Q1 2021 Trevi Therapeutics Inc Earnings Call

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Operator: I started in two. Please note that this event may be recorded. Various remarks management makes during this call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factor section of a company's most recent quarterly report on Form 10Q, which the company filed with the SEC this afternoon.

Earnings remarks management makes during this call about the company's future expectations plans and prospects constitute forward looking statements for purposes of the Safe Harbor provisions under the private Securities Litigation Reform Act of 1995.

Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section of the company's most recent quarterly report on form 10-Q, which the company filed with the SEC. This afternoon.

In addition, any forward looking statements represent the companys views only as of today and should not be relied upon.

Operator: In addition, any forward-looking statements represent the company's views only as of today; they should not be relied upon as representing the company's views as of any subsequent date. While the company may like to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so, even if its views change. Participating on today's call from Trevor Therapeutics are Jennifer Good, president and CEO, and Bill Forbes, Chief Development Officer. I would not like to turn the conference over to Jennifer. Please go ahead. Thank you.

The company's views as of any subsequent date.

While the company may elect to update these forward looking statements at some point in the future. The company specifically disclaims any obligation to do so even if its views change participating on the call on today's call from Trevi Therapeutics are Jennifer good President and CEO and Bill Forbes Chief Development Officer, I would now like to turn the conference over to Jennifer.

Please go ahead.

Thank you good afternoon, everyone and welcome to our first quarter 2021 earnings call and business update.

Jennifer L. Good: Thank you. Good afternoon, everyone, and welcome to our first quarter 2021 earnings call and business update. Joining me today on this call is Dr. Bill Forbes, Trevi's Chief Development Officer, who will be available to answer questions after my prepared remarks. Our last earnings call was only six weeks ago, so I will focus on giving an update on our clinical development progress and reporting our earnings for the first quarter. Our most advanced program in clinical development is paritis and parigo nodularis, or PN, which is a serious and debilitating disease characterized by papuels and nodules on the skin, as well as incessant and severe itching. There are currently no approved therapies for this indication. Parago nodularis is a chronic disease, and because of the repeated scratching, the papules and nodules can spread and continue to get worse.

Joining me today on this call is Dr. Bell Forbes Trevi, Chief Development Officer, who will be available to answer questions. After my prepared remarks.

Our last earnings call was only six weeks ago. So I will focus on giving an update on our clinical development progress and reporting our earnings for the first quarter.

Our most advanced program in clinical development as price and Prego, Nigel Arris, RPM, which is a serious and debilitating disease characterized by tap you also naturals on the skin as well as incessantly severe itching. There are currently no approved therapies for this indication prego, Nigel Erith is a chronic disease and because of the repeat it.

Wrapping the populace of nodules could've spread and continue to worst Morrison.

We estimate the global prevalence prevalence of pianists approximately 730000 patients with 300000 patients in the U S and 430000 in the rest of the world.

Jennifer L. Good: We estimate the global prevalence of PN as approximately 730,000 patients, with 300,000 patients in the U.S. and 430,000 in the rest of the world. Although there are biologics also in development for PN, we are the only non-biologic oral candidate in late phase development, which we believe potentially positions us with an important competitive advantage for the serious unmet need. We are currently conducting a phase 2B slash 3 trial in this condition, which we call our prism trial. The prism trial is recruiting in both the U.S. and Europe, and to date, we have more than 60 sites activated.

Although there are biologics also in development for Pn, we are the only non biologic oral candidate in late phase development, which we believe potentially positions us with an important competitive advantage for the serious unmet need.

We are currently conducting a phase two be slashed free trial in this condition, which we call our prism trial. The prism trial is recruiting in both the U S and Europe and today, we have more than 60 sites activated the primary endpoint in this study as a responder analysis based on the reduction in itch intensity as measured by the worst day.

Jennifer L. Good: The primary endpoint in the study is a responder analysis based on the reduction in itch intensity, as measured by the worst-ditch numerical rating scale after 12 weeks of blinded fixed dosing. We currently have randomized approximately 255 of the planned 360 subjects into the trial, or greater than 70% of enrollment. We are encouraged by the feedback from the sites and continue to have a very high percentage, greater than 95%, of eligible subjects that complete week 14 and roll over into the open-label extension portion of this trial.

Numerical rating scale after 12 weeks of blinded fixed dosing.

We currently have randomized approximately 255 of the planned 360 subjects into the trial are greater than 70% of enrollment. We are encouraged by the feedback from the sites and continue to have a very high percentage greater than 95% of eligible subjects that complete week 14, and rollover into the open label.

Extension portion of this trial.

This will provide not only long term safety data, but also important efficacy data around skin healing and quality of life for these subjects, we believe that by treating the symptomatic endpoint of reducing itch that an effective therapy has the potential to disrupt the itch scratch cycle, leading to skin healing and resulting in disease model.

