get detection of viral antigen via immunostaining. That is highly specific and reliable. We actually do have something that is reliable. Sadly, we don’t find that as a bullseye all the time. When we find that we can be a little bit more confident that we are making the accurate diagnosis. Never ever again do we want anyone to fall into this trap; I remember Dr. Pedersen decades ago saying more cats died because there was an FIP titer test than ever died of FIP. This was because as you are hearing many, many, many cats will have a titer, and whether it goes up 2-fold or 10-fold, or 30-fold it is irrelevant. If someone is running an FIP titer, and I don’t think our veterinary community is doing that anymore, it is not useful. Remember, every one of these words is right from the guidelines. The take-home here is we do have good tests – they are called reverse transcriptase PCR assays. The ones that are really exciting are the quantitative real-time reverse transcriptase PCR assays.
Slide 32 : Anti-FCoV antibodies
The other is actually that detection of the anti-corona viral antibodies is totally useless and that we can detect viral antigens, and that is quite specific and reliable. It is too much to absorb and is all in the handout.
Slide 33 : Standards and care
The next part of this is that we need to make the diagnosis so that we can treat the disease. I’m going to give you just one practitioner’s feel for how this has evolved. You are going to get expert comments from Peter and from Dr. Murphy coming up.
Slide 34 : FIP treatment
Everything you see here is incredibly easily accessible. Please go to Zen by Cat. It is a website called Zen by Cat. Everything you see here I’m sure is on Zen by Cat’s website. There is nothing revolutionary here.
FIP Warriors, 5.0, and Zen by Cat have 100% of this information. In my world of all the exciting things Dr. Murphy is going to be talking about—In my world, the only thing that exists right now is illegal GS441524. That is a long name for this one illegal drug that we will never get from the company that it is patented by, which is Gilead. The only available sources are illegal, and you have got to go through the black market. How could a veterinarian in good conscious treat—and this has now come out of many, many veterinary conferences. At the most recent veterinary conferences over and over again we are hearing that as long as you are not actively helping in procurement of the drug you have an ethical responsibility to help the client treat that pet. Veterinarians more and more are getting comfortable treating.
How do you get the drug, I’ll tell you. Someone comes in, I diagnose FIP because I know which test to run. Then I’ll say I can help you, but I can’t help you get the drug. Please go to Zen by Cat. Please go to FIP Warriors. Don’t tell me what you did but come back tomorrow with some medicine in your hand.
I’m going to tell you and Peter can probably tell you how that happens. I know what the sausage looks like, but I don’t know how they make that sausage. I know that the next day they come in with the medication. They are borrowing it from other people. They are passing it around.
Slide 35 : Treatment delivery
As a veterinarian, I don’t need to know that. As a veterinarian, I cannot draw it out of the vial and inject it into the pet. You can bring the drug in, and I can watch you pull it out of the vial and inject it into the cat. I can get you saline and teach you how to do it. I can sell you needles, and I can sell you syringes and I can sell you disposable containers. Most important, I can run a CBC profile, urinalyses and see what comorbidities are going on very early in the disease. These are sick, sick cats, and many of them even though we have a treatment, they may die before the treatment has a chance to help. We need to know what else is going on with that cat. I can help with that, and I can only help treat the cat with the brilliance of what Peter has been able to do and that is to magically get that medicine into the hands of a cat owner. We will learn a lot more about that when Peter talks and we will learn a lot more about exciting treatments that might be available when Dr. Murphy talks.
Your veterinarian cannot assist you in obtaining the medication, but we can, with a big CAN, assist in all testing. We CAN teach you proper techniques. We CAN know about the injectable versus the pill form. We can advise you on when to give what and why. Quite honestly, I think it is harder to give a cat a pill than an injection. I know in my hands, and please, Peter can probably tell you a lot more than I can tell you. I start with an injection for the first week or two anyway because I don’t trust starting with a pill. I start with an injection. An injection in my opinion is always preferable early in the treatment. Oral may be considered after remission of symptoms starts to kick in if you really hate giving the injections. The oral form, Peter you can please tell me if this is right or wrong. My intuition is that it costs 20 to 40 to 50% more than the injection. So, it is already $10,000, if you want to go and spend another $5,000 go ahead. I don’t know that. Fantastic.
You are going to learn a lot more about that. Remember, I have no contact or connection with the client getting the medicine or what they are paying for it. I don’t ask about that. In fact, I don’t want to know. It is not part of my world. Peter is going to be speaking to you and he will tell you how that magic works. I don’t know and I’m not allowed to if I want to keep my license intact and not risk my license. I’m thrilled that it is not as expensive. I’ve currently got three patients getting treatment. I don’t know what they paid for the drug. I don’t ask, they don’t tell me. I don’t even know. I will tell you that at this point unless Dr. Murphy tells me to treat differently I want 84 doses and I’m going to treat the whole treatment. So, 84 is not a magic number, it’s 12 weeks and we are just going to treat every single day for that 12 weeks, but there are always some buts.
Slide 36 : FIP GS441424 dosage
The dosage will depend on the presentation. If they have ocular or neurologic I’ll give more. We are not educated on this tremendously, it is by the seat of our pants, and we need more education. This is kind of what I do. If there are ocular signs I give a little higher dose. If they have neurologic signs I go higher. I may, even if I am really worried, I’ll either go to twice a day or even a higher dose. I definitely know if there is any kind of relapse I’ll immediately add another 5 mg. We don’t have clear written published guidelines like the diagnostic guidelines. It is the seat of our pants. Do you want to know how I know what to be treating?
I go to Zen by Cat’s website, and I see what Peter has figured out, I wait for Dr. Murphy to publish a paper and we are winging it. The true rock stars sitting right at that table over there, not a veterinarian, but I’m telling you that is where I’m going for my information. Then I can deliver the dosage. You all can go to Zen by Cat and get that information. You all can go to the EveryCat AAFP diagnostic guidelines.
Slide 37 : Treatment testing
It is very important to know, and I think it is important that veterinarians are involved. Veterinarians need to help you get an accurate diagnosis. If we start treating cats that don’t have the disease, they maybe have a coronavirus but never will get sick from the disease—we are going to create resistance, I believe in these medications. We really want to make sure that we are using the medicine in the cats that need it. I do believe we need to follow them along. I think there is a minimum of at least every four weeks during treatment, so we do a CBC profile and urinalysis. I actually believe more than that is very frequently needed because something is abnormal, and I need to follow it along. I can help with a lot of those things that are abnormal.
We absolutely need to monitor kidney function, liver function, anemia, blood issues, blood dyscrasias, total proteins, and electrolytes. There are things we can do to help if we have abnormalities there. This is not a lecture on treatment. I’m just telling you there are things your veterinarian can help you with.
