Novo Nordisk A/S (NVO) Q3 2018 Earnings Report, Transcript and Summary

Thank you, Lars. Please turn to slide 11. Last week, we announced the headline results from PIONEER 8. The 52-week type 2 diabetes trial investigated the efficacy and safety of 3 milligrams, 7 milligrams and 14 milligrams of oral semaglutide compared with placebo in 731 people with an average disease duration of no less than 15 years and all being treated with insulin at the baseline. When applying the primary statistical approach, the trial achieved its primary endpoint by demonstrating statistically significant and superior reductions in hemoglobin A1c and body weight with all three doses of oral semaglutide compared to placebo, both in addition to insulin at week 26. When applying the secondary statistical approach, i.e., investigating the effect on patients adhering to treatment, people treated with 3 milligrams, 7 milligrams and 14 milligrams oral semaglutide from a mean baseline of 8.2% achieved reductions in HbA1c of 0.5%, 0.8% and 1.2% at week 52 respectively, compared to no reduction in people treated with placebo, both in addition to insulin. In addition, from a mean baseline body weight of 86 kilograms, people treated with 3 milligrams, 7 milligrams and 14 milligrams oral semaglutide, experienced a weight dose ranging from 1.0 to 4.3 kilograms at week 52 respectively. And with a weight gain of 0.6 kilograms in the placebo group, there was a weight difference of around 5 kilos in favor of oral semaglutide at the 14 milligram dose. In summary PIONEER 8 shows that oral semaglutide brings close to two-thirds of insulin-treated type 2 diabetes patients with long-standing diabetes to the ADA target of HbA1c below 7% with a placebo-corrected weight benefit of around 5 kilo after one year’s treatment. Such data are unprecedented on all agent in this trial population. Additionally, at the end of the trial, the insulin dose was reduced by 7-insulin units per day for people treated through 14 milligram semaglutide, compared to an increase of 10 insulin units per day for people treated with placebo. With an average baseline dose of insulin close 60 units per day, this corresponds to reduction in insulin dose of more than 25%. Oral semaglutide was well tolerated not associated with increased hypoglycemia and exhibited a safety profile consistent with GLP-1-based therapy. Please turn to slide 12. In September, we announced the headline result from PIONEER 10. The 57-week trial investigated the safety, tolerability and efficacy of 3 milligrams, 7 milligrams and 14 milligrams oral semaglutide compared will 0.75 milligram once-weekly subcutaneous dulaglutide, the approved dose in Japan, in 458 Japanese type 2 diabetes patients inadequately treated with oral anti-diabetics. The trial achieved its primary safety endpoint, and furthermore, from the baseline HbA1c of 8.3%, people on treatment for one year with 14 milligrams oral semaglutide experienced a statistically significantly greater reduction in HbA1c of 1.8% compared to 1.3% with dulaglutide. Further weight reduction from baseline was also statistically significantly greater with the 14 milligrams oral semaglutide at week 52, with a decrease of 1.9 kilogram compared to a weight gain of 1.1 kilogram with delaglutide, providing a 3 kilogram weight difference between the two GLP-1 compounds. In the Japanese population the mean baseline weight was 72 kilos. As mentioned, the trial achieved its protocol-driven primary objective by demonstrating a number of adverse events with oral semaglutide that was comparable to delaglutide. The most frequently reported events were gastrointestinal. And the proportion of people discontinuing treatment due to adverse events was between 3% and 6% of people treated with oral semaglutide compared to 3% of people treated with delaglutide. Please turn to the next slide. Since August, we’ve reported results from PIONEER 5, 8 and 10, implying that we have now reported all Phase 3a trials except PIONEER 6 and PIONEER 9. Across the eight completed PIONEER trials, we’ve observed a consistently strong lowering of HbA1c for the 14 milligram dose of oral semaglutide ranging from 1.1% to 1.8% in patients completing the trials. With these HbA1c reductions, all PIONEER trials have shown statistically significantly improvements versus comparator therapies, including the leading injectable GLP-1 analogues liraglutide and dulaglutide. In terms of body weight, oral semaglutide 14 milligrams has demonstrated a consistent reduction ranging from 1.9 kilos to 5 kilograms. For oral end of trial data sets, the on-treatment results were in each case statistically significantly in favor of oral semaglutide versus the various comparators. The Phase 3a program was designed to support a start-and-stay treatment strategy for oral semaglutide across the type 2 diabetes lifespan, from diagnosis until late-stage insulin dependency. This ambition has been fulfilled by the PIONEER program, as evidenced by the finding that the majority of patients met the glycemic ADA target with a beneficial weight profile across the disease spectrum. Please turn to the next slide. In August 2018, Novo Nordisk acquired the UK-based company Ziylo. The combination of Ziylo’s synthetic glucose binding molecules and the state-of-the-art insulin design pioneered by Novo Nordisk, together seek to make development of the world’s first glucose-responsive insulin possible. Also, the first clinical trial of the next-generation oral GLP-1 OG2023SC has been initiated, investigating the safety, tolerability and pharmacokinetics of GLP analogue 2023. This quarter, we’ve also submitted three new drug applications in Japan: Xultophy, Fiasp and N8-GP respectively. Furthermore, we’ve initiated SELECT, the large cardiovascular outcomes trial, investigating once-weekly semaglutide 2.4 milligram in non-diabetic overweight obese people with established cardiovascular disease. SELECT is expected to enroll 17,500 people and have a duration of around five years. In October, we initiated a phase 1 trial with a long-acting appetite suppressing PYY analogue 1875. The trial is designed to investigate the PK/PD safety and tolerability, alone and in combination with semaglutide in obese people. Within our Biopharma portfolio, three key milestones have been achieved. Firstly, the successful completion of the REAL 1 Phase 3a extension trial with somapacitan in adults with growth hormone deficiency. Secondly, we’ve reported the successful completion of the Phase 2 trial explorer5, investigating the subcutaneously administered cross-segment antibody concizumab, in people with severe hemophilia A without inhibitors. Thirdly, we announced yesterday the acquisition of the U.S. and Canadian rights to Macrilen, the first and only FDA-approved oral growth hormone secretagogue receptor agonist, currently indicated for the diagnosis of adult growth hormone deficiency in the U.S. Please turn to the next slide. So far 2018 has been a positive and eventful year with an important hypoglycemia label update for Tresiba in the U.S., new product approvals, compelling data for somapacitan in children and adults, and above all, successful completion of eight PIONEER trials. For the remainder of the year, we expect the results from PIONEER 6 and PIONEER 9. Lastly, we expect the data from the second phase 2 trial with concizumab in inhibitor patients. With that, over to Karsten for an update on the financials.

