My name is Crystal, and I will be your conference facilitator today for Amgen's conference call on the approval of LUMAKRAS and the collaboration with Kyowa Kirin. All lines have been placed on mute to prevent any background noise. There will be a question and answer session at the conclusion of the last speaker's prepared remarks. In order to ensure that everyone has a chance to participate, we would like to request that you limit yourself to asking one question during the Q&A session. To ask a question, please press star, then the number one on your telephone keypad. To withdraw your question, press the pound or hash key. I would now like to introduce Arvind Sood, Vice President of Investor Relations. Mr. Sood, you may begin. Crystal, thank you. Good morning, everyone. Thanks for joining us this morning for this call. We have not one, but two topics to discuss today. You may have seen this morning that we announced an agreement to jointly develop and commercialize a novel molecule for atopic dermatitis. We have set up this call initially, of course, to discuss the approval of LUMAKRAS, our first-in-class KRAS G12C inhibitor. To discuss these topics further, I'm joined today by Peter Griffith, our CFO, Dave Reese, our Head of R&D, and Murdo Gordon, our Head of Global Commercial Operations. Each will make brief prepared comments, and we should have plenty of time for Q&A. With that, I would like to turn the call over to Peter. Peter? Arvind, thank you. Good morning, everyone. I'd like to add my thanks for joining us this morning. We announced the approval of LUMAKRAS past Friday and this morning we have announced a collaboration with Kyowa Kirin to develop and commercialize a first-in-class phase III-ready molecule for atopic dermatitis. These are examples of what we always do, start with patients in mind at Amgen. Our collaboration with Kyowa Kirin will allow us to address a growing unmet need around the world for patients suffering from atopic dermatitis. We will capitalize on genetic insights from deCODE to help inform development in other inflammatory diseases. The collaboration is a strong strategic fit with our long-standing expertise in immunology and inflammation, represents a significant addition to our portfolio of ENBREL, Otezla, tezepelumab, AMG 592, 570, 714, and AMGEVITA. Dave will go through this in additional detail, but LUMAKRAS' approval and this collaboration with Kyowa Kirin demonstrate Amgen's disciplined, predictable, and strategic execution of our capital allocation hierarchy. Which always begins with investing in both internal and external innovation to drive long-term growth. We want to invest in external innovation where we are the best or one of the very best investors. With our long, successful history with Kyowa Kirin and our decades of achievements in inflammation, this opportunity easily clears all of our hurdles. Our long-term record with Kyowa Kirin will also allow for prompt execution and maximize the value of the collaboration for all parties, and most importantly, patients. Today's announcement is our third deal in 2021, following on the recent Five Prime and Rodeo acquisitions. Our collaboration with Kyowa Kirin adds another phase III-ready asset to our pipeline of medicines with strong growth potential, and we continue to look for other opportunities that align with our disciplined business development strategy. Slide 6 steps through some of the relevant deal terms for this collaboration. Amgen will lead development, manufacturing, and commercialization of KHK4083 globally, except in Japan, where Kyowa Kirin will continue those responsibilities. Global development costs will be shared, except in Japan, and U.S. commercialization costs will also be shared. Amgen will make a $400 million upfront payment to Kyowa Kirin and future contingent milestones worth up to an additional $850 million. Finally, Amgen will book sales for KHK4083 in all markets globally, except Japan, and will pay royalties on future global sales. Let me now turn the call over to Dave. Dave? Thanks, Peter, and g ood morning, everyone. As Peter and Arvind mentioned, first we'll step through a little more detail on our partnership with Kyowa Kirin regarding KHK4083. Murdo and I will give a brief perspective on the launch of LUMAKRAS after the FDA's approval last Friday. Starting with our collaboration with KK, for those of you following along the slide deck, I'm on page six. KHK4083 is a clinically validated, phase III-ready, first-in-class, anti-OX40 antibody that has the potential to address a very significant global unmet need for patients with atopic dermatitis and potentially other inflammatory diseases where we intend to leverage our industry-leading platform at deCODE genetics to inform on the potential use of KHK4083 in indications beyond atopic dermatitis. Atopic dermatitis itself, as many of you know, is the most common form of eczema. It affects about 15%-25% of children and 1%-3% of adults. This constitutes more than 26 million people in North America, EU, and Japan alone, with particular unmet need in patients with moderate to severe disease. The incidence of this autoimmune disorder has increased two to three fold since the 1970s. It sits in a family of autoimmune diseases such as asthma or hay fever. The target itself here is OX40. OX40 is a member of the TNF receptor family, as you see on slide seven and i t has important co-stimulatory functions during T cell activation. It's important to mediate the survival and proliferation or expansion of both CD4 and CD8 positive T cells, and i t helps control effector and memory T cell responses. There's a lot of evidence that the OX40 pathway is upregulated and plays a pathogenic role in various autoimmune diseases, where upon activation, activates downstream signaling pathways that drive the expression of various pro-survival