HylaPharm aims to tackle canine cancer with first-of-its-kind chemotherapy

The Bioscience and Biotechnology Center (BTBC) in the Kansas City Animal Health Corridor has played host to a number of successful start-ups. Now, one firm currently based at the BTBC is looking to target a number of cancers in pets with what it believes is a novel chemotherapy. Animal Pharm analyst Sian Lazell spoke to HylaPharm to find out more.

University of Kansas (KU) spin-out HylaPharm is working on a targeted, injectable treatment for a range of cancers in dogs.

Dan Aires, chief executive of the company, explained his team are developing the first injectable, targeted chemotherapy to effectively treat locally advanced cancers.

“We’re covering virtually all solid cancers – that’s kind of new because until a couple of months ago, we were thinking we were going to be focused more on just oral and squamous cell carcinomas. Since then, we’ve seen the technology work in a broad variety of cancers,” he told Animal Pharm.

The firm’s HylaPlat injectable consists of established anti-cancer drug cisplatin complexed with hyaluronan. Dr Aires said the mechanics of cisplatin are already well understood by the US FDA, while hyaluronan is found naturally in the joints and skin, allowing local injection directly into a tumor.

Direct injection of the drug results in deep penetration into tumors, where it targets CD44 – a multistructural and multifunctional cell surface molecule – associated with aggression and cancer stem cell status. HylaPharm said the drug is retained in adjacent lymph nodes where locally advanced cancers metastasize.

Advantages of treatment
In terms of what makes HylaPlat stand out against conventional cancer treatments, HylaPharm believes there are a number of factors.

Compared to existing chemotherapy, the firm claims HylaPlat has a high therapeutic window and safety margin, delivers a high dose of the anti-cancer drug to both the tumor and lymphatic system, and hyaluronan actually binds to CD44 on cancers whereas conventional chemotherapy has no specific uptake by cancer cells.

Dr Aires added: “None of what we’re doing involves laboratory or artificial cancers. These are all otherwise healthy dogs, with owners, that got cancer.”

Speaking of the firm’s R&D progress, he said: “Through KU, our story reached a media outlet in Kansas City. Prior to that we’d been working through the University of Missouri (MU), which has a wonderful veterinary school but they’re in fairly a small community, so we were lucky to get one dog every three or six months – it was very slow.

“Then we were featured on television and suddenly, we had 30 dogs between just July and August. The owner calls and if they want to try the treatment and their veterinarian wants to try it, we will give the drug to the veterinary office, at no charge because this is all in the realm of research.

“The veterinarians typically charge $80 and they’ll sedate the dog, perform the injection, give the dog some antiemetic medications to avoid an upset stomach afterwards and that’s it. They can repeat it every three weeks as needed.”

Although HylaPharm has been on somewhat of a learning curve as it develops HylaPlat, Dr Aires said the firm has so far had some good responses.

“The original protocol called for four injections. Some dogs respond great after one but some cancers are much more tenacious and they take multiple injections,” he explained.

“In the initial trial at MU, we had some better and some worse formulations but we’ve now got our formulation issues settled. Of the dogs that received good formulations, three of the seven had complete responses that were durable. And two others had partial responses so it was a very high response rate.”

Determining course of treatment
Regarding duration of treatment, Dr Aires said HylaPharm are currently “playing it by ear”. He explained some cancers go away quicker than others and some owners push for a longer time with their pets, whereas others are happy if they can just spend a few more months with their dog.

“We treat until the cancer is gone or in some cases, the cancer gets smaller, the dog is happier, so the owner doesn’t really want to put the dog through more treatment because they’re just happy to have had some more time. There are very different approaches and it’s emotional as much as anything else.”

HylaPharm claims the side effects of the drug are generally “not clinically apparent”, meaning dogs seem to go back to their normal, healthy behaviour. Current chemotherapeutic treatments used by vets have numerous side effects – one of the major drawbacks of existing therapies.

“Often we’ll have a little bit of an increase in liver enzymes, which many cancer therapies have,” Dr Aires noted. “It’s a reason not to treat every day which is why we wait three weeks in between each treatment. Also, some dogs will have reduced numbers of platelets but again, that’s never been a clinically apparent issue. We don’t see bruising or bleeding or anything else. And the dogs are generally back to normal in three weeks.

“We’ve certainly had learning experiences along the way. For instance, we’ve learned that although with bigger dogs you can dose them on a milliliter per square meter basis, when you get to the smaller end of the spectrum, you don’t want to do that. You want to go to weight-based dosing, a lower dose.”

Treatment for different stages, easy access for owners
Moreover, it would appear the success rate of HylaPlat is broad in the types of cancers it can treat.

“We haven’t really collated the data yet but the difference now to when we started, is that we’re seeing good responses in all different stages of cancer, not just locally advanced, though we prefer locally advanced. It’s also all different kinds of cancers.”

Growing space for pet cancer treatments
Cancer is the leading cause of death in dogs over the age of two in the US. For some time now, a number of animal health firms have been developing new treatments. Despite this, the treatment area is yet to witness a truly blockbuster-sized drug.

Last year, Animal Pharm editor Joseph Harvey spoke to Merial, Aratana Therapeutics and VetDC – all of which are working on such treatments – to investigate why drugs specifically approved for canine and feline cancers have yet to form a valuable market space in animal health.

However, product approvals in the pet cancer field could gain pace in the next few years. VetDC recently achieved a significant regulatory milestone as it works to gain approval for its canine lymphoma treatment Tanovea.

