Trevi Therapeutics, Inc. Common Stock Morgan Stanley 24th Annual Global Healthcare Conference

Sure. First of all, thank you for having us. We appreciate it, and thank you for those of you that have hung around till the end of the day to hear us. Trevi is a simple story. We are a single-asset company focused in chronic cough indications. Three indications, idiopathic pulmonary fibrosis cough, other interstitial lung disease cough, and refractory chronic cough. There has been a lot of sort of movement on the competitive landscape around that. We have aligned with the FDA on our path forward and our lead indication of IPF cough. We have started those trials. We can get into more detail. We are in phase III, looking for a lot of data to start reading out some later this year and then second half of next year. It has been an exciting time to be in it.

I am joined by Jim Casella, who is our Chief Development Officer, so he has had a very busy summer sort of getting all this off the ground.

Yeah. Chronic cough has been an area that Big Pharma has been interested in for a while. Very big market. Just to orient you, just to kind of take each of the slices, idiopathic pulmonary fibrosis has a prevalence of about 140,000. 85% of them have cough. Two-thirds of them have uncontrolled cough. You can think about 100,000 patients. It is one of the number one complaints of these patients. We all know there has been a lot of work in IPF. Those are antifibrotics, slowing down disease. I think what our program brings to these patients is actually helping to manage their quality of life and day-to-day living. The other interstitial lung diseases, IPF is an interstitial lung disease, it is about half that market. You essentially double that whole opportunity. A lot of leverage in that market overall, with probably an additional clinical trial.

Refractory chronic cough is a very big opportunity. That is sort of 2 million to 3 million patients. A little bit blows up the specialty model we are in. The reality is, there has been, I think, 20 drugs tried in RCC, all of which have failed, and we should probably talk a little bit about why we think we are different. We are approaching that market. We are not going to change our specialty sort of focus there. We are going to go after the most refractory patients and maintain our pricing there. Each of these indications is quite large, and as I mentioned up front, we are alone left in these cough indications, so really exciting commercially. Final point on that is, maybe you are going to get to this later, but respiratory has been an area very manageable commercial-wise by biotech.

We are excited about the situation we are in.

Yeah, that's sort of the crux. When we got into this space, there was probably 20 programs going on, and most of the programs were dealing with cough through peripheral mechanisms in the lung, which sort of makes intuitive sense. I'm one of the two co-founders of the company, and my co-founder's a neurologist, and he had been sort of kvetching at me for a while that neurological cough is not a lung problem, it's a brain problem. It's a response to, if you think about IPF, it's essentially fibrosis of the lungs, and your brain's sending this signal acknowledging this fibrosis. Tom was convinced that whatever drug you treated this with, it had to be neurologically active. What's interesting about our mechanism, we work peripherally in the lung, but we also work centrally in the brain, so along that whole cough reflex arc.

I think as our data's rolled out, it's had a very big effect in almost everyone who's come on early. I think over time, these other mechanisms have failed. We're sort of left, and I think what we all take away from that is managing cough centrally is important.

Yeah. I'll touch on it. Jim, you add any color. I know you're going to get into a lot of trials, so.

Yeah You will be chatting away for a while.

Nalbuphine is an opioid, but as I like to explain to people, not all opioids are the same. There are four opioid receptors. When people hear the word opioid, they think of morphine, fentanyl. Those are all mu agonists. There is a class of drugs that are called mixed agonist-antagonists that were designed to get away from drug addiction. Our drug, nalbuphine, actually blocks that mu receptor and works at kappa. The experiment we were running is kappa helpful? That is kind of where we started off. The drug has been around as a subcutaneous injection for decades, so it has been unscheduled. We had to do some work. We did some human abuse potential work. We have done some respiratory depression work. All of that has been clean. We believe this drug is going to stay unscheduled. We picked this drug intentionally, because we thought we could get away from a lot of the baggage that has plagued opioids.