Amgen Inc. (AMGN) Earnings Call Transcript & Summary

Hello. Good afternoon. My name is Geoff Meacham. I'm the senior biopharma analyst here at Citi. I'm also the global health care lead. Welcome to today's 2025 Virtual Oncology Summit. We've had a lot of great discussions today with companies in the U.S. and Europe, obviously, focused on oncology, and we're thrilled today to have Amgen. And speaking on behalf of Amgen, we have Jean-Charles Soria. Jean-Charles, good to see you. Welcome.

Thank you so much.

We also have Justin and Casey from the IR team. So thanks, guys. Those would be for the questions that I'm probably shouldn't be asking, but the commercial ones. You guys will chime in as appropriate.

We're ready, Geoff. Thank you.

So I guess, Jean-Charles, just to start it off, give us the high-level view of Amgen oncology, what we could expect for this year, the pipeline? What are you most excited about kind of thing? And then we'll get into some of the assets, both portfolio and pipeline.

Well, thank you very much for the invitation and the opportunity to share a little bit about what we are doing in oncology. Amgen has a very long track record of developing first-class molecules that are really meaningful. And it started through a supportive care angle, but it transformed over the last decade on a significant effort in oncology therapeutics. And a lot of people do not fully appreciate how broad the oncology pipeline is. So just to give you an idea and set the scene, we have 9 ongoing Phase III trials in oncology. And I am sure most people would not have picked that number that -- that, by the way, stands across 5 different assets. So it's a significant reality. Our strategy in oncology is mostly focused on 2 angles. The first one is leveraging the immune system. And we do so by the use of T-cell engagers. So T-cell engagers are a modality by which you create an artificial synapse where you bring a T-cell in proximity to a tumor cell by a bispecific antibody and create this artificial synapse that allows the kill of tumor cells. That's very unique. And the other angle by which we develop our assets in oncology is the precision oncology, where we either target specific antigens for signal transduction modulation or specific mutations. So we have a meaningful presence now in oncology, and I'm very excited to be able to share with you some of the content today.

Great. Well, let's talk about what we can talk through some of the -- there's a lot of assets to go through. So let's start, I guess, with one of the assets that's growing pretty nicely, BLINCYTO. So talk a little bit about kind of the commercial success there, the physician feedback and maybe help describe some of the recent data, adult and pediatric that you guys have presented or talked about.

Sure. And thank you for this opportunity. So BLINCYTO maybe is our historical and most well-established T-cell engager from our BiTE platform. So -- we are in the business of developing T-cell engagers since our acquisition of Micromet in 2012. So a very long time. And we -- for the record, it is very important to realize, we are the only company with 2 approved T-cell engagers, one in hematology, BLINCYTO, which I'm going to give you more details and one recently approved for solid tumors, which is our IMDELLTRA for small cell lung cancer. And that's a journey that took us the capability to develop them in both the malignancies. Our excitement around BLINCYTO and the robust growth trajectory you mentioned just comes from the recent expansion of the BLINCYTO label that was approved by the FDA in the middle of last year, in the consolidation phase for patients with B-ALL. And that was based on a trial, the ECOG-ACRIN trial E1910. And those results have been shared very actively by our commercial teams, by our medical affair teams, engaging key academic regional, but also community-based customers. And that momentum is now picking up also in the European markets with the approval of this therapy also by the European Medical Agency recently in January of this year. So we see certainly an attractive and long-term BLINCYTO growth potential that will be sustained by the capacity of bringing BLINCYTO to earlier lines, but also the fact that we are developing now on top of the continuous IV BLINCYTO, a subcutaneous formulation for this asset.

And Jean-Charles, if I could just add a point that I thought was really worth noting, which is in the early days of BLINCYTO, there was some question around the approach in the platform. I think there was some view that perhaps it would be limited only to very late-stage patients, and there might be some side effect issues that would need to be managed that would limit the usefulness of the drug beyond that. Obviously, time has played out favorably, very favorably. Last year, we did over $1.2 billion with BLINCYTO, 41% year-over-year growth. And I think the key learning was that if you treat earlier lines of -- earlier lines of therapy, the patients actually do better, both from a safety and efficacy point of view. So again, it wasn't obvious years ago that, that was how it would play out, but we're obviously happy to see the momentum there.

Yes. And just to -- to react on that, Justin, if you allow me.

Please.

