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Bristol-Myers Squibb Co (BMY 0.54%)
Q3Â 2019 Earnings Call
Oct 31, 2019, 8:30 a.m. ET
Contents:
- Prepared Remarks
- Questions and Answers
- Call Participants
Prepared Remarks:
Operator
Good day everyone and welcome to the Bristol-Myers Squibb 2019 Third Quarter Results Conference Call. Today's conference is being recorded. At this time, I would like to turn the conference to Mr. John Elicker, Senior Vice President, Public Affairs and Investor Relations. Please go ahead, sir.
John E. Elicker -- Senior Vice President of Corporate Affairs & Investor Relations
Thanks Augustus [Phonetic] and good morning everybody, we're here to discuss our Q3 earnings results. With me, we have Giovanni Caforio, our Chairman and Chief Executive Officer; Charlie Bancroft, our Chief Financial Officer. They will both have prepared remarks, Chris Boerner, Chief Commercialization Officer and Dr. Samit Hirawat, Chief Medical Officer and Head of Drug Development will be here for Q&A as well.
I'll handle the legal requirements first. During the call, we'll make statements about the company's future plans, prospects that constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the company's SEC filings. These forward-looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any future date. We specifically disclaim any obligation to update forward-looking statements even if our estimates change.
We will also focus our comments on our non-GAAP financial measures, which are adjusted to exclude certain specified items. Reconciliations of these financial measures to the most comparable GAAP measures are available at our website. Giovanni?
Giovanni Caforio -- Chairman of the Board and Chief Executive Officer
Thank you, John and good morning everyone. I'm pleased to speak with you today about another great quarter in which we had strong operating performance, reported significant new data for our oncology franchise and made important progress to close the pending acquisition of Celgene and integrate the two companies.
Let me start with our oncology franchise and the recent results we announced for our lung cancer program. I believe we have an opportunity to play an important role in first-line lung cancer.
We now have a second trial demonstrating an overall survival benefit for the combination of Opdivo plus low-dose Yervoy in a first-line lung cancer population. Regardless of PD-L1 status or histology. With the results of both Checkmate -9LA and -227 coupled with the strength of our commercial capability, I feel good about our ability to maximize the opportunity we see in the first-line lung cancer market.
Let me quickly recap the findings from our two recent lung cancer studies. With Checkmate -227, we've learned that dual I-O offers a unique potential for long-term survival in first-line lung cancer. Physicians have told us that the depth and durability of response is important and we saw a clear contribution of parts when comparing Opdivo plus Yervoy to Opdivo monotherapy in PD-L1 expressors.
We also saw that Opdivo plus Yervoy has better overall survival outcomes than the PD-1 chemo combination in PD-L1 negative patients. As we described at ESMO in September, it is our view that the dual I-O regimen will play a role in the treatment of first-line lung cancer and this is supported by the feedback we have received from physicians. We also know that due to rapidly progressing disease, some first-line lung cancer patients need chemotherapy.
A key question for the Checkmate -9LA study was to determine whether a limited amount of chemo, two cycles would be enough to stabilize the disease for those patients and manage the early part of the curve, allowing for the potential durability of effect of dual I-O.
We are pleased with the positive interim analysis from Checkmate -9LA, which demonstrated a meaningful overall survival benefit from our I-O combination concomitant with a limited course of chemo. We expect to report this data at an upcoming medical meeting, likely in 2020. We also look forward to sharing the findings with health authorities soon.
At ESMO, we also presented important data that explored new approaches in difficult-to-treat tumors and reinforced the benefit of the Opdivo plus Yervoy arrangement. In addition to our first-line lung cancer data, we presented Opdivo plus Yervoy five-year overall survival data in metastatic melanoma. We also presented important data for other types of tumors, including prostate, cervical and esophageal cancers. We continue to see opportunities to broaden the use of our I-O medicines to benefit more patients and the breadth of data presented at ESMO is a good indication of our progress.
I'm looking forward to future data read-outs in our I-O development program, including adjuvant, beginning next year. As John mentioned, Samit Hirawat is here with us today. He can share his perspective on the full portfolio as well as his priorities for the development organization during the Q&A. Now let me turn to the third quarter results.
We continued to deliver strong results, driven by excellent commercial execution across our portfolio. Our teams have done a great job in a very competitive market for Opdivo and we're able to maintain strong market shares in key indications to date. Eliquis continues to show significant growth with potential for expansion moving forward. The Eliquis profile is strengthening globally as the product is already established as the global standard of care. This quarter, at ECC, we presented the largest real world data set of French atrial fibrillation patients, which confirmed Eliquis' best-in-class profile. Charlie will provide more color on our performance in the quarter and the potential opportunities that we see ahead.
