Bristol-Myers Squibb Company (BMY) Earnings Call Transcript & Summary

Good day, and welcome to the BMS ESMO IR event. 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, Justin, and good afternoon, everybody. Thanks for joining us today for our 2020 ESMO investor meeting. I just want to make sure that you're aware that we've posted slides to bms.com that you can use to follow along with today's discussion. And obviously, we'll have time for Q&A afterwards. But joining me today for the presentation are Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development; as well as Chris Boerner, our Chief Commercialization Officer. Giovanni Caforio, our Board Chair and Chief Executive Officer, as well as some other members of our oncology team are also here for the Q&A. But before we get going, I'll read our forward-looking statements. During today's call, we'll 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. With that, I'll hand it over to Giovanni -- or, I beg your pardon, to Samit.

Thank you, Tim, and it is a pleasure to be able to speak with you, especially right after a very, very important meeting that has just happened not only for the company but also for the patients that we serve in terms of bringing new medicines for the treatment of very serious diseases. So if we go to the next slide, Slide #4, this -- today and over the last couple of days, 3 important trials with the first-time data release were presented that have the potential to expand the use of Opdivo in tumor types that we are adding on overall to the overall development of Opdivo. But to start off, as you see on the left upper corner of the slide, we are pleased that our dual I-O option in first-line renal cell cancer continues to demonstrate durable survival after 4 years in CheckMate -214 study with more than 50% of the patients alive after 4 years. In terms of the first-time data release, study 9ER can potentially provide an important new treatment option for patients with renal cell cancer, combining Opdivo with CABOMETYX. As it relates to upper GI malignancies, earlier today, positive data were presented from study Checkmate -649, where we have the opportunity to be first in line in the first-line setting for gastroesophageal cancer, a tumor with a high unmet medical need. And in Checkmate -577, Opdivo showed a benefit in early-stage esophageal cancer, which is now the second tumor type where Opdivo has demonstrated benefit in early-stage disease. Slide 5, please. Going into just a bit of detail for CheckMate -9ER. Here, you can see the trial design, where a combination of nivolumab and cabozantinib was compared to sunitinib as a treatment for patients with previously untreated advanced or metastatic renal cell cancer. Nivolumab 240 milligrams was administered along with 40 milligrams of cabo compared to 50 milligrams of sunitinib. Patients included in trial encompass all risk groups, meaning those meeting favorable, intermediate and high-risk criteria. While the primary endpoint was progression-free survival, our key secondary endpoint in this study was overall survival along with overall response rate and safety endpoints. And you can go to Slide 6. You have most likely seen the presentation of the data day before yesterday when you saw these strong efficacy results. As a reminder, this trial met its primary endpoint of progression-free survival at an interim analysis along with overall survival, which not only showed statistical significance but also clinically meaningful improvements. As can be seen from the Kaplan-Meier curves, a 49% in the -- decrease in the risk of progression is very strong. In addition, there is a clear survival benefit that was observed across all patient subgroups, including across risk status and levels of PD-L1 expression. And the next slide, as we look at safety, by leveraging 40-milligram dose of cabozantinib, 9ER study delivered strong efficacy with a very encouraging tolerability profile. The discontinuation rate of 15% due to any grade treatment-related AE is lower than that of other TKI, I-O combos on the market today. Taken together, we believe that based on the combined efficacy and safety, Opdivo plus cabozantinib has the best-in-class profile relative to the other I-O plus TKI therapies. And Chris will take -- will talk more about the opportunity as we work towards bringing this regimen to patients in the future. We can go to the next slide, moving to the upper GI malignancies. We wanted to highlight another couple of trials for which we recently announced the top line data, and these 2 trials were just presented at the Presidential Symposia at ESMO. The first one is from large development plan for Opdivo in the metastatic setting. Patients are eligible for enrollment in CheckMate -649 study shown here if they have been diagnosed with gastric, gastroesophageal junction or esophageal adenocarcinoma and have not received prior treatment for their metastatic disease. The disease had to be HER2 negative. While this is a 3-arm study, the nivo, ipi arm data remains blinded until its final planned analysis, and these data are expected next year. Regarding the nivo, chemo arm, dual primary endpoints for PFS and OS in PD-L1 CPS more than 5%, which represents about 60% of the population enrolled in the study. OS was tested hierarchically, first in CPS greater than 5% (sic) [ greater than or equal to 5 ], then in CPS greater than 1% (sic) [ greater than or equal to 1 ] and then in all randomized patients. On the next slide, you can see that Checkmate -649 met both its primary endpoints. Shown here are the data of overall survival, showing a 29% reduction in the risk of death in patients with CPS greater than 5% and a 20% reduction in all-comers. This is the first time our PD-1 inhibitor has demonstrated a survival benefit in patients with gastric cancer, offering a potential new standard of care in a space where other studies have not been successful. We believe this is an important development for addressing our high unmet medical need for these patients and an opportunity for the company, which Chris will talk more about in a few moments. On the next slide, the safety data in the presentation confirms that the Opdivo chemo regimen tested in Checkmate-649 is tolerable and consistent with what we have seen with prior studies of Opdivo. On the following slides, switching gears to the early stage setting. This is a slide that I shared with you back in June