Bristol-Myers Squibb Co
NYSE:BMY
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Bristol-Myers Squibb Co
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Good day, and welcome to the Bristol-Myers Squibb 2020 Second Quarter Results Conference Call. Today's conference is being recorded. At this time, I would like to turn the conference over to Mr. Tim Power, Vice President, Investor Relations. Please go ahead sir.
Thanks, Rolando [ph], and good morning everyone. Thanks for joining us today for our second quarter 2020 earnings call. Joining me this morning with prepared remarks are Giovanni Caforio, our Board Chair and Chief Executive Officer; and David Elkins, our Chief Financial Officer. Also participating in today's call are Chris Boerner, our Chief Commercialization Officer; Nadim Ahmed, President Hematology and Samit Hirawat our Chief Medical Officer and Head of Global Drug Development.
As you note, we've posted slides to bms.com for you to follow along with David and Giovanni's remarks. Before we get going, I will read our forward-looking statements. During this call we will make statements about the company's future plans and 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 non-GAAP financial measures to the most comparable GAAP measures are available at bms.com.
With that, I'll hand it over to Giovanni on slide three.
Thank you, Tim, and good morning everyone. I hope that everyone is remaining healthy and safe. As we continue to navigate the impact of the pandemic, I want to thank our colleagues around the world whose commitment to our mission and dedication to our patients has enabled us to continue delivering our medicines to those who are relying on us.
Before starting the call, let me briefly comment on yesterday's news on Eliquis. We believe the IP for these medicine reflects the innovation we have brought to help patients with AF and VTE. In this regard we are very pleased by the Court's decision to rule in our favor on both patents.
Let's turn to slide four. We have delivered another very strong quarter with solid commercial performance including a promising start with multiple launches. Strong financial performance and the achievement of important clinical and pipeline milestones that reinforced our long-term potential.
Our ability to advance the business was enabled in part by our integration efforts. Our teams are working well across the organization. Our systems are coming together and we are on track to deliver $2.5 billion in synergies by the end of 2022.
With a strong foundation, a broad and deep portfolio and pipeline and significant financial flexibility, I have never been more confident in the future of Bristol-Myers Squibb. Before I discuss our results I would take a moment to talk about how our teams are coming back to the workplace and into the field.
We are taking a thoughtful and phased approach to our return to the workplace. Our timelines and circumstances vary by market. And we are taking significant measures to protect the safety of our colleagues, while we continue to deliver medicines to patients and enhance our long-term competitive position as a company.
In locations where country restrictions permit, and we can ensure the safety of patients providers and colleagues, we have resumed recruiting for our clinical trials. Our discovery researchers have returned to our laboratories to continue their vital work.
Depending on local and regional conditions in the U.S. and globally our sales and medical teams are continuing to effectively engage virtually, and where possible returning to the field. We also continue to support the global COVID-19 response effort in a variety of areas including working with researchers, the biopharma community and the broader life sciences industry, on ways to accelerate therapies for COVID-19.
While uncertainty remains with how the COVID-19 pandemic will evolve, we have plans in place to adapt and ensure that our business continues to operate well. Now, let me turn to the quarter on slide five. David will provide more details later in the call. So I'll take a moment to cover the highlights. First, I'm very encouraged by the resilience and strength of our business, and the robust demand for our medicines, enabled by strong commercial execution.
We posted $10.1 billion in sales. And while COVID related inventory and demand dynamics had an impact on sales of our medicines in Q2, underlying dynamics remain very positive and fully aligned with our expectations. During the quarter, we also made important progress with our pipeline.
We achieved two first-line lung cancer approvals for dual IO therapy. We delivered positive pivotal Phase 3 results for Zeposia in ulcerative colitis, which we look forward to discussing with health authorities and presenting at a future medical meeting.
And we also made good progress with the regulatory process for our cell therapy medicines, particularly the submission of ide-cel. Also during the second quarter, we have launched several of our new medicines and new indications. And while we are clearly in the launch cycle, early in the launch cycle, we are seeing encouraging initial performance.
We are off to a very good start with our Opdivo plus Yervoy launches in first-line lung with encouraging initial feedback from physicians and good indications of early adoption. This supports our expectation that Opdivo will return to annual sales growth in 2021.
We have launched Zeposia with a best-in-class S1P label in MS. And we are pleased with the feedback from customers so far, including with respect to the ease of treatment initiation. And we're very encouraged by the adoption we've seen with Reblozyl in MDS.
Early demanded trends support our view that this will be an important driver for patients and for the company. And we further strengthened our financial position with strong operating results and cash flow. The results we've delivered in the quarter provide a strong foundation for the future.
So looking forward, and turning to slide six, as we discussed during our investor series in June, we are executing on an unprecedented number of new launch opportunities. And across almost every one of our new products, we have the potential to build on our initial launch success, with additional new indications, benefiting more patients and growing our business.
We believe that the new products will bring into market provide us with an opportunity to renew our portfolio for the long term. In fact, we estimate that the new launches together with their lifecycle management opportunities could deliver approximately $20 billion in peak revenue on a non-risk adjusted basis.
During the quarter, we began to realize this potential having launched several new products and indications. And we also delivered key clinical data to potentially expand the use of Zeposia.
Later this year, we expect key data for our TYK2 inhibitor, which we believe is an asset with significant potential as a broad based autoimmune medicine. In fact, we have recently received Phase 2 data for TKY2 in psoriatic arthritis reinforcing this view.