Turning to our transaction with Celgene. I am pleased with the significant progress we've made to bring together two leading innovation companies united by a shared focus on transforming patient lives through science. While the transaction has been pending, Celgene has continued to deliver on their business priorities, and today they announced strong results for the third quarter. During the quarter, Celgene made significant progress on the late-stage pipeline.
The FDA approved Inrebic or fedratinib as the first new treatment in nearly a decade for patients with myelofibrosis. We were also encouraged to see the success of Celgene CC-486 study in acute myeloid leukemia patients looking for a maintenance option. I am very proud of the people at Bristol-Myers Squibb and Celgene. Both teams delivered terrific quarters and at the same time made meaningful progress toward the closing the transaction and planning for integration.
Importantly, we are on track to realize the expected $2.5 billion in the run rate cost synergies by 2022. During the third quarter, we achieved two key milestones in the process to close the transaction. We received approval from the European Commission in July. In August, we announced an agreement between Celgene and Amgen to divest OTEZLA for $13.4 billion in cash following the close of our acquisition of Celgene. FTC clearance is the remaining regulatory milestone to complete the Celgene transaction. We continue to expect to complete the combination of Bristol-Myers Squibb and Celgene before the end of 2019.
In the meantime, we are focused on building the organization structure of the new company with the goal of delivering on the promise of this combination for our patients, our employees and our shareholders. Following the announcement of my future leadership team in June, we announced internally the next layer of management in September. These leaders are now working on preparing for integration to ensure that we hit the ground running on day one.
To conclude my remarks, I'd like to reiterate how pleased I am with our continued strong performance. I am encouraged by the results we announced in our first-line lung program by enforcing the benefit of the Opdivo plus low-dose Yervoy arrangement and the potential opportunity to provide new treatment options to patients.
As we move closer to completing the Celgene transaction, I'm even more excited about the potential of the combined company. Both businesses are performing well. The pipeline is progressing and we have seen significant clinical and regulatory progress. I am looking forward to more news at ASH. Commercially, we're on track to support multiple future launch opportunities and I'm confident we are ready for the integration and our ability to execute as a combined company. With that, I'll hand it over to Charlie.
Charles Bancroft -- Executive Vice President, Chief Financial Officer and Global Business Operations
Thanks Giovanni and good morning everyone. We had another good quarter with important pipeline developments, strong product performance and continued progress toward closing the Celgene acquisition. Let's start with I-O performance. Our US commercial team continues to execute very well maintaining strong share in key indication. As expected, we continue to see the size of the eligible pool of second-line lung patients decline during the quarter. This trend has been in line with our projections and we continue to expect it to level off toward the end of this year. In the first line RCC space, we continue to perform well where Opdivo Yervoy remains a standard of care in intermediate and poor risk patients. As we've described in the past, TKI I-O combinations are expanding the use of I-O, mainly at the expense of TKI monotherapy. However, as we mentioned in Q2, there has been some attrition of new patient share for Opdivo Yervoy.
This, combined with the unfavorable inventory movement, affected US sales for Yervoy during the quarter. Also, remember that Yervoy is more sensitive than Opdivo to variability in first-line RCC demand because the dose schedule is front-loaded. Internationally, we continue to see good I-O performance in new launches such as renal and adjuvant melanoma with the second-line lung patient pool declining more slowly than in the US as we expected.
Turning now to Eliquis. Our commercial teams globally continue to execute very well by leveraging the differentiated profile of Eliquis, establishing Eliquis as the global standard of care. In the US, we delivered 23% revenue growth in the quarter. This was driven by significant demand generation with Scripps growing 30% compared to the same time last year. As expected, we saw increased gross to nets from the donut hole, impacting revenues during the quarter. As in prior years, we expect to see a significant impact from the donut hole again in Q4.
Internationally, we also saw strong growth as Eliquis is now the number one oral anticoagulant in multiple countries outside the US, while continuing to build momentum to overtake Warfarin countries such as France. During the quarter, we saw continued stable demand for Sprycel in the US. The inventory levels have normalized compared to a significant workdown that occurred in Q3 last year.
Regarding some key line items in the P&L during the quarter. Other income and expense benefited mainly from licensing fees in the quarter as well as higher royalties. Our tax rate was favorably impacted by one-time items in the quarter, which we anticipated in our full-year tax rate guidance of approximately 16%. Based on the performance of the business, we've updated our non-GAAP EPS guidance today for BMS on a stand-alone basis.
For the combined company as Giovanni has noted, we have significant opportunities ahead. Though we won't be in a position to provide guidance for the combined company until some point after the deal closes, let me remind you about some of the mechanics of the pro forma P&L. Starting with gross margin. This will continue to be primarily dependent on the product mix of the combined company. Eliquis, for example, will remain a headwind compared to the other products in the portfolio.
