Thank you and welcome to our briefing on the Quarter sales. Going right into the presentation on Slide 6. You have seen that we started with strong sales growth into the current year, 10 percentage points up in pharma, very much driven by the newly launched medicines 1% in diagnostics, so 8 percentage growth. For the group you see on Slide 7, we keep a good momentum on a quarterly basis. And turning to Slide 8, we have now 27% of our pharma sales coming from the more recently launched medicines. I'm interested to highlight three of them. OCREVUS, as you know the best launch ever at Roche continues to grow strongly. HEMLIBRA, really excellent growth now also in the non-inhibitor segment where we have received recently approval in the United States that was really driving the growth there. And then lastly for TECENTRIQ, we saw very strong sales growth, very much driven by the approvals in the new indications of triple negative breast cancer and small cell lung cancer. Turning to the pipeline on Page 9, you see that we have received another two breakthrough therapy designations in the first quarter on for VENCLEXTA and an additional one for GAZYVA. It's five Spark’s concerns we expect the transaction to close this quarter still in the first half of 2019. On Slide 11, I just highlight AAN, American Academy of Neurology which is upcoming and where we will present additional data on OCREVUS, very much look forward to that. We will also show combination data, Phase III combination data for satralizumab, a combination with steroids and we also very much look forward to give you an update on risdiplam, our molecule in SMA. Now based on the strong performance in the first quarter, we expect sales now to grow in the mid single digits. So raised outlook from low to mid single digits, which we gave you earlier this year, core EPS to grow broadly in line with sales, and on that basis to further increase our dividend in Swiss francs. And just the last comment on Slide 13, you see a high number of opportunities in late stage development. Let me just confirm and point out that we expect approval for entrectinib and polatuzumab still this year. And as far as risdiplam and satralizumab is concerned we expect filing still for the current year. On that positive note, let me hand over to Bill for pharma. Thank you.