We look forward to presenting the data at an upcoming medical meeting and embarking on a Phase 3 program in this indication. And finally in the very near term, we are looking forward to the U.S. PDUFA dates for CC-486 in September, Liso-cel in November.
And of course, beyond our new launches we have a pipeline full of promise.
Turning to slide seven. I am encouraged by the progress with the next wave of medicines that are emerging. Our pipeline includes more than six assets that have achieved proof-of-concept or are close to it, spanning multiple disease areas.
In IO, we have our LAG-3 inhibitor, relatlimab with potential Phase 3 data later this year or early next year, as well as Bempeg partnered with Nektar. In multiple myeloma, we have two cell modes; iberdomide and CC-92480, and our BCMA T cell engager.
In cardiovascular disease, we see promise in our factor XIa inhibitor. And finally in immunology and GI, we are looking forward to taking cendakimab into Phase 3 trials in eosinophilic esophagitis. All of these agents could have significant commercial potential.
When I look at our portfolio, I'm confident that the opportunities we have with our new launches, lifecycle management programs, and earlier pipeline assets have the potential to strengthen our position in key therapeutic areas.
Such as expanding our franchise in hematology and sustaining a leadership position in multiple myeloma, broadening our presence in immunology with our TYK2 inhibitor, and establishing a GI franchise starting with Zeposia and renewing our franchise in cardiovascular. Along with these opportunities, our financial flexibility enables the external sources of assets and innovation to complement our internal R&D efforts.
Now, moving to slide eight. Our future has never been brighter. In the first half of the year, we've executed very well, realizing a number of important accomplishments while integrating the company. These accomplishments all points to our opportunity to successfully renew our portfolio for the long term.
None of this would be possible without the tireless efforts of our extraordinary teams around the globe. I'm very proud of our colleagues and thank them for their focus and dedication. We have incredible talent in the company and it is our priority to continue to attract, retain and develop the best people.
Before I hand it over to David, let me provide our perspective on the recent executive orders in the U.S. We are supportive of increasing access to medicines and reducing the out-of-pocket cost of medicines for seniors. Actions like the rebate rule would help achieve these goals. However, the IPI would not.
We, the industry, physicians and patient groups are very concerned about and firmly disagree with the administration's decision to sign the executive order on IPI. We believe that IPI has the potential to impose price controls from countries where government run health care systems and price controls do not appropriately reward innovation, and where too often, patients do not even have access to new medicines.
The policy of importing price controls from foreign countries, which the administration has described as having socialist healthcare systems would have a significant impact on our industry in the U.S. Starting with ability to continue to invest in R&D, and lead innovative research to treat disease at a time when we are leading the fight against COVID-19.
I'll now hand it over to David to walk you through our financials for this quarter. David?
Thank you, Giovanni. Hello, everyone. And thank you again for joining our call today. As Giovanni mentioned, I continue to be very impressed by the execution of our teams in the wake of COVID-19.
Our exceptional second quarter and first half results have pick the resiliency of our portfolio. So now let's dig in a bit more on our recent performance turning to slide 10. We had a solid top line performance in the second quarter of $10.1 billion, including significant unwinding of the COVID related stocking in the first quarter.
On a performance basis, sales are flat year-over-year as inventory built in the first quarter reversed in the second. Importantly, if you look at our half year results, sales were strong at $20.9 billion growing 6% year-over-year with growth across the vast majority of our prioritized brands.
Now let's turn to our key brand performing starting with Eliquis on slide 11. Eliquis demand trends remain robust with double digit TRx growth of 20% in the U.S. versus prior year. As mentioned, we saw significant favorable impact from Channel and patient level stocking due to COVID in the first quarter, which as expected, largely reversed in Q2.
Second quarter global sales were approximately $2.2 billion growing 6% versus prior year. If you look at the sales in the first half of the year and wash out the quarterly noise, sales were very strong, up 21% versus the first half of 2019.
We would like to remind you of second half dynamics related to the coverage gap of Eliquis. As we've explained in the past, we accrue our liability related to this patient population when they entered the donut hole, which reflects a substantially higher impact in the second half of the year.
Recall that there's to step up in the liability in 2019, where the manufacturer responsibility increased from 50% to 70%. Though this factor has not changed for the full year in 2020, there are additional drivers to keep in mind.
First is our mix. Medicare is an increasingly large component of Eliquis. And second is the size of the coverage gap per patient. It increased in 2020 compared to last year. This further increases the gross to net accrual in the third and fourth quarters.
Because of these gross to net phasing dynamics as we've seen before, we expect Eliquis net sales in the second half of the year to be lower than the first half of the year, despite the strong underlying demand growth.
From a COVID perspective that we saw new-to-brand levels unfavorably impacted. We are seeing positive recovery signals of patient access to healthcare providers and cardiologists from the lows we experienced in April, May.
Looking forward, we continue to expect significant future growth driven by Eliquis's number one position among the NOAC class due to the coverage of total brand share to new brand share and continued erosion of warfarin.
Turning to Opdivo on slide 12. In the U.S., we continue to see strong share across key indications. Stabilization of IO eligibility in second-line lung and strong share within the RCC market.
With respect to COVID, we saw some demand pressures due to patient access to hospitals and infusion centers, which we estimate to be in the low to single mid digits. We're starting to see recovery signals with patients ability to access centers.
