Q4 2021 Trevi Therapeutics Inc Earnings Call

Good afternoon, and welcome to the Trevi Therapeutics Q4, and year end 2021 earnings conference call at.

Operator: Good afternoon, and welcome to the Trevi Therapeutics Q4 and Year-End 2021 Earnings Conference Call. At this time, all participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press the star key, then 1 on your touchtone phone.

Operator: To withdraw your question, please press star then 2. Please note that this event is being recorded. Various remarks that 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 annual report on Form 10-K, which the company filed with the SEC this afternoon.

Operator: In addition, any forward-looking statements represent the company's views only as of today and should not be relied upon as representing 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, it specifically disclaims any obligation to do so, even if its views change.

At this time, all participants will be in listen only mode should you need assistance. Please signal a conference specialist by pressing the star key followed by zero.

After today's presentation there'll be an opportunity to ask questions to ask a question you May Press Star then one on your Touchtone phone.

To withdraw your question. Please press Star then two please.

Please note this event is being recorded.

Various remarks that 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 annual report on Form 10-K, which the company filed with the SEC This afternoon.

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

Operator: I would now like to turn the conference over to Jennifer Good, Trevi's President and CEO. Please go ahead. Good afternoon, and welcome to our fourth quarter 2021 and year-end earnings call and business update. Joining me today on this call are Lisa Delfini, Trevi's Chief Financial Officer, and Dr. Bill Forbes, Trevi's Chief Development Officer. Lisa and I have some prepared remarks, then the three of us will be available for questions at the end. It has been an exciting few months at Trevi, and I am happy to share the progress we've made in advancing the development of both of our programs.

I would now like to turn the conference over to Jennifer Good try these president and CEO. Please go ahead.

Jennifer Good: We recently announced that our Phase II canal trial in chronic cough and IPF showed a statistically significant reduction in cough during an interim analysis that allowed us to stop the trial early. This news has gained a lot of external interest and allows us to accelerate our plans. Also, we completed enrollment as of January 31, 2022, in our Phase IIb-III PRISM trial in chronic paritis and PN. These are important milestones in our clinical development for our lead programs and allow us to shift our focus on preparing for the next stages in development.

Good afternoon, and welcome to our fourth quarter 2021 and year end earnings call and business update joining me today on this call or at least that Delphine, Travis Chief Financial Officer, and Dr. <unk>, Chief Development Officer, Lisa and I have some prepared remarks, then the three of us will be available for questions at the end.

Jennifer Good: Our most advanced program in clinical development is in severe chronic paritis in pragonodularis, or PN, which is a serious and debilitating disease characterized by papules and nodules on the skin, as well as incessant and severe itching. HADUBIO is being studied in PN in our PRISM trial, which is a 14-week phase 2b slash 3 trial. We expect to report top-line data in the second quarter of this year. We believe PN, due to the refractory nature of the disease, is neurologically mediated and potentially aligns well with the neuronal mechanism of our mixed agonist-antagonist drug.

It has been an exciting few months at Trevi and I'm happy to share the progress we've made on advancing the development of both of our programs. We recently announced that our phase two canal trial in chronic cough and IPF showed a statistically significant reduction in costs. During an interim analysis that allowed us to stop the trial early.

This news has gained a lot of external interests and allows us to accelerate our plans also we completed enrollment as of January 31, 2022, and our phase two B class III prism trial in chronic pruritus in Pn. These are important milestones in our clinical development for our lead programs and allow us to.

To shift our focus on preparing for the next stages in development.

Our most advanced program in clinical development is in severe chronic pruritus and prego, Nigel Air Scorpion, which is a serious and debilitating disease characterized by papules and I'll dwell upon the skin as well as an assessment and severe itching Adobe <unk> is being studied in pn in our prism trial, which is a 14 week.

As to be class III trial, we expect to report topline data in the second quarter of this year. We believe can do to the refractory nature of the disease is neurologically mediated and potentially aligns well with the neuron on mechanism of our mixed agonist antagonist drug.

