Trevena, Inc. (TRVN) Q3 2019 Earnings Call Transcript

Hello, ladies and gentlemen, and welcome to the third quarter financial Results and business update conference call. [Operator Instructions] As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Mr. Bob Yoder, Chief Business Officer. You may begin.

Thank you, and welcome, everyone. Thanks for joining us on this morning's call. With me today are Carrie Bourdow, our President and CEO; Mark Demitrack, our Chief Medical Officer; and Barry Shin, our Chief Financial Officer. Before we begin, we wish to inform participants that we will be making forward-looking statements on this call, which are made pursuant to the safe harbor provision of the private Securities Litigation Reform Act of 1995. You are cautioned that such forward-looking statements involve risk and uncertainties, including risk detailed from time to time in the company's periodic reports filed with the Securities and Exchange Commission and we undertake no obligation to update these statements beyond today. During today's call, Carrie will discuss some key corporate highlights, and Mark will walk through the top line data from our recently completed multi-dose healthy volunteer QT study. Carrie will then provide an update on our pipeline followed by a review of our third quarter financial results from Barry, before we open the call for questions. As a reminder, the materials containing the top line data and financial results that we'll be discussing today can be found on the Investors section of our website at www.trevena.com. I'll now turn the call over to Carrie.

Thanks, Bob. Good morning, everyone. Thank you for joining us. As you may have seen in our press release this morning, we are very pleased to announce today that we've completed the multi-dose healthy volunteer QT study for oliceridine. And we believe that we have a clear regulatory path forward as we've now completed all the items to address the CRL for oliceridine. We now turn our attention to preparing for NDA resubmission, which we expect to be in the first quarter of 2020. Earlier this year, you may remember that I laid out a plan to position oliceridine for resubmission and advance our pipeline and the completion of the healthy volunteer study represents the latest step forward in the execution of that plan, and it's an important milestone for the company. So let me turn the call over to Mark, who will provide a high-level description and a review of the top line results. As Bob mentioned, we updated our corporate deck on the Trevena website to include the study details, and there's a lot of data to review this morning. Mark?

Thanks, Carrie, and good morning, everyone. Today, I'm pleased to share the top line data from the multi-dose healthy volunteer QT interval study. We believe this data thoroughly addresses the request for additional data that FDA posed to us late last year and will allow us to move forward with our plans for NDA resubmission. We've previously discussed general components of the study design. And I'd like to take a few minutes to dive a bit deeper into some important details, connecting these design features to the questions we aim to answer. I'd also like to note that we appreciated the careful input we received from FDA during the development of this study on both the protocol and the statistical analysis plans. As background, in our Phase I program, we conducted a single-dose thorough QT study. We noted a small transient effect on QT interval, which was most clearly evident at the supratherapeutic dose at 1 hour after dosing. To better characterize this effect, we conducted cardiac safety ECG monitoring in our Phase III study program, focusing on that time window. In 2 controlled Phase III pivotal trials, involving nearly 800 patients, we saw no difference in QT effect between oliceridine, morphine or placebo at the 1-hour and the 24-hour time points after dosing. As we discussed in our original NDA submission and in our presentation to the advisory committee last year, we believe that any QT effect of oliceridine showed no evidence of a clinically meaningful consequence. After reviewing this data, FDA asked us to better characterize the full-time course of any potential effect. We believe this information will help clarify whether there was any late-appearing or accumulating effect of our compound. The study we developed in post consultation with FDA was conducted in healthy volunteers and included both placebo and the positive control. Importantly, FDA requested a multiple-dose study, unlike the more traditional thorough QT study designs, which involve only single-dose administration. This study was designed to obtain blinded ECG assessments at hourly time points across the 24 hours using state-of-the-art, digitally archived Holter monitoring methodology. This thorough examination of -- over 24 hours, provided a continuous data set of the time course of any QT effect under conditions of repeated dosing. We also worked carefully with FDA to develop a standardized dosing regimen, with bolus IV injections every 2 hours across the 24-hour dosing period. Subjects were dosed with 2 or 3 milligrams each injection, to a cumulative total daily dose of 27 milligrams, which is the maximum daily dose in our proposed label. I'll now discuss the data. Data from the trial were consistent with that of our prior studies, and there was no evidence of any late-appearing or accumulating effect. In fact, we observed the opposite, with the QT interval generally declining after approximately the 12-hour time point, despite continued dosing every 2 hours. On the primary endpoint, at 22 of the 24 time points, the placebo-corrected mean QTC change from baseline was less than 10 milliseconds. At 18 of the 24, the upper bound of the confidence intervals was less than 10 milliseconds. Among the secondary outcomes, the 24-hour time average QTC change from baseline was 4 milliseconds. I'd like to reemphasize that unlike our single-dose Thorough QT study, this was a multiple-dose study, with repeated dosing throughout the study period. At an individual subject level, there were no categorical outliers who showed a rate corrected change from baseline greater than 60 milliseconds or an absolute QTC interval greater than 500 milliseconds. This is an important consideration in the analysis of any QT study and provides insight into whether any mean changes are reaching well-recognized clinically meaningful levels of concern. We're also very pleased with the tolerability and safety findings from this study. Nearly all subjects, 59 of the 65 subjects dosed, reached the exposure goal of 27 milligrams, not missing a single dose. Remember, FDA asked for at least 20 subjects at that target. Of the 68 randomized subjects, only 4 were discontinued from the study. Three subjects had poor venous access and, thus, they were discontinued prior to the start of dosing. One subject was discontinued early in the oliceridine study period after receiving only 2 doses because of a nonserious adverse event. This subject was observed to have an asymptomatic and transient [ 4 beat run ] of nonsustained ventricular tachycardia, or NSVT. This subject demonstrated no evidence of meaningful QT interval change during the 2 doses of oliceridine. At the time of the event, it was found that the patient had hypokalemia, a compounded condition and risk factor for NSVT. It's also worth noting that 3 fronts of NSVT are well documented to occur in healthy volunteer studies. In addition, 1 patient completed dosing but was not evaluable due to equipment error, but this patient's course was otherwise unremarkable. There were no serious adverse events in this study. In general, adverse events were mild to moderate in severity, and consistent with the safety profile we have already documented in our original NDA safety database, which is comprised of over 1,800 subjects who received oliceridine. In summary, we're confident that the data we have now assembled is responsive to FDA's request. And we look forward to finalizing our progress toward resubmission of our NDA in the first quarter of next year. I'd like to conclude by commending the clinical development team for their extraordinary work, from driving multiple productive discussions with FDA to developing a protocol and moving it steadily and effectively through regulatory review and to meeting our study start and finish milestones. A significant amount of work took place to ensure that we could accomplish these achievements, and it's exciting to see the team's efforts pay off. Let me now turn the call back over to Carrie.

