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Edited Transcript of TRVN earnings conference call or presentation 8-Mar-17 1:00pm GMT

Thomson Reuters StreetEvents

Q4 2016 Trevena Inc Earnings Call

Kng Of Prussa Mar 8, 2017 (Thomson StreetEvents) -- Edited Transcript of Trevena Inc earnings conference call or presentation Wednesday, March 8, 2017 at 1:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Jonathan Violin

Trevena, Inc. - Senior Director of IR

* Maxine Gowen

Trevena, Inc. - President and CEO

* David Soergel

Trevena, Inc. - Chief Medical Officer

* Carrie Bourdow

Trevena, Inc. - Chief Commercial Officer

* Roberto Cuca

Trevena, Inc. - CFO

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Conference Call Participants

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* Jason Butler

JMP Securities - Analyst

* Biren Amin

Jefferies LLC - Analyst

* Douglas South

Barclays Capital - Analyst

* Jonathan Aschoff

National Securities - Analyst

* Alan Carr

Needham & Company - Analyst

* Christopher James

Ladenburg Thalmann - Analyst

* Michael Higgins

ROTH Capital Partners - Analyst

* Yasmin Rahimi

H.C. Wainwright & Company - Analyst

* Dana Ying

Aegis Capital - Analyst

* Rahul Jasuja

FBR & Company - Analyst

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Presentation

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Operator [1]

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Good day, ladies and gentlemen, and welcome to the Trevena full-year and fourth-quarter earnings conference call.

(Operator Instructions)

As a reminder, this conference call may be recorded. I would now like to introduce your host for today's conference, Jonathan Violin, Senior Director of Investor Relations. Please go ahead.

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Jonathan Violin, Trevena, Inc. - Senior Director of IR [2]

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Thank you and welcome everyone, thanks for joining us on this morning's call. With me today are Maxine Gowen, Trevena's CEO; Roberto Cuca, our Chief Financial Officer; Carrie Bourdow, our Chief Commercial Officer; and David Soergel, Trevena's Chief Medical Officer.

Before we begin, we wish to inform participants that will make forward-looking statements on this call which are made pursuant to the Safe Harbors Provision of Private Securities Litigation Reform Act of 1995. We caution 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.

I'll now turn the call over to Max who will provide and overview of our recently released OLINVO phase 3 data and our vision for establishing OLINVO's commercial value. She'll then review our financial results before opening up the call to questions. Max?

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Maxine Gowen, Trevena, Inc. - President and CEO [3]

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Thanks, John. Good morning, everyone. This morning I'm going to discuss our new Phase 3 product candidate, OLINVO, which is an IV drug for the management of moderate to severe pain. During the discussion I'll cover the following points.

What is the market we will be entering and why is there a need for a better drug. How will OLINVO compete in this market. What are the future trends that might affect OLINVO and how will OLINVO achieve formulary placement. And finally, what are our future plans.

Let's start by clarifying some facts about the IV pain market. First of all, it is a very large market about 200 million doses of IV opioids are used each year by about 50 million patients, this is because it is still the foundation of analgesic therapy and it represents about 50% of the overall IV analgesic market, other classes being anesthetics and non-opioids like IV.

The three main opioid drugs are used, fentanyl, which is potent and short acting and used mainly perioperatively and in the acute and then morphine and hydromorphone are used on the floor, about 50% each. These are all very old drugs, there's been no innovation in the opioid market in many decades.

So if we have all these drugs why is a new entrant into the market needed? Even though opioid analgesics are the most effective pain medicines and that's why they're used, they come with significant drawbacks. In the acute hospital setting the major problems are related to safety, tolerability and problematic pharmacokinetics and metabolism, so these drugs cause respiratory depression, nausea and vomiting and long acting active metabolites, and this drives three major problems.

First a risk of death or serious injury following respiratory depression or complications in certain surgeries following vomiting. Second, under-dosing to avoid the side effects that we just talked about which leads of course to poor treatment of severe pain. And third, costly complications and prolonged length of stay.

All of these add significantly to the total cost of care for patients and much research has been done in this field that has shown that patients who experience an opioid-related AE costs about 50% more to the hospital system due to the increased cost of treatment plus the increased length of stay. So nausea and vomiting are estimated to add about $500 to a stay and respiratory depression up to $28,000. These are just the costs in the broad population, not for the highest unmet needs that we are targeting, for example surgeries for which vomiting can cause damage, impacting the surgical outcome.

Of the 50 million IV patients annually that are using opioids about 32 million days of therapy are in the inpatient setting, assuming an average use of 2 days, and about 3 million days of therapy are in the outpatient and ambulatory surgery centers. So the inpatient setting is of course where most of the critically ill patients are treated and there is here the need is for a safer, effective drug to replace conventional opioids. In the outpatient or ASC setting one of the most important needs is to prevent the tolerability problems so that the patients can be moved rapidly through the surgical suite and discharged. And we think that OLINVO has benefits for use in both of these settings.

So how does OLINVO address these problems? It was specifically designed to be the Next Generation IV opioid using nobel prize winning scientific insights into the pharmacology of the mu receptor. This is the first new chemical entity in the opioid space since fentanyl, 50 years ago. And based on the benefits that we've demonstrated already in our Phase 2 trials so medicine was awarded breakthrough therapy designation by the FDA in January 2016, this is the first pain drug to get this designation. And also importantly this new medicine has a long patent life with the earliest expiration of the composition of [meta] patent in 2032.

