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Please could you walk us through your career path to becoming CEO at Trevi?
Yes, of course. I started off in accounting at Ernst and Young and worked in a lot of different industries. I was drawn to biotech very early in my career. I wasn't a scientist, but I could certainly understand the importance of solving unmet medical needs and the innovation side of things.
So, my career path journeyed through biotech. I ended up becoming a CFO, and eventually CEO, of a prior company which was eventually acquired by our partner. Coming off that experience, I co-founded Trevi. My background grew through finance, which of course, is super important in biotech. As you know, it's expensive to develop drugs, and I’ve found that I have become a good reality partner for a lot of the scientists and drug developers that are doing a lot of the heavy lifting. And then, it is my job to ensure we are adequately financed to execute on our plans.
I founded this company with a neurologist, Dr. Thomas Sciascia, about 10 years ago. It's been an amazing journey, trying to get the company from our kitchen tables (literally) and bring it all the way to the patient. We're now a publicly traded NASDAQ company with just under a $2 billion market cap, so have seen a lot of things during that run.
How does HaduvioTM work differently from standard cough treatments?
The interesting thing about the investigational therapy Haduvio (nalbuphine ER) is that it sits broadly within the opioid class of drugs, but it's in this subcategory called mixed agonist-antagonists. There were four drugs developed, which were designed decades ago to get away from all the addiction problems. When you think about drugs that are addictive, like fentanyl or morphine, those are all mu-agonists.
Nalbuphine actually antagonizes mu, so it blocks mu and then agonizes (activates) at kappa. Tom, my co-founder, had become interested in it because the kappa receptor had not been explored in any depth, but there was some preclinical data that suggested it could be quite helpful in cough. So, we started looking at opioid biology and felt that this could be a potential solution for patients because it was an unscheduled drug, but appeared to have the benefits of good efficacy and safety. The innovation with Haduvio is nalbuphine had previously only been available as a subcutaneous injection. We have developed a twice-a-day extended release (ER) tablet, which is much more patient friendly for chronic conditions. That's what led us here.
I would say in cough specifically, the scientific breakthrough that we brought to the field is that there had been a lot of work done looking at different peripheral triggers in the lung for cough. You think about idiopathic pulmonary fibrosis (IPF), it's a lung problem, so people were trying to treat cough through different pathways in the lung. Very early on, Tom had been saying to me that cough is not a lung problem, but a brain problem. It's a lot like pain.
So, our investigational therapy not only works peripherally in the lungs, but it also works centrally in the spinal cord and importantly, in the brainstem and in the brain. It basically reduces the amplification that goes on from the cough signal, when it gets to the brain. Our data turned the cough world a little bit on its head, because there'd been many different peripheral only mechanisms studied in cough, most of which failed. And then, we came along with this central mechanism, which answered this important question.
What’s the most important scientific insight in IPF?
So, let’s talk about the cough reflex and what is happening when you cough. We all have a cough reflex to protect us from things like smoke or things that we shouldn't be breathing in. But for people with IPF, the scarring of the lungs is signaling to the brain that something is wrong and patients cough so frequently that it lowers the threshold that triggers cough. This is called hypersensitization. So, things like stepping outside into cold air; talking on the phone, smelling someone's perfume, etc. can all trigger coughs because the threshold's been reduced.
Consequently, these people have to walk around all day trying to be really mindful about what triggers their cough. Once they start coughing, it's really difficult to stop. Patients often talk about coughing until they vomit before it stops.
So, the importance behind what we're doing is that we're working in the lung to settle down that signal in the first place, but then, importantly, going to the brain to reduce that hypersensitization, allowing patients to have a more normalized cough threshold.
How is Trevi designing trials for such variable cough symptoms?
Cough's an important aspect of the disease of idiopathic pulmonary fibrosis, and, because it is cough, the field has used an objective cough monitor to measure that cough is actually being reduced. It's a sensor on the chest and essentially it counts the number of coughs these patients have. So, the primary endpoint is a mean change in cough frequency from baseline to the end of treatment.
We then also measure other secondary endpoints that are patient-reported outcomes. How severe was your cough today? How was your quality of life? Regarding quality of life, as you can imagine, it affects their sleep; they experience pain, depression, a lot of social anxiety, etc.
So, we're able to measure all these other secondary endpoints from the patient's perspective. But the primary endpoint is an actual counting of coughs to know that it's coming down. And I should just mention, on average, these patients cough between 650 to 1,000 times a day. And 90% of that cough is in the daytime, because the chronic cough in IPF is neurological. Once you go to sleep at night, it pretty much settles down.
So, you can imagine coughing that much throughout your day and trying to live a normal life. There is such a stigma in public associated with cough. Patients have told us that managing cough becomes an all-consuming part of their day.
What’s the market size for chronic cough in IPF?
It's a specialty market. About 150,000 patients have IPF, and about two-thirds have a cough that's refractory, meaning that nothing works for them. So, call it 100,000 treatable patients.