Thank you, Mads. Please turn to slide 16. In the first nine months of 2018 sales decreased by 2% in Danish kroner and increased by 4% in local currencies. The gross margin decreased by 0.4 percentage points to 84.2%, measured in Danish kroner. Compared to the first nine months of 2017, the gross margin was negatively impacted by currencies, especially the depreciation of the U.S. dollar compared to Danish kroner, and lower realized prices in the U.S. This was offset by higher productivity and positive product mix. Sales and distribution costs increased by 3% in Danish kroner and increased by 9% in local currencies, reflecting a higher level of promotional activities in both North America and international Operations. R&D cost increased by 2% in Danish kroner and increased by 5% in local currencies, reflecting higher cost for both research and development. Administration cost decreased by 1% in Danish kroner and increased by 3% in local currencies. Operating profit decreased by 6% in Danish kroner and increased by 2% in local currencies. Operating profit was negatively impacted by around DKK 600 million in severance costs. Adjusted operating profit growth was 4% in local currencies. By the end of 2018, we expect the workforce to be reduced by 1,300 employees. The majority of the layoffs have been implemented. Net financials showed a gain of around DKK 0.8 billion compared with a loss of approximately DKK 0.8 billion in the first nine months of 2017. This development reflects a gain on foreign exchange hedging, mainly due to the depreciation of, especially the U.S. dollar versus the Danish kroner. Diluted earnings per share increased to DKK 12.40, corresponding to an increase of 3% compared to the first nine months of 2017. Please turn to slide 17. In line with our treasury policy, the most significant foreign exchange risks have been hedged primarily through foreign exchange forward contracts. The first nine months of 2018 incurred a gain of around DKK 0.8 billion compared with a loss of DKK 0.8 billion in the first nine months of 2017. This development reflects a gain on foreign exchange hedging, involving especially the U.S. dollar versus the Danish kroner. The hedging gain was partly offset by impact from depreciation of non-hedged currencies. Please turn to slide 18. For 2018, sales growth is now expected to be in the range of 4% to 5%, measured in local currencies. This reflects expectations for continued robust performance for Victoza and Tresiba, as well as the positive contribution from Ozempic, Saxenda and Xultophy. These sales drivers are expected to be countered by an impact from lower realized prices in the U.S., driven by lower prices in basal segments. Reported sales growth is now expected to be around four percentage point lower than local currency guidance. Operating profit growth, measured in local currencies is still expected to be in the range of 2% to 5% growth. The outlook reflects a planned increase in S&D cost to support commercialization of Ozempic, as well as severance costs. Reported operating profit growth is still expected to be around seven percentage point lower than the local currency guidance.We now expect financial items to be a gain of around DKK 0.5 billion. Updated guidance reflects the recent appreciation of the U.S. dollar compared to the Danish kroner and continued depreciation of several unhedged currencies. The effective tax rate for 2018 is still expected to be in the range of 19% to 20%. Capital expenditure is still expected to be around DKK 9.5 billion in 2018. For 2018, we now expect the free cash flow to be DKK 29 billion to DKK 33 billion. As a consequence of the increased expectations for cash flow in 2018, the Board of Directors has approved an expansion of the 2018 share repurchase program with DKK 1 billion to DKK 15 billion. This concludes the financial update. Now, back to you, Lars. Lars Fruergaard Jørgensen: Thank you, Karsten. Please turn to Slide 19. We are off to a very good start with Ozempic, thereby strengthening our leadership position in the expanding GLP-1 markets. Our other key innovative products Victoza, Saxenda, Tresiba and Xultophy continues the solid contribution to sales growth in the first nine months of 2018. Finally, we have made some important organizational changes aimed at boosting innovation in our R&D organization and redirecting resources in other parts of the organization to our further growth drivers. Operator, we’re now ready to take the first questions. And I kindly ask you to limit yourself to two questions. Thank you.

