Q2 2023 Trevi Therapeutics Inc Earnings Call

Yeah.

Good afternoon, and welcome to the Trevi Therapeutics second quarter 2023 earnings conference call.

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Various remarks that management makes during this conference 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 those 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 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.

<unk>, specifically disclaims any obligation to do so even if a change even if its views change.

I would now like to turn the conference call over to Jennifer Good Trevi as President and CEO . Please go ahead.

Good afternoon, and thank you for joining our second quarter earnings call and business update joining me today on this call. If we set Delphine Travis Chief Financial Officer, Lisa and I have some prepared remarks, then we will open it up for questions.

During the quarter, we continued to advance our clinical development plans for I had to be out in our chronic cough indications. Let me provide a brief update on each of our programs beginning with our lead program in chronic cough and I P F.

It is a serious end of life disease, chronic cough, and IPF impacts patients physically psychologically and socially decreasing their quality of life with no currently approved treatment options for chronic cough. There is an urgent need for new therapies chronic cough may also be a risk factor that plays a role in the progression of IP.

Yeah, the constant lung injury micro terrorists and potential inflammation caused by persistent cough and may lead to worsening of disease and potential worsening of outcomes for patients.

We are planning to conduct two studies in parallel during this next phase of development in our IPF chronic cough program. The first is a four arm phase <unk> dose ranging trial that will study three active doses I've had to be out and placebo. We are planning for a total and then the study of approximately 160 subjects and dosing.

For six weeks, we plan to conduct this study in multiple countries and sites to be able to complete enrollment in a timely manner. As you maybe aware there is a lot of development work going on with the anti fibrotic and IPF patients. So we expect that enrollment will be competitive we.

We feel we have a differentiated trial for patients and investigators as the only chronic cough study in IPF with previously reported positive data.

We have finalized the protocol for the dose ranging study and are in the process of working through various submissions to regulatory authorities. We have also completed country selection and are qualifying the sites working through budgets and preparing sites for the start of this trial. We estimate this trial will be initiated in the second half of this year subject to finalizing our regular.

So our interactions.

In parallel we are planning for a phase one b respiratory physiology study.

Yeah, there is class labeling carrying a generic risk of causing respiratory depression. This is not something we've seen in our safety data across our various studies to date and there is literature that suggests that mixed agonist antagonist switches the class B at St Pauls and have a ceiling effect on the impact on respiration, however, given the pulmonary.

And of the IPF population. It is important that we characterize as effect if any on respiratory depression in IPF patients Trevi is planning to extend out the phase one be impatient study in IPF patients that have varying levels of disease severity to determine if we see any clinically significant impacts on respiratory depression.

This study will help define the patient population for our pivotal program and ultimately the label.

We have received FDA feedback on the planned phase one B study have finalized the protocol and are working through preparations with the two sites that we'll conduct the study and preparations are being finalized and we expect to initiate this study in the second half of this year as well.

In addition to the studies in IPF costs. We have also completed a protocol for a phase two study in refractory chronic cough, our RCC, we believe that because to do be it works both centrally in the brain and preferably in the lungs Adobe how has the potential to provide therapy across a range of chronic cough indications regardless of what the underlying.

Diseases, we expect that this trial will look a lot like the canal trial, which was a dose escalating crossover design and we plan to enroll approximately 60 subjects there've been a lot of trials in RCC with only one mechanism, which has seen some success the pay to X rays, which mechanistically work peripherally in the lungs have.

We believe there is still a significant opportunity for a mechanism that works, both centrally and preferably to potentially provide strong and consistent efficacy in the most difficult to treat RCC patients, including those with high cost counts, but also among patients below the enrich the level of 'twenty cost per hour currently being used in <unk>.

C. C trials, we are leveraging the learnings from other companies in our development plans in RCC as we design our own study.

Our phase two IPF comdata and mechanism continued to garner a lot of attention at medical conferences during the quarter with oral presentations at both the American thoracic Society meeting as well as the American Cough Conference. We also have the data from the Canal trial results published in Needham evidence.

I think that speaks to the importance of the unmet medical need in these difficult to treat IPF cough patients and the medical community's interest in our program across cough indications.

The other indication we have ongoing work as the treatment of Prego Nigel Ers RPM. We are currently completing the data analysis from the one year open label extension study that was associated with prism and we intend to present that data at an upcoming Dermatology conference. We also plan to seek an end of phase II meeting with the FDA, which we expect to Rick.