This novel mechanism of actions involving the signal transduction downstream of the receptor has led us to develop a medicine that has strong opioid efficacy, lower levels of respiratory and GI side effects, predictable exposure with no known active metabolites which is very important for the safety in patients with kidney disease, and finally rapid onset. Reducing these dangerous and problematic side effects will have multiple benefits to patients and providers and payers as we will discuss.

Lets review some of the clinical data that we've generated comparing OLINVO with morphine. Starting with efficacy then, the most important feature for a new analgesic obviously for patients and also for regulators. We recently announced top line data from two Phase 3 pivotal trials showing strong opioid efficacy in both hard and soft tissue surgeries following the FDA guidance in order to obtain a broad indication for the management of moderate to severe pain.

We achieved highly statistically significant efficacy at all three dose regimens tested in both trials. We saw no unexpected adverse events in either trial and on this basis we are confident that we will gain regulatory approval for OLINVO with this broad indication statement.

We also show below the graphs the discontinuations for each group which we have not highlighted to you before. These were either for lack of efficacy or for problems with safety and tolerability. So these data also emphasize the strong efficacy of OLINVO comparable to morphine, but also suggest that the OLINVO regimen using 0.35 milligram doses allowed patients to dose themselves to the best balance of efficacy and safety and tolerability.

Another important feature of efficacy is the ability of the physician to use the drug as they are accustomed to using conventional opioids, adjusting the dose freely as they optimize therapy to the individual needs of each patient and this is the way physicians work with opioids and we have deliberately generated data using both PCA and bolus dosing over a broad range in our Phase 2 and 3 trials. Doing so clearly demonstrating the efficacy of OLINVO in comparison to morphine.

The data we are looking at here show changes in pain ratings from a bolus dose in a Phase 2 trial highlighting the rapid and powerful efficacy of OLINVO. The OLINVO doses are in blue again, with morphine in orange, and we've not found efficacy of this magnitude from any published randomized trial for any other drug.

A third aspect of the efficacy is speed of onset which you saw in the last slide and is again recapitulated here. So in the case of OLINVO this is a rapid and consistent effect through all our trials. Here we are showing onset after an IV bolus dose where it can be measured most accurately depending on the dose administered, meaningful pain relief, this is not just first pain relief, but meaningful pain relief measured with a two stop watch method occurs within two to five minutes, compared to morphine which takes between 20 and 30 minutes. And so this is important not only for the obvious reason of bringing the patient rapid relief from their severe pain, but because it greatly facilitates the titration that is always used. If a doctor and patient have to wait 20 to 30 minutes for maximal pain relief with a dose of morphine, there is a high likelihood of dose stacking and then overshooting the required dose and incurring more side effects later on.

Let's turn now to the safety and tolerability of the product. First we've measured respiratory safety in multiple different ways across five clinical trials and in each case have shown the benefit of OLINVO compared to morphine. Here in our Phase 3 APOLLO trials our key secondary endpoint was respiratory safety burdens, which we measure as the product of the incidents of a respiratory safety event and its average duration.

And although the variability and the duration in these events prevented us from reaching statistical significance, we saw a clear trend of improvement with this endpoint in both trials, reproducing the magnitude of reduction that we've seen in previous trials, about 73% in APOLLO-1 and 40% in APOLLO-2 for the 0.35 milligram dose. The significance of these respiratory events is illustrated by the mean oxygen saturation at the time of the event which we show above the graph, these were 84% and 88% respectively, truly severe events, and this in comparison to 97% for those not affected.

So note that the 0.35 regimen looks like a sweet spot. Recall the strong opioid efficacy provided by this regimen that we received just moments ago and this reduction in the measure here looks like a striking relative change. We've had the chance since we've achieved these data to do some market research both with our advisors as well as a blinded sample of physicians and both groups highlighted the 0.35 regimen as the one they can most readily envision substituting for morphine in most of their patients.

This chart shows the frequency of respiratory safety events in the two trials and these are new data that we are showing you today and in this case we not only again see the clear trends but also statistical significance in the 0.35 milligram group in APOLLO-1. These data very consistent with our Phase 2 results in which this was our pre-specified endpoint. So we are consistently seeing a meaningful reduction in respiratory safety measures with the 0.35 meg regimen which in APOLLO-1 was about a 50% reduction, both statistically and highly clinically significant. And we also believe that this level of reduction will provide meaningful reductions in the cost of care as well.

Additional objective Phase 3 measurements also support this benefit of OLINVO in this endpoint. Here we show oxygen desaturation as well as the use of supplemental oxygen in the two trials. Again, about a 50% reduction at the 0.35 milligram dose in APOLLO-1. We know from our market research that these objective measures are very important to physicians.

Moving on to GI tolerability, we again saw very consistent reductions in vomiting and antiemetic use at all three doses across the two trials. And note that the vomiting rates were always higher in the morphine group even though these patients were also taking the most antiemetics, so antiemetics is not the answer. Once again, the magnitude of the reduction is clinically meaningful to doctors and they provide clear cost-benefits in our planned upcoming health economic analyses.

One final and very important feature of OLINVO is its highly predictable pharmacokinetics and its lack of active metabolites. There is no change in the excretion of the drug in patients with chronic kidney disease which affects 13% of the US population. And this means that there's no need for dose adjustment with OLINVO in these very sick patients who are at elevated risk when given conventional opioids like morphine and hydromorphones, both of which have active metabolites and can accumulate in renal patients, and because of the difficulty in treating these very sick patients in pain, this is a really important feature to physicians.