If any kidney or liver issues arise or are present at time of diagnosis—more frequent testing is needed. There are costs involved with these treatments, but there are some nice things that we can do. I’m just throwing in a couple.
If they have pancreatitis or they have cobalamin deficiency, I can help that cat. I just need to know that it is there.
Slide 38 : Additional meds & tx
I do tend to see that those things are happening. I know there are lots of medicines I can play with. I can give Cerenia® for nausea, I can do an appetite stimulant. I actually don’t use mirtazapine now, I use Elura®. With Elura® they throw up, but then you give them the Cerenia® and they don’t throw up. I can give them B12 injections. I can help their liver disease and I can recommend for their GI signs probiotics. I can give them fluids. You can give them fluids. We might do antibiotics. This is mostly because Peter has written on his website that veterinarians should maybe be avoiding metronidazole and fluoroquinolones. I learned all that through Peter’s website. I avoid those things. That is where we are in veterinary medicine. We don’t have any standards. We don’t have a published set of guidelines yet for how we should be treating this disease.
Slide 39 : Additional thoughts
Here are just a couple of easy thoughts that I’m very convinced are important.
For some of these cats, I think you treat them, and I’ve not had this happen, but I’ve been told by others that you treat them and you are done with treatment and a month later you go to spay them and you will provoke FIP to become active again. What I am currently recommending is if they are young cats and they are not spayed or neutered, that at about 10 weeks of treatment with two weeks still to go and they are looking pretty perfect to me. While they are still on their medicine, I will spay or neuter them. If for some reason I delay it, I’m going to continue the GS441524 for two weeks after the surgery. I’m afraid that the stress of surgery is going to re-provoke the disease. Please ask Peter this question, I have never seen it, but I have been told that happens. Maybe I’ve never seen it because I follow this protocol. Guess where I might have gotten that idea – the Zen by Cat website. Some patients may need to have the dose increased and I think it is very important for vets to be very aggressive early. If I am not having success, I bump that dose up. I currently have three patients in treatment.
Slide 40 : Additional therapy
Additional therapies—I really like cortisone. I think it makes them feel better. It’s a short course. We are using prednisolone, not prednisone, so prednisolone. It’s a very standard dose. We taper it off over two to three weeks, but I think it gets them eating and drinking, and to me in my hands, the first few I treated I didn’t use cortisone. I use cortisone in most patients where I think I can get away with it, and I think it helps them.
Eating and drinking are essential. If I have to put a feeding tube in, I’m going to put a feeding tube in because they get better. If they just don’t die that first week, the second week they are going to be a lot better, and if they don’t die by two weeks they are probably doing a lot better. Again, Dr. Murphy can give you a lot more insight. His number of treatment successes are way greater than mine. Treatment works. They will be fully cured. That is really, really the message that you want to take home.
Slide 41 : Image of cat
You’ve got two great web resources that you can go to, and your vets can go to, and more is on the way. That is my cat, she does not have FIP. She is a very healthy, American Shorthair. For all you breeders out there, that is from Linda Bartlett, and that is from her Manx cat, and I bred and showed American Shorthairs for 18 years and ended up with, I think, 26 grand champions that I was very proud of. My last cat from my breeding program is 18 years old and still doing okay. We can keep our cats healthy. One more step in that direction.
The superstars are now going to follow the rock stars. We are going to learn so much from Dr. Murphy, it’s going to blow our minds and we are going to have a resource, all of us in this room that we never knew existed, and that is with Peter. I am just a ticket holder of a backstage pass. The rock stars are now going to follow so please help me introduce our first rock star, Dr. Murphy.
Slide 42 : Brian Murphy
Brian Murphy: I don’t know if I am going to live up to that. I’m also not going to go to the podium because I don’t like podiums. I don’t like hiding back there.
I’m going to say a bunch of pathology stuff so I hope that is okay. I know most of you aren’t veterinarians, but I’m a pathologist. I was a practitioner for a while in the Seattle area and I went back to become a pathologist. I’ve been at UC Davis now for almost 20 years. Mostly what I do with FIP is virology and pathology so I’m not a clinician anymore. I work closely with a clinician, Krystle Reagan, who has kind of taken the place of Niels. Niels retired more than 10 years ago or so. He has been working with me off and on, but he has kind of faded out and he is no longer working as a clinician, but Krystle is. Krystle and I kind of work as a tag team so it works pretty well. I do the virology and pathology and she does clinical.
This is a classic wet FIP cat which I’m sure you guys are familiar with now from the pictures you have seen.
Slide 43 : Wet FIP 1
This is what we know to be true.
Slide 44 : Effectively treated
We can effectively treat this disease and
Slide 45 : Can be cured
we can cure these cats.
Slide 46 : Ocular FIP
These two forms of the disease are the toughest to treat, but that doesn’t mean we can’t treat these. We just have to change our treatment protocol and timing to make it work.
I’m going to talk about antiviral discovery.
Slide 47 : Antiviral discovery
This is where GS came from, and I want to mention that all of my research has been funded by EveryCat, Winn Feline, the precursor to EveryCat, and we would not have identified GS441524 if it wasn’t for that funding through the Bria Foundation. That finding would have never been discovered and we would not have a cure for FIP except through the largesse of donors like yourselves and the foresight of Winn and EveryCat. I am very thankful for that. It has actually been a really fascinating road of discovery to go through here. I’m also very thankful for our funding.
I’m going to talk about how we look at antiviral drugs. As you all know, GS is a great drug, but it is in legalistic limbo because of Gilead’s board room decisions which I don’t really want to go into, I’m not really thrilled about it, but that is the way it is. Our way of addressing this issue is not to beat our heads against the wall, but to try to find other solutions to this problem.
Slide 48 : In vitro screens
We started doing in vitro screening for trying to find antiviral agents that work against the FIP virus about seven or eight years ago and we have been doing them ever since. We take our in vitro screens and we find candidate drugs,
Slide 49 : Clinical trials
and then we do clinical trials in cats with naturally occurring FIP. I’m very much opposed to doing experimental infections in cats. I won’t do it and we don’t need to do it because our goal is to cure cats with FIP and that means we don’t need to give them omental injections with virus and make them sick because we have plenty of cats that are already sick. That is actually a higher bar. It is actually easier to treat cats with experimental infection. It is actually relatively easy, and we have proven that multiple times. You can take 12 cats that are experimentally infected and then treat them appropriately and 100% of those cats will be cured. That is not true with natural infection. It is more difficult and the reason for that is we are dealing with a wild-type virus, we are dealing with cats that have other comorbidities. We are dealing with timing issues where a cat got infected in the past. We don’t know what the course of the infection was, and all of those things conspire to make it harder to cure those cats. I don’t care because our goal is to cure cats with natural infections so that is the bar that we are willing to meet.