Quest later this year. After this meeting we will determine next steps for the program.

Finally, we are conducting a human abuse potential study, which is required for the NDA filing note that the parental version of now butane is currently unscheduled and the U S by the drug enforcement agency or DEA. The objective of this study is to compare the likeability our abuse potential of oral and that'll be a theme to an agreed upon active.

Operator, which is butorphanol for this study the TARP analysis schedule for our drug.

The study is being conducted in two parts with the objective for the first part to characterize various butorphanol doses and choose a dose appropriate for the comparison against oral mouth you're fine.

We have completed part one of the study in a selected that now do you feel and Butorphanol doses for the second part of the study we have submitted this data to the F. D. A to get their comments. The second portion of the study is a randomized double blind active and placebo controlled five way crossover design to determine the abuse potential of three dose.

So as of now do you feel well relative to the selected dose of Butorphanol and placebo.

However, this portion of the study is now delayed a bit as earth, a nationwide shortage of IV butorphanol. The comparator drug in this study we were working to secure supply from the single source supplier in the U S. But then the plant was recently damaged due to a tornado and we will need to let the company worked through that matter before resuming supply.

Actions once we were able to secure I V B TARP and all and have them put from the FDA on the recommended doses. We will commence the final portion of the study importantly, this study is not on the critical path for any of our planned clinical trials.

In closing we are focused on getting these three chronic cough studies up and running and opening good sites to support strong enrollment we will announce studies as are initiated and provide more details on the study design unexpected timeline 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 June 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 second quarter of 2023, we reported a net loss of $7 1 million compared to a net loss of $8 1 million for the same quarter in 2022.

R&D expenses were $5 8 million during the second quarter of 2023, compared with $5 1 million in the same quarter. In 2022. The increase was primarily due to increased consulting and professional fees related to startup activities for the three planned chronic cough trials as well as an increase in personnel related expenses.

G&A expenses were $2 5 billion during the second quarter of 2023 compared to $2 7 million in the same period of 2022. The decrease was due to a reduction in market research costs.

Other income net was $1 2 million in the second quarter of 2023 compared to other expense net of <unk> 2 million in the same period of 2022. The change was primarily due to an increase in interest income due to higher cash balances and higher interest rates.

As of June 30th 'twenty, 'twenty, three our cash cash equivalents and marketable securities totaled $94 2 million compared to $120 5 million as of December 31, 2022.

As I discussed on last quarters call during the quarter, we elected to pay off our term loan in full the payoff amount was $6 5 million loans with Silicon Valley Bank now a division of first citizens bank and we paid it off to free ourselves of restrictions imposed by the lender or.

Our cash runway guidance that we will have cash cash equivalents in marketable securities into 'twenty twenty-six remains unchanged and we believe is enough to fund all the trials, Jennifer just discussed and give us good cash runway after the last readout.

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

Thank you we will now begin the question and answer session.

A question you May Press Star then one on your Touchtone phone, if you're using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two at this time, we'll pause momentarily to assemble our roster.

Our first question comes from.

Annabel <unk> from Stifel. Please go ahead.

Hi, everyone. Thanks for taking my question I just want to.

Go over really quickly the learnings you got from the other trials in RCC, you went pretty quickly and how.

How might this population behave differently from IPF, you mentioned that youre going to have the same trial design. So I just wanted to understand the specifics around that thanks.

Yeah. It's a good question Annabel I think the learnings have been around you know the endpoint that's what the objective cop monitor what's sort of nailed down and obviously the validation of counting and all of that I would say the biggest debate that comes around is what how much to enrich or not and rich and we've had a pretty healthy debate internally as you know the Pallas study how to think.

<unk> enrichment strategy around greater than 20, coffers and our data in IPF costs, though we did not see any difference based on level of cop and after attending some some of these medical meetings and having her on advisory boards.

There's a big unmet need for what physicians view as severe koppers that are in this 10 to 19 cost per hour they view that as severe disease.

And the Dallas data and I've heard even the Merck data really only works on sort of these higher cost counters, which is not a big portion of the market.

So we're going to stratify, our trial and actually have half the subjects come from this 10 to 19 cost per hour and greater than 20 cost per hour and we feel confident doing that based on what we saw in IPF cough and sort of how it responded in the various cost levels. So I would say that was sort of the biggest debate other than that similar protocol similar sort of income.