So we've talked about some key benefits of OLINVO for both patients and doctors and now let me spend some time talking about our commercial strategy. First, to orient those of you who may be less familiar with the process for hospital drugs, access to the hospital formulary is a key step in uptake. This happens when physicians request a new drug be added to the formulary, the pharmacy team then assembles the dossier of data which is then evaluated by the P&T committee which is made up of pharmacists, physicians and administrators of the hospital.

The first point to make is that physician advocacy is very important in this process. And also important, our market research to date shows a higher level of interest in using OLINVO among key prescribers, the anesthesiologists and surgeons, two groups that are among the most influential doctors on the P&T committee.

When shown the data or the profile of OLINVO they immediately identified key patient groups or key procedures where they believe the drug will be most valuable and those can be procedures where -- which elevate the risk of a respiratory depression, or patients who have higher risk of respiratory depression or vomiting, or procedures where vomiting would be detrimental to the success of the therapy, as well as those in severe or prolonged pain. This together represents about 30% to 40% of the in-hospital market opportunity and we believe this provides us with a clear entry into the marketplace, a strong reason for P&T committees to add this drug to the formulary and provides us also with a strong base from which to build the market and the uptake.

So in all of these segments there's a clear rationale for the use of OLINVO, both to offset the cost of opioid related AEs and to reduce the complexity of care. This we believe will lead to more widespread uptake as physicians experience the benefits and the ease of use of OLINVO.

Now in the preliminary market research we've conducted in the last week or so with a blinded profile of OLINVO's phase 3 results, we didn't show the actual data just a word profile, anesthesiologists and surgeons were consistent again in the patient groups they would choose to use OLINVO in and we were clear that in some cases these data were not statistically significant. And they again selected those at elevated risk from post-operative nausea and vomiting and opioid induced respiratory depression. Each of these subsets of patients again comprises about 20% of these physicians' case loads.

The second point to make about the formulary process is that the P&T committees who decide on formulary access take into consideration all the published data on the drug, not just what appears in the label. So all peer-reviewed published data are reviewed and as you can see here we have published much of our data and will continue to do so. These data all show the potential benefits of OLINVO in numerous trials using many different measures of analgesic efficacy, safety and tolerability in comparison to morphine. And again, in our research with pharmacy directors this head-to-head comparison with morphine is very important to them.

So one final critical aspect of formulary uptake then is of course a cost analysis, not just the cost of the drug but the potential cost savings achieved by reducing the opioid-related adverse effects. As I described a few moments ago, opioid related AEs result in significant cost to the hospital system. We know that opioid-induced respiratory depression while uncommon is incredibly costly and much more frequent in the at-risk patient groups that we have identified, including for example COPD, obesity, elderly, renal failure.

Likewise, while we know that PONV adds cost to a large percentage of procedures the biggest unmet need is in the procedures where PONV can damage outcomes, and in patients at elevated risk. Both again representing higher expected costs, even those that we've shown. We will be providing a clear health economic analysis of the product to the P&T committees using our own research and we believe already that our Phase 3 data shown on the right-hand side of the slide provides a strong foundation for these analyses, with the potential to reduce these costs by reducing the frequency of adverse events, we believe will support premium price for OLINVO.

Looking forward beyond approval, trends in inpatient care also online with the key drivers of OLINVO uptake. These are patients that continue to be the most challenging in the inpatient hospital setting where our efforts will initially be concentrated.

If you look at the demographic trends in the inpatient setting, the average hospital length of stay has now increased to 5.5 days. Two of the patient group in the hospital that are at highest risk of OR AEs, the elderly and the obese, are both increasing by double-digit growth annually.

We are of course including these exact patients in our ongoing Athena trial which should be reading out in the middle of the year. Athena should provide important information to regulators but also prescribers and payers on the safety of OLINVO across many surgery types and procedures, including patient groups such as the elderly and obese populations that we have been discussing.

So what's next for Trevena? Already we've been dramatically ramping up our medical affairs capabilities and this will continue. We'll be presenting our Phase 3 data for OLINVO initially in conferences in April and May of this year and the data will continue to rollout at the many pain conferences until launch and beyond. We expect to file our NDA in the fourth quarter and our confident in all aspects of the data package to support approval.

We are also planning to host an Analyst Day later this year to provide a deeper perspective on our plans. In addition, we must not forget that we're continuing to progress our research on TRV250, our innovative new mechanism of action drug for migraine, with the initiation of Phase 1 trials expected in the second quarter, as well as on our discovery portfolio which we expect to update you on later in the year.

And finally a quick note on our finances. Last year we had a net loss of $103 million, almost twice our net loss from 2015. But remember, in 2016 we initiated and virtually completed an entire Phase 3 program for OLINVO. So we expect 2017 expenses to decrease this year versus last year, primarily of course because R&D expenses will decrease now that we've finished all of those clinical trials. Our existing cash of $111 million should be sufficient to complete the OLINVO Phase 3 Athena study, submit the NDA, continue OLINVO commercial launch prep and complete the first in human TRV250 study, as well as continuing the progression of the pipeline.

So I'll close my remarks by reiterating our excitement in the profile of OLINVO, which have been echoed by doctors that we have spoken with, the first new drug with opioid efficacy in 50 years with the added benefits to bring multiple improvements to patients, doctors and payers, and a level of data, rigorous data at launch that I don't think we've ever seen previously. So I will now open up the call for questions.

