Indivior PLC (INDV) 2018 Q4 法說會逐字稿

Okay. Good morning, everybody, and welcome to the full year results for 2018 for Indivior. My name is Shaun Thaxter. I am the Chief Executive Officer, and I'm looking forward today with my colleagues, Mark Crossley, Chief Financial Officer; Javier Rodriguez, Chief Legal Officer; and Christian Heidbreder, Chief Scientific Officer to sharing with you the results from last year, our plans for this year as we continue to pursue our journey towards our vision to ensure that patients all around the world have unrestricted access to evidence-based treatments for the chronic relapsing conditions and the co- occurring disorders of addiction.

I will assume that you've read the forward-looking statements. And our agenda today is I will give an overview, then Mark will give a financial report, we'll have a legal update, and then we'll look at some new exciting scientific data on progress that's been made in our R&D and medical functions last year.

Well, clearly, 2018 was a challenging year with net revenues dropping from the prior year. This is reflecting 2 key drivers. First of all, the intensity of pressure on our SUBOXONE Film franchise in the U.S. from both the tablet sector, which had a very downward effect on pricing and rebating, and from the film sector where we had a pulse of entry of generic product from Dr. Reddy's in the middle of last year.

The second impact was, obviously, that SUBLOCADE got off to a slower-than-expected start, and I look forward to sharing with you the progress and the momentum that we're building on SUBLOCADE.

It is a tragedy that so many people continue to die from opioid overdose. The opioid epidemic continues to rage in America. But the silver lining to the cloud is that the environment, society's attitude, government legislation, regulation, the whole atmospherics in the environment are starting to shift towards being more supportive of treatment. Treatment is now seen as an important part of addressing the opioid crisis. This means that we saw across last year double-digit growth in the volume of buprenorphine medication-assisted treatment, and we believe that this growth will continue. This is a long-term problem. It is going to require a long-term solution. And it means that there's a very important role for Indivior to play in the years ahead.

Across last year, we were very disciplined and very prudent with our cash. We managed to pay off almost half of our outstanding debt, and we continued to put the other cash into investment behind our growth drivers and into -- onto the balance sheet, ending the year with $924 million of cash.

We made great progress in our pipeline. Not only did we start last year with the approval of SUBLOCADE, we also had PERSERIS approved. We had SUBOXONE tablets in China approved. And we managed to start to implement new studies that would pioneer the disease space, as R&D shifted its focus from Phase III implementation and regulatory approval into postmarketing studies, life cycle studies that will start to drive forwards our understanding of this disease space and create new science that will pave the way for further market development and further expansion of the number of patients that we'll be able to treat with SUBLOCADE. And Christian has some exciting data to share with you later in the presentation.

We have divested our rights to SUBOXONE tablet in China to help us focus on our core growth markets in the U.S.

And I also have to share with you that 2 of our early phase assets in the pipeline were discontinued. Early phase assets are always very high risk, low probability of success. And it's always very important to know when to quit on those assets and when to look at other assets, and Christian will share more about that later.

So where does this leave us for 2019 moving forward. Well, clearly, we have a lot of uncertainty about what will the true impact of generic film be on our business. We are still fighting. We're still asserting our intellectual property rights. We're going to the Supreme Court this week to see if we can continue to push on the potential generic entry next week.

Beyond that, we will continue to fight and assert our intellectual property, no matter what happens on Monday. If there is generic entry on Monday, it's very hard for us to actually predict what the erosion curves will look like. We've given you the building blocks and some analogs to help guide you and -- to how you should think about your models, and Mark will talk a little bit more about that later. So we're not able to provide full year guidance for this year.

We are, however, very pleased to share that we are issuing guidance of $50 million to $70 million on SUBLOCADE and that we have done a lot of work on our cost base to make sure that it's fit for purpose as we enter a potential phase of generic entry with an OpEx of $440 million to $460 million.

So there's 2 real key themes from 2018. We had to get ready for potential generic entry. We had to make sure that we had the right cost space, the right shape of investments. We had to make some choices, and we had to give priority to those things that will drive the greatest value. So from a growth point of view, we conserved our cash. We put it behind SUBLOCADE, we put it behind PERSERIS in the U.S. markets. In the short term, those are the major growth-driving opportunities.

The Rest of World does have potential. We have progressed our SUBLOCADE filings in some target markets. But for now, the key strategic financial role of Rest of World is to continue to generate that cash flow and to support the rest of the business as we move forwards.

I've already said, we voluntarily paid down our debt, we've reduced our operating expenses, and we are ready to launch our authorized generic, if required. So that will be done through our partner, Sandoz, and we are ready and fully prepared for launch.

So I'm very proud to be able to say that we've started the diversification of risk within our business. The fact that we have a lot of work to do on SUBLOCADE does not prevent us from also launching PERSERIS. Clearly, the main focus of our efforts and our investment and the weight and support is disproportionately behind SUBLOCADE rather than PERSERIS, but we still have enough investment in PERSERIS to able to drive the success of that product.

So we now have not only clear vision and a strong presence in -- with our addiction sciences, we now also have a behavioral health sciences group. And what this means, this is diversification, it's additional revenue growth as well as a broader scope for our business development in the future.

And I'm not sure whether everyone is aware because sometimes you say, well, why -- what's the link between schizophrenia and substance misuse? Well, 50%, not quite 50%, almost 50%, of all schizophrenic patients are also diagnosed with a substance use disorder. So if you look holistically at the patient, you actually see that there is a tremendous deal of overlap. Not something we can leverage in the short term, but as we move forwards and expand our understanding of these 2 patients and the relationship between those 2 diseases, an important growth opportunity.

Geographically, we know that we are focused in our big priority growth market, which is the U.S., but we haven't overlooked the opportunity to continue to expand our geographical global footprint. And as you know, we have sold the rights to our product in China. The idea is to shifts the whole commercial enterprise and the risk to the Chinese company. It will take us probably till the end of the year before that deal is fully executed. And I also want to make you aware that it is subject to a number of closing conditions. So one of the big closing conditions is, which -- what sort of illegal classification will the drug be given. But nevertheless, a good step towards delivering on our vision of treating patients all around the world.

So if you think about the near term, we've got some very innovative technologies. These technologies have very good efficacy, they clearly differentiate it. There are a lot of unmet needs, some of them that are obvious today. So in our U.S. core market, clearly, the focus of our effort at the moment is to establish a growth momentum, obtain penetration, let doctors who are currently in the disease state understand what the new opportunity and the new clinical benefits are that come from SUBLOCADE.

As we broaden our minds and we start to think about the medium- and the long-term, however, there are many segments of the market that are not even recognized yet, let alone developed.