Jennifer Good: With no approved therapies in this indication, we remain the lead oral therapy in development. Let me give you an update on our open-label extension study for PN. The percentage of subjects continuing into the open-label extension remains high at approximately 93%. 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 reducing itch, an effective therapy has the potential to disrupt the itch-scratch cycle, leading to skin healing and resulting in disease modifications over time.

With no approved therapies in this indication we remain the lead oral therapy in development.

Let me give you an update on our open label extension study for Pn the percentage of subjects continuing into the open label extension remains high at approximately 93%. 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 reducing edge and effective therapy has the potential to disrupt the itch scratch cycle, leading to skin healing and resulting in disease modifications over time we.

Jennifer Good: We see a significant market opportunity and estimate the global prevalence of PN at approximately 730,000 patients, with 300,000 patients in the U.S. and 430,000 in the rest of the world. Most of these patients have already tried and failed topical treatments, and we believe they will be eligible for an oral therapy like Kuduvio before turning to biologics. Turning now to our other clinical program, which is in Chronic Cough and Idiopathic Pulmonary Fibrosis, or IPF. This has been a very exciting couple weeks for this program.

We see a significant market opportunity and estimate the global prevalence of Pn is approximately 730000 patients with 300000 patients in the U S and 430000 in the rest of the world.

Most of these patients have already tried and failed topical treatments and we believe they will be eligible for an oral therapy like could do be out before turning to biologics.

Turning now to our other clinical program, which is in chronic cough and idiopathic pulmonary fibrosis or IPF. This is been a very exciting couple of weeks for this program. We were happy to report a positive result from a pre specified interim analysis, allowing us to end enrollment early save money and accelerate into the next phase of development.

Jennifer Good: We were happy to report a positive result from a pre-specified interim analysis, allowing us to end enrollment early, save money, and accelerate into the next phase of development. In this interim analysis, Hadoopio showed a 77% reduction from baseline at day 22 in daytime cough frequency, as measured by an objective cough monitor, demonstrating a 52% difference from placebo. The P value on this analysis of 26 subjects was P less than 0.0001, and conditional power was 100%.

In this interim analysis Adobe O showed a 77% reduction from baseline at day 22 in daytime cough frequency as measured by an objective top monitor.

Jennifer Good: These results were consistent regardless of baseline cough frequency or anti-fibrotic use, and we saw no impact from the treatment period in this crossover design. Patient-reported outcomes followed the same trend as the objective cost monitor and demonstrated a rapid response to treatment as early as the first week. Hadovio is the lead therapy in development and the only one that has shown positive results in the reduction of cost in this patient population. Hadovio was well tolerated in this study, with only one SAE that was not deemed to be treatment-related, and the adverse events were consistent with what we've seen in trials for Hadovio and other indications.

Demonstrating a 52% difference from placebo the P value on this analysis of 26 subjects with P less than 0.0001 and conditional power with 100%. These results were consistent regardless of baseline cough frequency anti fibrotic Qs and we saw no <unk>.

From the treatment period in this crossover design.

Patient reported outcomes, followed the same trend as the objective cost monitor and demonstrated a rapid response to treatment as early as the first week Adobe as the lead therapy in development and the only one to have shown positive results on the reduction of cost in this patient population.

<unk> was well tolerated in the study with only one SAE that was not deemed to be treatment related and the adverse events were consistent with what we've seen in <unk> trials and other indications.

Jennifer Good: We announced this week that the last patient was randomized in this study, and we expect approximately 40 subjects in total to be evaluated. With the strength of the p-value reported, we would expect to see similar results in the final data set, and we plan to announce top-line data on the full set of subjects in the third quarter of this year. We will look to present the full results at a medical meeting in the fall.

We announced this week that the last patient was randomized in this study and expect approximately 40 subjects in total that will be evaluated with the strength of the P value reported we would expect to see similar results in the final dataset and we plan to announce top line data on the full set of subjects in the third quarter of this year.

We'll look to present the full results at a medical meeting in the fall.