The BLINCYTO learnings over almost 15 years have become the blueprint by which we develop our T-cell engagers in solid tumors and allow the approval of IMDELLTRA for small cell lung cancer. So we have figured out that these T-cell engagers will have a better therapeutic index as you bring them earlier in the lines of therapy rather than just focusing on the late patients with highly burden -- tumor burden and multiple lines of refractory disease, the earlier you bring them, the better the therapeutic index, less toxicity, more efficacy. And that has been demonstrated for BLINCYTO now with E1910, but also recently with another pediatric collaborative trial that was presented at ASH as a plenary and had a New England Journal presentation. But that asset was being developed by this collaborative group. The -- on the basis of a very, very large trial, recruiting hundreds of patients across the world and -- by the Children Oncology Group. And they did an interim analysis. And the results were so spectacular that the trial was stopped and we have an improvement in a disease where you already have great results. And we got the 3-year disease-free survival to 96% when the standard with chemo was 88%. So few people will dare compete with an 88% disease-free survival. We did so because we -- and the Children Oncology Group obviously choose to use our assets because of the transformative nature of its mechanism of action. So that is another important one.

And then let me ask you in the -- as you moved up the treatment paradigm to earlier lines of therapy. Can you speak to broadly the duration of therapy that you're seeing kind of in the real world? And what do the data suggest that could ultimately be?

Well, for BLINCYTO, I would say we do not have yet as much data points as we had for the previous use in highly resistant chemotherapy ALL. But what we are seeing is sustained use. We are seeing, I would say, better tolerability. And that's exactly the reason why we are also developing the subcutaneous formulation, of which I will be happy to talk if you agree now. So we developed subcutaneous formulation for 3 main reasons. The number one is to improve the tolerability. The second one, to increase the efficacy. And the third one, to improve the patient experience. And in the subcutaneous BLINCYTO use, we already shared at an ASH meeting in 2022 that we were seeing complete responses in 67% of -- a limited number of 21 patients versus our historical CIV administration of 42% and this is why we are now embarking on a potentially registration-enabling study of subcutaneous BLINCYTO in adults and adolescents that have relapsed/refractory B-ALL that we expect to begin in the second half of this year.

And was the subcutaneous -- was the formulation and was that all developed in-house at Amgen? [indiscernible].

Yes. This was completely developed in-house. And it might seem simple. It might seem like a basic idea. It's a real tour de force because there are viscosity components, concentration component. So never underestimate how much effort is behind a pill or behind a vial.

Yes. No, I'm with you. And then last question, I guess, on BLINCYTO on subcutaneous. So the Phase II is a registration sort of Phase II? Is it -- do you have to follow patients up as long as you did in the pivotal? I mean, I wasn't sure what the regulatory requirements are for it.

So we haven't yet fully shared what is going to be our registrational study since we are in active discussions with regulatory agencies, but we will provide more details in the upcoming months.

Okay. That makes sense. Let's switch gears to IMDELLTRA, which you mentioned. So I guess, same question, give us a bit of a background to this. Early in the launch, much earlier, but talk a little bit about the adoption, the commercial experience relative to what you saw in Phase II and Phase III.

Thank you. So maybe to set the scene. Small cell lung cancer is the disease where IMDELLTRA is approved, correct? Small cell lung cancer is like 15% of lung cancers in the U.S., but it's really the form of lung cancer you don't want to have because it's very aggressive and has had very limited changes and improvements in survival. The setting in which we got an approval are patients who are chemorefractory and progressed on PD-1s. In that setting, the median survival is around 5 months. Our data that led to an accelerated approval showed a median overall survival of now 15 months, which is very transformative and an objective response rate that is unprecedented in that setting of 40% with 30% of the patients being stable. So it is deeply transformative, and we hope we're going to see that in terms of survival events. The majority of small cell lung cancer patients in the U.S. are treated in community-based hospitals. And that's where we're putting the effort to get them used to the mechanism of action of a T-cell engager to have the environment to monitor those patients because you have some of the side effects that they need to get used like some fever, some chills, but we are very, very confident on -- that we have a strong engagement. And at the end, whenever physicians start using IMDELLTRA, they feel much more confident and they see compared to the standard of care, how much better this is. So that's -- I share the beginning of the journey with this asset for which I have much more to tell you since we have so many studies [indiscernible].

Yes. Well, one of the studies DeLLphi-304, so first half of this year. Talk a little bit about that, I guess, a new data set, but obviously, we know the risk-benefit from prior studies, but how does 304 sort of inform your long-term view of the product?