Emergency rooms. You talk to any emergency room doctor, and they're just tired of seeing the same overdose patient coming in over time and time again, until one time till a day come and they don't see them anymore, very often because they overdosed and died and they didn't make it to hospital this time. Emergency rooms are crying out for something they can give to patients to help engage them with treatment before they lead them from the emergency room. That's a potential opportunity for us in the medium to longer term.

Prisoners on release. Prisoners come out of prison, and they often go back to their old drug-using ways. They use the same amount of heroin or their drug of misuse as they did before they went into prison, but their tolerance has come down and they overdose and die. Another important opportunity.

Prisoners in prison, another important opportunity. Not something that is possible to access with daily dosing because it's very difficult for the prisons to supervise that daily dosing and cope with the extra cost burden of all those extra staff and processes they need to run that. But a once monthly injection, that could be a different story.

Drug courts. There's a very big trend in the U.S. to start thinking about do we really want to keep sending as many prison -- people to prison. Is there an opportunity for a better way? Is there a technology that we could give to patients as an alternative to going to prison?

So these are not the focus of our efforts today because, clearly, we are getting on top of and making progress in generating momentum from the current prescriber base and patients in the current market. But as we think longer term, these are all future opportunities.

So I think that as we move our mind and we think about the future state, there are a lot of opportunity both for SUBLOCADE and PERSERIS that mean that we will create a sustainable organization with tremendous growth potential. And the intellectual property on these 2 technologies is long-range IP, and we continue to work on strengthening it all the time.

So fundamentally, all right, as we think, okay, we've had a really intense last 6 to 9 months in our business where naturally you get operational and you focus on what's in front of us. It's very important while we do that to recognize that the reason we're doing it is so that we can progress towards the longer-term opportunity.

We are the leader in addiction treatment. The new science that we're generating has never been generated before. We are pioneering, we are leading, we are visioning, and we are creating a future road map for the treatment of addiction medicine.

I've already spoken to the environment and how supportive that is, and I'm also very proud to say how well the employees within the organization have managed the last 6 months. It's been a very challenging environment, of course, as you get all the news. We've downsized a part of our organization. And yet, the vision and the purpose of the company continues to inspire our employees to keep driving forward despite the atmospheric noise. But we're behind all that now. Our culture is very strong, the organization is very resilient and everyone is very excited about the future opportunity.

So let's think about SUBLOCADE and PERSERIS now as 2 specific opportunities and to share with you some of the factual data as to why we are pleased with the progress that we are making.

Well, I think if you talk to opinion leaders and the wise people who've been doing this most of their careers, they would say, well, look this is really very simple. What we're trying to do in managing this patient population is we're trying to help them get off their drug of misuse. We're trying to keep them off their drugs, and then we're trying to create a life for them that is full -- filled back again with meaning and purpose. When you're trapped in the cycle of addiction, all you think about is your drugs. And you just live that every day, the short-term reward from taking the drugs. But if we can have meaning and purpose in our lives, we don't have as great a need for those drugs anymore. And SUBLOCADE provides a tremendous opportunity to help doctors as they lead patients on that journey. It's a once-a-month treatment. It's the only once-a-month treatment. It generates very sustained plasma concentrations. It blocks the subjective effects of opioids. So it is a technology, a unique technology, the only technology that offers all of these benefits that will enable the doctor to treat the patient with a product that gives that patient an opportunity to engage with the psychosocial support and the counseling, which is where the real power comes, as they start to look for meaning and purpose in their lives.

The new data you're going to see from Christian starts to suggest that we're getting a clearer idea of how long patients ought to say in treatment before they can hope to be successful in achieving abstinence.

So let's turn our attention now to some of the KPIs so that you can see the progress that's been made. While we continue to see very positive reports from patients, our access has inched up to 83%, and the prescription journey time line is being sustained at 15 to 22 days. So historically, we've shown you the graphs of the patient journey line. We're not going to do that anymore, but we will continue to report that we are maintaining our journey time lines in that range.

The dispensing yield continues to reflect the hard work that's going into the working on the prior authorizations and getting doctors' offices more competent, and we're seeing the institutionalization of the practices around the medical benefit. So we're seeing the yield continue to improve. Not yet at our target, but we're making good progress.

The healthcare prescriber base, we're seeing good progress in adoption. We're seeing progress in trial. And one of our key focus areas moving forward will be to generate greater rates of physician trial.

So let's just look at some of the specific numbers. By the end of the year, we had over 16,000 unique prescriptions initiated. This is a 50% improvement over the numbers we reported in quarter 3. With the unique patients injected, a 90% improvement. So we're really starting to see some momentum. We are not seeing the inflection point that would give us reason to believe that we're on an accelerated trajectory, but we're starting to see things move and we've building the momentum.

You can see the yield now is above 40%. And when we get to 50%, we will say, okay, we're in the range now of what everyone else has achieved after many years in the market, we're now at that 50% threshold. But as I've said before, that's our first milestone. We won't rest until we've really optimized the yield as best as we can. And that work is through the work I've described to you before with the work on the prior authorizations, the opportunity to move from medical benefit to pharmacy benefit, and we're making good, encouraging, systematic progress with that.

We've seen a 30% increase in the number of healthcare professionals who have initiated prescription journeys, a 60% increase in the number of healthcare professionals that have actually administered SUBLOCADE to patients and we've more than doubled the number of healthcare professionals that have administered to more than 5 patients. So this is really encouraging because although we would like to see a faster rate of trial, what it's showing is that when the doctors come in and they do trial, then they adopt very quickly, which is further reinforcement for the positive anecdotal reports we're getting from patients.

The repeat injection data sort of speaks for itself. Well, one of the things we're going to see in the data later is that it's starting to suggest that you get better treatment outcomes if you stay in treatment for longer. So whereas we're seeing in month sort of 4, month 5 and month 6 we're seeing that sort of retention in treatment rates are starting to tail away. When we have new science that will be a basis to say that, look, an -- a successful treatment doesn't mean that you've stopped taking your medicine because caregivers and family, they're quite happy for their patients, their sons and daughters and partners to go into treatment. But all too often, they measure the success of treatment as to when you stop taking your medicine because you don't need it anymore. And so there's a whole educational opportunity to do here. But of course, you can only do it on the back of very robust science, and we're starting to see that data.

So what are our priorities for SUBLOCADE for this year? Clearly, we want to continue with the good work and the momentum we've built with payer access quality. We want to continue to make sure that, that dispensing yield moves up towards our target of -- into the 60 to 70 range. We want to improve our commercial effectiveness. As you go through a launch, you get learning that you can incorporate to improve the effectiveness of how you communicate your messaging. We've done that with the sales force. We have a sales force meeting next week, and there's a refocus on how do we make the story more compelling and simpler to tell the doctors based on what we've learned.

