Transcription

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Title: Indivior Conference Call

Date: 17.08.2016

Speakers: Shaun Thaxter, Christian Heidbreder and Cary Claiborne

Conference Ref. No: EV00045519

Duration: 39:25

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Presentation

OperatorHello and welcome to today’s call. Throughout this session all participants will be in a listen-only mode, and afterwards there will be a question and answer session. Also just to remind you, this session is being recorded. Today I’m pleased to present Shaun Thaxter, CEO; please begin.

Shaun Thaxter Well, good afternoon to everyone in the UK and good morning to everyone in the US. Welcome to this call. Obviously the focus of the call is to give you the opportunity to ask questions following the positive top-line results of the phase III efficacy trial on RBP-6000, which of course is our once-a-month depot, buprenorphine, for the treatment of opioid use disorder. I’m Shaun Thaxter, CEO, and I have with me Cary Claiborne, CFO; and Christian Heidbreder, who is our Chief Scientific Officer. Christian will make a short statement, and then we will be happy to take questions.

Just before we start, I would to like to remind everybody that these are top-line results, and I’m sure you have many detailed questions that you, as well as we, are keen to have the answers to, but we don’t have the answers to many of the detailed questions at the moment because all of that analysis is to be worked on in the next months. But we’re very pleased, clearly, with where we are and very pleased to have the opportunity to share with you the information as far as we have it.

This is clearly very positive news but I should also, in the interests of fair balance, remind everybody that we still have, you know, a lot of work to do before we’re in a position to submit our NDA to the FDA. And if we do all that and keep to our current timeline, and if the FDA decides to grant a priority review status, then the earliest possible sort of approval for this would be at the end of quarter four 2017. So this is good news, and it keeps us on track with the guidance that we have given previously.

So just before Christian starts, I would like to say that, you know, we’re really starting to get a little bit of momentum going now. We’ve had a very positive outcome in the ANDA litigation; we’ve seen major legislative and regulatory change initiated by the US government that is creating a more positive future environment to enable patients to access treatment. So you can’t help but feel that this new development, drug development, is coming at a time when the environment is starting to show a lot more respect for people who are dependent on opioids as patients and creating the infrastructure to get those patients into treatment. And as a patient-focused business, we’re very pleased about that.

From a business point of view, clearly we are starting to build a strong cash position now. At the half year we published our second quarter of growth, following a couple of years of very challenging trading environment with generic competition and branded competition around the world. And we’re very pleased to be able to share that our buprenorphine Atrigel pipeline is very much on track, as is our Risperidone once a month Atrigel platform as well. So you start to wonder whether there’s a gravitational pull towards a slightly more optimistic outlook for our business as we move forwards, as we start to cross some of the risks off our list.

However, that said, I will hand you over now to Christian to talk about the focus of today’s call.

Christian HeidbrederThank you, Shaun and hi, everyone. So I’m extremely pleased to share with you today some very positive top-line results of our pivotal phase III trial of RBP-6000, our buprenorphine monthly depot. May I remind you that in this study, RBP-6000 was tested against primary endpoints and secondary endpoints. RBP-6000 achieved the primary endpoint of the cumulative distribution function of the percentage of urine samples negative for opioids, combined with self-reports negative for illicit opioid use collected from week five through week 24 of this trial. The statistical significance was very high, a p-value of less than 0.0001 for both dosage strengths versus placebo.

The secondary endpoint of treatment success was defined as any subject with at least 80% of urine samples negative for opioids, combined with self-reports negative for illicit opioid use, again from week five through week 24 of this trial. That was also achieved with very high statistical significance, a p-value again inferior to 0.0001 versus placebo.

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You may also remember that we received fast-track designation from the FDA for this product. With these phase III top-line results, we are now completely on track to complete the data analysis of this trial. And clearly a lot of work is now ahead of us between now and the first quarter of 2017, but this is totally in line with our previous guidance. We are also focusing now on the completion of the second phase III trial, which was a long-term safety extension study. I’ll give it back to Shaun now.

Shaun ThaxterOkay, well thank you Christian. So I think we will – that’s all we have to say. All the information to be communicated is in the press release. So we’ll give you the opportunity to ask questions now.

