Good day ladies and gentlemen and welcome to the Q1 2018 Strongbridge Biopharma plc earnings conference call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will be follow at that time. [Operator Instructions]. As a reminder, this conference call is being recorded. I would now like to turn the conference over to Ms. Lindsay Rocco of Elixir Health Public Relations. Ma'am, you may begin.

Thank you and good morning everyone. We are pleased that you could join us today for Strongbridge Biopharma's first quarter 2018 earnings conference call. Joining me from Strongbridge this morning are Matthew Pauls, President and Chief Executive Officer, Dr. Fred Cohen, Chief Medical Officer and Brian Davis, Chief Financial Officer. Before we begin, I would like to remind you that during this call, the company will be making forward-looking statements that are subject to risks and uncertainties that may cause actual results to differ from the results discussed in the forward-looking statements. Reference to these risks and uncertainties are made in today's press release and disclosed in detail in the company's periodic and current event filings with the U.S. Securities and Exchange Commission. In addition, this presentation includes non-GAAP financial measures. This presentation is not intended to be a substitute for financial results presented in conformity with generally accepted accounting principles in the US. Investors and potential investors are encouraged to review the reconciliation of the pro forma financial measures included in the company's earnings release. The most directly comparable GAAP information and a reconciliation between the non-GAAP and GAAP figures are included in the company's first quarter 2018 earnings release, which has been furnished on Form 8-K. I will now turn the call over to Matthew Pauls.

Thank you Lindsay. Good morning everyone and thank you for joining us. For today's call, I will provide a high-level overview of our first quarter results, an update on near-term commercial and clinical milestones as well as our key growth objectives as we look to the second half of 2018. I will then turn the call over to Dr. Fred Cohen, our Chief Medical Officer, to discuss our clinical development progress. Brian Davis, our Chief Financial Officer, will then discuss the company's first quarter financial results. We will then open up the call for questions. With that, let me start by saying this was a highly productive first quarter for Strongbridge Biopharma. Starting with KEVEYIS, our first quarter delivered strong revenues of $3.9 million, a 30% increase over the fourth quarter of 2017. Given the trend we have seen of increased revenue quarter-over-quarter, we are increasing our full year financial guidance for KEVEYIS from $16 million to $19 million to $18 million to $20 million. Our expectation for continued strong commercial execution is reflective of current market dynamics, including progress in reaching the diagnosed Primary Periodic Paralysis or PPP patient population, efforts to identify additional undiagnosed patients and importantly, the robust clinical benefit KEVEYIS provides. I would like to highlight our genetic testing initiative known as Uncovering Periodic Paralysis, which continues to be favorably received by both patient and physician communities. We are closely monitoring scientific advances in the genetic basis of PPP and are modifying our gene testing panels accordingly. For example, we will soon be adding an additional gene known as RYR1 to the focused PPP gene panel. In terms of recent scientific exchange, we presented new analysis for KEVEYIS at the American Academy of Neurology annual meeting last month. These data help validate the overall clinical profile…

Thanks Matt and good morning everyone. On the clinical front, with regards to SONICS, a Data and Safety Monitoring Board meeting held in late April recommended that the Phase III SONICS study continue as planned with no protocol changes. The top line results for SONICS primary endpoint remain on track for midyear. As a reminder, these results will be the first ever clinical results of RECORLEV when used to treat Cushing's Syndrome patients. During our Investor and Analyst Day in April, we provided a comprehensive review of the SONICS study, including the study's design, endpoints and statistical plan. I would like to take just a few moments to review this information with you in anticipation of the upcoming results. SONICS is an open label study that consists of three phases, a dose titration phase, a six-month maintenance phase and a six-month extended evaluation phase. The latter is primarily to ascertain whether the benefit that we are seeing during the first six months is maintained throughout a full year at the therapeutic dose. The primary endpoint of SONICS is clinical responder rate as defined by the proportion of subjects enrolled who have normal 24-hour urinary free cortisol or UFC after six months of treatment in the maintenance phase without a prior dose increase during this phase. In terms of secondary endpoints, we are assessing a variety of outcomes, including other cortisol measurements in the urine, saliva and blood. And importantly, we are also looking at things like Cushing-specific clinical signs and symptoms, depression symptoms, quality of life and changes in the biomarkers of Cushing's Syndrome comorbidities, specifically, diabetes, hypertension, hypercholesterolemia and obesity. And of course, we are looking very carefully at safety and tolerability. Regarding the statistics of the trial, the predetermined sample size was 90 patients and we ended up…

