Trevena Inc (TRVN) 2014 Q2 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Trevena second-quarter 2014 earnings conference call.

(Operator Instructions)

As a reminder, this conference call is being recorded.

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

Thank you, and welcome, everyone. Thanks for joining us on today's call. With me today are Max Gowen, our CEO; Roberto Cuca, our Chief Financial Officer; Mike Lark, our Chief Scientific Officer; David Soergel, our SVP of Clinical Development; and Bob Prachar, Trevena's SVP 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 risks and uncertainties, including risks detailed from time to time in the Company's periodic reports filed with the Securities and Exchange Commission, and that we undertake no obligation to update these statements beyond today.

During today's call, Max will provide a brief overview of some 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.

Thanks, John. Good morning, everyone, and thanks to you all for joining us. We're delighted to review our recent progress, and discuss the status of the programs. We remain committed to translating our biased ligand platform into a portfolio of novel therapies that target G-protein coupled receptors, and that offer a superior therapeutic profile for patients, providers and payers.

In addition to some exciting clinical progress during the quarter, I'm also happy to share how we've continued to evolve as an Organization. As we previously discussed, in April we announced the appointment of Bob Prachar to the position of SVP of Commercial and Corporate Strategy. Bob brings a keen sense of commercial strategy, and strong experience from his previous roles at Endo, Shire and Centocor. Bob worked with us full time as a consultant beginning in mid-2013, and was instrumental in setting program strategies ahead of our IPO.

In May, we appointed John Limongelli as SVP and General Counsel. John comes to us from Cigna Corporation, where he was VP and Corporate Secretary, and brings a wealth of experience in public biopharmaceutical companies, having previously held leadership positions at Adolor and Cephalon.

In addition, we recently appointed two new members to our Board of Directors. Barbara Yanni, who recently retired as Chief Licensing Officer at Merck, brings extensive financial and corporate experience to our Board. Julie McHugh adds remarkable commercial experience from her previous roles, including COO at Endo, and President at Centocor, where she oversaw the commercialization of Remicade. These additions to our Board of Directors reflect the continued maturation of our Company as a fully integrated biopharma company, focused on delivering novel, differentiated therapies to complement or replace existing inadequate medicines.

As I briefly mentioned, the second quarter saw significant progress in all three of our clinical programs, all of which are on track with our previous guidance, poised to deliver important clinical data in the coming months. For TLB-130, we were pleased to report this morning that our ongoing Phase 2 trial in post-operative pain has progressed from stage A to stage B, and we look forward to reporting data, at the latest, by the first quarter of 2015.

TRV-734, our oral clinical candidate for the treatment of moderate to severe pain, demonstrated CNS activity after oral dosing in its first-in-human study this quarter, and is now advancing to further clinical development.

For TRV-027, the BLAST AHF trial in acute heart failure remains on track to deliver data by the end of 2015. As you may recall, this program is the subject of an option agreement we entered in 2013 with Forest Labs, now Actavis. We remain closely engaged with our colleagues at Actavis, and are benefiting from the input they provide.

I should also note the recent issuance of US patent claims covering methods of use for TRV-027, including treatment of acute heart failure. This patent complements the previously issued US patent covering the composition of matter for TRV-027 through at least 2031. Together with issued and pending patents worldwide, we believe these patents establish strong protection for the future commercialization of TRV-027.

I'm very pleased with each of these developments, and with our expert team that continues to deliver important milestones on, or ahead of, schedule. More broadly, the maturation of our portfolio highlights that our platform has proven to be a valuable engine, delivering three NCEs with positive clinical data.

Let me now turn the call over to David to provide a more detailed review of our clinical progress.

Thanks, Max. I'd like to begin with an overview of our CNS programs, starting with TRV-130.

As you may recall, we believe that TRV-130 could replace current intravenous opioids by improving their narrow therapeutic window. The term therapeutic window refers to the difference between effective doses and doses that cause adverse effects. The narrow therapeutic window of unbiased mu agonists like morphine, hydromorphone and fentanyl, makes it difficult to effectively treat patients' pain without causing complications. These side effects, including respiratory depression, nausea, vomiting, constipation, and post-operative ileus, often necessitate further medical care, and can prolong hospital stay.

Even though we spend a modest amount on IV analgesics themselves, approximately $1.3 billion in the G7, we spend nearly 4 times that amount, $5 billion, on the costs of opioid-related side effects in the US alone. We believe that a new post-op analgesic that could reduce this cost burden would be an attractive option for payers, as well as physicians.