Internationally, COVID has impacted patient starts across tumors with melanoma being the most impacted. Despite COVID impact, our IO franchise has remain strong across all -- remain strong shares across all our key indications. Now moving to the frontline lung approvals for Opdivo plus Yervoy in May, based on Checkmate 227 and 9LA. We are very encouraged by how the launches are going.
While, it's still early days, we believe it's going well, if not better than expect, particularly in light of COVID and launching in a virtual environment. We've already achieved market share in the mid single digits. For 227 we are seeing use of Opdivo plus Yervoy across histologies and PD-L1 expression.
What we're hearing from prescribers is they are impress with the depth and durability of response, as well as the long term survival data. With respect of 9LA this gives physicians another option in first-line setting limiting the use of chemo and addressing the needs of patients with rapidly progressing disease. Based on these promising launches in the U.S. we expect Opdivo return to annual sales growth in 2021.
Moving on to our in-line multiple myeloma portfolio on slide 13, Revlimid and Pomalyst continue to perform well delivering strong year-over-year sales growth, up 6% and 21% respectively. Growth was primarily driven by increased treatment duration due to demand for Revlimid and Pomalyst based triplet therapies.
As previously mentioned, the impact of COVID on the brands is modest to the oral administration of the Revlimid and Pomalyst. There were some stocking impact in the prior quarter Ex U.S. However, the REMS program in the U.S. resulted in limited stocking compared to other brands like Eliquis. When looking at our sales year to-date, both Revlimid and Pomalyst grew double digits, up 10% and 25% respectively.
Now, I'd like to take a moment to highlight some of the recent launches on slide 14, starting with Reblozyl. We're extremely pleased with the virtual launch of Reblozyl, post the approval in April for Rx positive MDS associated anemia. Physician experience in beta thal and the MEDALIST data published in the New England Journal of Medicine in January, led to substantial acknowledgement of the clinical value of Reblozyl, and pent up demand leading to the MDS launch, which contributed to the strong sales in the quarter.
Physicians feedback remain positive with significant awareness of the approved. While still early, we are very pleased with the launch and patient retention of the product where majority of eligible patients have already received their second and third cycles of treatment.
We have recently received approval in Europe and we look forward to launching Reblozyl in the various markets across the world over the next six to 12 months. Now turning to Zeposia, we're also very pleased with our best-in-class S1P label in multiple sclerosis. And while very early in the launch, we are very encouraged on how things are progressing so far.
We have already made great progress on the payer front with strong day one access including Express Scripts. It is important remember that MS market does not change over quickly and it takes time to penetrate due to patients long duration on their medicine. With that in mind, we are pleased with the initiation we've seen across multiple prescribers and centers.
Now let's move to our balance sheet and the strength in our capital allocation on slide 15. We continue to generate significant amount of cash flow from operations with over $4 billion generate in the second quarter.
We ended the quarter in a strong liquidity position with approximately $22 billion in cash and marketable securities, reducing our net debt to $24 billion. Our capital allocation priorities remain unchanged, the leveraging and achieving less than one and a half times debt to EBITDA ratio by the end of 2023. We've continued our commitment to our dividend and investing in future innovation through business development.
So now let's turn to slide 16 and review the guidance. Last quarter, we provided assumptions around how we view the impact of COVID-19 crisis on our business. Our view today has not changed. As a reminder, we assumed the peak impact would occur in the second quarter with a return to a more stable business environment in Q3 and minimal impact in Q4. So far, the key factors we assumed are also playing out as we expected.
Those were products that saw significant advanced buying at the end of Q1 we'll see that inventory work down during the rest of the year, mostly in Q2, which I described earlier. The remaining inventory will work its way out in the second half of the year.
The second factor was the reduction in new-to-brand prescriptions and physician administered products during Q2, recovery in Q3 and fully recovered in Q4. And lastly, we were planning to resume all clinical trial activities by year end, where restrictions have been lifted.
Now based on this strength of our results in the first half of the year, we are narrowing our revenue range, updating our tax rate and as a result increasing our 2020 adjusted EPS guidance. We now expect revenue to be between $40.5 billion and $42 billion based on strong performance and currency improvement.
We expect expenses to be at the high end of arrange as we invest in our launch products and accelerate the resumption of clinical trial activity in the second half of the year. And we expect our tax rate to be between 16% and 17%, primarily driven by favorable post closed tax initiatives and earnings mix.
With these changes, we are increasing our EPS range to $6.10 to $6.25. A revenue guidance takes into account the donut hole effect affecting Eliquis in the second half of the year. And as I discussed earlier, as well as the competitive dynamics associated with some of our established brands.
Remember, as I mentioned earlier in the year we project revenue from our established brand portfolio to decrease about 30% for the full year on a performance basis compared to 2019, which is mainly coming from our international business.
Lastly, as Giovanni mentioned, we are on track to deliver the $2.5 billion of synergies by the end of 2022, with one-third of those expected to be delivered this year. Before we move on to question and answer, I want to close out by saying how delighted I am with our robust execution in the first half of the year.
I discussed a great deal about the financial strength of the company at our Investor Series a little over a month ago. Our performance in this global pandemic illustrates just how resilient our business remains, as well as our ability to be agile in a changing environment. I therefore remain confident in our long term outlook for the company.
I'll now turn the call back over to Tim and Giovanni for the question and answer.
Okay. Thanks, David. Rolando, could we go to our first question, please?
Absolutely. [Operator Instructions] And we’ll take our first question from Geoff Meacham with Bank of America.