Absolutely. So the Phase I -- Phase II data set I was referring to previously is the one who got us the accelerated approval by the FDA. DeLLphi-304, which is a randomized Phase III trial in the second line setting with the primary endpoint of OS is the one that will get us full approval. And it's the one who's going to unlock access to many other regions of the world. Remember, if you take European market, they don't have access to IMDELLTRA right now under an approval. So it's a very significant trial. The other element that is to me essential is that we believe because of the Phase I results and that 15-month OS in a setting where usually you get 5 months that the biggest benefit of our T-cell engagers is going to be seen not in the response rate, but mostly in the overall survival. A little -- remember, this is enhancing the immune system. This is a mechanism where we saw for other immune check blockers. This is not an immune check blocker, it creates an artificial synapse, but it enhances the same T-cells. We hope to see that same cell survival event and that's going to be very defining for the field and very important in how the field, the physicians are going to see the value of these assets. So we are very, very eager and happy to have that readout in the first half of this year.

And from a sort of line extension perspective, so first, it's logical that if you show that difference in treatment effect from 15 versus 5 and second line plus, what are the first-line newly diagnosed plans? And maybe walk us through that end of the market?

Yes. Thank you for that question. As I was saying, we are developing these T-cell engagers not in a vacuum but in a long decade history of drug development and development plans. And once we saw the Phase I/II data of IMDELLTRA, and I have clear line that this was likely to become an accelerated approval, we decided as a company to go broad and bold and started 3 Phase III trials. That's pretty significant. And the philosophy was, let's bring to earlier lines. So we went from the third line to the second line in DeLLphi-304, but then we also develop a protocol that is using IMDELLTRA and durvalumab in the first-line setting in small cell lung cancer, which is DeLLphi-305 and that's a maintenance trial. But we were also bold enough to go to even earlier settings, which is patients who have localized small cell lung cancer who have been treated by chemo and radiotherapy and in which we are exploring the contribution of IMDELLTRA, that's DeLLphi-306. So a lot of confidence on what this could bring to the patients [Technical Difficulty]. Let's go to earlier lines. Let's seek to have a more disproportionate positive impact by decreasing toxicity and increasing activity.

And from a combination, as you do that, you mentioned PD-1 combination. So talk a little bit about what synergies you could see from that from a mechanism standpoint? And would that obviously make you pretty well-established standard of care in adjuvant or first line, if that's successful.

Yes. Thank you. We -- we need to operate and develop IMDELLTRA in the context of what is the standard of care in the first-line setting. And in that first-line setting, the standard of care is chemotherapy plus a PD-L1, whether it is atezolizumab or durvalumab. We have shared data at the World Lung Cancer where we demonstrate that, that combination is absolutely feasible. And therefore, we are encouraged, and that's why we went on that frontline setting with the combination in the maintenance setting. So that's helpful. We are exploring many, many other combinations of promising small cell lung cancer assets with IMDELLTRA in Phase I setting, but it's too early to discuss them, but there are many ADCs and other molecules that are being developed in that setting.

Is there a potential -- I know small cell is, as you mentioned upfront, it's a particularly brutal and fast developing cancer, but is there an opportunity to go chemo-free within IMDELLTRA minus chemo, but with the PD-1, is that down the road a priority?

It's a great question. And it's something for which we do not have yet a registrational trial. But as I was saying, we are testing chemo-free combination in Phase Ib trials with, for instance, IMDELLTRA and certain ADCs or IMDELLTRA and other IO modulators because we would like a world where we do not need chemotherapy to treat those patients. But give us a little more time, and we will keep you posted of the results.

Yes. Makes sense. And I guess last question from a mechanism standpoint, what do you know about other solid tumors? Is there opportunities outside of the small cell potentially?

With IMDELLTRA specifically?

Yes.

Yes. Absolutely. So IMDELLTRA, is targeting an antigen called DLL3, delta ligand 3, and that is expressed in neuroendocrine tumors. And neuroendocrine tumors have the most aggressive form in the lung as a small cell lung cancer, but you have other types of neuroendocrine tumors. We have shared data publicly about the use of IMDELLTRA in neuroendocrine prostate cancer, but that neuroendocrine world also encompasses digestive neuroendocrine with pancreatic, gastric, intestinal and other tumor types. So as we advance, there is hope that this asset might play roles beyond small cell lung cancer.

Makes sense. Okay. That's helpful. Well, those are 2 exciting assets. Let's turn to xaluritamig, which is in prostate. And there's a lot of excitement for this from just given the really robust early to mid-stage data. Talk a little bit about the Phase III that you guys have just initiated and maybe the -- how -- what's the level of enthusiasm and walk us through kind of your high-level view of the Phase II prior data.

