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October 19, 2020
By Julie Wolf
Cayuga: Treating All Forms of Bleeding

Cayuga Biotech is a preclinical therapeutics company whose lead compound, CAY001, shows promise to change the way that severe bleeding episodes are treated. We spoke with CEO Damien Kudela, who explained the science and path forward for Cayuga.

Watch and read an abbreviated version of the conversation below.

How did you transition from academia to biotech entrepreneur?

I had never envisioned an academic route for my career and by the time I was done, I was looking for a new way to apply my scientific knowledge. Cayuga was seeded by a conversation I had in my 4th year of my Ph.D., where someone said that there was a real need for this technology and I should think about creating a company to advance it. Since we’d already been in the early stages of patenting my thesis and the CAY001 drug, I figured ‘I’ve already been a starving grad student; why not go be a starving entrepreneur as well?’

How do platelets work with polyphosphate to promote clotting, and where does CAY001 fit in?

If you think of a clot as a brick-and-mortar material, the platelets form the bricks. There’s a second compound called fibrinogen which is the mortar. That constitutes the physical clot. 

The problem becomes how to get that brick wall to plug the wound. Polyphosphate is produced by platelets and is essentially a catalyst for clot formation, a molecule whose job it is to speed things up. Adding polyphosphate helps the clot to form more quickly, which enables the clot to shut off the bleeding more quickly.

Bleeding causes a lot of negative outcomes for patients, so stopping the bleeding has many benefits. Not only are you saving their lives by reducing blood loss, but you can actually reduce the time it takes for them to heal as well. 

Bleeding causes a lot of negative outcomes for patients, so stopping the bleeding has many benefits. Not only are you saving their lives by reducing blood loss, but you can actually reduce the time it takes for them to heal as well. 

 

How does CAY001 differ from other pro-clotting drugs available?

Typically, many currently available drugs are recombinant factors that are either direct mimics of endogenous proteins or slight alterations of these same proteins. 

The issue with bleeding and clotting is that they are two sides of a seesaw. Typically, a patient is balanced flat but when they get injured, and start bleeding, the seesaw tips toward the dangerous effects of too much bleeding. Unfortunately, what can happen with recombinant drugs is that the balance remains out of whack; they can tip the seesaw in the other direction and they can have the dangerous effects of what’s called ‘throwing clots.’ 

This is a huge problem. All the drugs that treat bleeding currently have a black box label warning because of that. And doctors have to weigh a crucial decision in treating patients, asking whether the patient is critical enough to warrant the safety risk.

Using polyphosphate as a catalyst differs from these drugs because it has an effect on the rate, but it doesn’t affect the specific clotting factors present. For example, polyphosphate has its biggest effect on the clotting factor, thrombin. The patient doesn’t produce more thrombin. Polyphosphate has a more limited effect, so you can hopefully use it in a safer way.

What data support your hypothesis?

We’ve been looking at different tissues, specifically the lungs. This seems to be where a lot of nano-based drugs fail. Obviously, the liver is also a concern, because it plays such a huge role in clotting. And of course, the blood-brain barrier. 

What we’ve done is compared CAY001 to saline in a pig model. Pigs are hyper-clotters, so there was some evidence of clotting, but it was the same in both the saline and CAY001 drug-treated animals. That was likely the results of the pigs’ natural clotting cascade, but obviously, safety is the number one concern, especially in this field. The first question we’re always asked is, “is it safe?”

“Is it effective” is always the second question. We’re on the pathways and have very promising data that we’ve seen so far to lead us through safety, and the remaining IND-enabling studies as well as our clinical trials.

 

What will your clinical trials focus on for the first indication?

Until IndieBio, we were fully funded by DARPA and the Army. Obviously, bleeding is a huge problem on the battlefield and causes about 50% of deaths. There’s also a huge problem with bleeding here in the U.S., especially as patients age and may need to be prescribed anti-clotting drugs such as plavix or coumadin. The problem is that these patients are already in the clotting phase; they’re given anti-clotting drugs and they go back to a risk of bleeding. A lot of it is done because there is no treatment for bleeding.

There are other conditions where patients may benefit from a drug like CAY001. We’ve been focusing recently on platelet dysfunction. This could also benefit patients on chemotherapy who end up with thrombocytopenia, as well as patients who have congenital platelet disorders. We’ve identified a hemophilia-like genetic disease that affect platelets, as opposed to Factors 8 or 9. There’s a wide range of people who may benefit.

Obviously, everybody thinks the quantity of life is a major benefit, because bleeding can kill very quickly. Stopping a bleed also importantly enables patients to have a better quality of life, so they don’t have to worry about shaving or having an accident, whether the kitchen will be fatal. You can really help to give patients their life back.

 

Who is the Cayuga Biotech team?

I was at UC Santa Barbara, and the sole graduate student who really did any animal experiment at UC Santa Barbara was Kyle Ploetze. Kyle actually has a very good story of the first time we med; I’ll let him tell it another time. I ended up working with Kyle to test our new drug, and we hit it off while doing the test. The data worked well, and we got along well. Kyle and I jokingly refer to CAY001 as kind of our baby.

We were the two initial co-founders; in 2019, we needed to add a third person to do a lot of our quality controls. We were working on our manufacturing, and Nate, a postdoc at UC Santa Barbara, interviewed and we thought he was excellent, so brought him on board. It’s been excellent working together.

 

What are the next major milestones for Cayuga on the road ahead?

We had our first meeting with the FDA in May 2020, so we’ve gotten feedback. What we really need to do is finish our PK/PD and tox studies. These will help to figure how the drug is cleared and its toxicity; are there any adverse effects from the drug, what doses are safe, what doses are effective. Really, we need to determine it’s safe enough to move to human trials. We’re excited to present our data at Demo Day.

Learn more about Cayuga Biotech and all of IndieBio New York Class 1 companies at Demo Day.