My name is Crystal, and I will be your conference facilitator today for Amgen's conference call on the approval of Lumikrass and the collaboration with Kayo Acurin. 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 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 Lumicraft, our 1st in class KRAS G12C inhibitor. So to discuss these topics further, I'm joined today by Peter Griffiths, our CFO Dave Reese, our Head of R and D and Myrtle Gordon, our Head of Global Commercial Operations. Each will make brief prepared comments and we should have plenty of time for Q and A. So 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 Lumacraft this past Friday. And this morning, we have announced the collaboration with Keyua Curran to develop and commercialize a 1st 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 Keio Acura will allow us to address the growing unmet need around the world for patients suffering from atopic dermatitis. And we will capitalize on genetic insights from d Coat to help inform development and other inflammatory diseases. The collaboration is a strong strategic fit with our long standing expertise in immunology and inflammation and represents a significant addition to our portfolio of Enbrel, Otezla, tezepelumab, AMG 592, 5 70, 714 and AMGEVITA. Dave will go through this in additional detail, but LumaCrest's approval and this collaboration with Keyua Curran demonstrates Amgen's disciplined, predictable and strategic term growth.
We want to invest in external innovation where we are the best or one of the very best investors. And with our long Our long term record with Keio Current will also allow for prompt execution and maximize the value of the collaboration for all parties and most importantly, patience. Today's announcement is our 3rd deal in 2021, following on the recent 5 Prime and Rodeo acquisitions. Our collaboration with Keio Acura and as 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 KHK-four thousand and eighty three globally, except in Japan, where Kia O'Karin 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 $400,000,000 upfront payment to Keyyo Occurring and future contingent milestones worth up to an additional $850,000,000 And finally, Amgen will book sales for KHK-four thousand and eighty three 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 good morning, everyone. As Peter and Arvind mentioned, first, we'll step through a little more detail on our partnership with kelakiran regarding KHK-four thousand and eighty three. And then Murdo and I will give a brief perspective on the launch of lumacraft 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 6, KHK-four thousand and eighty three is a clinically validated Phase 3 ready 1st 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 dcodegenetics to inform on the potential use of KHK-four thousand and eighty three in indications beyond atopic dermatitis. Atopic dermatitis itself, as many of you know, is the most common form of eczema.
It affects about 15% to 25% of children and 1% to 3% of adults. This constitutes more than 26,000,000 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 2 to 3 fold since the 1970s and 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 7, and it 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 it helps control effector and memory T cell responses. There's a lot of evidence that the OX40 pathway is up regulated and plays a pathogenic role in various autoimmune diseases, where it 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. KHK-four thousand and eighty three itself is a fully human A Fuconsylated 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 keorwathiran. Early signs of activity we're seeing as early as a proof of concept Phase 1 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, iolectirin announced positive Phase 2 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-seventy 5, which represents an improvement 75% or greater from baseline and the investigator's global assessment score or IGA of 0 or 1 with an improvement of 2 points or more at 16 weeks. For that 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 adverse 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 3 program and with our partners at heliociran that will be the first order of business for us. We believe K-four thousand and eighty three represents significant opportunity in atopic dermatitis alone and that of course is our immediate focus.
But 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. And with that, Myrtle and I will now transition to provide a brief perspective on the LumaCRAFT launch.
Of course, we had FDA approval last Friday. For those of you following along, I'm now on Slide 9. Lumacrast represents the fastest development program in Amgen's history, and we're absolutely delighted to be able to bring this medicine to patients who have few good treatment options. You can see the patient statement. Lumacraft has indicated for the treatment of adult patients with KRAS T12C 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 lumacraft to patients in near record time. And 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 9 60 milligrams 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% to 3% in a variety of other solid tumors. Tumacraft really represents the culmination of the 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. And 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 LumaCrest clinical development program across 5 continents and have, of course, many combination therapies in development at this time.
On Slide 11, you can see our next slide, you can see that KRAS C12C 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 to 25 1,000 KRAS G12C positive patients in the United States each year, of whom approximately 13,000 have second or later lines of therapy and are the immediately addressable population by Lumicrast. On 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 the short duration of response.