Thank you. [Operator Instructions] We will now take our next question from Florent Cespedes of Societe Generale. Please go ahead. Your line is open.

Good afternoon, gentlemen. Thank you very much for taking my questions. First, on the short-acting insulin market, could we have an update on the dynamic of the market, notably in U.S. and in Europe, as we see some decline? And my second question is on NN9023, the next-generation oral GLP-1. Could you share with us what’s your goal, what you expect from this product, and how you will differentiate this drug versus oral sema, currently in the development? And if I mean, Mads, just a follow-up, could you tell us where do you stand regarding the cardiovascular outcome study discussion with the FDA regarding semaglutide program? Thank you very much. Lars Fruergaard Jørgensen: Thank you. I’ll start by answering the question, the short-acting, and Mads can go through the oral and CV. So first of all, when you look at our NovoRapid, NovoLog or short-acting franchise is actually one of the most stable franchises we have. So the deviations we see in this quarter is linked to the timing of the rebate adjustments we did last year, where we had a reduction or correction in the latter part of the year. And then also seasonality in supply chain both in the U.S. and AAMEO. So we do not see any underlying issues in the short-acting category, which is a quite stable market from a market share and competitive dynamics point of view. Mads, on next-gen oral and CV?

Yes. So the analogue 2023 is based on the original research on the series of compounds that led to semaglutide not supposed to exhibit greater efficacy per se than Sema, because it’s not really been possible to identify any GLP-1s that do so. However, it’s been optimized for oral exposure, that basically means that you can deliver lower oral dosing level achieve the same degree of exposure of the body or alternatively, you can go to the same doses with oral Sema and achieve a higher degree of exposure and hence a higher degree of efficacy. So what analogue 2023 enables is one of two things: either higher efficacy, implying that it could be developed for obesity, could be developed for NASH, could be developed for high efficacy in type two diabetes; or you can match oral Sema as we know today and that would lead to a reduction in the cost of goods sold. And all of that we’ll know a lot more about next spring when we report the data both from this trial and from the second-generation oral semaglutide tablet formulation. They’re reporting approximately at the same time. Vis-a-vis, the FDA and the CV discussions, we are essentially have had very constructive dialog with the agency, where basically they are confirming that we have promising data with the SUSTAIN 6, however they need some kind of confirmation before we can have a CV indication for Ozempic and that confirmation can actually come in the form of either a bridging study even with an oral route of administration of semaglutide such as the so-called oral trial. Or in the best of all worlds, if the PIONEER 6 trial designed only to show safety were to in the upside scenario, provides signs of efficacy i.e., improved cardiovascular performance, then of course, that dialog will be held with the FDA. So that’s where we stand today, planning for ORALSO trial, but eagerly awaiting PIONEER 6 data. Thank you very much. Lars Fruergaard Jørgensen: Thank you, Mads. Very exciting. Thank you, Florent. Next question please.

We will now take our next question from Sachin Jain from Bank of America. Please go ahead. Your line is open.