Hey guys. Good morning, and thanks for the question. Just had a few quick ones. On Opdivo based on demand trends you've seen so far in lung does that change your view of growth looking to 2021. Maybe just be helpful to get a little bit more detail of a commercial view looking to what happened in 2Q from lung? And then just with respect to the pipeline, TYK2 will be obviously a big growth driver in a category you have some experience with. When you look to that brand, maybe just help us with the opportunities that you see for TYK2 for differentiation? And what investments commercially that you'd have to make to really maximize the value there? Thank you.
Thank you, Geoff. So, two important questions. And as I mentioned in my remarks, we feel good about both with the opportunity for Opdivo. And the remarks we've made of first-line launch so far and TYK2 particularly as we've now seen a second Phase 2 study in psoriatic arthritis. But let me just ask, Chris, to give you more color on both Opdivo and TYK2.
Sure. So thanks for the question, Geoff. Let me start with first-line lung, because I think that's probably on a number of folks' mind. The lung launches are going very well and in fact are tracking at or maybe even a bit ahead of our expectations. Let me highlight just a few things. From a share standpoint, it's still very early days, but share is currently in the mid-single digits and we've seen very good momentum in the uptake here. Importantly, we've seen uptake across all PD-L1 segment, as well as across histology. And the uptake has been particularly good I would say in the PD-L1, one to 49 segment.
As expected, given the timing of approval and the relative immaturity of the data, the uptake of the 9LA regimen has [lag] [ph] 227. However, in recent weeks, we've even seen an uptake in the use of dual IO with chemo. And again, this appears to be across subgroups. So, good momentum on utilization. Execution has been particularly good, especially given the dynamics of COVID. Most of the engagements remain virtual. But we're seeing very good engagement between the sales force even in a remote environment with key customers. Physician reaction has largely been aligned with expectations in our previous conversations with depth and durability of response of these agents with a manageable safety profile being the primary message.
So what I would say is it's still early days, but we're very happy with the utilization that we're seeing. We've got good execution, physician reaction continues to be positive. And we're very pleased that in spite of entering first-line lung as the third company to market our shares. Now after eight weeks are putting us as having the second most widely used regimens in the space. And as it relates to the growth, as Giovanni mentioned, we still see Opdivo as a growth brand going forward. The fundamentals of the business today continue to be relatively strong. We've got relatively stable base of business in the U.S. The second-line lung dynamics continue to play out as we had expected both in the U.S. and ex U.S. The early launch and lung is performing well. And we've got good fundamentals ex U.S.
And then if you think about 2021, with the strong 9ER data that we talked about in the last quarter, we feel really good about the growth opportunities that we see for Opdivo starting in 2021. With respect to TYK, very excited, obviously about the data that we have already presented with Phase 2 and psoriasis, psoriatic arthritis, Phase 2 data is we think if it plays out in the Phase 3 going to be compelling. Remember, this is a disease area that's large, over 2 million people are diagnosed in the U.S., EU5 in Japan with psoriatic arthritis. And there's still significant unmet need here. Two-thirds of the patients, for example, who are stable on DMARDs, continue to have disease activity. And there's considerable dissatisfaction with existing oral agents when you look at the totality of the profile, both efficacy and safety. So, obviously, early days, but we're excited about what we're seeing there.
And we'll move on to our next question from Terence Flynn with Goldman Sachs.
Great. Thanks for taking the questions. Maybe just two for me as well. Just was wondering if you can give us an update on the timing of some of your Opdivo adjuvant studies, I know 816 for new adjuvant lung and 274 for bladder were potentially expected later this year. So just wondering, any update on timing and how you're thinking about those opportunities? And then the second I had is, I didn't see any mention of 2021 guidance in the release. Just wanted to confirm that there were no changes on that front? Thank you.
Thank you, Terence. Let me just briefly comment on guidance. And then, I'll ask Samit to give you a perspective on the adjuvant readout. So based on where we stand today, we are reaffirming the guidance for 2021. There is really nothing that has changed. The assumptions for COVID are playing out as we thought. The business is strong. We've given you some comments on early positive indicators. Of course, there is a number of considerations that we discussed the last quarter. They remain very valid today.
We've made a number of assumptions regarding COVID, particularly at the end of the year and into next year, I think we'll have to see how those play out. And obviously, as you know, there is significant variability there. And at this point, we've not really included any impact from U.S. Healthcare Reform in our assumptions, because there again, it's early days and difficult to understand what an impact may be. So -- but when you look at our assumptions and the strength of our business, we're reaffirming the guidance for 2021 at this point. Samit?
Yep. Thank you, Giovanni. And thanks, Terence for the question. For Adjuvant, certainly, many opportunities in front of us beyond the -- still available opportunities in metastatic setting. We're looking forward to a few readouts within the overall holistic program that we have across several tumor types. The ones that we're looking forward to in 2020 would be melanoma, Checkmate 915 potentially reading out towards the end of this year. And then of course, muscle invasive bladder cancer, Checkmate 274 is the other one. And then you already mentioned a potential PCR endpoint readout for non-small cell lung cancer at the end of this year. And then in 2021, we're looking forward to the readout for esophageal cancer as well, and then others come in 2022 and beyond.
Thanks, Samit. Orlando, can we go to the next one?
Absolutely. We'll take our next question from Chris Schott with JPMorgan.
