Trevena Inc (TRVN) 2014 Q1 法說會逐字稿

Good morning. My name is Eric and I will be your conference operator for today. At this time I would like to welcome everyone to the Trevena first quarter 2014 financial results conference call. (Operator Instructions). I will now turn the call over to Jonathan Violin, Director of Investor Relations at Trevena.

Thank you, Eric. Welcome everyone and thank you for joining us for today's call. With me are Max Gowen, our CEO, Roberto Cuca, our Chief Financial Officer, Mike Lark, our Chief Scientific Officer, David Soergel, our Senior VP of Clinical Development and Bob Prachar, Trevena's Senior VP of Commercial and Corporate Strategy. 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 provision of the Private Securities Litigation Reform Act of 1995.

You are cautioned that such forward-looking statements involve risk 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 the recent corporate highlights. David will then provide a detailed review of our clinical programs. 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.

Thank you John, and thank you all for joining us this morning. We are delighted to have the opportunity to review our recent progress and discuss the status of our programs. Our core focus at Trevena is translating our biased ligand product platform into a portfolio of therapies that target proven G protein coupled receptor or GPCRs, and offer a differentiated and superior therapeutic profile that's a value to patients and attractive to payors. Since the beginning of the year we made significant progress towards this goal.

We advanced each of our three clinical stage programs into important new trials, and we were pleased to report this morning the top line results from the first part of a Phase 1 multiple offending dose study of TRV130 which supports our recently initiated Phase 2ab studies. We also reported this morning we completed dosing in the first Phase 1 trial for TRV734, our oral follow on to TRV130. Let me begin today's call with a brief review of recent highlights. We recently advanced our lead CNS program 130 into a Phase 2ab bunionectomy trial. 130 is in development for the treatment of moderate to severe pain where IV treatment is preferred such as post operative pain.

The trend in post operative pain treatment is to add weaker analgesics to standard opioid therapies in order to reduce the opioid dose to mitigate the burden of opioid related side effects. To illustrate that point, approximately $1 billion was sent on IV analgesics to treat post operative pain in the US while the cost of managing opioid related side effects are estimated five times that amount or $5 billion based on published research. So the overall cost impact of post operative pain management is substantial and represents a significant opportunity for a better opioid. Our goal is to develop 130 as a better opioid with unmatched analgesia and reduced side effects. Just last week we had the opportunity to share the impressive data from our Phase 1b study for 130 at the American Pain Society annual meeting.

David will review the data momentarily and also discuss the results from the first part of the multiple ascending dose trail for TRV130. We are building on these data in our on going Phase 2ab trial which is evaluating 130 versus morphine in patients following bunionectomy surgery and we expect top line data from this trial in the first quarter of 2015, and if positive will provide us with a path forward to Phase 3 trials. As we announced today, we also completed dosing in the Phase 1 study for 734. 734 takes advantage of the same innovative mechanism of receptor activation as 130 and indeed has demonstrated a similar profile to 130 in pre-clinical studies.

We are developing 734 as a potential treatment for moderate to severe, acute and chronic pain. There is a major commercial opportunity for an oral opioid with an improved therapeutic index compared to current therapies such as Oxycodone. With over 150 million people suffering from chronic pain in the G7 market. Specifically our goal for 734 is to optimize analgesia while minimizing [on target] side effects such as respiratory depression, nausea and vomiting, and constipation which frequently prevent patients in severe pain from receiving an appropriate analgesic dose.

We expect to incorporate a tamper resistant or abuse deterrent formulation for the 734 marketed product in order to reduce the risk of abuse of the drug. Once we know we have a path forward with the compound we will begin to evaluate available technologies. In addition to our CNS programs, we're also enrolling patients in our Phase 2b trials for 027 in acute heart failure. The trial is proceeding as expected and we remain on track to announce top line data in the second half of 2015. This drug is a balanced vasodilator which also promotes cardiac contractility, a combination of effects we hope will provide benefits to these very sick and under served patients.

As we discussed previously, Forest has an option to license 027 following the completion of the Phase 2b trial and should Forest exercise its option we would receive a $65 million license fee and significant downstream revenues both pre and post launch, which we would then be able to reinvest and focus in our core CNS pipeline. In parallel with our clinical efforts we are working to build our organization to support our clinical and corporate objectives. Our January IPO strengthened our balance sheet and provided us with the funding to take 130 and 027 through important Phase 2 trials.

And we recently appointed Bob Prachar as VP of Commercial and Corporate Strategy. Bob has served as a consultant to the Company since last August and his extensive commercial experience in the life science industry will be inavailable for optimizing the development and commercial profiles of our program.

