Thank you for standing by, and welcome to the Trevena Incorporated Second Quarter 2021 Financial Results Conference Call. At this time all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. [Operator Instructions] I would now like to hand the conference over to your first speaker today Barry Shin, Chief Financial Officer. Please go ahead.

Good morning, and welcome, everyone. With me today are Carrie Bourdow, our President and CEO; Bob Yoder, our Chief Commercial Officer; and our Chief Medical Officer, Mark Demitrack. As a reminder, we'll be making forward-looking statements within the meaning of federal securities laws. These statements are subject to risks and uncertainties related to our business, including those covered in our filings with the SEC. We undertake no obligation to update these statements beyond today. I'll now turn the call over to Carrie for an overview of our second quarter and recent business accomplishments. Carrie?

Thank you, Barry. Good morning everyone. Thanks for joining us today. The second quarter marked our first full quarter of the OLINVYK launch. And with five months in the field, we now sit at 35 formulary approvals, over three times the number we have reported last quarter. We've recognized that COVID has had an impact on sales and formulary timelines have been delayed, but our team remains focused and adaptive and we have a lot to be excited about, both with the Linda can, our pipeline. With OLINVYK, we're on track to reach our year-end goal of 100 formulary wins and we're focused on that metric because when we get in front of a customer and present the OLINVYK profile their strong interest and physicians continue to be excited by the clinical data and the OLINVYK value proposition. Importantly, we're already getting positive feedback from physicians, who have the chance to use OLINVYK. We've also started two new studies to build on OLINVYK's unique profile. The first is a clinical outcome study led by Cleveland Clinic. Remember that Cleveland Clinic came to us with an interest in expanding upon our Phase 3 findings in three important safety areas that physicians care about: respiratory, GI and cognitive function. Patient enrollment is on track to start this quarter and top-line data is expected middle of next year. The second study is evaluating the effect of OLINVYK versus morphine on respiratory function in elderly and obese individuals. This study also builds upon previously published work and patient enrollment is well underway. We expect top-line data from this study by the end of this year. And finally, we continue to advance OLINVYK towards approval outside of the U.S. Nhwa, our partner in China recently began dosing patients in their Phase III trial. Once that study is complete, they expect it to have sufficient data in combination with our existing package to submit OLINVYK for approval. Beyond OLINVYK, we're advancing our pipeline through partnerships with globally recognized institutions. We were pleased that the first patient was enrolled in the TRV027 active COVID trial, which is being led by Vanderbilt University Medical Center and funded by NIH. For TRV045, our novel S1P receptor modulator, we're on track to file our IND for diabetic neuropathic pain this quarter. DNP is a significant market opportunity with 5 million people affected by this painful condition and few therapeutic options available. And the National Institute on Drug Abuse or NIDA has resumed their study of TRV734 for opioid use disorder. As we continue to battle the COVID pandemic, it's important that we don't forget about the other public health crises that take a toll on our communities. And I'm proud that Trevena is playing a role in developing solutions for some of the largest public health issues. To close, we have a highly skilled team with expertise in launching products, both prior to COVID and now during the pandemic. We have the resources, a great product and launch strategy, interesting new data coming soon, and we're well positioned to reach our year-end goals. So with that, let me turn the call over to Bob to talk more about the OLINVYK launch. Bob?