Yes. Thank you for this opportunity. So xaluritamig is a T-cell engager that this time is targeting a different antigen called STEAP1 is highly expressed in prostate cancer. And the reason and the basis of us launching a Phase III trial in the setting of patients with hormone or castration-resistant prostate cancer that were already exposed to taxanes was Phase I trial, where we presented in September 2024, a clear monotherapy activity that I'm not going to detail, we had objective response rates. We had the PSA, which is the biomarker of tumor expression of that disease, 90 and 50 drops. But our median OS on that Phase I trial in a heavily pretreated population of prostate cancer patients including patients with visceral metastases and liver metastases, which is very aggressive, was 17.7 months. And that is much better than the historical median survivals that are in the range of 12 to 15 months at best. So that's where we are engaging this. And the prostate cancer environment has heavily focused its development around androgen receptor modulation or PSMA targeting. STEAP1 is a completely new antigen. We are the most advanced STEAP1 clinical asset and therefore, very excited by the promise that this can bring for prostate cancer patients.

Let me ask you just on the mechanism. Talk a little bit about the history of the development here from a mechanism. And I agree with you, I hear that a lot from physicians, oncologists that there are so many PSMA assets that is sort of -- it's sort of old, right? But this is a brand new, I mean, first in many, many years, mechanism in prostate.

Yes. Well, STEAP1 has been a target that was known and it was -- it gave [ hopes ] to a lot of people to go after STEAP1 because opposite to DLL3 that is exclusively present in the surface of cancer cells and never present in normal tissue, STEAP1 has high expression in prostate cancer cells, but has a little bit of expression in normal healthy tissue. So the beauty here has been to engineer a T-cell engager that grabs STEAP1 with 2 arms and not just 1 arm. So it will only grab STEAP1 present in high density and not STEAP1 lousily present. So imagine a monkey that needs to grab 2 branches. Those are the 2 branches of STEAP1. You have only one, the monkey is not going to grab and stay here. So that was, I would say, the research beauty allowing us to unlock this target with the T-cell engager.

Perfect. Yes. And from a commercial perspective in prostate, there's been a lot in development in the upfront kind of hormone insensitive angle. So the XTANDI and ZYTIGA of the world and now you have next-gen versions of those. So talk a little bit about differentiation beyond the mechanism. How do you think you could differentiate from a safety, tolerability, but also efficacy as you move upstream?

So we intend, obviously, to use the same strategy of the blueprint of BLINCYTO that we used for IMDELLTRA [indiscernible] xaluritamig, which is -- let's not only focus on the most advanced patients, those who failed the standard of care who became hormone-resistant and who then became resistant to taxanes, let's try to bring this to earlier lines. And to do so, we have started some trials, Phase I trials in 2 specific and unique settings, which are neoadjuvant. This is before surgery, correct? And as a man, if you tell me there is a way to keep the prostate, if you have prostate cancer, I'm very interested, correct? That is a significant unmet need. There is no standard neoadjuvant therapy for prostate. Many, many drugs, and many, many molecules have been tested, but it's not approved. We're going to test, and we are testing that in a Phase I trial of xaluritamig and we hope to be able to show a signal that might give us a very different angle of development. The other one is, we are testing xaluritamig in patients with biochemical recurrence. So these are patients who were treated for the prostate cancer and then they just have a PSA who comes back without radiological evidence of disease. That's a very difficult situation for patients, correct? Because they say, my PSA is up, and you see nothing on the scans. We believe in that setting, low tumor burden, there might be a place for xaluritamig, and we are currently testing it also in that Phase I trial. So those are, I would say, innovative, creative, crafty ways of trying to bring this molecule to patients who need it.

For sure. Yes. And I guess for the neoadjuvant study, what sort of the next step after that? I mean, is there still a hurdle to show PFS or OS, which can be a very long interval, the way upstream in the treatment paradigm.

Well, the neoadjuvant world is one that is unfolding and has been changing, correct? And we have seen the breast cancer field showing us where to go. And then the lung cancer field is showing us how to go. In prostate, that discussion has never happened with the FDA or any regulatory agency. So I think here, we are very humble. We're going to see what are the results of the patients when they are treated with this asset. Once we do the surgery, we're going to evaluate what's the level of efficacy and engage with the regulatory authorities to see this is what we are seeing. What do you think is the best trial? What's the compromise because you are right. If you need to go for OS, it's going to take way too long time. Other endpoints that a regulatory agency might take, we're hopeful that if we see meaningful results, they might be creative and open to that dialogue.

Yes. And just on that note, I mean, I think PSA velocity has been mentioned as maybe a higher endpoint. Are there any other biomarkers that you could look at that could correlate, right, to a progression?

In more advanced setting, certainly, we have reported at ESMO last year, CTC conversion. So patients who have in a blood test, in a liquid biopsy presence of circulating tumor cells at high levels that have shown a conversion, like the CTC test goes to 0 under xaluritamig therapy. That's an alternative to PSA, correct? Like you are measuring a biomarker that is produced by the prostate, you can also measure the presence of circulating tumor cells in the blood and demonstrate that they are disappearing.