Jennifer L. Good: This will provide not only long-term safety data but also important efficacy data around skin healing and quality of life for these subjects. We believe that by treating the symptomatic endpoint of reducing itch, an effective therapy has the potential to disrupt its scrap cycle, leading to skin healing and resulting in disease modifications over time. Regarding enrollment, we have a good group of sites and continue to identify and implement strategies that support the sites to continue to find and recruit new subjects.

Vacations overtime.

Regarding enrollment we have a good group of sites and continue to identify and implement strategies that support the sites to continue to find and recruit new subjects. We continue to push for completing enrollment in the third quarter of this year, but we have broadened our guidance to the second half of the year knowing that enrollment during the summer months of July and August.

Jennifer L. Good: We continue to push for completing enrollment in the third quarter of this year, but we have broadened our guidance to the second half of the year, knowing that enrollment during the summer months of July and August may slow a bit, especially in light of easing COVID restrictions and the desire for people to travel again. We will announce when enrollment is complete, and I hope by our next earnings call, there will be a short runway left for enrollment in this study.

Flow a bit, especially in light of easing COVID-19 restrictions and the desire for people to travel again, we will announce when enrollment is complete and I hope by our next earnings call. There will be a short runway left on enrollment for this study.

In addition to executing on the clinical trial. The development team is preparing for next steps to move forward. In this indication. We are excited to announce that we recently received fast track designation from the FDA for this proposed indication. The fast track designation is intended to facilitate development and expedite the review of drugs to.

Jennifer L. Good: In addition to executing on the clinical trial, the development team is preparing for next steps to move forward in this indication. We are excited to announce that we recently received fast-track designation from the FDA for this proposed indication. Fast-track designation is intended to facilitate development and expedite the review of drugs to treat serious and life-threatening conditions so that an approved product can reach the market expeditiously.

Treat serious and life threatening conditions, so that an approved product can reach the market expeditiously.

Turning now to our second clinical program for chronic cough, and idiopathic pulmonary fibrosis or IPF.

Jennifer L. Good: Turning now to our second clinical program for chronic cough in idiopathic pulmonary fibrosis, or IPF. IPF is a progressive and severe condition in which there is scarring of the lung tissues. One of the leading debilitating symptoms of this disease is chronic coughing, which affects approximately 70 to 85% of these patients and for which there are no approved therapies.

<unk> is a progressive and severe condition in which they're scarring of the lung tissues. One of the leading debilitating symptoms of this disease is chronic coughing, which affects approximately 70 to 85 per cent of these patients and for which there are no approved therapies.

In the U S. We estimate that there are approximately 130000 patients with IPF and an equal amount in Europe.

Jennifer L. Good: In the US, we estimate that there are approximately 130,000 patients with IPF and an equal amount in Europe. Worldwide, it is estimated that there are in excess of 1 million patients that suffer from IPF. Due to the high five-year mortality associated with IPF, prescribers and patients are not only looking to slow the progression of the disease but also improve their quality of life. However, there are currently no approved therapies for this serious condition.

Why it is estimated there are in excess of 1 million patients that suffer from IPF due to the high five year mortality associated with IPF prescribers and patients are not only looking to slow the progression of the disease, but also improve their quality of life. There are currently no approved therapies for this serious condition.

We are conducting a phase II double blind crossover study with a 14 day washout period between each three week treatment arm. The primary endpoint assessment is the mean percent change in daytime cough frequency from baseline the daytime cough frequency as measured by a digital cost monitor between the treatment and placebo.

Jennifer L. Good: We are conducting a phase two double-blind crossover study with a 14-day washout period between each three-week treatment arm. The primary endpoint assessment is the mean percent change in daytime cost frequency from baseline. The daytime cost frequency is measured by a digital cough monitor between the treatment and placebo arms.

Oh arms. This trial is currently being conducted in the U K and given that this patient group is considered high risk if they contract COVID-19 due to their lung impairment. This trial have been more significantly impacted by COVID-19 restrictions than Rpms study, we are happy to see the lifting of the shelter in place for.

Jennifer L. Good: This trial is currently being conducted in the UK, and given that this patient group is considered high risk if they contract COVID-19 due to the trial or due to their lung impairment, this trial has been more significantly impacted by COVID-19 restrictions than our PM study. We are happy to see the lifting of the shelter and place restrictions for these patients in the UK, which were issued in early December. Due to their condition, IPF patients were prioritized for COVID vaccinations, and we estimate that most of these patients are now fully vaccinated.

<unk> for these patients in the U K, which were issued in early December due to their condition IPF patients were prioritized for COVID-19 vaccination and we estimate that most of these patients are now fully vaccinated.

We have been working closely with our centers to determine timelines for reopening of clinical research for this trial, we are seeing clinics begin to reopen and staff returning for research many of the staff and investigators had been prioritized to treating COVID-19 patients over the past year to date, we have several sites that have received approval to.

