A drugs life: How David Bruyettes biotech startup is changing the way veterinary products come to market

Maria Sbytova / stock.adobe.com

Back in the mid-1990s, a pharmaceutical company was investigating a new drug called sildenafil as a potential treatment for heart disease. The drug did not improve anyone's cardiac function, so the company began the standard procedures to discontinue the clinical trial. When investigators told the participants the trial was over, they refused to return the drug. Confounded, the doctors asked why the men would want to keep a drug that didn't do anything for their heart condition.

Thus began the development of Viagra, perhaps the most successful serendipitous discovery in pharmaceutical industry history.

Viagra follows the typical development arc for new pharmaceuticals: Scientists determine what a chemical compound does in the body, then see where it can be applied to human medicine. Lead with the solution, then find the problem. If a pharma company thinks a drug has potential, it launches a four-stage clinical trial. Ten years and $100 million later, about 14% of those drugs make it through the FDA approval process to market. The FDA mandates a drug be safe and effective. The pharmaceutical company that spends the $100 million mandates it be profitable.

David Bruyette, DVM, DACVIM

Somewhere in another part of the building, the animal health divisions of large pharma companies wait on the sidelines. “What typically happens in these big pharma companies is that a drug bombs on the human side and they give it to the vet side,” says David Bruyette, DVM, DACVIM, chief medical officer at Anivive Lifesciences. “Then they say, ‘See if you can make something happen with it.'”

If there's potential, the process starts all over again with a new veterinary trial. This laborious, time-consuming and expensive series of steps may explain why FDA-approved veterinary drugs are so sparse. But Dr. Bruyette thinks Anivive can change all that.

“It's not really surprising that 85% of the diseases that veterinarians face either don't have any treatment, or veterinarians tend to use human drugs off label,” says Dr. Bruyette. “It just doesn't make financial sense to spend 10 years and $100 million on a product that may only sell $10 million a year. And that doesn't mean that that product and that disease aren't important. It just means there are probably better ways to invest your capital.”

The intro that almost didn't happen

Dr. Bruyette's entrance into the startup world began three and a half years ago, with a random email sent through LinkedIn. At the time, he was medical director at VCA West Los Angeles. Before that, he was head of internal medicine at Kansas State. Well-entrenched in traditional clinical practice, Dr. Bruyette almost ignored the LinkedIn message from a 20-something entrepreneur asking if he knew anything about dog diabetes. Dr. Bruyette, a diplomate of the American College of Veterinary Internal Medicine, replied that he did. Eventually.

“I wrote him back. I said, who are you? I don't know you,” Dr. Bruyette says, laughing. “I couldn't find him on the Internet anywhere.”

The entrepreneur in question was Dylan Balsz, who had already launched several successful companies, including International Pet Solutions, which sells a “pet potty” called PetLawn. Impressed by Balsz's success, Dr. Bruyette agreed to meet him. Balsz shared that he'd been approached by a pharma company wondering if he had any ideas for determining whether one of its shelved drugs might be of use in the veterinary space. Although the drug wasn't applicable on the human side, much of the preliminary testing had already been performed.

“On the human side, to get a drug approved, you show that it's safe in rodents and then typically you move it into something larger,” says Dr. Bruyette. “The larger animal could be a primate or a pig. A lot of times, it's a dog.”

Much of this research is in pharmacokinetics, Dr. Bruyette continues: “Do dogs absorb it? What concentrations? Does it get in their blood? Is it safe?”

In a large company, this would be where the handoff to animal health would take place if the drug had no human application. But in smaller companies with no easy way to access the veterinary market, the products are simply shuttered.

The company that contacted Balsz hoped he might know how to discover whether any of those drugs might improve the lives of animals. Balsz knew business, but he had no background in veterinary medicine-hence his out-of-the-blue LinkedIn message to a prominent veterinary endocrinologist.

Dr. Bruyette was in. Although he and Balsz did not end up developing the original drug they explored, things were about to get even more interesting.

Re-inventing drug discovery

In talking about the drug approval process, Balsz and Dr. Bruyette questioned whether there was a way to more make it more efficient and streamlined. “Does it really need to take 10 years and $100 million to get a drug approved?” says Dr. Bruyette. Making the process more cost-effective would remove a huge barrier to new drugs entering the veterinary market. “Is there a way to leverage existing data and target an unmet need?”

His and Balsz's goal became even loftier than their original idea of taking human medicine's castoffs and trying them on animals. What if, they asked, they could use software platforms to develop potential new therapies more efficiently?

Fast-forward to today. If you look at the who's-who on the Anivive homepage, you'll notice that many on the list are software engineers and computer scientists. How does this jibe with the stereotypical image of the lab-coat-wearing, beaker-holding scientist we typically associate with pharma research? “The best way to develop a lead,” says Dr. Bruyette, “is to develop software.”

Turns out that software development has kicked off a new golden era of drug discovery, and it's all about the approach.

“We look for an unmet need-for instance, lymphoma,” says Dr. Bruyette. “And then we ask, OK, what's really needed for lymphoma patients? What we would like to have for treatment is a veterinary-approved drug with a good safety margin that can be administered orally, that works through a mechanism of action that's different from other chemotherapeutics that are out there.” Anivive takes a veterinarian's therapeutic wish list and, through specially developed software platforms, starts sorting through existing data to see if such a compound might exist.