Great. So as Severin mentioned a very strong start to the year for the pharma business. You can see here that the highlights in terms of revenues 10% overall growth in constant exchange rate, 12% in Swiss francs. And it was actually quite a broad-based effect with really the only exception being a little softness in Europe based on biosimilars. But I would say even there given the rate of decline in biosimilars that the minus 6% is still a pretty strong figure. But you can see obviously with US growing at 14%, international, outside of Europe and Japan at 17% and even Japan at 7% in a challenging Japanese market, we're very pleased with what we saw as a start to the year. And looking a little deeper at the specific products, again, you can see that the top four were all newer products led by OCREVUS with a growth about two thirds over last year. And again, you can see that in the US, in Europe and international, PERJETA, which will come back to you, but again sort of broad-based strength on uptake of affinity in the early breast cancer setting. HEMLIBRA very strong, both inhibitors and non-inhibitors and then TECENTRIQ based on new approvals. I'd also highlight that you can see sort of at the bottom of the slide, you see the biosimilar impact and I think again Q1 was really living out what we've been planning for many years and talking about for many years that we plan to have our new launches, offset the impact of biosimilars and in fact that we've done that in a very strong way. So if we drill down a little bit into the therapy areas, starting with oncology, very pleased to see 7% growth in Q1 despite the biosimilar impacts led by the HER2 franchise with 7% growth. And this is really to two main effects which is that the uptake of PERJETA and adjuvant setting, but also KADCYLA which is a newer phenomenon based on the KATHERINE’s data in patients who had failed in new additive therapy that finding that patients who got KADCYLA did better than patients on Herceptin and standard of care. And we saw early uptake of that spontaneous drug the head of the approval which we expect in the US shortly. Moving down to the other franchise, again, you can see strengthen with Avastin, which was partly due to newer indications like ovarian cancer, but also due to use of Avastin in combination with TECENTRIQ primarily in lung cancer. WE have a number of other indications that we're pursuing with Avastin into TECENTRIQ. So it's encouraging to see that. And then Hematology, will talk about a little bit more shortly. So drilling down a little deeper in HER2 franchise, you can see 36% growth in the US which is very strong on PERJETA. In the EU we’re up to 27%, so nice uptake of APHINITY. Again, this is just based on the data which suggests that you know three or four patients out of one hundred additional will be capable of having a cure with PERJETA. On KADCYLA again, the early impact of the KATHERINE data primarily in the US and we would look forward to seeing that impact of KATHERINE in the years ahead in other regions. In lung cancer, we're seeing the beginnings I think of a strengthening of the franchise and primarily we see this with TECENTRIQ and Avastin in first line lung cancer where we have the ability to treat patients with liver mets, I think that's been one of the more typical uses of the empower 150 results where you have patients with significant liver mets, especially larger tumors and the doctors are choosing Avastin and that combination for its ability to shrink the tumors and help the patients contend with their metastatic disease, but also the fact that were labeled to cover patients who previously had out positive patients or EGFR positive patients who've had progression on one of those therapies, so some advantages there. And then most recently the - with the approval in extensive stage small cell lung cancer, another really important setting and one that we see growth - you see growth in Q1 and we'll continue to see growth through the year. This slide shows the impact in TECENTRIQ, on small cell lung cancer and in second line where we still see gains in Europe and again, you can see a nice growth for TECENTRIQ 135% year-over-year and we believe we'll see this momentum maintained through the year, so it's quite a positive growth story for TECENTRIQ, and the results of Phase III studies that I've read out, we have additional approvals anticipated in 2019 in Europe and a number of pivotal studies which we’ll be reading out in the next three quarters. So good momentum for TECENTRIQ and hopefully good signs - things to come. On ALECENSA, primarily we're seeing gains in first line. We're now at above 70% share in the US and close to 70% in Japan. So now what we start to see is actually gains that accrued due to patients staying on therapy longer. So as we've sort of reached something probably close to the maximum share in new patients, but because patients live a long time without progression on ALECENSA we'll continue to accrue additional patients as new patients come in and the existing patients stay on longer. And we continue to pursue the launches in other territories, including Europe. In Immunology, we were led by Esbriet with 10% growth and it's a hard-earned growth because this is a difficult market and in terms of some of the patient characteristics and encouraging patients to stay on therapy. But our efforts have paid off. And this is an area we'll continue to invest. Also Actemra was strength despite competition of sort of similar MOA molecules, but we managed to grow it an additional 6%. And then Xolair also hanging in with a lot of competition in the asthma space. And there have been questions about you know how would we hold up. But I think the benefits of Xolair, both in asthma, with the broad approvals, including pediatric, but also in other indications like chronic urticaria has helped Xolair to maintain sales and in the face of additional competition. In neuroscience, beginning with OCREVUS, its a very strong story. OCREVUS has really the broadest possible label. So far OCREVUS has shown strong data in both relapsing-remitting disease, as well as sort of active secondary progressive disease and primary progressive diseases. The only - it's the only therapy that has shown an effect in primary progressive and is labeled for that. And really that sort of remaining part of that mass which is the non-active secondary progressive. These are patients who are no longer having relapses and no longer displaying sort of MRI lesion activity. And that's a very difficult to treat patient population. So - but in the other 90% we're having very strong uptake. We have 37% of new patients and switchers in the US, which I mean compared to if you look at the overall market share OCREVUS is at 16%, we're getting 37% of new and switch. So again it portends well for continued growth. If you look at this slide, I think if you look from quarter-to-quarter what we see is the underlying growth has been rather steady throughout the last five quarters. Perhaps Q4 was a bit soft and what we see in Q1 is a return to the - to the growth rate that we saw over the 2017 and 2018 period. So again, very strong results on OCREVUS and we see this continuing in the foreseeable future. Coming here to Hemophilia. We talked a bit about the different patient populations that would be eligible, but I think what's most notable is we're beginning to get approvals in the 9 inhibitor segment. We were approved in the second half of last year in the U.S. and have seen very strong adoption in the non-inhibitor patients. And then we were just approved in March in EU in that category. So we haven't actually seen the impact yet, but we look forward to that because the adoption as I mentioned has been really strong in the US. And patients are choosing that – that the option to have a good control of their disease with a - with a drug that could be dosed either once a week or once a month in a convenient subcutaneous form is very attractive. So again, really strong results and we look forward to benefiting many, many more patients with Hemophilia in the years ahead. And then in terms of the outlook, I think that the slide in the right sort of displays our momentum in terms of new product approvals and we're very pleased to see that we have now 27% of our total pharma sales from these products that we've launched in the past seven or eight years. And again, I think if you look at the sales not only is it 27% but the momentum is actually increasing on these new products. And we have more where they came from. So we will look forward to the approvals of both polatuzumab, entrectinib and oncology this year and then filings for satralizumab and risdiplam this year for approvals next year. You can look forward to seeing some additional data in the conferences ahead. Severin mentioned some of these at the AAN which will be in the second week of May in Philadelphia. But I think most notably risdiplam and SMA, satralizumab with the combination data with steroids and cetera [ph] in neuromyelitis optica, the Huntington's data will highlight both sort of how we came to chose - to choose the dose that we have in the pivotal study, but also more information from the pivotal study. The initial phase with the dosing and how we've made our decision around bimonthly and three times a year dosing which we're take him forward in Phase III. On OCREVUS, there's some really interesting data coming out, both on the long-term follow up, but especially I would say the PK/PD data and exposure response analysis from the Phase III studies, this answers some really important questions about how these all piece of therapies should be dosed in MS. And I think really highlights the importance of a high dose to obtain the maximum possible B-cell depletion early on to drive efficacy, particularly efficacy on disability progression which is sort of the ultimate goal in MS is preventing declines over time. So you can look forward to that, as well as strong safety updates. And at ASCO, another big year for Roche and Genentech at ASCO with VENCLEXTA, TECENTRIQ, PERJETA, Herceptin and also some good data from TECENTRIQ, Avastin and entrectinib. And then just again looking forward at some of the things that are coming, you can see a number of checkmarks on the slide. So it's actually been a early strong year for results and approvals, but we have some additional readouts coming and so I think probably, the VENCLEXTA, GAZYVA is certainly one that we’re looking forward to CLL 14 data in non-Hodgkin's lymphoma. And I think this is a really interesting one because it's a combination of two biologics and two biotech drugs in a chemo free regimen in CLL and something that could be very useful for patients. So with that, I'll turn it over to Michael Heuer, for the diagnostics update.