Unlike with BLINCYTO and IMDELLTRA were combinations, standards of care could work. I guess there is fewer options and IO isn't as prevalent, right, as in an indication like prostate. So talk a little bit about maybe the -- how you could navigate standards of care as you move upstream of the paradigm.

So it's very relevant that you point out that the classical immune check blocker, PD-1, CTLA-4s have not scored in prostate cancer, and it's a big disappointment. We are the most active immune enhancing therapy in prostate cancer. We reported response rates and PSA50, 90 drops in a very meaningful percentage of ESMO 2 years ago in an oral presentation. And we are obviously combining ourselves to modern oral ARDTs, enzalutamide and abiraterone, and that's being tested currently, and we will keep you posted with those results. But that Phase Ib is ongoing.

Okay. All right. So let's keep going. Fortunately, Jean-Charles, there's a lot -- there's a lot to cover. You guys have a pretty deep pipeline. So let's talk about gastric. So bemarituzumab Phase III. So maybe, again, talk a little bit about kind of the prior data as we look to the Phase III first-line data this year. Give us maybe a reminder of how we got here.

Absolutely. And then thank you, by the way, for the opportunity to just [indiscernible] how much activity and how rich the pipeline is in oncology at Amgen. A lot of people are focusing in other areas. But for us, it's great to be able to...

Yes. I told Justin, I wouldn't ask any merit type question. So.

And I do thank you for that, although it's, we believe, a fantastic drug. Bemarituzumab is a monoclonal antibody that specifically targets fibroblastic growth factor receptor 2b, okay? And fibroblastic growth factor receptor as the name stands is implicating in the growth of cancer cells, especially gastric cancer cells. So it's moderating the signal transduction. We acquired bemarituzumab via the Five Prime acquisition. They have Phase II data called the FIGHT study, where they demonstrated that a combination of bema with chemo was superior to bema, but in a Phase II trial, correct? And this was both for PFS and OS. So we now are going to be revealing in the first half of this year one of the 2 Phase II trials of bemarituzumab, which is FORTITUDE-101. This is a Phase III trial that combine bema plus chemo, modify FOLFOX6 to chemotherapy in the first-line setting of gastric cancer. But importantly enough, in the second half of 2025, we will also be able to hopefully see the data of an already fully enrolled second Phase III trial called FORTITUDE-102, which is the combination of bemarituzumab with chemo and nivolumab versus chemo/nivo because the world has changed since the acquisition of Five Prime and PD-1s are -- have become a standard of care in the front-line setting of gastric. So we have [indiscernible]. We are very excited that gastric cancer is important, up to 1 million person in the world and 25,000 people in the U.S. So more innovation is needed in that setting.

Yes, for sure. And I know the chemo combinations are interesting and you sort of implement into sort of the older standard of care. Is there a mechanistic basis for synergy with PD-1? Have you seen in Phase I or in animal models a lot of immune engagement, if you -- when you add the 2?

So we do not have a Phase II trial like FIGHT, but all our preclinical more pinpoints to the probability of this being a good combination, and this is why we embarked in that trial. And investigators with their feet they recruited quickly in both of our trials, and that's a very good sign. Because when people want to put patients in your Phase III trials, it means there is excitement, they have seen with their eyes, they talk among them, they have seen responses. So we hope to see the final data unveil.

Got you. And is there -- I haven't heard much on the gastric side about pre-metastatic adjuvant, neoadjuvant kind of -- I mean, is that even -- is that a segmentation here of the market?

Absolutely, there are collaborative groups that are exploring neoadjuvant settings. This is an area where we intend to work with either a collaborative group or an association to see what's the value of our asset and generate a signal before we embark in a Phase II trial.

Yes. In the mechanism, so when you look at FGF broadly, is there -- I know you guys are doing a basket study. There have been -- I think J&J and others have looked at this mechanism and a broad -- and I don't know if data are really mature yet. Is there something that kind of jumps out at you in terms of opportunities outside of gastric?

Yes. Thank you for the question, Geoff. So I think in the FGFR world, there are really 2 different beasts. There are the FGFR2 and FGFR3 mutations, which are targeted by oral kinase -- the oral inhibitors that you referred to, the J&J and others in development. But our MOA, our mechanism of action is very different. It's not targeting that mutation and the signal, is targeting the receptor. And therefore, we are exploring that in that basket trial, but with the humility of knowing that the real data we had was in gastric. And remember, if you look at KRAS, the activity you have in lung was not the same as we had in colorectal, we have to combine with our own anti-EGFR. So it's not just because the target is expressed in a tissue and then expressed in a different organ that is going to have the same level of efficacy. That's why we're doing the basket. We need a little bit more time before we are able to share what signals we are generating there.