Jennifer L. Good: We have been working closely with our centers to determine timelines for the reopening of clinical research for this trial. We are seeing clinics begin to reopen, and staff returning for research. Many of the staff and investigators had been prioritized for treating COVID-19 patients over the past year.

Jennifer L. Good: To date, we have several sites that have received approval to reopen their clinical research. It is encouraging to note that some of those sites have already started screening for our trial, and we expect to see enrollment resume this quarter. We will continue to work closely with all of our remaining qualified sites in the UK to get the study fully up and enrolling. As a reminder, this study is designed to enroll approximately 60 subjects with a goal of getting 44 completers.

We opened their clinical research encouraging to note some of those sites have already started screening for our trial and we expect to see enrollment resumed this quarter. We will continue to work closely with all of our remaining qualified sites in the U K to get the study fully up and enrolling.

As a reminder, this study is designed to enroll approximately 60 subjects with a goal of getting 44 completer. So if we can get some momentum in enrollment we are optimistic we can get this study finished.

Jennifer L. Good: So if we can get some momentum in enrollment, we are optimistic we can get the study finished. Just a quick update on Germany. As you may recall, Trevi was pursuing potential regulatory and ethics board approvals to add study sites in Germany.

Just a quick update on Germany, as you may recall, trevi with pursuing potential regulatory and ethics board approvals to add study sites in Germany. We did make good progress on that effort. However, we have decided not to pursue opening new clinical sites in Germany due to the estimated timeline and cost to add these additional sites instead in light of the ear.

Jennifer L. Good: We did make good progress on that effort. However, we have decided not to pursue opening new clinical sites in Germany due to the estimated timeline and cost to add these additional sites. Instead, in light of the easing of pandemic restrictions in the United Kingdom, we are focusing our efforts on the completion of enrollment in the U.K. With that summary of the current status of both trials, I will now review our financial results for the first quarter of 2021.

<unk> of pandemic restrictions in the United Kingdom, we are focusing our efforts on the completion of enrollment in the U K.

With that summary on the current status of both trials I will now review our financial results for the first quarter of 2021.

As a reminder, the full financial results for the first quarter of 2021 can be found in our press release issued ahead of this call and our 10-Q, which was filed with the SEC today after the market closed.

Jennifer L. Good: As a reminder, the full financial results for the first quarter of 2021 can be found in our press release issued ahead of this call and our 10Q, which was filed with the SEC today after the market closed. For the first quarter of 2021, we reported a net loss of 8.4 million compared to a net loss of 8.5 million for the same quarter of 2020. R&D expenses were 5.6 million during the first quarter of 2021 compared to 6 million in the same period of 2020.

For the first quarter of 2021, we reported a net loss of $8 4 million compared to a net loss of $8 5 million for the same quarter of 2020.

R&D expenses were $5 6 million during the first quarter of 2021 compared to $6 million in the same period of 2020.

The decrease was primarily due to decreased purchases up clinical trial supplies, which is largely based on timing and the completion of our phase <unk> clinical trial in patients with chronic liver disease that we conducted a year ago.

Jennifer L. Good: The decrease was primarily due to decreased purchases of clinical trial supplies, which is largely based on timing and the completion of our Phase 1B clinical trial in patients with chronic liver disease that we conducted a year ago.

These decreases were partially offset by an increase in activity and enrollment in our ongoing prism trial as well as an increase in personnel related expenses consulting and professional fees.

Jennifer L. Good: These decreases were partially offset by an increase in activity and enrollment in our ongoing prism trial, as well as an increase in personnel-related expenses, consulting, and professional fees. G&A expenses were 2.5 million during the first quarter of 2021, compared to 2.6 million in the same period of 2020. The decrease was primarily due to a decrease in stock-based compensation expense.

G&A expenses were $2 5 million during the first quarter of 2021 compared to $2 6 million in the same period of 2020. The decrease was primarily due to a decrease in stock based compensation expense.

We have remained at a relatively consistent run rate with respect to our overhead costs.

Jennifer L. Good: We have remained on a relatively consistent runway with respect to our overhead costs. As of March 31, 2021, our cash and cash equivalents totaled 41.6 million compared to 45 million at December 31, 2020. Our current cash position is expected to be sufficient to fund operations into the second quarter of 2022. Beyond the anticipated top line results from the Prism trial, and although we need to see another quarter or two of enrollment before we can understand the enrollment timelines for cost coming out of the COVID-19 restrictions, we believe it can also carry us to the full enrollment of the cough trial. That is all I have for our prepared remarks. Now I'll turn the call back over to the operator for Q&A.

As of March 31, 2021, our cash and cash equivalents totaled $41 6 million compared to $45 million at December 31, 2020.

Our current cash position is expected to be sufficient to fund operations into the second quarter of 2022 beyond the anticipated top line results from the prism trial, and although we need to see another quarter or two of enrollment before we can understand the enrollment timelines for cost coming out of the COVID-19 restrictions. We believe it can also carry.

To the full enrollment of the cough trial.