Slide 50 : Compound assessment
We do this with a series of different assays, so we do this viral plaquing assay and I’m actually going to describe it here because I think it is super cool and is actually not that complicated. I think you should know about it. Then we do viral knockdown. We do a cytotoxicity assay and then we check in normal cats, what we call SPF cats which are specific pathogen-free cats. These are cats that are in our nutrition colony at Davis. We treat them with the drug and then we draw blood periodically and then use a device or an analysis called HPLC to determine the metabolism of that drug. Why we are doing this is because we want to figure out the dose. Any time we find a new drug that we think is going to work we don’t just randomly give the cat dose X. We have to determine how that cat metabolizes the drug. If you don’t know this—cats are weird about how they metabolize drugs. They are not like humans, and they are not like dogs. They have a liver that is quite different. This is what makes cats uniquely susceptible to the toxicity of acetaminophen or Tylenol. They don’t do the same metabolism that a human or a dog can do. We have to be really careful when we give them new drugs that we have never tried in them because we can’t extrapolate drug dosages from dogs and human beings and rats, we actually have to do it in cats. Then we do clinical efficacy trials.
Slide 51 : FIP therapies
Here are some of the things we’ve tried, and other people have too. There is a long list of different drugs here and they mostly don’t work.
Slide 52 : Most don't work
They have been tried over and over again for the past probably 25 or 30 years. We went ahead and repeated all of those drugs and they basically are not effective against blocking the replication of the virus.
Slide 53 : Other drugs
Then these drugs came along. Here is the drug that some of you probably are aware of. GC376 was the first one. It is out of Kansas State. Virologists there discovered that drug and in cooperation with Niels at UC Davis through a Morris Animal Funded grant showed that the drug can cure cats. It was about 7 out of 20 naturally infected cats that were cured which is not as good as we would like. I personally think this drug is actually great. It is one of the best in vitro drugs that I have ever seen. It is better than GS, but the problem is I think we have the wrong dose. I think we need a higher dose.
This drug is actually owned and now patented by a company called Anivive and it is moving toward being available. A lot of people dismiss that drug because they look at Niels results of 7 out of 20 and are not very happy with that—why not use GS? This drug is going to be available. I don’t know what dose they are going to recommend. I would like to do a study where we redo those trials with a higher dose because that drug is incredibly effective and incredibly safe which means we have a high latitude of using different doses. Don’t dismiss GC376.
Nirmatrelvir and these other ones I’m going to talk about. Some of these you have heard about.
Slide 54 : Viral plaquing
This is our plaquing assay. This is a 96-well plastic plate. We use them all the time in research, and we put a bed of cells on here. These are cat cells, the Crandell-Rees feline kidney cells. We put them on the bottom and then we are going to add virus. This virus grows in these cells and kills them. You can imagine what is going to happen in those cells if I put a virus on and it kills the cells. Then the cells aren’t going to be there anymore.
Then we add a drug compound with the virus to the cells and see what that drug does. Does the drug stop the virus from growing? Then we are going to add the drug alone and the reason for this is I want to see if that drug is going to kill those cells on its own. That is cytotoxicity.
Slide 55 : Cells compared
We do all those four types of experimental treatments, and this is what it looks like. Cells alone are going to be blue—we’re going to stain them with a stain called crystal violet so I can see it. It also allows me to do something really cool which is to take a 96-well plate where I’m testing 25 different drugs and I can scan that with a plate reader and I can get data in one second. Then I can graph it so I can do it as a high throughput assay so we can screen a lot of drugs very quickly. I can look at it visually and say, “Yeah, these were all alive and then we had some virus that pulverizes the monolayer because the virus lives and reproduces in these CR-K cells and kills them, and we get holes in our monolayer and the scanner can read that.” The scanners can read absorption so the absorption here is going to be high and it is going to be low there. I can get a bar and I can get a standard deviation because we are doing it in replicates, bla, bla—and I can see when I add compound X, no cell death. That compound works. This would be a positive hit for us, and we would be jumping up and down and saying yay!
Slide 56 : Viral RNA "knock-down"
Another thing we do is called RNA knockdown, so we are basically doing exactly the same thing.
Slide 57 : 24 hours
Instead of doing a visual output, I’m going to isolate RNA from there and I’m going to look for virus. I’m going to measure the amount of virus by doing the test that Brian was talking about which is quantitative RTPCR.
Slide 58 : Drug compound
I’m going to do that so we have two different ways of looking at the virus. One is to look at the biological function of the virus. Does it kill cells or not, and the other is to quantitate the amount of virus.
Slide 59 : Monotherapy combined
This is my graduate student, Sarah Cook. This is one of her papers from 2021. We looked at a bunch of different—it says 90 here. We actually looked at more than that. We were only able to publish 90 because of an entanglement with Gilead. Suffice to say we looked at a lot of different drugs and we found basically that the drugs that work for SARS (coronavirus) also work for FIPV. This isn’t cats, this is in vitro. This is the first step on our way to finding cures is to look at what they do in vitro and in vitro means in glass or in plastic actually, in this case. We found all these drugs work and I’m going to go back over those. My pet theory for a long time has been, well what works for HIV, so human immunodeficiency virus is the magic bullet, is you give three drugs at the same time. That’s called combined antiretroviral therapy. I thought the same would be true for FIP. Niels and I have argued about this for almost a decade now. I’ve written many a grant to Winn about how we need to treat with three drugs. It turns out from this paper not so much. All you need is a really good antiviral. Niels was actually on that side of the fence forever and I’m on the side where we need three drugs. He says one good drug—no it’s three—no it’s one—no it’s three. It turns out unfortunately Niels was right on this and I was wrong. I didn’t recognize how good a really good drug is. The difference between HIV and FIP is that HIV never goes away. You need three drugs because you are fighting resistance of those viral clones that come up all the time. One drug alone doesn’t work, but we are not dealing with HIV. We are dealing with a virus that is nasty and horrible, but you can knock it out immediately or within a week and it’s gone and it doesn’t get resistance. One drug will do the job. I’m actually firmly in that camp now. I don’t think we need, even for neuro and ocular FIP – I don’t think we need triple therapy.
Slide 60 : Pharmacokinetics
This is Luke Wittenburg. He does something I can’t do which is pharmacokinetics, so we take these SPF cats and we give the drug by different routes subcutaneously, intravenously, or orally and then we take samples and we freeze those and we do his magic stuff which is HPLC.
Slide 61 : Screening compounds
The data looks like this—not my data, Luke’s data. I’m not going to go through this, but these are all the heavy hitters in SARS. The fact that we have a kill curve here where it drops off, this is a curve that tells us what the effective concentration of the drug is which is the first step to getting a dose. This tells us how effective is that drug. Is it a candidate for cats because it has to be 2 to 3 µmol or less—if it is 5, 6, or 7 µmol concentration, that is not going to work because we are not going to be able to get that drug to a high enough concentration in a cat. We are going to discard it. We are going to take drugs that get a dose or an EC 50 (effective concentration 50) that is very low; if it is one 1 µmol, which is what GS is, that drug probably or likely would work.
