Trevena Inc (TRVN) 2014 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Trevena fourth-quarter and full-year 2014 earnings conference call. (Operator Instructions). As a reminder, today's conference is being recorded.

I would now like to turn the conference over to Mr. Jonathan Violin, Director of Investor Relations. Sir, you may begin.

Thank you, and welcome, everyone. Thanks for joining us on this morning's call. With me today are Max Gowen, our CEO; Roberto Cuca, our Chief Financial Officer; Mike Lark, our Chief Scientific Officer; and David Soergel, Trevena's Chief Medical Officer.

Before we begin, we wish to inform participants that we will make forward-looking statements on this call which are made pursuant to the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such forward-looking statements involve risks and uncertainties, including risks detailed from time to time in the Company's periodic reports filed with the Securities and Exchange Commission and that we undertake no obligation to update these statements beyond today.

During today's call, Max will provide a brief overview of some 2014 and recent corporate highlights. David will then provide a detailed review of our clinical programs. And Mike will review the most recent additions to our product pipeline. Roberto will review our financial results, and Max will conclude with a review of important upcoming milestones. We will then open the call for questions.

I will now turn the call over to Max.

Thanks, Jon, and good morning, everyone. And thank you for joining us today. Since our IPO in January 2014, we have made tangible, meaningful progress across all areas of our business to support our pipeline of differentiated therapies, all of which are biased ligands and G protein-coupled receptors.

To begin with, for our acute heart failure program, we are progressing well with our Phase 2b BLAST-AHF trial of TRV027. We recently completed a prespecified interim analysis. And, as planned, we revised the trial protocol, allowing us to weight future recruitment towards the most promising dose.

We also expanded the size of the trial so that we could continue studying the remaining two doses, and we were pleased to report that our collaborator, Actavis, will fully fund this trial expansion with a $10 million payment, which complements their initial $30 million investment in 2013. With the largest study size, we now expect to report topline data in the first half of 2016.

We also progressed our lead pain program, TRV130, through a successful Phase 2a/b study in moderate to severe acute postoperative pain, generating data to suggest that it may offer a superior product profile versus morphine. The results reinforce our confidence in the program as we moved into a second Phase 2b study in soft tissue surgery and started planning for Phase 3 developments.

In 2014, we rapidly advanced our second opioid program, oral TRV734, through two Phase 1 studies. Our goal with this program is to offer an approved therapeutic profile versus oxycodone for the treatment of acute and chronic pain. And our Phase 1 studies provided key insights on activity that we will use to inform Phase 2 development.

In addition to reaching these clinical milestones, our research team had a very successful year. At the end of 2014, we expanded our pipeline by advancing TRV250, an oral delta receptor modulator into preclinical development as a potential therapy for treatment refractory migraine as well as other CNS disorders.

With our biased ligand approach, we believe TRV250 may avoid the problems that have prevented development of other delta receptor candidates. I am very pleased that our research team has delivered this fourth differentiated and promising biased ligand [NCE], in the seven years since we founded the Company.

And Mike and David will provide a detailed update on these programs momentarily.

In parallel with our clinical development efforts we have aligned our organization and business activities with our maturing pipeline. We significantly strengthened our balance sheet and increased our financial flexibility. Our January IPO, which raised $67 million, was followed by a $51 million follow-on financing in December. As we have transitioned from an early stage private company to a public company with programs approaching Phase 3, our Board has also evolved.

Most recently we welcomed Anne Phillips, Senior Vice President of Clinical, Medical, and Regulatory Affairs at Novo Nordisk to our Board of Directors. In addition, we expect to announce an appointment of an experienced executive to the role of Chief Commercial Officer at Trevena in the coming weeks. And, in recognition of his exceptional performance and leadership with the clinical team, David Soergel was recently to Chief Medical Officer for Trevena.

And, with that, I will turn the call over to David to provide a more detailed update on the status of our pipeline.

Thanks, Max, and good morning, everyone. I would like to begin with an update on our Phase 2b BLAST-AHF study for TRV027. We believe that, unlike other therapies, TRV027 can directly target the pathophysiology of acute heart failure via the critical angiotensin II type 1 receptor and produce potentially beneficial effects on the vasculature, the kidneys, and the heart.