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Questions and Answers

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Operator [1]

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(Operator Instructions)

Jason Butler, JMP Securities.

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Jason Butler, JMP Securities - Analyst [2]

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Hi, thanks for taking the questions. Just first one on respiratory safety, when you look at data for the respiratory safety burden and point end the event endpoint, it looks like morphine was pretty consistent in its results across the APOLLO-1 and 2 trials, but there were some difference between the 0.35 milligrams. Any color there and if you assume APOLLO-2 where there's a 40% treatment effect versus a 70% in APOLLO-1, is that still clinically meaningful in your view?

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David Soergel, Trevena, Inc. - Chief Medical Officer [3]

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Hi Jason. Short answer is yes, it absolutely is clinically meaningful. If you look at the numbers, we talk about respiratory safety burden in hours. So the way to think about this is in APOLLO-1 and in APOLLO-2 the morphine patients are at risk of having safety effects, respiratory safety effects, for about half an hour, which doesn't sound like a long time but it really is, so if your respiratory rate declines substantially and it is stays down for half an hour that can cause some really significant problems.

And you see that OLINVO in the APOLLO-1, as you noted, is a lot shorter so it is 0.1 hour which is about 6 minutes, so very, very short amount of time. And similarly there's still a substantial reduction when you are looking at APOLLO-2. And you also have to take into account the placebo effect so if you look at APOLLO 2, some of this is because of the relative complexity of soft tissue surgery trials in general anesthesia and so forth, but you actually see a placebo rate that looks like the APOLLO-1 rate.

So the placebo rate in APOLLO-2 looks like the APOLLO-1 rate in 0.35. And so if you subtract out the placebo rate in APOLLO-2 you get to a very short period of time, so we think it is absolutely is both clinically meaningful and very compelling data.

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Jason Butler, JMP Securities - Analyst [4]

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Okay, great and then second question, can you just talk about the real world management of patients with renal impairment and the burden that, or how that could be different with OLINVO?

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David Soergel, Trevena, Inc. - Chief Medical Officer [5]

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Sure, yes, I will take that too. So as Max mentioned, one of the major challenges with morphine is the accumulation of morphine-6-glucuronide, which is an active metabolite that can produce significant safety issues for patients who cannot excrete that metabolite. The 6-glucuronide is renally excreted and accumulates in renal impairment.

So two things change with OLINVO. The first is you can titrate -- like all patients in renal insufficiency patients, you'll be able to titrate patients to a level of pain relief quickly, as we pointed out, so the onset of action of OLINVO is much more rapid than what you see with morphine. So you'll be able to target the pain relief much more precisely and then you won't have any of these protractive effects produced by these longer-lasting metabolites.

So what it does for the physician, for the treating physician, is it gives them confidence that they can safely administer our drug and produce the level of pain relief they need to produce for their patient without incurring any longer-lasting safety effects.

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Jason Butler, JMP Securities - Analyst [6]

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Okay, great. Thanks for giving the new details this morning and thanks again for taking the questions.

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Maxine Gowen, Trevena, Inc. - President and CEO [7]

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Thanks, Jason.

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Operator [8]

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Biren Amin, Jefferies.

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Biren Amin, Jefferies LLC - Analyst [9]

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Yes, thanks for taking my question. I guess when you polled position did you evaluate the price sensitivity to OLINVO versus morphine?

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Maxine Gowen, Trevena, Inc. - President and CEO [10]

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Hi, Biren. I will let Carrie take that question. She listened in on a lot of those interviews.

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Carrie Bourdow, Trevena, Inc. - Chief Commercial Officer [11]

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Hey, Biren, how are you? We did not provide an actual price, but we described things like if this were priced at a premium to morphine we ask questions like if you had to present patient population to your formulary committee under recognizing the formulary committees are also thinking about cost and budget impacts. So those were the sorts of questions that we asked to simulate the real world.

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Biren Amin, Jefferies LLC - Analyst [12]

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Okay, got it. As it relates to, I think you quantified the cost of $510 for nausea, vomiting, upwards to $28,000 for respiratory depression, at least on the respiratory depression side, what accounts for that, is it the fact that these patients are taken in ICU? And is all respiratory depression events at that level and what's kind of the range of cost with that type of an event?

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David Soergel, Trevena, Inc. - Chief Medical Officer [13]

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I will answer that. So a couple things, first of all, the costs that we are showing as Max mentioned are from the published literature and in broad patient populations. And we've described some patient subsets, actually substantial sized patient subsets where this was a benefit, potential benefit of OLINVO is going to be much more straightforward, right? So patients who are already at high risk for respiratory depression where you are going to see these events occur more often based on the literature. And in certain surgeries where the impact of vomiting or PONV can be substantial, can challenge the outcomes for those patients.

So I think as we roll out our health economic data over the, before launch we'll be digging into these subpopulations and really understanding the economic burden in those groups and be able to describe that. Because I think that you're going to find that the economic burden is going to be much more substantial in that group -- those groups

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Biren Amin, Jefferies LLC - Analyst [14]

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Got it, and just on the financial side so you've got I think cash runway after Q2 2018, what are opportunities for non-dilutive financing? Is the Company engaged in discussions, ex-US?

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Maxine Gowen, Trevena, Inc. - President and CEO [15]

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Hi Biren. So yes, with the data in hand we are initiating conversations around ex-US potential partnerships and so we will keep you posted as those progress.

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Biren Amin, Jefferies LLC - Analyst [16]

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Great, thank you.