at our investor series, and let me remind you of what we believe. We believe that immuno-oncology can play an important role in early-stage disease. From a patient perspective, this is an opportunity to medically intervene early and provide a potential for cure of the disease. We already know that checkpoint inhibitors work in adjuvant melanoma, that these checkpoint inhibitors are active and are benefiting patients with melanoma in the long term. This is likely because the immune system is more intact in patients with early-stage disease. We've now seen Phase III data supporting the potential for Opdivo in early-stage disease across another tumor type that is beyond melanoma with Checkmate -577 in esophageal cancer. On Slide 12, you see patients with esophageal or gastroesophageal junction cancers having tremendous need of adjuvant options as the unmet medical need in this disease is very high. Esophageal cancer is the seventh most common cancer and sixth leading cause of cancer-related deaths worldwide. For certain patients who do not achieve a pathological complete response following new adjuvant chemoradiotherapy followed by surgery, the outcomes are particularly dismal. There is a frequent recurrence of disease for many of these patients as most patients, maybe up to 70% to 75%, have a tumor that fails to achieve a pathological complete response. These patients were generally live less than a year without disease progression with no established adjuvant option to turn to. Patients and physicians need new treatment options that can stem disease progression and prolong life. And that's -- as you can see on Slide 13, in CheckMate -577, we designed the trial to address this particular patient population facing high risk of recurrence. This trial studied Opdivo monotherapy versus placebo in patients with resected Stage II or III esophageal or gastroesophageal junction cancer who received chemoradiotherapy prior to their surgery. Patients were stratified by PD-1 status and histology, that is, nonexpressers versus expressers with a cut point of 1% for PD-1 and squamous cell or adenocarcinoma histologies. Primary endpoint for the study is disease-free survival with overall survival being the secondary endpoint. The overall survival endpoint has not yet been assessed, and BMS as well as investigators remain blinded to that data. On Slide 14 are the data you saw at the congress. I'll spend a few moments to touch on a couple of important things. The trial met its primary endpoint of disease-free survival in esophageal and gastroesophageal junction cancer as an interim analysis. It is important to note this is the first time a benefit has been demonstrated in this population, offering a potential option for these patients for the first time. You can see the strength of the benefit overall and across all subgroups, most notably, PD-L1 expression, tumor location and histology. Successful outcome in this trial further reinforces our view about the potential for Opdivo more broadly in early-stage disease setting. On Slide 15, you'll see the safety profile. Opdivo in CheckMate -577 was well tolerated with an acceptable safety profile consistent with what we know and have seen before. Overall, based on the combined efficacy and tolerability profile of this treatment, we believe that treatment rates for periadjuvant treatment could grow over time as physicians and patients recognize the promise of survival with Opdivo like we've observed in adjuvant melanoma as well. On Slide 16, here is another slide we shared in June. [ So this is basically a ] broad registration program now reflecting the additional trials, which we have read out. We are excited to see our adjuvant programs starting to bear fruit as well as realize these important near-term opportunities in first-line renal cell and first-line gastric cancer to potentially offer Opdivo to a broader range of patients. Now beyond these opportunities, our life cycle management program across various tumor types and stages of disease has both known and combination approaches. Two of these opportunities in particular are in combinations with new mechanisms like relatlimab and bempeg, which I will discuss briefly on the next slide. Now the journey in immuno-oncology doesn't end with life cycle management of Opdivo and Yervoy. We have 2 next-generation I-O mechanisms under late-stage development: bempeg, our IL-2 partnered with Nektar; and relatlimab, our anti-LAG-3. We are studying how bempeg can be combined with Opdivo, first, in melanoma and then in several of the other indications that you can see on this slide. As it relates to relatlimab, we are now testing this medicine in a randomized Phase II/III trial, looking at what added benefit relatlimab might demonstrate on top of Opdivo. Both these agents have the opportunity to provide additional therapeutic options for patients through next-generation immuno-oncology innovation. On the next slide, I just want to remind you of the mechanism of action that we are pursuing in immuno-oncology with our LAG-3 inhibitor, relatlimab. The hypothesis behind this agent is that LAG-3 expression is associated with T cell exhaustion, and that could be leading to a form of primary or possibly secondary resistance to PD-L1 blockade or PD-1 blockade. Now blocking LAG-3 expression using relatlimab could allow for T cell activation in instances where T cell exhaustion is causing that lack of response. Therefore, in addition to providing us with potentially registrational data from the ongoing first-line study in melanoma, this trial will provide us with data to probably inform potential life cycle management plans for future development of relatlimab. And in the next slide before I wrap up, I just wanted to summarize. We are excited about the data shared at ESMO and for the ability to build on our presence in first-line renal cell space as well as expanding on the I-O opportunities in the upper GI tumors. Opdivo and Opdivo-based therapies continue to offer life-extending options for patients facing serious cancers with unmet need, and we look forward to additional readouts from our robust program that we saw earlier across both metastatic and early-stage settings. We continue to invest in innovative next-generation mechanisms and await pivotal data from our late-stage I-O pipeline with relatlimab and bempeg. I will now turn it over to Chris to take you through the commercial perspective. Thank you.

