Indivior PLC (INDV) 2020 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Indivior PLC Full Year Results 2020 Conference Call. (Operator Instructions) I must advise you that this conference is being recorded today, Thursday, 18th of February 2021.

I would now like to hand the conference over to first speaker today, Mark Crossley. Thank you. Please go ahead.

Good morning, and good afternoon, everyone. Thank you for joining us to discuss our 2020 results and outlook. I'm joined by Ryan Preblick, our Chief Financial Officer; Christian Heidbreder, our Chief Scientific Officer; and by [Jon Wasserman], our interim External Chief Legal Officer.

We'll take the forward-looking statements as read and move to the agenda for today's discussion. I'll start with an overview of the 2020 results and then detail our strategy for which our #1 priority is realizing the full potential of SUBLOCADE on behalf of patients and stakeholders. Christian will then highlight R&D accomplishments and the progress we're making with our early stage assets. Ryan will then review the results in detail and cover the drivers of our fiscal year 2021 guidance. Then, of course, we'll open it up for Q&A.

Turning to Slide 5. I'm not going to spend a lot of time here since we preannounced our results in mid-January, but our overall fiscal year 2020 performance was very solid especially considering the challenges the team had to confront with the COVID pandemic.

Some highlights from my perspective. We saw continued adoption of SUBLOCADE, resulting in net revenue growth of over 80%, in what continued to be a difficult promotional environment. Additionally, we generated positive adjusted net income, and our ending cash balance was strong.

The strategic alignment actions that we announced at the end of Q3 2020 and that we have since completed, have fully aligned our structure with our strategy and positioned the group for sustained success. The major actions with this alignment have: one, accelerated our SUBLOCADE growth strategy with increased investment behind organized health systems; two, pivoted our R&D organization from a traditional pharmaceutical R&D model to more of a connect and develop biotech-like model focused on early-stage assets and generating evidence for SUBLOCADE and PERSERIS.

And lastly, it did have a byproduct of reducing our underlying OpEx significantly while ensuring we can fully support our growth initiatives. The net result is an organization structured to deliver on our strategic priorities and build long-term shareholder value.

Turning to the outlook. Ryan will detail our fiscal year 2021 guidance in a moment. But the takeaway for me is that we again expect to drive meaningful net revenue progression of SUBLOCADE. COVID will continue to be a factor until lockdowns ease and national vaccination programs achieve significant coverage. However, our current view is that beginning in half 2, we should start to experience greater access and in-person engagement with organized health systems and HCPs, resulting in the strong year-over-year growth Ryan will share.

Turning to our priorities. During the year, we've taken clear proactive measures to focus the group on these highest value at stake opportunities, which we think can best drive shareholder value. We believe all the building blocks are in place, the strategy, capabilities and resources, for us to be successful.

And crucially, we've delivered much greater certainty by resolving material legacy issues most notably, the DOJ and RB matters. Our focus is now 100% on executing the business.

So moving on to SUBLOCADE. It's clearly our top strategic priority and we remain confident in its peak net revenue potential. Our U.S. commercial team is through their reorganization and are invigorated and excited to be in a position to fully focus on execution. We have a clear, compelling and measurable strategy that I will now outline in more detail.

But first, I want to start by reminding everyone why we do, what we do at Indivior and why we are so passionate about our mission. Slide 7 shows the tremendous unmet need for treatment for abuse substances in the U.S., but particularly opioids.

COVID has clearly placed additional burdens on patients. Challenges to accessing treatment and stress associated with isolation have taken a further toll since the pandemic began a year ago.

While measures have been put in place to try and ease the burden on patients, overdose deaths are again rising. The U.S. government, thankfully, recognizes this trend and bipartisan efforts are ongoing to address the opioid epidemic.

The new U.S. stimulus package currently being debated includes $4 billion for substance use disorder treatment and Congress continues to consider legislation that would make access to medication-assisted treatment easier to obtain. Most importantly, the overriding intent is to continue to break down the barriers that exist to treatment and work towards normalizing OUD as a chronic recurring disease.

With an extremely low treatment penetration versus other diseases such as diabetes or heart disease, combined with increased fatal overdoses, the need for treatment has never been more urgent. Delivering on this need and breaking down the barriers to addiction treatment is at the core of everything we do at Indivior.

To step back for a moment on Slide 8. To remind everyone of our deep experience with what has become 1 of the cornerstones of medically assisted treatment, we launched the first buprenorphine based product for the opioid dependence treatment market in France in 1996, and we continue to be the leader after 25 years.

Buprenorphine was approved for the treatment of OUD in the U.S. in 2002 and is now recognized as the gold standard of evidence-based treatment for moderate to severe opioid use disorder because of its proven attributes outlined on this slide, of which I'd like to highlight just a few.

Buprenorphine stabilizes the physical needs of addiction. This means it's known to reduce cravings, withdrawals and block the rewarding effects of illicit opioids. These characteristics are important when a patient is fighting the hold of opioid addiction.