Trevena has a proven ability to move programs forward rapidly and efficiently from discovery into and through development, and our progress since January demonstrates our commitment to accelerating our clinical objectives. We are now focused on successfully executing our Phase 2 programs of 130 and 027, and supporting further development of 734. Let me now turn the call over to David to provide a detailed review of the programs.

Thanks, Max. Our clinical portfolio is very active and is progressing rapidly. We have two Phase 2 running, last HF for TRV027, and a bunionectomy trial for TRV130. We also recently completed dosing in our first Phase 1 study of TRV734 as Max highlighted. We are planning another TRV130 Phase 2 trial to start later this year and we continue to work to bring biased ligand development candidates forward.

I would like to begin with an overview of our CNS programs starting with 130. Opioids are the most effective treatments for moderate to severe post operative pain and are a fundamental component of physicians' tool kits. However opioid's high level of efficacy comes with significant side effects, and to date it has not been possible to separate these side effects from efficacy, making it challenging for physicians to adequately treat patients' pain. Using our biased ligand platform we designed TRV130 to address this need. Based on our data to date, TRV130 promises to be a potent analgesic with less respiratory depression and GI dysfunction compared to unbiased opioids like morphine, and could therefore become the opioid of choice to treat post op pain.

As Max noted we presented the full results from our Phase 1b trial for 130 last week at the APS meeting. Our goal of this study was to see if TRV130's efficacy, safety and tolerability could be differentiated from morphine. We did this in a randomized, double blind, placebo-controlled, five period crossover study enrolling healthy adult males. We tested three doses of TRV130, a high dose of morphine and placebo. We evaluated 130's efficacy using the well validated cold pain test. TRV130's efficacy was excellent.

All doses of 130 were analgesic and had a more rapid onset of peak analgesic effect than morphine. The higher TRV130 doses showed superior analgesic effects and a higher responder rate versus morphine. As you are aware, the major safety issue with unbiased opioids like morphine is respiratory depression. Respiratory depression can result in accumulation of carbon dioxide in the blood and cause organ damage and ultimately death. As predicted from pre clinical studies TRV130 appears to have less of a negative effect on respiratory drive than morphine. In the study we showed this using a technique called the ventilatory response or VRH test.

In the VRH test, healthy suggests breathe carbon dioxide, stimulating more rapid and deeper breathing. Unbiased opioids like morphine are known to blunt this normal physiological response. In our study morphine produced a profound and protracted negative impact on respiratory drive, appearing to last longer its analgesic effect in the cold pain test. This suggests when a patient's analgesia would be wearing off additional doses of morphine may produce a further negative affect on respiration. In contrast TRV130 produced less respiratory depression overall and the effect was brief. TRV130's tolerability at doses that provide superior efficacy also appears very attractive. We use visual analog scales to quantify opioid related adverse effect severity.

So in contrast to spontaneous adverse event reports which relied on investigators' assessment of severity with a VAS the subject study quantifies the degree to which they feel the drug effect. Using the VAS method, TRV130 was associated with less severe nausea than morphine. In addition, TRV130 treatment produced fewer episodes of vomiting than morphine treatment. In addition to being very uncomfortable, and in some cases treatment limiting, vomiting can delay post operative recuperation by delaying oral intake. These data indicate that TRV130 may have a better GI tolerability profile in addition to providing better pain relief. Other opioid-like adverse effects were comparable to morphine, but in the setting of far better analgesic efficacy.

So taken together these results suggest TRV130 may reduce patients' pain more effectively, act more quickly, produce less severe GI side effects and reduce the risk of respiratory depression resulting in improved margin of safety for dosing. Moving from the Phase 1b study to the TRV130 multiple offending dose study. The multiple offending dose study paves the way to start the Phase 2ab bunionectomy study by evaluating the maximum tolerate dose and PK of TRV130 when multiple doses were given, mimicking how 130 will be given in the bunionectomy study. This was a randomized, double blind, placebo controlled, study. We continued to measure pharmacodynamic effects of 130 including pupil constriction and cold pain test analgesia.

Overall the safety, tolerability, PK and PV data from this trial are consistent with earlier trials. TRV130 administration resulted in robust pupil constriction and produced a robust analgesic effect in the cold pain test. The second part of this trial is ongoing. The data to date therefore provide a clear rationale for continued development of TRV130 and last week we announced the initiation of our Phase 2ab bunionectomy trial. This is a multi center, double blind, placebo and active control trial with the goal of evaluating 130's efficacy and tolerability in the management of post op pain using the gold standard morphine as a benchmark.