Thank you, Bill. Good morning. Good afternoon, everybody. I'm happy to present the Diagnostics Division sales. With sales so roughly CHF2.9 billion we have 1% growth driven by molecular diagnostics, growing at 7% and diabetes care growing at 1%. Onetime effects impacted our centralised and tissue diagnostics units where we see a decline of 1% which unusual. Sales in centralised and point of cancer solutions were affected by distributors reducing inventors in China. A return to normal ordering patterns was observed at the end of Q1 already. Sales in tissue diagnostic were impacted by shipping delays of instruments into Q1 and we will resume shipments as abated [ph] and expect to completely resolve the issue within the next few months. Diabetes Care increased 1% mainly driven by 18% growth in North America due to recent management care contract wins and the good adoption of the Accu-Chek Guide and Accu-Chek Instant products. For the full year we expect our revenue growth going forward. Looking at our regional sales growth. This is driven by EMEA with 3% and Latin America with 8%. Asia Pacific saw 0% growth, while North America and Japan had negative growth of 3% each. And East Africa this grew at 1%, mainly impacted by sales in China. The reason for the decline in Japan is due to customer ordering patterns. Sales in the US were impacted by one-time supply chain effects in coagulation monitoring. This has been resolved and we are back to normal. Looking at the growth drivers. In our business areas, we see that centralised and point of care solutions continues to bring in the most revenue. Sales declined 1%, while the Immunodiagnostics business grew 3%, clinical chemistry was down 2% affected by reduced distributor inventory levels in China and onetime supply chain effects in coagulation monitoring business as I referred before. Sales in Molecular Diagnostics increased 7% making this unit the largest contributor to the division sales growth, driven by point of care molecular diagnostics was 18% growth, blood screening was 14% and the cervical cancer portfolio with 52% growth. Tissue Diagnostics sales were down by 1%. Sales were impacted by onetime supply chain effects caused by BenchMark ULTRA and Discovery shipment delays during the first quarter, resulting in lower instrument placements in North America and the Asia Pacific regions. Diabetes Care sales increased 1%, mainly driven by the new Accu-Chek Guide and Accu-Chek Instant, blood glucose monitoring systems, which have a great pick up in the markets. Roche started the collaboration agreement with Senseonics for the distribution of the Eversense insertable continuous glucose monitoring sensor in 17 additional markets. On this slide, you see that our strong commercial presence and broadest test menu, Roche is continuously outgrowing the market. And on the next slide, I would like to present some highlights of the first quarter. The cobas vivoDx system reinforces us tradition of innovation by offering a novel diagnostic technology to address a global threat of ever evolving drug resistance bacteria. We are currently in the process of engaging and organizing early access to keep customers in Europe to work with their CE Mark cobas and vivoDx system. Roche will also feature the system at the European Congress of Clinical Microbiology and Infectious Diseases. On the next slide, you see that the VENTANA PD-L1, SP142 Assay, the first FDA companion diagnostic approval for use in first line triple negative breast cancer or TNBC. This assay has been used for patients enrollment in the IMpassion 135 trial, where the first positive Phase III immunotherapy study was shown for first line TNBC. The tests has been designed to enhance visual contrast of tumor infiltrating immune cells stating, within tumor micro environment. On the next slide, you will see the product continue to 3.0. This is a proven global lab software solution for diagnostic laboratories that has to maintain high operational performance, quality, integration and security within the labs across multiple locations. One new feature that proves the intelligent routing of samples in high volume testing by dynamically adapting the changing lab conditions as priority testing to reduce time to results. New improved quality control features ensure that the highest quality results are important consistently. While new monitoring features secured high performance and stability of analyzer and reagents 24/7 without additional costs. The addition of more work areas for different clinical laboratory disciplines, such as molecular, hematology and coagulation enable lab staff to focus on what matters most to them. And following on our digital transformation journey. We launched the NAVIFY mutation profiler as a software, as a medical device, aiding labs to overcome a major workflow challenge containing the next generation sequencing, interpreting complex NGS data sets to identify clinically actionable findings and treatment options. NAVIFY mutation profiler combined with NAVIFY therapy matcher both [ph] as a curated knowledge base of genetic fragments to help interpret the clinical significance of the patients and identify suitable therapies. This is another leap in personalized health care and is becoming a leader in digital diagnostics. With cobas vivoDx, cobas infinity central lab and infinity in NAVIFY mutation profiler and therapy matcher, we have achieved important launches in Q1 2019. More to come as we move forward. And with this, I hand over to Alan for the financials.

Thanks, Michael. Let's go directly to 42 - hello to everybody out there. Thanks for participating. I think - starting with sales, I think my colleagues did a great deal and leading you through this we have great momentum as you have seen and has certainly encouraged us to bring the guidance up on the M&A side, when you look at Spark, nothing unusual here. Clearly an increase is expected in the first half of 2019. It's going to be an all cash transaction that will be financed by the available funds and our commercial paper program. And let me also mention that the transaction is not expected to have an impact on the financial guidance for 2019. With that, I come to the currencies and better do that on slide 43. And when you look at 43 you see the sales for the Roche Group in order of magnitude, so what has contributed where. And on the right-hand side you'll see that sales have grown by more than a CHF1 billion in Q1 2019 compared to Q1 2018 and concentrates with 8% and Swiss francs with 9% and the difference is a CHF149 million. And I will dig into this on the next slide. But on the left hand side let me mention here, you see the growth in the respective business areas. And Bill alluded to that, when he talked about pharma and especially pharma in Europe and then you see that we have a decline of - what minus 125. Last year we had the decline of a minus 166. So you see a really good momentum moving forward. And with that, let’s go to Slide 44. And this is the bridge for the development of group growth, first quarter in concentrates on the left hand side of it and in Swiss francs on the right hand side with 9.2% to be very precise and you see the currency impacts that we have seen in the first quarter. On one hand the US dollar which has strengthened gave us a positive plus 2.7 percentage points in growth and then you see against that negatively the euro was minus 0.5 percentage points and LatAm was minus 0.7 percentage point driven by Argentina and Brazil. With that let's go to Slide 45, and here is what we basically expect from the currency impacts for the year to go and there's a rather simple model. What we're doing here is that we are assuming that the March 31 first exchange rates remain stable until year end 2019, let me mention it's early days and these things will change for sure. But nevertheless it gives you a good guide how much the impact will be, but everything remains stable. And what you're seeing is basically for the rest of the year, so for half year, September year to date and full year we don't expect a lot, everything remains stable. As said, it's very hypothetical. When you look really left hand side, I think you see that the positive impact of the US dollar diminishing a little bit in our model. If you take that assumption into account that I've described before, whereby on the euro the negative impact remains stable, if you apply the assumption. With that, lets - once again to the guidance, very happy to bring the guidance up, group sales growth now assumed to be in – with the mid single digit growth and compared to a low to mid single digit growth that we expected before. Core EPS growth with that below broadly in line with sales growth as it is connected to sales and then the dividend outlook as Severin mentioned, further increase dividend in Swiss francs. And with that, we are very happy to take your questions.