In fact, up to 1 in 5 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 lumacraft is available. Now I'll finish just by mentioning on the next slide, are the 2 companion diagnostics that have been improved in conjunction with lumacraft. We've been happy to work with Guardant on a liquid biopsy kit, which is the 1st 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 VECTIVIX. This single gene test is well covered by Medicare as well as commercial insurers. As part of the development program, we've done concordance studies and found very strong concordance between the liquid biopsy and tissue biopsy assays.
So 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. And we intend to obviously expand that testing. And with the advent of the approval of lumacraz 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. And 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 coinsurance 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. And we're working with Longevity Foundation to build awareness with our customers and with patients to understand that lumacaraz is now available and that they may be eligible for treatment if they have progressed on their frontline therapy. Lastly, Amgenesis offers others financial support options for any insurance type referrals. And we've been extending the Amgenesis 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.
And we believe that having lumacaras 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 benefit from. We also believe that we have an improvement, 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.
And obviously, we are hopeful that we'll be able to continue to
Then on the next slide, you can see that really our Then
on the next slide, you can see that really our strategy, as outlined by Dave Reese, has been exemplified by lumikra's launch. There are many, 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 and D organization for working so hard, so diligently through a pandemic over the last 3 years, which is quite remarkable to bring a product to the market so quickly after more than 4 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 everything we can into ensuring that patients who are eligible for this product are able to access it and able to afford it. And 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 and
A. Your first question comes from the line of Michael Yee with Jefferies.
Hi, good morning. Can you hear me?
Yes, I can hear you just fine, Mike. Go ahead.
Hey, Arvind. Happy Tuesday. My question was around the commercial launch for KRAS and just trying to compare KRAS to other target therapies that have launched over the past few years. Maybe you could talk about either tailwinds or headwinds. I think maybe better testing and increased testing and awareness.
But at the end of the day, there's a lot of different drivers there. So 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. And of course, in many settings, the testing was to exclude patients with RAS mutations from treatment as is the case in colorectal.
So 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 results somewhere in their pathology report. Now what we're working on is making sure that 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. So if you get a long 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. And 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. So that's one thing that's a little bit different than say the kind of the Ross 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 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. Similarly, sales people have been trained and in place for months now. This is an example of how ready we are within an hour or 2 of the approval. All of our healthcare professional website was up and running and providing information to them.
So 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. And so 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. But 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. 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? And 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. Yes, we can't really go into much more detail on the efficacy profile now until those data are presented publicly. Obviously, impressed with what we saw. And I think the biggest area of differentiation here is the unique mechanism of action. And 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.
So 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.
Dave, I was hoping
to ask 2 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 4 weeks time points being robust action. I'm just wondering how you think about that and if you agree with that. And then second, can you comment at all on what we should be thinking in terms of broadly in terms of the royalty rate? Thanks.
Maybe I'll take the first part of that question and then ask Peter or Murdo to comment on the second or Arvind. Yes, Terrence, 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. And 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.
So 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, you're going to take the second part on royalties?
Yes, Dave. Thank you and good morning, Matthew. We're going to make a $400,000,000 upfront payment to curing keloids we mentioned, future milestone payments potentially worth up to an additional $850,000,000 and 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 multiyear period. And
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.
Good morning, guys. Congrats on the early approval and deal and thanks for taking the question. On the lumichrast label, I don't think the pneumonitis or the liver monitoring was surprising, but were there any other things that were additive that you guys weren't expecting? And 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.
Yes, Jeff. I'll start there and Murdo can chime in if he wishes. We think the label quite accurately reflects, of course, the clinical data that we've generated to date, very good tolerability profile in terms of oncology drugs, as I've said before, in 30 years of drug development in this field, this is one of the best behaved molecules that 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% 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 pretreatment with check point inhibitors in at least 1 or 2 cases, immediate pretreatment with radiation therapy to the chest or chest wall, of course, which are well recognized causes of, pneumonitis. So 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 Lumacraft. So it will be 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 of quick ones. On LumaCrest, the LST rate was low double digits in the label. So 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? And then for KHK-four thousand and eighty three, I mean, to your point, is the thinking here, I know you were testing 2 different dosing regimens, the half life is 29 days,
should we assume this
is monthly dosing? Thank you.