Q&A

OperatorThank you very much. Ladies and gentlemen, if you would like to ask a question please press 01 on your telephone keypads. You can withdraw your question at any time by pressing 02 to cancel. And there will now be a brief pause while questions are being registered.

And our first question comes from the line of Trung Huynh of Credit Suisse. Please go ahead, your line is now open.

Trung Huynh Hi, thanks for taking my questions. I was just wondering if you can tell us the main differences in the treatment adverse effects you’ve seen, the depot versus the film? If you can’t tell us for this particular clinical trial, could you tell us what you’ve seen in the past? And what percentage of patients have had mild and severe injection site reactions?

My second question is: are you able to tell us if you’ve seen any differences between the two different dosing regimens, the six injections of 300mg versus the two 300mg injections and four 100mg injections?

And then finally, we’ve seen antipsychotic depots take time to establish themselves in the US; is there anything Indivior is doing to prepare physicians to use this depot and change the mind-set of the American psychiatrists from, like, a pill-popping culture? Thanks very much.

Christian HeidbrederAlright, thanks a lot for the questions. Regarding your first question, regarding the adverse events and the serious adverse events: the data that we collected so far clearly indicate that the product was extremely well tolerated. We see only minor variation between placebo and the two-dose regime. For example, in terms of serious treatment-emergent adverse events, we actually had a higher incidence in the placebo group rather than the active: 5% in the placebo versus on average a 2.8% in the active groups. So the safety profile of RBP-6000, as we have seen in previous clinical trials, is very positive.

The second question regarding the dose regime, you’re absolutely right. We had the three arms in this trial: placebo; and then we had a group of patients on 300mg for two months, then staying on 300mg for an additional four months; and the third group was 300mg for two months, then shifted to 100mg for the remaining four injections or four months. Right now, it is too preliminary to actually elaborate on a potential differentiation between the two dosage strengths. You may or may not know that we actually collected 13,000 PK samples, and it is going to be very, very important now to understand the relationship between exposure levels – that is, plasma concentrations of buprenorphine – and the response rate. This is an analysis that is currently not available. We are currently working between now and the end of the year to actually perform these very detailed analyses to provide what we call a PK/PD relationship, that will allow us to understand really the relationship between, again, exposure to the product and the pharmacodynamic endpoints.

Last but not least, you may remember that we performed a very, very detailed and very complex PK receptor occupancy analysis that will allow us then to really establish a relationship between exposure, pharmacodynamic effect and receptor occupancy in the brain. So that is coming between now and the end of the year.

Regarding the third question, I think that Shaun will answer your question on the antipsychotics.

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Shaun Thaxter Yeah, I think it’s interesting that you focus on why would a depot technology be of interest here. Well, clearly diversion and misuse is, you know, an inherent part of how addicted patient populations behave. Despite our best efforts and despite the medical profession’s best efforts, you know, there’s always the subpopulation of patients who, it seems, will divert and misuse their medication. And we want to do everything that we can to create an environment and medication choices that bring that risk down as low as possible. So I think the depot will be very attractive to doctors. As you’ve already identified, the trailblazing has already been done by the antipsychotics. So I think people’s reservations about depots generally have been overcome. And doctors will be particularly motivated, because if you inject the product into the patient, of course, one would think that the patient isn’t therefore able to abuse it or divert it to anyone.

So as interesting as all of that is, of course, that’s not the exciting story here. The exciting story that we’ve just got, you know, some very positive results on is that we are looking at transforming the way that medicine is practised by being able to offer receptor blockade. And so this is a whole new scientific medical story, and you will be aware from the guidance that we’ve given for this year that we are increasing our investment in the business in educating the medical profession, you know, about blockade and the science and how this technology is expected to work. And so we are recruiting medical scientific liaisons at the moment to begin that work. So we feel that we’re very much on top of the story.

Trung Huynh Thanks very much.

Operator Thank you. Our next question comes from the line of Graham Parry of Merrill Lynch. Please go ahead, your line is now open.

Graham Parry Okay, thanks for taking my questions. So just going back to, firstly, a question on safety: Chris, the treatment discontinuations due to severe adverse events were a little bit higher, albeit in terms of absolute numbers quite low. Can you give us any colour as to what the AEs that actually caused discontinuations were, and specifically was that injection site reaction or pain?