First question comes from the line of Richard Parker at Deutsche Bank. Please go ahead.

Hi. Thanks for taking my questions. It's Richard Parker from Deutsche Bank. I've got three, if that’s okay. And firstly on Avastin, Herceptin, Rituxan. You had a good performance of Avastin and Herceptin in the international markets in particular. And I just wondered if you could talk about the price difference for those big three drugs in international markets, particularly in China where you've had NRTL inclusions and - versus Western markets. And I'm wondering how we should think about that segments of those sales being protected from biosimilar pressures, given maybe less room for price leverage in that segment? The second question, I wondered if you could talk about a little bit more what we can expect for AAN from the Huntington's program in terms of longer term, clinical follow up, I'm wondering when you might be able to make a decision as to whether that data could be filed above or whether we'll have to wait for the Phase III? And then third question, I just wondered if you could give us your thoughts on potential longer term competition for the HER2 franchise. We've seen some significant business development in that area and I wondered whether you've got any plans to develop your own next generation products to improve on projected KADCYLA? Thank you very much.

Yes. Thanks for the questions. So on the first one, which I think you're - you're sort of getting out as are the other prices in places like China on Avastin, Herceptin, MabThera, low enough that, that provides protection from future biosimilar competition. And I guess what I would say on that is, while we have substantially discounted those products in order to gain broad coverage and in emerging markets including China, I wouldn't want to provide a reassurance that the prices are so low that there won't be a space for biosimilars. I mean, I think there still is room for biosimilars there. I think probably our source of competitive advantage in a place like China will be that we do have an attractive price and we have a trusted product. And I think that there'll be relatively little biosimilar activity or competition against those products, maybe one competitor each in the next few years. And I think on that basis we feel like we can continue to compete and grow in China. The second one about the Huntington's data and when we'll be able to decide whether we can file with what we have versus waiting for Phase III. I think we've already pretty much commented on it. We had some initial promising discussions with regulatory authorities. Obviously disease is an extraordinarily high unmet need. There's really no therapy available. And so I don't think I really have anything to add. We will -- we will be taking the data as it emerges from the several studies we're running and sharing them with regulators. And so I think, it's too early to really give a more specific timeline. But we are hopeful that there'll be a sort of a faster market option available. And I say hopeful because the patients are definitely needing it. And then the last question about long-term competition in the HER2 space. I think as we've been very involved in the HER2 area for many years and have run studies in different segments including HER2 low, including, everything from neoadjuvant to adjuvant, first, second, third line, and with combinations and without combinations, I think it would be worth noting that -- you sort of know when you see it. And I think that there's a lot of – yes, there's a lot of mileage ahead for any product that's coming into that space in terms of safety questions, combine ability questions, efficacy questions in the different settings. So I think we're not overly alarmed. We've got a strong portfolio still emerging from research and early development in HER2 space and we think we'll be a leader there for many years to come.

Great. Thank you.

Yes. I have a question here via the telephone line. Michael this is going to you too. It's from Michael Leuchten from UBS. He asks if the inventory reduction in China, you believe is a question for China itself or is it more Roche specific question? Is what the first question he had, yes?

Thanks for the question. And in China I cannot comment whether this is that general Chinese situation. We see this specifically with our distributors. They trigger these changes by efficiency improvements that they wanted to achieve in their supply chain. And that meanwhile since March we feel really very positive sign since the distributor inventory indicating that the market growth remains very strong. I think that being shown also during the fourth quarter from the in-market sales perspective that we see with our products. A return to normal ordering patterns was observed, and we believe return will continue in good Q2 and as we go forward.

So Michael Leuchten has a second question on HEMLIBRA. So he asks about the overall safety efficacy profile going forward and how you see the value proposition value proposition for HEMLIBRA in view of the fact that it's new drugs, new introduction, questions on safety efficacy balances now and going forward?

Yes. So I think, we always have our viewpoint on this, but it's also what's more important is what are the key opinion leaders think, what are the patient advocates in the case of hemophilia. Patients are very involved in these decisions and I think we're very pleased with the response we see from both groups that we have a very nice safety profile, its that's holding up very well. We continue to update the safety profile with findings as they come or committed to that. We post updates every quarter in terms of observations, things like deaths or adverse events in the various update, for example, we did list three additional deaths in our safety database. Obviously very unfortunate that - that well any time there's a death it's obviously a great loss. In these cases though, once again there was no causation or - these deaths were not attributed to HEMLIBRA treatment. So I think that the safety profile is holding up very well, meaning we move forward with competence.

Thank you. Next question.

Next question from the phone is from Tim Anderson. Please go ahead.

Thank you. Couple of questions. First one is on adjuvant data with TECENTRIQ and specifically what we may see in 2019 on our radar, had been triple negative breast and bladder, but on triple negative the slide 30 shows that you had an interim analysis that has subsequently passed. And I'm guessing that suggests we won't see any data at ‘19. So if no data in ‘19 when might we see data? And is bladder still potentially on track to read out in ’19? Second question goes back to Huntington's. Just if you can just describe it a little more detail whether you have any data at this point showing that lowering the mutant protein with your product is translating specifically into a clinical benefit not just biomarker engagement? Thank you.