Buprenorphine is a relatively safe medication, which has a ceiling effect. Importantly, in layman terms, once reaching a moderate dose of the medication, its effects no longer increase, leading to blunting of the euphoric and rewarding effects as well as, and quite importantly, respiratory depression.

Lastly, a key item that ties this all together is that buprenorphine has a higher affinity to the mu-opioid receptor. This means that when buprenorphine has a 70% to 80% receptor occupancy, it prevents other opioids with lower affinities, such as heroin, from binding to the receptors and causing euphoria. Taken together, buprenorphine has very attractive characteristics in the OUD disease space.

Led by Christian and his team, our leadership position at Indivior derives from the combination of our deep patient and HCP understanding as well as our significant and specialized scientific expertise and knowledge of the brain disease model of behavioral disorders to deliver novel treatments for chronic and relapsing conditions and the co-morbidities of addiction. Through these efforts come successful treatments that continue to contribute meaningfully to helping patients in their journey.

On Slide 9, with SUBLOCADE, we once again have moved the OUD treatment paradigm forward by further leveraging the attractive characteristics of buprenorphine with a novel, long-acting injectable designed to maintain therapeutic dosages for the entire month. For those less familiar with the rationale underlying SUBLOCADE, by combining the profile of buprenorphine with the ATRIGEL prolonged release delivery mechanism, we are able to deliver therapeutic levels of buprenorphine of over 2 nanograms per milliliter over an entire month, resulting in a 70% receptor occupancy.

While this sounds quite scientific, the result is that SUBLOCADE provides consistent and sustained therapeutic levels of medication. No daily ups and downs, and there's no supplemental booster or rescue dosage required. Simply put, 1 treatment decision, one-time per month while blocking the euphoric effects of opioids.

When combined with the appropriate psychosocial care, SUBLOCADE can help OUD patients regain their lives. This is a transformational shift in treatment and scientific understanding, which Christian and his team continue to broaden on each day, as he will speak to later.

As with any paradigm shift in technology, it's not always an immediate path to new understanding and uptake. We are clear that SUBLOCADE requires continued new prescriber education and dissemination of the underlying science.

Additionally, we've had to consider the new prescribing behaviors and drug handling requirements for this practice-changing treatment. Nevertheless, despite the early challenges and, of course, unforeseen ones brought about by the COVID pandemic, we successfully adapted our organization to deliver the message so that we're now reaching the right target audience, which I will come to next. The net result is we're generating meaningful quarter-over-quarter net revenue growth.

On Slide 10, you'll see the strategic alignment we completed has fully focused the U.S. SUBLOCADE team on penetrating the organized health system channel. We believe our continued success in this channel will meaningfully accelerate net revenue growth moving forward. This alignment has included adding dedicated account managers to open up access across targeted organizational health systems and evolving our sales force platform with greater focus towards them as they have the necessary support network surrounding the physician to support his or her prescribing choice.

To be clear, we're not ignoring our historic core prescriber base, but rather, we're looking to accelerate strategic progress by targeting where the largest growth opportunities are. Continued health care consolidation has and is expected to continue to push more prescribers and patients into the organized care setting.

We are targeting activation of the top 500 high-value organizations. In 2020, our teams more than doubled the number of organizations that we can access and sell to with over 200. So we're making good progress, but we still have work to do to capture the full potential, and this will be a fundamental driver in the achievement of our net revenue ambitions.

It's important to note that these organizations very often contain multiple facilities that our sales force can then start opening up to SUBLOCADE once access is in place at the parental level of the organization. The sales cycle is longer because we're dealing with larger organizations that need to ensure their processes are compliant with laws, regulations and the REMS supporting an injectable Class III controlled drug across their system.

This work is worth it. Once we do become activated, our teams are able to marshal and quickly engage HCPs and initiate prescriptions.

Turning to Slide 11. We've outlined the path and milestones for achieving our $1 billion net revenue goal. First, working with third-party and internal experts, we've updated our estimate of the number of diagnosed OUD patients to just over 3 million. Our estimate is based on the absolute number of claims in the U.S. and is only 33% of those suffering from misuse of opioids in the U.S.

Second, today, we have over 29,000 unique SUBLOCADE patients or a market share at just under 1%. This compares to 17,000 a year ago. We are targeting 183,000 SUBLOCADE patients, which would put our steady-state market share goal at 6% of diagnosed patients to get to our target net revenue.

Currently, SUBLOCADE is experiencing patient treatment persistency of 5 to 6 months. And while we're continuing to generate evidence through the recovery study, the longer treatment duration leads to better abstinence rates and quality of life. This length of treatment is consistent with our planning assumptions for achieving our goal.

I'll now detail the additional building blocks that underpin our confidence in achieving our peak SUBLOCADE net revenue goal, which are centered on the continued solid underlying market growth we expect, our ability to access patients by continuing to penetrate the organized health system channel and increasing the relevance and evidence for treatment with SUBLOCADE.

Starting with the basic question and our basic assumption that this is a high-growth market, with the horrific impact of the disease on patients, family members and society, the unfortunate answer to this question is yes. And we're still only in the early stages of market development as the FDA-approved buprenorphine for OUD in 2002.