That is all I have for our prepared remarks, now I'll turn the call back over to the operator for Q&A.

[laughter].

We will now begin the question is from session.

Operator: Thank you. We will now begin the question and answer session. To ask a question, you may press stars and one on your Touchtown phone. If you were using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press Starvin 2. Today's first question comes from Annabelle Simini on behalf of Steve-Hol. Please go ahead.

Yes of course.

One on your Touchstone.

Oh yeah.

It was reasonable.

So from a whole possibilities.

A question please push close in June.

So there's always Washington comes from Edibles, you're moving.

Uh huh.

Hi, Thanks for the quick update I actually wanted to ask.

Annabel Eva Samimy: Hi, thanks for the quick update. I actually wanted to ask a bigger picture question about the opioid approach. It's not quite the same mechanism, but I think the oral capo opiate receptor is validating and shows activity in two periodic populations. So clearly, there's something to, at least the CAPA approach, and I realize that yours is a little bit different with the dual mechanism.

Bigger picture question about the opioid approach.

It's not quite the same mechanism, but I think so.

Oral Kappa opioid receptor.

Was validating and shows activity and to predict population. So clearly there's something to at least the cap of approach and I realize that yours is a little bit there from what the dual mechanism, but I guess, what we have evidence of now is the fact that.

Jennifer L. Good: But I guess what we have evidence of now is the fact that the behavior of these two periodic populations is really very difficult to peg. And, you know, even in an AD population where the it is very consistent, I think, you know, it's still very difficult to understand the behaviors of different itch populations. So what is it that you can draw from some of these studies and what can you do to, I guess, manage what could be a very variable population, even in PN where itch is, is, endemic to the problem? So maybe you can just speak a little bit broadly about that.

Behavior of these two parotic populations are really very difficult to peg.

And you know even in a day population, where it's just very consistent I think.

You know, it's still very difficult to understand the behaviors are different each population. So what is it that you can draw from some of these studies and what can you do to I guess manage what could be a very variable population even in P and where it is.

Yeah.

And going back to the problem.

So maybe you can just speak a little bit broadly about that.

Go ahead bill.

Yeah. Thanks, Jonathan Thanks, Annabel for the question.

Bill Forbes: Yeah, thanks Jennifer. Thanks Annabel for the question. Let me kind of step through because, obviously, we've given this a lot of thought.

Well, let me kind of skeptical because obviously, you've given us a lot of thought I think.

Bill Forbes: I think the cap agonist that you may be talking about is actually an opioid peptide. As you know, with our nalbucine oral formulation, our molecule is very well behaved from an absorption, distribution, metabolism, and excretion perspective. Our formulation scales within our dosing range in a linear fashion, and it prolongs the half-life from the parental formulation that's been on the market for decades to this oral formulation. It increases it from two to nine hours. So we know that Nalbufine has a well-characterized safety profile. It's got decades of use as a parental.

Capex and if so you may be talking about is actually an opioid peptides.

As you know with our net abusing the oral formulation of our molecule is very well behaved from an absorption distribution metabolism and excretion perspective, our formulation scales within our dosing range in a linear fashion.

And it prolongs the half life from the peripheral formulation that's been on the market for decades to this oral formulation. It increases it from two to nine hours. So we know that they'll be using other we'll characterize safety profile. It's got decades abuses of control we have over 800 patients in controlled clinical trials using the oral formulation.

Bill Forbes: We have over 800 patients in controlled clinical trials using the oral formulation. So I think in many respects, as we look at this from a safety and efficacy perspective, our small molecule is very well-behaved. As we take a look at the different populations, I mean, one of the things that we've done a very good job of using this formulation and this product is that we're able to show dose response, and I think our uremic paritis data is key to that.

So I think in many respects as we look at this from a safety and efficacy perspective, our small molecule is very well behaved.

As we take a look.

Uh huh.

At the different populations I mean, one of the things that we've done a very good job at using this formulation.

And using this product is that we're able to show a dose response and I think are you laying at pruritus data is.

These key for that we know that this drug is from based upon that 373 patient study looks safe and is very effective in it and it teams and.

Bill Forbes: We know that this drug, based upon that 373 patient study, looks safe and is very effective, and its effectiveness increases with dose. dose in a statistically significant manner. So I think that when we start to compare different Kappa agonists, and in our case, we have dual mechanisms, so you're right, we're not talking about the exact same mechanism here. But we do believe that there continue to be results that show that that part of the mechanism is successful in treating paritis.

And its effectiveness increases with dose and a statistically significant manner.

I think that when we start to compare different Kappa agonists and in our case with dual mechanism. So you're right. We're not talking about the exact same mechanism here, but we do believe that.

There continues to be results that show that that part of the mechanism.

Festival and treating pruritus, what we believe is that our drug working not only politically but centrally.

Bill Forbes: What we believe is that our drug working not only peripherally but centrally will have a much more potent effect, because we believe that each pathway has been implicated from opioid receptors that exist on the skin into the peripheral neurons, into the spinal cord, all the way up to the brain. So the ability for us to penetrate all those areas and be effective, we feel good about our opportunities here.