Thanks, Samit, and good afternoon. I want to pick up where Samit left off and talk a bit about how we think about the data presented at ESMO from a commercial standpoint and how it fits into the broader I-O growth narrative for the company. Starting on Slide 21. As we've discussed previously, we've built a very robust business in I-O of just shy of $9 billion globally last year. This reflects over 400 global approvals in a dozen tumor types and the majority of which BMS I-O is now standard of care. This book of business provides a strong foundation for continued growth in 2021 and beyond. And an important component of that growth was obviously the launch of first-line lung cancer in the U.S. earlier this summer. Those launches continue to proceed well, and I'm happy to discuss that further in Q&A, as you like. We also, last week, received a positive CHMP opinion for Opdivo + Yervoy combined with 2 cycles of chemotherapy, and we look forward to launching that regimen in Europe in the coming months. At ESMO this year, we saw data across 2 other tumor types that will also be important contributors to near-term growth. So let me spend a few minutes providing a commercial perspective on these. I'll start with renal cell carcinoma on Slide 22. RCC accounts for roughly 1/4 of Opdivo sales in the U.S., with Opdivo + Yervoy garnering approximately 35% share in the first-line setting. As you can see on the left-hand side of this chart, the vast majority of this use is in patients with intermediate and poor performance status, which is our labeled indication. We've maintained this very strong position in first-line renal in spite of significant competitive pressures here in large part because of the impressive long-term benefit of dual I-O therapy. This long-term benefit was reinforced with the 4-year survival data presented over the weekend, which you see on the right-hand side of this slide, with over 50% of patients alive at 48 months and a relatively stable hazard ratio compared to the last data update at ASCO GU. Moving on to the next slide, Slide 23. It's into this context that we anticipate introducing the 9ER combination. Over the last number of months, we've had the chance to discuss with key customers the highlights of the data Samit just went through and which were shared at this conference. The consistent feedback we hear is that the Opdivo plus cabo regimen compares favorably to existing I-O TKI options as evidenced by the impressive OS and PFS benefit that compares very well against existing therapies and a very manageable safety profile. Given this profile, we see multiple opportunities to build upon our existing position in this market by displacing existing single-agent TKI use, which you'll note from the previous slide still accounts for approximately 20% of current frontline use. We also see the opportunity to extend the benefit of Opdivo-based therapy into the favorable-risk patients with this regimen, which, as I mentioned, is currently off label for us. And finally, we see the opportunity to compete effectively in patients receiving currently available I-O plus TKI options. Importantly, once approved, we'll be the only company to offer multiple I-O-based options to renal cell cancer patients, both dual I-O and, what we believe is the most compelling, I-O plus TKI option. Moving on to gastric cancer on Slide 24. We are very excited with the opportunity to bring I-O therapy to first-line gastric patients. As noted on this slide, gastric cancers, including gastroesophageal junction cancer and esophageal cancer are among the top-10 deadliest cancers worldwide. They are also cancers where we have seen limited advancements in over a decade, resulting in a substantial need for therapies that improve survival in the metastatic setting and, as we'll discuss on the next slide, prevent recurrence in locally advanced disease. With the CheckMate -649 data Samit just reviewed, we are very excited with the potential to be the first and only I-O regimen demonstrating a superior survival benefit versus chemotherapy in non-HER2-positive disease across upper