Thank you Fred. For the three months ended March 31, 2018, basic and diluted net loss attributable to ordinary shareholders on a GAAP basis was $28.7 million or $0.66 per share compared to a basic net loss attributable to ordinary shareholders of $29.5 million or $0.83 per share for the same period in 2017. Net loss for the three months ended March 31, 2018 was lower than the same period in 2017, primarily due to the combination of net revenues recorded in 2018 from sales of KEVEYIS, which was launched in April of last year and a lower unrealized loss on the fair value of warrants recorded in 2018, offset in part by increased operating expenses associated with the commercialization of KEVEYIS. For the three months ended March 31, 2018, non-GAAP basic and dilutive net loss attributable to ordinary shareholders was $14.3 million or $0.33 per share compared to a non-GAAP basic and dilutive net loss attributable to ordinary shareholders of $10.4 million or $0.28 per share for the same period in 2017. The increase in non-GAAP net loss was primarily due to increased operating expenses associated with the commercialization of KEVEYIS, offset in part by net revenues recorded from KEVEYIS product sales. The company recorded net revenues from sale of KEVEYIS of $3.9 million and cost of goods sold of $700,000 for the three months ended March 31, 2018. No revenue or cost of goods sold were recognized for the same period in 2017. Research and development expenses were $4.9 million for the three months ended March 31, 2018 compared to $3.5 million for the same period in 2017. The increase during the 2018 period was primarily due to expenses related to the RECORLEV LOGICS clinical trial. Selling, general and administrative expenses were $12.4 million for the three months ended March 31, 2018 compared to $7.4 million for the same period in 2017. The increase during the 2018 period was primarily due to cost of the commercial or corporate infrastructure necessary to support ongoing commercialization of KEVEYIS. Strongbridge has $92.4 million of cash and cash equivalents and $86.5 million in outstanding debt as of March 31, 2018 compared to $57.5 million of cash and cash equivalents and $40 million in outstanding debt as of December 31, 2017. The company believes the combination of the existing cash resources and potential additional borrowings available under its credit facility will provide sufficient cash resources under its current operating plan, which includes both the commercial launch of MACRILEN and the potential U.S. regulatory approval and launch of RECORLEV to achieve consistent positive cash flows from operating activities. And operator, with that, we are now ready to open up the call for questions.

[Operator Instructions]. And our first question comes from the line of Annabel Samimy from Stifel.

Hi. Thanks for taking my question, guys. Congratulations of a good quarter. I wanted to ask you to clarify the comments you made about the powering for SONICS. I am not sure if the patients didn't titrate it, have a high higher response? Can you just explain that a little bit more in detail just so we can understand how many patients titrate, who doesn't titrate and how that affects things?

Annabel, thank you for the question. This is Matt. I will ask Fred to answer that question. Fred?

Hi. So yes, just to clarify there. So the primary endpoint, as I mentioned, is those who are normalized at the six-month time point on the mean 24-hour urinary free cortisol. But that also includes a requirement that they not have had an increase in their therapeutic dose during the six-month prior period during the maintenance phase. So as a sensitivity analysis, we will also be looking at those who did have a dose increase during that phase. So you would expect that there will be some proportion of patients who actually did require a dose increase in order to maintain a normality of UFC. This would be expected. In terms of how many to expect, I can't really give you an estimate of that right now. Again, we are blinded to all the data. So I won't even want to have sort of a guess.

Okay. I understand now. And the titration period, I imagine that's probably related to the tolerability of the drug. I know that ketoconazole, obviously, has some pretty nasty side effects, GI side effects, I think, the enantiomers have as well. Any sense of how these patients are responding? And how high the patients could titrate to at this point? And whether you have baked in some good discontinuation rates related to that?

So again, look, I can't comment on the disposition of the patients during the dose titration or in maintenance phase. We are blinded to those results. The study is well powered. We have, as I mentioned, 90% power to exclude a 20% response rate overall. During the dose-titration phase, the goal is to achieve normalization of UFC. Short of that, the secondary goal will be to achieve at least a partial clinical response. And as to what proportion are achieving that response, I don't know. We certainly would, with ketoconazole, many patients do achieve normalization, but some don't. The response can be heterogeneous. So I really can't comment more specifically on that at this point.