Jennifer Good: Bill and his team are also in parallel planning the next clinical study, which we intend to design as an adequate and well-controlled trial, as well as preparing for discussions with regulatory authorities. This data set is exciting and is initial validation of our hypothesis of the mechanism of Studio and treating cough.

Bill and his team are also in parallel planning the next clinical study, which we intend to design as an adequate and well controlled trial as well as preparing for discussions with regulatory authorities.

This dataset is exciting and has initial validation of our hypothesis of the mechanism of studio and trading costs and as a team we are determining our path forward not only in this indication, but also other chronic cough indication chronic cough and IPF as an indication and a much larger opportunity for chronic cough Bolton.

Jennifer Good: And as a team, we are determining our path forward, not only in this indication, but also other chronic cough indications. Chronic cough and IPF is an indication in a much larger opportunity for chronic cough, both in other interstitial lung diseases, as well as the growing opportunity in refractory chronic cough. This global chronic cough market is estimated to be approximately $10 billion. To give you more background on IPF, it 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 up to 85% of these patients and for which there are no approved treatments.

Their interstitial lung diseases as well as the growing opportunity in refractory chronic cough. This global chronic cough market is estimated to be approximately $10 billion.

To give you more background on IPF is a progressive and severe condition in which theyre scarring of the lung tissues. One of the leading debilitating symptoms of this disease is chronic coughing, which affects up to 85% of these patients and for which there are no approved therapies in the U S. We estimate that there are approximately 130000.

Jennifer Good: In the US, we estimate that there are approximately 130,000 patients with IPF and an equal amount in Europe. 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 the patient's quality of life. It has been a busy few months in both of our studies, but we still have a data-rich few months ahead of us. In the second quarter, we will complete the double-blind portion of our paritis trial in PN and report top-line data.

With IPF and an equal amount in Europe 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 the patient's quality of life.

It has been a busy few months and both of our studies, but we still have a data rich few months ahead of us in the second quarter, we will complete the double blind portion of our <unk> trial in Pn and report topline data. We will also complete the dosing and the remaining subjects in our cross trial in IPF and report out the data on the full set of <unk>.

Jennifer Good: We will also complete the dosing of the remaining subjects in our COFT trial in IPS and report out the data on the full set of subjects in the third quarter. In parallel, we are actively preparing for the next stage of development for both of these indications as well as planning for indication expansion in both chronic paritis and chronic COFT. One final comment before I turn it over to Lisa to review the financial results. We will be hosting a KOL call on Wednesday, March 30th from 8 to 9 a.m. Eastern Time.

Objects in the third quarter in parallel we are actively preparing for the next stage of development for both of these indications as well as planning for indication expansion in both chronic pruritus in chronic cough.

One final comment before I turn it over to Lisa to review the financial results, we will be hosting our kao I'll call on Wednesday March 30th from eight to nine a M. Eastern time on that call Bill will review the interim result, as well as provide additional new analyses and importantly, we will be joined by Dr. Lisa Lancaster.

Jennifer Good: On that call, Bill will review the interim results as well as provide additional new analyses. And importantly, we will be joined by Dr. Lisa Lancaster, who is a professor of medicine at Vanderbilt University School of Medicine. Dr. Lancaster is also the medical director of the Interstitial Lung Disease Program at Vanderbilt University Medical Center and a medical advisor for the Pulmonary Rehabilitation Program at Vanderbilt. She has deep experience with patients with interstitial lung disease, including idiopathic pulmonary fibrosis, and will be helpful in describing the disease and suffering of these patients. We invite you to join us on that call. We will be issuing a press release next week with information on how to register.

Who is a professor of medicine at Vanderbilt University School and the school of Medicine. Dr. Lancaster is also the medical director of the interstitial lung disease program at Vanderbilt University Medical Center, and a medical adviser for the pulmonary rehabilitation program at Vanderbilt She has deep experience with patients with interstitial lung.