molecules, increases cytokine production, and as noted, creates the generation of both effector and memory T cell subsets. KHK4083 itself is a fully human, Aq-calculated antibody that has a presumed dual mechanism of action, both blocking OX40 signaling and enhancing antibody-dependent cell-mediated cytotoxicity of effector T cells that in fact, is believed to lead to the depletion of those cells, including pathogenic cells over time. Now, of course, what we find most compelling about the collaboration is the clinical data generated to date by Kyowa Kirin. Early signs of activity we're seeing as early as a proof of concept phase I study in patients with moderate to severe atopic dermatitis, where various improvements in disease markers and clinical symptoms were observed. In February of this year, Kyowa Kirin announced positive phase II results from a double-blind, placebo-controlled study of 274 patients with moderate to severe atopic dermatitis, a study that was conducted in the U.S., Japan, Canada, and Germany. The primary endpoint was successfully met with a statistically significant improvement in the percent change from baseline in the Eczema Area and Severity Index, often called the EASI score, at 16 weeks compared to placebo. There was also improvement in various secondary endpoints such as the EASI-75, which represents an improvement of 75% or greater from baseline, and the Investigators' Global Assessment Score, or IGA, of zero or one with an improvement of two points or more at 16 weeks, so t hat score, lower is better. Interestingly, further improvements in efficacy were seen in these measures after week 16, indicating perhaps ongoing and cumulative effects of the therapy. Common treatment emergent adverse events included fever, nasopharyngitis, worsening of atopic dermatitis, and chills, and in general, the adverse event profile was reported to be well-tolerated. Key next steps here include discussing with regulatory authorities the phase III program and with our partners at Kyowa Kirin, that will be the first order of business for us. We believe KHK4083 represents a significant opportunity in atopic dermatitis alone, and that, of course, is our immediate focus. As I noted, there's also the potential in additional inflammatory diseases. We're going to explore the role of the OX40 pathway in human disease, not only through additional preclinical models, but through deCODE genetics, where we have already begin work to potentially prioritize additional indications. In closing, I'd like to say that for myself, I think and all of us at Amgen, we're thrilled with this renewed partnership with KK and the opportunity to bring a medicine to market for patients where there is residual, very significant unmet medical need. We're going to bring all of our development, manufacturing, and commercialization expertise to this challenge. With that, Murdo Gordon and I will now transition to provide a brief perspective on the LUMAKRAS launch. Of course, we had FDA approval last Friday. For those of you following along, I'm now on slide nine. LUMAKRAS represents the fastest development program in Amgen's history. We're absolutely delighted to be able to bring this medicine to patients who have few good treatment options. You can see the indication statement. LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C mutated locally advanced or metastatic non-small cell lung cancer, as determined by an FDA-approved test, who have received at least one prior systemic therapy. The FDA took advantage of various accelerated review pathways to bring LUMAKRAS to patients in near record time. This is an accelerated approval based on overall response rate and duration of response. I should point out that in a few days at the ASCO meeting, we will be presenting updated data from the pivotal phase II trial, including overall survival data as well as additional biomarker analyses. The recommended dosage is 960 mg once daily, which can be taken with or without food. Turning to slide 10, as I'm sure all of you are aware, KRAS has been a holy grail target in oncology for 40 years, challenging to drug because of the structure of the molecule. It is a relatively frequent mutation in non-small cell lung cancer, adenocarcinomas in particular, where roughly 13% of these tumors bear the G12C mutation. It occurs in other tumors, such as colorectal cancer, at a frequency of 1%-3% in a variety of other solid tumors. LUMAKRAS really represents the culmination of a strategy we put forward in oncology several years ago, predicated on the belief that oncology of the future would represent the marriage of immuno-oncology and precision oncology. Within precision oncology, we elected to focus our efforts on what we believe were very high-value targets. We now have over 900 patients enrolled in the LUMAKRAS clinical development program across five continents and have, of course, many combination therapies in development at this time. Slide 11, or next slide, you can see that KRAS G12C is one of the most prevalent driver mutations in lung cancer. As I mentioned, it occurs in about 13% of individuals, roughly comparable to the frequency of EGFR mutations. That translates to about 20,000-25,000 KRAS G12C positive patients in the U.S. each year, of whom approximately 13,000 have second or later lines of therapy and are the immediately addressable population by LUMAKRAS. The next slide, you can see that until today, there have been no therapies available for patients whose tumors bear the G12C mutation. Chemotherapy is most commonly used in this setting, but historically has had relatively low response rates and a short duration of response. In fact, up to one in five patients whose tumors have KRAS G12C mutations don't receive systemic therapy or don't go beyond first-line therapy because of comorbidities and the lack of good treatment options. On