Okay. So it's titrating to response and not necessarily titrating limited by any adverse events?

Well, that's correct. We titrate to the clinical response. But if the patient has reached the maximum daily does, that's it, they can't go any higher. So if they haven't achieved any sort of clinical response at that point, they will have to discontinue from the study.

Okay. And if I could just squeeze one more in about MACRILEN. So what are the key rate-limiting stuffs at this point for launching MACRILEN? And are you going to be approaching the TBI market right away? Or are you first starting with just the pituitary centers and endocrinologist? And at what point can we start expecting your penetration into a broader population? Thanks.

Yes. Sure. Thanks for those questions, Annabel. With regard to MACRILEN, if you think about when we executed the deal, it was mid-January. By the time we really get it in-house, it's February, mid- to late February. And so we are just a couple of months into launch planning. We are way ahead of the game as you might expect because we started early. And really the only rate-limiting pieces to this is just us wanting to have everything lined up and make sure that when we launch, we launch flawlessly. So really the only rate limiters are us making a decision to wait until the July time frame. That's really it. And then with regard to the targets, I mean clearly, going to the pituitary centers, which we are already interacting with them as we speak. We actually regularly have inbound interest from around the country from endocrinologists, endocrinology practices, pituitary centers, institutions. Given the fact that MACRILEN is disruptive technology, it's the first and only oral drug approved by the FDA and the endocrinology community has been incredibly receptive. The TBI opportunity we are not going to wait on. That will be a market development opportunity we will pursue in parallel to the fastest, quickest, most rapid penetration of the current existing 40,000 to 60,000 AGHD assessments that take place annually. The great news is, as I mentioned earlier, the quant work that we did prior to doing the deal and then work we have done subsequent to that has just shown an improvement to us that endocrinologists are going to test more patients for AGHD because of MACRILEN's availability. They just are. They know them. They know the patients they want to test. And they are really interested in getting going on that. In parallel to that, the TBI opportunity, we are already having discussions with advocacy groups that are very keen to have their constituencies potentially assessed for AGHD. So we will be doing both in parallel.

Okay. Great. Thank you.

And our next question comes from the line of Hartaj Singh from Oppenheimer & Co. Your line is now open.

Great. Thank you. Can you hear me?

Yes. We can. Thank you, Hartaj.

Yes. Great. Thanks Matt. Apologies, if there's any background noise. I am in not a good place. On KEVEYIS, your first quarter did better than what you had expected. I know that you sure see seasonality from those therapeutic products. These days that seasonality is getting worse. Can you just talk a little bit about what you saw in the first quarter? It seems like better than even maybe you had expected. And then, what metrics do you look for, Matt, to see if the product is performing better than expected? And then, lastly, any color or thoughts on how your pricing is looking across all the patients you have on the book? Thank you.

Thank you, Hartaj. Yes. So we have said this before and we will continue to say this that when you have the first and only therapeutic approved in an ultra-rare, ultra-orphan condition like this, Primary Periodic Paralysis and you are effectively launching it, even though, Taro had launched it previously, so it's technically a relaunch. When you are organizing and structuring a market like this, an ultra-rare market, it is lumpy from quarter-to-quarter and it takes time. It just does. So I think, what we can continue to expect, we can continue to expect to see, overall, throughout the year, the market continue to grow and KEVEYIS obviously continue to grow. I do think that there are times where as you are building the market and you are identifying new opportunities and exploring those opportunities that those take time to continue to bring to fruition and mature. And I think what we saw in the first quarter was starting to see the benefits of the expanded commercial effort, including the expanded sales team, the introduction of our patient access managers. I think we are starred. We are on the front-end of the genetic screening program that we launched in October. Starting to see some of that come to fruition. But I think, again, we are working very hard every day to continue to structure and organize the market. And what we look for, quite frankly, is getting, there's no question, the market's there. We are seeing that. It is getting the market structured and organized and those of the real markers for us is creating centers of excellence and being able to get patients to physicians who understand PPP, who diagnose and treat it and try and to be able to facilitate that. That's the real upside here and the real true marker. And I think your third question was on pricing. Can you clarify that question, please?