Additionally, fellow US firm ELIAS Animal Health is moving forward with development of its own cancer treatment for use in combination with chemotherapy. ELIAS Cancer Immunotherapy is designed to tackle B-cell lymphoma in dogs and is currently undergoing clinical trials.

Moreover, companies are still coming to the fore with R&D efforts for cancer treatments. In August, companion animal therapeutics firm PetLife Pharmaceuticals secured InnoVision Therapeutics as a drug development partner to work on pre-investigational new animal drug studies for Vitalzul.

Aratana Therapeutics already has products on the market for lymphoma with Blontress (canine lymphoma monoclonal antibody B-cell) and Tactress (canine lymphoma monoclonal antibody T-Cell).

Several start-ups presenting at this year’s Kansas City Animal Health Corridor Investment Forum are also aiming to address cancer with their technology.

Industry expert Dr Linda Rhodesrecently told Animal Pharm areas such as anemia, diabetes, “and of course, cancer where extensive research is ongoing for humans, will be fertile territories for new products for pet therapeutics” in the years to come.

Dr Laird Forrest, chief operating officer at HylaPharm, added: “On top of all this, HylaPlat doesn’t always need to be administered at a big veterinary clinic. We have some vets that are basically farm vets and they don’t even need to anesthetize the dog, they can just give it an injection.

“A lot of the vets we work with are in small clinics and they are able to give chemotherapy too. So even people with less facilities than your primary care physician are treating cancer.”

Dr Aires said such a benefit means a treatment like HylaPlat would be not only be easy for veterinarians to administer but in turn, be more available to owners.

“It’s a real paradigm shift from going to the hospital, starting an intravenous treatment for thousands of dollars, to frankly a very cheap cancer treatment,” he said.

“We’ve seen this has been very appealing to the families of the dogs involved and we’re hoping it could lead to a different way to treat canine cancer.

“Currently owners will see a treatment and they’ll talk to their vet, they’ll ask what it costs and then they don’t bother. Now, in the very early stages of their pet’s cancer they’ll see a lump is growing, a biopsy will show it’s a cancer, then they will realize there is a fairly reasonable alternative treatment that they can pursue with their own vet to either cure their dog of cancer, in some cases, or to at least palliate life for a while and have a few more months or years with the dog.”

Dr Aires said HylaPharm is hoping its technology is something that could be widely used, as opposed to being a very niche product.

“In practical terms, the low price means we have developed a treatment for potentially millions of dogs, whose families don’t necessarily have the resources to go through with a multi-thousand-dollar cancer treatment that may or may not work. The goal is being able to bring something out that’s 90% cheaper, that could actually help a ton of dogs,” he said.

Crossover to other species?
Dr Aires said generally, HylaPlat seems to be more tolerable than current treatments – but does it have the potential for use in other species such as cats?

“We’ve talked about it. Cats usually tolerate some of the slower release platinum drugs but they don’t tolerate cisplatin. HylaPlat has a very small amount of initial cisplatin release and most of it is a slower release. So it might be fine in a cat but we’re waiting for some of the vets we’re working with to reach out to us, as they’re starting to understand how the drug works. A few of them know that if they see a cat with cancer, there’s nothing else they can do and the owner wants to try this, we can try it.”

Company still in early stages
At present, HylaPlat is in trial stages. Dr Aires said despite the company feeling the technology is largely ready the size of HylaPharm has some constraints.

“The thing is, we are a very small company. A larger company that has a sales organization can cover more ground,” he told Animal Pharm.

However, the firm’s technology has already gained a minor use, minor species (MUMS) designation from the FDA, so should have a quicker path to market.

The company is starting to work towards a new animal drug application but Dr Aires highlighted the amount of work required in getting HylaPlat through federal approval processes, followed by setting up distribution plans and other factors involved in a launch.

“We’ll probably do best to partner up with a business that has deep experience. We are talking to people and are in discussions,” he commented.

Hylapharm ‘open’ to support
HylaPharm is currently funded by angel investors and its founders. When asked if the company is actively seeking funding, Dr Aires commented: “Like any small company, we’re open to it. We’re a little unusual because we’re university oriented, so we’re currently unpaid.

“With additional funding we could move things along by expanding trials and starting the regulatory process – there’s a lot we could do with more funding.

However, with Dr Aires’ background in human health – he is director of the division of dermatology at KU – and Dr Forrest’s role as an associate professor at KU’s department of pharmaceutical chemistry, is HylaPharm’s focus solely on animal health?

“We’re focused on both animal and human health. We’re thrilled by the kinds of responses we’re getting in dogs. The idea is that it could be a comparative medicine where we want to have a canine component and a human component,” Dr Aires said.

“At this point, animal health is way in the lead for us. We have the MUMS designation and the technology is out there working. Whereas with humans, there are a lot of hoops to jump through before we can get a treatment into a person, let alone get it out to a wider market. So animal health is paramount but we’re not abandoning human health at all.

“Getting a drug into the human market costs, for example, $100 million and it’s very important when you’re trying to do that kind of project to de-risk it. What better way to de-risk it than to say, ‘look, this is being used in our best friends, who sometimes weigh 100lbs and have spontaneous cancers that are the same types that we get, they’re using it and doing well with it’?

“Animal health and human health are, I think, synergistic. I don’t see them as being competitive at all. Our hope would be to have both of them flourish because the animal side enhances the human side.”