Regarding OpEx, it will be important to add back Celgene's stock-based compensation to the non-GAAP OpEx of the combined company to be consistent with the BMS practice. We also expect roughly one-third of the $2.5 billion of synergies to be realized next year.
[Indecipherable] for the combined company will include interest expense from existing debt from both companies, including the $19 billion of acquisition-related debt we raised earlier this year at an average rate of 3.5%. After the close, the share count will increase by the number of shares outstanding for Celgene at close as well as the dilution from stock-based compensation, partially offset by the ASR.
When we look at the P&L of the combined company, we are very encouraged by the accretion and earnings power of the company moving forward. Regarding capital allocation, we see significant cash flow generation for the combined company and we plan to continue to employ a balanced approach to capital allocation. We initially projected in excess of $45 billion of free cash flow over the first three years for the new company.
Though free cash flow will be slightly lower due to the absence of operating cash flow from OTEZLA, this doesn't include the $13.4 billion we respect -- we expect to receive on a pre-tax basis from the sale to Amgen. The substantial cash flow generation will allow us to delever, increase the dividend, fund the ASR and invest in innovation. Reducing debt and delevering, excuse me, and delivering on our commitment to achieve gross debt to EBITDA at less than 1.5 times in 2023 is central to maintaining strong investment grade credit ratings.
The proceeds from OTEZLA will be prioritized to reduce near-term debt and avoid excess initial leverage. We remain committed to the dividend as evidenced by our 10-year track record of continual dividend increases and as we previously mentioned, we've modeled annual increases in our pro forma financials.
We've increased our ASR from $5 billion to $7 billion and we expect to execute the ASR after close. We will continue to be active in the business development in the near term, focusing on early stage and smaller deals. where we reduce debt and rebuild balance sheet flexibility.
To close, we've had very good operating performance during the quarter and with strong business momentum for both companies, we are well positioned to embark on our next chapter as a combined company following the close. Now, I will turn it back to John to start the Q&A.
John E. Elicker -- Senior Vice President of Corporate Affairs & Investor Relations
Thanks Charlie and Augustus. We can go to the Q&A session now. And just as a reminder in addition to Giovanni and Charlie, both Chris and Samit are here to answer any questions you might have. Augustus?
Questions and Answers:
Operator
Thank you, sir. [Operator Instructions]. Our first question will come from Terence Flynn with Goldman Sachs.
Terence Flynn -- Goldman Sachs -- Analyst
Thanks for taking my question. Just wondering if it's reasonable to assume that the Checkmate -9LA data are stronger than the -227 data across both PD-L1 in PD-L1 negative patients given the trial unblinded on an interim analysis. And then, wondering if the plan is to file these data separately then -227.
And then the second question I had just relates to Opdivo for 2020. Last quarter, I think you said you're expecting some pressure next year just given the third quarter trends and the recent clinical data, any updated thoughts you can share there on the outlook for growth. Thank you.
Giovanni Caforio -- Chairman of the Board and Chief Executive Officer
Thank you. So obviously, as you know we're not going to comment on interaction with regular -- regulatory authorities or our regulatory strategy. As we did mention, we are planning obviously on sharing data from -9LA with health authorities around the world. Samit will give you a perspective on on the results and the data and Chris will comment on Opdivo performance.
Samit Hirawat -- Chief Medical Officer, Global Drug Development
Thank you, Giovanni and just to reiterate, I think Giovanni had already said in the beginning and we are truly happy with the results of -9LA and putting into perspective, the two positive trials certainly bodes well for the combination of nivolumab plus Ipilimumab. I think it's going to be very important to then look at the data when we are able to present it at future medical meeting to understand the outcome for patients in terms of the efficacy when we combine two cycles of chemotherapy right upfront in combination with nivolumab as well as low-dose ipilimumab in terms of safety management and overall outcome and how the curve might be impacted and if the early part of the curve can then be carried through the rest of the curve. We obviously cannot compare and convey what the results are in terms of the comparison of -9LA versus -227. We can't comment on the biostatistical analysis plan itself and as Giovanni said we will not comment at this time about our regulatory strategy of filings. But let me pass it a Charlie -- to Chris for more comments.
Chris Boerner -- Executive Vice President and Chief Commercial Officer
Yeah, thanks, Terrence. We're obviously from a commercial standpoint, very pleased with the data that we saw in the front line lung cancer over the last few weeks. Looking for -- and we're also very much looking forward to the regulatory discussions that will take place, and ultimately being able to commercialize in first-line lung, given the competitive dynamics in the US and the timing of those regulatory interactions though we do still see Opdivo under pressure in 2020.