Trevena's biased ligand platform delivered TRV-130, a new molecule that is differentiated versus morphine in pre-clinical and early clinical studies. We recently published the results from our Phase 1b experimental medicine study in the leading journal, Pain. In this healthy volunteer study, TRV-130 was more effective than morphine in evoked pain analgesia, and achieved peak effect more rapidly than a high dose of morphine.

In this study, morphine caused respiratory depression that outlasted its analgesic effects. This could lead to dangerous accumulation of carbon dioxide in the body when additional doses of morphine are given. In contrast, TRV-130 was more analgesic than morphine, but produced only a transient effect on respiration. In addition, TRV-130 exhibited better GI tolerability than morphine, fewer subjects vomited after TRV-130, and effective doses of TRV-130 produce less severe nausea than morphine.

On the heels of these exciting experimental medicine data, we announced the initiation of a two-stage Phase 2a/b study of TRV-130 in post-bunionectomy pain this May. This is a multi-center, double-blind, adaptive, placebo-controlled trial, with a goal of evaluating TRV-130's efficacy and tolerability in post-operative pain, with reference to morphine.

Approximately 400 patients will be recruited, who will undergo first metatarsal bunionectomy, and then randomized to receive TRV-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. These measures of efficacy are also appropriate for pivotal Phase 3 studies. The trial is designed to enable Phase-3 development by providing information on dose and interval ranging, while further exploring differentiation of TRV-130 versus morphine.

We announced completion of Part A of the study this morning. 150 patients were enrolled in Part A, who, after meeting entry criteria, were then randomized into the six treatment groups: placebo, morphine, or one of four doses of TRV-130. Each treatment was given every 4 hours for 48 hours. This pilot phase gave us preliminary information to guide the initial dose selection for the first cohort of the adaptive Part B of the study.

While the sample size of Part A was not intended to provide statistically robust measures, it did reveal signs of analgesic efficacy, allowing us to start Part B. In Part B, up to 10 successive cohorts of 25 patients will be randomized to two adaptive dose regimens of 130, morphine, and placebo. By the end of the trial, we expect to have optimized TRV-130's efficacy and tolerability in comparison to morphine, allowing us to prepare for Phase 3 trials. Recruitment has gone very well so far, and we expect to report top-line results from this trial in the first quarter of 2015, at the latest.

I'd now like to spend a few minutes on TRV-734, our oral follow-on to TRV-130. This molecule shares the same novel mode of action and pharmacology as TRV-130, and is intended to bring the potential benefits of TRV-130 to the treatment of acute and chronic moderate to severe pain. The opioid-related adverse events we discussed for post-operative pain are also problematic for oral opioids, although opiod-induced constipation becomes more prominent as therapy continues. Our pre-clinical studies suggest that ligand bias may improve constipation. Both TRV-734 and TRV-130 had less of an impact on GI motility than morphine and oxycodone, while producing equivalent analgesia.

In June, we reported the results of our first-time-in-human study of TRV-734 ahead of schedule. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of TRV-734 in healthy volunteers. After oral dosing, TRV-734 demonstrated dose-related increases in plasma concentration, reaching peak concentrations about an hour after dosing.

We used pupil constriction as a biomarker of analgesic efficacy in this study, as we did successfully in TRV-130's early development. At 80 milligrams and higher, TRV-734 produced noticeable effects on pupil constriction, and the range of the effects seen with oxycodone in other studies. The duration of the effect on pupil constriction was approximately 4 to 6 hours. The maximum tolerated dose in this study was 250 milligrams, and was a result of opioid-related adverse events.

Since there was no comparator on this study, we cannot yet conclude that TRV-734 differentiates from unbiased opioids like oxycodone; but the range of tolerated doses causing pupil constriction suggests that analgesic efficacy may be separable from opioid-related adverse events. In light of these data, we announced last week that we'd initiated a multiple ascending dose study of TRV-734. This study will include oxycodone, so that we can begin exploring differentiation of TRV-734 from the current market leader.

Finally, I'd like to share a brief update on TRV-027 and the ongoing BLAST AHF acute heart failure trial. As you may remember, TRV-027 acts as a vasodilator, while simultaneously increasing cardiac performance through its unique biased ligand mechanism of action. Based on pre-clinical and clinical data, we believe this may translate to benefit the three key organ systems affected in acute heart failure: the blood vessels, the kidneys, and the heart.

BLAST AHF is a Phase 2b trial of 027, a randomized, double-blind, placebo-controlled trial of TRV-027, administered along with standard of care in patients with AHF. We announced the dosing of the first patient in January. Here's where we are now: We've received health authority approval in 11 countries, and two-thirds of planned sites globally have been opened. We will continue to activate additional sites over the course of the next few months, and anticipate that the data will be available in the fourth quarter of 2015.