In the BLAST-AHF trial, TRV027 is being evaluated in patients with acute heart failure, using an innovative composite endpoint. This approach allows us to test 027's effects on several clinically important outcomes, including mortality, worsening heart failure, hospital readmission rates, dyspnea, and hospital length of stay.

The study design was recently published in the March edition of the Journal of The American College of Cardiology -- Heart Failure under the state-of-the-art heading. When we started the trial, three doses of TRV027 of 1 milligram, 5 milligrams, and 25 milligrams per hour were tested versus placebo, both in addition to standard heart failure therapy. We have planned to evaluate the safety and efficacy data approximately halfway through the trial. The aim of this interim analysis was to focus the remaining patients on the single most promising dose of TRV027 and placebo.

Working with the study DSMB, the steering committee, and our collaborators at Actavis, we recently completed this analysis. Based on interim data from 254 patients, we will wait future enrollment towards the most promising TRV027 dose of 5 milligrams per hour, and increased target enrollments in this study from 500 patients to 620 patients. This increase in sample size allows us to collect additional dose-ranging data and be even better prepared for Phase 3 trials while maintaining study power.

In addition, the DSMB and steering committee determined that patients with lower blood pressure could safely enroll in the study. These patients have few proven therapies so we are pleased to be able to evaluate TRV027 in this broader patient population.

As Max noted, Actavis will fund the trial expansion which, we believe, reflects their continued enthusiasm for the program.

Moving on to our CNS programs, our lead program is TRV 130, which is being developed for in-hospital treatment of moderate to severe acute pain. TRV 130 is a small molecule biased ligand at the mu opioid receptor with a unique chemical structure. We believe that the TRV 130 may have a superior clinical profile versus morphine which often fails to effectively manage pain and causes efficacy-limiting adverse effects.

According to market research and other studies, inadequate analgesia efficacy is clearly an unmet medical need. In a large market research study published in 2012 by Decision Resources, enhanced analgesic efficacy was the most commonly cited reason to prescribe a new postoperative analgesic. We believe that TRV 130 may be able to meet this need and be a best-in-class analgesic, particularly for the most severe and difficult-to-treat types of pain in the hospital.

In November, we announced positive data from our Phase 2b trial of 130 for the treatment of moderate to severe acute postoperative pain following bunionectomy surgery. As you may remember this was a very successful clinical trial which showed that TRV 130 is a remarkably effective analgesic with a very rapid onset of action. In this study, TRV 130 at 2 milligrams and 3 milligrams showed statistically superior analgesic efficacy compared to morphine 4 milligrams when pain was most severe.

In the trial, after the first dose of morphine, the average numeric pain scores were reduced from seven out of 10 to a four or five out of 10. So on average, after morphine, patients were still experiencing moderate pain. In contrast, TRV 130 at 3 milligrams reduced pain from a score of seven to a score of one. So in our study, patients suffering from severe pain experienced little or no pain after a single 3 milligram dose of TRV 130.

We believe that this level of efficacy is unprecedented in well-controlled clinical trials, with any analgesic. In addition, the onset of meaningful efficacy for the two higher doses of TRV 130 was less than five minutes, significantly faster than the greater than 20 minutes it took for morphine to work.

Importantly, this profound level of efficacy was achieved safely. Trends in oxygen desaturation, a measure of opioid-induced respiratory depression favored TRV 130 over morphine. Over the 48-hour study period, the tolerability profile of the highly effective TRV 130 doses was similar to that of the less effective dose of morphine.

Our data therefore suggests that TRV 130 could have a wider therapeutic index compared to morphine, which means that we could show either improved efficacy with similar safety and tolerability as a conventional opioid on one end of the spectrum, or similar efficacy with improved safety and tolerability on the other end.

In the bunionectomy study, improved accuracy was a clear differentiator and suggested that TRV 130 may be able to control pain better in current opioids like morphine. And pain control is, after all, the goal of giving a strong analgesic.

For our broad acute pain label, the FDA's recent guidance indicates that well-controlled pivotal trials in both a hard tissue surgery like bunionectomy and a soft tissue surgery need to be performed. In January we initiated a Phase 2b soft tissue surgery trial in patients who have undergone abdominoplasty surgery as a potential prelude to a similar study in Phase 3. In this trial, we are evaluating the administrative of TRV 130 placebo or morphine in a patient-controlled analgesia or PCA device, a common way to deliver opioids in the hospital.