However, as we've said consistently, the trajectory of growth beyond 2020 is going to be dependent upon new indications and based on the data readouts we've seen thus far and the continued very strong execution of our commercial teams, we feel pretty good about returning to growth in 2021. Now the shape of that growth will continue to be a function of additional data readouts in the metastatic setting. Those include 9ER and first-line renal, Checkmate -648 in first-line esophageal and first-line gastric cancer from Checkmate -649. All of those will read out in 2020 and then we also expect to see adjuvant programs to begin to read out in '20 and 2021 and those as you know, will include bladder, melanoma, gastric and neoadjuvant lung cancer.
John E. Elicker -- Senior Vice President of Corporate Affairs & Investor Relations
Thanks Terence, Can we go the next question please, Augustus?
Operator
Certainly. We'll go next to Geoff Meacham with Bank of America.
Geoff Meacham -- Bank of America Merrill Lynch -- Analyst
Just had a couple. Thanks for the question, guys. On the renal marker, I just wanted to get a sense for what you guys are seeing first-line versus second-line trends just given the compared dynamic during the quarter. And then just to follow up on a prior comment from Chris just earlier. I know you guys are, have already offered a perspective on what to expect for 2020 I-O trends, but with the early interim look for -9LA and the -227 refiling, is it reasonable to assume a tick up, let's say, in the second half of 2020 as the first-line lung data are digested and rolled out in the marketplace? Thank you.
Chris Boerner -- Executive Vice President and Chief Commercial Officer
Yeah. So, thanks, Jeff. Let me just start with renal. Obviously, we had competitive impact from I-O and TKI in the earlier part of this year post the launch of those regimens in the first half of the year. However, what I would say is in first-line renal today as we look at our on-label population our shares holding around 30% to 35%. That's been relatively consistent, frankly, over the last number of months. The competitive share that we've seen I-O TKI take has mainly been coming as was mentioned earlier from TKI monotherapy and we've actually seen growth in the I-O class share in first-line renal as a result of that. But as I said, our shares holding in the 30% to 35% range and that's been stable really over the last number of months.
With respect to second-line or share, and second line is roughly 36%. We do see that decline in the eligible pool and second line as a result of first-line dynamics. But I think one thing to keep in mind in renal that's different from, for example, lung cancer at least as of to-date and that is in the renal cell market while you see a decline in eligibility in second line, you also see Opdivo plus Yervoy playing a role in the first-line setting and obviously at least right now, that's not the case in non-small cell lung cancer.
And then respect to 2020 and '20 and growth for Opdivo beyond 2020, I think I would just refer back to the -- to the answer I gave to Terrence's question. I think that we're going to have to see how the dynamics play out with respect to the timing of regulatory interactions. But I think right now we still do see Opdivo under pressure for 2020. But as we get beyond 2020 and certainly into 2021, metastatic and adjuvant programs will readout and we very much continue to see Opdivo as a growth brand.
John E. Elicker -- Senior Vice President of Corporate Affairs & Investor Relations
Thanks, Jeff. Augustus, can we go to the next question please?
Operator
Yes, sir. Will come from Chris Schott with JP Morgan.
Chris Schott -- JP Morgan -- Analyst
Great, thanks very much. Just coming back to Opdivo Yervoy and first-line lung and I realize you can't talk about the -9LA data at this point, but just maybe bigger picture question. As you think about the role of chemo induction followed by dual I-O as compared to just a Opdivo Yervoy alone strategy, at this point is there -- do you see one of those profiles really standing out relative to the other in terms of what's going to be optimal kind of treatment profile for those agents in front-line lung sort of get just more kind of qualitative sense of is -- is one really kind of looking at like the front-runner versus the other?
My second question was just was on leverage. I know it's been a few moving pieces over the course of this year with the OTEZLA sale et cetera and we get the longer-term leverage targets. But can you talk about your expected leverage and debt profile as we look at 2020, should try my hands around how quickly your balance sheet is going to be back at a point where we can think about the company looking to deploy capital again? Thanks so much.
Chris Boerner -- Executive Vice President and Chief Commercial Officer
Chris, maybe I'll take the first question and then I can turn it over to Charlie for your second question. The way we think about -9LA frankly is very much in the context of -227. And as you recall from the conversation we had at ESMO, we see first-line lung cancer still as a market with significant unmet need. For example, the majority of patients treated with standard I-O plus chemotherapy are going to relapse within a year. And based on the conversations that we had with the physicians going into ESMO and certainly since ESMO, they see a few things.