the next slide, you can see that KRAS testing in non-small cell lung cancer is recommended now in multiple clinical guidelines, including various pathology associations, ASCO, as well as the NCCN guidelines. We expect the latter will be updated relatively soon now that LUMAKRAS is available. I'll finish just by mentioning on the next slide are the two companion diagnostics that have been improved in conjunction with LUMAKRAS. We've been happy to work with Guardant on a liquid biopsy kit, which is the first FDA-approved test using next-generation sequencing in the liquid biopsy setting. National Medicare coverage is already established for non-small cell lung cancer testing. We also worked with QIAGEN on their therascreen RGQ PCR assay which is a tissue-based assay. This kit is well established in the marketplace, where it is used in colorectal cancer to actually select wild-type patients who are available for anti-EGFR antibody therapy such as Vectibix. This single gene test is well covered by Medicare as well as commercial insurers. As part of the development program, we've also done concordance studies and found very strong concordance between the liquid biopsy and tissue biopsy assays. With that, I'll turn things over to Murdo, following which we'll have plenty of time for questions and answers. Thanks, Dave. On slide 15, you'll see currently the campaign that we're running to ensure that we are driving awareness of the availability of the KRAS G12C testing. As Dave outlined, currently about 50% of patients have been tested for their KRAS G12C mutational status. We intend to obviously expand that testing. With the advent of the approval of Lumakras and the now actionability of the KRAS G12C mutation, we think that that will rise fairly rapidly. The other thing just to note is that the majority of non-small cell lung cancer patients are treated in a community oncology setting. Of course, we're working with the large networks in oncology to ensure that they also have testing availability in their ordering system at the point of clinical care. On the next slide, you can see that we're not doing this work on our own. We've been in the market now for several months with a Biomarker Assist program. This program allows us to help patients with the out-of-pocket costs associated with their deductible, co-insurance, or co-payment related to their test. We also have extensive programs in the Amgen FIRST STEP program, which helps commercially insured patients pay their out-of-pocket prescription costs. We're working with LUNGevity Foundation to build awareness with our customers and with patients to understand that LUMAKRAS is now available and that they may be eligible for treatment if they've progressed on their frontline therapy. Lastly, Amgen Assist offers other financial support options for any insurance type referrals, and we've been extending the Amgen Assist program across the entire portfolio of Amgen products. On the next slide, basically we are very focused on providing value to patients, oncologists, and of course, the healthcare system at large. We believe that having LUMAKRAS available at the U.S. list price of $17,900 per month represents indeed good value. The first part of our value story is that you do have a targeted precision oncology therapy biomarker, which narrows the treatable population to 13% non-small cell lung cancer. That reduces the exposure of patients to a therapy that they may not benefit from. We also believe that we have a significant improvement over the standard of care in advanced non-small cell lung cancer, delivering this targeted therapy really, that has very good response rates and highly tolerable, allows patients a very good option should they progress on their frontline therapy. Obviously, we are hopeful that we'll be able to continue to demonstrate the safety and efficacy profile of LUMAKRAS with additional clinical work that's underway. On the next slide, you can see that really our strategy, as outlined by Dave Reese, has been exemplified by LUMAKRAS launch. There are many people who should feel extremely proud of this. Our investigators, the patients that volunteer for our early clinical trials, and I'd be remiss if I didn't thank David Reese and his entire R&D organization for working so hard, so diligently through a pandemic over the last three years, which is quite remarkable to bring a product to the market so quickly after more than four decades of scientific and industry pursuit. Amgen really has drugged the undruggable, and it's a fantastic time for patients. We've prepared for this day. Everyone here at Amgen is extremely energized, and we'll be putting everything we can into ensuring that patients who are eligible for this product are able to access it and able to afford it. With that, I'll turn it back to Arvind. Okay, great. Thank you, Murdo. Crystal, let's go ahead and open it up for Q&A. As a reminder, in order to ensure that everyone has a chance to participate, we would like to request that you limit yourself to asking one question. To ask a question press star then the number one on your telephone keypad. To withdraw your question, press the pound or hash key Your first question comes from the line of Michael Yee with Jefferies. Hi, good morning. Can you hear me? Yeah, can hear you just fine, Mike. Go ahead. Hey, Arvind, h appy Tuesday. My question was around the commercial launch for KRAS and just trying to compare and contrast to other targeted therapies that have launched over the past few years. Maybe you could talk about either tailwinds or headwinds. I think about maybe better testing and increased testing and awareness. At the end of the day, there's a lot of different drivers there. Maybe you could just talk about that and compare and contrast to other targeted therapy launches that we've seen in the industry and how you're thinking