As treatment continues to normalize and MAT penetration increases, we expect continued strong underlying market growth. Legislation and further funding efforts will also help drive treatment growth. Our assumption, which is supported by market experts is that BMAT growth will continue to grow on a volume basis in the high single-digit to low double-digit range moving forward.

Second, we've completed the alignment to focus our resources on the organized health system channel. This strategy is working, and today is generating the vast majority of SUBLOCADE's growth, just over 70% exiting 2020. Here, you can see the growing percentage revenue from organized health systems as we gain penetration.

We would expect that the majority of SUBLOCADE net revenue will come from this channel as we exit 2021. Included within the organized health system strategy is the opportunity we see within the criminal justice system.

We believe SUBLOCADE's attributes of monthly rather than daily treatment decisions and its sustained efficacy are ideally suited to prisons. This opportunity is new for us. We've had success with trials in Pennsylvania, New Jersey and New Hampshire. COVID has had a disproportionate impact on access in these institutions. But as and when the pandemic begins to fade, we see a significant new opportunity for SUBLOCADE.

The other 2 elements of our SUBLOCADE strategy are outlined on Slide 14. These involve: first, increasing our ability to address the most urgent of today's challenges in the OUD space; and second, building the evidence base for the sustained treatment persistence with SUBLOCADE.

In the first instance, we filed a label extension describing buprenorphine's potential impact on fentanyl induced respiratory depression. As you know, fentanyl is a powerful synthetic opioid that's easy to manufacture and distribute. It is 50 to 100x more potent than heroin, and combined with its low cost, this has led to its entrance into the supply chain. Oftentimes, those abusing opioids don't even know that fentanyl is present in their drugs.

According to the most recent data available you see here on the left of the slide, synthetic opioids are now the leading cause of accidental opioid-related drug overdoses with almost 80% of the 59,000 involved deaths, involving synthetic opioids, mainly fentanyl. You see here the major acceleration of those fentanyl instances.

Additionally, we're focused on generating evidence, demonstrating that longer treatment may lead to better outcomes. Our proprietary long-term recovery study suggests higher levels of abstinence may be achieved with increased length of treatment. With the average length of treatment today for medically assisted treatment at 5 to 6 months, this study shows there's tremendous opportunity for an increase in abstinence rates if patients remain in treatment for 12 months, all of which is incredibly helpful to patients staying on their recovery journey.

Now turning to our progress in diversifying revenue. I'll cover off our progress with PERSERIS and plans for the OUD franchise outside the U.S., and Christian will cover milestones related to our early stage assets.

The key message with PERSERIS is that we still believe in its product profile, patient benefits and growth opportunities. As the new launch in competitive -- in a competitive and well-established market, the in-person restrictions posed by COVID really had a detrimental impact on our ability to educate HCPs and to drive more meaningful growth in 2020. That said, I'm extremely proud of the resilience of the commercial team continues to show through the pandemic.

I think a critical point and 1 which should provide you with some reassurance is that once HCPs gain experience with PERSERIS, they tend to use it quite widely, driving double-digit share in their patients. As we get into a normalizing environment, we'll be looking to potentially increase investment in a growing differentiated product.

Just to finish up on Slide 17 with our ex U.S. plans. The opportunities we are pursuing are organic only and focused on launching our OUD products in new geographies, where we believe the new products will be seen as an advantage based on their differentiation compared to the legacy tablets.

Recall that we have not historically launched film in the European Union. And of course, SUBLOCADE is as new a treatment paradigm in the rest of world as it is in the U.S.

In 2020, we saw some early success with SUBLOCADE or SUBUTEX prolonged release, as it's called in rest of world, generating $4 million of net revenue under the pressures of COVID. We expect these new products will begin to reverse the mid-single-digit erosion the rest of world business has experienced over the last 5 years.

This will allow us to return to growth in our ex U.S. business and contribute towards our revenue diversification. This will also help us in meeting our vision that patients around the world will have access to evidence-based treatment for the chronic conditions and co-occurring disorders of addiction.

So with that, I'm going to go ahead and hand over to Christian for his scientific update.

Thank you very much, Mark, and good morning, good afternoon, everyone. I will now give you a high-level update of some of our R&D activities in 2020.

And first, if you move to Slide 19, you can see some of our peer-review publication, summarizing 4 main research themes that generated new evidence in support of SUBLOCADE.

First, we confirmed the long-term safety and efficacy of SUBLOCADE after 12 months of treatment. Second, we showed that participants receiving SUBLOCADE over a 12-month period reported better health, higher medication satisfaction, increased employment and decreased health care resource utilization compared to placebo. Remember that placebo here was psychosocial counseling only.

These findings also show that patient-centered outcomes that can be measured easily may help clinicians assess their patients improvement. So again, a lot of focus on patient-reported outcomes, which, as you probably know, are scrutinized by regulatory agencies around the world, the FDA in particular.

Third, we released our 1-year data points from our RECOVER study. You may remember that RECOVER is a 2-year real-world observational study looking at long-term recovery in a cohort of people with moderate to severe opioid use disorder who used to participate in 2 of our Phase III clinical trials of SUBLOCADE.