We'll continue to expand the healthcare professional prescriber base. We want more trial. You will probably not be aware that over the last 2 or 3 years, there's been a huge explosion in individual physicians' offices joining networks, whether it's a hospital network or a community network or a network of other practices that are in their own specialty. These are called independent distribution networks. And often, once you sign up to a hospital group, if you want to prescribe a product like SUBLOCADE, you have to get the policy of the group changed and -- to enable you to do this because you're now a part of someone else's operating model and you're governed by their rules. There's about 100 of these, and we are targeting them. We are making good progress in getting them interested in amending their policies to allow a SUBLOCADE treatment through their networks. And this is another barrier that we will break down across the year.

As we have a very robust and far-reaching network, we will continue to build our investment in patient awareness. So we know that if the patients go to the doctor and ask for information about SUBLOCADE, that's a very positive thing. You don't want to overdo it before the doctor network is in place, but we are working on this. So we will simplify the treatment journey and continue to attract new doctors. Once we're through this phase, we will then start turning our attention to some of the market development opportunities we talked earlier, looking at emergency rooms and elsewhere. So beyond the obvious, there is future opportunity.

So let's just have a little think about PERSERIS. We're very pleased with the label that we got on PERSERIS. I think one of the more interesting things about this is that label does not recommend supplemental dosing. So PERSERIS is going to be launched into a highly competitive market. It'll be a niche play, a follower in many ways. But still we have unique differentiation that brings real value to the patient because if you're schizophrenia patient, you don't like taking your medicine. So if you can take a once-a-month injection and you don't have to take any supplemental dosing, that is a big deal if you happen to be a schizophrenia patient. It doesn't sound like much to us, but it's really meaningful to them.

We get to target dosing on the first day, and the plasma levels are sustained throughout the whole month. So I think that this is something that is going to generate a lot of interest with the physicians.

Our launch formally starts next week, but we've already had our payer teams out there. We've got access at 38%, and we're targeting comparable access with our peers so that from a managed care point of view, there's no blocks or reasons that are artificially put in the way of PERSERIS. So that whole experience should be very different to the SUBLOCADE experience because one is pioneering a new market, one is plugging into already systems. We're going to the doctors who know how to do this. We're going to the doctors who already prescribed long-acting technologies, and we're focusing on our key attributes.

So I think, as you can tell, we're quite enthusiastic about the year ahead, and look forward to it with great enthusiasm.

I will hand over now to Mark, who will take us through the financials.

Thanks, Shaun, and good morning, everyone. I'll take you through the results for 2018 and then outline our guidance for 2019.

So on the income statement, we're providing an overview of the fourth quarter and full year on an adjusted basis. As always, we've provided the full reconciliation in the appendix.

Starting with the headline numbers. Net revenue of $1.05 billion was in line with revised 2018 guidance of $990 million to $1,020 million. With net income of $272 million, it was up modestly from 2017 and ahead of our revised guidance of $230 million to $250 million. Given the challenges to the top line, the net income line shows the interventions made in relations to our cost structure, reduced finance expense and 10 point year-over-year improvement on our tax rate.

Turning first of the top line. The overall dynamics are the ones we've been discussing throughout the year. In short, benefits from double digit volume growth in the U.S., our largest market, were more than offset by a 4 percentage point decline in SUBOXONE Film share, mix impact of this portion -- disproportionate growth in the lower margin government channels and tactical rebating. Meanwhile, in the Rest of World, modest growth in Australia and Canada was essentially offset by austerity impacts and increasing competitive pressure in certain EU markets.

If we look a little more in detail at the U.S., the strong overall market growth we are seeing is largely being driven by increased federal funding to address the opioid prices in the U.S., so the year-over-year growth in state and federal Medicaid program was disproportionally higher in 2018 versus the total market growth rate. This funding has driven increased treatment capacity, which sets the stage for continued good growth in the U.S. (inaudible) markets moving forward.

Within our U.S. performance, SUBLOCADE net revenue for 2018 was $12 million, in line with our expectations outlined in late December.

If I turn next to the drivers of overall margin performance, sales deleveraging was the main driver of lower operating income and margin in 2018. Our gross margin was in line with our expectations and the range we've seen all year. The key year-over-year variance arose from channel mix as well as the ongoing production of an authorized generic version of SUBOXONE Film as a preemptive measure in the event we faced the at-risk launch by generic companies.

Looking at the operating expense components of SG&A and R&D, the story is essentially that we launched 2 new important products while taking substantial interventions to lower our cost base. And you can see here that the overall OpEx declined $41 million year-over-year, despite the significant launch investments, outlined in our 2018 guidance shared last February.

Taking into account, the offset of these increased investments, cumulative cost interventions versus plan '18 exceeded our $55 million guidance. These costs actions were taken to help protect the business from the threat of at-risk and included reductions of our global and area headquarters' teams of over 150 FTEs, a reprioritization of R&D activity and reductions in third-party and other discretionary spending.

Looking at R&D expense, the substantial declines you see here reflects the narrowing down of ongoing activities, mainly to those critical to support SUBLOCADE and PERSERIS. Additionally, as you'll have seen in the press release, we decided to terminate Arbaclofen Placarbi and ADDEX lead compound as specific challenges in each case reduced our assessment of their probability of success.

Further down the P&L, we benefited from lower net interest and tax expense. The substantial reduction in net interest was mainly driven by a combination of the favorable terms from our renegotiated loan as well as lowering outstanding principal from prepayment actions during the year.

Meanwhile, our adjusted tax rate of 15% for the year reflected the combination of both the new U.S. tax law as well as our ongoing tax planning strategies in line with our operating model.

On to cash. As Shaun said, we have strengthened our financial position significantly in 2018, exiting the year with $924 million cash despite repaying $235 million of the outstanding principal of the term loans. Our net cash position consequently improved by $305 million to $681 million.

Given the likely arrival of generic film competition, we consider it prudent to maintain our cash position to protect the business by keeping us compliant with our debt obligations and protecting our ability to invest behind SUBLOCADE and PERSERIS.

I'll briefly touch on cash conversion. The reduction in cash generated from operations in 2018 primarily reflected lower underlying operating profit, which add backs the provisions for both periods. Net cash, however, improved modestly from the combination of significantly lower net interest expense and lower tax expense. As a consequence, we've converted 90% of our adjusted operating profit into net cash, a step-up from 2017.

If I move next to guidance for 2019, I'm sure you all will recognize the substantial uncertainties we now face given likely generic competition in our largest market. The main uncertainties, of course, relate to the ultimate number of generic providers in the near term, the erosion rate of SUBOXONE Film in the U.S. and degree of success we achieve with our own authorized generic. As a consequence, we're currently not able to give you net revenue and net income guidance for 2019. We do, however, intend to provide guidance at Q1 earnings where we expect to have a better understanding of the dynamics in the evolving film market in the U.S.