Asian exclusion criteria.

Okay.

Great and then just want to confirm you said butorphanol.

It's not a rate limiting step for any of the trials not not IPF or RCC correct.

Correct, it's only a rate limiting step to getting to our fine human abuse potential data, but no impact on the clinical studies.

Great. Thank you very much.

Thank you Annabel.

The next question comes from Serge Belanger from Needham and company. Please go ahead.

Hi, good afternoon.

Just a couple of quick questions I guess first one.

Maybe the number of sites, you're targeting for the phase <unk> dose ranging trial.

In the past you mentioned that the.

The enrollment process.

For Oh this draw about 200 patients would be about 12 months.

Just curious if you feel.

In that same ballpark given your comment that this could be a competitive enrollment.

Thanks.

Yep.

Two good questions the number of sites for the to be we're still finalizing that we're doing a lot of the site qualifications, but it's going to be approximately 60 to 70 sites. So we're bringing on a lot of sites to be able to sort of move through this quickly and so that is underway I think as far as the 12 month enrollment one adjustment when we.

Initially started we thought it would be approximately 200 bed as we fine tuned our statistical assumptions on the end is gonna be 160, so that is helpful and and yes, we do think it's still a 12 month enrollment.

Yeah.

Great.

Thank you Serge.

And Rohit.

Yeah.

The next question comes from Leland <unk> from Oppenheimer. Please go ahead.

Hey, good afternoon, and thanks for the update and taking our questions.

Wanted to ask on the human abuse potential.

Study, obviously, you're testing dose doses that are much higher than those in our in the work Youre doing in both IPF chronic cough in RCC. Just wondering you know if you do start to see some liability at those higher doses that are that are beyond what would be contemplated for the.

The potential indications would that.

Potentially have an impact on.

Labeling or D restrictions, how should we think about kind of what the potential scenarios would be.

From the state of things.

Yeah. It's a good question Leland I get this question a lot about sort of what success here and Theres no sort of silver bullet because as you know the DEA is going to look at a lot of things in totality, you know or clinical databases et cetera, but I think generally we're going to have a low dose of now you've seen sort of the marketed dose of now and then.

High dose, which we've done all the work around that it's going to be sort of three X the marketed dose.

And we've already done work around characterizing all those doses and inter.

Interestingly you do not see an increase in any kind of likeability as you get to those high doses it is tolerated which as interesting.

Interesting, but you know not shockingly the capa ends up sort of getting swamped that receptor and so you get a lot of those just for side effects that really sort of come in hard when you get up to those high doses. So so we're not expecting to see that I think if you did I mean that will definitely factor in and I think that's somewhat what's may be.

Harper and I'll schedule for drug so I think the real answer would be if you saw an increase in liability around now do you feel that's doses got higher you've kept would compare with that high dose looked like two butorphanol. If they're similar then you could be talking about a schedule for type drag, which you know and the conditions were in these are serious conditions a lot of these patients are on opioids.

So we don't see that is impacting the market.

Got it okay, and giving given the butorphanol.

Shortage. It sounds like this is going to go past yearend do you have do you have a sense of when we might be able to see these data, presumably first half 'twenty four or just wondering if you can share. Thank you.

Yeah, no. It's a good question, we definitely won't get to year end, because we needed to be dosing in June and July which as we were working that problem sort of last call. You know it just depends this is pfizer's plant and when that can sort of play through we are in conversations with them they've actually been quite receptive and help false I'm, hoping when this sort of gets settled out that maybe we.

We can get that in house and we'll keep people updated for now we haven't put out any new guidance just because that's very out of our control as you can imagine.

Yep understood alright, thanks, very much for taking the questions.

Yeah. Thank you Leland.

The next question comes from Thomas Smith from Leerink Partners. Please go ahead.

Hi, This is Matt she wants with Arthur Tom Smith.

So the first question is like what are the gating factors to initiate three.

Three clinical trials and I will try all will likely.

He initiated first and I have a follow up.

Yeah sure. So the gating factors really are primarily around just getting regulatory clearance, we're pretty much ready to go protocols are written we're getting sites contract. Then you know getting them all ready to go it's just a matter of getting final sign off from the regulators and everything in place.

My guesstimate of the first study ready to go is actually probably the RCC trial.

Got it and what strategy.

Do you plan to implement to compete with other compatible program in chronic cough idea.