First, there is considerable need for additional options given the unmet need in first-line lung cancer. And second, they see opportunity for dual I-O therapy. They're impressed with the tail of the overall survival curve that they saw from -227, the complete response rates and importantly the duration of those responses they view is very compelling. And you see -227 is providing an important option with a manageable safety profile for patients who don't need or want chemotherapy. What -9LA does in the way we think about it is for patients who do require chemotherapy, the question really is whether a limited amount of chemotherapy, in this case two cycles, adds value to dual I-O therapy. Obviously, we just got the topline data. We haven't gone through all the specifics. So we can't comment on that. However, what we can say is we're very pleased that we have a second trial demonstrating an overall survival benefit for the combination of Opdivo and low-dose Yervoy and remember this was a study that was regardless of PD-L1 status or histology.
And we do believe that -9LA and -227, coupled with the strength of our commercial organization gives us a real opportunity in first-line lung cancer and one that we can capitalize and we very much look forward to the opportunity to do so. And so with that, maybe I'll turn it over to Charlie.
Charles Bancroft -- Executive Vice President, Chief Financial Officer and Global Business Operations
Yeah, thanks Chris for your question. As I talked about my comments, and we've talked about in the overall deal dynamics, deleveraging and getting back to our balance sheet flexibility is really important although as I -- as we've continued to mentioned during early stage deal is already included in our cash flow analysis. But let me just kind of walk you through the math. We have already taken out $19 billion in loans as you know, we've talked about that. Celgene has $20 billion in debt outstanding plus $6 billion [Phonetic], at the end of 2019, we'll have, as a combined company, $45 billion in debt, which is significantly less than we originally considered given the OTEZLA sales and cash flow generation. As we exit 2020, we expect to be about 2.5 times debt-to-EBITDA leverage.
John E. Elicker -- Senior Vice President of Corporate Affairs & Investor Relations
Thanks for the questions, Chris. Augustus, can we go to the next one please?
Operator
That will come from Tim Anderson with Wolfe Research.
Tim Anderson -- Wolfe Research -- Analyst
Thank you. Staying with Opdivo, it's been my assumption, I think it is most analysts on the Street that Opdivo will remain in the second spot in the I-O space in terms of the league tables among competitors. Are you confident that Opdivo will remain the second biggest brand in that space over time? I look at a company like Roche for example even knocking out trials consistently and you're really seeing an uptick in that program, and I'm wondering, I'm wondering if you're confident that you can remain in the number two spot.
Second question, going back to -9LA. Do you think that you have to show a PFS benefit not only an OS benefit, which you've talked about, but a PFS benefit as well for that trial to be commercially meaningful?
Giovanni Caforio -- Chairman of the Board and Chief Executive Officer
Thank you, Tim, let me just start and then I'll ask Chris to comment further. So let me just say that we feel very, very good about where we are with Opdivo. The performance in the marketplace is quite strong. We've demonstrated our ability to maximize every opportunity we get. Now, as I said, we have a real opportunity to play a role in first-line lung cancer with a differentiated regimen. It's the third time that we have an overall survival advantage for Opdivo plus Yervoy in the front-line setting in an important disease that gives us confidence that as we think about the rest of our metastatic program there are really important to studies that read out in the next 12 to 24 months.
And then as we said in the past, the next wave of growth for I-O in the adjuvant setting, I think Opdivo is very, very well positioned to compete there. Chris?
Chris Boerner -- Executive Vice President and Chief Commercial Officer
Yeah, so what I would say is that, I mean I think Giovanni has really highlighted kind of how we think about Opdivo overall and I think I would -- the only thing I would add to that is, remember, we have 19 separate indications. We continue to have an important and leading market share in the vast majority of the indications in which promoting. So we feel pretty good about where Opdivo sits today as well as the growth opportunities in light of the not only results that we've seen in lung cancer, but also the opportunities that we have with additional data read outs into the metastatic setting as well as in the adjuvant setting.
With respect to your question regarding -9LA and whether or not there is a specific target that we would have to hit with respect to the data that we see there to be competitive, look, if you look across the range of studies that have read out in first-line lung cancer, not only from our studies, but also from Merck and Roche and you look at all of the data that's read out across those studies, you see a fairly broad range in terms of the hazard ratios for OS, hazard ratios for PFS, as well as response rates and durability of response and that variability increases as you start looking within specific subsets. So we don't actually see a specific hurdle rate that we're going to have to overcome. What we think about in this market is really what physicians have played back to us. There is significant need in spite of all of those data readouts in first-line lung cancer.
There is a role for dual I-O therapy to play in this setting based on the strength of the data that was presented with -227 and we are very much excited about the opportunity that -9LA can play. As I mentioned earlier, -227 is for those patients who may not require chemotherapy. -9LA has a really important role to potentially pay for those patients who do and given that along with the strength of our commercial and medical organizations, we're excited about the opportunity we have.