In this study, in particular, we showed that 75% of participants who were previously treated with SUBLOCADE for 12 months, self-reported sustained opioid abstinence for the first full year of the RECOVER study versus only 24% of participants who are treated for up to 2 months only. So this data clearly suggests that long-term treatment, including counseling, may positively assist patients in focusing on their recovery, including discontinuation of illicit opioid use, improvement in health and lifestyle and reengagement with family, friends and community.

Fourth, we completed our fentanyl study. As you know, unfortunately, fatal respiratory depression is the main risk associated with opioid use and abuse. Opioid induced respiratory depression is actually driven by molecules that bind to the new opioid receptors. And such binding induces very complex changes in respiratory depression that result in breathing slowing down, becoming irregular and potentially culminating in what we call fatal apnea, which is the major cause of death in opioid overdose.

Because buprenorphine binds new opioid receptors with high affinity and slowly dissociates from the receptors, we actually hypothesized that high sustained buprenorphine plasma concentrations could actually reduce the frequency and magnitude of fentanyl induced respiratory depression. And in fact, in this study, we showed that sustained buprenorphine plasma concentrations of 2-nanogram per mil and 6-nanogram per mil were effective in reducing the frequency and magnitude of respiratory depression induced by fentanyl at doses that unfortunately caused apnea during the placebo study period.

Some of these studies now are helping us to support potential SUBLOCADE label changes. I listed here a few of these projects. There is currently 1 remaining post marketing requirement study that we are currently working on, that is looking at 2 things: First, a rapid induction that is how do you rapidly induce treatment with SUBLOCADE following a single exposure to transmucosal buprenorphine. And in the same study, we are also trying to characterize better the patient subpopulations that may benefit from the highest maintenance dose of SUBLOCADE of 300 milligram.

And thirdly, we submitted a dosage to the FDA to guide -- provide guidance as to how you transition patients who have been clinically stable on transmucosal buprenorphine onto SUBLOCADE. We also submitted additional data on our formation safety as well as the fentanyl study that I briefly described.

If you move to Slide 20, here is a brief summary of some of the work that we have done in support of PERSERIS. As you know, the Positive And Negative Syndrome Scale, what we call the PANSS scale, is a widely used psychiatric instrument aimed at assessing the core symptoms of schizophrenia. And what we have done here is to take a deeper dive into the 30 items grouped into the 3 scales, the positive, the negative and what we call the general psychopathology scales.

And so here, we provided additional data analysis, showing actually, for example, that the 120 milligram of PERSERIS was actually also effective against the negative symptoms of schizophrenia. We performed additional analysis there that we presented in different conferences last year as well as the peer-review publication that you see there that was published in the Journal of Clinical Psychopharmacology where we basically characterize the long-term safety and efficacy of SUBLOCADE over a 12-month period.

Again, on the right-hand side, you can see that we are using some of these data and new data as well to potentially have new label changes. For example, we completed a study that looked at how you transition patients who have been receiving 6 milligram of oral risperidone onto 180 milligram of PERSERIS in the form of twice 90-milligram. We also explored additional and alternate injection sites, moving away from the abdominal region and exploring back of the arm injection sites.

Last but not least, PERSERIS was approved in Canada on November 19, 2020. And as you know, this is a partnership with HLS Therapeutics.

If you move to Slide 21. This is a brief update as to where we are with our early stage assets. First, our selective OX1 receptor antagonist, INDV-2000, which, as you know, is a non-opioid strategy mechanism for the treatment of opioid use disorder.

We received an NIH HEAL Grant back in 2019 in order to perform clinical, nonclinical and pharmaceutical development activities. The FDA-approved our IND in February 2020, and we initiated our Phase I single ascending dose at the end of July 2020.

And so far, 7 cohorts of subjects has been successfully dosed. We are currently working on 8 cohort, and we hope that we will have preliminary results sometime in the third quarter this year. I'm also pleased to announce that the second year of the grant was actually awarded in September last year, which allows us to pursue the clinical, nonclinical and pharmaceutical development activities.

The second asset is INDV-1000. This is a selective GABAB Positive Allosteric Modulator that we are developing in partnership with Addex Therapeutics for the treatment of Alcohol Use Disorder. We made some significant progress there on our lead optimization program with the identification of new chemical series leading now to optimized leads that will be ready by the end of this quarter for what we call the Late Lead Optimization program, hopefully leading to some molecules that will be then ready for IND preparedness in 2022.

Finally, if you move to slide -- the next slide, you can see an overview of our conferences in 2021, you can see that it's a pretty heavy program. And 1 novelty for 2021 is that in addition to targeting the regular addiction medicine and neuroscience conferences, we are also going to expand the conference plan for audiences that are directly linked to organized health systems. So you will see our presence in these conferences as well.

And on that note, I will hand it over to Ryan, our Chief Financial Officer.

Thank you, Christian. Good morning, and good afternoon. We had a good quarter, which capped off a solid year, and we enter 2021 in a position of strength to continue to execute our strategy.

