A list of health problems that should be solved pet-first

An open call for pitches

It is way easier and cheaper to develop treatments for diseases in pets than it is to develop treatments for diseases in humans. Because of this, my company is trying to pursue a cat-first development strategy, where we’ll develop treatments for pets first, then transition to humans.

But, this easier, cheaper development path comes with a tradeoff. The animal market is much more immature than the human health market. Revenues per drug are lower; there’s little in the way of basic research, and few animal health companies are willing to invest in any treatments that aren’t commercial stage. I’ve talked about all these issues before.

One of the most basic mistakes that I see people make when they come into the animal health space is overestimation of market opportunity. I’ve made this mistake myself. It’s an easy mistake to make: you see statistics like 60 million cats in the US, you see a statistic about some disease having a 1% prevalence rate, and then you think about your friend who spent $10k on their cat’s medical treatment. So you multiply 60 million*1%*10,000 and you get $6 billion, forgetting about what percentage of those 60 million cats belong to people who literally don’t have $400 in their bank account (and, of course, no insurance), nevermind $10,000.

The reality of the situation is that the single highest earning drug in animal health of all time makes about a billion a year (a biologic for canine atopic dermatitis), and everything else, currently, makes less than that. Most animal drugs are lucky to crack $50 million a year, especially cat drugs. 

This is a picture of the dog who invented Apoquel and Cytopoint, the canine atopic dermatitis biologics that make $1b+/year. His human hands helped him with the lab work and the Lab work. He is the wealthiest dog alive.

That being said, there are still major, uncracked problems in animal health that could be worth $100+ million/year, and possibly $1+ billion/year. These same uncracked problems are, not coincidentally, $1+ billion/year problems in humans.

Consider this my open call for pitches. If you are trying to work on the ideas below (or any other $100+ million/year problem) and are interested in trying to make them work for pets before humans, contact me at trevor [at] highwaypharm.com . I’ll help any way I can.

1. Affordable cancer treatments

Lots of pets get cancer, like somewhere around 25% of dogs and 20% of cats. Lots of pets die of cancer, including for me, personally, 2 rats and 3 dogs (all Labrador Retrievers).

Cancer in humans has, of course, been a major sink for research dollars and time since Nixon’s War on Cancer, with, to be honest, questionable bang for our buck¹. But, I think we can say that now, in the year 2024, cancer treatment options for human are pretty good on average, with some cancer treatment options verging on excellent, depending on the type of cancer. 

What they aren’t, however, is cheap. Keytruda (pembrolizumab), for example, is an incredible drug for a range of cancers, but it’s about $14k per month. This is not such an issue for humans on insurance, but it’s out of reach for almost all dog or cat owners.

I think there’d be a huge opportunity in the pet world for drugs like Keytruda (checkpoint inhibitors) that could be priced at even $1k/month. This would have to be paired with relatively cheap diagnostics, like tumor sequencing, but those are also becoming more common.

Keytruda alone would be a massive market in dogs and cats. About 20-30% of all human cancer can be treated with Keytruda. If we assume that’s also true in dogs and use the National Cancer Institute’s number of 6 million dogs diagnosed with cancer each year, we end up with roughly 6 million dogs diagnosed with cancer each year * 30% = 1.8 million dogs eligible for Keytruda each year. That’s a maximum market size of $1.8 billion per month for dogs alone, or $21.6 billion/year.

We’d have to adjust these numbers down because not all pet owners can afford $1k/month and not all dogs would be on Keytruda for a full year (although some would be on Keytruda for more than a year). But, still, adjusting down from $21.6 billion/year gives a lot of room before we’d get below $1 billion/year.

Merck, the makers of Keytruda, can’t provide a lower cost version of Keytruda themselves without cannibalizing their human sales. However, anyone who could figure out how to make cancer drugs as effective as Keytruda and offer them cheaply to pets could not only unlock a huge pet market, but also a huge human market as well for the enormous number of people who desperately want cancer treatment but they (or their national healthcare system) can’t afford $100k+year.

2. Affordable organ transplants or synthetic organs 

Cats and dogs, like humans, get organs that age. About half of geriatric cats get chronic kidney disease, while up to 75% of dogs can have heart problems. One potential fix for this is to fix the affected kidney or heart. Another potential fix is to replace the affected organ.