about comparing. Thank you. Okay, Michael, I'll take that one, and Dave, if you'd like to add any commentary, please jump in. Mike, the first thing I would comment on is because the KRAS pathway has been known to be a driver mutational pathway in cancer for so long, there has been RAS testing. Of course, in many settings, the testing was to exclude patients with RAS mutations from treatment, as is the case in colorectal. The fact that you've got the test available commercially in the market already and that any good reference lab is routinely doing KRAS panel testing on patients with non-small cell lung cancer, that gives us a very strong baseline. As I mentioned in my opening remarks, about 50% of patients probably have a KRAS G12C status result somewhere in their pathology report. Now, what we're working on is making sure that result is not in the back pages of that report, but goes on the front page, which is where all the actionable mutations like EGFR and ALK are. If you get a lung panel today, KRAS G12C may not be on the front page of that path report. That's what we're working on with pathology, with pathologists, and with oncologists. We've been doing that for some time, but it's obviously a lot easier now that you have a drug approved to action against that mutation. That's one thing that's a little bit different than, say, the ROS products or even ALK at the very beginning of the XALKORI's approval and launch, where ALK testing was relatively low. The fact that we've been campaigning for over a year now in creating awareness of KRAS G12C affecting about 13% of patients, the fact that we have very good reimbursement programs assisting commercially insured patients and other programs assisting a broader population of patients, both with biomarker testing and with out-of-pocket expenses related to their prescriptions. Those are all very positive things in terms of the launch conditions. We've had trained, ready-to-go field medical teams in place for months now. Salespeople have been trained and in place for months now. Just as an example of how ready we are, within one hour or two of the approval, all of our healthcare professional website was up and running and providing information to them. This is a well-oiled machine that's running extremely effectively. The one caveat I would extend is that we are still launching into an environment that has been impacted by COVID. We are hopeful that we're able to reach customers through the extensive digital channels that we've opened up and through our field people as well. That's the less predictable piece of the launch that I would just note. Thanks, Mike. Your next question comes from the line of Terence Flynn with Goldman Sachs. Hi, good morning. Thanks for taking the question. I was just wondering, Dave, if you could share any more details on the efficacy profile of the anti-OX40. Is this more comparable to DUPIXENT or more like a high-dose JAK in terms of efficacy? If you can't really provide any details there, maybe you could just elaborate on areas of potential differentiation versus those other agents. Thank you. Thanks, Terence. Yeah, we can't really go into much more detail on the efficacy profile now until those data are presented out publicly. Obviously, we were impressed with what we saw. I think the biggest area of differentiation here is the unique mechanism of action. Given the residual unmet medical need, the large numbers of patients who often cycle through different therapies, we think there's a real chance to, with a differentiated product here, make a real impact. Of course, we'll have more to say once the investigators are able to present those data publicly. Your next question comes from the line of Matthew Harrison with Morgan Stanley. Great. Good morning. Thanks for taking the question. Dave, I was hoping to ask two things on OX40 as well. One, it looks like the onset of action from the data that I've seen is a bit slower, more out to maybe four weeks time point, so you'd be robust to action. I'm just wondering how you think about that, and if you agree with that. Then second, can you comment at all on what we should be thinking in terms of broadly in terms of the royalty rate? Thanks. Yeah, maybe I'll take the first part of that question and then ask Peter or Murdo to comment on the second, or Arvind. Yes, Terence, I think your supposition regarding the onset of action is correct, probably related directly to the mechanism of action. As I noted, we believe this has a dual mechanism, both blockade of OX40 signaling, but then also depletion of critical OX40-bearing T cells over time. Because that depletion takes some time, that may account for the slower onset of action. It also may account for the observation, as I pointed out in the phase II trial, that in some patients, continued improvement beyond the 16-week standard endpoint timing was observed. More to come there, but we think there's good biological plausibility for this, and it's simply something that the physician community will need to be educated on. Peter, are you going to take the second part on royalties? Yes, Dave. Thank you, and good morning, Matthew. We're going to make a $400 million upfront payment to Kyowa Kirin, as we mentioned. Future milestone payments potentially worth up to an additional $850 million. We are going to make significant royalty payments on any net sales in the United States and significant tiered royalties on net sales ex-U.S. Of course, that's excluding Japan. We do expect future milestones are going to hit cost of sales over a multi-year period. As you know, under our non-GAAP accounting policy, the upfront payment will be excluded from our non-GAAP amounts. Arvind? Your next question comes from the line of Geoff Meacham with Bank of America. Morning, guys. Congrats on the early approval and deal, and thanks for taking the question. On