Hi. Sachin Jain here from Bank of America. Two questions please. Firstly, I guess, expecting to give you a perspective on the recent Lilly GIP/GLP data. And then any plans you might have to both high doses and pick your triple agonist or potentially resurrecting the GIP/GLP that you didn’t continue last year. And then secondly, on numbers, obviously a restructuring program has happened. Could you provide any context what the annualized savings from that would be and in context of a 4% Part D headwind into next year? Thank you. Lars Fruergaard Jørgensen: Thank you, Sachin. Let me start by giving an overall strategic perspective on it, and then Mads can go a bit more into our scientific response. So first of all, I think what drives the value of the segment is continued innovation and we have seen that until now that for each and every time we have seen a new launch of efficacious GLP-1 agent, we have seen a larger market growth. We are seeing that now with our launch of Ozempic as well. So looking ahead, I welcome that Lilly also make a bet on innovation. There’s still some time to go before they can enter the market. And in that period, we have ample of time to establish Ozempic as a new golden standard and we have an opportunity to hopefully also launched all semaglutide. So the overall value of the market will be benefiting from two companies competing with similar tactics and say the short to medium-term tactics is still in favor of Nordisk. And then we are quite confident that we can also in terms of our next-generation product do something that’s competitive vis-a-vis Lilly. So, Mads, can you elaborate a bit on that?

Yes, Lars. So the first and most obvious thing that’s already ongoing is the emergence of a high dose Ozempic, of course, driven by step two and other relevant clinical data that may be needed for such a dose upgrade vis-a-vis the diabetes label. And that would enable Ozempic to remain unbeaten even in the face of the Eppendorf, the dual agonist from Eli Lilly, we believe. Then you also mentioned that we have in multiple dosing clinical trials both the triple agonist the targets the GIP, the glucagon and the GLP-1 receptor simultaneously and also a dual agonist known as 1177. The emergence or the resurgence of the MAR709 compound that came into Phase 2 when we acquired the Richard DiMarchi company is unlikely, because we do not believe that the ratio of agonist on the two receptors is ideal for that compound neither is the duration of action. But you also correctly allude to the fact that driven by the acquisition of the Equilibrium MB2 company with Richard DiMarchi, we of course, have access to numerous pharmacological tools ready to go with the GIP compounds dual agonist, triple agonist and whether they be for fixed dose combination or for that matter for chimeric or hybrid molecule information, all of that is of course in the pipeline and these are things that, of course, we analyze for the long haul, but for the short-term high doses together with good success on the oral Sema and existing Ozempic a clear way forward for us. Lars Fruergaard Jørgensen: So in summary, we welcome continued competition; it’s good for the patients, it’s good for the market and we are confident in both the short, medium and long-term competitiveness of Novo Nordisk in this. And Karsten, can you talk a bit through to the restructurings?

Yes, so the restructurings, what we have been out saying is that in terms of layoffs, we are looking at 1,300 employees by end of year, of with the majority has taken place as of now. And the cost included in our third quarter results are DKK 600 million, and the fact that the total cost related to the layoffs contained in our guidance for the full year. In terms of impact on 2019, let me just remind you that as we have previously announced then our guidance for 2019, we will issue that 1st of February. So we’re not going to provide any more detailed guidance on 2019 at this point in time. Lars Fruergaard Jørgensen: Thank you, Karsten. And thank you, Sachin. Next question please.

[Operator Instructions] We will take our next question from Peter Verdult from Citi. Please go ahead. Your line is open. Peter, your line is open. Please go ahead. Lars Fruergaard Jørgensen: Seems like we have a technical challenge there. So maybe you can move on to the next question. Peter can come back later.

Yes. We will take our next question from Trung Huynh from Credit Suisse. Please go ahead. Your line is open.

Hi, guys. Just two from me please. Firstly, in the past you’ve noted GLP pricing is limited versus the insulins. Now, you are through your 2019 contracting. Have you seen any significant change in this dynamic given the GLPs are now becoming a much bigger part of treatment? And then the other on Biopharm. Just wondering if you can give a bit more color on why Jesper’s stepping aside as the Head of Biopharma. You only moved him into this role at the start of the year. Is there any change in the strategy of this division? Thanks very much. Lars Fruergaard Jørgensen: Thank you. So on GLP-1 pricing we see an unchanged competitive situation. So there’s not much news there. I think it’s really important to underline that we see a very strong market growth of some 25% and we are growing on par with the market. We remain very confident and optimistic about the future of our GLP-1 business. In terms of Jesper, Jesper has been 20 years with Novo Nordisk and has been a fantastic colleague and contributor to both the team and the Company. And I have had a dialog with Jesper about what he wanted to do. And Jesper has had a wish to find more time in life to pursue other activities. So this is a dialog and say an agreement that we have landed together. So there’s nothing in relation to the Biopharm strategy or anything linked to this. Jesper’s done a fantastic job in establishing a strategy whereby we can accelerate growth both on getting more out of what we have, so the organic initiatives; and also zooming in on what we believe could be interesting bolt-on acquisition opportunities, and we actually landed a small one yesterday. So highest regards about Jesper’s performance. And now we have Ludovic Helfgott coming in and he host a fantastic pleasure of actually having an updated strategic plan on his desk the first day he arrives. So he can hit the ground running. So no change in overall strategy in this regard. So it’s business as usual. Thank you very much.