Disease, including idiopathic pulmonary fibrosis and will be helpful. In describing the disease and suffering of these patients. We invite you to join us on that call. We will be issuing a press release in the next week with information on how to register.

Lisa Delfini: That is all I have on the business update. I will now ask Lisa to review our financial results, and then we will open it up for questions. Thank you, Jennifer. And good afternoon, everyone.

That is all I have on the business update I will now ask Lisa to review our financial results and then we will open it up for questions.

Lisa Delfini: As I always need to remind you, the full financial results for the three and 12 months ended December 31, 2021 can be found in our press release issued ahead of this call and our 10k, which was filed with the SEC, just a few. During the fourth quarter, we raised $14.8 million in financing, which enabled us to end the year with a cash balance of $36.8 million. As Jennifer noted, we were able to end enrollment in our canal trial early, which provided cost savings that will help us accelerate the planning for the next clinical trial for chronic cost and IPF.

Thank you Jennifer and good afternoon, everyone as I always need to remind you the full financial results for the three and 12 months ended December 31, 2021 can be found in our press release issued ahead of this call and our 10-K, which was filed with the SEC just a few minutes ago.

Lisa Delfini: For the fourth quarter of 2021, we reported a net loss of $8.5 million compared to a net loss of $9.5 million for the same quarter of 2020. R&D expenses were $6.2 million during the fourth quarter of 2021, compared to $6.6 million in the same period of 2020, primarily due to decreased purchases of clinical trial supplies, partially offset by increased activity in our canal trial, as well as an increase in personnel-related expenses due to increased headcount. G&A expenses were 2.1 million during the fourth quarter of 2021 compared to 2.6 million in the same period of 2020, primarily due to decreased market research costs.

During the fourth quarter, we raised $14 8 million and a financing which enabled us to end the year with a cash balance of $36 8 million as Jennifer noted we were able to end enrollment in a canal trial early which providing cost savings that will help us accelerate the planning for the next clinical trial for chronic cough and I P F.

For the fourth quarter of 2021, we reported a net loss of $8 5 million compared to a net loss of $9 5 million for the same quarter of 2020.

R&D expenses were $6 2 million during the fourth quarter of 2021 compared to $6 6 million in the same period of 2020, primarily due to decreased purchases of clinical trial supplies, partially offset by increased activity in our canal trial as well as an increase in personnel related expenses due to increased head count.

G&A expenses were $2 1 million during the fourth quarter of 2021 compared to $2 6 million in the same period of 2020, primarily due to decreased market research costs.

Operator: This concludes our prepared remarks, and I will now turn the call back to the operator for Q&A. We will now begin the question and answer session. To ask a question, you may press star, then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys.

This concludes our prepared remarks, and I will now turn the call back to the operator for Q&A.

We will now begin the question and answer session.

To ask a question you May Press Star then one on your Touchtone phone.

If you are using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two.

Operator: To withdraw your question, please press star then 2. At this time, we will pause momentarily to assemble our roster. Our first question is from Annabel Samimy with FIFO. Please go ahead. Hi. Thanks for taking my question. So, I had a couple. The first was on the canal program.

At this time, we will pause momentarily to assemble our roster.

Okay.

Our first question is from Annabel <unk> with Stifel. Please go ahead.

Hi, Thanks for taking my question. So I had a couple of them. The first was on.

We are now program, so I'm curious to know.

Annabel Samimy: So, I'm curious to know what you expect the development path to be from this point forward, and I ask because there are a couple of other chronic health studies going on in the P2F3 space. And I know it's not specifically related to IPF, but I'm just curious to know if you believe that there's broad activity or applicability for your program. Is there the same broad applicability of those P2F3 inhibitors to move into IPF? So, I'm just curious to know how the landscape plays out.

What are your expected development path B from this point forward and I ask because there are a couple of other chronic cough studies going on in the pizza industry space and I know, it's not specifically related to IPF, but I'm just curious to know if you believe that there is broad.