Thanks, Mark, and thank you and your team for all your work in completing this study. So let me spend a few minutes talking about the potential market opportunity for oliceridine. Each year, over 45 million patients come into a hospital setting and are treated with drugs like IV morphine for acute pain. As the number of painful surgical procedures and complex patients increases and the economic burden on hospital systems continues to grow, there remains a significant need for effective, well-tolerated IV analgesics to help manage acute pain. While our main focus has been on oliceridine this year, we've also been able to advance our pipeline, and this morning, I'm pleased to announce that we've initiated the acute migraine proof-of-concept study for TRV250, another new mechanism of action, this one at the delta receptor. The delta receptor's an interesting target. It's responsible for pain, anxiety and mood regulation in the brain. We're studying migraine first, and it represents another large market opportunity with significant unmet medical need. There are approximately 650 million headaches treated annually in the United States. A novel aspect of this study is that we are also evaluating the ability of TRV250 to reduce symptomatic anxiety, which occurs in roughly 50% of migraine patients. So as I said, we've now initiated this proof-of-concept study, and we currently expect that we can report top line data in the second half of next year. Let me now turn the call over to Barry to review our key financials.

Thanks, Carrie. We disclosed key financial measures earlier today in our press release and full financial statements in our Form 10-Q. For now, I'll summarize the headline numbers. For the third quarter of 2019, we reported a net loss to common stockholders of approximately $8.6 million or $0.09 per share compared to approximately $4.5 million or $0.06 per share for the third quarter of 2018. This increase in net loss and net loss per share is primarily due to increased research and development expenditures in connection with our healthy volunteer QT study. Cash, cash equivalents and marketable securities were $44.7 million as of September 30, 2019. We believe this amount, together with interest income, will fund our operating expenses, debt service and capital expenditures into the third quarter of 2020. We'll now open the call to questions. Julie, I'll turn things back to you.

[Operator Instructions] And your first question comes from Jason Butler with JMP Securities.

Congrats on the results. I guess, just the first question, do these data have any change or -- just on how the drug would be used in clinical practice? Is there any data here that changes how you previously proposed the label in the last submission? Or how you think about the use of the drug and, again, in practice?

Thanks for the question. From our perspective, it doesn't change how we've been thinking about it and how we've been positioning it. I don't really want to get in front of the FDA as it relates to the label, but as you heard Mark say, we think this data's strong. We think it answers all of the questions that the FDA has for us. And so we're looking forward to resubmitting in the first quarter. Mark, I don't know if you want to add any comments or...

No, I mean, I can just echo what Carrie said, Jason, that we studied a dosing regimen that was consistent with our proposed labeling. And as you can see from the data, the effect dissipates over the course of a steady interval. So we will bring this labeling recommendation forward at this point.

Great. And then, Carrie, just one second question from me. Looking forward to 2020 as you get the resubmission back under review, can you talk about what activities you'll be undertaking to prepare for a launch?

Yes. Great question, Jason. Thank you. And let me just dole also for folks that haven't been following maybe the time lines. So with a resubmission in the first quarter, we expect that we'd have a Class II review, which is 6 months, and then we'll have DEA scheduling on the back end of that, so another 3 months. So the expectation is that we would potentially have an approval the second half of next year. We've actually spent a lot of time already thinking about the commercial strategy, the value proposition, the positioning. We're beginning to build out our internal team and thinking through additional work we want to do as we get closer to potential approval.