We will enroll approximately 400 patients who will undergo first metatarsal bunionectomy, and are then randomized to receive 130 morphine or placebo to manage their post op pain. Pain intensity and pain relief will be measured using validated rating scales at multiple time points up to 48 hours during the study period. Similar approaches have been used in registration studies of other pain products so the data from this trial will help us greatly to design the Phase 3 program. The bunionectomy study will be conducted in two parts. First we will enroll 150 patients into six groups in a pilot Phase, part a of the study. 25 patients per group will be randomized to either one of four dose levels of TRV130, morphine, or placebo.

Each treatment will be given every four hours for 48 hours. In part b we will enroll approximately 10 successive cohorts of 25 patients, who will be randomized to two adaptive doses of 130, morphine, and placebo. As each cohort finishes we will use the data to refine the doses for the next cohort and optimize tolerability and efficacy compared to morphine. This study is designed to enable Phase 3 development by providing information on dose and integral ranging and furthering the differentiation of TRV130 versus morphine. We expect to report top line results from this trial in the first quarter of 2015.

As part of our Phase 2 program for 130 we also plan to launch a Phase 2 soft tissue surgery trial in the fourth quarter utilizing, in this case, a flexible dosing paradigm. The aim of this study will be to evaluate TRV130's efficacy and tolerability again in comparison to morphine, but this time using as-needed dosing in the soft tissue surgery model. As you are probably aware, opioids are most frequently administered when the patient feels pain and asks for medication rather than at a fixed time. The study design is now in process with the goal of further differentiating TRV130 versus morphine. Now to TRV734, our oral follow on to 130.

In pre clinical studies TRV734 demonstrated an encouraging therapeutic profile with a potent analgesic effect and a reduced impact on GI motility at equi-analgesic doses compared to oxycodone. We are excited to have completed dosing in our first Phase 1 study for 734. This trial will give us several important pieces of information. The extent of oral bio availability as well as the safety, tolerability, PK and PV of single doses of 734. The potentially efficacious dose range will be evaluated using pupilometry, an approach we used successfully for TRV130. These key top line data will be available mid-year ahead of schedule.

Turning now to TRV027 for acute heart failure. 027 acts as a vasodilator while simultaneously increasing cardiac performance through its unique biased ligand mechanism of action. And this may translate to a benefit on all three key organ systems affected in acute heart failure, the blood vessels, the kidneys, and the heart. Pre clinical and clinical data support the candidate's potential to be an important new therapy for HF patients. We are advancing our Phase 2b BLAST-AHF trial, a randomized, double blind, placebo-controled trial of 027 administered along with standard of care in patients with AHS. We announced the dosing of the first patient in January and are building momentum in the trial.

We received health authority approval in nine countries and now have 28 sites open globally. We will continue to activate additional sites over the course of the next few months and continue to expect the data available in the second half of 2015. We are confident in the trial protocol and end points and believe the innovative design of this study will generate the data that will be needed to optimally design the Phase 3 program. We will present the designer rationale and the poster presentation at the EFC Heart Failure meeting next week in Athens. In addition, Peter Pang, co-chair of our steering committee will highlight 027 as part of a symposium presentation on new drugs in development for heart failure.

In summary, we have very active clinical development programs which are on track to deliver key data. We look forward to sharing more with you on future calls. Now I pass the call to Roberto for a view of our financials.

Thanks, David. Our financial results for the quarter reflected the continued progression of our pipeline, and our transformation into a public company at the beginning of this year. General and administrative expenses increased by $1.3 million for the first quarter of 2014 compared to the same period one year ago primarily as a result of head count and salary costs, including compensation expense associated with stock options, as well as insurance costs and professional fees all resulting from our operating as a public company.

R&D expenses were $7.6 million for the first quarter of 2014 versus $2.1 million in the first quarter of 2013. The increase was primarily driven by clinical research expenses for the Phase 2b study of TRV027 that we announced the start of in January,clinical research and manufacturing and formulation expenses for TRV130, and expenses associated with the progression of TRV734 from pre-clinical to clinical studies.

We reported a net loss attributable to common shareholders of $9.4 million or $0.59 cents per share for the quarter ended March 31, 2014, as compared to a loss of $3 million or $4.30 per share for the same period of 2013. This includes non cash charges of $29,079 for the accretion of preferred stock in 2013 and -- 2014 and 2013 respectively

We ended the quarter with $91.3 in cash and cash equivalents, and we continue to expect this will be sufficient to fund our operations to the end of 2015. I will now turn the call back over to Max for closing comments.