Turning to Slide 24. As Mark noted, we are pleased with our full year 2020 results, given the highly challenging backdrop the pandemic presented.

We recognized the potential impact on our business early and took decisive actions ensuring we can maintain supply of our treatments, invest to advance our leadership in U.S. addiction and deliver on our compliance and governmental commitments. As a result of our successful execution in 2020, we have the financial flexibility, cost structure and a focused strategy to drive long-term shareholder value.

I'll briefly touch on our results for the quarter and year before providing our outlook for 2021 and outlining our capital allocation priorities. As expected, our results for the quarter and year were in line with the prelim financial information we shared in mid-January.

Starting with the top line. Full year 2020 total net revenue was $647 million. The expected decline versus the prior year of 18% mainly reflects SUBOXONE share loss and the discontinuation of the AGx program in 2019. The decline was partially offset by strong net revenue progression of SUBLOCADE to $130 million, which represents an 81% increase versus full year 2019.

We are pleased that in the face of COVID-19, SUBLOCADE continued to show solid sequential growth in the back half of 2020, capping off the year with net revenue of $39 million in Q4, representing an 18% increase versus Q3. You should note that Q4 net revenue benefited from some year-end trade stocking. However, if we look at baseline dispensed volumes, SUBLOCADE was still ahead 14% sequentially, which underscores the commercial organization's commitment to the patient and its ability to adapt to the new operating environment.

Now looking at SUBOXONE Film. Average share in full year 2020 was 21% versus 32% in full year 2019. Lower share was the principal driver of the decline in total net revenue year-over-year. However, compared to full year 2019 exit share of 24%, SUBOXONE Film was resilient during the year and exited 2020 at 21%. This performance remained above our expectations, both our expectations and industry analogs, for a drug facing 4 generic competitors for a second year.

For the avoidance of doubt, we have not promoted SUBOXONE Film since 2018. And as part of our resolution with the government, we have agreed to continue as such. Rather, we believe external factors, including the addition of telemedicine with the start of OUD MAT during COVID, solid market growth and continued access by payers in the face of the pandemic, are contributing to SUBOXONE's performance.

We continue to caution that we see no structural reason that SUBOXONE will not ultimately reach share levels that are consistent with observed industry analogs. For Q4, SUBOXONE Film revenue increased versus both the prior year and sequential quarters.

Comparison versus the prior year was aided by the adverse impact in Q4 2019 of a federal law change relating to our authorized generic, which dramatically increased the mandated rebate in government channels. Having addressed this matter last year, this has an approximate $47 million negative impact on Q4 2019 net revenue. Compared with Q3 2020, Film increased 19% sequentially from stronger market growth, stocking and accrual adjustments for state Medicaid channel.

Now looking at PERSERIS, we saw net revenue of $14 million for the year, which was in line with our expectations. However, after a strong Q1, its growth, post the onset of COVID lockdowns, was relatively flat when excluding trade stocking in Q4. This dynamic is directly linked to the sharp reduction in face-to-face interactions with the HCPs which are crucial during a new launch in an established disease space.

Turning to the rest of the world business, which had a modest net revenue decline of 3%, our focus is the net revenue diversification we introduced new products -- as we introduce new products. SUBLOCADE net revenue from outside the U.S. was $4 million. Along with the approval and launch of SUBOXONE Film in the European Union and U.K., we are expecting these products to grow and become a more meaningful portion of net revenue as we look forward.

Continuing down the P&L. Gross margin of 86% for full year 2020 on an adjusted basis was within our expectation. The 400 basis point increase over 2019 on the same basis mainly reflects the discontinuation of the AGx, which carried a lower gross profit. We expect the 2021 gross margin to be lower than 2020, which I will also discuss with guidance.

Adjusted full year 2020 OpEx, which we define as SG&A and R&D combined, the $467 million we reported was in line with the expectations we communicated in our mid-January performance update. The main drivers of the lower-than-expected OpEx were COVID related impacts, chiefly tech transfer costs, which have been planned for 2020, but will now occur in 2021 and lower T&E expense.

Q4 2020 also included a favorable nonrecurring accrual adjustments for non vesting share awards. Q4 this year further benefited versus the prior year from lower SUBLOCADE marketing expenses as 2019 included DTC ad development and media placement costs. As I'll discuss in a moment, while we expect the completed strategic alignment to generate a further reduction in OpEx in full year 2021, we will be looking at opportunities to further support the growth in the U.S. business primarily SUBLOCADE.

Finally, quickly turning to the bottom line. The combination of over-delivery on key top line and expense items generated solid operating income as well as both pretax and net income for both the quarter and year.

Now turning to cash and the balance sheet on Slide 25. As you see, we ended 2020 with a gross cash balance of $858 million and net cash balance of $623 million. These amounts reflect the initial $103 million payment made in November as part of our settlement with the DOJ and net working capital changes. As a reminder, on the DOJ item, there is no payment due in 2021. Thereafter, we will make annual payments of $50 million through 2027, with a final $200 million payment due December of 2027.