the LUMAKRAS label, I don't think the pneumonitis or the liver monitoring was surprising, were there any other things that were additive that you guys weren't expecting? How should we think about some of the safety warnings as you look to combination therapies down the road or maybe moving up to earlier lines of therapy? Thank you. Yeah, Geoff, I'll start there, and Murdo can chime in if he wishes. I think the label quite accurately reflects, of course, the clinical data that we generated to date. Very good tolerability profile in terms of oncology drugs. As I said before, in 30 years of drug development in this field, this is one of the best-behaved molecules we've seen. The monitoring for liver function tests is quite common with small molecules, and this is something that oncologists do, of course, routinely. We don't really think that's going to be an issue at all. The pneumonitis you mentioned, I should point out that there's a background rate of pneumonitis of between 0.5% and 1% in patients with non-small cell lung cancer. Some of the patients with pneumonitis, for example, here also had confounding factors such as immediate pre-treatment with checkpoint inhibitors in at least one or two cases, immediate pre-treatment with radiation therapy to the chest or chest wall, of course, which are well-recognized causes of pneumonitis. As in many of these cases, it's hard to disentangle. We'll have a perfect look at that in the randomized phase III trial of Taxotere versus LUMAKRAS, and I'm quite confident in what the safety profile will look like there. Your next question comes from the line of Yaron Werber with Cowen. Great. Thanks for taking my question. David, for you, if you don't mind, just a couple quick ones. On LUMAKRAS, the LFT rate was low double digits in the label, I think it was around 12%, which is roughly 2x what we saw in the prior data. Maybe just give us a sense what accounts for the difference. For KHK4083, to your point, is the thinking here, I know you were testing two different dosing regimens. The half-life is 29 days. Should we assume this is monthly dosing? Thank you. Thanks, Yaron. The LFT safety information in the label always represents the most up-to-date information that we've got, and again, we think it's a very accurate reflection, and we're very pleased with the overall safety profile. What you're seeing is really the state of the art in the program right now. In terms of the half-life, we're not commenting specifically on dosing right now, but based on the half-life on some of the clinical data, one could envision that reasonably infrequent dosing will be a target here. More on that when the clinical data are presented a little bit later by our investigators. Your next question comes from the line of Ronny Gal with Bernstein. Good morning. Thank you for taking my questions and congratulations on the approval and the deal. Just a quick question for Murdo, i f you can discuss the prevalence pool versus the incidence pool for LUMAKRAS. It seems that there must be a lot of patients out there who are currently diagnosed and could be waiting for this. I had a few beginning to go into the incidence pool. As we think about modeling this, is this a real consideration, or is this something that you don't believe will happen? Yeah, it's a tough question to answer, Ronny, and it's one that we're struggling a little bit with ourselves. The challenge with these advanced second-line non-small cell lung cancer patients is they are very sick, and they're progressing fairly rapidly after they go through front-line therapy with immunotherapy or checkpoint inhibitors. That prevalence pool could be quite constrained by the fact that the mortality is high for these patients in second-line, which is, of course, why there is an urgent need for better options in second-line, like LUMAKRAS. That being said, anecdotally, we hear a lot from oncologists who have patients waiting for the therapy. Over a 12-month period, we are modeling off of the incidence pool rather than the prevalence pool. Your next question comes from the line of Umer Raffat with Evercore ISI. Hi. Thanks so much for taking my questions. I had two today, if I may. One on each, if I may put it that way. On OX40, what were the dose levels in phase II, and can you characterize the safety profile? Because that was a big question heading into that phase II. I ask because there's a lot of fever, chills, and even oral sores observed in phase I at the 10 mg/kg dose, and I'm just trying to understand how competitive that safety profile would be. Clearly, this is probably a diligence issue you guys went through. On KRAS, I guess my main question is there's been a lot of investor questions around the integrity of price point if a 240 dose is approved down the road. Normally this doesn't matter because all dose levels are priced flat, so patients can be on whatever dose and it's the same price. In this case, since 960 is taken as a function of multiple pills of lower strength, I'm just trying to understand how you guys intend to present and price the lower doses such that if there were to be a lower dose approved, the price integrity stays intact. Thank you. Great. Thanks, Umer. I'll take the first question on OX40 on the safety profile and then turn it over to Murdo Gordon for LUMAKRAS pricing. As we mentioned in our opening remarks, we were obviously impressed with the safety profile. As you pointed out, fevers and chills were not uncommon as reported in the phase I study. Typically, as with many antibodies, this tends to be a first dose phenomenon. Our belief is that in looking at the overall adverse event profile, it can be quite competitive. Of course, safety is paramount in this patient population where long-term dosing is required for disease control. We would expect full reporting of the safety data when the investigators