This device allows the patient to self-administer study medication to achieve the desired amount of pain relief and trade that off with negative side effects they experience. PCA also reduces the peaks and troughs of pain relief since patients can control when the next dose of pain medication is given. Approximately 200 patients will be assigned randomly to a postoperative regimen of TRV 130, placebo, or morphine in a two to one to two ratio, respectively, for 24 hours after surgery beginning when postoperative pain becomes at least moderate in intensity.

We remain on track to report topline data from this study in mid-2015. This study is progressing in parallel with our ongoing preparations for Phase 3 clinical trials of TRV 130.

In summary, we have learned crucial information about TRV 130. We know the effective dose range. We know how well 130 works compared to a standard opioid. We know how quickly it works. And we know how long the effects last. These are the pieces needed to design and execute the successful Phase 3 program which we expect to begin in the first quarter of 2016.

Now to review TRV 734, our second CNS candidate. TRV 734 is an oral follow-on to TRV 130. TRV 734 shares 130's novel mode of action and is intended to bring the potential benefits of 130 to the oral treatment of acute and chronic moderate to severe pain.

Opioid-related adverse events seen in postoperative pain patients are also problematic for oral opioids, the most troublesome of which is constipation which, unlike many side effects, becomes more prominent as therapy continues. Our preclinical studies suggest that ligand [bias] may reduce constipation. Both TRV734 and TRV 130 had less of an impact on GI motility than morphine and oxycodone, while producing equivalent analgesia.

In our first clinical study, we found that TRV 734 was indeed orally bioavailable and produced notable effects on pupil constriction at doses of 80 milligrams or higher. We also found that, even without formulation work, TRV 734 had a duration of activity that was consistent with four to six times a day dosing, which is a norm for opiates for acute pain.

When we initiated a multiple ascending dose study last August, this study included oxycodone as a benchmark to give us some practical experience with oxycodone before including it in Phase 2 studies. We reported the results from this trial last month. At doses between 80 milligrams and 175 milligrams, TRV 734 performed similarly to 10 milligrams of oxycodone in the Cole pain test while showing promising trends in safety and tolerability, including in the bowel function index, a validated measure of opioid-induced constipation.

Given the small number of volunteers in the trial and the short duration of dosing, we did not expect to find any differences between 734 and oxycodone. So these favorable trends were encouraging and were consistent with our preclinical data.

As with 130, we believe there is value in a novel analgesic that either has superior efficacy to oxycodone with similar safety and tolerability, or has similar efficacy with improved safety and tolerability.

The next step for TRV 734 is to formulate the drug appropriately to support development. Both Phase 1 trials have tested neat powder in a capsule. We believe that there are many formulation options that may further enhance the performance of TRV 734 as it moves into Phase 2 trials.

We are testing some of these formulations in a Phase 1 PK study which we expect to read out this year.

I will now pass the call to Mike Lark, our CSO, to introduce the newest entrant into our biased ligand portfolio, TRV 250.

Thanks, David. As Max mentioned at the end of 2014 we advanced a new internally discovered product candidate, TRV 250, into preclinical development. 250 is an oral, small molecule, G protein biased ligand targeting the delta opioid receptor. This receptor, which is distinct from the mu and kappa opioid receptors, has long been of interest for drug discovery. Hundreds of publish preclinical experiments suggest benefits of activating the delta receptor in a variety of CNS indications without the additional liability associated with mu opioid receptor activation.

However, seizure liability has hindered drug development targeting the delta receptor. But research from our labs suggests that a biased ligand like TRV 250 could minimize that risk.

We have profiled TRV 250 in a range of pre-clinical models, including testing for seizure liability, and believe that 250 may safely harness the benefits of delta receptor modulation. We plan to initially focus development efforts in treatment refractory migraine headaches and have initiated IND-enabling studies with an anticipated IND filing in 2016.

More broadly, looking across our portfolio, we strengthened our IP estate in 2014. We received a US methods of use patent for TRV 027, including methods for treating acute heart failure as well as other cardiovascular indications, providing coverage until at least 2029. This complements our previously granted composition of matter patent for TRV 027, which provides protection until at least 2031.

We also obtained patent coverage for the TRV 027 composition of matter in Japan, China, and New Zealand, with claims pending in other regions, including the European Union. In addition, we received a composition a composition of matter and methods of use patent for TRV 130 in the US, which is expected to provide coverage until 2032.