For now, we've tried to be as helpful as possible by provide guidance for our OpEx base of $440 million to $460 million, as this is under our control, and net revenue guidance of $50 million to $70 million on SUBLOCADE.

Before turning to more detail on OpEx, I'd like to remind you of some of the key market and financial dynamics associated with generic entry moving forward. First, should a generic film launch, we expect the impact to be immediate and material with up to 70% loss of our share immediately and 90% loss of share up to month 12.

Second, we will launch an authorized generic to gain share of the generic market and preserve cash. With the potential for 3 or more generics launching, analogs indicate 78% to 80% off-branded price and 25% to 35% share of the generic market.

With these impacts on off revenue, there are also a number of one-off potential impacts to cash that you should take into consideration.

With declining revenues, our networking capital will drive our use of cash as sales returns and rebates provided for higher net revenue levels, primarily to government payer, are payable in the 9 to 15 months post launch of generics. With the issuance of the mandate, Indivior is subject to potential damages to DRL and Alvogen.

Additionally, we continue to be involved in advanced negotiation with that DOJ. While our best estimate of settlement remains at $483 million, you will notice that during the most recent quarter, we've shifted over $100 million from short to long term, reflecting our belief we could achieve a multiyear settlement. We expect the most recent restructuring to have another $12 million to $15 million of one-off cash impacts.

And lastly, given the refinance of debt, there is a de minimis principal payment, and we expect capital investments to be in the range of $20 million in 2019.

Shaun spoke earlier about our contingency planning, which is focused on maintaining our focus on cash generation, which, at 90% cash conversion, we've done well this year, actively managing our capital structure to provide flexibility on our debt covenants. Including the $235 million of debt reductions, we're now below the $250 million net cash offset at $243 million of principal.

We've also readied the launch of the authorized generic and completed steps that have operate -- optimized our operating structures, and I'll share a little more detail on that now.

So looking more closely at our OpEx guidance. In total, you'll see we expect to deliver savings of around $140 million this year when we compare it to our 2017 actual adjusted OpEx base of $586 million. This is despite launch investments for both SUBLOCADE and PERSERIS outlined in our 2018 guidance shared last February. This results in cumulative cost interventions versus plan 2018 of several tens of millions above our $135 million to $155 million commitment last fall.

These cost actions included reduction of our global area headquarters teams, consolidation of our R&D and medical organizations, for a total reduction, including the '18 actions, of over 300 FTEs in total. Additionally, as talked earlier, we've reprioritized R&D and completed reductions in third-party and other discretionary spending.

Such deep cost savings measures have not been easy. But as you know, the overriding principal is to ensure we preserve our ability to drive the success of SUBLOCADE and PERSERIS and maintain our minimum $250 million cash target. In this way, we believe we are best positioned to return Indivior to profitable long-term growth.

So with that financial review, I'll hand it over to Javier to update you on the legal matters.

Thank you, Mark, and good morning, everyone. By way of update on legal matters, government investigations continue, as do negotiation to resolve them, and we continue in advanced discussions with the Department of Justice.

Last week, certain Kentucky public health agencies filed suit against Indivior and several opioid pain product manufacturers, alleging misleading marketing practices in connection with the sale of opioid products in the U.S. This is the first of the national class-action opioid claims made against Indivior as part of a manufacturer group of defendants. We have not been served with the complaint. And if served, we intend to vigorously defend ourselves. However, these claims, if pursued, present civil liability risks for Indivior.

Now as you all know, on November 20, the CAFC issued a decision vacating the preliminary injunction against DRL. On December 20, Indivior filed a petition for rehearing and rehearing en banc of the decision of the CFAC. And on February 4, the CAFC denied the petition and ordered that the mandate issue on February 11. Issuance of the mandate would allow DRL to enter the market on an at-risk basis.

In response to that decision, on February 5, Indivior filed an emergency motion to stay the mandate, pending a decision on the appeal to 514 patent and a decision by the Supreme Court on Indivior's forthcoming petition for certiorari.

On February 11, the CAFC denied that motion. So we immediately responded by filing with the CFAC an emergency motion to stay the mandate, pending resolution of the forthcoming application for an administrative stay to the Supreme Court. Now that motion was also denied and the CFAC ordered that the mandate will issue on February 19.

We believe and continue to believe in the validity and forcibility of our patents. So we will file a petition with the Supreme Court to stay the mandate, pending outcome of the forthcoming petition for certiorari, seeking to overturn the CAFC's PI vacatur. Now again, if the mandate issues, we expect DRL will immediately launch on an at-risk basis.

Teva will also be in a position to launch its 16-milligram buprenorphine/naloxone film product on an at-risk basis, pursuant to an agreed stipulation whereby Teva agreed to be bound by the outcome of the litigation against DRL.

In parallel with the DRL matter, Indivior filed a temporary restraining order and preliminary injunction motion with the District Court of New Jersey against Alvogen on January 22. On January 24, Indivior was granted a 14-day temporary restraining order preventing Alvogen from using, selling or offering to sell their generic product in the U.S. and from importing the product into the U.S. Now Alvogen subsequently received FDA approval for this generic product on the same day.

The court scheduled a hearing on the PI for February 7. However, on January 31, we entered into a stipulation with Alvogen, which prevents them from launching their generic product in the U.S. unless and until a mandate issues in the DRL PI appeal. As a result, the February 7 PI hearing was canceled. We posted a bond to cover potential damages to Alvogen in the event that they ultimately prevail in the underlying litigation. As with DRL, we expect that if the DRL PI mandate issues, Alvogen will launch immediately at-risk.

So as Mark and Shaun mentioned, we intend to launch an authorized generic of SUBOXONE Film with our partner Sandoz upon confirmation of the ability of generic buprenorphine/naloxone film time to the market.

Per court order, Indivior cannot authorize the launch of a generic until the mandate in the DRL PI appeal issues. Now it's possible that other companies may also launch generic buprenorphine/naloxone film products following Indivior's launch of its authorized generic product.

Now the consolidated CAFC appeals on the 514 and 150 patent against Actavis, Teva and DRL as well as the CFAC (sic) [CAFC] appeal against Alvogen on the 514 patent are all fully briefed. The CAFC has yet to set a date for oral argument and has indicated that the appeals will all be heard at the same time.

Now in connection with the emergency motion for stay on February 5, we also filed a motion to expedite the CAFC appeal's hearing, in support of the granting of those emergency motions. DRL posed that motion, Alvogen didn't take a position and the CFAC (sic) CAFC granted that motion and ordered that the CAFC appeal on these 514 and 150 cases will be placed on the next available oral argument calendar.