Our cash performance continues to be driven by our solid operating performance, chiefly SUBLOCADE's strong growth along with the continued performance of SUBOXONE Film. This last item, in particular, is helping us maintain relatively stable net working capital where government payables are continuing to be replenished from stable SUBOXONE Film share performance in the U.S. However, we continue to caution that any acceleration in erosion of branded SUBOXONE Film will result in a material use of cash as the replenishment rate of government payables would slow.

In terms of capital allocation, our near-term priorities remain investing behind our depot technologies in the U.S., supporting the launches of SUBLOCADE and SUBOXONE Film in the rest of the world business as well as maintaining our strong financial flexibility to meet our compliance and governmental commitments.

Now turning to full year 2021 guidance on Slide 26. Our base case assumption is that health care systems will approach normality in the second half of the year as COVID vaccine programs are successfully deployed and pandemic restrictions subside. This operating backdrop should allow us to progressively resume in-person interactions with HCPs, including those in OHS.

As Mark indicated, this is critical, in particular, to communicating the transformational benefits of SUBLOCADE and to growing our new patient enrollments. In this base case scenario, we expect total net revenue of up to $625 million, including SUBLOCADE net revenue of $185 million to $210 million and PERSERIS net revenue of $17 million to $20 million.

We are also providing a downside scenario in which pandemic restrictions continue through the second half of the year, resulting in us maintaining our currently limited access to HCPs. On this basis, we could see total net revenue for the year up to $60 million lower at approximately $565 million, with SUBLOCADE and PERSERIS net revenue as low as $170 million and $15 million, respectively.

To be clear, however, this cautious scenario is not our base case, and it represents a tougher backdrop than you will see baked into other pharma companies' guidance. However, we felt it was important to give you an idea of the sensitivity should the pandemic impacts continue.

The group's total net revenue range is also informed by better-than-expected U.S. film share retention that we observed in Q4 of 2020 and which has carried through so far in 2021. On this basis, we expect film share to be relatively flat in Q1 with modest share losses anticipated in Q2 and continuing throughout 2021. We remain mindful that greater formulary scrutiny by payers could accelerate share erosion despite the worsening opioid crisis.

With regard to rest of the world, we expect the erosion rate of recent years to ease in 2021 as we gain increasing contributions from SUBLOCADE in Canada and Australia as well as the film launch in Canada and Europe. We are looking forward to SUBLOCADE reimbursement approvals and launches in additional to new European markets, including the Nordics, but expect the impact to be minimal in 2021.

Looking at gross margin expectations, we expect a transitory mid- to high single-digit decline in adjusted gross margin primarily due to current product and regional mix. We expect gross margin to return to the mid-80s in 2022 as the more profitable SUBLOCADE is expected to become an even larger portion of total net revenue.

With regard to OpEx, we expect a meaningful decrease in the underlying level compared to the $466 million for 2020. As I noted, full year 2020 OpEx was lower-than-expected due to some nonrecurring impacts in part related to COVID. The expected decline in underlying OpEx reflects the completion of the strategic alignment actions we took in Q3.

However, based on a continued net revenue upside we have realized from SUBOXONE Film since we announced those actions, we intend to deploy a portion of this over-delivery back into the business as working dollars. We are looking past the COVID pandemic and committed to support the uplift in SUBLOCADE net revenue we are seeing from the OHS channel as we work towards delivering on our growth strategy. We're also considering expanding our commercial capabilities to accelerate the penetration of PERSERIS as we get into a more normalized environment in the second half of the year.

Based on the foregoing factors and assumptions, we expect OpEx to be in the range of $420 million to $440 million, excluding possible exceptionals. The net effect implies a reduction in OpEx of 6% to 10% versus 2020 OpEx. We will continue to monitor the film business and reserve the right, if appropriate, to invest further in the growth of our LAI technologies. Considering these factors, we expect to be profitable on an adjusted pretax basis for full year 2021.

Finally, just quickly on Slide 27, in reference to Mark's discussion of our strategic priorities regarding operational excellence, you can see that we have analyzed and stayed ahead of trends to consistently adjust our cost base in line with our net revenue expectations. We have completed 3 cost programs over the last 3 years, generating real pretax savings of over $150 million, while continuing to support the growth of our new depot technologies in the U.S. and approvals and launches of new products in key geographies outside the U.S.

With that, I will hand it over to Mark for closing comments.

Thank you, Ryan. I'd like to reiterate my excitement at being CEO and my commitment to lead Indivior to future success. We've derisked the franchise. We look forward to focusing on strong execution in 2021. We have the right product, the right strategy and a structure which is fully aligned. The team has now a clear opportunity to demonstrate success and value creation with its #1 strategic priority SUBLOCADE. Execution is the sole focus for 2021.

Now I'd like to open it up to Q&A, please.

(Operator Instructions) And your first question comes from the line of Max Herrmann from Stifel.

Great. 3, if I may. Firstly, just in terms of the guidance and what's implicit in terms of market share for SUBOXONE Film in the U.S. at the end of 2021? I believe you talked about 21%, 22% share at the end of 2020, where do you see that in that guidance coming out at the end of 2021?