Have a much potentially a better effect because we believe that the H pathway yeah. It is.

Been implicated from opioid receptors that exist on the skin into the peripheral neurons in the spinal cord all the way up to the brain. So the ability for us to penetrate all those areas and to be effective we feel good about our opportunities here. So.

I think as it relates to showing significant benefit in these different populations. They are difficult to treat which is why we like our mechanism.

Bill Forbes: So I think as it relates to showing significant benefits in these different populations, they are difficult to treat, which is why we like our mechanism for them and, you know, much better than some of the competition. Maybe with that, I'll pause, and if you have any questions.

And how much better than some of the competition.

Maybe with that I'll pause and if you have any questions.

Annabel Eva Samimy: Yeah, just one more on the population of PN, the actual PN population. Do they have variable itch in such a way that sometimes, you know, it could be It could temper, it could have a placebo response, it could, you know, anything in the population that we should be concerned about?

Yeah, just just one more on the population and the actual pn population do they have.

Variable edge.

In such a way that sometimes.

You know it could be.

It could temper it could have a placebo response. So good you know anything in the population that we should be concerned about.

I think the way that we've recruited this particular study I mean, one of the things that we've done it you know the difficulties in recruiting. These patients is that we're looking for a homogenous patient population, where they the score at baseline seven are greater on the W. I N R rests on it and that scale goes from zero to 10.

Bill Forbes: I think the way that we've recruited this particular study, I mean, one of the things that we've done, you know, the difficulties in recruiting these patients is that we're looking for a homogeneous patient population where they score at baseline seven or greater on the WI NRS, and that scale goes from zero to 10, so it's an 11-point scale. And they can't have any scores that are less than six. So they're actually very, they seem to be

So it's an 11 point scale.

And they can't have any scores that are less net six so they're actually very they seem to be scoring very consistently at baseline of course once they get into the study then we anticipate that the drug will have a treatment effect, but I think for the most part what we're looking at here is a fairly stable and consistent popular.

That's not to say that there isn't a placebo response.

On the placebo response from the Pn studies can be around 20%.

Yeah, Phil I would just add to Annabel Yeah. I think the question Youre asking is is there things about P. M that we worry about I mean, I can tell you what I've thought about over time is obviously, there's a lot of underlying triggers of edge atopic Derm, you know uremic pruritus, sometimes they don't know and so the different sort of variability and I know FDA is gonna be inter.

Bill Forbes: I would just add to Annabel. I think the question you are asking is.

Said to see that I do think since our drug works false as Bill mentioned centrally and peripherally that is helpful. There.

But it'll be interesting in our phase two data we didn't see any differences depending on what the trigger was but that's always obviously on my mind, even though they all have T N and I think sales right, we force as well as homogenous population as we can there are underlying diseases that triggered pn in the first place.

Okay, great. Thanks for the color.

Annabel Eva Samimy: Okay, great. Thanks for the color.

Hmm.

Our next question comes from Gary Bachman with renewables.

Operator: And our next question today comes from Gary Naughman with BMO Capital Markets. Please go ahead.

Go ahead.

Hi, good afternoon.

Gary Naughman: Hi, good afternoon. So from last quarter to this quarter, you went from about two-thirds enrolled to 70% enrolled over a few months. So definitely some progress there. But have you hit a little bit of a wall in terms of the pace of accelerating enrollment? You mentioned the timeline for the data. It could be a little pushed out, more because of the summer slowdown. But I'm curious what you've been seeing in the

So from last quarter to this quarter you went from about two thirds enrolled to 70% enrolled over a few months.

Definitely some progress there, but have you hit a little bit of a wall in terms of pace of accelerating enrollment you mentioned timeline for the data could be a little pushed out more because of the summer slowdown, but I'm curious what you've been seeing in the last few months.

Bill you want to comment on that yeah, Yeah, No I mean, it's as you pointed out and as Jennifer mentioned earlier I mean, obviously you moved your guidance from Q3 to second half and so one of the things that were kind of seen as a little bit of a rubber band enrollment by month by month.

Jennifer L. Good: Bill, do you want to comment on this? Yeah, go ahead.

Bill Forbes: Yeah, no, I mean, as you point out, and as Jennifer mentioned earlier, obviously, we moved our guidance from Q3 to the second half. And so one of the things that we've kind of seen is a little bit of rubber banding on enrollment by month, month by month. So it makes us, I mean, I think the thing that gives us confidence is that when we talk to our study staff, the study staff, and the investigators, we find that they're very positive about the ability to keep things moving at a good pace.

It makes us I mean, I think the thing that that gives us confidence is that when we talk to our study staff to the study staff and the investigators where we're finding that they're very positive about the ability to keep things moving at a good pace, but we wanted to try to give the best guidance, we can and obviously, we'll continue to to update.