Okay. That makes sense. I guess broader question, just given this was an asset that you guys brought in via acquisition. When you think about the Micromet and the BiTE platform, and all the bispecifics and T-cell engagers you guys have developed in-house on the back of that, how do you think about oncology BD going forward? Is it mostly technology specific? Is it sort of tumor type, whether liquid or solid tumor specific? And do you look for unmet needs or ways that you can leverage in-house? Like I wasn't sure if the thought process has evolved towards oncology or hem/onc BD.

Thank you for the question. As I was telling in the introduction, we have 2 pillars in our vision. One is enhancing the immune system. The other one is precision oncology, correct? So things that will fit these 2 concepts are very much on target. We also are very logical about our strongholds, commercial strongholds, where we already have assets in oncology and where we want to create synergy. And so we will follow that matrix correct on that. But the bottom line to your question is we follow the data and the science. If the data and the science are compelling, we will make a potential BD play. You are very well aware of the number of billions of dollars we spent recently acquiring Horizon Therapeutics, a great acquisition, but a company like ours, hopefully is going to stay active in BDs including in oncology. And we are scanning the world because we recognize that the best science is not just in Amgen, it exists outside of Amgen. So we are very, very active in that regard.

Well, the 2 technology verticals that you mentioned, Jean-Charles, where they cover the majority of things in development, and obviously, small molecules are pretty standard, but other technologies, say, cell therapies, is there a higher hurdle to add a new tech platform to Amgen in your same markets like in oncology or hematology?

Well, cell therapy has complexities that T-cell engagers don't have. T-cell engagers are vials with the therapy ready to go. Cell therapy, you need to harvest the cells, you need to pretreat the patient, you have a risk of not having the product at the end. So we are watching that, but it's true. We have not made -- invested in that area for that reason. But we remain driven at the data. We're looking at how things are going to unfold. Right now, the data shows there are limitations, we don't have with our own T-cell engagers, so that's where we're putting our assets. On the precision oncology, it can -- we are completely open to monoclonal antibodies to small molecules, to antibody drug conjugates. That's also precision oncology. So keep tuned, and we're going to hopefully show you that we are actively looking.

And maybe one -- maybe one adjacent comment to that. I'm sure you're aware, Geoff, that we're also setting BLINCYTO in autoimmune disease. And it just, I think, emphasizes Jean-Charles' point, that having it as a kind of off-the-shelf T-cell engager that makes it, I think, is helpful as we look at it in even different settings.

Is there a process either Jean-Charles or Justin, where you can -- you have an initial data set for a T-cell engager like BLINCYTO and somebody outside of the hem/onc, kind of, R&D team says, "Hey, look, this may be effective." I wasn't sure like the level of cross-pollination that you may get with the immunology or inflammation team, right? Because you're right, a lot of these assets, not just BLINCYTO may work in a lot of immunology diseases for sure.

Yes. Well, my boss, Jay Bradner, our EVP of R&D, is very focused on making sure we unlock the full potential of any asset, no matter what swimming lane it is, no matter which TA it stands and bring it to where it needs to be in the other TAs if the science justifies it. So yes, we have dedicated efforts, very structured efforts. And when need be, the appropriate project management, scientific brainstorming to see whether some assets should just belong to this TA should go to I&I. It is clear, as you stated, that oncology and inflammation are looking at very common targets, but it's the yin and the yang. In oncology, where we try to activate the immune system. In inflammation, we try to damper it, but it's the same targets, just different angle. So -- but the same will be true for rare diseases. We are looking at, is this asset makes sense in a rare disease setting versus another TA setting. So that's a very clear and important focus because the patients are the ones we serve, and we want to make sure we serve as many patients as possible, whether it is oncology or immune disease like IBD and others.

I got you. I know your answer is going to be the science is what drives it. But to what degree does the commercial team kind of chime in to say, here's an unmet need in oncology or hematology or you're studying this, but the MAX opportunity, the TAM is more modest, like I wasn't sure if Murdo and Jay, any sort of interact to the point where it can drive some oncology/hematology development decisions.

Well, I can tell you they interact very much, and it does -- I also interact with my counterpart, Senior Vice President of Commercial, because we owe it to the patients, correct. And we don't have the monopoly of intelligence or [indiscernible], our commercial colleagues have great ideas. So yes, we have continuously that discussion, sometimes divergent opinions, but many, many times, we create a shared reality and a better understanding, and they can highlight very good opportunity. So I reassure you this -- the biggest challenge in pharma is the continuing between research, development and commercial, correct, RDC. Well, we put a very intense effort to make sure that continuum is hyperconnected at the top of the house at the SVP and VP level because you need to have that clarity of thinking. If I develop something that commercial considers it cannot bring to the patient, I'm not doing my duty, correct? The bottom line is this to be developed. So we have a healthy dialogue, and I think it enriches our way of thinking.