present those data a bit later. Murdo Gordon? Yeah. The consideration of the 960mg versus 240 mg study was taken into account when we were planning the launch price of LUMAKRAS. As you rightly point out, there are ways of preserving a price point in the market that we think represents good value for the product. Of course, we're working on different dose presentations that could be available should that comparative dosing study show that you can hold the efficacy as demonstrated at 960 at the lower dose of 240 while improving tolerability. If that scenario occurred, we would have dose presentations ready and available to preserve the value price point that we've already set in the market. The next question comes from the line of Geoffrey Porges with SVB Leerink. Thank you very much for taking the question and congratulations on really significant news. Just with respect to LUMAKRAS, Murdo, could you talk a little bit about your expectations in the market for the proportion of patients that will be second-line and third-line, and then how do you think the duration of treatment is likely to play out in the real world between those two different populations? Thanks. Yeah. Thanks for the question, Geoffrey. We're not commenting on duration of treatment until we see more mature data continue. That's a question I know I'll get a lot, but the best way, unfortunately, to get duration of treatment in the real world is to have 24 months of actual real-world experience, and then you do a look back on it. It's going to be some time before we know what the effective real-world duration of treatment will be. That's the first challenge. As to the mix of 2nd-line versus 3rd-line, the vast majority are going to be 2nd-line patients. Again, to my earlier comment of, unfortunately, the high mortality rate in advanced non-small cell lung cancer patients, there's just a larger pool of 2nd-line versus 3rd-line. I also think with the availability now of LUMAKRAS to target KRAS G12C, some of the persistence with first line therapy might diminish in terms of, you see a little bit of PD-1 recycling between first line and second line. If you're a KRAS G12C patient, that may not be a choice that you want to make. You may work with your oncologist to look at something like LUMAKRAS before you would do that. There's a number of things that happen in the market right now that I think could shift or could change now with the advent and approval of LUMAKRAS. Your next question comes from the line of Salim Syed with Mizuho. Great. Congrats on the approval and the OX40, guys. Just one on LUMAKRAS for me, if I can, just a quick one that follows the pricing question. Peter, when you guys are structuring these clinical collaborations on the combo data, is there anything precluding you guys from partnering with another compound of the same mechanism? For example, like you guys just restructured the Revolution Medicines SHP2 collaboration. You're now taking control of when you're going to release that data, et cetera. I presume you may think there's a problem with the therapeutic index there. I'm curious if there's something there in general that you can speak to that would allow you to partner with other SHP2s outside of RevMed. Just a quick one on the pricing question. Was the mechanism, Murdo, that you guys were speaking to here potentially pulling the 960 mg dose from the market if the 240 mg looked similar? Thank you. Murdo, I might invite you to do a clean sweep on that. I think you might have more information on number one than I will. Well, actually, I think Dave's in the best position on number one. Yeah. Let me tackle that. I'll go with the first one there. Go ahead, Dave. I think as we said before, the collaboration with Revolution Medicines on both sides is non-exclusive. Of course, either party would have the ability to engage in various other partnerships. I think that's as far as we can go right now. As we've mentioned before, we're moving forward with the combination trial with Revolution Medicines' SHP2 inhibitor, and we'll disclose those data once we've got an acceptable body of information. Murdo? Yeah. On the pricing question, we're considering a number of different pricing potential impacts to the product and a number of different clinical trial scenarios on that comparative study. I think it's premature to speculate as to what we would do with specific dose presentations. We obviously have a very strong manufacturing operations team here at Amgen, and they're working on different presentation options and formulation options to give us the flexibility we might need, depending on the outcome of that dose comparative trial. Your next question comes from the line of Mohit Bansal with Citigroup. Great. Thanks for taking my question. Congrats, hope you got to enjoy some part of the long weekend, as you were clearly working through this. Maybe an OX40 question. Literature suggests that OX40 could be implicated with multiple pathways over and above IL-4 and IL-13. It could be TNF, interferon gamma, IgE. It seems like it has the potential for broader activity. Do you anticipate this resulting into a more potent effect? Dave, you mentioned that it could be a patient could cycle through. Do you see this potentially becoming a second-line kind of therapy? Conversely, do you see any impact from the systemic safety point of view, given the broader indication here? Thank you. Sure, Mohit, t hanks for the question. As you indicate, OX40 does occupy a position of centrality in controlling T cell function in a number of these autoimmune disorders. We think that is the reason for the efficacy data that have been generated to date. As I said, we've been reassured by the safety profile that we've seen, which will be presented in full at a later date. Then finally, because of the importance of this pathway, as you indicate, and as