Thank you Carrie. With our first full quarter of launch complete, we continue to make progress towards our year-end goal of 100 formulary wins. 123 institutions are currently reviewing OLINVYK at various stages and 35 accounts that added OLINVYK to formulary. At the same time, it's no surprise that COVID has impacted our field activities. But as the pandemic evolves, so are we. Here's where we're at. Through the end of May, rep live engagements were holding up at around 70%, which really compares favorably to reported industry benchmarks. Over the past six to eight weeks, we've started to see that level of live engagement decline as certain regions have started shutting down again. Additionally, formulary reviews, which historically have a seasonal slowdown during summer months have been further delayed. But here's what we know, when we are able to engage with the customer, either live or virtually, the response is consistently positive. We continue to hear that OLINVYK's unique profile and value proposition resonate with physicians. For example, we're hearing great feedback about OLINVYK's use in the ambulatory surgical setting. Physicians point to the rapid onset and duration of effect as the two main attributes that allow them to use OLINVYK in the perioperative setting all the way through patient discharge. And in the inpatient setting, we're hearing that clinicians are impressed with the gastrointestinal tolerability profile of OLINVYK, particularly for open GI procedures, where the use of an IV opioid is necessary, but so is minimizing adverse events such as postoperative vomiting. We also know that health care decision-makers, like P&T committee members, have found the health economic model to be very beneficial in their assessment of the full value prop for OLINVYK. Based on the early traction and positive feedback, we're expanding our outreach and access opportunities for OLINVYK. So here's what we're doing there. First, we plan to target more physicians who are key stakeholders at large influential institutions who can serve as OLINVYK advocates during the formulary review process. To do this, we're adding five medical science liaison so that our full MSL team can now target approximately 500 physicians at top academic medical centers and other important institutions. Our MSL team is comprised of PharmDs with deep experience in health economic data and modeling. They've got the right credentials and experience to communicate OLINVYK's compelling clinical profile and health economic data. Second, we're expanding our list of target accounts to approximately 700 hospitals, representing approximately 60% of the IV opioid market. These new accounts represent a significant growth opportunity for OLINVYK. In closing, over this past quarter, we tripled our formulary wins and continued to grow the number of accounts that are moving through the P&T review process. When we get in front of our customers, they tell us they like OLINVYK's differentiated profile and value proposition. And we're hearing positive things from customers who are using OLINVYK. We're hiring additional MSLs to expand our outreach to health care professionals and extending our field coverage to include additional high-volume accounts. We started this launch at the height of the pandemic, and we know how to do this in a virtual environment. While we all certainly hope that an expanded shutdown is not coming again, we're taking steps to be as effective as possible if we return to that environment. I am firmly convinced in the long-term value of OLINVYK and the positive change it brings to the management of severe acute pain. Let me now turn the call over to Mark to provide a quick overview of where we are with our pipeline.

Thank you, Bob. As you've heard, we've implemented many important initiatives to support the launch of OLINVYK, among which are the two post-approval clinical studies. One in collaboration with Cleveland Clinic and the other conducted at Leiden University Medical Center. We also recently announced publication of our 28th peer-reviewed manuscript, which continues to strengthen the already substantial OLINVYK evidence base of scientific literature available to our customers. In addition to our progress with OLINVYK, we've continued to advance our pipeline assets towards key milestones. With TRV027, the two COVID-19 platform trials evaluating our compound continue to move forward. We were pleased to announce that the nationwide ACTIV trial supported by NIH and led by Vanderbilt University Medical Center recently began dosing patients. In addition, start-up activities for the REMAP-CAP trial based in the UK are ongoing. We also are eagerly awaiting the interim data from Imperial College London's proof-of-concept study. That study completed enrollment in the second quarter, and the research team at Imperial College expects to report their top-line outcomes by year end. Recall that prior to transitioning into the REMAP-CAP and ACTIV trials, this study underwent an interim analysis by the study's data monitoring and safety committee. Their review found no safety concerns associated with 027, and acknowledge that the study's progress supported advancing 027 to larger trials with efficacy endpoints. We look forward to seeing what the data from all these studies tells us about TRV027’s impact on severe organ damage, mortality and recovery among COVID-19 patients. With TRV734, NIDA is currently screening patients for their opioid use disorder proof-of mortality study. And finally, this quarter we're on track to file our IND for TRV045, our S1P receptor modulator in diabetic neuropathic pain. And we begun planning for the Phase 1 development program for this novel compound. Over the next few months, I look forward to updating you as we continue to make progress across our pipeline. Let me now turn the call over to Barry to discuss our second quarter financial results. Barry?