Now in terms of the District Court cases, the case in Delaware against Actavis on the 305 and 454 patents has been scheduled for trial to begin on December 16. Claims construction is fully briefed, and a markman hearing is scheduled for March 6.

The New Jersey case -- the New Jersey District Court cases against DRL and Alvogen on the 305 and 454 patents have not yet been scheduled for trial, and claims constructions and markman hearing have been pended and stayed, waiting on the issuance and outcome of the DRL PI appeal.

Now for your reference, I've attached a slide that lays out certain ANDA litigation milestones in these legal proceedings, along with estimated time lines.

Thank you, and now I'll turn it over to Christian for an R&D update.

Thank you, Javier, and good morning, everyone. So I will give you an update on the R&D activities, starting with the early stage development assets, and then, of course, an update on where we are with R&D activities to support SUBLOCADE.

So early stage asset development. First, an update on Arbaclofen Placarbil. Over the last couple of years, it is very clear that we significantly improved the overall profile of Arbaclofen Placarbil through our clinical develop and reformulation plans. That said, there are some risks related to 2 main challenges with the molecule, the variability and absorption on one hand and then the enzyme converting Arbaclofen Placarbil into R-baclofen is probably more a freak in nature. And these risks must be addressed before any further development.

The development of Arbaclofen Placarbil for the indication of alcohol liver disease and cirrhosis has additional development hurdles. For example, extremely challenging patient recruitment, but also a very high level of not only morbidity in these very sick patients but morality during the conduction of the trials.

So together, if you look at the risks and, at the same time, the need to refocus our R&D priorities, we made the final recommendation to stop any further development of Arbaclofen Placarbil and rather refocus our skills towards the GABAB positive allosteric modulator family of molecules in the context of our collaboration with Addex Therapeutics.

Talking about Addex Therapeutics' collaboration and the lead molecule ADX71441. We unraveled some new risks directly linked to that particular molecule. So we do not believe that this is a so-called class issue. So we have no doubt about the validity of the molecular target that is the GABAB receptor. So the risk here is some seizure risks in a particular species that is the dog. That species is very sensitive to seizure. And unfortunately, we need to take these risks now. Even if only in one species, we need to take these risks into account in the full development plan.

So the decision is to deprioritize the development of that lead molecule, and rather refocus our skills to our backup programs. There is a significant medicinal chemistry effort currently going on in partnership with Addex Therapeutics to identify new leads and optimize these lead molecules.

C4X3256, this is our selective orexin 1 receptor antagonist. Things are progressing well there, the finalization of all the preclinical studies and the readiness to go to First-Time-in-Human.

And last but not least, our selective dopamine D3 receptor antagonist that is currently going through finalization of target validation and IND preparation.

Let me talk about SUBLOCADE. And now, first, SUBLOCADE in the U.S. You may remember that at the time of approval of SUBLOCADE in November 2017, we had several postmarketing requirement and postmarketing commitment studies.

So the postmarketing requirement, first nonclinical studies. All these studies are now completed, and all reports are due to the FDA by the second quarter of this year. Most of these reports have already been submitted to the FDA. And again, we are completing on track with the final delivery by the second quarter this year.

Postmarketing requirement, clinical studies. There are 2 studies. The draft protocols were submitted to the FDA last year. They are currently going through review with the FDA, and hopefully, we will find an agreement with the FDA by March this year in order to start these studies.

Postmarketing commitment. These are not studies, these were additional data analysis. And again, we submitted all these data analysis in May 2018, and they are currently under review by the FDA.

Life cycle evidence and generation and optimization studies. We are now channeling our focus around 4 main studies. The first one is the Epidemiology of Buprenorphine Abuse, Diversion & Misuse. We are really trying to understand here the root causes of buprenorphine misuse and the diversion into United States. A publication was released last year, and we are currently on track to release several publications on the subject.

Secondly, VOTIVE study. This stands for Virginia opioid overdose treatment initiative. As Shaun said, the current protocol in the emergency department is, of course, to resuscitate the patient and then, basically, send the patient out with a recommendation to go see a physician to treat the Opioid Use Disorder challenge. The problem is that we believe that we have a unique opportunity to actually take care of these patients and treat them -- initiate the treatment with SUBLOCADE while they are in the emergency department, and this is what this study is all about.

Thirdly, a fentanyl blockade study. Here, what we are doing is to assess whether higher plasma concentrations of buprenorphine, similar to those produced or delivered by SUBLOCADE, can actually block the respiratory depression effects of a very opioid, such as fentanyl. That study is now completed. We are currently analyzing the data, and we are targeting the final clinical study report in the third quarter this year.

Then last but not least, Global Real-World HEOR, Health Economics and Outcomes Research end points. We did a lot of studies, and I will show you a few examples on HEOR endpoints, as part of the pivotal history trials. But now that SUBLOCADE is on the market, we have an opportunity to really measure the impact of SUBLOCADE on the quality of life of our patients far beyond clinical efficacy and safety.

Talking about patient-reported outcomes. We now are working on the full data analysis of the 12 months' long-term safety extension study that was our second Phase III trial. We are also working on the RECOVER study. In December last year, we finalized the report on the 12 months' data point. And then we are pursuing the RECOVER study now up to 24 months, and we will have the last subject visit in March this year with a final and complete study report in December of this year.

In ex U.S., we received approval of SUBLOCADE in Canada on the 21st of November last year, and we filed successfully in Australia, New Zealand, Israel and Europe according to a decentralized procedure. All this has been completed by November last year. And we will dedicate a significant amount of time in 2019 to actually answer the queries from all these regulatory agencies.

Two publications I want to draw your attention to. First, the -- all the pivotal data of our Phase III placebo control study will be now available in The Lancet next week. The second one is dedicated to what is really a unique study in the world, the so-called RECOVER study. We published a few weeks ago all the design characteristics and the patient characteristics of the RECOVER study. So I encourage you to have a look at that publication.

Talking about the RECOVER study. Clearly, in a Phase III trial, we are mostly interested in those patients staying in treatment and you assess the clinical efficacy and safety of your product. But very importantly and very rarely people focus on all those subjects dropping off treatment. This is what we did with our RECOVER study. We basically followed -- this is longitudinal study, we followed patients after a specific duration of treatment with SUBLOCADE. What did we do then to try to understand what happened to these patients when they are no longer in SUBLOCADE treatment? Well, you can see a whole area of parameters that we monitored, such as mental health, physical health, housing, insurance coverage, cravings, withdrawal symptoms, drug use pattern, non-SUBLOCADE treatment when they are off SUBLOCADE, and then, of course, a whole area of health-related quality-of-life measurements.