Great. Thanks so much for the questions. I guess first for me was on TKY2. Can you just elaborate a little bit more on the safety profile of the product that you saw in the psoriatic arthritis study. Is anything new to report relative to what you saw with psoriasis? Or is it a similar kind of profile that you saw there? And then my second question was coming back to Opdivo in first-line lung. Just any comments of where you think you can get to from a share perspective given this strong initial launch? And when we think about the ex-U.S. opportunity here, can you just compare and contrast how you're thinking about that versus the U.S. given the lack of a 227 label Ex U.S.? Thanks so much.
Thank you, Chris. Samit, why don't you start on TYK2 and Chris can provide some update on Opdivo.
Thanks, Chris, thank you for the question for TKY2, as already alluded to a little bit by Giovanni and then Chris, earlier, really excited for TKY2 overall. And we've seen the profile as you saw in psoriasis in the Phase 2 study. And we see similar results in terms of trending, in terms of safety and really looking forward to presenting this data in the next medical conferences. Overall, as we've said, we are excited about the data to be able to now plan the Phase 3 program in psoriatic arthritis, and looking forward to the readout towards the end of the year for the psoriasis program for the first study, and then the second study in the first quarter of next year. So nothing to report as differentiation at this time from what we've already known from a safety perspective. So Chris, do you want to take over the Opdivo question?
Sure. Thanks for the question, Chris. So one of the things that we're most pleased about with respect to what we're seeing in the early dynamics in the U.S. is that, as we had suspected, physicians are not pigeonholing the dual IO regimen to a specific patient type. In fact, as I mentioned before, we're actually seeing good uptake of the 227 regimen and really across segments across PD-L1 expression levels as well as across histologies. What I would say with respect to the patients that have gone on therapy thus far, within the one to 49 segments, the patients are generally those who are requesting non-chemo options or they may be frail patients who can't tolerate chemotherapy.
We are seeing some utilization in the greater than 50% population for patients who want or maybe need a more aggressive option than single agent PD-1. And then with a 9LA regimen, we're seeing patients who are young, maybe they're fit patients with severe disease, but they're motivated to have a more aggressive option. So those are the types of patients that we're seeing right now. Importantly, as I think about the opportunity to continue to grow here, again, I think we're going to continue to emphasize the opportunity for dual IO patient -- dual IO therapy across all patient subtypes. We have not seen as much utilization yet in the PD-L1 negative, unknown or untested segment, that's an area where IO is generally underpenetrated. So that's obviously an opportunity with a 9LA regimen. So we think we have a number of opportunities where we can continue to drive utilization across patient segment types in the U.S. Outside of the U.S., obviously, we won't have 227 on label. However, I'd say a couple of things. First of all, that data will be publicly available and obviously as appropriate, our medical teams will be engaging on that. But 9LA data by the time we launch will obviously continue to mature. That data does provide us an entree into the PD-L1 negative. So those are some of the dynamics that I think will be at play as we get into the ex U.S. market. But, again, I think we'll continue to update you as we get closer to the timing of that approval.
Okay. Thanks Chris.
And we'll move, Rolando for the next one.
Okay. And next we'll hear from Tim Anderson with Wolfe Research.
Thank you. I have a question on the Eliquis patent ruling. Your press release last night, you said, you expect generics sometime after 2026, but before 2031? I think everyone on the analyst side expects generics around mid 2027, I mean, you get pediatric exclusivity. But I'm wondering that exclusivity could actually extend beyond that based on that press release language. You've done settlements with lots of generic challengers. You've never made any of those terms of public. So is there a reasonable possibility that generics don't arrive until something like 2028? Or maybe even later? And then on ozanimod and ulcerative colitis from the True North trial, will there be something differentiating in the data relative to the current in market competitors, beside this just being a different mechanism?
Thank you, Tim. Let me let me start on Eliquis, and then Samit will provide some comments and True North. So first of all, let me say, we've always been confident in the strength of the IP for Eliquis. And as you alluded to, and just as a background, the IP covering Eliquis is a composition of matter patent, which expires in November of 2016, with a potential pediatric extension to May 27, and a formulation patent, which expires in 2031. And we're very pleased with the outcome when the strength of both patterns has been confirmed yesterday.
So this does mean that there is potentially some extension beyond the 2026 composition of matter patent. Obviously, if we are successful at maintaining the formulation patent upon appeal. And you are right that we've settled with a number of companies and the terms of those settlements are confidential.
Giovanni, thank you, I'll take on ozanimod question. Thanks for the question, Tim. I think a couple of things to note. Number one, the current treatment pattern for patients with ulcerative colitis, primarily this is dependent on biologics. And I think there is still an underserved patient population because of the need for additional treatments. And a therapy that is safe, effective and can actually be delivered orally is going to be important. And then, if you recall the trial actually enrolled patients both who were biologic naive, as well as biologic pretreated. So there is an opportunity over here for patients to be treated in the pre biologic setting as well.
Zeposia, as you've seen from the MS label is a best-in-class safety profile with the absence of the first dose monitoring both for the cardiovascular aspect of it and then lack of required broad based ocular testing in this drug. Now from the Phase 3 UC trial perspective, as we look at Zeposia and obviously, the data will be presented in the future medical meeting, but it is not only met the primary endpoint, but we see very important, very significant results in the secondary endpoints as well, including the improvements in the endoscopic findings, which is very uncommon for many of the drugs out there. And these are very stringent definitions that have been used in the trial.