And your next question comes from Douglas Tsao with H.C. Wainwright.

Maybe, Mark, this is a question for you. How common is it to see this type of trend in terms of the results and the QT values in terms of the dissipation over the course of this 24 hours? And is this something typically seen with pain drugs?

So there's 2 parts to the question that you're raising. One is in regard to the study design itself and how often in a study design like this do you see this pattern of effect. Kind of the short answer to that is there are not that many study designs that are done as repeated dose Thorough QT studies, as you probably know. A vast majority of the use of the TQT study design is for single-dose testing early in Phase I. From our perspective, the pattern that we see is absolutely clinically reassuring. And it addresses a question that FDA was inquiring about, which is about the time course over 24 hours. You remember, in our Phase III sampling, we tested at 1 hour and at 24 hours. So we now have filled in that interval of time pretty exhaustively. So it's kind of a unique data set in that regard. So hard to reference relative to other [ confluence ] who've not done a similar type of study design. The second part that you're raising is in regard to other compounds of this class. And part of the answer relates to the fact that, again, this level of exhaustive review of cardiac safety is just rarely available when looking at products like this. So kind of difficult to answer that question. But we're certainly not alone with a small QT effect.

Okay, great. And then just on the 250 study, is that going to be enrolling patients, and forgive me if you mentioned this, is this going to be enrolling in the U.S.? Or is that going to be international -- an international study?

That's an international study. We've been conducting this with an expert research organization outside the U.S., who has particular expertise in migraine and the use of the nitroglycerin infusion model. In fact, we've collaborated with them on an actual clinical validation study of that model preparatory to this project.

Okay. And then just in terms of the interest in terms of symptomatic anxiety. Is that going to be patients with like general anxiety disorder or maybe, Carrie, could you give a little more detail in terms of the sort of indication that you would be sort of thinking about that?

Yes. So I'll -- there's a reason I hired a neuroscience expert as a Chief Medical Officer. So I actually will defer to Mark, because it's an area that he's been really interested in with TRV250, and specifically with the delta receptor. So I know he's passionate about it. Go ahead, Mark.

Yes. So there's a distinction, that you're raising, Doug, between the diagnosis of generalized anxiety disorder and what we're referring to, which is situational or symptomatic anxiety. The latter being much more a common phenomena, and it can complicate the -- an individual patient's experience of the severity and pain associated with the migraine, in fact. So formally diagnosed GAD is less prevalent. What we're looking at here, since we have a single-dose study design, it really would not be practical for us to be answering the question about treatment of GAD as a disorder. That would require repeated doses and as a later target of study, but it's important that we see that as a potential area of interest down the line, obviously. In the near term, the first goal will be to use this study in an opportunistic way. Since we know that situational anxiety will occur in a fairly robust fashion, in association with acute migraine sufferers, this study gives us an opportunistic way of looking as a secondary outcome measure, as to whether or not there's any signal of benefit. If there is, that guides us then about designs and targets for future work.

But, Doug, I will say, from a commercial opportunity, there are no migraine agents out there that could treat both migraine and anxiety. And as I mentioned in my section that there are about 50% of migraineurs, migraine patients, that have situational anxiety. So it's a really interesting opportunity for us to understand the compound for migraine, but then, as Mark said, also explore some future potential opportunities.

Okay, great. And then, so are you going to be -- the final question for me. Are you going to be enriching the migraine study to try to make sure that you get enough patients who also suffer from situational anxiety?

The plan right now, we expect to enroll about 120 migraine patients. Mark, I don't know if you have any additional details?

Well, the short answer, Doug, is no. There's no specific enrichment. But based on the epidemiology of the symptom accompanying acute migraine, we believe there should be a robust enough representation of that symptom in the population that we can actually use as a secondary endpoint, as we are.

I am showing no further questions at this time. I would now like to turn the conference back over to Carrie Bourdow, CEO.

Thank you, and thank you, everyone, for your questions. As you've heard this morning, we've made significant progress in 2019. And as a result, 2020 is shaping up to be a transformational year for the company. We have the right leadership in place to accomplish our goals. And I think you've heard from the folks that are around the table here, I am so pleased to be working with this team. Mark, as many of you know, has a tremendous amount of clinical trial design experience and post-market clinical development in neuroscience, and he'll oversee the plan to advance oliceridine in the pipeline. Bob Yoder, our Chief Business Officer, and I have successfully launched multiple products and have experience in commercializing assets. And finally, Barry brings a wealth of strategic and financial experience that will be invaluable as we continue to explore the right strategic partnerships for Trevena. So I am very excited about our path forward. Let me conclude by thanking the people who participated in the oliceridine healthy volunteer QT study. I'd also like to thank everyone here at Trevena for their dedication, resourcefulness and focus over these mission-critical months, I know you remain committed to developing novel medicines for patients with CNS disorders. Thank you, everyone, for joining us this morning.

Ladies and gentlemen, this concludes today's conference. Thank you for your participation, and have a wonderful day. You may all disconnect.