So this slide is to give you a flavor of the pool of patients that we currently have. So you ended up with patients who were exposed to SUBLOCADE treatment for different durations. So we have a first group there of patients who received less than 2 months of treatment. Then you have a group of patients who received 3 to 5 months of SUBLOCADE treatment. A third group exposed to 6 to 11th month, and then about 50% of the pool of patient, basically, received SUBLOCADE for 12 months. And now what is fascinating with this study is that you can follow these patients after different duration of the treatment with the SUBLOCADE medication.

So we're currently analyzing all these data. You can imagine that we have hundreds of variables, but I will give you a flavor of what we are trying to achieve now with this data. And you can look, for example, at the past month's opioid abstinence by length of SUBLOCADE treatment. So for the sake of the argument, you can use as a reference those patients who were exposed to SUBLOCADE for less than 2 months and then basically compare to these patients, you can see that the odds of achieving post month abstinence is about 3x higher if you were on SUBLOCADE for 3 to 8 months. It's almost 7x higher if you were on SUBLOCADE for 9 to 12 months, and 10x higher if basically you manage to stay on SUBLOCADE for 13 to 18 months.

So I think that for the very first time, we now start understanding the impact of duration of treatment. And perhaps, now I have a much better understanding of what could be the optimal duration of treatment for patients suffering from Opioid Use Disorder.

A lot more coming in this field. As you can imagine, we are currently going through all the data analysis. And it's not over because as you have seen, the RECOVER study will be extended all the way to 24 months.

Peer review publications priorities in 2019. Clearly, a lot of focus on SUBLOCADE with all these patient-reported outcomes. Then we will look at the long-term safety, tolerability and efficacy measurements on SUBLOCADE; the full exposure-response analysis and how that actually translates to clinical endpoints; the SUBLOCADE RECOVER 12-month data points; and then we will have a focus on PERSERIS with the long-term safety, tolerability and efficacy.

And last but not least, we used a very similar approach than the one we used for SUBLOCADE by following the health-related quality of life of those patients suffering from schizophrenia and who participated in our pivotal Phase III trials.

Last but not least. Our conference presentations will focus on 4 major events. First, the AMCP Managed Care & Specialty Pharmacy Annual Meeting that will be held in San Diego at the end of March. We will be at the American Society of Addiction Medicine at the beginning of April. We will be at the American Psychiatric Association in San Francisco in the middle of May. And last but not least, we will be attending and presenting at the CPDD meeting in San Antonio. I will not go into the details, you will read that in the leaflet. But for each of these conferences, we will have a mixture of presentations in support of SUBLOCADE and PERSERIS.

Thank you very much, and back to you, Shaun.

Thank you very much, Christian. Just tantalizingly teasing and whetting our appetites with some high-level data, and there's a tremendous amount of more data to come.

So just to wrap things up then, where are we? We continue to invest in the same strategies and focus in the same areas, as we have. Our vision remains unchanged, our strategy remains the same. Yes, because of some financial constraints, we're having to narrow that strategy in some instances, but still focusing on the big growth drivers we've always believed in.

We see that we're starting to see some momentum in SUBLOCADE, still not at the point of inflection, but good progress being made. So we continue to build the resilience of our franchise, build the resilience of our assets, build the resilience of our capability as an organization. And in order to drive that through all the short-term and medium-term challenges that we have, the resilience of our culture. And I'm very proud of the commitment, the agility, and the passion that our employees still continue to show for our vision and how that translates into value creation for you, our shareholders.

We continue to develop our innovative pipeline, and by innovative pipeline, of course, we're really referring to the evidence base of the medicines.

Our vision is to ensure the patients all around the world have unrestricted access to evidence-based treatment. And it's that new evidence, it's the new science that delivers on our commitment to pioneer treatment to help transform the lives of patients, and that's what we do. And we're going to see a lot more focus in SUBLOCADE study development.

We continue to expand our global treatment. We now are going to give patients for the first time opportunity to receive treatment in China, which we're very proud of.

I -- our Rest of World business outside of the U.S. continues to be very resilient.

We have very talented people out there advocating for patients every day. And we see that business still generating very good cash flows for us.

We will selectively invest in target markets with SUBLOCADE and PERSERIS as we evaluate the opportunities and think it prudent to do so.

And we continue to develop and fortify our business. We've maintained a very strong discipline across our base business, our cash flows and our capital structure, to ensure that whilst we protect from the downside scenarios, we do maintain and retain sufficient investment to deliver on the growth drivers that we've always been committed to.

So thank you very much for participating. I'll thank my colleagues for their presentations. And very happy to take questions.

It's Graham Parry from Bank of America Merrill Lynch. And a few probably more for Mark, actually, just trying to get -- dig into the numbers a little bit here.

So on the cost allocation between the $440 million and $460 million for the year. Can you help us understand the split between SG&A and R&D, and potentially, if you can disclose it, U.S. versus ex U.S.? How much of that cost is allocated specifically to SUBLOCADE? And essentially, what I'm trying to do is help us work out what's the breakeven on SUBLOCADE? Should it not make your $1 billion target?

Secondly, could you add a bit more color to the comment you made on the sales returns and rebates and potential gross margin impacts from a generic launch on Monday.

Should it come, any mix differential you can help us with on SUBOXONE Film versus SUBLOCADE?

And then, thirdly, you have $724 million of trade payables at the end of the year. Could you just help us understand the terms of those? And the risks that they may pose to cash?

I think, that might have been more than 3, Graham.

So let's talk through the $440 million to $460 million. We don't break that out with regards to U.S., Rest of World or how much is on SUBLOCADE versus the other portions of the business, so I respect why you'd want to know that.

But it's just not a level of granularity that we give at this time. What I can say is that with the interventions we've made, both on the refi of debt, the paydown of the debt and these interventions, we feel comfortable with regards to making it through the transition period with $250 million of cash and an ability to fuel SUBLOCADE and PERSERIS both to drive growth in the out years.

As it relates to sales rebates and returns, on a move-forward basis on the brand, I wouldn't see any real change with regards to those, the generics will come in, but the rebates will stay in place to keep our place on formulary.

There has been a bit of a trend of tactical rebates moving forward. There could be some pressure there, but nothing more we think than what we've experienced in recent years.

Gross margin is a great question. I think what you'll see moving forward is that there is mix impact as we launch and authorize generic, which would be at a discount to brand, but your absolute dollars per film, well, will be the same, so you can see a contraction there, as the mix hits there.

And our Rest of World business will be larger where pricing is at a discount.