Secondly, just following up on the question around the differences between the two dosing groups: at the moment is the plan to file both, or is the idea to try and identify the right one for filing and just file one dose?

And then thirdly, could you give us an update on your thinking or market research you have on the proportion of patients that you do think would be eligible for monthly injectable therapy due to diversion and abuse? Thank you.

Christian HeidbrederThanks again for your questions. So going back to the adverse events, and more specifically the injection site reaction, we have not seen any major concern other than those that we already identified in the previous trials; that is, a very acute pain at the time of injection that dissipates in the very, very short term, typically within two minutes after the injection. That was certainly not a reason for discontinuation. The main reason across the groups for discontinuation was related to lost to follow-up of patients, which is very typical in that patient population, especially since we took all comers in this trial. And then another typical reason is withdrawal from consent.

Second question regarding the dosing and the possibility to file both dosage forms: of course, this is the plan, this is still the plan. As I said, what is very critical now over the next few months is to understand the exposure/response relationship. And we’re currently working on analysing, as I said, more than 13,000 PK samples in order to establish that relationship.

I think that Shaun may comment on the market research.

Shaun Thaxter Yeah. I mean, we’ve previously guided to a sort of $400–700 million peak sales range, but I think you start to think that, with the stronger sustainability of our business and the resilience shown in the Suboxone film, which will give us a very strong franchise to leverage when we launch the depot, the sort of trend in the legislative environment, that you would certainly be feeling optimistic about the top end of that range.

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Interestingly enough, when we first did our market research on the Suboxone film, the market research said that we would get about a 21% market share, but we all know what happened there once doctors and patients started to experience the benefits of the products. So we take a lot of reassurance that this, from what we can see so far – and as I’ve said, for fair balance, there’s more analysis to be done and more data to be gathered as the safety trial continues – but from what we’re seeing so far, this product is behaving exactly as we would hope.

Graham ParryThank you.

OperatorThank you. Our next question comes from the line of Max Herrmann of Stifel. Please go ahead, your line is now open.

Max HerrmannThank you. Afternoon; morning in the States. Just three questions. Firstly, just wanted to understand: in terms of adverse events, you talk about severe and serious. I’m usually used to just sort of serious adverse events and the adverse events, so I just wanted to understand what the ‘severe’ treatment-related adverse events were?

And then secondly, just in terms of – you obviously have, I guess, some data you want to present at Congress or at scientific presentations, the actual absolute percentage of patients who achieved the clean urine tests.

And I wondered how that compared – if you can’t give us specific numbers, if you could say how that compared to the tablet trials that you’ve obviously previously run? Are you seeing better control of the opioid addiction compared with what you would see with the tablet?

And finally, just to get some view on your discussions currently with the payers, and what that infers with regards to pricing potentially of RBP-6000. Thank you.

Christian HeidbrederOkay. So regarding your first question on adverse events, severity versus seriousness. Seriousness, not severity, actually serves as a guide for defining regulatory reporting obligations. So serious adverse events are defined when the patient outcome is one of the following: either death, life-threatening, hospitalisation, disability or requires an intervention to prevent a permanent damage or disability. Severity is the magnitude of the adverse event, and is typically categorised in terms of mild, moderate or severe. So that’s the difference between severe versus serious, seriousness versus severity. Again, there is no reason to believe, based on all the safety data that we have seen right now, there is any area of concern on RBP-6000. As I mentioned before, some of the adverse events’ prevalence was actually significantly higher in the placebo group compared to the active groups.

Regarding presentation of the data to Congress, we are certainly going to do that but not before we have the full picture. And the full picture is going to take us several months. As I mentioned before, one main focus now will be to complete the analysis of all the TLFs in this trial; secondly, perform the pharmacokinetic analysis to establish the exposure, response and ultimately receptor occupancy relationship; and then of course the focus on the completion of the long-term safety extension study. As you know, patients have the possibility to move now, to go over to the long-term safety trial, so that we are trying to achieve, at the very least, 100 subjects exposed to RBP-6000 for at least one year.