GI tumors. From a commercial standpoint, I'd highlight a few things about the opportunity here. First, the early feedback from physicians with whom we've shared these data has been very promising. Specifically, they note the compelling survival benefit that offers the potential to improve on current standard double chemotherapy in these upper GI tumors. The fact that clinical benefit was shown across PD-L1 expression levels is also viewed as important as is the fact that these benefits were accompanied by a generally manageable safety profile. Second, I would also note that while this is a new tumor for I-O, this is a customer set we know well and which has experience with I-O and Opdivo-based regimens in other tumors. Bottom line, we're very excited about the opportunity we have in metastatic disease with CheckMate -649 data. Moving on to Slide 25. The 577 data give us the opportunity to move I-O therapy into early-stage esophageal cancer. As we have discussed within the context of our adjuvant melanoma experience, we know that when we are able to introduce effective biotherapies in early-stage disease, we have the opportunity to not only treat the set of patients being treated with existing therapies but also expand the pool of patients available for treatment. In fact, in melanoma, we saw greater than twofold increase in treatment rates. In early-stage esophageal cancer, as Samit noted, there is a significant unmet need for patients. Only about 45% of Stage II/III patients today receive neoadjuvant chemotherapy plus radiotherapy, and the treatment rate post CRT and resection is extremely low. Moreover, among those who undergo surgery with CRT, the majority do not receive a complete response, portending a high risk of recurrence and progression to metastatic disease. Finally, while neoadjuvant and perioperative chemotherapy is used in a number of patients, there are still no systemic adjuvant therapies available for patients, and outcomes remain poor. Based on the 577 data presented at ESMO, we believe we have the opportunity to drive adoption of adjuvant Opdivo across upper GI tumors post CRT and surgery. As Samit highlighted, the study demonstrated a highly significant and meaningful increase in disease-free survival. That benefit was seen across subgroups. And importantly, given this is early-stage disease, the benefit was accompanied by a well-tolerated safety profile. Obviously, it's still early days, and we'll continue to engage customers now that the full data set has been presented. But we think Opdivo has an important role to play for Stage II/III patients with esophageal and gastroesophageal junction cancers. Next slide, please. Let me close here on Slide 26. As we've discussed previously, we have a strong base of business today across multiple tumors globally. We are happy with the early experience we're having in first-line lung cancer with our U.S. launches and look forward to the launch of the 9LA regimen in Europe in the coming months. And we're very pleased with last week's positive CHMP opinion supporting that launch. At this conference, we've heard about data in 2 additional tumors that will be near- to medium-term catalysts for I-O growth. In renal cell carcinoma, the updated 214 data for Opdivo + Yervoy continue to emphasize the longer-term durable survival benefit seen with dual I-O therapy. Data from CheckMate -9ER allow us to build upon this leadership position by providing what we believe is the best-in-class I-O TKI option for patients, and we see meaningful opportunities where we can grow our business with this regimen. CheckMate -649 and CheckMate -577 provide us the opportunity to establish I-O and Opdivo specifically as an important treatment option for patients with upper GI tumors in both frontline metastatic setting, as well as early-stage disease. Collectively, the data presented here are part of a robust set of life cycle options for our existing I-O agents as well as the potential we have with next-generation assets, including relatlimab and bempeg. And with that, I'll turn it back over to Tim to moderate the Q&A.