So overall, what I would say is from a safety perspective, as well as from the efficacy perspective, you will see that this drug, which can be given orally is differentiated. And we are looking forward to the dialogue with the health authorities and agencies for submission. Chris, I wonder if you would like to comment as well?
Sure. The only thing I would add to what you said, Samit, is that remembering UC, the unmet need here is really for oral options with efficacy that's comparable to biologics, but with a better safety profile than you see with existing biologic agents in JAK inhibitors. There's obviously in this space, a lot of competitive noise and the data are going to evolved and clearly we need to wait for the full True North data set to be presented. But based on what we know today, and the data that we've seen, we feel very good about the Zeposia profile. And you see the efficacy appears to be in line with biologics, but with better safety and specifically, we're not seeing either here or in the MS profile, the rates of serious infections or thrombosis or malignancies that have led to black box warnings for a number of the TNF inhibitors and JAK.
So, given the chronic nature of this disease, we think Zeposia is going to have a role to play. It's an oral agent. As you noted, Tim, in your question, it has a unique mechanism of action, which actually is important given the chronic nature of this disease, and it offers a better benefit risk profile potentially than existing agents.
Thanks, Chris. I think we're ready for the next, Orlando.
And we'll go to the Steve Scala with Cowen.
Thank you. If I can ask three follow-up questions. First on Eliquis. Are the settlement dates fixed now although undisclosed, or in some way are they dependent on the 2031 patent? Secondly, you've said many times that Opdivo is likely to return to growth in 2021. Can you clarify. Is that for the full year? The second half of 2021? The fourth quarter 2021? And is it dependent on Adjuvant lung approval? And then lastly on ide-cel. Has the FDA indicated that they still plan to review ide-cel in an eight months review cycle or have they not said that one way or the other? Thank you.
Thank you, Steve. Let me maybe take the three very quickly. So as I mentioned, the details of those settlements which are complete are confidential. And again, as I said, there is clearly potential for some extension beyond 2026. I would say in between 2026 and 2031, depending on the outcome of the appeal. And I don't think there's anything more than we can say about that. With respect to Opdivo, what we've commented on, is that the brand has an opportunity to grow in 2021. We're not really providing quarterly breakdowns of that -- of the growth. But we feel really good about where we are based on the strength of the current business and what Chris, as mentioned earlier, about first-line lung and the approval potential in first-line renal based on 9ER. And this would be the main driver. I think the only thing we can say for ide-cel is what we've already communicated. We have requested a priority review. But it's obviously the agency's decision to make that comment. Samit anything.
Yes. I think in addition to that, we have a breakthrough therapy designation as well. So overall, the agency will take a look at the data itself, which we are really excited about. And then, of course, the overall status of the program that we have.
Chris, anything to add on Opdivo?
No. I think you've covered Opdivo well. What we've said is that the trajectory of the growth will be determined by the Adjuvant indications that we feel very good about the growth opportunities starting in 2021 based on the dynamics I've mentioned.
Great. Can we go to next one, please.
And we'll hear from Khushal Patel with Guggenheim Securities.
Hi. Thanks so much for participating on behalf of Seamus. So, in terms of the reaffirmation of the 2021 EPS guidance. I was just wondering in relation to that how the integration efforts and just expense management in the P&L was progressing? And how that might play through in 2021, especially with R&D increasing, as trials ramp up presumably? And just push and pull for I guess, the synergies there. And then potentially any comments in regard to the elections? And then the second question just with a cash pile building up. Wondering how the team is thinking about deals in the future, maybe bolt-ons. Just any color there would be nice? Thanks.
Thank you. David?
Yes. So thank you for the question on the integration and synergies. Look, as Giovanni and I both said on the integration side of things, we're really pleased with how quickly everything has gone. And we're very fortunate to get the vast majority of people in the roles over 90%, prior to COVID situation hitting us, which was very fortunate, because everybody knew the roles and the reporting relationships. And that really enabled everyone to come together. I think also just having a crisis like this, everyone's working remotely and getting through it and the way everyone's reacted to focus on meeting patient needs and making sure we're getting product at the door has really -- I think the cultural integration has sped up. And we've seen that through the surveys. We've done from an employee engagement perspective.
You also know, on the integration side of things we mentioned before that we announced all the major sites around the world and there was a high overlap there. So people know where they're going to be working. So again, that helps from a cultural aspect. On the synergy side, as I said in my call, things are going very well. We're going to achieve one-third of those next year. I think the team is doing an amazing job. Within a couple weeks after us closing the deal, we got all of our major suppliers together, and we saw about a billion dollars of the $2.5 billion coming from third-party -- from third parties. And we feel very, very confident in how we're executing against those synergies.
Yes. With respect to capital allocation, you had a question. Nothing really has changed with respect to capital allocation. And what I would say is that as we've said in the past, our priority for capital allocation, the central pillar of that has always been to continue to source externally innovation through business development. So that's very much a priority for us. And as you know, we look at business development from the perspective of deals that are sort of aligned strategically with therapeutic areas. We know well, where there is a potential for breakthrough science and obviously, we're disciplined from a financial perspective.
So we're very active, looking at potential deals across the board to strengthen our discovery platform, increase the number of collaborations we have and pretty much across the board. So you are right that our financial positions continues to strengthen and business development remains an area of focus for us.
Thanks, Giovanni. Orlando. Could we go to the next one, please?
Yes. We'll hear from Andrew Baum with Citi.
