Trevi Therapeutics, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

No, at a high level, I think Trevi has been on a journey. We're in a unique place. We're a single asset company. We've got a mechanism we'll probably talk more about, work centrally and peripherally. We have found our way to the cough space, specifically IPF cough, ILD cough, and refractory chronic cough. It's been an interesting journey because as we've been working in this field over the five years, I think we've made a scientific breakthrough around, and kudos to my co-founder who's a neurologist. He kept saying to me, "People are thinking about cough as a lung problem. It's a brain problem." And sure enough, our central mechanism has put up very consistently good efficacy data, which is nice. I think the other dynamic that's gone on, I'm sure we'll spend some time talking about, is the field was very crowded when we got in.

All peripheral only mechanisms, all of which have failed. We are sitting in these three very big unmet need areas, and we are all alone at this point. We are into phase IIb and III, depending on the indication. We have got good alignment with the FDA, and I feel like it is a pretty clear path forward. We just need to execute.

Yeah. OCEAN-1 and OCEAN-2 are the trial names we have for our IPF cough, idiopathic pulmonary fibrosis cough. For those of you that do not know, about 85% of IPF patients cough. It is one of their number one complaints of the disease. It is a big deal to the patient. We had run a very positive phase IIb study, went to FDA. Agreed with them on essentially one really robust, big study, which is a 52-week study. It has got a 24-week efficacy endpoint, and importantly, that study has 300 patients. Because of our big effect size, you do not need a lot of patients here. We ended up powering that study through all seven secondary endpoints, including things like dyspnea, breathlessness, which is the other complaint these patients have, clinical meaningfulness, all things that are robust in the label.

In that meeting, the FDA suggested to us we consider running a second confirmatory trial, and this was in the era of Marty Makary saying everybody only has to do one pivotal. The division director said, "Look, we think it would be in your best interest to run a second study. It only has to be 12 weeks, not 24, and you only have to power through your primary and key secondary." That study is 200 patients, 12-week efficacy endpoint. The other study, the bigger study, is 300 patients powered through all endpoints, 52 weeks with a 24-week efficacy endpoint read. To be clear, we will not read that out till we unblind the full study.

We get asked the same question.

How do you respond? That is the question I was asking everybody that I could get to.

I did get some intel this weekend, so it is some hot off the press information. From Trevi's perspective, the only thing we really had to care about, the drug effect, I mean, obviously we care for patients, but did not really impact our program. There has been a placebo effect problem sort of that ran through the Merck program that I think Bellus/GSK did a lot of work to try to manage better. They made sure they truly had RCC patients in. They did some placebo run-in work, yada di yada. The news that we got this weekend, because apparently GSK has announced. They made an announcement in July that the trials failed, and they were terminating the program. Nothing else. They gave no other data.

What we learned is that data has been shared with the investigators in the RCC study that were in their study, who are also now our investigators. The word through the investigator grapevine is it wasn't a placebo problem. Placebo was well-behaved. The drug just didn't work. I guess in one of the two studies, drug was actually worse than placebo. Not shocking that they didn't want to put out that data. They just, I think, pulled the Band-Aid off and moved on. We interrogated that a bit, that our assumptions are fine. Nobody seems worried placebo effect can't be managed. These were two 1,000-person studies. To be clear, our Phase III, because it's an sNDA, we need one study, and it's probably only going to be about 300 patients.

I think our ability to get the right sites, the right patients, we've implemented all the things that I think Bellus and Glaxo left behind as good learnings. We should be able to get through this, I think.