Together with granted and pending patent applications worldwide, we are building a comprehensive and enforceable patent portfolio to protect the commercial potential of our key assets. These achievements reflect the strength of our research organization. I am extremely proud of our productivity: four differentiated MCEs discovered in seven years, supported by a broad and growing patent estate. I look forward to providing additional updates as our programs advance.

Now I will pass the call to Roberto to review our financials.

Thanks, Mike. We disclosed key financial measures earlier today in our press release, and expect to file full financial statements later today in our Form 10-K. For now I will summarize the headline numbers.

For the fourth quarter we reported a net loss attributable to common stockholders of $13.3 million, or $0.45 per share, compared to $7 million or $7.48 per share for the fourth quarter of 2013.

For the year ended December 31, 2014, we incurred a net loss attributable to common stockholders of $49.7 million or $2.02 per share, compared to $23.6 million or $29.71 per share for full-year 2013. The increase in that loss from 2013 to 2014 was primarily due to development expenses associated with our advancement into a Phase 2b clinical trial of TRV 027 and the initiation of a Phase 2a/b clinical trial of TRV 130, as well as increased headcount to support drug development and increased operating costs resulting from our becoming a public company.

We ended 2014 in a strong financial position with cash, cash equivalents and investments on the balance sheet of $106.9 million. I will now return the call to Max for closing remarks.

Thanks, Roberto, and thanks also to David and Mike. As you've heard, it's been a highly productive year for us and we look forward to building on this momentum in 2015. I'd like to close our call with a summary of our key objectives and expected milestones for the next several quarters.

First, we look forward to publishing the full data from our Phase 2a/b trial for 130 in bunionectomy patients in the coming months in a peer-reviewed journal.

Toward the middle of this year we expect to report top line Phase 2b data for TRV 130 in patients following abdominoplasty surgery. Planning for our Phase 3 program is progressing in parallel with the Phase 2b trial, and we expect to talk more about plans there in the second half of this year, and launch the first Phase 3 study in the fourth quarter of 2016.

We also expect Phase 2b data for TRV 027 in acute heart failure in the first half of 2016, and expect to refine guidance on that timing as we get the study recruitment back up to steady-state over the coming months. We look forward to continued progress and updating you on our programs over the course of the year.

Thanks to all of you for your interest in for your time today. And now we can open the call for questions.

(Operator Instructions). Jason Butler, JMP Securities.

Congrats on the progress. Just wanted to follow up on TRV 130. Could you talk about what the kinds of Phase 3 preparation work you are conducting now is? And what would the rate limiting steps to initiation of the Phase 3 trials are, other than the bunionectomy study? Are you planning on having an end of Phase 2 meeting with FDA, for example?

Hi, Jason. Well, we are doing a lot of work right now actually, designing the Phase 3 program. As I mentioned, we are also in the process of -- the final stages actually of recruiting a Chief Commercial Officer, and we think that that person is going to be very valuable in helping guide our planning for Phase 3.

We'll wait until we fully fill out the profile of the drug with the Phase 2 study that's ongoing. And are obviously doing quite a bit of work in terms of CMC; manufacturing a drug product for the study.

And we're in the process of putting together the dossier for the end of Phase 2 meeting, as far as we can do that at this point. We will be expecting obviously to have an end of Phase 2 meeting and we are targeting that for the end of this year.

And I'll just ask David if he has anything to add to that.

No, I think that covers most of it. Jason, you know we do have some Phase 1 work on going with TRV 130 that'd part of the end of Phase 2 meeting at the end of the year. So those, in combination with the data from the two Phase 2 trials, I think, will make up a very nice dossier for the end of Phase 2 meeting.

Great, that's helpful. And then just a quick question on expenses. Can you give us any color on how we should think about operating expenses in 2015 relative to 2014, or cash burn?

We don't provide specific guidance on OpEx, either R&D or SG&A. What we have said is that with cash on hand as of the end of this year, plus the second tranche of the debt facility that we are now entitled to draw on, that should suffice to the end of 2016. What I will say, though, is that we are continuing to do Phase 2 study work in 2015. We are preparing for initiating Phase 3 work in 2016, and so there could be some natural growth of expenses over the periods.

Helpful. Thanks. Thanks, again, for taking the question.

Alan Carr, Needham.