Thanks very much, Chris. And as a reminder, as well as Chris and Samit, we have Giovanni Caforio, our Board Chair and Chief Executive Officer, on the line for Q&A as well as some of the folks from our oncology team as well. So with that, Justin, if you don't mind, can we go to the first question, please?

[Operator Instructions] Our first question will come from Chris Schott with JPMorgan.

Great. And congrats on the data here. I just had 2. Maybe first on adjuvant esophageal. Can you just talk about the penetration rates you've seen with Opdivo and combos in adjuvant melanoma? And should we think about that as a decent analogy when we think about what you can achieve in this esophageal setting? And is there any like similarities or differences that you'd highlight there? And maybe just also give an update in terms of where you stand in terms of the frontline non-small cell cancer launch in the U.S. type of share that you're seeing? I think with the 2Q results, you talked about some very encouraging trends. And can we maybe just get an update of how that's progressed over the last, I guess, 1.5 months or so since that last update.

Sure. Thanks for the question, Chris. As you know, the penetration we've seen in adjuvant melanoma is roughly around 40%. That was a tumor where treatment rates were very low when we launched I-O into that setting. We've grown those treatment rates to upwards of 80% today. I think there are some fundamental differences as you look into esophageal cancer. First, this is a setting in which you've seen very little systemic use of any agents for patients in the adjuvant setting. This is an area where it's not really one disease, it's actually multiple diseases. So as you may know, 577 is a study that covered esophageal adeno and squamous cancers as well as gastroesophageal junction cancers. So I don't think you can really compare in terms of the underlying dynamics of melanoma to what we see in this particular space. What I will say is comparable, though, is the level of benefit that we're seeing with I-O therapies. We're very excited with the data that we've seen with 577. Remember, this has the opportunity to be the first I-O to market in the early-stage esophageal setting. The data here are very compelling, a doubling of PFS with a manageable safety profile. And based on that, we think we have the opportunity to significantly improve on the outcomes for patients, which, as Samit noted, the majority of patients, in fact, about 3/4 of patients, who undergo CRT and resection do not actually get a pathological CR, and that portends very bad outcomes for those patients. And so we're excited about the opportunity that we have here. I would just be a little bit reluctant to do a simplistic look at what our penetration rates were in melanoma and applied it in here. These are different diseases.

With respect to first-line lung business...

[ Can I continue? ]

Sorry. Sorry, with respect to first-line...

Go ahead, Chris.

Yes, let me make a few comments. And then we have the head of our U.S. business, Adam Lenkowsky on, and he can jump on as necessary. What I would say is we continue to be very happy with the performance of the launch. As I mentioned in the second quarter call, we're seeing penetration rates in the mid- to upper single digits. We'll obviously give you an update on that as we get into the third quarter call. We continue to see very good execution here. We've reached a high percentage of the high-prescribing physicians in this space. This is, as you know, a space where the community physicians are very important. And so we've been targeting those physicians who have experience in the community setting with Opdivo and Yervoy in other tumors. And again, that's an area where we see very good engagement. And we're particularly excited because, as we noted on the second quarter call, we are not seeing physicians pigeonhole the use of Opdivo and Yervoy in lung cancer into a specific patient type. We're actually seeing use really across a broad swath of patients. The majority of the use is in the PD-L 1% to 49% segment. We are seeing some use above 50% PD-L1 expression. We're starting to see a pickup in the PD-L1 negatives and nonexpressers. That's the regimen that is covered -- or that's the space that's covered by the 9LA regimen. So overall, very happy with what we're seeing in first-line lung. Adam, anything to add there?