Thanks, Mark. We reported 35 formulary wins today and $178,000 in Q2 net sales for OLINVYK, in part due to longer time lines in this pandemic environment. We continue to believe these formulary wins are the best leading indicator in the hospital launch. Our net loss for the quarter was $14 million compared to $6.2 million for the same period last year. This change is mainly due to expenses associated with the first full quarter of the OLINVYK launch. Our operating expense was $14.2 million for the quarter, and we expect this to increase moderately in the second half as we continue to commercialize OLINVYK and advance our pipeline assets. We finished the quarter with $91 million in cash and equivalents, which we continue to believe will fund our operations through the fourth quarter of 2022. We'll now open the call for questions after which Carrie will provide some closing remarks. Operator?

Thank you so much. [Operator Instructions] First question from Brandon Folkes from Cantor Fitzgerald. Your line is open.

Hi, thanks for taking my question. Maybe firstly, on OLINVYK, just can you just elaborate in terms of where you've seen the product getting used and maybe some reorders at this stage? And then the decision to expand the targets at this stage of the launch. Can you just talk about if there's any change in thinking about converting the initial targets there? Is this just sort of COVID, obviously, things aren't very fluid. So just any color on that decision to expand the target at this stage versus continuing to drive home those initial targets? And then lastly, just you're putting in a lot of work to produce a lot of very good data over the next 12 months on OLINVYK. Any accounts asking you to wait and see those results ahead of adding to the formulary? Thank you.

Thanks Brandon. So I'll start and then I'll turn it over to Bob for additional color on the accounts. So where we're getting used, we had, I think, described the fact that we would get initial use in community hospitals because they tend to have fewer processes, and that's actually what we're seeing. Early on, we had some large academic medical centers come into the mix, which was great. And we're still seeing that. We've had couple of integrated health systems come into for formulary wins. I think that's really interesting. We're also seeing ambulatory surgery centers because, again, they tend to have fewer processes. So where we're getting the use and the reorder is in some cases it's with those ambulatory surgery centers. Although there are a couple of the institutions, the large cancer institution that I mentioned on our last quarter call, they've also had an opportunity to use it and reorder. So I think that's really good news. But back to the comments we were making on the call that when physicians use it, they like it. They like what they see. They're seeing the fast onset and they're continuing to use it. Bob, do you want to talk a little bit about, Brendan, I think what you're describing are the 700 hospital targets that we're expanding, correct?

Correct, yes.

Yes. Yes. Bobby, you want to talk a little bit about that?

Sure. Yes. Hi, Brandon. So the thinking there is that what we've kind of learned that our team has the capacity to go a little deeper and you might recall our initial targets were a combination of high volume accounts who had demonstrated sort of a prior history of early adoption. And so we're still focused on those. You should maybe think about this more just kind of dipping down into the next least tier or high priority targets. These are still a high volume targets. If you think about it, roughly 1,200 hospitals do close to 80% of the overall IV opioid market. So we're still in that upper tier of opportunity, but we just learned that our team had the capacity to begin to go out to these other hospitals and try to move them to the top of the funnel so to speak in terms of the P&T review process, while they're still moving the other ones through, there's other 123 while they're still working those as well.

The other thing I'll add is that, well, of course, what we're seeing in the pandemic is that folks are working virtual again, right? And so that, that efficiency that happens when people are able to have conference calls in the morning with physicians on the east coast and then in the afternoon with folks in other parts of the country, we're going to try to leverage that. When we initially launched, we said, let's pick the top 500 accounts, that's about 40%, 45% of the ideal opioid volume. We were looking for triggers. We were looking for when is the right time for us to delve a little bit deeper. And we think we have an opportunity to go. As Bob said, maybe not to the full 1,200 but with the same footprint of reps because of the virtual engagements go a little bit deeper. The other question you asked was around the data. We're not having formulary committees talk about asking for the additional data set. The plan all along was to launch with this core foundational set and then continue to build on as we were describing, right? The respiratory, the GI, I think cognitive function is going to be a really interesting area for us. Mark, will provide a little bit of the color that we're getting from the physicians that are using the drug. And they're describing that, that potential improvement in cognitive function that we've heard about in our open-label safety study. So it's really our plan to continue to build on the data set, that it's not getting in the way of existing formulary discussions that we're having.