Wondering if you can comment on a couple of things, one of them with 027. If you could comment on the selection of 5 mgs as opposed to the highest or the lowest dose for emphasis in the next part of the trial. The relative contribution of safety and efficacy, or efficacy in deciding on the dose. And then also maybe you could talk a bit about 250, and why migraine. Thanks.

Hi. Good morning, Alan. I will let David take the question on 027.

Sure, yes. Hi, Alan. So we, as I said during the call, we looked at data, both safety and efficacy data from 254 patients -- placebo, 1 milligram, 5 milligram, and 25 milligram an hour. The steering committee and the DSMB, after reviewing those data, determined that the 5 milligram an hour dose was the most promising of the three, and therefore patients would be overweighted to that arm as we progressed in the study.

What we've done -- what we've been very careful to do is to maintain the study's power, as I said during the trial. So, at the end of the trial we'll still have adequate power to detect the effect that we were expecting at the beginning of the trial. So, the relative contribution and safety -- as you know, in acute heart failure, safety and efficacy of are two sides of the same coin. If you produce too much pharmacology in patients you can see effects on safety and actually that can also come out in some of the efficacy endpoints. So, it's a little difficult to dissect those two.

And with respect to 250 and the selection of migraines. Why that one might be best, and why that's the best indication?

Mike, do you want to take that?

Yes, so Alan, this is Mike. Migraine remains a significant unmet need. There's 12 million patients treated annually for acute episodic migraine. And triptans work well in these patients, but 20% to 30% of that population either can't take them or don't benefit from them. So there is a significant opportunity there. We have very strong data pre-clinically that TRV250 will work there. Thinking about aggressive developments, we think we can get an early clinical read as well in migraine and understand both the efficacy as well as the seizure risk for the compound.

So, a lot of reasons to consider that as our lead indication. We also think -- as I mentioned, and I think Max mentioned in her piece as well -- that the compound has the potential for treating other CNS indications, so we'll be considering those options as we advance the compound in development as well.

Great. Thanks very much.

(Operator Instructions). Hugo Ong, Jefferies.

This is Hugo just speaking in for Biren Amin. Just on 130, on the ongoing Phase 2 abdominoplasty surgery trial, how would you expect dosing to potentially impact the efficacy, given that it's the patient controlled analgesia trial versus, say, the bunionectomy trial?

Hi, Hugo. I'll let David take that.

Yes. Great question, Hugo. As you recall, the bunionectomy trial is fixed dosing, so whether or not patients needed a dose of medication they received it every three or four hours over the 48-hour period. That's obviously a fairly contrived way of administering pain medication to patients. Typically, clinically, patients ask for pain medication when they need it.

PCA administration is the most refined way of patients asking for pain medication. In other words, they push a button and they receive the drug when they need it.

So, it's a directly clinically relevant administration paradigm that I think resonates very, very strongly with practitioners. So, these type of data, I think, will be very instrumental in showing practitioners how TRV 130 could add to the therapeutic armamentarium.

Great, great. And what are the assumptions in the trial?

Which assumptions of what?

Just like your statistical assumptions?

Okay. Yes, so it's a Phase 2 trial, as you know. If you remember from the bunionectomy study, we had group sizes of about 30 patients, and we were able to statistically separate from placebo with those group sizes.

In the abdominoplasty study, with a lot of caveats because the administration paradigm is very different, we have a little bit over twice as many patients exposed to each of the active treatment regimens. So, 80 per active group planned versus 40 on placebo that we would expect that that would be able to provide separation.

Got it, okay. And just last question on TRV 734. You guys talked about exploring new formulations. Does that include an obese-resistant formulation?

At this point we're not actively exploring that. I think that we will really need to see the benefits on the activity of the drug before we move into that space.

Got it, understood. All right. Thanks for taking my questions.

Thank you. And I'm showing no further questions from the phone lines at this time. I'd like to turn the conference back over to Mr. Jonathan Violin for any further remarks.

Thank you. I'd like to remind listeners that a replay of this call would be available from the Company's website at www.trevenainc.com. On behalf of the management team at Trevena I'd like to thank everyone for joining us today. I'll be available to receive any further inquiries following the conclusion of this call.

With that, operator, please conclude the call.

Thank you. Ladies and gentlemen, thank you for participating in today's conference. This does concludes the program and you may all disconnect. Have a great day, everyone.