Thank you. Lars Fruergaard Jørgensen: We have Peter back on the line.

Yes. We’ll now take our next question from Peter Verdult of Citi. Please go ahead. Your line is open.

Sorry for that my handset died, but just two questions. Just, Lars, you – yeah, just for you, it’s good timing. Part D, can you just confirm that it represents about 15% of Novo’s Group sales, I just wanted to check in with you on the latest thoughts on potential reform. I mean, would Novo consider launching second brands to deal with a rebate-free world in Medicare, so you don’t impact your commercial book of business? And then Mads, can we just go back and pick up on the conversation we had at EASD, and follow-on from Sachin’s questions, just on GLP/GIP. Can you comment at all whether you have any GLP/GIPs in research that have the same sort of preferential agonism for GIP over GLP as the Lilly compound has. I’ll be interested in your thoughts there, and how quickly you might be able to get that into the clinic. Lars Fruergaard Jørgensen: So, thank you, Peter. So in terms of – if I heard you right, Medicare Part D, I don’t know if we can get the 15% from we have hardly any exposure Medicare Part D. So –

Part D, D for Donald Trump. Lars Fruergaard Jørgensen: Okay. All right. So I think we spoke about that after Q1 where we saw the change in cohorts cap funding for 2019, and there’s nothing new to that, that’s unchanged compared to what we said, 1% to 2% impact on the topline. In regards to operating in a world without rebates or potentially launching products at a lower price without rebate, it’s something we have looked into and we can handle it. It’s unfortunately not as simple as just launching another product, because it introduces some complexities both in the supply chain and also in the physician’s office having to prescribe another product. So it’s a change we can pursue, but we do not believe that it’s solving the problem right now, because it will create other issues. So it’s not something we’re pursuing actively as we speak.Mads, on the EASD discussion.

Yeah. So, Peter, there are two ways you can achieve the desired ratios of agonism versus different receptors where there are two or three receptors. One despite creating dual or triple agonistic molecules, that is like what we have in the multiple dosing with a triple agonist, that’s a single molecule. The other option is, of course, to take a ideal GLP1 molecule like semaglutide and ideal GIP molecule with a similar half-life semaglutide that are compatible with each other and then explore which ratio is the ideal in an FTC fixed-dose compound so to speak. So those are clear options. When that is said, our believe is that Ozempic, given at a high dose to people with diabetes of 2.4 milligrams is currently ongoing already in the STEP 2 trial is something that will basically in principle years ahead of the Eli Lilly launch still make Ozempic unbeaten from a efficacy perspective. But the other options are fixed dose combinations and hybrid molecules with the defined ratios and of course they do exist as you can imagine in the DiMarchi Labs.

Thank you. Lars Fruergaard Jørgensen: Thank you, Mads; thank you, Peter. Next question please.

We’ll now take our next question from Michael Novod of Nordea. Please go ahead. Your line is open.

Thank you very much. It’s Michael from Nordea. Two questions. One to Lars around comments you made in Danish media that you do see competition on the insulin side, perhaps not increasing that much and potentially also that we should revise – pass our most bearish expectations around where pricing is. Maybe you could help elaborate a bit more on that also after we saw Merck-Samsung not go for the basal insulin generic. And then secondly on obesity. You do have very strong traction in obesity. I’ve asked this before, but do you have any considerations around starting more to active promotion, D2C campaigning, et cetera, or do you still see that insurance coverage is too low in the U.S., for example? Lars Fruergaard Jørgensen: Thank you, Michael. I will start by the pricing questions, then Camilla can give some perspectives on our ambitions in trying to expand the obesity market. So I think it’s important to operate with different scenarios for how the future pricing environment can go forward, and then look at what are the triggers for these scenarios to come into play. And if you look at the downside scenario, that’s one where one or more additional biosimilars come to market and then kind of reopen all the contracts and you get another tough rebating round. With Merck-Samsung pulling out, I do not obviously know their calculation, but I would imagine that that’s based on a commercial assessment that right now there is a situation where we are at a rebating level and contracting composition across the players that makes it difficult to come in and succeed commercially in that area, which obviously means that I think that scenario becomes less likely and the scenario where you say that, okay, we have reached rebate levels that are low. And if you have to unlock some of these contracts and move patients across, there is a risk associated with that, because if you don’t manage the volumes, the financials does not add up. So I’ll just say that since our last discussion a quarter ago, there’s been that one change that I think the likelihood of the low-end scenario has become less likely as one of the contenders in that scenario has pulled out. But I’m not giving any guarantees, I’m just trying to say that it’s important to operate with different scenarios and then look at what is the relative likelihood across those scenarios. So I, in my account this is a – I’m optimistic about the price environment going forward in the U.S. basal category. Camilla, on obesity and some of the tactics we could deploy to grow that category.

