Q3 2023 Trevi Therapeutics Inc Earnings Call
Good day, good afternoon, and welcome to the Trevi Therapeutics Q3, 2023 earnings Conference call.
At this time, all participants will be in a listen only mode should you need assistance. Please signal conference specialist by pressing the star key followed by zero.
After todays presentation, there will be an opportunity to ask questions to ask a question you May Press Star then one on your phone to withdraw your question. Please press Star then two please note. This event is being recorded various remarks that management makes during this conference call about the company's future expectations plans and prospects.
Cause 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 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 it's used change I would now like to turn the conference.
Over to Jennifer Good Chevy's, President and CEO. Please go ahead.
Good afternoon, and thank you for joining our third quarter earnings call and business update joining me today on this call are my colleagues, where you said Delphine Travis Chief Financial Officer, and David Clark Chief Medical Officer.
Lisa and I have some prepared remarks, then we will open it up for questions.
We have continued to advance our clinical development plans for <unk> in both of our chronic cough indications, including idiopathic pulmonary fibrosis and refractory chronic cough as well as the human abuse potential study, let me provide a brief update on each of these programs I will begin with our phase Iia refractory chronic cough.
Study that was recently initiated we have named this the river study.
Refractory chronic cough or RCC affects up to 10% of the adult population and it's defined as a persistent cough lasting greater than eight weeks despite treatment for an underlying condition or when no cough associated conditions can be identified RCC is caused by cough reflex hypersensitivity in the central and prep.
All nerves and has a significant impact on patients' physically psychologically and socially 72% of high and moderate Koppers report, they're caught being uncontrolled. There are currently no approved therapies for RCC in the U S EU or U K.
The key point of differentiation for <unk> in chronic cough is the mechanism of action, which works both centrally in the brain and preferably in the lungs, we believe Adobe O central and peripheral mechanism has the potential to work in more patients than peripheral only mechanisms like the P. Two X rays and potentially provide a stronger risk.
Sponsor cough reduction when we look at the competitive landscape in RCC and number of other mechanisms have been studied with little success, even the P. Two X three inhibitors have mixed results, but there are two P. Two X three therapies in late stages, one being reviewed by the FDA and the other in phase III trials.
However, importantly, both of these compounds have been shown to have non statistically significant effects in <unk>.
RCC patients with moderate cost frequencies at 10 to 19 cost per hour, we believe that based on the data from our I P. F cough trial and the drugs mechanism of action that had to be a may work in both the moderate and high cost frequencies.
When you look at the RCC patient distribution, 44% of the patients are estimated to have moderate cough frequency, whereas only 29% have high Capri Quincy.
So theres a potential Adobe one may address close to three quarters of the RCC market, whereas P. Two X rays may only be effective in less than a third of the market there.
The River trial is a standard phase two a crossover design that has been running all the cough trials. It is a double blind randomized placebo controlled two period crossover study evaluating the reduction of costs and approximately 60 subjects. These subjects will be randomized with a one to one stratification between those with 10 to 19.
<unk> cost per hour moderate frequency coffers, and those with greater than or equal to 220 cost per hour high frequency coffers.
Each treatment period will last 21 days separated by a 21 day washout period subjects on Hadoop, Yeah, we'll have the twice a day dose titrated weekly from 27 milligrams up to 108 milligrams across the dosing period.
The primary efficacy endpoint is the relative change in the 24 hour cough frequency at day 21 from the treatment period baseline for <unk> compared to placebo as measured by an objective cough monitor.
The study will also explore secondary endpoints, including patient reported outcome measures for cop and quality of life.
We are excited to have initiated this study and expect to report topline data in the second half of next year next a brief update on our lead program in idiopathic pulmonary fibrosis or IPF chronic cough IPF is a serious end of life disease chronic cough is reported by approximately 85% of patients.
Suffering from IPF and has similar physical psychological and social impacts to that of our C. C. But may also be a risk factor that plays a role in the progression of IPF.