The sad part about IPF is that the average lifespan is about three to five years, and cough is typically present at the very beginning of the disease and present throughout the disease. Cough is often what gets people diagnosed with IPF. They get this chronic cough and, once they chase it to the ground, they find out they've got IPF. So, I think for those patients, having an option to treat their cough is an important aspect of treating their disease. Concerning pricing in this area; if you follow the antifibrotics, like Ofev or Esbriet, they're priced at roughly $150,000 per year. Boehringer Ingelheim just had a new drug approved, Jascayd, that's priced close to $200,000 per year.
The comps in the space are very high. It's not a particularly managed category; a lot of that's because it's small. Payers recognize cough as a very debilitating aspect of the disease. So, we're doing some payer research now, but it appears that you've got an ability to have specialty pricing here. We don’t expect payer coverage to be a big problem.
Importantly in the US, all these patients are seen at these interstitial lung disease (ILD) care centers. There are about 80 in the US. So, with a small sales force, you can detail this very effectively. We estimate that about 50-75 reps are needed to get to the pulmonologists that treat these patients. It's very executable for a small biotech company.
How does Trevi plan to communicate the therapy’s value to payers and clinicians?
The fact is that it's a very serious unmet need for the patient. Even though the antifibrotics may slow disease progression, they do nothing for how the patient feels, or functions, on a daily basis. What patients with fibrotic lung disease complain about is cough, fatigue, and dyspnea. We think those are all intertwined.
We're going to be sharing more data on fatigue and dyspnea as we move forward. If we get approved, we may be dosed in conjunction with the antifibrotics, hopefully extending life, with Haduvio potentially improving the overall quality of life for those patients. When you talk to a patient, remaining quality of life is very important to them as their days are miserable.
We were just on a call with a patient group, last week, and they talked about how they manage their entire day around their cough. If they have to go to the store, for instance, they'll try to go at 7:00 AM, when no one's there. Or if they wake up and have a coughing fit, they don't even try to go out. Everything in their day is based around their cough.
What are the factors shaping adoption of a symptom-targeted therapy, like Haduvio?
Well, we would make the case that the symptom is part of the disease. There's actually been some early papers written - if you have progressive fibrosis lung disease, and you're coughing constantly on lungs that are already fibrotic, that trauma potentially worsens the underlying disease.
Now, this is something we'll have to evaluate in our one-year extension studies, but I think that a lot of the experts feel that a cough is inextricably linked to the disease and the condition. So, there will be more to come on that with time, but I do think this is an important aspect of the overall management of the disease.
So, your actual question was about the adoption curve. I've heard several treating physicians answer this question. If you've got someone with an IPF diagnosis, they're essentially on a clock. There's really no reason to hold off from prescribing this drug to them. Otherwise, you're just giving away days of their life. So, every time we've tested this, there's a pretty quick adoption uptake around the drug, just because they're looking for something to treat what's bothering these patients so much.
What’s your capital allocation strategy as Trevi advances?
Fortunately, we had data in 2025, in our two lead indications of idiopathic pulmonary fibrosis (IPF) chronic cough and refractory chronic cough (RCC) and both were really strong data sets. So, we were able to raise $115 million, giving us just under $200 million in total.
That capital will allow us to fund the pivotal program for IPF and the next RCC study. We’re then going to expand into other interstitial lung diseases, beyond IPF, which also involve fibrosis and chronic cough. So, we'll be able to fund that next study as well, and get through all that data by late 2027.
So, we are well funded. We're able to advance each of our programs through the next round of clinical development and, I think, create a lot of shareholder value in the meantime.
Do you work hand in hand with patient groups and academic institutions?
Yes, with both. The academic institutions are critical thought leaders and investigators, so we've been getting advice from them all along. The patient advocacy groups are also so important – they give you direct access to the patient voice, which is always so important in drug development.
What would success look like for Trevi a couple of years from now?
For Trevi, it’s all about focus and execution. We have one investigational asset focused on three very severe cough indications, with very little competition. I tell people all the time that we are going to stay focused on delivering a therapeutic option for this big unmet need.
Initial data on the drug has been very encouraging. We've got a team that can run good clinical trials. We will align with the regulatory authorities on the path to approval. Success in the next two years is clearly about getting these trials completed; having positive data; preparing for filings in the US and Europe; and, in the meantime, working with patients and pulmonologists, so they understand the value of Haduvio and are ready when it comes to market.
What advice would you give to a future biotech executive, planning on their path toward commercialization?
I think, in our business, you always lead with the patient need. If you're focused on the patient, and if you've got innovation which offers a potential solution then it's really just a matter of finding your way through it.
So, my advice would be to focus on the patient need first and let that always lead your decisions. Clearly, we have to be capital efficient, make good business decisions and all that, but, typically, where there's high unmet patient need, the rest of that follows. And, as all of us know, perseverance and a little luck also helps.