Samit Hirawat -- Chief Medical Officer, Global Drug Development
And Chris, this is Samit. And just to add a couple of more points that -9LA if you remember, the primary endpoint in the trial is overall survival. Secondary endpoints does include PFS response rate, duration of response safety et cetera. Second point is that we started the study at the end of 2017 and enrollment in 9LA finished only in the early part of this year.
So from a follow perspective, the duration is relatively short. And so this data will continue to evolve and mature and as Chris has said earlier, we just saw the topline data. At this time and as more data is available and we dig deeper into it will be able to comment more as we present the data sometime next year.
Giovanni Caforio -- Chairman of the Board and Chief Executive Officer
Thanks for the questions. Tim, can we take the next one please against us.
Operator
Thank you. The next question will come from Seamus Fernandez with Guggenheim
Seamus Fernandez -- Guggenheim -- Analyst
Thanks for the question. So one question just on from an investment perspective. As you think about the -9LA results, can you guys talk to us about the strategy going forward, do you see more opportunities to invest behind triple regimens on a go-forward basis? Are there other tumor types beyond lung cancer where you would see a similar type strategy worth investing behind or perhaps even see an opportunity to invest behind this combination in the adjuvant setting or should we think about it more as a dual I-O -- I-O strategy similar to the -- the trials that you started recently competitively in the stage 3 setting.
Second question is, as we think about the opportunity, Chris, in across IBD and also some of the other inflammatory conditions you're sort of exiting psoriasis because of the OTEZLA transaction. Can you just help us understand a little bit more the the efforts that you're going through to kind of prepare to rebuild your presence, not just in psoriasis but also in in the IBD space as you think about ozanimod and the tick 2 assets coming on in 2020 and 2021. Thanks.
Samit Hirawat -- Chief Medical Officer, Global Drug Development
Thank you for the question. And let me just take it from the two questions that you asked for, in terms of the nivo/ipi combination. So already, as -- this is already mentioned earlier, there are several trials are ongoing looking at the combination of nivolumab plus Ipilimumab and some of them combining that also with chemotherapy, you will see that we have trials ongoing in the Phase 3 setting, Checkmate -648 in the esophageal cancer and bladder cancer, nivo IP and chemo and versus standard of care chemotherapy and gastric cancer, mesothelioma, [Indechipherabl]. All these data will continue to evolve in 2020 2021 timeframe and then of course we'll continue to look for additional opportunities where we can develop this combination.
Going forward, we are quite confident, because now that we are using in many of these trials low-dose ipilimumab, we will be able to manage safety as well and also the experience of the physicians will continue to grow. On your second question regarding the psoriasis space related to OTEZLA divestiture versus what we are doing in that space, we certainly are looking forward to quite excitedly to our TYK 2 inhibitor. TYK 2, as you know is differentiated from the JAK inhibitors, which are not specific and through the inhibition of its activation domain as multiple downstream effects, which leads to many of the side effects that we see.
The TYK 2 inhibitor that we have, which is BMS 165, was very specifically designed to target a pseudo kinase domain. What it does is that it interrupts the signaling of the IL-23, IL-12 and type 2 interferon pathways, and therefore it's quite specific in terms of its efficacy as well as safety not causing the neutropenia or the [Indecipherable].
So we are looking toward the readout of the Phase III studies that are currently ongoing toward the end of 2020 and early '21 as well as other indications where the Phase II studies are ongoing in psoriatic arthritis, as well as in IBD. We already mentioned a Phase III program with ozanimod as well in IBD.
So we're looking forward to seeing that data as well toward 2020 and, but let me just pass on to Chris to add additional color.
Chris Boerner -- Executive Vice President and Chief Commercial Officer
Yes, let me just add a few things from a commercial standpoint. Obviously, the TYK program is very exciting. The initial indication, as you know, will be in psoriasis. That's a very large opportunity as you're aware. Prevalence for psoriasis in the US, EU 5 in Japan is on the order of 2.3 million patients. This is a big opportunity and based on the data that we've seen coming out of the Phase II with the 75% response rate with the positive 75 score, we think that TYK is going to play an important role. For those patients, who are looking for biologic like efficacy, but with the safety and convenience and oral and obviously that's just the first opportunity that we have with TYK, IBD is a very large market, roughly $17 billion worldwide.
There are about 1.5 million patients diagnosed with this disease. And as we've discussed previously, the vast majority of those still or not, not ultimately treated with systemic therapies because the lack of really efficacious and safe products. The way we look at this from a commercial standpoint in terms of building it out, number one, we're building out obviously the ozanimod team working with our Celgene colleagues today. Obviously, there is an initial focus on MS, but we do have an eye toward the broader IBD opportunity and remember BMS has a history in Immunology. So we know the space well and that's something that we will obviously as we become a combined company bring to bear. So I'm actually quite confident that we'll be in a position to capitalize on these opportunities.