Productivity or applicability for your program is there the same broad applicability of those pizza <unk> three inhibitors to move into IPF. So I'm just curious to know how the landscape landscape plays out thanks.

Thanks.

Thanks Annabel.

Jennifer Good: Thanks. Thanks Annabel. I'll answer that, although Bill will jump in if you want to add anything. Yeah, so we have always believed that our mechanism could work broadly and for cough. I mean, as you and I have discussed, opioids have been known to work in cough for a long time. IPF cough, I think, is considered a very severe and serious form of cough.

I'll answer that although bell jump in if you want to add anything yeah. So we have always believed that our mechanism could work broadly in cost I mean, as you and I have discussed the.

Opioids have been known to work in cost for a long time IPF cough I think is considered a very severe and serious form of Cogs as a matter of fact, some of the pizza extra hasn't been studied in IPF cost, Jeff of Pixar and actually failed there.

So we feel that the fact that we work there is a good sign.

Considering both refractory chronic cough and other interstitial lung disease path as we move forward I think once we read out all our trial data will probably step back and think of the best way to build out the company, but I do feel that the mechanism is could.

Jennifer Good: As a matter of fact, some of the P2X3s have been studied in IPF cough, Jeff Epixand, and actually failed there. So we feel that the fact that we work there is a good sign. We are considering both refractory chronic cough and other interstitial lung disease cough as we move forward. I think once we read out all our trial data, we'll probably step back and think of the best way to build out the company. But I do feel that the mechanism could be broadly applicable to cough. Yeah, no.

Could be broadly applicable to cough.

Yeah no.

Bill: Okay. Sorry, go ahead. Bill has a more informed perspective.

Oh, sorry go ahead.

So I don't have the more of them.

Bill: See if he wants to add anything to my comment. No, not necessarily to that, but just kind of getting to Canale and kind of next steps. I think he started there, Annabel.

If he wants to add anything to my comment I know not necessarily to that but just kind of getting too to canal and kind of next steps I think he started their annabel.

Bill: You know, one of the things that we're obviously anxious to do is complete this study and report out the top-line results. At the same time, we're going to be moving things forward on the regulatory front, and we're also starting up discussions with ILD centers around the United States. So we anticipate the next study will be in both the U.K. and the U.S. So, you know, obviously, we're anxious to get in with the FDA and talk to them about, you know, next steps and what we need to do.

One of the things that we're obviously anxious to do is complete the study and report out the top line results at the same time, we're going to be moving things forward on the regulatory front. We're also starting up discussions with ILD centers around the United States. So we anticipate the next study will be in both the U K and the U S. So you know obviously we're anchor.

Just to get in with the FDA and talk to them about.

Next steps and what we need to do I anticipate that that meeting with the FDA will take place in Q3, and then we'll try to get things up and running soon thereafter.

Bill: I anticipate that that meeting with the FDA will take place in Q3, and we'll try to get things up and running soon thereafter. Okay, and I guess the reason why I ask is, you know, you've got... 36.8 million in cash, and these are relatively large markets that can potentially be very costly to develop. So I'm trying to think about how you might benefit from this program going forward, especially in light of some, well, research research has shown some failure in IPF, but there are others that have shown success in chronic cough, perhaps have a better profile than the ones that have failed. So I'm just a little curious, you know, the extent to which you might have to invest in this to position yourself in a very, very, very large market, potentially Yeah, so Annabel, you're right.

Okay, and I guess the reason I ask is you know you've got.

$36 8 million in cash and these are relatively large markets, but that could potentially be very costly to develop so I'm trying to think about how you might from this program going forward, especially in light of some.

Well teach out students have shown some failure and in IPF, but theres others that have shown success in chronic cough and.

I'll have a better profile than the ones that have failed. So I'm just little curious you know the extent to which you might have to invest in those to position yourself.

A very very very large market sequentially.