Great. Thank you very much.

Great.

Thank you so much. Next question from Jason Butler from JBS Securities. Your line is open.

Thanks for taking the questions. First one, just in terms of the formulary approvals or reviews, can you speak to what the rate approvals on the first or subsequent review cycles is in line with what you'd expected? And then I have a couple of follow-ups on the pipeline.

Great. So I will say that I've been launching drugs a long time. No one's really being able to look at our historical benchmarks and see some of the expectations. Given the pandemic, things are taking longer, both in terms of having the meetings and then the reorder rates or the order rates after the meetings. But Bob, I'll let you talk a little bit more about the rate of approval. I think our team has done pretty well. We're winning more than we're not, which is good news.

Yes, absolutely. Jason, so we definitely are winning the majority. And I guess the other color I'd give you is the couple of the initial denials. A few of those happened in advance of our team being deployed out there and able to run the P&T committee through the full data set that Mark's team has put together. So – and as you sort of alluded to, I mean, these are – we call these initial denials. I mean it's not a denial that we never go back to. So in those couple of initial denials, we've gone back and we're reengaging with the advocates and so forth and trying to take another swing at it as well. And so the team will continue to push even on those accounts where we saw an initial denial.

Great. And then on the respiratory study that we'll get data from later this year, can you speak to the endpoints there and just what data we'll see in the top line release? And then for 045, any more details you can give us on the Phase I plans, and how and when we would get proof-of-concept results? So obviously, in addition to the ascending dose work you do in healthy volunteers, how quickly could you start to include DNP patients into the development program? Thanks.

Yes. Great. Mark. You want to talk about both the OLINVYK? Yes, go ahead.

Yes. Jason, so the respiratory physiology study, as you may remember, this is built on a collaboration that we've had with Dr. Dahan at Leiden University and he has innovated a technique that's called a clinical utility function analysis, which is a way of looking in a combined outcome at analgesic effect, the benefit of a drug and then respiratory compromise the risk associated with the drug. So you basically have a graph. That's looking at the probability of analgesia versus the probability of respiratory depression over the concentration range of the drug. So it's a very innovative way of looking and graphing risk benefit. And when we looked at that in our initial data with Dr. Dahan’s help, we saw a striking difference between OLINVYK and morphine across their effective plasma concentration ranges with OLINVYK, having a much higher probability of producing analgesic benefit compared to respiratory depression. Analgesia is measured in the laboratory setting by several different experimental pain models cold pain tests and electrical pain stimulation. Respiratory function is measured in a rigorous way by looking at entitled CO2 and respiratory rate in response to graded inhalation of CO2. So these are very, very tightly controlled laboratory conditions that allow us to interrogate the respiratory physiology apparatus in the brain. So that's what we're doing in this study. This study in particular is building on the earlier work by examining an older overweight age group. So it allows us to see, what we expect to be an even more exaggerated difference between OLINVYKs profile compared to morphine in the study that as I said, that data will be on track to report out by the end of this year.

Mark, do you want to talk about 045 and your plans there?

Sure. So you asked about 045, where obviously we're on track to file the IND this quarter, as I said, and we've already begun preparations to begin the initial Phase I work shortly after that. And as you said, that initial work first dosing will obviously occur in a healthy volunteer population. We are already in the planning phase of moving quickly into a patient-based model, so more to come on the details of those designs in the coming – in the coming months.

Okay, great. Thanks for taking the questions.

Great. Let me, the other comment I wanted to make on the respiratory physiology study is that when Dr. Dahan, - when we Publish that data and Dr. Dahan presented it at conferences people found it as Mark said, really interesting. It's the models are accepted and by formulary committees, and the question was, well, what does it look like in your challenging patients? Right. So again, it's another way that we can expand the data set in connection to the launch strategy. So I think this is going to be a really great set of information for us at the, at the end of this year. Operator, next question?

Thank you so much. Next question from Douglas Tsao from H.C. Wainwright. Your line is open.