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Operator [17]

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Douglas South, Barclays.

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Douglas South, Barclays Capital - Analyst [18]

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Hello, can you hear me?

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David Soergel, Trevena, Inc. - Chief Medical Officer [19]

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Yes.

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Douglas South, Barclays Capital - Analyst [20]

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Going back to some of the market research, just curious in terms of the ballpark that you are thinking of in terms of premium to opioid. Obviously if look at some of the recent new novel analgesics that have come to market or formulations, they've come at a considerable premium to something like morphine. There's a wide spread, are you still thinking around that level or potentially something maybe a little bit closer and which you can get a broader adoption of the product?

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Carrie Bourdow, Trevena, Inc. - Chief Commercial Officer [21]

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Hi, Doug, it is Carrie. Now that we have the Phase 3 data in hand I will be doing pricing research and I think we will be able to provide a range at some point. We are continuing to hear as you are hearing those branded benchmarks. Most likely it is because those are the only branded agents that have launched this generic marketplace in the last five years.

So we continuing to hear reference points from our market research with Ofirmev and Exparel, even those are not competitors and those branded benchmarks are coming back to us. So if you remember, Ofirmev launched around $60 is now I think up around $140 a day, and Exparel is about $100 a day. But I will be able to provide information after we do our own research at a later point in time.

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Maxine Gowen, Trevena, Inc. - President and CEO [22]

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I think maybe just one thing to add, Doug, is that we are conscious that it is not easy to get strong uptake unless you're on a formulary, so that will be certainly something that we will be bearing in mind as we price the drug. (Multiple speakers)

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Douglas South, Barclays Capital - Analyst [23]

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I was going to ask in the initial round of market research have you had a chance to poll hospital pharmacists or has this largely been physician-based right now?

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Maxine Gowen, Trevena, Inc. - President and CEO [24]

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This was just anesthesiologists and surgeons so far, so the major research is about to be kicked off.

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Douglas South, Barclays Capital - Analyst [25]

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Okay. Great, thank you.

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Carrie Bourdow, Trevena, Inc. - Chief Commercial Officer [26]

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Physicians that are P & T committee members and so I think that's been helpful for us as well.

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Douglas South, Barclays Capital - Analyst [27]

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Okay, great, thank you very much, Carrie.

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Operator [28]

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Jonathan Aschoff, National Securities.

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Jonathan Aschoff, National Securities - Analyst [29]

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Thank you. I was wondering what can be the most compelling safety information that could come from your non-randomized safety trial to help you penetrate outside the subpopulations you just described earlier?

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Maxine Gowen, Trevena, Inc. - President and CEO [30]

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So I will just make some general comments and David may wish to be more specific. But I think generally although the data are from our APOLLO trials are very important in terms of gaining approval, and I think all practitioners understand why those trials don't necessarily look exactly like real life, they are always very interested in hearing about information on patient groups that they themselves are practicing in. So I think that's the major benefit that we will have.

We will be able to say that we have safety data in patients who have had bariatric surgery or colectomys, or what ever kind of surgeries, because this is a very much a broad-based trial. And we'll also be able of course to add information around bolus dosing which is being used in this study as well as PCA. So I think all of that data is actually very meaningful to the practitioners who will ultimately use the drug.

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David Soergel, Trevena, Inc. - Chief Medical Officer [31]

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Absolutely. The other thing that is very helpful about Athena for us is that we get feedback from the sites about how the drug performs in their hands. So we learn about our drug at the same time as the sites get experience with the drug, and as Max said in patient populations that are much more likely to be hospitalized than patients who had (inaudible) surgery. So we get those types of -- pieces of feedback from the centers that really help us understand our drug and the that it might offer to patients.

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Jonathan Aschoff, National Securities - Analyst [32]

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Okay, thanks for that, I was also wondering why the newly disclosed discontinuation rate was similar between OLINVO and morphine? Was that from the deliberate pushing of what it was randomized to, prior to getting into rescue therapy?

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David Soergel, Trevena, Inc. - Chief Medical Officer [33]

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Are you referring to the discon rates?

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Jonathan Aschoff, National Securities - Analyst [34]

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Yes.

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David Soergel, Trevena, Inc. - Chief Medical Officer [35]

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So as Max said, the discontinuation rates were either because the patient withdrew from the trial because of lack of efficacy, so these are permanent discontinuations. In the placebo groups it is going to be patients who are dropping out for lack of efficacy and saying I'm just going to go to standard of care, I'm done with their trial. In the active treatment groups it is a combination of lack of efficacy and adverse effects. So --

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Jonathan Aschoff, National Securities - Analyst [36]

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What's on the ATM?

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Maxine Gowen, Trevena, Inc. - President and CEO [37]

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I'm sorry?

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Jonathan Aschoff, National Securities - Analyst [38]

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Do you have an ATM out there?

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Maxine Gowen, Trevena, Inc. - President and CEO [39]

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We do.

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Jonathan Aschoff, National Securities - Analyst [40]

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And what is left on it? I believe you used some of it over the fourth quarter?

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Maxine Gowen, Trevena, Inc. - President and CEO [41]

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Roberto, would you like to take that question?

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Roberto Cuca, Trevena, Inc. - CFO [42]

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There's about $39 million left on the ATM.

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Jonathan Aschoff, National Securities - Analyst [43]

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Okay, thanks, guys.

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Operator [44]

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Alan Carr, Needham & Company.