Bill Forbes: But, you know, we wanted to try to give the best guidance we could, and obviously, we'll continue to update the guidance as we go along here. But, I mean, I feel good that the centers are completely engaged. I mean, we're talking to them on a very regular basis, on a daily basis. And we get responses from them. They are pushing as hard as they can. But as we get into this, as Jennifer mentioned, as we see the summer months coming up, we anticipate that there may be some difficulties with people trying to take vacations on the study staff side and also on the patient enrollment side.

Guidance as we go along here, but I mean I feel good that the centers are completely engaged I mean, we're talking to them on a very regular basis daily basis, and we get responses from them day. They are pushing as hard as they can but as we get into this is as Jennifer mentioned is because we see the summer months coming up we anticipate that the.

There may be some difficulties with people trying to take vacation on the study staff side and also on the patient enrollment side. So.

Yeah, and I would add Gary your last update was half as you know only six weeks ago. So it's sometimes it's just where you cut these things and we do start around so yes. It does go up and down but we've been general generally I would say averaging around 15, sometimes it's 12, sometimes it's 'twenty, but it seems to consistently kind of come around that number.

Bill Forbes: Yeah, and I would add, Gary, our last update was, as you know, only six weeks ago. So sometimes it's just where you cut these things, and we do sort of round. So yes, it does go up and down, but we've been generally, I would say, averaging around the 15, sometimes it's 12, sometimes it's 20, but it seems to consistently kind of come around that number.

But to answer your question I think a little more directly I kind of look at the last couple of months in the last couple of months of enrollment seem to kind of keep pace with some of the best months from previous from them from there.

Bill Forbes: But to answer your question, I think, a little more directly, I kind of look at the last couple of months, and the last couple of months of enrollment seemed to kind of keep pace with some of the best months from the previous year or so. So in a way, we feel good about the activity in the last couple of months.

The previous year or so so in a way we feel good about the activity in the last couple of months, but looking forward.

Gary Naughman: But looking forward, you know, we obviously know that we have to continue to increase enrollment as this goes through a difficult time of the summer months. Yeah, so just on that last point, Bill, like, you know, are a lot of these PN patients presenting at these sites, or do you need to sort of spur that, you know, I don't know, enthusiasm or awareness in the community? So what initiatives do you have to maybe accelerate, especially as we get into the summer?

Obviously now that we have to continue to increase enrollment as it goes through a difficult time in the summer months.

Yes, so just on that last point, though.

One are a lot of these pn patients presenting at these sites.

What do you need to sort of spur that you know I don't know enthusiasm or awareness in the community. So what initiatives do you have to maybe accelerate especially as we get into the summer and then I think you mentioned Jennifer that Youre at 60 sites.

Gary Naughman: And then I think you mentioned, Jennifer, that you're at 60 sites. Any chance you could add to that, or it sounds like you feel very good with the current sites, but do you feel like you need more?

Any chance you could add to that or it sounds like you feel very good with the current sites, but do you feel like you need maybe a bigger number of sites out there.

Gary Naughman: But do you feel like you need maybe a bigger number of sites out there?

Go ahead Bill Yeah, No I think let me let me talk about the number of sites I mean, we look at this constantly and we've still got a couple of sites that are coming on board here. So it's not that we're not adding sites, but we've had a lot of great activity, particularly in the U S, Germany and Poland.

Bill Forbes: Go ahead, Bill. Yeah, no, I think I'll talk about the number of sites. I mean, we look at this constantly, and we've still got a couple of sites that are coming on board here, so it's not that we're not adding sites, but we've had a lot of great activity, particularly in the U.S., Germany, and Poland. They've done a lot of the heavy lifting on this study, and we see activity picking up in our other countries, France and Austria.

They've done a lot of the heavy lifting on this study and and we see activity picking up in our other countries, France and Austria.

I think from a from a site perspective, we feel like you know the horses that we have right now can take us through this last leg of enrollment.

Bill Forbes: So I think from a site perspective, we feel like the horses that we have right now can take us through this last leg of enrollment. As far as the initiatives that we do, we do what you'd expect us to do. We do a lot of advertising. We're constantly refining that, and we learn what works and what doesn't work. We have sites that are extremely successful with it, and we have sites that we're still working with to try to find a better way to advertise and recruit them.

As far as the initiatives that we do we do what you would expect us to do we do a lot of advertising we're constantly refining that we learn what works and what doesn't work. We have sites that are extremely successful with it and you have sites that were still working with to try to find a better way to to do advertising in and recruit them, but as far as with at the site level the initiatives that we have.

Bill Forbes: But as far as at the site level, the initiatives that we've done, we started to roll those out in February and March, and they're taking hold now. So I think in many respects, you know, we're hopefully going to get the fruition of all of that and try to drive this home. But trust me, every day we wake up, this is what we hunt.

Done we've started to roll those out in February and March and are there. They are taking hold now so I think in many respects.