Yes. Sorry, Matt. I mean, I know that companies are always limited by what they can get as pricing but just any thoughts on what you are looking on for pricing across patients? Or is that going in line with what you had expected when you had relaunched the product? Just any color that you can provide us for that variable of the revenue equation? Thanks.

Yes. Thanks for that. Yes, so when we acquired KEVEYIS, really this was all about us taking a leadership role in Primary Periodic Paralysis and taking on the challenge of organizing, structuring and leading the PPP market. This was not around a price-driven play at all. And we have taken one price increase since we acquired KEVEYIS. And our continued growth is really predominantly focused on penetration. So patient acquisition and retention versus price. We didn't build the investment thesis and the business case on that and that hasn't changed.

Great. And I have just one follow-up question to ask and thanks Matt for that, which is that your new genetic testing and I know that you had mentioned that the testing is sort of being asked for a lot of centers. When do you see, is it two quarters, four quarters, eight quarters? I know it's hard to some times think about these or forecast these, but when you see that starting to flow through in terms of just getting additional patients from these genetic testing? Thank you. That's my question.

Yes. Sure. No problem. So that is hard to ascertain. Effectively, we launched in October. What I can say, Hartaj, is that we have been very pleasantly surprised with the number of samples that have been submitted. And as you can imagine, those samples and those data will be helpful as we roll out our patient registry in the middle of the year and launch the first, really the first and only in the United States, Primary Periodic Paralysis patient registry. So we have been very, very happy with the utilization by the community of the genetics reading program. These are programs that take, these are not months, these are more like years where you really see significant payoff for the ecosystem. But it builds and I do think we are starting to see some of that. And a good example is this, academic institutions, for example, places where when we rolled out this program, they became much more interested in having dialogue with us about where we want to go in PPP, in KEVEYIS and the genetic screening program. So there's been really interesting byproducts to the genetic screening program above and beyond helping to diagnose and hopefully treat more PPP patients earlier.

Great. Thank you Matt. Thanks a lot.

Thank you.

And our next question comes from the line of Liisa Bayko from JMP Securities. Your line is now open.

Hi guys. Congratulations on a good quarter and thank you for taking my questions. First one just is, as you kind of approach launching MACRILEN to the marketplace, can you give us any further thoughts on pricing?

Thanks, Liisa, for the question. The short answer is, no. We are currently doing a deep dive with regard to pricing and we are really in the final stages of our pricing work. I will say that, I won't give you specifics and can't give you specifics on where we are going to land from a pricing perspective. I will say the receptivity from payors and endocrinologists and others in the ecosystem has been very positive. So that's one. And two, I will also say and I will remind you that this is disruptive technology as the first and only oral drug approved by the FDA to diagnose and potentially, help endocrinologists better treat, not with MACRILEN, but by diagnosing with MACRILEN, via MACRILEN, treatment of AGHD. And the response has been very positive. So we will have more color or clarity obviously as we get closer to July with regard to pricing.

Okay. Great. Thanks. And then one last question for me. I think you pretty well articulated that the ketoconazole sort of study that led to the European approval is really not a fair comp and benchmark for RECORLEV because that you are doing a very rigorous, controlled analytical study and that was more of a sort of a retrospective study with potentially loose definitions, et cetera. At the same time, can you maybe tell us what has your feedback or research been on the kind of profile that docs are looking for to really start reaching for MACRILEN instead of ketoconazole in terms of with the efficacy and safety profile look like? And just trying to, kind of, understand as we receive the data, like how it will be positioned relative to that other drug? Thanks.

Sure. Thanks for the questions, Liisa. Regarding RECORLEV or levoketoconazole, which, as we all know, is one half of or a single enantiomer of the racemic mixture or the off-label for Cushing's Syndrome ketoconazole. The target product profile for levoketoconazole is that it will be a potent cortisol inhibitor that will be very well characterized by two Phase 3 studies, labeled specifically for Cushing's Syndrome. And not only will it be a potent cortisol inhibitor, so the ability to really rapidly and in a sustained way manage cortisol, but it could potentially have a cardiovascular risk factor profile that's unprecedented, quite frankly, compared to the currently approved therapies and in addition, the off-label therapies currently using Cushing's Syndrome. So you think about CRP, C-reactive protein, HbA1c, blood glucose, lipids, blood pressure, weight, those are the risk factors which, by the way, are key secondary endpoints in the SONICS trial. Those are the things that are really the demise often, unfortunately, for Cushing's Syndrome patients. So when we think about RECORLEV, number one, the fact that we will have the best half of the racemic mixture, we believe, that has very well characterized into one large, long Phase 3 study, one short, placebo-controlled, randomized withdrawal study. So labeled, very well characterized, cardiovascular risk profile factors could potentially be differentiator. And we think there is also a potential just based on the profile that the liver function impact could be different from ketoconazole, not benign but different for sure. We are very assuming that. So I think that's the way we look at it and I think it's very fair to assume that a target product profile like that is reasonable. Fred, do you have any comments?