Constant lung injury micro tears and potential inflammation caused by persistent coughing may lead to worse health outcomes for our patients such as increased respiratory hospitalizations mortality or need for transplant with no currently approved treatment options for chronic cough in IPF patients and providers have an urge.
Need for new therapies.
We are planning to conduct two studies in parallel during this next phase, it's about development and our IPF chronic cough program. The first is a four arm phase two b dose ranging trial that will study three active doses of <unk> and placebo. We are planning for a six week trial in approximately 160 subjects.
We plan to conduct this study in multiple countries and sites to be able to complete enrollment in a timely manner. We are on schedule with our regulatory interactions and I've received approvals to proceed in some of our planned countries. We expect this trial to be initiated in the fourth quarter of 2023 and will provide top line guidance.
When we announced the trial.
In parallel we are planning for a phase one b respiratory physiology study in IPF patients that have varying levels of disease severity. The purpose of this study is to determine if we see clinically significant impacts on respiratory depression than any subgroups. This study will help define the patient population for a pivotal program.
And ultimately the label we expect to initiate this study in the first quarter of 2024.
Finally, we were able to make progress on re initiating the human abuse potential study, which is required for the NDA filing recall that we had two hurdles. We had declare the first was getting Fda's agreement with the proposed IV Butorphanol dose we plan to a dose in the liability portion of the study we receive that agreement from the.
F D. A during the quarter second we were working to secure supply of IV been harping on all from a single source supplier in the U S, which we were also able to do.
The final portion of the Hap study is a randomized double blind active and placebo controlled five way crossover design to determine the abuse potential of three doses of oral now being seen relative to the selected dose would be a tour for Dol and placebo. The primary objective is to evaluate the likeability if now bufete as.
Fair to both placebo and Butorphanol and the primary endpoint is a drug liking that scale.
We expect to begin dosing in this study in the first quarter of 'twenty 'twenty four with data expected in the second half of 'twenty 'twenty four.
As you can see it is a busy time clinically for the company, bringing up these four studies and we look forward to conducting and reporting results on all of these trials.
I will now turn it over to Lisa to review our financial results. Then we will open it up for any questions you may have.
Thank you Jennifer and good afternoon, everyone.
The full financial results for the three months ended September 30th 2023 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.
For the third quarter of 2023, we reported a net loss of $7 7 million compared to a net loss of $8 3 million for the same quarter in 2022.
R&D expenses were $6 3 million during the third quarter of 2023 compared to $5 8 million in the same quarter in 2022.
The increase was primarily due to startup costs and consultant services associated with our chronic cough program as well as an increase in personnel related expenses. These.
These increases were partially offset by a decline in clinical development expenses related to our completed phase two b III prism and phase two canal trials as well as decreased purchases of clinical trial supplies.
G&A expenses were $2 7 million during the third quarter of 2023, essentially flat compared to $2 6 million in the same period of 2022.
Offsetting these increases in expenses was an increase in other income net which was $1 3 million in the third quarter of 2023 compared to 100000 in the same period of 2022.
This change was primarily due to an increase in interest income and reduced interest expense due to the pay off of the SBB term loan in may of 2023.
As of September 30th 'twenty, 'twenty, three our cash cash equivalents and marketable securities totaled $88 9 million compared to $120 5 million as of December 31, 2022.
We expect cash burn to ramp a bit over the next several quarters as we conduct the trials as Jennifer discussed today.
Our cash runway guidance that we will have cash cash equivalents in marketable securities into 2020 six remains unchanged and we believe there is enough to fund all the trials, Jennifer just discussed and gives us good cash runway after the last readout.
This concludes our prepared remarks, and I will now turn the call back over 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 youre using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two.
The first question comes from Annabel Sammy from Stifel. Please go ahead.
Hi, Thanks for taking my question. So just on first on the RCC trial, what do you see it in such a pickle ramp up time for RCC.