Secondly, just in terms of the $1 billion target, I see you talk about half the market potentially moving or being available to buprenorphine users through the OHS networks. How does that impact the potential peak sales expectations?

And then finally, just in terms of litigation, obviously, great to see the Reckitt Benckiser disputes cleared up and obviously the DOJ. I wonder whether you could outline a bit more. Are there any other risks that you see in terms of in the litigation that's still ongoing? And just update perhaps with Dr. Reddy's as well with the patent litigation.

Max, good to get your questions. I'll start with the SUBLOCADE and the litigation and then hand over to Ryan with regards to the film. As it relates to the $1 billion and our confidence with regards to that and the assumptions, I think the first thing is, you can see the strategy working.

We're continuing to expand the access to over 200 organized health systems. Enrollments are now broadly in line with pre-COVID levels and organized health systems continue to account for the majority of our growth. We've seen strong quarter-over-quarter growth, Q3 over Q2, Q4 over Q3 and expecting the easing of the headwinds on COVID.

When you look at the share assumptions, the strong market growth that's occurring in the business with low double digit, high single digit. And then you look at the support of the normalization of the disease space and with the support from Congress and the funding, we expect that to continue.

And as we continue to penetrate the organized health systems, the share expectations of getting to kind of mid-single to high single-digit shares to get to the $1 billion seem quite attainable. So that's kind of our views on that $1 billion target.

As it pertains to the litigation, I think you're right, Max. We are excited to have the 2 major overhangs behind us with regards to the DOJ resolution as well as the RB resolution.

The balance of the litigation that's out there is a bit more normal with regards to a pharma company our size, and we continue to focus on the resolution of those. We have strong defenses in them, and we'll look to continue to progress on those.

You specifically mentioned some of the ANDA work, and I know some of the procedural items on that continue to progress as we move forward. And with that, I'll hand over to Ryan as it relates to the guidance implications in film share.

So as we said in the past, with the 4 generics out there, there is nothing structurally in a market that would prevent the branded film to continue to erode in line with the analogs. And just as a reminder, we have not promoted it since 2018 and will continue not to as part of the DOJ agreement we made last year.

In regards to your question about the share and/or phasing, we plan on relatively flat share in Q1, which at this point is about 20.5%, modest share erosion in Q2. And then starting in the second half is where our planned assumption is in line with analogs for the balance of 2021 into 2022. So now that would be the color that I can give to you at this point on the film share.

And your next question comes from the line of Harry Sephton from Jefferies.

Thanks for the presentation. I'll start on SUBLOCADE. So thanks for the detail around the addressable OHS market. And you said that you're currently in around 200 of those out of the around 500 potential target.

Can you maybe give us an indication as to what you're anticipating sort of the quarterly growth in adding new OHS -- new systems each quarter. And then also, could you give us a rough idea of -- you've shown the increased penetration within those channels, but do you have an idea of your relative share of OUD patients using SUBLOCADE within the Organized Health Systems that you're currently in? That would be a great place to start.

Thanks, Harry. And we are quite proud of the fact that over the first 2 years of our pivot to the organized health that we're in those 200 and marching towards the 500. And importantly, those are the parent organization, and there's many, what we call children organizations under those that also get opened up and give us broader access to HCPs.

With the COVID overlay in the year, we've increased investment and continue to try and open up incremental organized health systems moving forward, both the parents and the children. We've not communicated a goal on that externally, but expect sort of similar growth in the year ahead from what we've experienced in the past.

With regards to the penetration on a share basis, I think within organized health systems, you don't have the same level of granularity of data that you do when you utilize a specialty pharmacy to deliver to our heritage sort of doctors' offices. And so this share becomes a bit murkier on that.

And so we think the revenue is the best sort of indication and KPI with regards to our progress. And you can see that continuing to grow, exiting the year at 38% of the overall SUBLOCADE revenue.

Okay. And maybe just to quickly touch on the specialty pharmacy distribution, since you mentioned it. Do you have any potential future models where you might look to roll out SUBLOCADE, for example, through the sort of regular pharmacy network and maybe utilize some of the sites that those pharmacies have on sites to inject patients? Or is there currently limitations within the SUBLOCADE REMS program that could potentially restrict that being a future possibility?

Yes, that's a great question, Harry, and I think it's 1 we hinted at in the Q3 results that, that these alternate injection facilities, which is what you're kind of hinting at in the -- whether it's a pharmacy network or potentially other sort of clinic environments where in schizophrenia, for example, patients are able to go there and get their injections if their primary provider don't want to do injections.

The tough part on that 1 right now is the way the laws are written, is that sort of model is not allowed. And so we're working within the government to try and talk to them about that, about that being a barrier to access to treatment. But we won't be able to really explore that unless there is a law or regulation change within the new administration.

Do you have a rough estimate of when we could maybe hear any news on potentially looking -- or the current administration, I know that they stopped some plans coming through from the previous administration, but when they might announce some new regulations coming through that could potentially expand care. Is there any timing on that?