Slide 62 : And the winners are
Here are the drugs that we found would work.
Slide 63 : Inhibitors & analogs
GC376 is an antibodies drug. Nimatrelvir in combination with another drug called ritonavir is called Paxlovid™ and you have probably heard of Paxlovid™. You might have even taken Paxlovid™ when you had a coronavirus infection. We found that drug is very effective. It was on that last page. It is probably one of the best in vitro drugs that we’ve seen but we’ve never trialed it in cats yet because we haven’t done the pharmacokinetics and we are working on that.
GS you all know about. We get our source from China, not from Gilead. I still have some GS in the freezer from Gilead, I am supposed to destroy because our agreement ran out on not the friendliest terms.
Remdesivir is the drug they are trying to protect. That is their human drug. It’s an IV drug that is given to very seriously ill COVID patients in the hospital and we have clinical trials running right now with remdesivir and I’ll talk about those.
These two drugs are owned by Merck. The EIDD stands for Emory Investigational Drug Development and that was then sold to Merck, and Merck is using one of those drugs—the 2801, and that is molnupiravir which is a drug you may have heard of. The three drugs that we use for SARS right now remdesivir, Paxlovid™, and molnupiravir all work against FIP and we are establishing data right now to see if they work in cats with FIP because that is not the same. Working in a plastic dish against virus is all very well, but we need to prove that it actually works in cats.
Slide 64 : Antiviral to market
Here is our mantra that I’ve been working under ever since I started working with FIP which has been more than 10 years – can we get an effective safe affordable and available FIP antiviral to market?
Slide 65 : Antiviral to market
All these words are important. I don’t think it’s a success if it costs $10,000 to treat a cat and cure them with 90+% effectiveness—that is not a success. Success is an affordable—key, affordable, safe, effective and it has to be available which means it needs to be able to get into the hands of veterinarians so they can actually prescribe it.
Slide 66 : Clinical trials
I’m going to talk about our clinical trials here for a little bit.
This is Krystle an internal medicine, infectious disease fellow. She was a fellow, now she is 100% clinician.
This is Amir Kol, who is a clinical pathologist and he and I and Krystle have a grand funded through the National Institutes of Health on FIP.
Slide 67 : Clinical trials
We have four trials currently ongoing. I’m just going to put them all up here.
Slide 68 : Oral GS vs REM
One is a GS versus remdesivir, so we have 19 cats. This trial is completed and we are writing this paper right now. I’ll just give you the synopsis—remdesivir works so it is not that you are all going to go marching out to the pharmacy and buy that. I don’t actually think you can get the powder form. The injectable form is called Veklury® and that is not the form you would want to use for the cats. By the way, everyone, these are oral now. We are not doing injectables.
Brian was talking about starting with injectables. We just do oral. I had trepidation too. I was a clinician and I agree, treating cats with oral capsules isn’t the easiest thing and there are some cats that are impossible to pill. I’m pretty good at pilling cats and I cannot pill some cats. It’s dangerous and those cats will destroy the pill.
I was worried when we transferred over to doing all oral it might be a problem. We have really good vet techs and they have been training the people to do it, and we have never had a problem with any of our cats and I don’t really understand that because I think we do get a cat once in a while that just doesn’t want to be pilled and it hasn’t been an issue. There are huge problems with injections as you probably are aware. Cats don’t like it. The reason they don’t like getting injected with GS is because the pH is acid and the reason it is acid is because that drug does not dissolve in neutral buffered solution. There has been a lot of work to try. We’ve tried, but we haven’t been able to do it, to get it into a liquid injectable form at a pH 7 and we’ve not been able to do it. I think it is achievable, but it is going to take a big effort. We decided to just forego that whole problem and give it as an oral capsule. I think that is the solution. I think the dose is a little higher. Remdesivir works, and GS obviously works.
Slide 69 : MSC therapy
We also did this mesenchymal stem cell therapy with GS. It would be GS with or without mesenchymal stem cells. The mesenchymal stem cells we have also been used for cats with gingivostomatitis which is a horrible disease in some cats. It gets cats euthanized so some of these cats are not treatable. They are treated with prednisone and they are treated with dental extractions and treated with a variety of other things. MSCs show the greatest promise for those cats because they are immunomodulatory and FIP is a weird disease that is associated with a cooperative badness between a bad virus and a cat that is predisposed to act inappropriately to that virus. The cat is partially to blame. For the cat that gets FIP, it is this marriage of the worst worlds. A bad virus in a cat that immunologically is predisposed to be overly exuberant, part of the injury of FIP is because the cat is attacking its own tissues. That is the reason, prednisone seems to be helpful, but this is also true of SARS coronavirus patients that are doing really poorly in the hospital. They will give them dexamethasone to suppress their immune system. Why? It is because part of the problem is that the immune system is causing tissue damage. That is definitely true with FIP so we thought MSCs might hold some promise, so we did this study right here. This is NIH funded because it is a model. We proposed it as a model for children who have been infected with coronavirus. That is completed.
Slide 70 : Dry FIP
This is a group out of Utah called Best Friends and they wanted a way of treating their cats with dry FIP. We had a number of cats with dry FIP and what we did here is we doubled the dose. This is oral too so oral GS and oral remdesivir and double the dose.
Slide 71 : Oral molnupiravir
This is the most recent one, so EveryCat funded this about a year and a half ago. We have five cats enrolled with three more to go. These two trials are still ongoing. We hope to finish this trial in the next month or two so by the end of the summer we will be done with these trails, and we have other ones planned with nirmatrelvir.
Slide 72 : Image
This is Julie Pires, she is one of our veterinary technicians and she runs our clinical trials group. This is a huge issue with getting these cats on trial and treating them. They have to come in every week to be looked at. It’s an enormous clinical machine that I am not involved with at all except I get samples to analyze so I am very thankful that we have our clinical group.
Slide 73 : Mr. Miyagi
I’m going to show you some of our cats.
Here is a classic wet FIP cat. This is Mr. Miyagi, and he has got this big, bloated belly. This cat didn’t actually act very sick, but it had a big, bloated belly. Then this is down the road after he had been treated.
Slide 74 : Lily
Here is one of our many, many Bengals. We have more Bengals than any other purebred cat. I’m not sure why that is, and Krystle was remarking when she gave a talk and she showed this picture. She said I had no idea there were so many sub-breeds of Bengals. I didn’t know that either. Apparently, there are lots of different subtypes of Bengal cats.
Here is the cat—scrawny and small, and then Lily down the road after she was doing much better.