Hopefully, we're going to get the fruition of all of that and try to drive this home, but trust me every day, we wake up this is what we have and.

And it's it's what our investigators and coordinators and studies that are hunting, so well driving as hard as we can.

Gary Naughman: And that's what our investigators and coordinators and study staff are. So, you know, we're driving as hard as we can. Okay.

Okay, and then just last quick one on Ips, it's nice to see that that's opening up a little bit and youre getting some progress there, but how many sites have resumed screening and also here. How many do you still have to reopen if you're just going to be focusing on the U K.

Operator: And then just last quick one on IPF, it's nice to see that that's opening up a little bit and you're making some progress there, but how many sites have resumed screening, and also here, how many do you still have to reopen if you're just going to be focusing on the UK? And is there any other sort of backstop if the UK isn't enough, if Germany doesn't make sense? Will you reconsider Germany at some point? It seems like you're pretty confident you can.

And is there any other sort of backstop.

The U K isn't enough to Germany, it doesn't make sense, where you reconsider Germany at some point.

It seems like you're pretty confident you could get it done in the UK, but just wanted to confirm that thanks.

Serge D. Belanger: you get it done in the UK, but just wanted to confirm that. Thank you. Yeah, and I think this was obviously a strategic management call as we kind of looked at the timelines for opening up centers in Germany, how long that would take to complete that process, and how much time the German investigators might have to enroll. So we're looking to actually pivot away from Germany, and what we'll look at is adding sites in the U.K. Right now, about a third of the sites seem to be engaged in screening at this point in And I think June's going to be a very good month for us to understand exactly who's all in.

Yeah I think this was obviously a strategic management call as we kind of looked at the timeline for opening up centers in Germany, how long that would take to complete that process and how much time, the German investigators might have to enroll so we're looking to actually pivot away from Germany, and and what will look at us.

Adding sites in the U K and I would say right now about a third of the sites are seem to be engaged in screening at this point in time with the rest of them coming online I think June is going to be a very good month for us to understand exactly who is all in and and we would call setup with the investigators and study staff to go through.

Bill Forbes: And we have calls set up with the investigators and the study staff to go through how to get this. And I think the fact that we're screening now will hopefully result in some randomizations here in the not too distant future. But, you know, that's how screening goes. Sometimes, not everybody gets through.

How to get this and I think the fact that we're screening now hopefully will result in some randomization here in the not too distant future, but you know that's all screening go sometimes not everybody gets through but we feel good that the centers are are engaging they're ready to come back to work pivot away from the COVID-19. As you know these are pulmonary centers in the U K. So they got pulled in.

Bill Forbes: But we feel good that the centers are engaging. They're ready to come back to work, pivot away from COVID. As you know, these are pulmonary centers in the U.K., so they got to be pulled into the COVID treatment nightmare. And so as they come back and do their day job here, doing research, we're looking forward to getting some good activity out of this in June and July.

That's the end of the COVID-19 treatment nightmare, and so as they come back and do their day job here doing research.

We're looking forward to getting some good activity out of this in the June July timeframe.

Okay, great. Thanks for the additional color thanks, Gary.

Gary Naughman: Okay, great. Thanks for the additional caller. Thanks, Gary.

My next question.

Operator: And our next question comes from Serge Belliger with Needham and Company. Please go ahead.

Bolger with Needham and company. Please go ahead.

Hi, good afternoon.

Serge D. Belanger: Hi, good afternoon. I have just a couple questions for you.

Just a couple of questions from me maybe I missed this in your prepared comments, but any update on.

Serge D. Belanger: Maybe I missed this in your prepared comments, but any update on patients rolling over into the extension study, and are you seeing kind of similar trends of discontinuation? And then, anything we can glean from the recent CARA study readout. I know it's a different itch indication, but it is a similar end point. So do I know anything about the placebo effect that we saw that could be useful as we look at the prison trial readout?

Patients rolling over into the extension study and are you seeing kind of similar trends.

Discontinuation.

And then.

Yeah.

Anything we can glean from the recent.

Terrorists study read out I know, it's a difference.

Occasion, but it is a similar end point, so I don't know anything about the placebo.

In fact, we saw.

Be useful as we look to.

<unk> trial read out.

So I'm going to make a couple comments and then you should add your color Serge I'm happy to reread My script in a private setting you know, let's say clean out everything, but we did that we are greater than 95 per cent still we've had very good.

Jennifer L. Good: So I'm going to make a couple of comments, and then you should add your color. Serge, I'm happy to reread you my script in a private setting, you know, so you clean out everything. But we are greater than 95% still. We've had very good success with people that make their way through the study stay on and not only roll over, but go all the way to the end and get a year of treatment.

Success with people that make their way through the study stay on and not only rollover, but go all the way to the end and get a year of treatment. As you know these patients don't have sort of other alternatives as.