Jennifer Good: I mean, there's a lot of indications here, which could get very expensive. I should just comment that IPF cost and PN will be our priority, the data, assuming that, you know, they are both successful. Those are both serious unmet patient needs, and we're committed to sort of finishing what we start. Where we move into, part of the consideration will be the cost of the program, the overall pricing, the unmet need, all those kinds of things. And we'll have to do that mindfully. I mean, we're definitely mindful of our stock that's in the market cap.

Yeah, So annabel Youre right I mean, there's a lot of indications here, which could get very expensive I should just comment that IPF Cos N. P. N will be our priority. The data assuming that you know are both successful and those are both serious unmet patient needs and we're committed to sort of finishing what we start where we move into part of the consideration will be the cost to the.

Grams, the overall pricing the unmet need all those kinds of things and we will have to do that mindfully. I mean, we're we're definitely mindful of where our stock sits in the market cap. So you know I think there's opportunity to do that it's something we'll revisit them I know Lisa you may want to add something about cash runway planning yeah. So you know our cash gets us through the data readouts in both of the clinic.

Jennifer Good: So, you know, I think there's a lot of opportunity to do that. It's something we'll revisit. I know, Lisa, you may want to add something about cash, runway, and planning.

Lisa Delfini: Yeah. So, you know, our cash gets us through the data readouts in both of the clinical trials and then, you know, the time to start preparing for the next clinical trial. And, you know, we will need to raise money for the next clinical trial. We will be considering that.

Trials and then you know the time to start preparing for the next clinical trial and Ah you know we will we know we need to raise money for the next clinical trial, we will be considering that you know we know we've added value to the company as a result of this these cough results and we'll be considering that you know as we can.

Lisa Delfini: You know, we know we've added value to the company as a result of this – these COF results, and we'll be considering that, you know, as we get through the results in this. Okay, and then, just really quickly, on the Sci-Tech profile, I know that from a mechanism standpoint, there was the nausea and vomiting that you had initially tried to address in terms of titrating patients and getting them to the right level.

Get through the the results in the end of the year.

Okay. Okay, that's fair.

Just really quickly on the side effect profile I know that.

From a.

I guess the.

The mechanism there was the the nausea and vomiting that you had initially try to address them in terms of our you know titrating patients are getting the right level did you find that the patients in the study had.

Lisa Delfini: Could you find that the patients in the canal study had just as much issue with that titration period and nausea and vomiting? Would that be something that could exacerbate that population, given that their condition already puts them kind of in a vulnerable state as far as nausea and vomiting are concerned? I'm just curious to know how you balance the potential early-stage side effects with the actual condition itself.

You know.

Just as much issue with that but titration period, and nausea, vomiting would it be something that could exacerbate that population given that their condition already.

<unk> put some kind of in a vulnerable state as far as nausea and vomiting.

I'm just curious about how you balance the pencil early searchlight effect with the actual condition of the call.

Bill: Yeah, just a couple of comments. Obviously, this patient population does an awful lot of coughing, and so vomiting is actually an issue with this patient population. You can imagine if you're coughing up to 90 times per hour that you might get into some of that.

Just a couple of comments I mean, obviously this patient population does an awful lot of coughing and and so vomiting is actually an issue with this patient population you can imagine if you're coughing up to 90 times per per hour.

You might get into some of that but.

Bill: But, you know, we've reported that from a blinded perspective. We had five AEs that dropped from this study. We don't know what treatment arm they were in when they dropped, but one was anorexia, one depression, one nausea, vomiting, one insomnia, fatigue, and one agitation, anxiety, and dyspnea.

We've reported data from a blinded perspective, you know we had five day. He's a drop from this study we don't know what treatment arm. They were in when they dropped but one was anorexia wanted depression, nausea, vomiting, one insomnia fatigue, and one agitation anxiety dyspnea I think overall, we've been very happy with the Tolerability that we've seen in this study.

Bill: So I think, overall, we've been very happy with the tolerability that we've seen in this study. We dose titrate it up, as we did in the PRISM study. So, you know, as I said, overall, we're happy with what we see. But the other thing is, you know, with the antifibrotics, there are a lot of GI side effects with the antifibrotics also, and we know that, you know, just short of 50 percent of the population was on antifibrotics in this study.