Slide 75 : Daisy
Here is Daisy one of our dry FIP cats doing much better, so before and after. She is not grooming, and this is a typical thing we see with the young kittens that have FIP. One of the things that might clue you in that a cat might have FIP is they don’t groom. There are 100 other things too, but that is one of them.
Slide 76 : Grayson
This is Grayson, with this cat let’s see if you can tell me what part of the cat is abnormal.
This is a CNS or central nervous system infection and FIP hangs out right around the ventricles of the brain. It’s called periventriculitis and this cat has got hardcore neurological disease. It is looking pretty bad.
Slide 77 : Grayson
This is Grayson about I think three weeks or four weeks after treatment started. He still obviously still has some neurological deficits but is better and able to walk on his own. Then this is down the road. This cat I think is still on trial but is doing better all the time.
Slide 78 : What we learned
What we’ve learned is the majority of FIP-treated cats have done well clinically. If they are going to die they are going to die in the first week. That is not always because they got really, really bad FIP disease. Sometimes it is because they have something else going on too like bacterial sepsis. Bacteria in their blood in addition to FIP or they have something like pneumonia in addition to FIP, and the antiviral drugs are not going to do very much for those other diseases. We have seen several that have had heart disease so cats that have had cardiomyopathy in addition to FIP. The cat is just as FIP, so we have a really, really, firm criteria for getting one of our cats into the trial. We have to have a solid diagnosis, so we have to know for sure that cat has FIP and that is not so easy sometimes, especially for dry FIP. We need to know for sure that they have it.
Slide 79 : Cats that fail
If they fail we try to do a necropsy on all those cats. Doing a necropsy is what is, from my viewpoint, is actually the most important part of this trial. We could just throw drugs out there and treat a lot more cats than we are doing. What we are trying to do is find out an established dose and we are trying to establish treatment protocols; so how long do we need to treat these cats? When is a cat going to respond appropriately and when is a cat not going to respond? If a cat fails why does it fail—that is what we are really trying to do here. When we have a cat that fails we do a necropsy, and we do all these different things. This is histopathology looking at the tissues microscopically. We are going to do immunohistochemistry which is identifying how much virus is there in the cat’s tissues. We are going to collect the fluid and do a number of things with it. We are going to take tissues and do drug analysis on those tissues so we can get more information on dosage. One of the things that is hard to do for the dosage studies, the pharmacokinetic studies, is to give the cat the drug and then we can draw the blood. What I don’t want to do is give the cat the drug and then kill the cat and then get the eye and find out how much drug is in the eye and how much drug is in the blood. That is actually super important because one of the problems with treating animals with drugs is how much the drug actually gets to where you need it to be. How do we treat the brain? There is less drug that gets in the brain than in the blood and the only way we really know that is by doing tissue analysis. This gives us that opportunity without killing cats. This cat died because it didn’t respond well and we are trying to figure that out. This gives us also the opportunity to figure out how much of the drug is in the liver and how much is in the brain and how much is in the eye. It is super important. One of the reasons that I think GC376 is less effective or seemingly less is the ability to penetrate through the blood-brain barrier is poor. Our data suggests about 20% and we can improve those odds by jacking the dose up —that’s why I would like to increase the dose on those cats. Then we are going to do a bunch of PCR stuff.
Slide 80 : Gross necropsy
Here are the kinds of lesions we see. These were identified 40 years ago so we are seeing all those things. We are also seeing heart disease pneumonia, tracheitis, and bacterial sepsis. Those are, I guess it is not surprising that those cats died because the deck is so stacked against them. We actually have saved at least one of the cats that had bacterial sepsis. Krystle was astute enough to figure out the cat wasn’t just sick from FIP and had something else wrong, so she did a blood culture and found out it had bacteremia which means bacteria in the blood. Treated appropriately, that cat was circling the drain for about a week. I thought we were going to get him in on necropsy and then he pulled out and is doing fine.
Slide 81 : Untreated FIP
This is a kidney. There is a little bit of icterus or jaundice here. This is the immunohistochemistry of the kidney. These brown dots are virus. That is viral antigen in the kidney. Here is the eye with inflammation of the eye. This is the back of the eye in the choroid and here is virus, FIP virus embedded in that choroid. This is uveitis or the ocular form of FIP and that is inflammation in the liver or hepatitis.
Slide 82 : Chickee wet FIP
Chickee was treated for four days so this is inflammation in the peritoneum and liver, and you can see lots of inflammation here. Then if we try to stain it with IHC there is nothing, and that is because four days of antiviral therapy is sufficient to knock the virus down below detectible limits.
Slide 83 : Chickee 4 days after
That is how impressive these antivirals are. This cat still died, but it wasn’t just because of virus. It was because there was so much tissue damage because the cat attacked its own tissues in the process of trying to kill virus, the cat is attacking its own tissues and that is part of the problem with FIP. We did real-time, and we found virtually nothing. A normal cat is going to have like a million copies of virus—28 copies is barely detectible.
Slide 84 : Teddy molnupiravir trial
Here is a cat that failed the molnupiravir trial which is the EIDD. This is a Burmese, peritonitis, wet FIP, hepatitis, aspiration pneumonia—that is not FIP. This cat was force fed by the caretaker with a bottle and this is what happens if they don’t want to take that bottle. This actually happens all the time with foster kittens and foster puppies, is that over-exuberance in trying to force-feed them leads to aspiration pneumonia. The death here is aspiration pneumonia—not drug failure.
Slide 85 : Teddy slides
This cat was treated one day. I don’t think we gave this drug a firm enough chance. Here is the inflammation in the lymph node and there is the viral antigen so lots of virus here. One day of treatment. If this cat didn’t have aspiration pneumonia, I think we would have been able to save it.
Slide 86 : Antiviral treatment
Here is a graph—here is what it looks like. The viral load at the beginning is between 100 and 10 million copies. Then cats that die at 21 days show no virus, 11 days, no virus, 7 days a little bit of virus; so, we can’t detect viral antigen after this point like 2 days in. That virus drops very quickly. Those drugs work, every one of those drugs work even though these cats died. They didn’t die because of uncontrolled virus and they didn’t die because of a mutation of the virus that escaped antiviral pressure. That is not the reason for their death.
The drugs are amazing actually. I’m blown away at how effective these drugs are; for the amount of time that we have been searching for a drug like this to work, and then finding so many in the last 10 years is astounding.
Slide 87 : RT-PCR assays
I’m not going to talk about these, but we do a number of different PCRs and I would disagree that we have no way of PCR testing. I hear what you are saying. In order to identify FIPV by PCR you have to do a whole bunch of tricks and we have figured that out. It has taken us years, and this is not a commercial assay and it never will be so you have to sequence it. You have to amplify a part of the spike and then you have to sequence it. There is a code in there that tells you it is not enteric coronavirus, and it is FIP, but it requires sequencing. That requires a lot of effort, so it is never going to be used as a diagnostic test. That is the genome.