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Alan Carr, Needham & Company - Analyst [45]

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Hi, thanks for taking the questions. Can you follow up on John's question a little bit more, are you going to be capturing the same sort of high resolution safety data which you were in APOLLO-1 and 2 in Athena? And then also can you go over where things stand with CMC and review the supporting study that you've done and if there's any other clinical supporting studies that are dated, thanks?

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Maxine Gowen, Trevena, Inc. - President and CEO [46]

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Hi, Alan. I will let David take the first question.

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David Soergel, Trevena, Inc. - Chief Medical Officer [47]

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Yes, so hi, Alan. The APOLLO studies were designed to very rigorously assess safety, tolerability and efficacy. So I think as we talked about in a previous call, we had individuals who were specifically trained and allocated to evaluation of respiratory safety for example in APOLLO.

We did not have that level of assessment in Athena. ATHENA is a more of an all comers type of trial as you can see on the slide, we have over 40 centers participating and we don't have that level of rigor of assessment of respiratory safety. We do capture adverse events like nausea and vomiting and those types of measures and of course if anything significant happens to a patient we capture that as well.

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Maxine Gowen, Trevena, Inc. - President and CEO [48]

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Alan, on the CMC side we're feeling as comfortable as one ever can. We have done multiple commercial scale batches, that's all complete.

We have a very robust and repeatable set of processes for the API and the drug product. We are using only US-based contract manufacturers, so all of the anticipated data that we will need for filing is on track.

And I think your other part of your question was there any other additional clinical studies that we need?

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Alan Carr, Needham & Company - Analyst [49]

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Supporting ones. You've done renal and I think you've done others too, anything else? That needs to be done?

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Maxine Gowen, Trevena, Inc. - President and CEO [50]

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Renal impairment study we've done, the ADME study, therapeutic study and a hepatic impairment study, all of those are either complete or nearly complete, there's nothing else outstanding.

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Alan Carr, Needham & Company - Analyst [51]

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Okay and I guess one last one, your plans around migraine, any guidance here on the scale of this first Phase 1 trial? And design?

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Maxine Gowen, Trevena, Inc. - President and CEO [52]

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So I think the Phase 1 trial is going to be a fairly traditional Phase 1 trial with single ascending dose looking at PK and tolerability in particular. We are initially using subcutaneous dosing and we do have an oral arm in the trial as well. So that's essentially what we have planned.

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Alan Carr, Needham & Company - Analyst [53]

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Great, thanks very much.

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Maxine Gowen, Trevena, Inc. - President and CEO [54]

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Thank you.

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Operator [55]

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Christopher James, Ladenburg Thalmann.

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Christopher James, Ladenburg Thalmann - Analyst [56]

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Good morning. Thanks for taking the questions and congrats on your progress. Beyond what's going to be generated with Athena, do you have any plans to do any formal studies in high-risk patients?

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Maxine Gowen, Trevena, Inc. - President and CEO [57]

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So at this point we don't have any specific plans, Chris. I think what we need to do right now is assemble all the data, don't forget we still have not seen anything other than the top line data yet. So get very familiar with the data, get out and start testing the data and talking to physicians and payers about what we have in order to really identify what the most important future studies might be.

And I think with that information in hand we will be in a much better position to decide whether or not and indeed which kind of studies that we need to do. So I do imagine that there will be future trials. I cannot right now tell you what they will be.

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Christopher James, Ladenburg Thalmann - Analyst [58]

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Thanks. Based on your discussions with the doctors, do you anticipate any initial restrictions to access by hospital pharmacies or do expect this to be used initially broadly or restricted over time then go broadly, and how should I think about the uptake?

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Maxine Gowen, Trevena, Inc. - President and CEO [59]

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I think most new drugs are restricted one-way or another and that's what we would expect. I think that if our drugs are restricted to the most at-risk patients for the adverse effects that we know come along with opioid use, that's a very substantial percentage of the hospital inpatient population, as we've discussed. So while we would expect initially some restrictions, we think it would be a fairly broad based group.

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Christopher James, Ladenburg Thalmann - Analyst [60]

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Great, that's helpful, and then in your discussions also with the docs can you give us a sense of the understanding of the [beta areston] pathway? And I would assume that most physicians are comfortable with new receptor drugs but do you plan to do any special or do you need to do any special educational efforts on that front?

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Maxine Gowen, Trevena, Inc. - President and CEO [61]

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I think we will continue to highlight the mechanism of action of the drug. I think that it does seem to resonate very well. You don't have to get into all of the nitty-gritty details about how this works, but just talking about downstream pathways that mediate the good and the bad effects does seem to be helpful to physicians and resonate with them. I think we will continue to focus on that.

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Christopher James, Ladenburg Thalmann - Analyst [62]

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Great, thanks for taking my question.

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Maxine Gowen, Trevena, Inc. - President and CEO [63]

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Thank you, Chris.

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Operator [64]

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Michael Higgins, ROTH Capital Partners.

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Michael Higgins, ROTH Capital Partners - Analyst [65]

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Good morning guys. My apologies, lots of calls this morning.

I have a question on the pharmacoeconomic data. I believe you mentioned some comments there. What's the timing for that and can we assume it may be broken out by the patient type and setting? Thanks.

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David Soergel, Trevena, Inc. - Chief Medical Officer [66]

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Yes, hi, Michael. So we are undertaking some of that work now. It is hard to predict when we are going to complete it all and be able to present it and publish it. But it is certainly in our plans to keep digging into the potential cost savings benefits of OLINVO, and especially in some of these at-risk patients.