Yes. So today we have 650 million people suffering from obesity and I should know only 2% of those are being treated with the pipeline that we have in obesity and it is clear that is going to be one of our four focus areas for the future. And we have just recently looked at what are some of the barriers to obesity treatment, a big part of that has to do with recognizing this as a disease. So that’s clearly something that we will be working on going forward. Second driver is the number of physicians that are actually able to treat this disease which is initiatives we have also taken to support on in a number of countries. And then finally, we also noticed that because obesity is not recognized as a chronic disease, we do see that patients with drop-off treatment relatively early after having initiated the treatment simply because they see a weight loss. So we are looking at how we can work with patient support programs that will support the patient to see a continuous weight loss respecting that this is a chronic disease. So those are some of the elements we are working on and you will see us do more investments in this area, but hopefully also more returns. Lars Fruergaard Jørgensen: Thank you, Camilla. Thank you, Michael. Next question please.

We will take our next question from Richard Vosser from J.P. Morgan. Please go ahead. Your line is open.

Hi. Thanks for taking my questions. Just going back to the high dose Ozempic, when looking at the Phase two data with higher doses in diabetic patients, can you give us your perspective on whether you will see higher HbA1c reductions? I think we obviously can think that the weight will be substantially higher when you increase Ozempic doses to higher levels, but there seem to be some plateauing of the HbA1c drops in the Phase 2 data. So what is your modeling tell you about that going forward? And then secondly, just thinking about the formulary changes that we’ve seen in 2019, we’ve seen some losses that some of your competitors in the Medicare area in terms of their coverage on lives, yours is I think broadly the same. So what sort of volume share gains do you think you can get a hold of in 2019, we’ve obviously seen some good volume in 2018 that you’ve been able to capture? Thanks very much. Lars Fruergaard Jørgensen: Thank you. Mads, on high dose Ozempic.

Well, Richard, yes, if you are referring to the only full data set that we have across to dose response relationship for semaglutide in the injectable version, that is indeed the Lancet paper that came out a few months ago and kind of compiles all the data that we have from Phase 2. Now do bear in mind that that was an obesity trial in close to 1,000 patients treated for about a year, and they were either totally non-diabetic or only dysglycemic, i.e., having a pre-diabetes defined by the hemoglobin A1c level of being below 5.7 and 6.4. This also means that it’s very difficult to make any guesstimations on the A1c effects of semaglutide in a non-diabetic population. But what I can tell you is that we have explored using HOMA-B, beta-cell function; and HOMA-IR, insulin resistance assessment. And what it tells us is that in as much as you tend to now it gets a bit nerdy in as much as you hit the 90%-plus efficacy level on the dose-response curve for beta-cell activation, probably at levels around the one milligram semaglutide dose, you’re in a different situation when it comes to body weight, where you have not even leveled out at 2.4 milligrams, because of the excellent penetration of sema into the brain that also means that the HOMA-IR, the insulin resistance measures, they improve with the higher doses of semaglutide. And with improved insulin sensitivity, there is a secondary effect on the beta-cell in that each insulin molecule works better and you get a secondary effect on hemoglobin A1c. This, you cannot see in the pre-diabetic population, there you have to go into overtly Type two diabetic population and that’s what we’re doing now. And I would actually expect to see a rather significant secondary effect on A1c despite the dose-response curve being homosaturated for the beta-cell, it’s secondary to the improved insulin sensitivity, that is relatively unique to semaglutide, we’ve did not see it for Lira and I’ve not seen it for Dula. Lars Fruergaard Jørgensen: Thank you, Mads. In terms of formulary changes next year, we see overall an unchanged access environment. So our focus is on winning market shares with Tresiba and Xultophy and obviously Ozempic. So we don’t see a significant, say, shift in volumes coming from contracting, but we are quite confident that we can continue our strong commercial execution based on these key products. Thank you, Richard. Next question please.