The comparison versus the tablet is not really relevant at this stage. As you know, first of all this was not a head-to-head comparison between RBP-6000 and the tablet. Second of all it was a six-month trial, and we just don’t have comparative data. But this is certainly something that we are currently doing right now. We will try to at least historically put the RBP-6000 data into the right context. Any other comparison is quite irrelevant. There have been questions also regarding the comparison with our product versus Probuphine. We have to be very careful in establishing these comparative analyses. For example, in our trial all comers and patients seeking medication assistant treatment were welcome. It was not the case for a trial such as the Probuphine one, where basically patients had to be behaviourally stable for several months and abstinent for at least three months. So – on a sublingual dose of buprenorphine of 8mg. So the trials are completely different, and they cannot be compared.

The last question was regarding payer and pricing, and I think that Shaun will address that question.

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Shaun Thaxter Yes, we’ve been having dialogue with payers within appropriate compliance and regulatory context, of course, about the future potential for this medication. And we’re having very positive conversations. Part of that, of course, is health economics, and you will have already seen that a number of publications have come out of our Health Economics team quantifying the true cost, not only to payers but also to society, of opioid use disorder. And that, you know, payers are very receptive to this technology for all the obvious reasons.

I think that if you – we’re clearly not going to say what price we expect to charge with this, but we’ve often said before that if you took the schizophrenia depot products and the sort of range of prices that they charge and said, ‘Well, would it be reasonable to use those as an analogue and think that you might price somewhere in that range?’, I would say that would be a very reasonable thing to do. But obviously we’re not going to share what our actual price is going to be.

Max Herrmann Thank you.

OperatorOur next question comes from the line of Peter Östling of Pareto Securities. Please go ahead, your line is now open.

Peter ÖstlingOkay. Thank you for taking my questions. I have a couple of ones, if I may. Firstly, you talked about this a little bit already, but could you elaborate a little bit more about the future positioning of a product like this? What patients do you think will be most suitable to use this? Is it naïve patients, patients that has been on another product for some time and they’re stable, or any other kind of category? And also, if you can just comment on the kind of potential cannibalisation on your current business.

The next one is around the device, or the syringe or the delivery device: will you use the same device in the commercial product as the one that you now use in the phase III studies?

And my last one is: are you planning to seek approval for this product in the future on other markets also? Thank you.

Shaun ThaxterOkay. I’ll take a couple of those and then hand over to Christian. In terms of sort of positioning and exact target patient population, we don’t actually have approved labelling yet. So I can’t get ahead of myself for compliance reasons in terms of speculating too specifically. Clearly I can outline what I hope that the benefits of this product will be, and what we hope that, when we’ve completed all the analysis, the results will show. And clearly our expectation is that we will end up with a medication here that is injected into the patient once a month. So you would hope that, once the product’s injected, therefore it’s not going to be removed by the patient and therefore you’re going to be able to reassure the doctor and the patient that the patient is going to receive their correct dose of medication every day for the full month.

This reduces the potential for the product to be abused or diverted because the patient, if everything plays out correctly, won’t be able to hold the product in their hand, therefore they can’t physically give it to somebody. And, you know, clearly this is going to have many benefits to patients as well as doctors, because one of the things that patients say is they want to be protected from themselves on the days that they don’t feel like staying in treatment. They like the idea that they will be able to already have their medication on board and they’re not burdened with that responsibility. So therefore you reduce the number of the dosage administration days from 365 days a year down to 12 days a year. And that’s a very, very attractive choice for patients, we believe. And anything that works well for patients in this disease space is going to be compelling, not only to doctors and payers but also good for the community, because we’re going to see more people having more successful clinical outcomes in treatment and the reduction in diversion and misuse, which always is an unhelpful aspect of this disease space.

In terms of cannibalisation rates, again I’ve sort of made my comment on that. Clearly the more attractive this is for patients, the more patients will ask their doctors for it. And what we also know in this disease space is that it is a therapy area where, if the patients like it and the patients want it because they’re more likely to adhere to it, that doctors take that into consideration when making that decision. And I think that’s why Orexo particularly and BDSI have struggled, is because they’re not offering new choices that are attractive to patients.

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Christian Heidbreder There were two other questions that I’ll be very happy to answer, one on the syringe delivery system. Yes, the system that we used in the clinical trials will be the same that will be commercialised.