I don't have visibility of that, Harry. I know those are actively being managed. I know President Biden was 1 of the original kind of authors of DATA 2000, so you have strong administrative support. And we look forward to partnering with them to help continue to normalize the disease space, break down barriers and increase access to treatment moving forward.

Great. And that's very helpful. Maybe just touching on the financials. I saw in the fourth quarter, your underlying administration costs are around $60 million, which compares to about $40 million in the base quarter. I guess that's quite a significant step-up. Just curious what the bridge there is?

And then maybe also tying into that, for your OpEx guidance going into this year, does that embed any potential digital marketing activities to SUBLOCADE going into the back half of the year? Or -- yes, that would be helpful if I can get some clarity on that.

So I'll start with the second and then hand it over to Ryan for the first. I mean, we have some base levels of digital marketing that we have, search engine marketing, awareness with regards to SUBLOCADE because we no longer promote the film that are always ongoing.

If you are inferring a DTC program that's a bit more robust with television and things of that nature, that effort is still not considered in any of the guidance as we continue to see the impacts of the pandemic bringing that and reservicing that when patients don't have quite the same access to their HCPs and to the organized health systems. Now it's kind of not the time to think about that, but that's something we'll reassess as we move forward and assess the market.

So with that, I'll go ahead and hand over to Ryan with regards to the admin expenses in Q4.

So in Q4, the increase from Q3 to Q4 was driven primarily by higher R&D expenses because we did mention in Q3, unfortunately, tied to COVID, we weren't able to scale up completely all of our R&D projects, the trials. So now in Q4, we were able to get some of those going again.

So that's 1 of the increases, as well as we took the opportunity to do some digital work in Q4 to set us up for a strong 2021 start. But I would like to call out, as I did in my script, there were some supply projects that we did have planned in 2020 that due to COVID we couldn't get some of the personnel out, some of those expenses will move into 2021, and those are built into my guidance, our guidance.

And your last question comes to the line of Paul Cuddon from Numis.

The first question is on your SUBLOCADE dose assumption from your 180,000 patients. I mean, that would sort of imply around 5 or 6 doses per patient per year. And I wonder how that compares to what you're seeing now from a number of doses and dose retention?

Secondly, could you just help me with SUBOXONE Film underlying Q3 to Q4 performance, stripping out the accruals in line -- so the rebate impact in '19 and accruals in 2020? And I'll have a question after that as well, but perhaps those 2 first.

Sure, Paul. And I'll start with the SUBLOCADE, and then I'll hand over to Ryan on the underlying film growth because there are some items in the base period and stuff that have some explanations.

I think when it comes to the retention and treatment on -- I think you're right, it kind of infers this 5 months or so of treatment. That's about what we're experiencing, if you look at the average retention data that's out in the market.

Now I think Christian -- I referred to and Christian spoke to our RECOVER study, which shows that on SUBLOCADE, patients' ability to maintain recovery in abstinence is enhanced considerably when they stay in treatment for 12 months. So we're continuing to share that sort of evidence base, whether doctors should take that and start to advise patients with regards to the benefits of that, which could potentially impact length of treatment, it could be beneficial moving forward. But in our planning assumptions, we've kept with kind of current experience.

Ryan, could you talk to some of the underlying dynamics with regards to the film in Q3 versus Q4?

So I'll break that down into 2 pieces. The sequential growth that we saw in film from Q3 to Q4 was primarily tied to trade stocking that occur in Q4 as well as, as we mentioned in the script, during the year, we made some accrual assumptions on channel mix. Those were trued up in Q4 as well. So those are the 2 drivers of why Q4 of this year was higher versus Q3.

And then when you look at the comparative of Q4 this year versus last year, we get the benefit because last year, when we still had the AGx, the federally mandated rebate at that point was almost 100%. And so now that we have discontinue the AGx, the re-rate went back to its normal level. And hence, you're seeing some favorability in Q4, but that's solely the reason. So it's not that it's higher volume in Q4 of this year versus last. It's simply tied to the UI.

Okay. So I mean, should I, therefore, assume that Q4 underlying ex stocking was flat on Q3? Or -- I mean, I just need sort of to know flat, up slightly, down slightly?

I would say directionally, yes. Share didn't change too much between Q3 and Q4. So on a normal basis, I would agree with that.

So which one? I gave you 3.

Well, the 1 that's relatively flat to our Q3.

Okay. And lastly, just a question, I mean, you're very specific on not promoting SUBOXONE Film. The restriction on the promotion of SUBOXONE Film, is that just for Indivior? Or is that on the brand?

It is specifically with regards to our agreement with the Department of Justice and it relates to clinical specialists and that activity within the U.S. So it's an Indivior and Department of Justice compliance agreement.

There are no further question at this time. Please continue.

With no more questions, I'd like to thank you for your continued support of Indivior and its team. We look forward to continued engagements in our 1 to 1 following the fiscal year-end earnings and then upcoming conferences regarding our role as the leaders in addiction and the excited -- exciting, excuse me, growth thesis that we have ahead of us. Thanks very much, and have a great day.

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