We dose titrated up as we do and in the Prism study. So as I said I think overall, we're happy with what we see the other thing is you know with anti fibrotic Theres a lot of Gi side effects with anti fibrotic also and we know that there are you know just short of 50% of the population was an anti fibrotic.

This study so with that we we understand that theres already a side effect profile from from one of the leading therapies in the area.

Bill: So with that, we understand that there is already a side effect profile from one of the leading therapies in the area. Okay, great. Thank you. Thank you. The next question is from Serge Belanger with Needham & Company. Please go ahead. Hi, good afternoon.

Okay, great. Thank you.

Thank you.

The next question is from Serge Belanger with Needham <unk> Company. Please go ahead.

Hi, Good afternoon couple of questions for me the.

Serge Belanger: A couple of questions for me. The first one, a follow-up to just the previous question here, did you use the same dose and titration protocol in the canal trial as you're using in the PRISM study? It was altered a little bit in the canal study. We did 27 to 54 milligrams in the canal study and then continued to dose escalate up to 108 and then to 162.

The first one a follow up to.

Just the previous question here.

Did you use the same dose and titration protocol in the trial as Youre using the Prism study.

It was altered a little bit in the canal study, we did 27% to 54 milligrams.

The Canal study and then.

Continued to dose escalate up to want to wait and then to 162, we obviously and at the same at the same dosage 162, B I D.

Bill: We obviously end at the same dosage, 162 BID. And Bill, you might want to mention why we did that. You were trying to get some dose response data, right? It really wasn't to do with tolerability.

And Bill you might want to mention why we did that you were trying to get some delta on state I write it really wasn't to do with Tolerability Yeah, No. That's an important point.

Bill: Yeah, no, that's an important point. You know, originally when this study was designed, we got VitaliJack recordings at baseline and then weeks 1, 2, and 3. So when the study was designed, we tried to get some dose response at each of those, trying to get to the 54, the 108, and then the 162 on the VitaliJack recordings. So that's why it was altered a little bit. Unfortunately, we had to drop the VitaliJack recordings at weeks 1 and 2 because of COVID, and we couldn't have the inpatient visits that we wanted to. But, you know, we did maintain the VitaliJack at baseline in week 3.

Originally when this study was designed we got Vitale of Jack recordings of weeks at baseline in the weeks one two and three so when the study was designed we tried to give some dose response at each of those I'm trying to get to the 54. The one Oh wait and then the $1 62 at the Vitale Jack recording So that's why it was it was altered a little bit.

Unfortunately, we had to drop the vitale of Jack recordings at weeks, one and two because of Covid and we couldnt have the inpatient visits that we wanted to but we did we did maintain the vitale Jack the baseline and week three so.

Hopefully that answers your question Sir.

Serge Belanger: So hopefully that answers your question, Serge. Yeah. And secondly, just thinking about, uh, the timing of the PRISM trial readout as we get closer, only a few weeks into the second quarter here. I think in the past you've talked about around a four-month period between the last patient enrollment and potential readout. Is that a good way to think about it?

Yes.

And secondly, just thinking about it.

The timing of the Prism trial read out as we get closer.

Few weeks.

To.

Second quarter here just in the past you've talked about around four months period between the last patient enrollment potential readout is that a right way to think about it yes.

I think you should look at it as the end of Q2 as one law readout will come.

Got it okay. Thank you.

Again, if you have a question. Please press Star then one.

Bill: Yeah, I think you should look at it as the end of Q2 is when our readout will come. Got it. OK. Thank you. Again, if you have a question, please press star then 1. The next question is from Nathan Weinstein with Aegis Capital; please go ahead. Hi, thanks. Good afternoon, Jennifer, Lisa, and Bill. Thanks for taking my questions, and congratulations on the progress, including particularly the strong interim analysis from Canal. Actually, my first question is just on Haduvio for severe pruritus in patients with PN.

The next question is from Nathan Weinstein with Aegis capital. Please go ahead.