Slide 88 : Spike sequences
I’m not going to talk about this, but this is a test that we have done. It actually was started by Gary Whittaker at Cornell. This guy right here who is a brilliant virologist at Cornell, and what he is fishing for and what we have adopted is this furin motif cut slide, so on the cell, there is an enzyme on the cell that breaks the S1-S2 that allows the virus to get in. A lot of this is known because of SARS corona, but Gary’s paper predated SARS corona. Gary was working on this and figuring out FIP entry into the cell before they ever knew anything about SARS because it didn’t exist. If we amplify this part and then sequence this I can tell if it’s FIP versus a non-pathogenic form.
Slide 89 : Serology
Serology, Western blot—I’m not going to talk about it, but we are doing all those too.
Slide 90 : Paxlovid
This is new or fairly new, so the FDA just granted full approval for Pfizer’s drug, Paxlovid™; so that is that drug that is a combination. It is nirmatrelvir which is a protease inhibitor like GC376, and it has another drug in it called ritonavir, so we are working on this right now. We are doing pharmacokinetics on cats with this drug and then next year we hope to try it in cats.
Slide 91 : Acknowledgements
This is Mr. Biscuit, he was a clinical trial cat. He was actually infected experimentally with FIP. I was not involved with this and was not in agreement with it, but nonetheless, 12 cats were infected experimentally. He is an SPF cattery cat, and he was cured and then they all got adopted, so Niel has adopted two of them. I adopted one and other faculty and staff at Davis adopted all those cats. I want to again say how appreciative we are for our funding agencies, and you can see how Winn Feline has just a long list of various grants that they have funded with us and all of these other agencies. I’m so appreciative about that. I want to give time for Peter to talk so I am going to move on to that. I think there is a question-and-answer thing at the end so we can talk about that.
Slide 92 : ZenByCat
Peter Cohen: Full disclosure—people make me nervous, so I am going to pretend you are all cats. I practiced in front of my cats, and they all loved me.
My name is Peter Cohen, and I am one of the co-founders of Zen by Cat. I got involved in the fight against FIP when I had the great fortune to meet Dr. Niels Pedersen in 2016 when my cat Ms. Bean was diagnosed with FIP, and I got into the first trial. I brought Ms. Bean up there and she qualified. When I met Dr. Pedersen I was so grateful that Ms. Bean was going to have a chance and I said, “How can I help?” What can I do? He said, money, we need money. I took out a checkbook, this is when we used checks, and I wrote a $500 check which to me was a lot of money and I handed it to him. Then the look on his face made it clear, and I said “Oh, you mean big money.” He said, yes. He told me that FIP researchers around the world needed a million dollars a year to end this disease. I decided to create Zen by Cat. Zen by Cat is a legal nonprofit and I set it up specifically to guarantee that 90% of every dollar raised actually went to FIP research. We kept just 10% which is not enough to run a charity and I made up the difference.
Ms. Bean got into the trial and unfortunately, she didn’t survive the trail. She was there at UC Davis for four weeks. She went up and down and eventually she had a seizure and Dr. Pedersen himself had to euthanize her.
The following week when I was going up to get the ashes of Ms. Bean, the night before I was contacted by these very happy humans whose little FIP kitten Smokey had gotten into the trial. I believe he got in because Ms. Bean had died. This was a very small trial with 20 cats I believe. They were all excited, but they needed help with the logistics. They were in LA and it’s a nine-hour drive. In the conversation, it came up that they were kind of like a home private shelter. I knew that UC Davis cannot use shelter cats in their studies. We then had a longer discussion, and it was decided that Smokey’s best chance was for me to adopt him and to take him to UC Davis.
I drove to LA and met him in a parking lot. The owners—remember the parking lot because that will come back in this story. I signed the papers, and I adopted him and took him back to my house and wrote to Dr. Pedersen a very happy e-mail saying, “Hey, I’ve adopted Smokey and I’m going to bring him in tomorrow.” When I woke up the next morning I found a very angry e-mail from Dr. Pedersen who told me there is no way he can treat Smokey. One, because he is a shelter cat and that is against the rules, and more importantly because I’ve already had a cat in the trial, Ms. Bean, and it would look like favoritism. I sat down on the floor with Smokey for 10 minutes having no idea what I was going to do. I decided and wrote Dr. Pedersen back and said “Look, he is not a shelter cat, I legally adopted him and he got into the trial before I was connected. There is no favoritism and I’m bringing him up and I hope you change your mind.”
That seven-hour drive was very long and very terrifying, but when I got there, to his credit, he was very gracious. He said, “Look, I understand it’s not your fault and it certainly is not Smokey’s fault.” Then Smokey was let into the trial. He went on to become one of 7 cats out of 20 who survived. He was treated for eight days at UC Davis and then sent home and completed 11 more weeks of twice daily very painful GC376 injections. His last injection was on October 25, 2016, and he is 7 ½ years old now and a very happy healthy cat.
From 2016 to 2019 with Zen by Cat I learned a lot. Dr. Pedersen had warned me how hard it is to get humans to donate money, but we grew steadily. Then in 2019, I was contacted by a cat parent who told me about her little FIP kitten, Henry. She had read about Smokey’s treatment and the trials, and she had gone online and amazingly had found a Chinese online company that would sell her their version of GS441524. She had bought it and it was working and she had connected a few other cat parents with these drugs, and she reached out to me and wanted to know if I would help her start a group to save today’s cats. I agreed and I licensed FIP Warriors® to her. I had trademarked the name and so in 2019 Zen by Cat’s mission changed and Zen by Cat’s mission focused on funding research and FIP Warriors® was set up to help cure today’s cats. That grew from one cat parent and little Henry to today FIP Warriors® has groups all over the world in every country. The American group alone has almost 50,000 members. We have saved over 100,000 cats.
To be clear, I am not a vet and in fact FIP Warriors® and the admins around the world, they are the heroes, they are the ones. The way it works is we get contacted 100 times a day. Someone says they have an FIP cat. We find someone that is treating nearby, it doesn’t matter whether the cat is in Moscow, Istanbul, or Tennessee—we can usually find someone treating, and within 24 hours that person meets the person who is treating, and they are loaned a vial of drug. This is the connection to Smokey in a parking lot. I adopted him in a parking lot and now all these people meet strangers in parking lots and get these drugs to inject in their cats. We understand this is not a perfect system. Nobody wants it this way. It’s kind of shocking that seven years after Smokey was treated and four years after 2019 when FIP was determined to be a treatable disease, these drugs are still only available on the black market, not approved or whatever you want to call them. They almost all come from China. The way it works is we connect them and get them started on their treatment with FIP Warriors®. The admins then help people start buying their own drug. They help them with the dosing, and they help their vet talk to other vets so they can become comfortable to treat their cat. As I said, it’s an amazing organization—the FIP Warriors®. I want to be clear that it is separate from Zen by Cat. I remain focused on raising funding for FIP.