This should be an easier process than it is in humans. There are, unfortunately, no shortage of dogs and cats that are killed in shelters, put down by vets, or sacrificed for science. So, logically, there are plenty of organs that could be transplanted into a dog or a cat. However, in reality, almost no dogs or cats ever get organ transplants, because the cost of doing so is very expensive, the logistics aren’t there, and veterinarians don’t have the necessary training.

If someone could figure out how to get the cost of a cat kidney transplant down, this would open up a huge market. This probably wouldn’t be a winner-takes-all therapeutic market, though, and would probably be more like a specialized animal health hospital with a big logistics arm, unless there was a key market innovation that allowed for easy transplantation². So, probably not $100m+, there, for any individual company.

The winner-takes-all therapeutic market would be in the technically harder thing, cheap synthetic organs. Right now, artificial hearts go for about $1,000,000 all told³, and artificial kidneys are still in testing. In order for artificial hearts to be feasible for pet owners, I’d think that would have to come down to like $10k for each, with the idea being that middle class pet owners would be willing to pay that much for a literally life-saving treatment .

Claude claims that the materials for each artificial heart are about $10k, total. But, some major part of that is the bespoke nature of the artificial heart, and the fact that companies can’t save much money by saving on the material cost of the heart. So, let’s say we can get the material cost of artificial hearts down to $5k. Now we have $5k left to pay ourselves and the veterinary surgeons who are going to transplant the heart for us.

Let’s earmark $3k for the veterinary surgeons and their staff, or $600/hr for 5 hours. At this rate, we’d have to make sure that transplanting this heart isn’t much more difficult than repairing an ACL on a dog (i.e. requires roughly 6 months of training). I think we’d be able to do so if we also focused on making the artificial heart much easier to transplant than a normal heart. It already would be, naturally, given that artificial hearts don’t suffer tissue death outside the body, but there’s additional room for improvement.

Take the 10-20% of cats and dogs that die of heart disease each year as your total possible market, and that gives us maybe 1.5 million potential customers at $2k per heart. So, we get roughly $3 billion/year in potential revenue, which, as before, we’d have to modify down, but it sounds pretty good as a starting point.

And then, again, letting the rest of the world get a cheap artificial heart is a big deal. While the current number of people who are in line for a heart transplant is only in the thousands, some big part of that is how expensive and complicated heart transplants are. Considering that 1,000,000+ people get heart surgery each year, I’d bet there are way more people who would get an artificial heart transplant if it was safe, cheap, and reliable.

3. Predictable, safe, non-invasive behavioral modification for anxiety and reactivity

Pretty much all dogs and cats are reactive in some way or another. Even my dog, who’s generally very sweet (although incredibly hyper), gets so upset around his nails being cut that he’ll snap at the vet if they try to do it. Some large proportion of dogs or cats are so reactive that they force their owner to change their lifestyle or even put their pet down.

The treatments that exist for reactivity and anxiety are entirely drawn directly from people and are about as blunt as you’ve grown to expect from drugs for mental health. In broad terms, there are tranquilizers like trazodone, benzos like Xanax (alprazolam), and SSRIs like Prozac (fluoxetine). None of these drugs are great. They make the dog or cat appear drugged, don’t work in particularly stressful situations, and, in the case of SSRIs, take a while to start working.

What pet owners want is a treatment that consistently and predictably treats anxiety and reactivity without any side effects. So, Rover or Fluffy can still act cute and energetic most of the time, but they don’t attack the mailman/you/the neighbor’s dog on sight. 

Now, I understand that, for most people in the neuro field, this is the equivalent of saying, “I want to eat all the ice cream in the world and not get fat”. Like, yes, that is what people with reactive pets want, and that’s also what people with anxiety or panic disorders themselves want, but it’s not going to happen.

However, I think the research that’s being done right now on invasive and non-invasive brain stimulation (i.e putting electrodes inside the brain or using focused ultrasound outside the brain) might be the key to this. Retraining a dog or cat’s brain to see certain situations as nonthreatening by stimulating different parts of their brain could be a relatively rapid, predictable way of modifying behavior.