So when you look through the data, when you look through the literature, there are clear patient populations that are highlighted with respect to opioid use respiratory depression and we want to get an even more granular view on the burden of those events in those particular patients, and that doesn't really exist in the literature right now.

So similarly for PONV, there's a lot of information on broad populations, but as you saw during the presentation we are focusing in on even those patients who are at even higher risk. And so similarly we want to dig into those numbers and be able to give you a much more granular view on the cost impact in those particular patients.

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Michael Higgins, ROTH Capital Partners - Analyst [67]

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Just a follow-up to that, how do you generate that kind of granular view on those patient types without there being sufficient clinical data in the literature?

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David Soergel, Trevena, Inc. - Chief Medical Officer [68]

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There are large databases of, as you know premier database, various databases of patient care out there that you can access.

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Michael Higgins, ROTH Capital Partners - Analyst [69]

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Got you. Makes sense. Another question on --and as I dig in you may have touched on this, did you combine the APOLLO studies to see if there was more of a statistical separation by dose versus morphine?

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David Soergel, Trevena, Inc. - Chief Medical Officer [70]

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Short answer is we did not. There are some things that you can combine in clinical trials. There are other things that are a bit more challenging to do that with. These two studies, although they were designed to be very similar in terms of all the procedures and so forth that were conducted during the trials, they are very different models so it is difficult to combine the two studies in that way.

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Maxine Gowen, Trevena, Inc. - President and CEO [71]

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Also (multiple speakers) very different, really challenging to know how to do that properly.

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Michael Higgins, ROTH Capital Partners - Analyst [72]

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Yes, I agree, maybe difficult -- wouldn't be shocked in an [ad-com] of the outside people that come in may want that, if not post approval. Somewhere along the way I would think somebody would put those together, even though it is a bit clouded, I agree.

Then just to follow-up on 250, looks like result in Q4, the number of doses you're testing in the [ascending] trial?

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Maxine Gowen, Trevena, Inc. - President and CEO [73]

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That usually depends in Phase 1 on how the safety looks, obviously you dose usually to a dose limiting safety issue and that's what we will do.

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Michael Higgins, ROTH Capital Partners - Analyst [74]

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Got you. Appreciate it, thanks, guys.

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Operator [75]

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Ed Arce, H.C. Wainwright & Company.

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Yasmin Rahimi, H.C. Wainwright & Company - Analyst [76]

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Great, thank you, this is Yasmin on for Ed. Thank you for taking my questions. One question on TRV250, simply can you provide us any insight on the size of the trial and maybe some of the costs associated with it?

And then the second question is on Athena, in what format should we be seeing the data? Would be upcoming at scientific meeting or potentially released later on?

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Maxine Gowen, Trevena, Inc. - President and CEO [77]

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So the Phase 1 trial I would say is a very standard Phase 1 trial. The data on Athena, we don't have any plans right now. We don't -- the Athena trial is a little bit difficult to put a hard and fast time line on because it is an open label trial which we have to -- we're doing to satisfy safety concerns or safety requirements, I guess, by the regulators. And you only finish that trial when you see that you have enough data with sufficient breadth and depth, and only know that once it happens, so it is hard to know exactly when the trial will end.

Right now we are assuming that the year based on the current recruitment and the current mix of patients that we are seeing recruited, assuming that's going to continue. So can't really give you any more information on that.

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David Soergel, Trevena, Inc. - Chief Medical Officer [78]

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I guess that's absolutely right, think the other thing to note is the sort of -- what's not really traditional about Athena relative to for example the APOLLO studies or other well-controlled trials is that there's a feedback mechanism that occurs within Athena as I alluded to. We hear back from sites about their experience with their patients at their center. There may be opportunities to talk about certain patient subgroups and their data depending on what we hear from the centers, but it is a bit more open as Max alluded to with respect to the timelines and the data flow.

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Yasmin Rahimi, H.C. Wainwright & Company - Analyst [79]

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Great, thank you so much for taking the questions.

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Operator [80]

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Dana Ying, Aegis Capital.

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Dana Ying, Aegis Capital - Analyst [81]

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Hi, good morning, and thanks for taking my questions. So if I look at the side effect profiles between APOLLO 1 and 2, I think the data is stronger on the hard tissue side, hard tissue kind of procedures versus the soft tissue. So your market research do you get a sense that maybe physicians may choose OLINVO in certain types of procedures versus others?

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David Soergel, Trevena, Inc. - Chief Medical Officer [82]

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So a couple of things to just comment on with respect to the design of the two trials. APOLLO-1 as you alluded to is a hard tissue model where patients have local anesthetic and sedation and then the next day they participate in the study, so there's no residual anesthetic left onboard in these patients so the data tend to be much cleaner in these hard tissue models compared to the soft tissue models.

What we are seeing between the two trials is actually a very similar profile with respect to the safety and tolerability and efficacy of OLINVO. And so our expectation is that this profile would translate to, no matter what type of pain you have or whatever the source of your pain, you would be a candidate for the treatment with OLINVO.

I guess with respect to market research, I guess that's a separate question --

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Carrie Bourdow, Trevena, Inc. - Chief Commercial Officer [83]

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Physicians are saying the same thing, so as these two trials are translating into that broad indication for the management of moderate to severe pain, and then they are thinking about their own patient population, translating that they would be able to use this drug in multitude of patients and surgeries. So they are thinking about it then based on their own particular practice. Not necessarily hard tissue, soft tissue but really if I'm an orthopedic surgeon I'm thinking about my practice tends to be more hard tissue. If I'm a colorectal surgeon I'm thinking about my practice which tends to be more soft tissue.