How competitive is the enrollment and the development landscape here outside of the trials that you just mentioned and I guess the same goes for IPF just as your waiting to start. These trials are you seeing any competitive development that you might that might tick patients away from the trials and then slowly.
Yeah.
Thank you Annabel I'm going to let David go ahead and answer that since he is leading this charge.
Thank you very much Jennifer important question. So in terms of the ramp up so the reverse study in RCC patients.
Or are we are targeting having all of this planned 14 studies.
Up and running in early first quarter.
And actually a substantial number of these sites would be targeted to be online at the end of fourth quarter.
The challenge is it's a small study of 60 patients and we have heard from many of the Pea is who a lot of whom are also involved in other phase III RCC work right now.
They certainly do not anticipate issues with competition for ongoing other RCC studies.
One of the factors there is as we have publicly disclosed the enrollment will be a one to one enrichment strategy. So.
Half the subjects.
20 per hour call frequency.
The 10 to 19 category. So that I think that is one factor that we did that.
Help us with recruitment for the study so we're not anticipating any problems there.
Moving on just does that answer your question on the RCC before I begin today Carl study.
Yes. It does so so for coral study could you reiterate obviously one of the same question basically yeah. So what we've heard so far for the mm for the carnival for the phase II B in the Ips cough subjects is what were planning there is to have the majority of studies of the <unk>.
<unk> centers up and running by the end of first quarter.
So as we've announced we will be we will be start initiating that study in the near future.
In Q4.
But with the majority of centers are active in Q1.
What we've heard again, we've been in discussion with a lot of the investigators school that study.
The what we've heard and what has been reflected from the individual investigators. It's usually been in IPF study it would usually be a batch of recruitment scenario recruiting for and Ips.
These modest modifying program study and that's what the investigators would anticipate for this study so right.
Right now we are not to come back to your question, we're not expecting significant issues compared to other disease modifying programs, if anything expectations for enrollment to be higher.
And those disease modifying programs, yeah, Annabel I would just add I think we've been really thoughtful I'm, having struggled with difficult to recruit conditions in the path of having plenty of sites. We have about 60 sites for IPF to enroll 160 patients sort of spread across 10 countries. So I hope that we've got sort of some good.
Frank behind it to be able to get enrollment done it in a timely manner. Okay, great and then if I could just ask a follow up.
On the on the Pn program, we saw the the the safety data from the all in the comment that the patients continue to see benefit on a W are on the on the W. I N a score.
Is there any magnitude that you can share with us and.
To the placebos have any chance to crossover in this trial I can't remember if that was one of the components.
And can you share whether there is any healing evidence.
So that was a teaser that little efficacy comments. So yeah. That's what happened at the end of the when you finish the double blind everybody rolled onto drug. So the placebo did have a chance to come and study them. We are at a future meeting gotta put out the efficacy data around this which will have skin healing data. We've got some pictures they've got koala.
If life data and as you might imagine when you have your edge go down consistently over a year and people stay on it for a year. So do you have other measures as you saw in our double blind study tend to follow but we didn't want to put that out at the speeding because we wanted to be able to do that at a future meeting. Okay. And are you are you close to an end of phase two meeting now with F. D. A.
Hey.
So as you heard we've been very busy so I would say the end of phase two meeting slipped a bad where where we plan to request that in the first quarter, but we want to make sure. We have a full briefing document ready to go when we do that request, which will also actually drop on questions. We may have been related to our cost program because the underlying molecules. The same so we.
Pay requesting a meeting in the first quarter and it takes roughly 70 days to get a meeting from there okay. Great. Thank you.
Yeah. Thank you Annabel.
The next question comes from row on Mesa from Oppenheimer. Please go ahead.
Hey, everyone. Thanks for that Ben.
And Vishal just two questions for me.
If you could give you an idea of how should we think about where do viewers will fit in the IPF patient treatment regimen.