Thanks, Roberto. The first few months of 2014 has been a period of significant clinical and corporate progress for Trevena. We successfully executed our clinical strategies for each of our candidates, further demonstrated the clinical potential of our biased ligands, and strengthened our balance sheet to support key studies.

We have a number of remaining goals for the year and important milestones for our programs on the horizon in 2014 and 2015. For 734 we expect data for the Phase 1 study to be available mid-year providing key data on its oral availability as well as its tolerability and pharmacodynamic dose range. For 130 we plan to initiate a second Phase 2 efficacy and tolerability study for 130 in the fourth quarter,and report top line data from our ongoing bunionectomy trial in the first quarter of next year.

For 027, data from the Phase 2b BLAST-AHF trial is expected in the second half of 2015. And finally from our platform we expect to nominate a delta opioid candidate later this year. We are proud of the progress that we have made over the past few months, and we look forward to building on this momentum and updating you on our programs over the course of the year. We will now open the call for questions.

(Operator Instructions). And our first question comes from Alan Carr of Needham. Please go ahead.

One, can you go over a bit more about the 130 MAD trial that's moved into its the second part? If you can talk more about finding some of the first one and then the expectations for the second part there how that will be helpful? And then regarding the delta program, do you have any higher resolution on when you expect to nominate a candidate? And when that might move into the clinic next year? Thanks.

Hi, Allen, thank you. So I will direct the first question on the MAD study over to David and then perhaps Mike can pick up the question on the delta program.

Yes, sure. Hi, Allen. The multiple ascending dose study was again a multi dose study to pave the way into the bunionectomy trial where we are administering multiple doses of drug to patients after surgery. The first part of the study looks at individuals who are cytochrome P450 2d6 non-poor metabolizers, and the second looks at CP 2d6 poor metabolizers in whom we expect the drug levels to be longer lasting and therefore to have the pharmacodynamic effects last longer as well.

Allen, this is Mike. The delta program is progressing as we expect . We are on track to nominate a compound from this program before year-end. Currently we are optimizing the drug-like properties of the compound as we are progressing it forward. The plan would be to then initiate IND enabling studies and complete those studies towards the end of 2015.

Great, Thanks very much.

Our next question comes from Ying Huang from Barclays.

Good morning. Thank you for taking my question. I have a question about the Phase 1b data you presented at American Society for Pain last week. It looks like among the three doses tested, the high dose which is 4.5 milligrams, you do see a similar incidence rate with the side effect as compared to morphine. The 1.5 milligrams may not be quite efficacious. 3 milligrams looks okay. I was just wondering what your thought was in terms of what dose will give you the best balance of safety and good efficacy compared to morphine there?

Good morning, Ying. I will let David pick that one up.

Hi, Ying. So you have to look at the efficacy side of the equation when you are evaluating the adverse events too, right? So I agree the 4.5 milligram dose, we saw similar levels of adverse events and indeed in reported in a visual analogue scale measured adverse events as well with the 4.5 milligram. But it was a lot more effective than the 10 milligram dose of morphine. So if you look at the overall therapeutic index of the drug, in other words, the therapeutic benefit versus the side effects TRV130, even at 4.5 milligrams is superior to morphine.

In terms of the 1.5 milligram dose, actually in terms of peak effect had a similar peak effect of analgesic efficacy as that high dose of morphine on the trial. Although the effect appeared to be a little bit shorter lasting than we saw with morphine. So the key outcome of this bunionectomy study is to answer the question you asked. Identify the dose range and the interval that optimizes TRV130 in comparison to morphine. So we expect those data to be available again first quarter of next year.

Thank you.

Our next question comes from Ritu Baral from CanaccordPlease go ahead.

Hi, guys, thanks for taking the question. Could you walk us through part a and part b of that trial in a little more detail? I got the overview, but when you talk about especially part b, ten cohorts of 25 patients each, are those different doses as well as different dosing frequencies? And how are you treating the patients in the cohort? Are they all the same dose, all the same frequency?

Hi Ritu. It is a complicated and unusual -- complicated and unusual and, I think, very creative trial design which is designed to really nail down the optimal therapeutic window. So it probably does bear a little more explanation. David?

Yes, this is where a picture would really help, Ritu. Part a of the study is all fixed, right? We have four different dose levels of TRV130 in part a. So 25 individuals will receive doses of 1 milligram, 2 milligrams, 3 milligrams, and 4 milligrams of TRV130.