I said in my opening remarks, we are working with deCODE in part and bringing all of our immunology experience to bear to inform the development of the molecule, potentially in other indications in autoimmune diseases beyond atopic dermatitis. With our partners, we'll talk about that at the appropriate time when we have a clear pathway. Your next question comes from the line of Dane Leone with Raymond James. Hi, thank you for taking the questions, and congratulations on the approval of LUMAKRAS and also the Karuna deal. I'll keep it brief, getting late in the call. Just firstly, in terms of LUMAKRAS, could you just update us in terms of how you're thinking about potentially expanding the market beyond the second line now, and more specifically, from a commercial standpoint, the status of getting approval outside of the U.S. and Europe and then in APAC? Secondly, on OX40, could you just give us a quick view of when that data might be presented? Thank you. Yeah. I'll start with the first part of that, then ask Murdo to comment as well. We're filed in eight or nine jurisdictions around the world. U.S., Europe, Australia, Canada, Japan. Regulatory reviews are ongoing in these areas. In general, the conversations are quite positive. I think regulators recognize the real unmet medical need here. We'll provide updated guidance as we can look at potential timings of approvals outside the U.S. Of course, in terms of earlier lines of therapy, the combination therapy program continues to move forward with over 10 combinations in the clinic now. We'll start sharing data from some of those combinations in the second half of this year, which is almost upon us. Of course, at this point, we're really going to be guided by the clinical data in terms of which combinations to really advance. In terms of OX40, we anticipate that the data from the phase II trial will be presented later in this year, in the second half, at this year's annual European Academy of Dermatology and Venereology meeting. That congress is one of the sort of premier dermatology congresses, typically held late September or early October. That's where we anticipate data presentation. Murdo, I don't know if you want to add anything. I would just mention that we've also opened up a number of early access programs in a number of countries, particularly in places where they help bridge to fully reimbursed patients. Given the speed at which Dave's team's been able to file this product in a number of different markets, my team's tracking very closely to be able to submit to reimbursement authorities upon approval. Sometimes it helps when you have data being gathered in early access programs that you have rolling in countries, and I think that we've done that very well to date. Your next question comes from the line of Cory Kasimov with JP Morgan. Hey, good morning, guys, t hank you for taking my question. I have a follow-up on the pricing of LUMAKRAS from a different angle. The combination opportunities have obviously been a big focus as we await initial data on that front. I'm wondering how we should think about pricing or if pricing in the future could be impacted down the road should those combos move forward into the marketplace and/or LUMAKRAS potentially moves up in lines of therapy. How static is the price point from your point of view, or might this be dynamic as you materially expand the market down the road? Thank you. Yeah, it's a difficult question because it involves some hypotheticals on what the optimal dose will be in some of those combinations. For the most part, we think we've got the bookend of scenarios covered, Cory, and I think we're able to preserve price over time with different presentation launches that we'd be able to put into the market, allowing for combination use as well as a potential change in the monotherapy use, pending the outcome of the dose comparative trial. Your next question comes from the line of Michael Schmidt with Guggenheim. Hey, guys. Good morning. Congrats on the LUMAKRAS approval as well from me. Another one for David. When we think about potential future label expansion opportunities, particularly in first-line non-small cell lung cancer, how should we think about the efficacy benchmarks here when we think about a potential accelerated approval strategy, perhaps specifically in the STK11 patient population? What is a good historic benchmark for response rate in those patients, David? Thanks, Mike. I think that's a hard question to answer. I think we're still defining precisely what the natural history is for those patients. I think it's also, none of these markers are absolutes. What's implied in your question, for example, is less of a response to checkpoint inhibitors, but that's not absolute. It's our general supposition that it's likely that the FDA will require some sort of randomized trial ultimately, in the first line. In the interim, clearly, we want to generate data in these different subsets of patients. As I noted, we'll have updated biomarker data here in a few days at ASCO. As we pointed out in the past, I think this is also not a one-gene story here, and so simply looking at a single mutation may not be an adequate guide to understanding the relative likelihood of response or resistance. I think it's going to be a complex story, perhaps ultimately requiring randomized trials in early lines of therapy. Your next question comes from the line of Alethia Young with Cantor Fitzgerald. Hi. Thanks for taking the question. This is Nina on for Alethia Young. Congratulations on the approval and collaboration. Very exciting. We had a question on the OX40 asset. How do you think about positioning of this asset versus other plays in the AD space like DUPIXENT and some of the other orals in clinical development? Thanks. Sure. I'll start there and ask Murdo to comment if he wishes. As I noted, it's got