And also could you maybe remind us if there any differences between the results.
Moderate or severe cough, a certain the kenosha and.
And if so does this data point.
More likely benefit and monitors your cough and refractory chronic cough.
Yeah.
Yeah. So I'll take the first part David do you want to comment on the second part to that sounds good. So the treatment regimen. It's interesting I sat through a lot of calls we did a lot of research last summer with not only patients, but also treaters and payors around this exact question and you know the the anti.
Fibrotic, they're challenging for patients a lot of patients discontinuing early because a lot of the Gi side effects and the other thing. We also heard as a patient can't mess. They can't detect the fact that they're progressing slower I mean, it's been shown they do extend life, but they still do decline. So it's hard for a patient to really detect the fact they are declining.
Slower than they would and one of the things we heard from a lot of the investigators is because the response from our trial was so dramatic and in really a difficult aspect of this disease that a lot of these treaters would probably start actually with prescribing our drug get a win with these patients so they're feeling better coughing laugh.
And then move them on and they thought they might have a better success rate of keeping our patients on the anti fibrotic. So basically what we heard is cough is present in this disease from the beginning it stays there all the way through the and so it was really seen as a treatment that would be used early on and continued throughout the course of that disease and I'll, let David.
Speak on the cough counts and why we think it could work in both moderate and severe happy to do that so in the canal study the IPF coal subjects.
What we basically looked at post hoc analyses looking at baseline call frequency.
Affect the efficacy signal and there was lots of relationships. So even those subjects who sell into the into the lower baseline co frequencies have the same efficacy signal.
Hi, Thanks, Duane call frequency subjects that was one of the rationales when we were looking at the enrichment strategy, but we've just disclosed for the RCC reverse study why we're going for the one to one in Richmond. So that we can in essence assess both the moderate cough frequency population with 10 to 19 and the high court.
Frequency that are being focused on with the P. Two X three programs equally we really wanted to get a good look and that lack of a baseline call frequency to efficacy effect into now we think is supportive of that approach and we think because the drug works centrally at the brain stem, which mediates coughing and breathing that it really should work across kafka.
So you know as long as you get some minimum level why theres not so much variance.
Thanks, so much.
Thank you Ryan.
The next question comes from Thomas Smith of Leerink Partners. Please go ahead.
So that is how much are you there.
The next question comes from Sean Kim of Jones trading. Please go ahead.
Yeah, Hi, Thank you for taking my questions.
A question that I have is.
Or is she trial.
So given that you are straddles fine for moderate versus Didier I'm just.
Just curious did you hear the professional statistical Hum plan for those two groups.
You know, whether youre going to be seeking statistical signature because it.
It tends to moderate animals to sit here introduce Julien also combined.
And beyond the statistical skin scanner chickens, or what you think would be clinically meaningful reduction, especially reported a moderate group. Thank you.
Yeah, David Thanks.
You for that question so.
So with the end of 60 that we're studying in Aruba.
We have powered it for 45% treatment effect.
Now do you see okay, so a 25%.
Effect greater than our anticipated placebo effect, which we expect to be.
Assumed to be 20% in that study.
So that's for the total population of 60 subjects.
We think that is appropriately conservative clearly we saw much greater than the 25% separation from placebo, we saw double that.
<unk>.
Now study as you know in the IPF population. So we think we've been conservative what that means is if we get an effect size, which is larger than 25% versus placebo and we would actually have 80% power in both subgroups.
So if we increased more than our conservative 25%.
Versus placebo effect size, we would be powered at both of the groups of approximately 30 subjects each.
Does that address your question.
Yeah.
Yeah, David He he also asked about clinical Meaningfulness, you know what was defined as clinical meaningfulness, yeah and that really sets.
About about 20% to 30% is believed by the majority of experts to beat the sort of range that is clinically significant if you are looking at these reductions in cost frequency and that was one of the reasons that we've set this 'twenty the ability to power the 60 subjects with a 20 to detect a 25%.