John E. Elicker -- Senior Vice President of Corporate Affairs & Investor Relations
Thanks Seamus. Can we take the next question please?
Operator
That will come from Steve Scala with Cowen.
Steve Scala -- Cowen -- Analyst
Thank you so much. Charlie, did you provide the key aspects of the combined P&L because you think consensus is too high? I'm curious why you did it now versus in the pas4t or upon closing. Second, the raised full-year EPS guidance implies Q4 will be down between 6% and 7%. That's striking because it's been a very good year. Why will Q4 EPS be down so precipitously? And then if I might quick for Samit, you said -9LA follow-up is relatively short, Keynote 189 hit with a median of 10 to 11 months. Should we assume something similar for -9LA? Thank you.
Charles Bancroft -- Executive Vice President, Chief Financial Officer and Global Business Operations
Yes. Thanks, Steve. So, in regard to just giving some perspective on the combined P&L, there has been some analyst to modeling, particularly as we think about stock-based compensation, in particular so that we wanted to get -- be a little bit more specific how we're going to handle it in addition to how we think about the share count. So I think that's fair. In regard to the fourth quarter, there is a number of things at play. If you think of the sales related to the business. So as we've talked about before, we saw the ups of business in July, the Eliquis donut hole continues to get slightly larger as we think about the fourth quarter and we've talked a bit. We've already talked on this call, a little bit of the Opdivo flattening as we got into the third and fourth quarter.
That coupled with historically we always have more OpEx in the business as we -- in the fourth quarter.
Samit Hirawat -- Chief Medical Officer, Global Drug Development
And in terms of the question around -9LA, of course, we will not compare this trial at this time to any other including Keynote 1-8-9 and we obviously cannot compare how the results will be presented in terms of the comparison to what we had, we have seen with the Keynote 1-8-9 at this time.
John E. Elicker -- Senior Vice President of Corporate Affairs & Investor Relations
Thanks, Steve. Can we take the next question please?
Operator
That will come from Umer Raffat with Evercore.
Umer Raffat -- Evercore -- Analyst
Hi, thanks so much for taking my question. And I appreciate you bearing with me on these two questions. First, there has been confusion in the marketplace on your ongoing Eliquis patent litigation, specifically as it relates whether salt forms that are appropriately tied in the written description of the patent or not.
My question is given that there is an amide on the chemical structure isn't it fairly straightforward for a regular chemist to be able to make some form of Eliquis. And secondly, I want to touch up on the lag 3 trial readout in melanoma for second half 2020. I realize this topic doesn't come up very much on the calls. My question is, I know there is a randomized Phase 2 and a Phase 3 component of this trial. Has there been a readout of the randomized Phase II internally and is there anything we can learn from that? Thank you very much.
Giovanni Caforio -- Chairman of the Board and Chief Executive Officer
Thanks, Umer, let me just, let me just ask, answer your question on the Eliquis pattern first. So a couple of things. First of all, we feel very good about the IP position for Eliquis. You may remember there were about 2,000 challenges to the IP of Eliquis. Over 20 generic companies have already settled with us and I think that speaks to the strength of our IP position.
There are a small number of generic companies that are continuing to challenge the patent. There has been some news regarding the fact that there was an out-of-order witness that testified in the last couple of days. There was really a scheduling issue the trial really starts today, and I can just say we feel very good about the fact that we have a strong patent estate for Eliquis. Samit on --
Samit Hirawat -- Chief Medical Officer, Global Drug Development
Thank you, Giovanni. And in terms of the lag 3 trial, as you know, it is trial looking at a combination of lag 3 plus nivolumab -- versus nivolumab in the first-line metastatic setting for melanoma. It's a seamless Phase II-III study. So we have not seen the data. The trial continues to enroll patients in the study and as you already pointed out data will be available at the -- toward the end of 2020. So we will be able to communicate at that time.
John E. Elicker -- Senior Vice President of Corporate Affairs & Investor Relations
Thanks Umar Can we take the next question, Augustus, please?
Operator
That will come from David Risinger with Morgan Stanley.
David Risinger -- Morgan Stanley -- Analyst
Yes, thanks very much. So I have a question about future trials. So -9LA was triple therapy including two cycles of chemo. But we had understood that Bristol was looking at chemo priming or sequential therapy with Opdivo and Yervoy following chemo. So, can you remind us, do you have any registrational trials that we should be watching in the future with chemo priming or sequential therapy?
And then second, with respect to Opdivo's outlook for 2020, could you just please provide some color on how we should think about the momentum in the US relative to ex-US? Thanks very much.