So I think you could expect somewhere between depending on where that mix ends up. You could see high single digits erosion potentially in the gross margin, 5 to high digits, somewhere in that range.

And I think the last one I had, and this is adding up to more than 3, Graham, is the $724 million of trade payables.

And I think the key one in there that I would really draw your attention to is really the $510 million that's on there in the rebates and returns.

That's the piece that will really potentially negatively impact working capital moving forward.

And I think, the way to think about that in your models is we will have a certain amount of net revenue erosion on the Film business. I think, a proportional amount of drop in those payables associated with Film, because most of those are Film, there is a small portion, that's Rest of World, $30 million to $40 million or so. And then you'll have a pickup of additional sort of working capital associated with SUBLOCADE and PERSERIS that would partially offset that.

So I think, if you work through where your revenue drop-off is and think of it as generally proportional, I think, you can get to a good spot.

Max Herrmann from Stifel. I've got 4 questions as well. Just one on SUBLOCADE, interested in understanding, how many physicians are doing the book-to-bill? And whether that's an increasing element? And how you may encourage that, just trying to understand, whether doctors are putting in fridges in their practices, and you're seeing a change in that based on making themselves more accessible to SUBLOCADE?

Secondly, just on the target physicians. I know you were looking at about 6,000 high subscribers. I think 2,430, I think you say, have now prescribed.

I'm just trying to understand that there is still a lot that happened from high subscribers are -- it's hard to understand, given the high unmet medical need in this area, why they haven't?

Third question is just in terms of retention rates, I mean, they obviously are continuing to decline from your study -- the RECOVER study, it's sort of implying that patients are being taken off treatment rather than relapsing onto -- back into abuse habits.

So just trying to understand why that number is now, I think, 35% after 6 months?

And then finally, just RECOVER study going onto that again, it seems kind of -- my understanding was that patients don't stay on treatment, and those that stay on treatment the shorter length of time, aren't they the most likely to relapse into sort of abuse treatment, so sort of -- isn't that self evident sort of part of that study?

Okay, all right. So first of all, the buy-and-bill segment of the market. Yes, we do see this is something that is growing, the Q codes came in halfway through this year. And we see the development of that sector progressing.

Clearly, it's not something we can do is to go in and persuade doctors that they should buy and bill and teach them how to do it.

That's a very much a no-go area for us for compliance reasons, but nevertheless, it is a sector that is growing. So we are seeing that building. We haven't broken it out or given specific numbers publicly, but we see that improving.

With respect to the target physicians, there's a number of things going on here.

One of the challenges, there's -- there are a number of many physicians that are part of these IDN networks, that we talked about earlier, so there is policy development work to do there. Also our clinical specialists, our clinical liaisons have been spending a lot of time helping doctors as they learn how to do this.

And as doctors get up -- the current doctors get up to speed, that will give them more time available to go and target the doctors who have not yet come into this disease space.

And we do know that you get early adopters and people who kind of wait a bit to see what everybody else is doing. And as this starts to gather the momentum, some of those doctors feel more comfortable coming in.

So we continue to work through the publications that we generate the advocacy of the new science, at clinical conferences, and this will create some more supportive environment.

We've also learned as we've gone through the year, the more persuasive way to tell the story. We've got a huge amount of science. And I think our people have got more expert in knowing which parts and elements of the science are most interesting to doctors.

And so there's a helpful effect there. So there's no one magic wand, but across the board, as you look at the various factors that help impact that.

With retention rates, one of the things that I think is very interesting, that is emerging from the RECOVER study, is this idea that if you, for many patients, if you stay in treatment longer, you're more likely to be able to achieve abstinence.

Now philosophically, with drug addiction around the world, there is this sort of inherent belief structure that you got to get off the drugs as fast as possible.

There is still this legacy thinking that while you might have come off your street drug, but now you're on another drug, so you're still on drugs, and we need to get you off all drugs as quickly as we possibly can. So that can drive a detox mentality, which may not be the best solution for many patients. Well, we've never known the answer to how long should a patient stay in treatment, so I think it's very powerful about the RECOVER study, for the first time, it's generating data that says, well, look hang on a minute, we've actually got scientific evidence here that kind of flies in the face of this sort of detox, aggressive detox philosophy, and starts to create the debate, well, how long should patients be in treatment? This data suggests that there are patients that are more likely to achieve long-term abstinence, if they have a longer period of time in treatment than a shorter period of time.

So we're not making promotional claims here that we are allowed to talk to doctors about because -- definitely not allowed to do that yet.

What we're just sharing with you is the cutting edge of the new science that is emerging that through appropriate publications and sharing through the proper processes will eventually start to shape the development of the market.

Christian, is there anything else you wanted to add on the...

No, just in addition to abstinence, which is, obviously, the focus here, I think, it's very important to look at all the others measurements that we took into account.

But that directly related to the quality-of-life. But very importantly, the employment rate, for example, it becomes very clear that all the data converge to the same point, that is if you have the chance to remain in treatment for longer period of time, you basically recover your life. You're better participant in your community, you pay taxes, because you're employed, and there is a cascade of events. And this is why we call that study the RECOVER study. It's all about recovering your life.

It's Paul Cuddon from Numis. Just 2 questions for me, firstly building on, sort of, Max's question for the number of active prescribers. And kind of getting into sales force effectiveness here. There's a big pool of potential prescribers here.

I'm asking myself questions as to kind of what proportion of your sales force have previously sold more scientific long acting medications, is that part of an issue here for the clinical liaisons. And for the reps. And perhaps you can help me with that.

Secondly, on the dynamics of the potential imminent generic film launch with tablets with likely SUBOXONE brand having longer-term value, I mean, how do you think about that potential cannibalization? And in light of Dr. Reddy's, kind of, reported issues with manufacturing Film presentation could it be a bit more resilient that we might fear.

Okay. So with respect to sales force effectiveness, we had a very thoughtful, very careful diligent approach to evaluating all of our salespeople across the year, last year.