Thanks, Tim. Let's see, maybe coming to the second question first. I think that you know, we won't - we won't have strong confidence in the clinical effect of reducing the Huntington's protein until we have a large controlled study. So I don't think there's anything new to say about that. I think you know, what we do know is this is a disease that's caused by the accumulated effect of mutant Huntington's protein and we have an agent that lowers the levels of Huntington protein and we and I think that the scientific experts in the field and the regulatory agents are hopeful that that will have an important benefit there. But we're going to have to wait on the data to know for sure. In terms of the question you had about neoadjuvant and adjuvant data with TECENTRIQ. So TNBC we did pass an interim analysis. We don't think we'll have the final analysis though in neoadjuvant until the second half of 2020. And then in terms of adjuvant, we are hopeful to have adjuvant data in high risk patients with metastatic bladder cancer in - yet and in Q4 of this year. And I think I'll have to follow up and see if there's anything more I can say about adjuvant. But I think you may be aware of the list of studies we have, but I don't have any updates on readout time lines on this.

Thank you.

Next question is from Steve Scala, Cohen & Co. Please go ahead.

Thank you. I have three questions. First, Roche has warned several times now that treatment breaks and presumably softer sales between previous cycles is expected, but it doesn't seem to happen. Our new patient starts and launches overwhelming treatment breaks or our treatment breaks not occurring to the extent you expected? So that's the first question. Second, concerning the VENCLEXTA BELLINI trial, what have you learned post the recent stoppage of enrollment and is the study still on track for completion in September of this year? And then lastly. I apologize another Huntington's Program question. You mentioned the dosing data at AAN, but just to clarify, may we also see efficacy data in small numbers of patients at the meeting? Or is there no chance of that? Thank you.

Right. So maybe going in reverse order. Yes, you shouldn't expect to see efficacy data in Huntington's disease at AAN. That's coming later. In terms of your question about VENCLEXTA and BELLINI, the study of VENCLEXTA in chemo in multiple myeloma, so we announced earlier that the results while we stop the BELLINI study and the FDA placed a partial clinical hold on the VENCLEXTA studies in multiple myeloma, based on safety findings which was basically an imbalance of deaths in the VENCLEXTA arm versus the control arm. We're still investigating sort of the cause of this, but I think we did see some encouraging signs in the BELLINI study in terms of based on biomarkers. And so we're not – we’re saying - we're taking it you know the finding of the imbalance and deaths very seriously in terms of what it means and what multiple myeloma. But we're not counting ourselves out of multiple myeloma with VENCLEXTA yet because we do see some promising indications in the biomarker subsets. And let's see your first question is about treatment breaks with OCREVUS and I have to say this is something we've been watching closely and we see the treatment interval is actually quite tight. It's very close to the label recommendation which is twice a year. And so it's not a question of new patient starts or overwhelming the effect - the effective treatment breaks are offsetting it, but we're not really seeing that as a phenomenon right now, that the dosing is being followed very - or that the recommended dosing is being followed very closely by the physicians and patients.

There is a question from Marietta Miemietz from the - from Primavenue, and she was asking about the margin outlook in specifically in Diagnostics. We usually do not comment on margins for the subdivisions, but Michael seems to want to do more certainly, any comments on that.

Yes. I'd just like to iterate our core guidance, which is to increase earnings broadly in line with sales. I just want to point out that the increase of the sales guidance indirectly of course this is also an increase of our earnings guidance, but we wouldn't go into detailed margin discussion on the divisional level.

Okay. Thank you.

Next question from the phone is from Matthew Weston, Credit Suisse. Please go ahead.

Thank you very much. Three questions if I can please. The first coming back to international growth and really asking around the sustainability in pharma of the very strong growth rates we're seeing at the moment. Bill do you envisage that we'll see - we're essentially seeing a bolus of China growth being driven by the listings of the products that will moderate as we get towards 4Q or do you believe that this double digit growth rate is more sustainable? Secondly, can we have a quick update on expectations for US biosimilar entrance with respect to Rituxan and Herceptin and Avastin over the course of the next couple of months? Are we had any changes in terms of your view of settlements and the risk of at risk launches? And then one final question Bill, I was intrigued with your commentary around data of OCREVUS at AAN with respect to the response being linked to the depth of B-cell depletion. Am I reading it right that essentially your contrasting high dose deep B-cell depletion with potentially more mild continuous B-cell depletion we could see from a competitor with monthly dosing and you believe your show data to say that that depth of depletion is necessary to get maximum efficacy?

Yes. Okay. Thanks. Thanks for the questions Matthew. Let's see, the first one you asked about sales in China, is it sustainable. I mean, I think what we are seeing is truly extraordinary and it's actually very encouraging to see, really hundreds of millions larger population being - having the possibility of treatment with drugs like Herceptin, MabThera, Avastin. I mean, there certainly is a new uptake effect that is occurring right now that can't be sustained forever. But we do believe that we'll have sustained growth in China through 2019, 2020 and beyond. So it's a good harbinger of things to come. But I think to think we would continue to see as the rates we've been seeing it for the last two quarters that might be a little a little more than we could hope for but. But I think again continued strong market for those drugs in China as well as we're seeing a strong uptake of drugs like PERJETA and we're encouraged with the launch of ALECENSA in China as well. So I think the development in China is really positive both in terms of broadening access, but also the fact that that the Chinese regulators are being much faster to approve new drugs and we're able launch them. So I think we're quite optimistic about our future in China. In the US there's now a lot more to say than what we've said already about biosimilar entrance. We do expect to see biosimilars competition for Rituxan and for Herceptin in the second half and with Avastin potential biosimilars competition would probably be not until Q4 at the earliest. And let's see, your last question, right about the OCREVUS data. I mean I think you have to form your own conclusions, but I think we chose to go with the IV dose knowing that you know from a pure convenience standpoint subcutaneous is generally better than IV, but also knowing the nature of the and ICD 20 therapy and the history with Rituxan, with GAZYVA, Rituxan in immunology with Rituxan in oncology that this really is an area where you benefit from getting a dose and a deep suppression of the B-cells that are implicated. And we also know that these B-cells lurk not only in n the periphery but they're lurking in the bone marrow. They're in CNS in the case of MS. And so we did a lot of thinking and study and back - this goes back even 10 to 12 years ago about the best way to dose these drugs and we concluded that IP was the way to go and that a less frequent dosing was all that was required with IP and so we went with that. And I think that the new data that that we're seeing coming out of the reanalysis of the. Phase III data is really sort of adding to that. In addition some of the leading researchers in MS have been looking at this question of what does it take to really stop progression because as you as you probably know the field has done much better. For example at suppressing MRI activity. We're really good at stopping lesions, but not as good at stopping progression. And there's been this emerging hypothesis that what's going on is that there is a residual sort of auto immune activity that's taking place at a level that doesn't show up in the MRI and to show up as discrete lesions. But it's sort of a smoldering activity. And the way to get out that is a more profound suppression of the offending immune cells and the analysis I think it will show that AAN is strongly supporting that. So I look forward to more discussions on that as we as we present the data.