Exercise because that is clinically relevant to patients which is believed to be by experts in the field.
Okay, great. Thank you very much.
Thank you Sean.
The next question comes from Serge Belanger from Needham and company. Please go ahead.
Hi, good afternoon.
Thanks for taking our questions.
I have two I guess first on the cough program can you maybe talk about the.
Pathology differences between IPF cough and.
Refractory chronic cough.
Do you think.
<unk> mechanism of action.
To be more effective in one disease or another.
And then.
On the Pn program.
If you've had any discussions about partnering and how you would describe the level of interest for that program.
David Why don't you take the first one I'll take the second one yeah no. It's a really important question. So coke hypersensitivity is a key driver in both IPF and refractory chronic cough as you know so there is a similarity in terms of underlying what is driving both of these conditions, even though the pathophysiological emission.
Asia is different in these two conditions, but it leads to the same sort of degree of cough hypersensitivity.
I mean, all key differentiation factor as Jennifer talked about jewelry her presentation that you've heard from US before is the key here. So we've got proof of activity, which is good. We also have the central activity, which differentiates us in the nation states that activities suppressing.
<unk>.
Brain basal cough reflex center and the federal the higher level set of all control of it that is the key differentiation so that in essence.
We believe that central activity and its ability to be independent of what would be the triggering mechanism is it is going to drive effects in both of these indications and other indications.
Thank you Sir for the Pn partnering question, Yeah, we continue to be in touch with our parties interested our colleague Farrell with off at bio Europe. This week continuing those discussions so we're clear on where the interest lies here who's interested as we've always said, we would like to get through the F. D. A meeting and be clear about the path forward and why.
Blackstone and then well make decisions at that time about.
Whether we license the drug or not at that time, so yeah. Good interest still.
Thank you.
Thank you.
As a reminder, if you have questions. Please press Star then one the next question comes from Mack, Montana Mom Tani from B Riley Securities. Please go ahead.
Good afternoon, and thanks for taking my question. So appreciate the comments on the RCC landscape I was curious what you might be looking for Abby Diaz com coming up.
One of the D C.
Who knows that dimension and then the second question was.
On the R&D filing sorry.
Sort of remind us of it.
Doug.
Process.
Yeah. So the outcomes that great question and David you should add any color I'm going to watch the whole day, I think it'll be really telling them you know what the F. D. A R. How they focus on with Jeff of picks and as you know it was a small sort of placebo adjusted change, but they did have statistical significance them. They were required to go back and do some.
Work so I.
I my expectations are the drug likely gets approved Merck certainly putting a lot of resources behind getting ready to launch it but I think we'll be watching that just to learn sort of what the position is how people view what I'm I don't know David if you have anything else regulatory wise you are looking for no similar to what you've said.
Chevy I would just my own personal comment from listening to a lot of experts in this field I certainly share your view I hope they get approved mhm because of the medical need in this field I mean, yes. It is true.
And do you want to take that one.
Or are we at with getting in I N D. Open so the I N D mm is progressing for the.
Respiratory physiology study, so we would expect to make an announcement.
On that and timing so that's in the near future. So that we were on track for having that submitted.
If in the near future.
Got it and maybe just one quick question if you can.
Would qualify.
Any.
<unk> been on.
Or you know what I mean.
And oney.
Any cash inflow humira have somehow credentialing partnership discussion.
Note that the cash runway includes our existing cash so no no additional cash influx assumed.
Yeah.
And our inflow.
Okay. Okay. Thanks for that clarification I appreciate you taking my questions.
Yeah. Thank you Matt.
Yes.
I'm not showing any further questions. This concludes our question and answer session I would like to turn the conference back over to Jennifer good for closing remarks.
We would like to thank everybody for participating in today's call. We will be attending the Stifel Conference next week, and we hope to see some of you there. Thank you.
The conference has now concluded. Thank you for attending today's presentation you may now disconnect.