And yes, it is true that some of our people -- salespeople, prove to be more effective in this new reality than others, where there is a different prioritization of skills. It is a more specialist job. It demands a slightly different approach. And you have some people that are very agile and they just figure out what's required and they get there themselves. Then you have the middle group of people that need a little bit of coaching and support, and then they get there. And then you've got the group of people who just really haven't made the transition and are not likely to make the transition. So we've evaluated all of our salespeople, and we did have a group of people that we have, unfortunately, had to say to those people look we're really sorry. We really like you as people. You've done a great job. You've been very passionate and committed to the vision. We're grateful for everything that you did, and you're one of the people who helped us get to where we are. And we don't believe that you're one of the people that is going to help us to get to where we need to be. So we have reengineered our sales force, and thanked the people that we don't believe are going to be sufficiently effective in the future to deliver on the vision. And for every employee in the company, it's great privilege to serve this vision and you stay and you do it for as long as you're able to help further the agenda and just for some people it meant that their phase of making that contribution was over. So we have had a performance evaluation. We have selected people who have proven that they can do this. We have said goodbye to the people that can't. We've made adjustments in the management of the sales force. We've taken the learning of how to optimize messaging and we have put additional training in. So it's very important to continue to enhance the effectiveness of the sales force and to make sure that we really understand what's going to be required to move forwards, and we've done that. We've also done some territory alignment modeling optimization, with ZS Associates. So we've really been very thoughtful about, okay, what do we know now that we've been doing this for 9 months. What changes do we need to make and how do we better position ourselves for a more successful outcome moving forward than we've had in the past? And you have to be really ruthless, where nobody likes doing it, but you have to and we've done it. The second question was with respect to the film launch. Well, I think, you know this is why it's so difficult for us to really be able to offer guidance on this, we simply don't know what the erosion curves will look like. We do know that there's potential for multiple generic entry that has huge pressures on volume. That has big pressures on price. We don't have insight into what the quality of the products will be. So any subtle movements on any of these things can have quite a big impact. So whilst we think the most likely thing that will happen is that industry analogues will apply, we simply don't know.

It's Nick Nieland from Citi. Just had a couple of questions on PERSERIS, please. So can you apply any of the learnings from the SUBLOCADE launch to smooth the rollout of PERSERIS? And given that there's an existing long-acting antipsychotic market, we do expect the launch of that product to be faster than SUBLOCADE has been this year. And dare I ask you to give us a bit of guidance for that product for 2019?

Okay, so first question what learning did we have? Well, I think, the two markets are very different. In that SUBLOCADE, we're teaching doctors to do a whole new thing and we know how difficult that can be. So it makes sense with our PERSERIS sales force rather than to go out and try and re-create that experience in schizophrenia, let's go to the doctors who are already very familiar with long-acting injectable technologies. Doctors who know the process. They already have the capability, they've learned all the billing. We didn't that choice in addiction, but we do in PERSERIS. So we do have a sales force of 50 people. So we don't have full national coverage with salespeople. We have to exercise choices. We're very happy with the people that we've chosen, and so we will launch with that level of capability. You can ask me about the guidance, we haven't given guidance for PERSERIS. But what's different about PERSERIS than SUBLOCADE is, of course, you'll be able to track the progress through IMS data. That IMS data is not available for SUBLOCADE, that's why we want to show you KPIs, that's why we want to give you as much transparency as we're able to do to help you because you do need to measure how things are going but you can do that with PERSERIS through IMS sales data. James?

It's James Vane-Tempest from Jefferies. Just one question if I can please. And that is as you've given SUBLOCADE guidance, I'm just curious what your assumptions is for pricing and the value proposition if there's a contraction in the film price. How payers might view the relative differential between SUBLOCADE versus the film in your assumptions?

Yes, we obviously anticipate that these pricing dynamics will come when we set the price for SUBLOCADE. So it's not something we think will have material impact. It's another reason why it's important to generate the health economic data, right? Because we're not trying to justify the increased price versus film, we're trying to show that in absolute terms this is a tremendous economic value. And if we do this right, no one else will have comparable data. So they'll make their decisions based off the data that they have.

I think, schizophrenia is a great analog where there's been generics there a long time on the oral side, but yet the LAI side is growing at 25% on the value. About half of that is volume, about half of that is price increases on per annum basis. So just one analog for you, James. Graham?

Just one follow up, Graham Parry from Bank of America. Could we perhaps just talk a little bit more about the shift to the pharmacy benefit from the medical benefit which you touched on, that how far through that are you? What's the prospect of in pharmacy, healthcare practitioner, administration to overcome a lot of the sort of teething issues that you've had around specialty pharmacy distributions. Is this going to go all the way that way? And is it going to help drive inflection in the future do you think?

Yes, we've got a number of accounts that have expressed an interest in moving to the pharmacy benefit. We're working through that at the moment and that's something that, as we move through the year, we think, that coverage on the pharmacy benefit will start to build. We haven't given any specific numbers around that. But that together with other measures, we think, will continue to build the yield, and we're very pleased with how the yield is progressing. We would, obviously, like it to be higher. But being realistic, we're progressing well on that measure.

Herrmann from Stifel again. Just in terms of patient retentions, going back on to this issue about whether you'll -- retention on SUBLOCADE and the film and the tablets. How much of that is from a physician trying to say well now you should abstain and try and get your life together with abstinence rather than buprenorphine or whether these patients are actually just stopping treatment entirely and just going back onto opioids. So I just, I mean, obviously...

I think, it's largely driven by the patients, where the patient's not coming back. But if you think of the pressures the patient is under, the patient is living in an environment where the expectation is you will stop taking your drugs as soon as you can, right. Well, okay, your street drugs for sure but not necessarily your medicine. But in order to be able to advocate to the patient that you ought to stay on your medicine for a given period of time. You need the science and evidence base to support that decision and to suggest that's the right thing to do. So I think, there's a broader holistic sort of environmental education and transition that needs to take place. Because if you're at home and the people you're with are expecting you to stop taking your medicine, right, that's all putting pressure on you to say, okay, I think I can do this now without my medication. So we need to really bottom out what the science is really telling us because we haven't absolutely got conclusive or anything we can really claim or say at the moment, but the indications are that there's sort of 12 to 18 months’ time period that patients benefit from being in treatment. Once we can scientifically prove that, then we can go out and share it with people. Then doctors have a basis for thinking, all right, I lose most of patients after 2 or 3 months. How can I, as a physician, now what can I do to try and keep them in treatment for longer because I know because of all this new science that if I keep them in for treatment for longer, I'm going to get better outcomes and that gives you a platform to talk to the patient, to talk to the carers and the family around that patient, ask them not to discourage their patient from coming in for their medicines because over 2 years, they are more likely to get a better outcome if they stay in for treatment for longer. Staying in treatment is a good thing not a bad thing, and they should provide the encouragement and support, so there is a very sort of real environmental education to be done. Well, this is all about the long-term future of the product. This is not about anything we're going to be saying in the coming weeks. This is really when we talk about our $1 billion potential and saying well, how do we get beyond this sort of nuts and bolts of 41%, 42% yield. And how do we start to imagine how the environment is going to involve? How do we see the progression of the evidence base and the expansion into these new market opportunities of the emergency room, prisoners on release, prisoners in drug courts. When we have all this evidence, those opportunities will come.

Okay. Well, thank you very much indeed for your continued support and interest in Indivior. We are very grateful for it and we will look forward to seeing at our events through the year. Thank you.