The software delivers an initial set of compounds. Then the process of elimination begins. “Do those compounds interact with a target that we know is present in lymphoma?” Dr. Bruyette says. “Is there a mutation in dog lymphoma cells and human lymphoma cells that would generate a target, and would this drug interact with that target?” The list of 20,000 becomes 10,000.

“Then we ask how many of those 10,000 compounds have data,” says Dr. Bruyette. The team also researches whether any of the compounds are already protected by a patent. Eventually, the list is whittled down to just a handful. With that list in hand, Anivive approaches the groups working with the drugs.

“We go out to whoever those people are, whether they're universities or pharma companies. We take an option so we can learn a little bit more about the drug. And if we like it, then we end-license it for veterinary use,” says Dr. Bruyette.

Anivive's internal regulatory team has experience taking therapeutics through both the FDA and USDA approval processes and eventually to market. The importance of the regulatory component can't be underestimated-particularly when it comes to determining whether a new product falls under the auspices of the FDA or USDA. In human medicine, it's easy: it all falls to the FDA. In animal medicine, there used to be a clear delineation: FDA for drugs that treat, USDA for vaccines that prevent. But today's newest biomedical technologies can blur the lines.

“The FDA has ruled that viral vector gene therapies are therapeutics. They're not biologic in nature,” says Dr. Bruyette. “But Cytopoint is a monoclonal antibody that went through USDA. Things that rely on the host to elicit the response, like a biological response modifier or monoclonal antibody-those are USDA products.”

Sometimes not even the agencies themselves are sure where to file a product. What if something is therapeutic by virtue of its immune-modulating properties? One product under investigation by Anivive is just such a compound. “We actually had a joint meeting with the USDA and FDA and presented our information to them and said, 'Where does this go?'”

At the moment, the product is available only through clinical trials under the FDA's pre-approval compassionate use provision.

‘We're an unmet needs company'

Nowhere is the need for novel drugs more apparent than in veterinary oncology. Before Tanovea's initial approval in 2017, there was no FDA-approved treatment for canine lymphoma. Patients were presented with the same off-label treatment options for decades: chemotherapy protocols like CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], and prednisolone), corticosteroids or imminent death. Options are similarly sparse with other neoplasias.

In its short time in existence, Anivive has launched investigations into 14 compounds; two are nearing the final stages of the approval process. The first is an oral product for lymphoma treatment. Imagine, for a moment, instead of the weekly IV infusions, telling clients about an effective oral medication. What might that mean for the thousands of afflicted pets diagnosed with lymphoma every year? And that's just the first product on the list.

Dr. Bruyette says Anivive's approach of starting with the end goal instead of the drug itself is unique among companies. “I think that's the thing that separates us,” he says. “We're not an oncology company; we're not an infectious disease company. We're an unmet needs company.”

Starting with the unmet needs of the field allows Anivive to target heavy-hitting diseases often considered a death sentence. In addition to the lymphoma treatment, Anivive plans to introduce a coccidiomycosis (valley fever) vaccine licensed from the University of Arizona, a feline infectious peritonitis (FIP) antiviral product licensed from Kansas State University and a recombinant angiotoxin-targeting hemangiosarcoma treatment currently in trials at the University of Minnesota. Any one of those treatments would be a major victory in veterinary medicine, but to move all of them forward at once-well, that's unheard of.

These partnerships have the benefit of streamlining both cost and time to approval. “It's significantly less money because we'll be able to leverage things like manufacturing. A lot of the time these companies already have worked out how to make it,” says Dr. Bruyette. “There'll be clinical studies they've already performed that may help us offset the costs of safety and toxicity studies.” This allows Anivive to produce drugs for smaller, often-ignored markets. Dr. Bruyette estimates that the time needed for their first drug's development and approval process will be shrunk from 10 years to somewhere between three and five.

What frustrates you the most?

While the current drugs are limited in availability to clinical trials through universities, Dr. Bruyette notes that general practitioners will be able to participate in future trials. “Cancer studies typically are going to be done at private practices or universities with oncologists,” he says, noting that participants must be willing to follow the stringent requirements of the FDA. The FIP treatment, however, “will be a general-practice-driven product.” Anivive's software platform has an arm specifically designed to identify and recruit general practitioners for clinical trial participation when the time comes.

Dr. Bruyette emphasizes that they view every practitioner, both specialist and GP, as being a part of this new process. “We want to hear from them. What are the diseases that you guys see that are the most frustrating to you?” he says. “What are the diseases that you want to see successful therapies for, either because they're associated with a very poor prognosis or the treatments are difficult or expensive? We really want to partner with the general practice doctor to bring things into the clinic that they'll actually use and that they need.”

Imagine the possibilities.

Anivive's official launch event took place at this year's ACVIM Forum June 6-8 in Phoenix, Arizona.

Dr. Jessica Vogelsang is a certified veterinary journalist, a regular contributing writer for a number of publications, author of the memoir All Dogs Go to Kevin, and creator of the popular blog Pawcurious.com.