We’ll now take our next question from Michael Leuchten from UBS. Please go ahead. Your line is open.

Thank you very much. Good afternoon. Two questions please. One on International Operations, if I look at the insulin franchise in Q3, the growth was a little bit slower than expected and it seems to be soft across a number of products. Just wondered if there’s any explanation or it was just normal sensitivity in the quarter. And then sorry, Mads, just going back to the GIP/GLP data, Lilly is very aggressively communicating that they think they can show data take into discontinuations down well into the single-digits. Given what you know about the PK/PD of GIP/GLP and what the dual-agonism does in the pancreas, how like of a scenario is do you think is it somebody can get discontinuations into arranged that is below what we’ve seen the GLP-1s across the board so far? Lars Fruergaard Jørgensen: So should you start with Mads, since we were down this alleys just a minute ago.

Yes. Well, to be honest, Michael, very difficult for me to speculate on. I would say though that there is the notion that GIP and GLP-1 do each in their own right, have the ability to promote some degree of nausea by mechanisms that seem to be not totally overlapping, i.e., one plus one might equal to, at least, that’s what we’ve seen. We also saw that in the MAR709 trial. So in order to go to a low-single digit discontinuation rate with such a high degree of efficacy, you’d have to have a very, very subtle escalation, dose escalation over many, many months, I would suggest. But I don’t really have any comments. There you should trust the Lilly colleagues in their predictions, I guess. Lars Fruergaard Jørgensen: Thank you, Mads. And Mike, can you share a bit of light on insulin performance in Q3?

Yes. I think, the quick answer is that we see across the board no major change at all. In International Operations, a good part of the insulin is still composed of human insulin and tendering versus last year tendering versus quarter-to-quarter, of course, creates the fluctuations you see in Q3. But if you take a look at some of our key brands, Tresiba, Xultophy, Fiasp, Ryzodeg, they are all doing fantastically well also in Q3. So no issues whatsoever. Lars Fruergaard Jørgensen: Good. Thank you. That’s encouraging. Thank you, Michael. Next question, please.

We will now take our next question from Keyur Parekh from Goldman Sachs. Please go ahead. Your line is open.

Good afternoon and thank you for taking my questions. Two please. The first one is, can you just share your thoughts on how the recent guideline changes from both the ADA and the EASD kind of shape your outlook for the GLP-1 business, especially as it relates to the non-U.S. markets? And then secondly, one for Camilla. Camilla, as you think about kind of the strategic positioning for oral semaglutide, can you help us think about how the Lilly data changes where you think oral semaglutide might play longer term? Thank you. Lars Fruergaard Jørgensen: Thank you, Keyur. Mads, first on the guidelines.

Yes. I think, Keyur, that now with the adoption of the final guidelines, we are actually seeing two very prominent drug classes right up there in the pole position after metformin, of course, and that is obviously the GLP-1 agonist, and it’s also the SGLT2 inhibitors. In terms of atherosclerosis and CBD, in general, they single out GLP-1 and SGLT2 with an emphasis on GLP-1 for atherosclerotic cardiovascular disease and there the rank order is actually Victoza above Ozempic above Bydureon, and no others mentioned. And that’s just based on the burden of evidence and how robust the data. That’s good news for both of our GLP-1 agonists. And as you know, ex-U.S. we already have all the wonderful SUSTAIN 6 data in the label for Ozempic. So that can be adopted by the colleagues in the area right away. On the downside, there was a downgrade on the renal indication where I guess because of credence and other excellent kidney data coming out in the SGLT2 class, now there is kind of a favoring of SGLT2 in renally impaired patients and then followed by GLP-1. But in patients that actually have inadequate renal function, I guess, below 45 or so, then they actually have GLP-1 in the pull position and that would again be the novel compounds, because they are the ones that have data. And finally, I think for weight concerns, they explicitly mention again GLP-1 and alternatively SGLT2 and there – they actually rank order Ozempic above Victoza above Trulicity. So I think overall, this is really good news for patients and it’s also really good news for the most GLP-1 portfolio. Lars Fruergaard Jørgensen: Thank you, Mads. Camilla, as far as the latest data from Lilly, have any impact on how you see oral sema?

So oral semaglutide, it has the potential to be positioned as the best OAT in the market and we have readout eight of the ten PIONEER trials now, that have shown very consistent data. So we need to remember that 65% of patients in the diabetes market are treated by tablets and this is of course also a potential for oral semaglutide to move into this particular space, so whereas just around 6% are treated on injectable GLP-1s. So there is a big potential for oral sema outside the injectable space as well. Lars Fruergaard Jørgensen: Good. Thank you, Camilla. Thank you, Keyur. Next question please.