Thank you.

Next question is from Richard Vosser, JPMorgan. Please go ahead.

Hi. Thanks for taking my questions. A couple please. Firstly, just thinking about US price reforms, perhaps you could update us on how you're seeing these reforms develop, how receptive has the administration been to your proposals around Part B reform? And maybe some comments on how likely you now see international reference pricing or maybe over the last few days Medicare for rule being adopted? And then second question just going back to HEMLIBRA and the uptake, perhaps if you could give us a bit more color on the uptake in non-inhibitors what share of patients do you think that you have at this point, and especially centers relative to maybe more community hospitals and what the feedback has been there and maybe a split of revenue between non-inhibitors and inhibitors if possible? And then finally actually one final question just thinking about TECENTRIQ, the label update for small cell lung cancer and triple negative breast cancer didn't mention anything about antibody levels. It has – has this now been put to bed with data the ease to make it to the FDA. I think it was due to be there and in Q1 is that now off the table as a as a concern? Thanks very much.

So it's a long list. Let's see. I guess, the first one, yes, we could spend all afternoon talking about the healthcare reform and pricing pressures and in the U.S., but let's not do that because I don't think we would add much value to the discussion. I think we continue to have good discussions with other stakeholders, including other pharma companies, providers, payers, other entities in the administration about some of our proposals for reforming pricing and introducing market based competition in Part B. I think it is true that there's -- there's a lot of competing proposals in Washington coming from very different sources and the range is quite extreme, including things like this, sort of so-called Medicare for all. I think in terms of international reference pricing I think this is something where we and the rest of the industry, but a lot of other folks that that are knowledgeable in health care, I think is a really bad idea because we think the price controls that exist in countries like the UK, it is not good for innovation, it doesn't support innovation and at a time where the biomedical research and development enterprise is never making - it's never made more gains. And today to introduce things that would severely limit innovation it just seems like it's really a horrible idea for humankind. And so we'll continue to oppose those things, but meanwhile we press ahead and we try to offer concrete proposals and we try to make sure that our behavior is consistent with our values and I think we've done that in terms of pricing and everything else. In terms of HEMLIBRA, the question is about non-inhibitors and market share. I think in the US we may be approaching 10% market share in non-inhibitors and this is based on approval in what was it September, October last year. So I think it was a very quick uptake. People were wondering - we were wondering, what would the rate of uptake be for patients that are - I would say in quotes kind of “well control” because they don't have inhibitors. And I think what we're finding is that the ability to give up the frequent IV infusions for those patients who were on prophylaxis or the ability to have control and to have more freedom in life, freedom from bleeds and from having to avoid activities for those patients who are on demand and not on prophylaxis is proving quite compelling. And we just have a really strong package, with the option of once a month dosing, a very reasonable price. It's very popular. We have broad coverage and from a payer standpoint and now we have the approval in Europe and just in March. So we're looking forward to hopefully similar types of trends. You asked about the specialists versus community. There are some specialists who've gone very rapidly to converting patients over HEMLIBRA, but we see also quite healthy adoption in the community. And then you asked about the share of revenues that was non-inhibitors versus inhibitors and I think what you can think of is our sales in Q3 was virtually entirely inhibitor patients and then almost all of the change in sales since Q3 is in non-inhibitor patients, so that's a pretty good way to think about it. We had highly penetrated the inhibitor population by the end of Q3. So think of that as a baseline. And finally you asked about drug antibodies with TECENTRIQ. We were still analyzing this. We have numerous Phase III trials and Phase II studies and we have large datasets on this. So far we're not finding any - anything that's very concerning about it, but we know we take it very seriously and we'll continue to study this matter and provide updates to regulatory authorities on it. So I think that's an ongoing discussion we're having with the FDA and other regulatory bodies, but we feel like we're sort of on top of it and we'll continue to evaluate it.

Thank you.

Next question comes from Simon Baker, Redburn. Please go ahead.

Yes. Thank you for taking my questions. A couple if I may please. Firstly, on European Rituxan and Herceptin sales. We saw relatively certainly to market expectations better performance from Rituxan, a weak performance for Herceptin and I was wondering if we could read anything into that from the - with regard to the trajectory of biosimilar penetration, is it a case of relative to what we expect and perhaps what you expected that initial erosion is quicker and then starts to abate over time. So any color you could offer there would be helpful? And then secondly moving on to Diagnostics. I wonder if you could give us any quantification of the impact of the distributor inventory level changes in China. I know you said that it is now resolved somewhat I just wonder if you could quantify the impact in Q1? Thanks so much.

On the – I’ll take a biosimilars in Europe in MabThera, Herceptin. I'd say that the pattern is very similar for the two drugs. And the reason - I think you say that sort of better performance on MabThera this year. I think that's really because there is not so much left to lose for another reason. We had a steep loss in 2018 on MabThera. And so this year there's not as much to lose. And with Herceptin is a similar pattern, but maybe six or nine months later.