Good morning. And thanks for taking the questions, just maybe starting points, curious in terms of, and I say, ask this, knowing that it's very early days, but in terms of the hospitals that are now using OLINVYK. I'm just curious in terms of what, how they're doing. So are they stocking it on the shelf? Are they ordering it ahead of cases that they think it would be most appropriate? And also, do you have a sense of which patients it's being used in most? Is there a particular sort of high risk patient, be it age, obesity, that they're gravitating to more, more towards right now?

Yes. Great question. And I'll say, let me start with just the stocking, then I'm going to turn it over to Mark. Who's been talking with a lot of these physicians that are using it. It depends, right. If they've been using it and they know they're going to use it in a certain patient population or a certain surgery, particularly in the ambulatory surgery centers, they're ordering it ahead. If it's someone that's, brand new and they're beginning, right, there. We've gotten on formulary and they want to order then, then it's been, it's not that it's not ordered ahead, but I think it's really interesting. We have some ambulatory surgery center physicians that are using it in younger patients than what we originally positioned it and in the inpatient setting, it's more of that challenging patient, but let me, not steal Mark's thunder because he's got some really good, I think, cases to describe.

Yes, Doug, good morning. So what we're hearing, let me talk first to sort of expand on what Bob commented on, on the ASC side. One of the things that early on was recognized by clinicians is the profile of OLINVYK lends itself as an analgesic to use throughout the case from beginning to post procedure with the intent of more rapidly moving the patient through the ASC setting. And that – and we've heard that, that's working and clinicians have been quite satisfied with OLINVYK's performance in that way. Within the inpatient setting, I'll give you an example. One of the messages that we hear quite consistently is that this is a very attractive option in the setting of the complex patient. And what they tell us is that the respiratory profile, the really insufficient patient and the patient at higher risk of postoperative nausea and vomiting are ideal candidates for the use of OLINVYK. And this is in the setting, in many instances, we've heard cases of open abdominal procedures, which are very complicated painful procedures where these risk factors combine to make the case clinically quite challenging. Another very, very interesting aspect though when we hear about the inpatient settings, and this comes up quite a bit is what we heard in the ATHENA study. Carrie touched on this earlier. And that is that the reorientation, the ability for the patient to participate in their own recovery, their level of alertness and the lack of sedation is one of the most distinguishing characteristics that a clinician notices in the use of OLINVYK. And it makes me that much more excited about the idea of digging into this further in the outcome study that we had planned.

Okay, great. And if I can ask another follow-up just in terms of the formulary approvals that you are getting, are they fairly broad-based right now? Or are there being restrictions placed on them? Thank you.

Carrie, would you like me to take that?

I’m sorry, I was on mute. I'm happy for you to take it, but I had already answered it.

Sure. Go ahead.

Yes, even in the – So we're not actually seeing patient restrictions where if we are seeing, in some cases, restrictions where if the physician, a colorectal surgeon is the one that Mark described is asking for it, it's restricted for their use. But beyond that, we're not seeing a lot of the restrictions to certain patient types.

Okay. Great. Thank you so much.

Yes. Great.

Okay. Thank you so much. There are no further questions at this time. Carrie, please go ahead.

Well, thank you all. Thank you for your questions. As you can hear, we're pleased by the progress that we've continued to make on the OLINVYK launch, both in terms of increasing our formulary wins and advancing our post-approval plan. The fact that we've more than tripled the number of approvals since first quarter, especially given the unique environment that we've all had to navigate, that suggests to us that formulary committees recognized OLINVYK's value. And there is a lot to look forward to with data from the first OLINVYK post-approval study expected by the end of this year, continued progress on the launch, our IND filing for TRV045 this quarter. TRV027 top line data from Imperial College, an update from patient enrollment from the two COVID studies. So as you can hear, there's a lot going on. We look forward to updating you on all of these fronts as we continue to remain focused on providing innovative medicines for patients and health care professionals. And thank you again for joining us. That concludes today's call.

That does conclude our conference for today. Thank you for participating. You may all disconnect.