We will now take our next question from Wimal Kapadia from Bernstein. Please go ahead. Your line is open.

Hi. Great. Thanks very much for taking my questions. Wimal Kapadia from Bernstein. I have a question on obesity. So I guess, Mads, what did you see in the original PYY products that gave you confidence in moving another into the clinic? So any color there would be helpful. And then when will we see more data from the early stage pipeline? So, in particular, thiamine analogue, the triagonist and even the dual GLP-1 glucagon agonist? And then my second question is just tied to an earlier comment around innovation in the GLP-1 market and expansion. The class today has about close to 5% of the volumes in the U.S.. I guess, I’m just curious to see – does Novo see a limit to the penetration of the class longer term? Thank you very much. Lars Fruergaard Jørgensen: Thank you. Mads, on obesity.

Yes. So on PYY, there’s this interesting notion that as a stand-alone therapy unlike Amlin. Amlin 833 has shown weight reductions up to 1% per week for a total of seven weeks, meaning 7% weight loss in seven weeks in human beings, which is relatively amazing. But if you look at PYY, this is not the case. PYY seems to be a little bit like GIP does in the context of type two diabetes, where GIP only works in the presence of GLP-1, pretty much the same may well be the case for PYY in the case of weight loss that there is an interaction probably at the level of the nucleus between PYY and GLP-1. And that’s why we need to optimize the PYY for penetration into the hypothalamus and then there is a good chance of really exciting weight loss profiles in humans, at least, if they are to behave as the rodents that we’ve tested. In terms of when we get data from the early portfolio, this is the last meeting we are having this year because we are in Q3. So I guess my answer would be next year. Lars Fruergaard Jørgensen: Thank you, Mads. And in terms of how far the GLP-1 class can make it, it’s not something we have a, say, a set view on, but it’s clear when you look at the profile of the GLP-1s, what they do to patients, this is a very attractive treatment to be on. We see strong growth currently, so for the short-term, we believe this dynamics will continue, but we cannot give you an answer for how big it will eventually be. Time will tell. With that, we have time for one last question. Thank you, Wimal.

We will now take our next question from Carsten Madsen from SEB. Please go ahead. Your line is open.

Thank you very much. Carsten Lonborg, SEB. Two questions. First of all, regarding the donut hole funding gap, on the Celgene’s recent conference call they were also asked about this and they kind of left an impression that there are still something to be worked out, basically saying that this is something that could change as we in the year before final legislation is actually passed. I was just wondering whether you have also since the – a change since Q2 where you commented on the donut hole funding gap and whether you think is setting stone what should happen in 2019 or not? And then final question, Victoza in Q3, in China, you delivered 190% local currency growth. How much of this is sort of changes in the channel and how much is the underlying demand for Victoza? Thanks. Lars Fruergaard Jørgensen: Thank you, Carsten. You’re right that the way the whole increased funding or the coverage gap came in kind of overnight, hitting in a big national bill, came as a surprise. So lot of strong efforts is being done in the U.S. to reverse it partly. I know that – and of course, the industry is participating in these discussions and lot of good thoughts are going into it. I think, in today’s environment, I think it’s quite challenging to roll back something that has already been implemented on the account of supporting the drug industry. And if you were to do it, you would need to have – need to find the money somewhere else and probably from another pharmaceutical category or – and I just think it’s low likelihood that we will see this being reversed. It doesn’t mean that we are giving up and we should keep pushing for it, because I think the way it was implemented overnight and the specific impact, I think, is probably not the right way to manage cost and the patients are not benefiting from this, and I think that was the overall aim. So I think better ways to lower through our cost for Americans than what was put in place here, but I’m not overly optimistic that this will be reversed. Mike, on Q3 Victoza in China?

Yeah. So we are very happy with the Chinese Victoza performance throughout the year, you should probably not get too hooked on the quarterly numbers again so much. If you take a look at the first nine months, the growth has been 89% and spot on to our own projections and expectations and that’s what you should basically except I think the opportunity is high. You should note that the GLP-1 market in China is relatively small compared to the rest of the world. So we have a lot of opportunity and we have reorganized ourselves and made some large investments also in terms of a sales force. So we do have high expectations. And so far, the first nine months has lived up to that. Lars Fruergaard Jørgensen: Thank you, Mike. Thank you, Carsten. This concludes our conference call. Thank you for participating and feel free to contact our Investor Relations Officers to ask any further questions you might have. Thank you and have a good day.

This concludes today’s call. You may now disconnect.