The barriers to this aren’t trivial. Invasive brain stimulation requires either a human or robot that can perform brain surgery, neither of which exist for vets right now and which would have side effects of its own. Noninvasive brain stimulation, on the other hand, shows more promise, especially transcranial magnetic stimulation and transcranial direct stimulation. Both of these have been used in rats to reduce anxiety.

Right now, though, noninvasive brain stimulation means dealing with a complex, clunky device. It’s hard enough to do it on a human, nevermind an anxious cat or dog. In order for this technology to make it into the mainstream, it has to be as easy to use as a beep collar: snap on, wait for your pet to freak out, and press the button to calm it down. Repeat until your pet no longer reacts to the bad stimulus.

Do this right, and it could be an almost universal treatment for pets. I know a lot of humans who’d want to have this, too. Imagine pressing a button every time you get a panic attack or find yourself stress-procrastinating and - poof! - the anxiety goes away. Pretty good pitch, right?

4. Reversal of fibrosis and organ aging (kidney, liver, pancreas, glaucoma)

As mentioned before, all pets have organs that age. One possibility is to replace those organs. This is difficult.

Another possibility is to reverse the aging of those organs. This may be easier. Probably the easiest path to doing this is to clear up the fibrosis that occurs with organ aging. Fibrosis, or the buildup of scar tissue, is an inevitable result of aging in any organ. Organs get injured, they get repaired, and the repair process leaves behind a scar. Rinse and repeat enough times, and you get an organ that’s more scar tissue than normal tissue, with the poor performance to match. While fibrosis may not be the sole or even the main cause of aging in an organ, it makes the organ perform worse, as useful space and tissue in the organ is clogged up by scar tissue.

There are many different organs in dogs and cats that get fibrotic as pets age. In cats, kidneys commonly get fibrotic, while in dogs, the pancreas commonly gets fibrotic⁴. Clearing out that fibrosis would help aging pets.

There’s a pretty long list of antifibrotic drugs, from TGF-beta inhibitors to mTOR inhibitors to antioxidants. Sorting through all of them will probably be a topic for a later blog post, although (spoiler alert) it has a pretty significant intersection with my current work, so I’m going to have to think carefully about what I say. 

Any company that wants to argue that their specific antifibrotic drug will work in say, glaucoma, will have to argue that theirs is somehow better than everyone else’s, probably through in vivo work in the animal in question. This raises the difficulty level, but it’s still doable. There are animal models for inducing kidney injury or pancreatitis, which are possible (although depressing) to do in dogs or cats. Then, you just need to make the leap from repeated induced kidney or pancreatic injury to chronic kidney disease or pancreatitis, which is a little questionable but might be useful.

Although, personally, I think a better option would be to work on aged animals of certain breeds that naturally develop chronic kidney disease or pancreatitis at high rates. This would require more work and probably a specialized lab, as there are approximately zero labs that have dog breeds other than beagles or really any specialized cat breed. Or it would require close partnership with a group that already works with a lot of those animals, like a specialized animal rescue. 

So, again, harder difficulty, but the payoff would be twofold: a more realistic animal model of whatever chronic disease you’re looking at, and less moral culpability for inducing a debilitating chronic disease in a helpless animal. All that would be left to do is try out your antifibrotic drug of choice (or a range of antifibrotic drugs) on this model.

This would be particularly exciting especially because these trials are super difficult to run in humans. They take a long time, you’re dealing with very sick people, and the progression is hard to predict. As a result, pretty much none of these very common chronic diseases have particularly good therapeutics. Getting good results for a therapeutic in, say, chronic kidney disease in animals would be a strong signal that we’d be able to get our first good result in humans for this disease. 

5. Cure for osteoarthritis 

Pretty much all aged humans and animals suffer from osteoarthritis. This isn’t a surprise. Osteoarthritis is really just insufficiently repaired injury to the joints. Your joints are put under constant stress, both by daily living and by one-off traumatic events. In children and young animals, these stresses heal quickly. In old people and old animals, they don’t heal quickly, and sometimes they don’t heal at all. 