Slide 93 : FIP Warriors
Since 2019 we’ve saved over 100,000 cats. These cats, this is 1,200 cats. These are just the cats listed on my website. If you go to my website these are chronologically listed, the ones on the left are from 2016, 2017, 2018— all those cats died. We mark on them little rainbows as they crossed the bridge. Even though they died these people shared these stories and a lot of them became donors to pay it forward and to try to cure this disease. Then in 2019 when these drugs became available, these pictures on my website—instead of having rainbows we started having red crosses which we used to indicate that they are under treatment. Then we started having little suns to show that they are cured. All the pictures on the right are filled with sunshines, little red crosses, and very few rainbows.
Zen by Cat, as I said, was set up to fund FIP research and people ask me why should we donate to Zen by Cat. Why not donate directly to the EveryCat Health Foundation, whom we give all our money to anyway?
The answer is this. When you give us $10, $9 of it goes to EveryCat and they spread it around the world to all the different researchers. One thing is it helps offset our outreach costs, our websites, and our advertising so we can help cure today’s cats. None of the money comes to me. As someone mentioned, I have a house built for cats. I have 29 cats and they have lots of videos, including Smokey. We use the fame of my house to help raise money. Our main program is getting people to sign up for $10 per month automatic donations. What I found was when we would have fundraisers, which we still do the same, people donate all the time. We are trying to get away from that. We are trying to get more people to just give $10 per month. Dr. Pedersen had told me he needed a million dollars per year. That is only 5,000 people giving $10 per month. With over 100,000 cured cats we should be able to get to this number. I ask everyone in this room, if you have been touched by FIP, please consider joining our FIP Warriors®. If you like cat videos please check us out zenbycat.org. FIP Warriors® 5.0, they are the true heroes. If you contact me, I will put you in contact with them. As I said, we can cure, the cure rate for these drugs is about 90% and that includes all forms—wet, dry, and neurological. If we can get the cat started and the cat can go all the way through the 12 weeks, 90% of them get cured.
The last thing I will say is the cost has come way down. When we started in 2019, it was costing $5,000 to $10,000 for these drugs. Now there are so many online Chinese sellers we try to curate them, but the cost associated for wet FIP is $600. It goes up from there based on the weight of the cat. Neurological is the hardest to cure. They are all treated with the same drug. Most of the time we use GS, sometimes GC and that is the main drug that we use. The cost is definitely not prohibitive.
Slide 94 : Cat images
This is Smokey. He loves to wear hats and clothes. As I said, he is helping us pay it forward. He has many, many videos and some of them have gone viral and millions of people watch him. We use him to help get more people to sign up. Some people think it is cruel to dress cats in clothes. I swear to you, this is play for him. He has more clothes than me. As you can see, I actually wear this shirt every day.
I will also tell you if you sign up for $10 monthly donations we will give you a free shirt. Yours will have sleeves. We’ll give you a free shirt, but the shirt actually costs us $12. When you give us $10 per month, the first month $9 goes to EveryCat, $1 goes toward the shirt and it takes us a year to pay for the shirt. If you quit early and some people do, we make it easy to quit, I pay for the difference. We take very seriously that the money has to go to the researchers. I want to make sure that everyone knows that.
Slide 95 : FIP Warrior Club
Then the last thing, this is it. This is our Warrior Club at zenbycat.org. You can find lots of videos. Also, we are on Facebook, Instagram, TikTok; if you just like cat videos please check us out.
Thank you for listening, and I’m happy to answer questions either after or as part of this segment.
Steve Dale: Thank you, Peter, thank you.
Slide 96 : VIN Paul Pion
Peter Cohen has done more for cats than tuna, I believe. Really, you are quite incredible.
All right, so I’m going to get to some questions. I’ll get to as many as I possibly can. Please forgive me if I don’t get to all of them. First of all, you all have to—and I’ll let you share the one hand-mic over there, guys. When I get to the questions, two of you, unless there is a burning desire to have more of you, just for the sake of time answer the questions at tops.
I’m asking you all a favor. Can you say, “I ought to be fired”?
I ought to be fired, not you! Here’s why. I did a very bad thing. I introduced the Winn Board Members or the EveryCat Health Foundation board members that were at the time in the room. Do you know what I didn’t do? I forgot one. I don’t know how I did that. He is the incoming president, Dr. Dean Vicksman is here. I do mention the board member, I can say nothing bad about because he is after all our attorney whom I mentioned earlier. He is now in the room, George Eigenhauser is right over there. You all know George, I’ll tell you what I was so impressed about. Well, there are 700 things I was so impressed about over the course of time as I began to know George. At the first meeting, because he predated me on the board, at the first meeting I was at he said something instantly. He said, you know, we ought to do something about shelter cat studies and he went on about shelter cats which only proves what I have known all along. Everyone in this room cares about not only pedigree cats but all cats. Thank you!
Slide 97 : Q&A
Now, let’s get to these questions. As I say, I’ll get to as many as we possibly can.
Have we made any progress in finding a gene that makes a cat susceptible to FIP in the first place? Whoever wants to handle that – one or two people?
Panel Answer (Dr. Murphy): No. Niels did a lot of work on that with purebred cats and tried to identify susceptibility and resistance genes and basically didn’t. I’m not saying there isn’t, but I think Niels would agree that he didn’t unearth any of those.
Steve Dale: Next question: To quantify FIPV decreasing so very fast after treatment; then why must we treat a cat for 84 days? That is part one of the question. Part two is: Can we use nonsteroidal anti-inflammatory drugs instead of oral steroids?
Panel Answer (Dr. Holub): The 84 days—we just follow the current recommendations that are just scattered out there. We really don’t know. I believe there is an effort to try to get that treatment window lower and lower. As a clinician, we have very little guidance. Until we get somebody telling us to treat for less than 84 days, we know we are curing them if we treat for 84 days. Just out in the field we are not comfortable changing that protocol. I don’t know of any research that is out there now to have less days; if there were we would do it. We need our rock stars to tell us.
Panel Answer (Dr. Murphy): It’s a complicated question. My own personal opinion is wet FIP can be cured probably in two weeks for an uncomplicated case, but we haven’t done that because it is a risk. Niels has always thought that you are going to create resistance because you are not going to quite get rid of the virus. I think our data now suggests that the virus is gone.
The reason we treat for 84 days right now is because we don’t know if the virus has already flown the coop and is in the brain or eye even if they have no clinical signs. If it is in the brain or eye we are treating because we think it holds out there because the drugs don’t penetrate well. That is a subset of animals, but yes this is a huge problem, and it is something that we are trying to address. Not right now, but it is a plan.