Thank you. Couple of questions, please. Firstly, to Giovanni, could you give us the true level of concern in the industry. But also in Bristol regarding the President's executive order on most favored nation's IPI that you referred to in your opening comments. Extensively, it would seem that the requirements for having favorable CBO score and the HHS being able to validate that is a requirement, which doesn't seem likely given what happened last time.
So what is the real risk that that changes, and therefore, this proposal has lags? I'm just trying to understand how real the threat is. And whether something has changed and we shouldn't be quite as relaxed as we are given the last time round. Second, perhaps Samit could talk to some of the forthcoming data at ESMO. You have a deep tranche of immuno-oncology agents, CCR-25, IL8 among others, what data will we see at ESMO?. And then finally, just on the COVID impact For Eliquis ex U.S., particularly in Europe, where obviously there's a delay in reimbursement. How much scope do you see for NOAC market share increases as a function of COVID? And trying to keep patients out of medical centers from getting their INR measures? Thank you.
Sure. So let me let me start on government related issues. Samit will cover ESMO, and Chris maybe can give you some insights into your question on demand. So first of all, let me say, Andrew, I think it's really early to provide any more granular assessment. As you know, we have not seen the IPI executive order yet. And so with respect to that, there is there is some level of uncertainty with respect to really what is in the order and what a path to implementation may be. I want to say, again, what I said in my opening remarks, we feel very strongly that it is not the right direction for the U.S. to go. I think our view is shared not just across the industry, but providers and patients associations and other policy stakeholders are aligned with our view. I think the solution to patient affordability issues in the U.S. is to work on patient affordability issues. It is really not to import models and pricing levels that are not working internationally into the U.S.
And quite frankly, the IPI doesn't do as much for patients as we should be doing for patients. So our industry continues to be really open to discussing different types of solutions with the administration that would help patients more, but also would enable us to continue to invest in innovation. I think it's really important at a time in which everybody understands the importance of our industry, which quite frankly, is primarily a U.S. industry in fighting disease. The impact of IPI in the version, at least we knew would be extremely significant on our industry and the ability to continue to invest in innovation.
And we hope that and we hope that we are able to move into directions that are better for patients in the U.S. From our perspective, when you think about our portfolio, it's clearly much more differentiated today than it was in the past across multiple segments. And when you look at our sales, it's about 40%. internationally and 60% in the U.S. Part B just as a reference point, it's about 15% of our business. With respect your question about the rebate rule, I think we would have to see how HHS goes about really thinking about the various sort of implications of a rebate rule and assess what the cost of that would be versus the benefits. So I'm not sure, I can really speculate on how that would be certified and whether the issues that were raised in the previous version would even be an issue at all at this point. I think that's just much as I know at this point. Samit?
Thank you. Thanks, Andrew for the question on the ESMO. I think the way to look at it is there are several presentations or data that are being presented at ESMO primarily from the Phase 1 studies and some updates. But the most important one to focus on would be Checkmate 9ER for renal cell cancer, because that certainly is a differentiating therapy. And as Chris mentioned earlier, as well as you heard in the other comments in earlier presentations inclusive of all subtypes are both in and inclusive the favorable risk population, which is currently not covered to our data in the dual IO setting. There will also that update on the dual IO with a four-year follow up for that study. So those two are going to be key as they provide a better way to look at treatment for patients with renal cell cancer with a dual IO, and then of course, we're looking at potentially getting the 9ER approval later. And so that will certainly provide an additional way to treat these patients for a safe and effective medicine perspective. There was a third question on…
Yes. Thanks Andrew for the question on Eliquis. So let me just say at the outset that fundamentals for Eliquis remains very strong both in the U.S. and ex U.S. With the number one OAC in 12 markets now globally. We're the number two in five additional markets. And the fundamentals, again are very strong. With respect to COVID impact, there are really two things that are at play. As David mentioned, there's an inventory work down of the inventory build that we saw in Q1. That's the largest COVID impact that we've seen for the quarter. That's mainly been in the U.S., though not exclusively, but the main impact was in the U.S. And then there's been a smaller impact on demand and that's reflective of the fact that the OAC market has been impacted by new patient volume that has come down. The negative impact was most significant in April. It's begun to recover. We've really not seen an impact on total patient volumes.
As you note, one of the potential upsides for Eliquis has been -- first of all, that Eliquis has been disproportionately unaffected by COVID relative to other players. And then secondarily, we have seen as you alluded to in a number of markets, the desire to try to keep patients out of hospitals and institution. And that's impacted warfarin share. So we've seen a decrease in warfarin share from about 16% at the end of the first quarter to about 14% in June. And that's reflective of -- we think new patients initiating on DOACs as opposed to warfarin. As you alluded to unlike warfarin, DOACs don't require extensive monitoring or dose adjustments. And so as a result, we've seen some IDNs and a number of governments seek to reduce exposure of those patients and Eliquis has disproportionately picked up that share loss. So that's certainly been an opportunity coming out of COVID.
Thanks, Chris. Let's go to the next one.
And we'll hear from Navin Jacob with UBS.
Hi. Thanks for taking my question. Can you hear me okay?
Yes, Navin.
Perfect. Thanks. Just a few if I may. On Reblozyl, a strong quarter. Wondering how much inventory build there was relative to demand. And if you could remind us about the timing of the first-line MDS study readout. Are there any interim analyses that could happen earlier than the final look? And then also the timing of the MS study, please? And then just a question on your early stage pipeline. I think you recently moved your LPA antagonist into Phase 2 for IPF. Wondering if you could discuss any kind of activity that you may have seen in Phase 1b that moved that decision to move that asset into Phase 2?