That's fantastic. Yes, that's some good background. Well, let's keep going on the pipeline. So AMG 193, non-small cell for MTAP patients. So talk a little bit about, again, the background here, the development and the opportunity before we get into kind of Phase III.

Yes. Thank you. This is a precision oncology asset. It's the first in class small molecule methylthioadenosine MTA-cooperative protein arginine methyltransferase 5 inhibitor. So it's a PRMT5 inhibitor. For those who I lost during my lengthy sentence. It inhibits PRMT5, but it will inhibit PRMT5 in a very well-defined genetic setting where you have high NPA and when do you have high NPA is when you have certain deletions like MTAP deletion, correct? So that...

So this is a matrix. Is it fair to say that extracellular matrix type of...

No, it is intracellular, but the beauty is that PRMT5 is expressed in cancer cells and normal cells. And that's why the first generation PRMT5 inhibitors did not went through the whole journey, and we're stopping Phase I because there was activity, but there was toxicity, notably hematological toxicity. The beauty here is that we have developed -- well, you could call conditional PRMT5 inhibitor, it only really inhibits PRMT5 when you have high MTA, which happens only in cancer cells who are MTAP deleted. It's almost a little bit like the synthetic lethality idea that you use for PARP inhibitors and being BRCA. And here, it's a little different. It's a genetic event called MTAP that makes this work with the PRMT5 inhibitor.

Got you. Okay.

So that asset in-house grown. We have an ongoing Phase Ib study, I mean and some other protocols. As you highlighted, we've recently initiated the Phase II study of AMG 193 in non-small cell lung cancer patients with MTAP-null status, and this study will help address the regulatory requirement of those optimization. But I want to highlight that AMG 193 is still being explored in a broad Phase I, Phase Ib trial with different patients having MTAP-null solid tumors and it's also been explored in combination with standard of care in what we call master protocol of MTAP-null thoracic malignancies and also an MTAP-null gastrointestinal tumors and notably pancreatic cancer. So we are exploring that range of tumor types, and we are exploring both the monotherapy and the combination with standard of care, whether it is chemo or IO and don't ask me which one is winning, we need a little more time to tell you which one is going to be the one that we're [indiscernible].

But non-small cell lung is the initial kind of development indication?

Non-small cell lung cancer is where we took the Phase II trial to do what is called a randomized dose optimization, which is request by Optimus and why we went there is because that's where MTAP-null is the most prevalent, but that doesn't mean that we are not seeing, and we presented this as an oral ESMO presidential symposium. We saw activity in pancreatic cancer and many other tumor types, and we are also exploring that in that setting.

Got you. Is there a need given the -- the biomarker component, I mean, I know this is, what, 10%, 15% of tumors.

Overall, around 15% and then the prevalence is going to be very different according to the tumor types. But yes, you need to enrich and you -- we are either looking at next-generation sequencing of the tumor, most of the classical approved, FDA approved NGS will report MTAP deletion. We are looking also at immunohistochemistry. And we hope to see with partner biomarker companies we can develop liquid biopsies to detect T-cell status. So it's an important endeavor. It's a little bit more complicated because you need to find those patients, correct? So if you go with your 15%, well, you need to screen 8 patients to find 1 positive, but it's the way of precision oncology.

Is it similar to kind of how Amgen developed KRAS G12C to add the diagnostic to a panel, this shouldn't be that challenging though, would it over time?

It is indeed similar. The only difference is that for mutations you are trying to pick up a positive signal. And picking up a positive signal is always easier than picking up a negative signal. In that case, we're looking for the deletion of a gene. So I will spare you the genetic complexities of detecting a positive versus a genetic -- negative signal. It's a little more challenging. But in NGS reports, we're finding these patients. In immunohistochemistry, we are finding those patients. The main reason is we will need to have more of that reflex testing by the pathologists, but they need to see the data that this is transformative and it's worth screening.

I got you. Okay. Yes. While we're on the topic of targeted therapy, so LUMAKRAS has been -- has been with a lot of fanfare at Amgen when you first launched in G12C non-small cell lung. And obviously, there's some activity in colorectal as well. So can you maybe give us a status update on where you are with the investment there to move? I know combinations and other tumor types were in the mix and in some cases are commercial, but maybe just give us a status quo of where we are with the development there.