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Maxine Gowen, Trevena, Inc. - President and CEO [84]

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I'd also direct your attention to the placebo rates of all of these effects in APOLLO-2 which were consistently higher, and that goes along with David's earlier comments about the design of the trial. So actually if you subtract out the placebo rates, the other rest of the data look very much more similar between the trials.

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Dana Ying, Aegis Capital - Analyst [85]

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Okay, thank you. Turning to the migraine drug. So there's a whole class of CGRPs are currently being developed I think most of them are in Phase 3 development. So from mechanism of action standpoint how would you differentiate TRV250 versus that CGRP drugs?

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Maxine Gowen, Trevena, Inc. - President and CEO [86]

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TRV250 has a completely different mechanism of action, it works at the delta receptor in the brain. And so our expectation is that the CGRP agents are going to be effective in some patients in reducing the incidence of migraines. I think that the data that I have seen reduces migraines by a few days a months in very severe patients.

I think that however there are still going be very large number of individuals who experience a very large number of migraines and so the initial indication for our program is for the acute treatment of migraine episodes. So again, I think that not all migraines respond to a single class of agent and we would imagine that if there are new mechanisms that are effective they will be useful to these patients.

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Dana Ying, Aegis Capital - Analyst [87]

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Just a quick follow-up. Do you potentially be expecting quicker onset of action?

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Maxine Gowen, Trevena, Inc. - President and CEO [88]

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Yes, that is something we don't really have any information about right now in humans. That will wait for us to get our first human data.

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Dana Ying, Aegis Capital - Analyst [89]

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Thank you for taking my questions.

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Operator [90]

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(Operator Instructions)

Rahul Jasuja, FBR & Company.

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Rahul Jasuja, FBR & Company - Analyst [91]

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Hi, guys. So I noted that the 0.35 milligrams dose really had the lowest discontinuation rate. And looking at that dose and looking at slide 15, trying to clarify here the disconnect between the vomiting and the antiemetics use for that dose and also the disconnect and APOLLO-1 and APOLLO-2. So could you add some color on that maybe?

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David Soergel, Trevena, Inc. - Chief Medical Officer [92]

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Yes, I can take that. So on slide 15 if you look at the blue box below the graphics, there is an endpoint there that we talk about vomiting or antiemetics use. So it is proportion of patients who either had vomiting or needed antiemetics. So it synthesizes the two trials, as you see in both trials the 0.35 regime we saw 40% reduction in that endpoint compared to morphine.

So that is a simple way of thinking about upper GI tolerability at large, so in APOLLO-1 we see the beneficial effects on upper GI tolerability manifest as reduced antiemetic use and APOLLO-2 we see the benefits on upper GI tolerability manifest as statistically significant reduced vomiting rates. It is ultimately with the profile is, is that the drug has better upper GI tolerability compared to morphine.

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Rahul Jasuja, FBR & Company - Analyst [93]

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So just looking at the antiemetic is used post the vomiting, the use of antiemetics in APOLLO-1 with the 0.35 dose was less after vomiting while in APOLLO-2 it was conversely the opposite. Anything should we read into this as to the nature of the trials or the patient subsets here?

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David Soergel, Trevena, Inc. - Chief Medical Officer [94]

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I see what you are saying. The use of rescue antiemetics in this trial was -- so if a patient had at least moderate nausea or vomited they could receive a rescue antiemetic, so it is not necessarily that the patient had the vomit and then they would get an antiemetic. That's why we showed this other analysis, this vomiting or rescue antiemetic use because the numbers are not the same.

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Rahul Jasuja, FBR & Company - Analyst [95]

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Okay, got it, thanks.

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Operator [96]

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Douglas South, Barclays.

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Douglas South, Barclays Capital - Analyst [97]

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Maybe from a bigger picture, I don't know if your market research has shown this yet, but just curious if physicians tend to see oliceridine as a better opioid, or one with a cleaner profile or do they see this alternatively and I understand that it's still working on the opioid receptor, but do they see this as a real tool to reduce their opioids consumption? Because obviously that is a real focus on hospitals right now and having downstream effects in terms of sending home a patient with like OxyContin, et cetera.

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Maxine Gowen, Trevena, Inc. - President and CEO [98]

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I think that what they're focusing on in the hospital is reducing the opioid-related adverse effects. And I think that -- I don't know whether you are referring to reductions in overall opioid use in the community, I think that focused more on the oral drugs that are prescribed to be taken home. But I do think that they see this drug as an opportunity to reduce the opioid-related adverse effect in that practice, and that is of course what they really are dealing with on a day-to-day basis and what causes these increased costs in the system.

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Douglas South, Barclays Capital - Analyst [99]

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Okay, great, thank you.

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Operator [100]

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At this time I'm not showing any further questions and would like to turn the call back over to Jonathan Violin for any closing remarks.

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Jonathan Violin, Trevena, Inc. - Senior Director of IR [101]

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Thank you and thank you, everyone for joining us today. I'd like to remind you that a replay of this call will be available on the Company's website at www.Trevena.com.

On behalf of the management team at Trevena I'd like to thank you all for joining us and as always we are available if anyone has additional questions. With that, we will end the call.

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Operator [102]

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Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program and you may all disconnect. Everyone have a great day.