Jennifer L. Good: As you know, these patients don't have any sort of other alternatives. As far as discontinuations are concerned, and Bill can add more color there, I would say it's in line with where we thought. I think we've continued to manage that down.

As far as discontinuation from Bell can add more color there I would say it's in line with where we thought I think we've continued to manage that down and Bill you may want to comment a little bit on that in relation to the <unk>, but I would say on the carrot studies, because I studied them to surge with that eye, they're placebo effects actually have been in the.

Jennifer L. Good: And Bill, you may want to comment a little bit on that in relation to the SSRE. But I would say on the CARA studies, because I studied them two-thirds with that eye, their placebo effects actually were in the same range that we've typically seen in these studies. I think they were, what, 19, 20 percent.

Same range that we've typically seen in these studies I think they were what 19, 20%. So I think that's helpful. I mean, my feeling on care of my own bias I believe in the opioid mechanism I think Kappa agonists work I think that bill alluded to in his comments I think the challenge Terra has outside of its injected.

Jennifer L. Good: So I think that's helpful. I mean, my feelings on care of my own bias, you know; I believe in the opioid mechanism. I think cappaginous works.

Jennifer L. Good: I think, as Bill alluded to in his comments, I think the challenge Tara has outside of its injectable formulation is, just do they really have that oral formulation down? And I think they've struggled to show that in a way that's sort of convincing. So I thought a lot of it was just validating. I think atopic derm is a tricky indication. There's a lot of multifactoral stuff going on there with inflammation and itch and everything else. But those are my thoughts. Bill, you should chime in with your thoughts as well. Yeah, you know, I guess so.

The formulation is just do they really have that oral formulation down and I think they've struggled to show that in a way that's sort of convincing so I thought a lot of it was validating I think atopic derm is a tricky indication there's a lot of Mac multifactorial stuff going on there with the inflammation and itch and everything else, but so those are my thoughts affiliation.

And with your thinking as well.

Yeah, I, you know I guess.

Bill Forbes: Yeah, you know, I guess from that, she pretty much covered anything I would probably add color on, but I think, you know, if you take a look at their study, obviously, they had an interim review, and they actually ended up picking a dose, so they had three active doses versus placebo. That's not what we did here.

Bill Forbes: We had a sample size reestimation. As I mentioned before, because the formulation and the molecule are well behaved, we knew what our dose was going into this study. So we didn't have to worry about picking a dose amongst different doses. We just, all we had to do was make sure that we had promising conditional power and then to end up with what the final end should be for the study. So we end up with a power of 360 total patients, 180 per treatment group.

From that I pretty much covered anything I would probably guide, Colorado, but I think you know if you take a look at their study obviously, they had an interim review and and they actually ended up picking a dose. So they had three active doses versus placebo.

Not what we we did here we had a sample size re estimation.

To my comments before because the formulation and the molecule well behaved we knew what our dose was going into this study.

And so we didn't have to worry about picking a dose amongst different doses. We just all we had to do was make sure that we had promising conditional power and then to end up with what the final.

And should be for this study so we end up with a power 360 total patients 180 per treatment group I think Kerry I ended up with about 120 patients per group between the two doses or placebo and the active dose that they chose.

Bill Forbes: I think Kara ended up with about 120 patients per group between the two doses, placebo, and the active dose that they chose. So, as we kind of look at those results, different indications, as you pointed out before, surge, you know, and so there's, we have to always be cautious about that. And they do end up enrolling patients that have a seven or greater on the, on the, edge scale.

So I mean, as we kind of look at those results different indications as you pointed out before surgery.

Bill Forbes: So we are enrolling the same number, seven or greater, on our WI NRS. But I think in many respects, you know, we feel good about the position we're in. We feel like we're powered up, and we feel like we've got our dose.

And so there's we have to always be cautious about that they do end up enrolling patients that have a seven or greater on the on the gauge scale. So.

So we are enrolling the same.

Number seven or greater on a W. I N R S.

But I think in many respects.

Good about the position we're in we feel like book powered up and.

We feel like we've got our dose.

Okay.

Uh huh.

Our emotional and any further questions. So this concludes our question and answer session.

Operator: I am not sending any further questions. So this concludes our question and answer session. I'd like to turn the conference back over to Jennifer Good for closing tomorrow.

This book.

Good for closing remarks thank.

Jennifer L. Good: Thank you. We'd like to thank everybody for participating in today's call. I'd also like to thank the Trevi team, our study investigators, and all of the subjects who continue to participate in our clinical trials. I hope everybody has a nice summer. Thank you.

Thank you we'd like to thank everybody for participating in today's call I'd also like to thank the Trevi team our study investigators and all of the subjects, who continue to participate in our clinical trials I hope everybody has a nice summer. Thank you.

Sometimes you will recall from some small concluded once you all for attending today's presentation, you may notice much of Orange and have a wonderful day.

Operator: And thank you, ma'am. The conference is not concluded. We thank you all for attending today's presentation. You may now as well connect your lines and have a wonderful day.

Okay.