I think you said it well. We're very encouraged by the uptake. It's still early. We're approximately 3 months post approval. We knew entering the market this was going to be an entrenched market with KEYTRUDA and KEYTRUDA plus INLYTA. But as Chris mentioned, our share in just over 3 months is now in the mid- to high single digits, and we're seeing continued growth. And we're seeing use across all PD-L1 expression as well as in squamous and in nonsquamous. What we're hearing back from our physicians is our profile for both 227 and for 9LA. The profile is differentiated. The durability, the 3-year landmark survival and chemo-free messages are all resonating. And we've shown that we're increasing awareness, particularly in 9LA because 9LA launched after CheckMate -227. And we're seeing uptake now with that regimen largely in the negative. Our team has done a very nice job with remote engagements. We've been, almost exclusively, virtually engaging our customers. And we've penetrated our highest-value customers over 60%. We're focusing on our O + Y prescribers as early adopters, and we've been ahead of our competition in share of voice. Lastly, I'll mention, you probably have seen, we launched a national direct-to-consumer campaign last week to help educate patients and hopefully drive patients in to ask and have a dialogue with their physicians around Opdivo and Yervoy and the durability and chemo-free option for long-term survival.

Our next question comes from Seamus Fernandez with Guggenheim.

So just wanted to get a quick sense. When we look at the tolerability of the 9ER regimen, frankly, this looks better tolerated than any other TKI regimen. It looks better tolerated than Opdivo + Yervoy. Why wouldn't this be your sort of leading option particularly given the robust PFS? Obviously, that was a message from the discussion. And then separately, just wanted to get a better sense in the gastric cancer setting. Would you guys -- help us understand where the most likely first-line gastric cancer opportunity you believe is? Is this really an area globally where you expect [ you can invest in ] cancer plus chemo to be in the 5%-plus patient population, 1%-plus PD-L1 positive? Or is it your expectation that the benefit is actually across the entire patient population? I know it's statistically valid in the overall population but just wondering how you expect treatment to evolve globally given the results presented over the weekend.

Sure. Thanks, Seamus. I'll take that. And then Samit, you can obviously add in as you need to. So with respect to first-line renal cell, I mean, I think that you characterized the way we see 214 and 9ER pretty well. I mean I think that, in fact, the discussions summarized it as well. We think we have the best-in-class I-O TKI regimen with Opdivo plus cabozantinib. And I think the data that we've seen with 214 both from an efficacy and safety standpoint continues to impress with the long-term durability of that. In terms of how this ultimately will be used, we actually think that there's an analog to the way that physicians have begun to think about these regimens in first line with what we saw in second line. When we launched I-O in second line, what we saw is physicians were choosing to use TKIs for those more aggressive patients, patients where you needed to get an immediate response. And those -- for those patients where you could allow I-O time to work, they would opt for I-O therapy. That's begun to be the approach that physicians are using as they think about 214 and existing I-O TKI option. So we're very happy now to be the only company that have multiple I-O approaches to offer in this space. We think we've got a best-in-class I-O TKI with Opdivo, cabo, not only from an efficacy standpoint but also a very good safety profile. Again, as the discussion mentioned yesterday, good opportunity for us to -- over the weekend, good opportunity for those patients who need a very quick response. But then for those patients where you're looking for a long-term benefit, 214 provides an option there. And so happy to be able to have both of these regimens available for renal cell patients. And I think that's roughly how we're going to see that segment out. With respect to how we think about gastric and first line, I think that the 649 data has clearly demonstrated an improvement across all patient segments. The data is particularly strong, as you noted, in CPS greater than 5%. What's on label is ultimately going to be a regulatory discussion. We'll have to see how those discussions play out both in the U.S. and ex U.S. What I would say is that given this is a space where we've not seen much in the way of innovation in over a decade, given the significant unmet need here, I think you're likely to see physician interest certainly in the U.S. to be in a very broad patient population. As you get outside of the U.S., given the HTA dynamics, we may see a different set of dynamics play out there. But again, we're going to have to wait and see how the regulatory discussions go, and it's certainly our belief that the benefit here is across the entire population.