No. I think that was a great summary. Thanks.

And what are the current trends for ketoconazole in the marketplace? Because I was always surprised that how much off-label usage there is, about one-third of patients, I think, in the LA case study that you guys conducted some years ago. Is that kind of still the case or has there been any changes?

Yes. It's tough, unless you do some quantitative survey work and just get estimates. We don't really know. There was a time where Cushing's Syndrome patients who needed medicinal cortisol control therapy and this was pre the current approved therapies, it was upwards of 40% to 50%. Now there's estimates of 20% to 30%. It just depends. It's still being used, there's no question. It's being used less for a couple of reasons. One is obviously the two new approved drugs over the last few years. And second, we continue to enhance safety warnings, seems like on an annual basis. Now ketoconazole continues to becomes more and more encumbered by additional safety related warnings. And there's no real good control over ketoconazole's use in Cushing's Syndrome. I mean, no one really knows, right. There is no oversight.

Okay. Great. Thank you so much for answering my questions.

Thanks Liisa.

And our next question comes from the line of Elemer Piros from Cantor Fitzgerald. Your line is now open.

Yes. Good morning. Matt, I was wondering, if you could comment on roughly how many patients currently are on KEVEYIS? And maybe a part B to this question is, what sort of retention rate do you see over the last year? I know it's fairly early in the launch. And maybe just an additional one. If you could talk about the reimbursement cycle from the time from the script is written and to actually receive reimbursement for KEVEYIS?

Yes. So let me start in reverse. As we have said previously and thanks for the questions, Elemer, on reimbursement cycle. The great news about KEVEYIS is, number one, payor coverage continues to be a lot broad and deep and significantly wide open. So we are thrilled with that. That's one. Two, as we have said previously, the cycle time from start form before all coming in to shipment, the great news here is that this is not months, this is more like weeks. And it continues to get better. So we continue to really focus on shortening down that cycle time. So again, it's more like weeks and it is definitely not months or month. With regard to patient numbers and retention. We haven't commented on that since we started giving guidance. And I will just reiterate the fact that we took our revenue guidance up from $16 million to $19 million to $18 million to $20 million this year. So we are not giving specific patient numbers nor retention numbers.

Okay. Thank you. And maybe a MACRILEN question. What is the benchmark on the currently used tests that you would use and I presume determine a premium to those to you eventual pricing?

Well, this is a very curious thing given the fact that ITT and GST are both off-label and there are so many pieces to both of them procedurally that go into the cost structure. So we have looked at ranges of $1,000 to upwards of $3,000, depending on what are some of the side effects that they experience. You just don't know. So it's not out of line to think that ITT or GST approximately are in that range, a couple thousand dollars approximately. Again, these are estimates and we use sensitivity analysis or ranges that we have been able to kind of build out. So at that point you kind of say, okay, we have disruptive technology in MACRILEN, right. I mean, there's no question. It's incredibly more safe, more convenient and more accurate. I mean, it's just better. So we are working on it right now as we speak, Elemer, about what that premium is.

Okay. Thank you very much Matt.

You are welcome.

And this concludes our Q&A session. I will like to turn the call back to Matthew Pauls, Chief Executive Officer, for any further remarks.

Thank you everyone. As I highlighted during our recent Investor and Analyst Day, we are working every day to build a differentiated rare disease company that is making a true difference in the ecosystems that we are involved in and we are doing it the right way. We are very proud of that. As we head into an incredibly exciting and transformational time for the company, we would like to take a moment to thank all of our stakeholders who helped us to get where we are today, our dedicated employees, our trusted scientific advisors, the engaged patients and advocacy groups who keep us motivated and of course our investors who believe wholeheartedly in our vision. Thank you for joining today's call and for your continued support.

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