Yeah. So there's only one other competitor program in IPF chronic cough, it's an area of drug it's a phase two program that that drug did not have success in RCC. So we don't view them as a big competitor I think their overall studies only looking to enroll about 80 patients or so so we don't view them as.

With a competitor I view the more competitive landscape is competing for the IPF patients because there is a lot of work going on in anti fibrotic and I P F.

So I think what our competitive advantage will be where one of the only trials and cough. So you know for people that have severe cop I think that's gonna be intriguing to them. We also running a short study at six weeks the the anti fibrotic trials a lot of them are you know one year commitment. So I think for a patient to be able to get into a six week trial there. So.

Copper is this could be an intriguing proposition for them and we're just quite frankly, bringing up enough sites that are you know we can spread this out and get this done in a rapid time.

Mix change and maybe one last question from us with more recently and resubmitting the NDA for the Awesome OCC dropped my does it change your thought on that.

Julio plan in our D. C. Just you plan to find a partner to advance.

I can see beyond <unk>.

It's a good question, Matt I think our plan is to do the development work here and understand sort of the value of the asset and create optionality here I do think youre right that marketing in RCC is a different sort of animal than marketing and specialty condition like IPF, but those are all things that can be sorted out later.

There's plenty of people interested in this cost space I think if we can put up good data, especially I really think it's intriguing if we're able to work more broadly in this patient population of severe coffers that doesn't have to be someone rich I think that all of a sudden makes us asset best in class. So so we'll work through the development work and sort out.

How we commercialize our best later.

Got it thank you so much.

Yeah. Thank you Matt.

The next question comes from Tony from B Riley Securities. Please go ahead.

Good afternoon team. This is William wood on for Mark Thanks for taking our questions.

When did you broke the butorphanol shortage.

Knowing the FDA feedback and depending on the timeline for the actual shortage there a scenario where you redo part one.

Receipt or are there other options, you're considering maybe worst case scenario.

I think worst case scenario, so the only way I think.

I don't think we'd have to redo part one I guess theres a chance that the agency says they want us to look at a different dose we did look at multiple doses there.

For some reason they wanted us to look at a different dose we would just have to doses small cohort and generate that data, but I think the structure, we put together scientifically sound, but but we do want that validated before we run a whole Likeability study I think to your point worst case scenario would.

It would be we'd have to pick another comparator that wasn't butorphanol and we'd have to get agreement with the agency that that was a good it penthouses and probably that likely either one. The problem is you don't really get out of these issues. All these old IV drugs, they're all sort of in short supply because there's basically one manufacturer. So I'm, hoping we don't.

Get to that point, but if we do then we'd probably be talking with the agency about what would be another likely comparator, which like I said it was sort of a coin toss between butorphanol penthouses in when we did it at the time. So I think either of those would be fine for US and then we would have to repeat the dose work.

Alright.

And then additionally, when I know Europe is quickly approaching in early September where.

Where we expect to see the pacify low dose morphine study readout will be presented there how.

How should we think about that data in terms of how my read through to your now B C and D. R.

Yeah, and we'll have a whole team of D. R. As up anyone's, they're happy to connect you to our group there yeah. So I mean, William you and Ive talked about this before I mean, I'm gonna be surprised it's a morphine trial at morphine use now in cop logos marketing more in the U K less here because of the whole opioid restrictions and that'd be super.

Price if it doesn't work the lead investigator on that his Doctor Molyneaux, who was in our study as wild ride investigator. So I'm going to I think the read through is the mechanisms right that opioids work and cough.

I think a low dose of morphine is always going to have challenges. It is scheduled to opioid you know its generic youre not going to be probably be able to get IP around that at all so I actually think it validates a mechanism and doesn't compete compete commercially with what we're doing.

Yeah.

Understood and then one just very quick last one.

Like in your past P. R R.

Or from one to the RCC was slated for third quarter analysis second half should we read that as a pushback or more just a generalization.

It's more just burbidge I think in our Q, you'll see we still say third quarter I think in some of my remarks I might say later this year, but it's just more of a casual comment.

I appreciate it thank you for taking my questions.

Yeah. Thank you William.

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

We would like to thank everybody for participating in today's call. We have several upcoming conference says that we are participating in starting next week with Stifel, which are detailed in our earnings release issued today, we hope to see some of you at these meetings. Thank you.

The conference call has now concluded.

Thank you for attending today's presentation you may now disconnect.

Okay.

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