Our next question comes from Steve Scala with Cowen.

A few questions. First, Asian markets, as you've noted, are key to the GI indications. What are the time lines for filing in Japan and China? And can you remind us of the Bristol-Myers Squibb Asian footprint in terms of sales force? Secondly, Bristol has a digit, but it gets little attention. Now that a second company has shown positive results, is your view changing? And then thirdly, if you will allow me, Bristol recently said that the liso-cel plants had not been inspected yet. Can you tell us if the dates have been set to inspect each plant?

Samit, do you want to start?

Sure. Maybe we can start with -- well, in the order that you asked. First of all, in the Asian market of the filing time line around the data for gastrointestinal tumors that -- we're just studying the upper GI because, obviously, very important data. And we see the data applicable from these global studies both in the adjuvant setting as well as in the first line setting. So we have a global registration strategy always that we work through and. Since the trials, have enrolled from across the globe, we will be discussing these. We cannot today tell you exactly the time line because there are lots of presubmission meetings that we have to carry out with health authorities. But as the time lines become more finalized, we will certainly communicate those, but we are working towards those aspects of filing. From a TIGIT perspective, certainly, we are looking obviously at the data that were presented recently at ESMO from other companies. We have our own TIGIT, as we have said before, which is in Phase I right now. We are continuing to evaluate that. It's not that we changed our strategy. We just have to wait for the Phase I data to read out from both the safety perspective, dose perspective and any hint of activity perspective, and then we will be able to share further what our development plan will be for TIGIT. The third question you asked was about liso-cel. And as we have recently communicated, both myself as well as Giovanni and others, we have not spoken publicly. But we do -- we continue to work with the FDA in terms of assessing when the inspections will be. These plants have not yet been inspected. Just a reminder, we do have a breakthrough therapy designation. I remind you that we have a PDUFA date in November. As soon as the FDA will inform us, we'll certainly take that into account. But right now, we don't have a date for inspection at the time, and so they have not been inspected yet. Thank you.

And just very quickly on the presence in Asian markets. We have a presence in all of the key Asian markets. And certainly, as you know, gastric is an important potential opportunity in those markets.

Our next question comes from Geoff Meacham with Bank of America.

And congrats on all the updates at ESMO. For Chris, on 9ER, I just want to understand the commercial positioning of nivo, ipi versus nivo, cabo. Just what are the puts and takes for I-O, I-O versus I-O TKI share in renal? And then for Samit, data for 649 look strong. But looking at the tail of the curve, it's not really close to what you see in other I-O sensitive tumors in terms of long-term OS benefit. Do you think gastric is just a difficult indication that's less immunogenic or I-O doublets or triplets needed in your view to improve OS further?

Maybe I'll start, and then I'll turn it over to Samit. I think with respect to the puts and takes for 9ER, as I said earlier, I think that as we look at where 214 and 9ER would be positioned, I think you're likely to continue to see physicians look to I-O TKI options for those patients who need a more immediate response or have a more aggressive disease, and then they'll opt for 214 potentially for those patients with less aggressive disease, where they have more time for I-O therapy to work. The other thing I would note is that 9ER, because it included patients across performance status, gives us the opportunity to promote in the favorable patient population, which, as I mentioned in the presentation, we don't have the ability to do in 214. So that's something that is somewhat unique to 9ER and is an important opportunity for us. And with that, I'll maybe turn it over to Samit.