Absolutely. So this is obviously a target where few people in the world were expecting Amgen to be the first to score and have a actionable inhibitor. We encounter as we develop this asset, one limitation with many KRAS G12C inhibitors have encountered, which is the challenge of combinability with PD-1s, correct? That being said, we have 2 ongoing Phase III trials for LUMAKRAS. One is in the frontline setting of non-small cell lung cancer, where in patients with PD-L1 negative status, we are combining LUMAKRAS with chemo and comparing that with chemo plus pembro, the standard of care. And that is a commitment we made to FDA for full approval. And the other Phase III trial we have is in colorectal cancer, CodeBreaK 301, where we are combining chemotherapy with our Vectibix, anti-EGFR antibody with sotorasib, and that trial is enrolling. Let me remind you that recently, we got the full approval, not the accelerated approval of LUMAKRAS plus Vectibix in patients with colorectal cancer on the third line, remember, so that's important. And we remain committing to this asset. We follow the science, we follow the clinical data and we will be able to share those results on time.

Let me ask you, just as a follow-up. When you look at LUMAKRAS itself, just given the dosages, I know, is there an effort to kind of further optimize the binding and to try to get the dose down? I mean, it's a decent amount of drug. And I mean it's obviously still highly effective, but I wasn't sure if there is a next-gen kind of LUMAKRAS kind of that Amgen has kind of working on.

Thank you for that question. There has been indeed some discussion about is 960 milligrams the right dose, where we did a randomized Phase II trial of 960 versus 240 in lung cancer. And we also did a Phase III trial of LUMAKRAS 960 plus Vectibix versus LUMAKRAS 240 plus Vectibix versus the standard of care in colorectal cancer. Both of those trials highlight that 960 is the right dose and FDA has approved 960 as the right dose. There is even a recent JCO position paper by our colleagues of the regulatory agencies explaining why 960 is the right dose. Now obviously, we have still interest in that setting, and I will not give you more details, but our research colleagues that develop this beautiful KRAS G12C inhibitor are looking obviously at what else they can develop. And stay tuned, we will be able to share more soon.

And along those lines, some other companies are studying beyond G12C, G12D and other mutations. When you first developed LUMAKRAS, was expanding the mutations part of the priority? Or was it just to get kind of the G12C across the goal line?

I think from a chemistry point of view, these are 2 very different approaches. As we were raising, we focus on G12C, the most prevalent one. But it is very, very clear that the need goes beyond G12C and going G12X or pan-RAS approach are probably very interesting ways to look at it. Our research team are still very committed. And hopefully, we will be able to share with you some exciting news in the near future.

Got you. Okay. And last question, and I guess, we'll come back to the very beginning about what excites you. There's a lot here. I suspect most investors wouldn't be able to name a lot of the assets that we were talking about today, just given all the MariTide kind of overlay. Is there something like in the Phase I -- like what could be a kind of disruptive transformational that at Amgen in the early pipeline that you'd like to highlight either through its mechanism or through its potential differentiation or the modality.

Well, listen, I think the take-home message I would like everyone to have is, we are very excited to bring transformative innovation in hard-to-treat cancers. And we have a robust pipeline with very strong momentum. As I say, we have 9 ongoing Phase III trials with 5 different assets. Only this year, we're going to be reading out 3 Phase III trials. We just spoke about them. That's significant. We are expanding our -- by platform. And you heard about BLINCYTO, xaluritamig, tarlatamab, and the fact that we are moving them to the earlier lines of therapies. And we have other earlier BiTEs. But I don't pick up a favorite child. They have not self-declared themselves. They are too early. We have other signal transduction inhibitors entering the clinic as we speak. What I want people maybe to remember is T-cell engagers may be deeply transformative by the survival benefit that we bring. And how true that statement is, it's going to be -- it has been revealed for BLINCYTO in a very dramatic and clear way. It is just because the survival is so much better than people are prescribing so much more BLINCYTO. But for tarlatamab, IMDELLTRA, we're going to hear the results in this first half of the year. So that's going to be very important. And finally, our precision oncology efforts remain very, very much alive. And we spoke about 193, we spoke about bema. We have other assets coming to the clinic, but again they have not self-declared themselves. So I'm excited about the future of Amgen in oncology. I'm more excited even as a physician who treated lung cancer patients who are over 20 years in academia about changing the standard, correct? Small cell lung cancer patients, once they fail chemo, PD-1, PD-L1, if you see them at this time of the year in February, the bad news is that they are unlikely to be there at Christmas. We want, as a company, to change that reality. We want to give them more Christmas and we are very passionate about that. So thank you again for the invitation.

Yes. No, fantastic. Thank you so much Jean-Charles and also Justin and Casey. It's been a great conversation. So I appreciate the time, and have a great rest of your day.

Thanks so much.

Thank you so much. Appreciate it.

All right. Take Care.