We expect to provide more guidance on the timing of the trial on the next quarterly call. The study design uses an innovative composite end point that captures clinical events important to patients, physicians, payers, and the FDA, including worsening heart failure, which the FDA highlighted as a potentially approvable end point at the recent serelaxin outcome.

As you've heard, we've been quite busy. We're excited about the progress with each of our programs, and we look forward to sharing more with you in future calls. Now I'll pass the call to Roberto to review our financials.

Thanks, Dave. We disclosed key financial measures earlier today in our press release, and we'll be filing full financial statements later today in our form 10-Q. For now, I'll summarize a few of the headline numbers. Net loss attributable to common shareholders at the end of the second quarter was $11.5 million, or $0.44 per share, as compared with a net loss of $4.8 million, or $6.30 per share for the second quarter of 2013.

Research and development expenses were $9 million in the second quarter of this year, versus $3.5 million in the second quarter of 2013. The increase was primarily driven by clinical research expenses associated with the January 2014 initiation of the Phase 2b study for TRV-027, and the May 2014 initiation of the Phase 2a/b study of TRV-130.

General and administrative expenses were $2.5 million for the quarter, versus $900,000 in the prior year's quarter. This increase is primarily attributable to higher employee headcount, stock option compensation expense, and public company operating costs, following the Company's January 2014 initial public offering.

Cash and cash equivalents totaled $81.6 million as of June 30, 2014. We continue to expect that this will be sufficient to fund operations through the end of 2015, and we remain on track to meet previously announced milestones for the delivery of important data from all three of our clinical programs during this time.

I'll now turn the call back to Max for closing remarks.

Thanks, Roberto. Thanks also to David. As you've heard, it's been a productive quarter for us, and I'd like to close our call with a summary of our key objectives for the next several quarters.

For TRV-130, we expect to report data from Part B of the ongoing bunionectomy study, at the latest, in the first quarter of 2015. We'll have more precise guidance for you as Part B progresses. We plan to initiate a soft tissue surgery study for TRV-130 using as-needed dosing by the end of 2014, and we'll speak more about the design of that trial next quarter.

For TRV-734, we expect to have results from the ongoing multiple ascending dose study in the first half of 2015. Again, as the trial progresses, we'll have more precise guidance for that timing.

For TRV-027, data from the Phase 2b BLAST AHF trial is expected in the second half of 2015. This data triggers Actavis's option exercise position; and if the option is exercised, we would receive a significant up-front payment, and downstream milestones and royalties.

Finally, from our platform, we expect to nominate a candidate molecule targeting the delta opioid receptor for a CNS disorder later this year. We look forward to continued progress, and to updating you on our programs over the course of the year. Thanks all of you for your interest and for your time today. We can now open the call for questions. Operator?

(Operator Instructions)

Our first question is from Alan Carr with Needham and Company.

Hi, thanks for taking my questions -- a couple of them. One of them is -- wondering if you can comment at all on the move from Part A to Part B with the TRV-130 trial. Maybe what two doses you started off with in Part B? Also, can you comment a bit -- you mentioned earlier in your prepared comments about Actavis being involved in the 027 trial. I'm wondering if you could comment on the extent that they're involved. The third is around abuse liability trial. At what point would you be thinking about doing one of those for your -- the two pain programs? Thanks.

Hi, Alan. Thanks very much for those questions. I will direct the question -- the first question about the Part A to part B on to David.

Hi Alan, thanks for your question. As we've discussed in the past, this trial is designed as an adaptive dose ranging study. We're going to be exploring a range of doses in Part B, and potentially changing doses every week. We are not providing the precise doses that we're starting off with, because that's just the starting point for the trial.

Thanks, David. I'll pick up the Actavis question. You were asking about the level of involvement in the 027 program. As you know, we have designed and are running the clinical trial. Obviously we have quite a lot of updating conversations with Actavis. I'd say where they're more involved is on the CMC side, as they are thinking about how to prepare CMC activities for later-stage development, and ultimately launch. We've also been working together on some activities which we hope might give us some additional IP coverage. Those of the real areas of working together.

On the abuse liability studies for 130 and 734, we don't currently have plans to launch those trials, those studies. We know that they do need to be done. We'll probably schedule those later on in development once we have our Phase II data.

Okay. Thanks for taking my questions.

Thank you. I'm not showing any further questions. Please proceed with any closing remarks.

Well, thank you all for joining today's call. As always, we are available to answer any other questions after the call. You can certainly direct those through John. Thanks very much, everyone.

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.