a unique mechanism of action. Not all of these patients have their disease that is controlled with existing therapies. Patients tend to cycle on therapies. Given the widespread prevalence of the disorder, we think there's still very large, significant residual unmet medical need. That, we think is where KHK4083 will play an important role, we hope. Murdo? Murdo, I think you're on mute. Yeah, you're muted, Murdo. Okay. Can you hear me now? Thank you. As Dave mentioned, what we've got is an opportunity to serve a lot of patients who may be refractory or suboptimally treated with currently available agents. Expanding from there, I also think just with the portfolio of products that we have in inflammation and our strength in dermatology in particular, it really affords us an opportunity to position this product favorably against competition in the market, but also helps us position it well within our own portfolio. We have a very strong global footprint in dermatology and in inflammation, and we also enjoy having multiple biosimilars in inflammation in our portfolio. That positions us well to be a good commercial partner, in fact, maybe the ideal commercial partner to commercialize the OX40 asset. Your next question comes from the line of Kennen MacKay with RBC Capital Markets. Hey, thanks for squeezing me in, and let me offer my congratulations as well. I just want to go back to one of the comments around comparing the potential launch here for LUMAKRAS in KRAS G12C versus some of the prior agents in this space, specifically the ALKs. I also wanted to get a perspective on sort of EGFR and the maybe second generation, next generation EGFR inhibitors. I just want to understand, again, the dynamics behind why this launch should look quite a bit better maybe than some of those agents and, if I may, just also how pricing of this agent, I think you mentioned $17.9K per month could influence that as well. It does seem like it's a price for a very broad market there. Yeah. Let's start with the price. We did obviously look at the significant improvement that we've made on 2nd-line treatment options in non-small cell lung cancer. As a monotherapy treatment there, we think that this is priced very well compared to other targeted medicines available in the market for other driver mutations. I'm just characterizing the launch broadly. Look, it's really hard to tell because of the variability of our reach to customers right now to use analogs from pre-COVID times. I think it's an unknown variable in the launch. We think that we've got all the right channels open to all of our customers. We think patient movement, in the U.S. at least, is returning to close to pre-COVID levels, although we're still, on a cumulative basis, down between 5% and 10% of patient diagnoses in oncology. With improved vaccinations and improved patient movement, we hope to have a very strong launch. Your next question comes from the line of Chris Raymond with Piper Sandler. Oh, hey, thanks for squeezing me in as well. Maybe just a pricing strategy question, I guess, for Murdo, to the extent you can answer it. We've been hearing from an increasing number of companies that there's a sort of an effort, I guess, with newer therapies to affect more of a narrow international pricing band as you launch. I know you don't want to give up too much on your ex-US pricing strategy, is that sort of the way Amgen is thinking about new therapies going forward, is trying to affect a more narrow band as you launch internationally? I think we're always managing an international price corridor to as narrow a variable as you can. I think in this case, the challenge we have is our comparator in the second line non-small cell lung cancer setting is, of course, generically available chemotherapy. We're hopeful that we can convince reimbursement authorities that this targeted medicine offers significant value because you're focused on 13% of patients from a budget impact perspective for single-payer systems outside the U.S. That's attractive. We'll also hope to show them that from a value perspective, given the profile of this product, the response rates, the tolerability, the convenience of a once-a-day oral therapy, and its comparative price versus other targeted medicines that are used in non-small cell lung cancer, that we can keep as narrow a price band as possible. It's easier said than done. Okay, Crystal, as we are at the top of the hour, why don't we take one last question, please? Your next question comes from the line of Matt Phipps with William Blair. Thanks for squeezing me in. Congrats. Just a quick one on the OX40 asset. Wondering if you have any comments on that phase II ulcerative colitis trial that didn't seem to show any efficacy benefit, and if we should really be thinking about autoimmune disease where there's a clear T-cell mediated impact? Yeah, no, it's a good question. It's something we're taking a look at. As I said, we're digging in, of course, further to the science here with our immunology group and our partners. We are leveraging insights from deCODE genetics. We'll have a little more to say about indications beyond atopic dermatitis that we think fit the biologic and clinical hypothesis here as we go forward. The ulcerative colitis data will be presented also in due course. Again, very enthusiastic about this asset, differentiated mechanism of action, very plausible science and genetics. A great partner. We're really looking forward to helping them take KHK4083 forward. Arvind? Okay. Thanks, Dav e. With that, let me thank everybody for your participation this morning, at this early hour this morning. If you have any follow-on questions, topics you would like to discuss, of course, feel free to reach out to me and the balance of my team. Thanks again, and hope you have a good day. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.