Yes. Thanks, Yaron. Yes, the LFT, the 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 quite pleased with very pleased with the overall safety profile. So 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 you can 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 Rani Gao with Bernstein.
Good morning. Thank you for taking my questions and congratulations on the approval on the deal. Just a quick question from Murdo, if you can discuss the prevalence pool versus the incidence pool for lumacraft, it seems that there must be a lot of patient out there who are currently diagnosed and could be waiting for this I had a few beginning to go into the incidence pool. So as we think about modeling this, is this a real consideration or is this something that you don't believe will happen?
Yes, 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 frontline therapy with immunotherapy or checkpoint inhibitors. So 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 lumacrasp. That being said, anecdotally, we hear a lot from oncologists who have patients waiting for the therapy. But 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 2 today, if I may. 1 perhaps on OX well, one on each, if I'm going to put it that way. So on OX40, what were the dose levels in Phase 2? And can you characterize the safety profile?
Because that was a big question heading into that Phase 2. And I ask because there's a lot of fever, chills and even oral sores observed in Phase 1 at the 10 milligram per kilogram 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. And then on KRAS, I guess my main question is, there's been a lot of investor questions around the integrity of price point if a 2 40 dose is approved down the road.
And 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. But in this case, since 9 60 is taken as a function 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 for lumacraft 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 1 study.
Typically, as with many antibodies, it tends to be a first dose phenomenon. Our belief is that, when looking at the overall adverse event profile, it can be quite competitive and 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 we when the investigators present those data a bit later. Murdo?
Yes. The consideration of the 960 versus 240 milligram study was taken into account when we were planning the launch price of lumacrasp. And as you rightly pointed out, there are ways of preserving a price point in the market that we think represents good value for the product. And 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 those presentations ready and available to preserve the value price point that we've already set in the market.
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 Luma Crafts, Berta, 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.
Yes. Thanks for the question, Jeffrey. We're not commenting on duration of treatment until we see more mature data continue. And 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. So 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 second line versus third line, the vast majority are going to be second 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 second line versus third line. I also think with the availability now of lumacraft to target KRAS G12C, some of the persistence with frontline therapy might diminish in terms of you see a little bit of PD-one recycling between 1st 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 lumikraz before you would do that. So 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 lumacrasp.
Your next question comes from the line of Salim Syed with Mizuho.
Great. Congrats on the approval and the OX40 guys. Just one on Lumikraft for me, if I can. Just a quick one on the follow-up to 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 Medicine Ship 2 collaboration, you're not taking control of when you're going to release that data, etcetera. I presume you may think there's a problem with the therapeutic index there. So I'm curious if there's something there in general that you can speak to that would allow you to partner with other ship to outside of ResMed? And then just a quick one on the pricing question. Was the mechanism, Murdo, that you guys were speaking to here potentially pulling the 9 60 milligram dose from the market if the 2 40 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 1 than I will. Well, actually, I think Dave is in
the best position on number 1. Let me talk Go ahead.
I think as we for it's the collaboration with Revolution Medicine on both sides is non exclusive. So 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 REVOLUTIONSHIP-two inhibitor and we'll disclose those data once we've got an acceptable body of information. Murdo?
Yes. And on the pricing question, we're considering a number of different pricing potential impacts to the product and a number of different clinical trials scenarios on that comparative study. So I think it's premature to speculate as to what we would do with specific dose presentations. But 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 and hope you got to enjoy some part of the long weekend as you were clearly working through this. Maybe on OX41 question, literature suggests that OX40 could be implicated with multiple facets over and above IL-four and IL-four and IL-four and IL-four and IL-thirteen, it could be TNF and interferon gamma, IgE. So it seems like it has the potential for broader activity.