Thank you, Navin. Why don't we ask Nadim to start and then Samit will cover a couple of your pipeline related questions.
Great. Navin, thanks for your question. So one thing I do want to reiterate that you heard earlier. Overall, we're very encouraged by the launch of Reblozyl, and especially the ability of our commercial teams to pivot to a virtual launch. And we have seen good early adoption so far, especially and I think some key factors here are the significant unmet need in MDS, especially in ESA refractory patients, the unique mechanism of action of Reblozyl of course, our field teams that have very good experience and knowledge of MDS and relationships of MDS prescribers has allowed us to get that access. And we have we have good access with players, now that we have a permanent J-Code since July.
So coming back to a question, Navin. There are some kind of short term dynamics here, partly COVID and the impact of blood shortage. On your specific question about inventory, this is a product that's shipped directly to our customers and sites. So that isn't really in play here. The one area that is -- could be a little bit in play here is, of course, of a new treatment addressing a significant unmet need, you do get a pent up demand with new oncology agents. So there likely is somewhat of a bolus effect going on. But as I said, we're very pleased with the progress so far. And the teams focused on both new patient initiation as well as patient persistence and what we're seeing is encouraging.
We're seeing new patients continue to initiate and we're seeing most patients go on to receive their second and third treatment. Customer feedback remains very good. Brand awareness is high driven by our field team. So we are encouraged. But as you as I said earlier, there is a little bit of a bolus effect too. So we'll see how that dynamic continues to play out through the rest of the year. But very pleased with the progress so far. Samit?
Yes. Thank you. From the COMMANDS study perspective, it's a Phase 3 study. As you know, in the first line setting which includes both RS-negative and RS-positive patients and that study is currently enrolling. We're looking at readout coming in 2022 -- late 2022 timeframe. The myelofibrosis study is just starting off. So that will take a little while to get going and we'll obviously provide the timelines again 2022 and beyond.
For the interstitial pulmonary fibrosis side, as you are aware, we had presented the data and publish the data in IPF as well, where we've seen interesting results, where the side effects were there for the blood pressure effects as well. So we are now investigating the -- in the Phase 2 study looking at seeing what we can do in terms of management of the side effect and the molecule is going to be investigated there, which will then decide how we proceed further with that molecule into a later stage trials. But we have to wait to see the data when it reads out.
Great. I think we have time for maybe one very last quick question, Rolando.
All right. We'll get that question from Matt Phipps with William Blair.
Thanks for taking my questions. Just ahead of the ESMO presentation of 9ER data. Can you remind us on your positioning of that regiment in RCC? Do you think you can meaningfully grow Opdivo total sales in RCC? Or is it really more going to just shore up Opdivo across the different regimens? And then just a quick second one, with some of the COVID related impacts on infusion center access, have you all thought about accelerating time launch for subcutaneous Opdivo? Looks like you recently started another trial that's combined with subcu Opdivo and Yervoy? Thanks.
Thank you, Matt.
Sorry, Giovanni, maybe I'll start with renal cell. So, just the baseline of where the business is today, Matt, is that market share is roughly unchanged from the last quarter. Our overall share of people you're avoiding first time renal is between 30 and 35% on the upper end of that for Opdivo and Yervoy in first line renal is between 30% and 35%. On the upper end of that for labeled indication. And then importantly, we are under penetrated as you would expect in the favorable patient population, which is currently off label. And the way we're thinking about 9ER is, first of all, we're very happy with the data that we've seen both on OS and PFS.
We're also very encouraged by the safety profile. And so as we think about positioning this agent, while it's still early days and we need to see the full data set being presented. We think these provide -- these data provide a very compelling opportunity with respect to existing IO/TKI options. So there's a clear opportunity we think to drive share from existing IO/TKI regimens in this space. Second, TKI monotherapies still a fairly sizable percentage first-line use. It's about 30% in first-line today, mostly in the favorable population. We think that's an opportunity for us as well, because remember, 9ER was conducted across risk status as well as included -- it included the favorable patient population.
So we think there's a real opportunity for us to continue to drive share in that population as well. And so, I think that -- the last thing I would say about the opportunity we have here is to remember our position in renal cell we have both mono therapy in the second-line setting we have Opdivo and Yervoy in first-line. And this gives us a options with IO plus TKI in fact will be the only company with that many different modalities at play. And so we think we're going to have a very strong position with 9ER and first-line is going to be an important opportunity for us to continue to grow the brand starting in 2021 when it's approved.
Thank you, Chris. And when it comes to subcu development, so we are continuously working on that and making good progress on that and looking forward to the readouts of the Phase 1 study where we're looking at the PK parameters, where we'll be able to then compare it to the IV parameter. And then concert with our communications with the health agencies.
Thank you.
Thank you. And thanks everyone. Again, thanks for participating in the call. In closing, let me just say again. We had a very successful quarter. I'm very proud of our teams have executed despite the challenges of the pandemic. We advanced our pipeline. We delivered strong commercial execution. We've continue to supply our medicines to patients. And we are very well positioned for the future. Our pipeline has increased potential to transform patients lives through our science. Thanks everyone for participating in the call. And as always, our team will be available to answer any other questions you may have. Thank you.
And ladies and gentlemen, that does conclude today's call. We thank you for your participation. You may now disconnect.