Hi, Thanks, Good afternoon, Jennifer Leif and Bill Thanks for taking my questions and congrats on the progress, including particularly the strong interim analysis from can now.

Actually my first question just on <unk> for severe severe pruritus in patients with Pn them. I think you mentioned during the prepared remarks, the potential to be utilized in the protocol prior to biologics could you share a little bit more about that in terms of what that might mean, either compare contrast to that class sort of what the ramifications could be for share capture.

Bill: I think you mentioned during the prepared remarks the potential to be utilized in the protocol prior to biologics. Could you share a little bit more about that in terms of what that might mean, either compare or contrast to that class, and what the ramifications could be for share capture?

Nathan Weinstein: Yeah, it's a good question. I mean, biologics are obviously important, but they're not for everyone.

Yeah. It's a good question I mean biologics are obviously important they're not for everyone. I think theres an opportunity from a payoff perspective, depending on where we choose to price the product to maybe kind of step through therapy. I also think oracle's are generally more just easier for patients generally a preferred method. So we are thinking about that aggressively.

Jennifer Good: I think there's an opportunity from a payer perspective, depending on where we choose to price the product, to maybe become step-through therapy. I also think orals are generally just easier for patients, generally a preferred method. So we are thinking about that aggressively as it's good for the patient and, from a payer perspective, it's probably less expensive than biologics. Okay, great. Fair enough.

It's good for the patient and from a payer perspective, there's probably less expensive than the biologics.

Okay, Great Fair enough and then maybe just one follow up for me, obviously, you've mentioned the IPF cough and P. And those are the focus but you have you know a pretty.

Nathan Weinstein: And then maybe just one follow-up for me. Obviously, you've mentioned that IPF, COF, and PN, those are the focus, but you have, you know, a pretty deep pipeline that could be some attractive indications outside the lead. What's on the table? Could partnering be a strategy, or can you just speak to, you know, what you might pursue there strategically?

Deep pipeline that could be some attractive indications outside the lead you know what.

It's on the table could partnering strategy or could you just speak to what you might pursue there strategically.

Jennifer Good: Yeah, so we have been in partnering discussions, really getting people ready for the data, for the past years. And I would say our focus in partnering is around geographic territories. So, clearly, Asia, Japan, and China and sort of related territories and also Europe.

Yeah. So we have been in partnering discussions I'm really getting people ready for the data over the past years and I would say our focus on partnering is around geographic territories, So clearly Asia, Japan, and China and sort of related territories, and also Europe, where a small U S based company and I think we feel we can do well here and I think comfortable developing in <unk>.

Jennifer Good: We're a small US-based company, and I think we feel we can do well here and I think I would be comfortable developing in Europe, but certainly, finding a partner in Asia to help advance the drug and a marketing partner in Europe are things that would be advantageous here for the company and the asset. So that's the focus of our conversation. Okay, fantastic. Thank you so much for the thoughtful answers. I'm looking forward to seeing progress during the rest of the day.

Europe, but certainly finding a partner in Asia to help advance the drag in the marketing partner in Europe are things that would be advantageous here for the company and the asset. So that's the focus of our conversations.

Okay fantastic. Thank you so much for the thoughtful answers I'm looking forward to progress during the rest of the year. Thank you Nathan.

Nathan Weinstein: Thank you, Nathan. I'm not asking any further questions, so this concludes our question and answer session. I would like to turn the conference back over to Jennifer Good for any closing remarks. We would 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 patients who have participated in our clinical trials. Thank you. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect. Smith, Leland Gershell, Debanjana Chatterjee, John Gionco, Debanjana Chatterjee, Trevi Smith, Debanjana Chatterjee, John Gionco, Leland Gershell, [music].

I'm not showing any further questions. So this concludes our question and answer session I would like to turn the conference back over to Jennifer good for any closing remarks.

We would 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 have participated in our clinical trials. Thank you.

The conference has now concluded. Thank you for attending today's presentation you may now disconnect.

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