So do you anticipate this resulting into a more potent effect as in and then and Dave you mentioned that it could be a patient for cycle 2. So do you see this potentially becoming a second line kind of therapy? And conversely, do you see any impact from the systemic safety point if we given the broader implication here? Thank you.
Sure, Amit. Thanks 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.
And then finally, because of the importance of this pathway, as you indicate and as I said in my opening remarks, we are working with d code 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. And with our partners, we'll talk about that at the appropriate time when we have 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 LumaCrest and also the Kirin deal. I'll keep it brief, getting late in the call. And just firstly, in terms of LumaCrest, 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? And then secondly on OX40, could you just give us a quick view of when that data might be presented? Thank you.
Yes. So, Jan, I'll start with the first part of then ask Murdo to comment as well. We are filed in 8 or 9 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. And so we'll provide updated guidance as we can look at potential timings of approvals outside the U. S. And then 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.
And of course, there were 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 on 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 on late September, early October. And so 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 has been able to file this product in a number of different markets, my team is tracking very closely to be able to submit to reimbursement authorities upon approval. And 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 today.
Your next question comes from the line of Cory Kasimov with JPMorgan.
Hey, good morning guys. Thank you for taking my question. I have a follow-up on the pricing of Bloomacrafts, but from a different angle. The combination opportunities have obviously been a big focus as we await initial data on that front. So I'm wondering how we should think about pricing or pricing in the future could be impacted down the road should those combos move forward into the marketplace and or lumichrast potentially moves up in lines of therapy?
I mean, 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.
Yes, it's a difficult question because it involves some hypotheticals on what the optimal dose will be in some of those combinations. But for the most part, we think we've got the bookend of scenarios covered, Corey, 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 lumapress approval. That's all from me. Another one for David.
When we think about potential future label extension opportunities, particularly in first line non small cell lung cancer, How should we think about the efficacy benchmark 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?
Yes. Thanks, Mike. I think that's a hard question to answer. And I think we're still defining precisely what the natural history is for those patients. I think it's also with the none of these markers are absolutes.
And so 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. Well, 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. So 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. This is Nina on for Alethia. And 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 to Aaron 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 set therapies. Patients tend to cycle on therapies.
So given the widespread prevalence of the disorder, we think there's still very large significant residual unmet medical need and that we think is where KHK-four thousand and eighty three will play an important role we hope. Murdo?
Murdo, I think you're on mute.
Yes, you're muted, Murdo.
Okay. Can you hear me now? Thank you. So as Dave mentioned, what we've got is an opportunity to serve a lot of patients who may be also think just with the portfolio 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. So 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.
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 lumacraft in FG12C versus some of the prior agents in this space, specifically the ALKS. Also wanted to get a perspective on sort of EGFR and the maybe 2nd generation, next generation EGFR inhibitors. 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 $17.9 per month could influence that as well.
It does seem like it's a price for a very broad market there.
Yes, let's start with the price. We did obviously look at the significant improvement that we've made on second line treatment options in non small cell lung cancer. And as a monotherapy treatment there, we think this is priced very well compared to other targeted medicines available in the market for other driver mutations. And then 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 really 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% 10% of patient diagnoses in oncology.
But with the 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.
Okay. Thanks for squeezing me in as well. Maybe just a pricing strategy question, I guess, for Murdo, to the extent you can answer it. So 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 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 2nd line non small cell lung cancer setting is, of course, generically available chemotherapy. So 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. But 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 and congrats. Just a quick one on the OX40 asset, wondering if you have any comments on that Phase 2 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?
Yes. It's a good question and 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 and we are leveraging insights from decode genetics. And so 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. And the ulcerative colitis data will be presented also in due course.
So again, very enthusiastic about this asset, differentiated mechanism of action, very plausible science and genetics and a great partner. KHK-four thousand and eighty three forward. Our KHK-four thousand and eighty three forward. Arvind?
Okay. Thanks, Dave. So with that, let me thank everybody for your participation this morning, at this early hour this morning. And 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.