Four milligrams of morphine or placebo, and then those groups will be evaluated at the end of part a and then we'll select in part b adaptive doses of TRV130 to optimize the dose range of 130 versus morphine. To answer your question directly in part b each group of 25 individuals in that study are different individuals. Obviously you can only have two bunionectomy surgeries, one on each foot. So each group of 25 are different and they are not crossed over.

Got it. And when are you administering the -- when are you administering 130? At what point post surgically? Are you waiting a certain amount of time, or is it right on exit?

One of the big advantages to the bunionectomy surgical model is it has been refined over the last 20 year for just this purpose. So the way the surgery is done the individual has the bunionectomy surgery and they actually have a popliteal block, they have a block placed that runs a short acting sodium channel [but local] anesthetic into the nerve. And then that block is discontinued on the next day very early in the morning. The effects of that local anesthetic then wash out over the next few hours and the individual starts to feel pain. That's when the individual is evaluated for participation in the trial. They have to have at least a pain score of four out of ten to be randomized into the study.

That's the four at the next morning when the block wears off?

Correct.

Got it . I guess it is not a relevant question for the soft tissue trial because that will be on an as needed basis. What are the parameters around the doses and the potential dosing regimens that are even allowed to the patients around that trial?

We are in the process of designing that and those are some of the key questions we are considering at this point, what the optimal dose range is to go forward with and how to administer it, and in what patient population.

Got it. Thanks for the clarification.

Our next question comes from Jason Butler of JMP Securities. Please go ahead.

Hi, thanks for taking the question. I just had a follow-up on the therapeutic window concept. When you speak to physicians and other health care providers do you get feedback on what is more important, getting more efficacy, or better safety? And are different people willing to offset one of those two components for the other?

Great question. I think I will pass that over to Bob for the first response and maybe David will have a follow-up.

Thanks, Jason for the question. It is a good one. What we found in talking to both physicians and payors is a slightly different point of view. Physicians are always going to look for their number one priority increased analgesia, and they are excited about what they have seen in the early going with the product.

When probed a little deeper they also want to see that analgesia delivered with a better tolerability profile for any equal analgesic versus morphine. So they want a double-double. Payers also acknowledged that efficacy is an important attribute. I think from their point of view safety is as least as important and we see that translating more directly to an economic benefit in their system if they can get people through the system faster and out of the hospital.

That's great. Thanks. And then just one quick follow-up , in terms of the data you are seeing for faster onset of action from the Phase 1 studies, is there any mechanistic rationale as to why the drug would work faster than morphine?

Yes, there is. Mike?

The pre-clinical data indicates we have rapid distribution to the brain, and we actually saw rapid efficacy in our pre clinical models as well.

Great, thanks for taking the questions.

And our final question comes from of Biren Amin of Jeffreys. Please go ahead.

Yes, thanks for taking my questions, guys. I guess I will start off with the bunionectomy trial. Maybe if you could go over the doses you will evaluate in the part a section of the trial? Thanks.

Sure, David?

Sure. Bunionectomy study in the first part of the trial it is doses between 1 milligram and 4 milligrams and it is 1milligram, 2 milligrams, 3 milligrams, and 4 milligrams administered Q four hours. In part b we will be changing the doses of TRV130 with any degree of exactness as we like because it is an IV drug, to try and optimize the performance characteristics compared to morphine.

(inaudible - multiple speakers) could have different doses. You could go up and you could go down depending on what you see from the previous data.

So, David, I guess you are not restricted to the four doses going into part b? You will make adjustments accordingly on the part b doses?

Correct, That's right.

And then on the morphine, is it the 10 milligram dose you are evaluating in both part a and part b?

No, the typical dose of morphine to use in this model is four milligrams Q four hours. That will stay constant throughout the trial.

Got it. And then after the part a section is completed, will we get communication from the Company as to which doses you are moving forward with for part b?

No, That's not planned at this point.

Regarding the Forest transaction with Actavis, does this change Forest's thinking at all on 130? Sorry on 027.

Thought you knew something I didn't know there. We have no reason to believe that it's changed their thinking at all. We continue to have frequent and very positive interactions with the team we work with at Forest regarding the program. I guess they will have a portfolio review as these companies do when they put their portfolios together. We see no reason to believe why they would have changed their view in the program.

Great, thank you.

That concludes our Q&A session. I would like to turn it back to Maxine Gowen for closing remarks.

I will just thank you all for joining the call today. As always we are available to answer any follow on questions you would like later today. Thanks a lot, everyone.

Ladies and gentlemen, this does conclude today's conference. Thank you for your attendance. You may now disconnect. Everyone have a great day.