On the Diagnostic side, they cannot give you the details numbers, but they can only refer to as significant impact of the efficiency improvements in the distributor's inventory levels and we compare that always with the in-market sales and there we see major risk capacity between what is going out to the market, what was in the inventories of their distributors and we see also the pick up now of the sales and purchases from the distributors to Roche since March. So this was that individual topic, single event in the month of January and February, and we are above that and we see a positive development now going forward.

Thanks so much.

Next question comes from the line of Luisa Hector from Exane. Please go ahead.

Oh hello. Good afternoon. I have a few more questions on international sales please. I noticed that Rituxan was a bit weak and I just wondered if there was anything specific behind that in the international region. I'm sorry if I missed it, but did you actually give the China pharma growth in the quarter please. And whether any – in pharma now was there anything in terms of stocking or tenders that you would mention for the quarter? And then a second question on HEMLIBRA. Just looking at that European label, so good to see the approval, but as you flagged it the full year results, the label is restricted to severe patients for the non-inhibitor group. So just wondered what would be required to then expand the label or do you need another study or is it can you use real world data for example? Thank you.

Okay. Let’s see, so the first question was about MabThera and international. Yes, I don't think there's any particular trend there other than that there are some noncomparable biologics and biosimilar competition in the international region to both MabThera and Herceptin. And in the case of Herceptin we have stronger new uptake in China. It was offsetting the biosimilars in noncomparable biologics. So I think that's just probably the difference between Herceptin and MabThera. You asked about China growth. And we do provide that on the on the higher web page, if you want to look at the details on that, you can find it in I think just check it there. And then HEMLIBRA you asked about the effect of being limited to severe patients in Europe and I think the slide we showed in my presentation gave the segmentation - the patients segmentation and the bottom line is depending on the country and which study you look at, severe patients are between 50%, 60%s, up to 70% of the patients. But in terms of use of factor A or the use of the bypassing agents in the case of inhibitor – of inhibitor patients, it's a much higher proportion, so up 85% or 90% of the market. So we don't believe that the limitation of the European label is severe. We'll have a significant effect on the ultimate potential HEMLIBRA in Europe. Yes, and I'm looking at our web page for the China sales growth in the quarter and it was up 63%. So a very strong result, I think by that by any account.

Thank you.

Next question comes from the line of Peter Welford from Jefferies. Please go ahead.

Hi. Yes. Couple of follow-up questions, please, if you don't mind of OCREVUS. First of all, just with regards to the PPMS and RMS split, I wonder if you're willing to give any sort of detail on that. And also any sort of rough percentage of those patients who are coming back, the new starts for the second infusion. Is there any sort of safety you have on the I guess discontinuation rate prior to the second infusion? Secondly is then just on a Herceptin highlight [ph] in the U.S. I appreciate it's still early days, but any sort of feedback you have on the adoption of that in the US since approval. I guess you didn't draw any comparisons to how you saw is adopted in some of the key European markets when you also got that approval? And then just finally on - sorry, going back to Huntington's again, but just curious given the change of the protocol and obviously the stop to the generation trial. While you did that protocol change to change the dosing to Q3. I'm just wondering whether or not that change in dosing schedule has any impact on the regulatory discussions and I guess what I'm wondering is do you have to get some sort of data on the effect of the Q3 and dosing before you're able to go back to regulators, given obviously that's a pretty lengthy dose interval for many patients? Thank you.

Okay. Okay. Let's see. Let me - let me try to answer, if I miss one of your questions please go back. As I was taking notes, but I'm not sure I got them all. But yes about OCREVUS and the retreatment rates and we’re not providing specific numbers on that, but it's - the retreatment has been very strong. The vast majority of patients are getting the second dose and third dose frankly higher than what we had anticipated before the launch. We continue to follow that very closely. But I would say by any precedents of other chronic therapies I've been around and it's very strong. And I think it's basically that combination of very strong efficacy, the fact that they only have to get dosed twice a year and that the side of high profile is quite good. So again, very encouraged by what we see there. Yes about the Herceptin subcu launch in the US and I think we'd commented before that your subcutaneous dosing, well, it's a nice convenience advantage for patients in the US health care system. Physicians are very comfortable with IV dosing, that's very much there. Their system and they're set up, so that the amount of uptake of subcu is quite small and -- both for MabTherea, for Rituxan. And now with Herceptin subcutaneous we only just recently received the approval, but we don't anticipate it will be a major part of the market. But we think it's a good option for patients to have. And then you asked about the dosing change in the pivotal studies for the ALECENSA therapy for Huntington's and we don't think that - I mean, we basically we - we were following a monthly and a by-monthly approach and the early data that we were looking at suggested that there wasn't an incremental benefit or monthly over a by-monthly and so we decided to drop that arm. And then because we had the option to explore two arms we decided to look at a less frequent industry basis. So I think you said three month limit is actually every four months. So there's dosing - some patients being dosed every two months and others every four months. And - but we don't anticipate that to have an effect on our discussions regarding a faster market approaches for – yes, with the regulatory authorities. Did I answer your questions?

That's great. Thank you.

Thank you.

Next question comes from the line of Naresh Chouhan, Intrinsic Health. Please go ahead.

Hi, there. Thanks for taking my questions. Just want to ask in - in the US was there any material price rise on Avastin? And then with TECENTRIQ in the second line it would seem based on some of the concessions we had with KOLs with the second-line setting – in the second-line setting, TECENTRIQ has become standard of care placed with KEYTRUDA use in Europe, at least. Would you - are you seeing that and could you help us understand what the penetration rates in the second line and also in the first line are in the US and Europe? Thank you.