And the last question was about seeking approval in other regions than the US: yes, we are currently planning clinical development plans in other geographies. Our plan was always to wait until the top-line results of the US trial in order to optimise the clinical development plans in other parts of the world.

Peter Östling Okay, thank you.

OperatorThank you. Our next question comes from the line of Sarah Potter of Deutsche Bank. Please go ahead, your line is now open. Sarah Potter, you may go ahead and ask your question. If you have your line on mute, please unmute it and go ahead.

Sarah PotterHi, sorry about that. I was on mute. Can you hear me now?

Shaun ThaxterYeah, hi Sarah.

Sarah PotterHi. So firstly: with the health economic data, do you have everything that you need now to have full payer discussions? Or are you still waiting for more data and do you expect to generate more data over the next 12 months?

And then secondly, just on the label that you may hope to get: does the trial design allow for you to potentially get a broad label, so one for new use as well as switching of stable users? I know they just had to be induced for two weeks on the film products before, but just checking your hope that you would get a broad label?

And then finally, maybe just a financial question actually. So you have highlighted already that you are spending a little bit more now to get the medical liaison officers in: do you envisage that further investment will be needed through 2017 to launch this product? Or is the hiring and what you’re spending now going to be sufficient in the backdrop of what you already have in this space to successfully launch the product? Thank you.

Christian Heidbreder Okay, let me start with the health economics and outcomes research data, which is a very important question because in fact it was part of the clinical endpoints. This is not available right now as part of the top-line results. It is going to be part of the work over the next three to four months. There are two parts of the health economics and outcomes research data. The first part are all the endpoints, EHR endpoints that has been collected during this six-month trial. And then we will continue to collect EHR data endpoints on the long-term safety extension study so that, by the time of the NDA submission, we will have EHR data on patients that have been treated with RBP-6000 for at least one year, which – you are right, our data that are going to be critical for pricing and payer negotiations. Even more importantly, it will give us a very detailed analysis of the quality of life of these patients treated with RBP-6000 for a very extended period of time.

Your question regarding labelling, I cannot answer right now for obvious reasons. This is a question of negotiations with the FDA. The only thing I can tell you is that the trial was designed to have all comers; of course, within the context of inclusion/exclusion criteria from a clinical development perspective. But that is a significantly different patient population than most of the trials that have been conducted so far in the field. And I think that the financial questions will be answered by Cary.

Cary ClaiborneI’ll take that.

Christian Heidbreder Unless you want me to.

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Cary ClaiborneSo as Shaun indicated, we definitely have investment this year in 2016 related to pre-commercialisation activities for this. Unfortunately, you know, we’re not in a position to give any guidance for 2017, but when we do provide that guidance in the beginning of 2017, we’ll get more specific about our launch costs and pre-commercialisation. But you can rest assured there will investment again in 2017, but I can’t really get any more specific than that.

Sarah PotterThank you.

OperatorThank you. Our next question comes from the line of Paul Cuddon of Numis Securities. Please go ahead, your line is now open.

Paul CuddonGood afternoon guys, and congratulations on the results. Just two quick ones from me. Firstly, on the definition of moderate to severe patients when you’re taking all comers in the trials and quite how restrictive that might be for the kind of commercial positioning?

And secondly from a physician’s perspective, having a monthly depot versus daily tablets that may take closer monitoring: from their perspective, in light of the CARA Act and increased capacity for physicians to treat, how much more convenient for the physicians will the monthly depot be? Thank you.

Christian HeidbrederSo I’ll take the first question regarding the inclusion criteria on moderate to severe. Our population in terms of opioid misuse disorder, this is probably the broader range of the patients you may include. This was also part of negotiations we had with the Food and Drug Administration at the end of phase II meeting, when we built together, seeking their wisdom, the phase III trials, both the safety/efficacy and the long-term safety trial.

Regarding the convenience to physicians –

Shaun ThaxterYeah, I think that if you’re a physician in any disease space, you want what’s best for your patients and you want something that works very well, where the sort of efficacy and safety risk/benefit is a good trade in your judgement. And you want the patient to be able to comply and be comfortable with it long term. So I think that the once-a-month aspect of this appeals to all of those standard boilerplate things. But then when you think about our patient population specifically, you really start to say, ‘But it’s a lot more compelling than that, isn’t it?’, for a number of reasons. So let’s just consider a couple of those.