Panel Answer (Dr. Weigner): For the most part, no, you can’t use nonsteroidal anti-inflammatories in cats. They don’t metabolize them properly. There are some that your veterinarians can use, but in general, you don’t want to use anything over the counter that is a nonsteroidal anti-inflammatory in cats.
Panel Answer (Dr. Holub): There are a lot of anecdotes, but we need our rock stars to publish, and that is happening. We need Peter to let us know that on his website.
Panel Answer (Peter Cohen): Really quickly, it is absolutely true that cats are cured in less than 12 weeks. The 12 weeks came from that first trial, that’s what they determined the dose that cats were surviving. We are just afraid to change that. We have lots of evidence because lots of people run out of money, or other reasons, or like you they just can’t stick the cat anymore and there have been cats cured. We are just afraid to lower it on our own. If you can afford it, we push people to do the 12 weeks.
Steve Dale: You know what? This is exactly why we need to, along with so many other reasons Dr. Murphy mentioned, continue to work toward raising money so we can give people like Dr. Murphy resources to do what he does.
Does a cat that has been treated and cured of FIP now have antibodies that prevent it from being re-infected?
Panel Answer (Dr. Murphy): We don’t know. Antibodies are actually part of the problem with FIP. The immune function that actually cures them is probably cell-mediated immunity so antibodies—unlike humans with SARS in which antibodies play a huge role—antibodies are maybe actually part of the problem with FIP. That is one of the things that is very interesting about FIP. We don’t know if they can get re-infected. We haven’t tried to do that and I haven’t heard anecdotal reports of a cat that has been infected, cured, and then years later gets FIP. Have any of you?
Panel Answer (Dr. Weigner): There have been some relapses, but I haven’t heard of any getting new infections.
Panel Answer (Peter Cohen): In our experience, cats that have completed treatment and then completed 84 days of observation after that relapse is extremely rare. There are some cases, but I can count them on my hand. Out of all the cases that we know of I have no idea. I think of Smokey’s chances of getting FIP to me as a layperson to be the same or less than a cat that hasn’t been treated. We won’t know until he lives his full life.
Steve Dale: From a breeder’s perspective, where is it best to keep our numbers low to keep stress levels low? By stress what do we mean?
Panel Answer (Dr. Holub): Actually, I think as breeders the most important thing you can do is get chronic shedders out of your cattery and work with your veterinarian because they can run fecal samples on those cats, find your chronic shedders using RT-PCR testing. There is a protocol in the guidelines for how to do that. Test your cats, find your chronic shedders. Move your chronic shedders out of your cattery and that is in the guidelines and that is a recommendation of the guidelines counsel.
Steve Dale: All right, we have about five minutes here because they are going to throw us out of the room so we have a hard stop. I want to get as many in as we can. Be cognizant to keep the answer short if possible.
Is it possible or realistic to attempt clearing catteries? That’s an old question, right? It has come up over and over again. Can you clear catteries of the enteric feline coronavirus?
Panel Answer (Dr. Murphy): There is a paper out of Bristol, in England, where they eliminated FIP using GS, not FIP but feline coronavirus in cats that had feline enteric corona. Not FIP, but you can eliminate it. If you want to search that it is Bristol, Addie I think is the lead author A-D-D-I-E. Yes, it can be done, but it means treating every one of the cats with GS. I’m not sure what their treatment was—if it was 84 days or what, but it can be done.
Steve Dale: Is it possible that the mutation of the feline coronavirus occurs in stressed cats because the immune system is compromised—and there is a word there I can’t read—similar to what happens to bacteria when antibiotic therapy is not completely producing mutated resistant bacteria? Interesting question.
Panel Answer (Dr. Weigner): It’s different with bacteria from viruses, but for the most part stressful events as in most mammals produce quite a bit of cortisone which, as you know, in the short term can be helpful, but in the long term it does decrease their immune system. It can make them more susceptible then to becoming infected.
Steve Dale: Is there a need for more cats in trials? If so, how can I contact you? Not me—a question from the back of the room.
Panel Answer (Dr. Murphy): We have only four or five more slots, but we are opening a new one next year with Paxlovid™. I don’t know anybody else running trials right now. Peter was saying, well I don’t know what—you said –how many? 10,000 cats? How many cats have been cured that you know of?
At 100,000 cats, I said 53 and you might go well why does it matter with 53? It’s because our trials are really expensive. It costs a minimum of $35,000 to run one of those trials. The NIH trial is $350,000. All of our trials together are well over a million. That is four trials of 53 cats. It is really expensive to do this kind of science because we are paying for almost everything including drugs and all the treatments, and a post if they die we have to do all those tests and whatnot. I know that’s not really answering your question, but hopefully next year there will be openings for a new trial and you can contact me if you have a cat—so we have a couple openings right now. We’ll be opening other ones later.
Steve Dale: You mentioned cardiomyopathy. Which came first, the FIP or the heart disease? Are they related in any of these cases?
Panel Answer (Dr. Murphy): We don’t know. I’m actually peripherally involved with that. That is Krystle Reagan and her resident. They are writing a paper right now on heart disease and FIP, what is the relationship? Is it causal or is it just happenstance that a cat that has congenital or whatever the pathogenesis of the cardiomyopathy is happens to get FIP. I don’t know the answer to that. I think that is very difficult to disentangle.
Steve Dale: This will be the last question. Where’s Shirley? Shirley says she has an FIP survivor which is great. Your question is, when the hell, I added those two words! When the heck will vets be legally allowed to advise, prescribe, and treat?
Panel Answer (Dr. Weigner): We can advise and help in many ways as Brian already mentioned, but we’ll be able to treat as veterinarians as soon as there is an approved drug to treat COVID on the market. Right now, Paxlovid™ has received full approval as about two weeks ago. We don’t actually have studies done for Paxlovid™ yet to see if that is something that we can use in cats safely. Molnupiravir is probably the closest then to becoming approved. It is already approved for emergency use. We can’t use that until it gets full approval. Once it is fully approved vets can use it by what’s called off-label use. If it is legal for people we can use it in cats off-label. So, in the near future.
Slide 98 : Thank you
Steve Dale: How many of you want to see us continue to support FIP studies?
How many of you want to see Dr. Murphy continue to work on FIP and have his colleagues do the same?
You have to help. They can’t do this without money. I’m not ashamed to beg for dollars. Whether it goes directly to the EveryCat Health Foundation or it goes to the amazing Zen by Cat, I don’t care. I will say we don’t give you a T-shirt. He gives you a T-shirt, and it is a very cool T-shirt. Does it have sleeves? Mine will. I have never seen him with sleeves. He doesn’t wear sleeves.
Peter Cohen, thank you very much. Dr. Drew Weigner for all his years committed to the EveryCat Health Foundation. Going back even more years, Dr. Brian Holub, and from the University of California, Davis, Dr. Brian Murphy. Thank you all very much. It’s you we thank for your support.