See on Avastin, okay, so we haven't had any price increases in the US since last July. And I think any price increase we had on Avastin was rather modest in 2018. So I think we're mostly seeing a volume effect on Avastin. The price effect would be very minimal. And as I think I mentioned mostly is due that on new indications like ovarian cancer as well as the use of Avastin in combination with TECENTRIQ. In terms of second line use of TECENTRIQ and I guess you said first and second line and lung cancer in the US. So again, with the place where we're hearing from physicians that they're liking to use TECENTRIQ is in the patients that have been previously received an EGFR inhibitor or and ALK inhibitor or patients with large metastases, large tumor volumes, where they're keen to debulk the tumors, and they know the effect of Avastin and many of the Empower 150 regimen which is TECENTRIQ, plus Avastin, plus chemo had a very high response rate and strong and a tumor effect and so that's where we're seeing most of the use they're in first line. And second line is it's tough competition between TECENTRIQ, KEYTRUDA and Opdivo. All three products had good data in the second line and I think it's more of kind of tough battles and because we were third to market, that's in lung cancer that's a harder area. In terms of - in the EU we've done rather stronger in second line, in first line it's too early to say because we've just been approved with Empower 150 regimen in Europe and haven't yet had approval in the small cell lung cancer. But we look forward to that later this year. Next question?

Next question comes from the line of Sachin Jain, Bank of America. Please go ahead.

Hi. Sachin Jain from Bank for America. Thank you for taking my questions. Just two questions, firstly on the Spark acquisition and SPK 8011 [ph] product for hemophilia, I wondered if you could just comment on the competitive profile versus a BioMarin gene therapy? And your level of comfort that you've acquired a potentially best in class asset or any other factor behind that acquisition? And then secondly, just apologies going back to Huntington's. Just a follow up on two comments. Firstly on efficacy functional outcomes, correlation to protein, I believe, you had post-talk analysis at AAN last year correlating protein reduction to functional outcome. So I just wanted to clarify your prior comment Bill, do you not put a lot of credence in that post-talk analysis or is data internally potentially changing? And then on the filing strategy, that your partner is being fairly vocal that you have an agreement to use a Phase I open label extension in comparison to the natural history study. I just wanted to check whether that was correct and if it is you essentially just waiting for the data to discuss for the regulators or are there any other factors still pending in that discussion? Thank you.

This is Severin Schwan. So just comment on hemophilia and the Spark acquisition. So we expect data still this year, competitive data which will further inform us. Spark is at the earliest stage in terms of the development. So it's - simply there's enough time to abate for the clinical data to see how the different opportunities for patients will eventually play out. But from all of what we have seen, we think that Spark has a good chance to be a better position in this market. Bill, over to your.

Yes, thanks Schin. On Huntington's, I appreciate you asking. But there's really - there's really no news there. Basically - so there's no - you asked whether there's some change in the internal data, change in our view, there's no change in the outlook. I think my answer was did you mentioned in post-talk analysis and correlation and that's all good and nothing's changed on that. But I was - I think what I was answering earlier is when will we know what the clinical impact is. And I guess I would say the word no is a high bar and we'll know it when we have randomized controlled data. We're optimistic with what we have. And again because of the high unmet need in Huntington's both we - the Huntington's community and the regulators are looking at innovative ways to make the product available. But there's really no news on it. We're going to get the data from the studies we're running. We will. We will continue to share it as it emerges with the regulatory agencies and we will all be working on the most expeditious possible waiting to make the products available to patients. But in the meantime I don't think there's anything else to say and we'll be waiting on those results.

Is there any comment you can make to your partners commentary re your filing strategy?

I don't think there's anything else to say.

Thank you.

Yes.

The last question is from Graham Doyle from Librum. Please go ahead.

Hi. Thanks for taking my questions. And just two please. One on HEMLIBRA, assuming Sparks gene therapy does indeed work. What type of patient population do you envision staying on HEMLIBRA? And then just second on OCREVUS and considering this sort of potential competition in a subcut form, obviously this been discuss a little bit earlier. Do you think you'll be able to replicate the data you have shown, the efficacy you have shown with the intravenous form of OCREVUS in a subcut conversion? And does it leave that option open longer term? Thank you.

Right. So on the hemophilia and how is HEMLIBRA positioned against the potential gene therapy. Again, it will very much depend on the data. We still have to wait for the data and analyze how response rates are, how safety portfolios throw up et cetera for the various patient groups. But we could well see a situation where we have a complementary positioning that is still used for factor VIII, for example, in very mild patients there will definitely continue to be a market for HEMLIBRA and then depending on the data for gene therapies they are a potential option for a number of patients as well. And it might also be that all the time you need a combination, we don't have long term data yet. By the very nature of the development of this new modalities and – but it will also depend a lot on how the effect from gene therapies plays out in the long term and you could potentially even see for those patients who go on change therapies or combination with the medicine like HEMLIBRA all the time. So really bottom line is that the - we have to wait for the data to be more granular of how the market will segment in the future.

Great. And regarding OCREVUS and you mentioned subcutaneous, I mean, it's - I think probably the most important factor is that the IV formulation is well tolerated. It happens every six months and patients are typically going in to see their senior physician about every six months. And so I think what we're finding is that the combination of the current OCREVUS profile of the dosing profile, safety profile, the tolerability in terms of sort of nuisance side effects and things that are seen with other MS therapies. And then just really the compelling efficacy which is ultimately the name of the game, it makes OCREVUS a very attractive option. And so I think if we were considering what are the benefits of a different dosing regimen we have to consider also that we have 37% of basically switches and new starts in a market with - I don't think - I think we've lost count, will be 13 or 14 or 15 products. So we're by far the number one news product. So I think that kind of puts it in context and obviously we keep our options open in terms of alternative dosing approaches, but I don't think there's any more at this point.

That's right. Thank you.

So thank you very much for attending our briefing today. Thank you for your interest and have a good day.