First of all, when patients divert and misuse medication, eventually someone is going to get busted and arrested by the police. And when someone gets arrested the police with narcotics, the DEA end up getting involved. And then eventually the DEA will take a visit to the physician’s office. So when you’re about the scribble on the prescribing pad, as a doctor you’re very aware that this may well end up with a visit from the DEA if the patient you’re prescribing the medication to does something that they’re not supposed to do. But being a good doctor and wanting to help people, you do everything you reasonably can to help the patient and act in good faith, but at the end of the day it’s down to the patient to comply and to not end you up in trouble. So it’s very compelling for the doctor to want to give a depot product rather than daily tablets, because it reduces the potential for them having to justify their medical practice to the DEA and law enforcement.

Above that, the adherence opportunity is very, very compelling. We know that about 50% of patients drop out of treatment in the first month to six weeks. So we think that this will have the potential to retain patents in treatment for longer, and a patient in treatment is better than a patient outside of treatment. I think most people who you talk to would agree with that.

So very important, of course, that with any medication it is provided within the framework of appropriate counselling and psychosocial support, because the medication takes away the withdrawal symptoms and the cravings but the real healing begins when the patients starts to evaluate why they are taking opioids in the first place and to address those underlying issues. So we

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would always, and have always for the last 14 years, been very strong advocates that any medication should be provided within the framework and context of psychosocial support.

Paul Cuddon Thank you.

OperatorThank you. Our next question comes from the line of Stuart Goldberg of Litespeed Partners. Please go ahead, your line is now open.

Stuart GoldbergGood morning. A couple of quick questions. Christian, for you, discontinuations: you’ve talked about lost to follow-up and withdrawal of consent. So I was wondering if you could give us a little more colour on percentage of the – if you knew or if you can give us an idea of what percentage were from those two categories?

And then second, we were talking about the antipsychotics in many different forms today. There’s supposed to be an FDA meeting and an update on RBP-7000: can you give us an update on that or anything you can on the risperidone product? Thanks.

Christian HeidbrederSure. Regarding the discontinuation rates, lost to follow-up was between 12% and 23, 24%. Subject withdrawal of consent oscillated between 18% and 20%. The discontinuation due to adverse events was very low: it was about 2% in the placebo and between 3–5% in the active groups.

Regarding the RBP-7000: yes, you are correct, we had a pre-NDA meeting with the Food and Drug Administration earlier this month. This was a very positive meeting whereby the FDA agreed with us with our NDA submission strategy across all functions, including chemistry, manufacturing and controls, clinical and regulatory.

Jamie ZimmermanHi, it’s Jamie popping on. Does that mean that we are further along in the process to partner or sell that product?

Shaun ThaxterWell, as you know, we’re in the process on that. Certainly this meeting was something that was an important part of that process and people involved in the process were keen to know the outcome, so it gives us permission to keep moving forward with that.

Jamie ZimmermanWell, congratulations guys. I think you’ve done a great – there’s a great benefit to Americans. It’s going to be a great product, it’s very exciting.

Shaun Thaxter Thank you.

Stuart GoldbergThanks, guys.

Operator Thank you. Just to remind participants, if you would like to ask a question please press 01 on your telephone keypads. You can cancel at any time by pressing 02 to cancel. We will now have a further pause while questions are being registered.

And we have not further questions on the line at this time, so I’ll return the call to our speakers for closing comments.

Shaun ThaxterOkay, well thank you very much everybody for your interest and being on the call today. Clearly we are very pleased with the results that we’ve had. Again, for fair balance, there’s still a lot of work to be done; so we want to celebrate the milestone and be

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pleased with ourselves, but at the same time not get carried away. And we look forward to continuing to share good news with you in the future. As you know, we have the top-line safety results due on the once-a-month risperidone product in quarter four; we have the next big news on the once-a-month buprenorphine in quarter one next year; and we have the Science Day in December to look forward to. So I hope that we will see many of you there, and if you get the opportunity to come and see us at one of the health care conferences between now and then or one of our roadshows, we’d be delighted to see you. So thank you very much.

OperatorThis now concludes our call. Thank you for attending; participants, you may disconnect your lines.

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