Samit Hirawat -- Chief Medical Officer, Global Drug Development
Thank you for the question. Maybe I can I can take the first one in terms of the future trials in the, how we think about I-O and the chemo and sequencing. At the current time we don't have trials that are looking at the sequencing of chemotherapy followed by I-O or I-O for the chemotherapy as such, but certainly it's an idea that we may explore in the future with the new trials that we will be planning and looking at. And our second and third generation I-O compounds yet to be developed in the future, but there are no registration trials that we have at this time that we're looking into this sequencing.
Chris Boerner -- Executive Vice President and Chief Commercial Officer
Yeah, David, let me just comment on the Opdivo question. So with respect to US versus ex-US, we continue to see opportunities to grow the business outside of the US and that's based really on a couple of things. First, the strength of our business across our core tumors, renal melanoma and second-line non-small cell lung cancer as well as the timing of access in a number of countries, ex-US. The US is under pressure as we mentioned previously, and really that's a function of primarily competitive dynamics across lung cancer as well as to other indications, head and neck and small cell. Let me describe what that, what that looks like.
So in all three of those cases, it's really a function of the decline in the eligible population in later lines where we have the bulk of our business today. We've talked at length about the situation in second-line lung cancer with approvals of I-O agents in first-line continuing to decrease the eligible pool in second line. That same dynamic is played out or is playing out in head and neck with competitor approvals earlier this year in first-line and in small cell with Roche's recent approval in the first-line setting.
What I will note across all three of those, however, is that we continue to maintain a leading share in second line, albeit within a declining eligible pool and our stable and our shares and head and neck and small cell in the second and third line, and both of those indications we expect to be stable in next year. Again it's a function of the declining eligible pool in those markets.
John E. Elicker -- Senior Vice President of Corporate Affairs & Investor Relations
Thanks, Dave and Augustus, I guess it looks like we have one more question in the queue.
Operator
Yes. And that final question will come from Navin Jacob with UBS.
Navin Jacob -- UBS -- Analyst
Hi, thanks so much for taking my question. Just on Checkmate 816 neoadjuvant lung study. I think the PCR endpoint is expected in the first half of 2020. I think you recently added Opdivo plus chemo arm in addition to Yervoy plus Opdivo arm. I just wanted to clarify if the timeline is still first half 2020 and just wondering what we could learn from that as it relates to your adjuvant long study. And if you could remind us when the adjuvant long study readout, please?
Samit Hirawat -- Chief Medical Officer, Global Drug Development
Sure. I will take on the question, so thank you for that. So certainly the nivo IP versus nivo plus chemo versus chemo are the three arms that are being investigated in that study. As you know, at this time, we have a PCR endpoint but -- from a regulatory perspective, that is certainly something that we need to continue to discuss with the health authorities and how we will then be able to take that forward in terms of utilizing that data for the adjuvant setting and how we will utilize that data in terms of making future decisions. Adjuvant study as such, also is a separate study looking at CheckMate -427, which is nivo versus observation and then there are other studies in the early stage lung cancer.
So at this time, I think our only communication to you would be that the data does become available for PCR in 2020 and we will continue to focus as we go forward in terms of looking at the data for the adjuvant trial from 816 as well.
Giovanni Caforio -- Chairman of the Board and Chief Executive Officer
Thank you, Samit. And thanks, everyone. So in closing , let me just reiterate. This is an exciting time for Bristol-Myers Squibb. We delivered another strong quarter, demonstrating our ability to execute on commercial priorities, advance our pipeline, while we work to close the Celgene acquisition and plan for integration. I'm excited about the promise of our future and the opportunities we have ahead of us to help even more patients prevail over serious diseases. Thanks everyone for participating in the call, and have a good day.
Operator
That does conclude today's conference. Thank you all for your participation. You may now disconnect.
Duration: 48 minutes
Call participants:
John E. Elicker -- Senior Vice President of Corporate Affairs & Investor Relations
Giovanni Caforio -- Chairman of the Board and Chief Executive Officer
Charles Bancroft -- Executive Vice President, Chief Financial Officer and Global Business Operations
Samit Hirawat -- Chief Medical Officer, Global Drug Development
Chris Boerner -- Executive Vice President and Chief Commercial Officer
Terence Flynn -- Goldman Sachs -- Analyst
Geoff Meacham -- Bank of America Merrill Lynch -- Analyst
Chris Schott -- JP Morgan -- Analyst
Tim Anderson -- Wolfe Research -- Analyst
Seamus Fernandez -- Guggenheim -- Analyst
Steve Scala -- Cowen -- Analyst
Umer Raffat -- Evercore -- Analyst
David Risinger -- Morgan Stanley -- Analyst
Navin Jacob -- UBS -- Analyst