The only actual “cure” for osteoarthritis in people or animals is to replace the joint. This is about $30k per joint in humans, and about $5k per joint in cats or dogs. This is, of course, prohibitively expensive for most people, especially outside of the US. It’s also only really effective for hips, knees, and shoulders. Spinal replacements, especially, have noticeably bad outcomes, but tend to be something people want replaced.

It would be great to get these costs to go down, although there’s always going to be a floor of how low the costs can go, given the time required by highly trained professionals (the cost of the joint replacement itself is only about $1500, even for humans, so way cheaper than an artificial heart) And, even if the costs do go down, like by an invention of a new technique that makes joint replacements quicker, it’s hard to imagine how a single company could capitalize on it themselves. The only exception I could imagine is if there was some way to productize the new technique (e.g. a robot that does joint replacement surgery or an external joint replacement), but that’s outside my realm of expertise.

The $1b+ opportunity in animals would be a curative therapeutic option, beyond just anti-inflammatories. Stem cells were supposed to be that option (and are still marketed as such by unscrupulous human and animal health clinics), but have had limited success, to put it generously. As it turns out, if you just randomly put stem cells in an injured joint, the stem cells don’t really know what to do, and don’t automatically turn into productive parts of that joint.

However, I still think that basic idea of regenerating the joint is what’s necessary to cure osteoarthritis and unlock this therapeutic opportunity. I’m not sure if this will be in the form of providing some sort of scaffolding for stem cells (like artificial cartilage) or maybe somehow retraining the reparative capacity of the joint (like by epigenetic modulation, growth factors, or even bioelectricity). Regardless, there’s a big opportunity there for basically all aged animals, including horses or zoo animals. Osteoarthritis comes for us all.

6. Treatment for dementia

I probably don’t need to belabor the point that dementia in people is a big deal with no good solutions. Everyone and their mother have an opinion about dementia and why the amyloid hypothesis isn’t working. or at least not well. I also won’t opine on what a better treatment would be, although I have my ideas.

Instead, I just want to point out that dogs get canine cognitive dysfunction, which is very similar to dementia, and elderly dogs get it at double digit rates. Sedentary dogs also get it really frequently, which means elderly sedentary dogs end up with an incredibly high rate of dementia. This means that any lab that keeps dogs until a natural death is almost guaranteed to have a high percentage of dogs with dementia.

So, instead of testing out a dementia treatment on a person or a monkey, or, you know, trying to somehow give a mouse Alzheimer’s, any researcher can test a dementia treatment on a comparatively rapidly progressing naturally occurring model of dementia in dogs. If it works, awesome, now you have a dementia treatment for dogs and strong evidence for one in humans.

The only caveats are:

1. There’s no universally agreed upon test for dementia in dogs, and it’s always hard to tell the difference between a dog who can’t do something and a dog who doesn’t feel like doing something.

2. People’s complaints about doggy dementia are mostly around them pooping in the house or being reactive. These are related to, but not the same as, being cognitively disabled. So, a successful treatment for dogs would need to consistently fix these types of symptoms, while that’s not true for a successful treatment for humans. In other words, it’s possible to develop a treatment for dogs that’s not good for humans.

But, these are challenges worth fighting through. Given that even getting to humans in dementia is at least $15 million, and getting to an approved drug is probably around $1b, being able to test dementia drugs more cheaply and quickly is worth a lot. It’d be much easier to have an iterative approach with a model population like dogs, where you can see if the treatment works in probably like 6 months in a completely captive population. If it doesn’t, revise and repeat.

1. I’ve written about cancer’s perverse development incentives before. 

2. In terms of patentable moats, I can imagine some sort of genetic editing of either donor or recipient to make immune rejection less likely. I can also imagine technology that allows for longer preservation of organs from donor to recipient to allow for an easier supply chain. But, that still means you’d need someone to actually do this stuff who could handle the complicated logistics, like maybe one of the veterinary hospital chains.

3. Although I’m also seeing $200k in some places, so I don’t know. Point is that it’s a lot.

4. If I wanted to start a fight, I’d say that the canine brain also gets fibrotic in the form of amyloid plaques, and this may be a cause of canine cognitive decline a.k.a. doggy Alzheimer’s. But, I’ll save that for a future blog post.