Amgen Inc. (AMGN) Earnings Call Transcript & Summary

My name is Crystal, and I will be your conference facilitator today for Amgen's conference call on the approval of LUMAKRAS and the collaboration with Kyowa Kirin. [Operator Instructions] 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 1, but 2 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 had set up this call initially, of course, to discuss the approval of LUMAKRAS, our first-in-class KRAS G12C inhibitor. So to discuss these topics further, I'm joined today by Peter Griffith, our CFO; Dave Reese, our Head of R&D; and Murdo Gordon, our Head of Global Commercial Operations. Each will make brief prepared comments, and we set up plenty of time for Q&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 LUMAKRAS this past Friday. And this morning, we have announced a collaboration with Kyowa Kirin to develop and commercialize a first-in-class Phase III-ready molecule for atopic dermatitis. These are examples of what we always do, start with patients in mind at Amgen. Our collaboration with Kyowa Kirin will allow us to address the growing unmet need around the world for patients suffering from atopic dermatitis, and we will capitalize on genetic insights from deCODE to help inform development in other inflammatory diseases. The collaboration is a strong strategic fit with our long-standing expertise in immunology and inflammation, and represents a significant addition to our portfolio of ENBREL, Otezla, tezepelumab, AMG 592, 570, 714 and AMGEVITA. Dave will go through this in additional detail. But LUMAKRAS' approval and this collaboration with Kyowa Kirin demonstrates Amgen's disciplined, predictable and strategic execution of our capital allocation hierarchy, which always begins with investing in both internal and external innovation to drive long-term growth. We want to invest in external innovation where we are the best or one of the very best investors. And with our long, successful history with Kyowa Kirin and our decades of achievements in inflammation, this opportunity easily clears all of our hurdles. Our long-term record with Kyowa Kirin will also allow for prompt execution and maximize the value of the collaboration for all parties and most importantly patients. Today's announcement is our third deal in 2021. Following on the recent Five Prime and Rodeo acquisitions, our collaboration with Kyowa Kirin adds another Phase III-ready asset to our pipeline of medicines with strong growth potential. And we continue to look for other opportunities that align with our disciplined business development strategy. Slide 6 steps through some of the relevant deal terms for this collaboration. Amgen will lead development, manufacturing and commercialization of KHK4083 globally, except in Japan, where Kyowa Kirin will continue those responsibilities. Global development costs will be shared, except in Japan. And U.S. commercialization costs will also be shared. Amgen will make a $400 million upfront payment to Kyowa Kirin and future contingent milestones worth up to an additional $850 million. And finally, Amgen will book sales for KHK4083 in all markets globally, except Japan, and will pay royalties on future global sales. Let me now turn the call over to Dave. Dave?

Thanks, Peter, and good morning, everyone. As Peter and Arvind mentioned, first, we'll step through a little more detail on our partnership with Kyowa Kirin regarding KHK4083, and then Murdo and I will give a brief perspective on the launch of LUMAKRAS after the FDA's approval last Friday. Starting with our collaboration with KK. For those of you following along the slide deck, I'm on Page 6. KHK4083 is a clinically validated, Phase III-ready, first-in-class anti-OX40 antibody that has the potential to address a very significant global unmet need for patients with atopic dermatitis and potentially other inflammatory diseases where we intend to leverage our industry-leading platform at deCODE genetics to inform on the potential use of KHK4083 in indications beyond atopic dermatitis. Atopic dermatitis itself, as many of you know, is the most common form of eczema. It affects about 15% to 25% of children and 1% to 3% of adults. This constitutes more than 26 million people in North America, E.U. and Japan alone, with particular unmet need in patients with moderate to severe disease. The incidence of this autoimmune disorder has increased two to threefold 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 costimulatory 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 upregulated and plays a pathogenic role in various autoimmune diseases where it, upon activation, activates downstream signaling pathways to drive the expression of various prosurvival molecules; increases cytokine production; and as noted, creates a generation of both effector and memory T cell subsets. KHK4083 itself is a fully human afucosylated antibody that has a presumed dual mechanism of action, both blocking OX40 signaling and enhancing antibody-dependent cell-mediated cytotoxicity of effector T cells that, in fact, is believed to lead to the depletion of those cells, including pathogenic cells over time. Now of course, what we find most compelling about the collaboration is the clinical data generated to date by Kyowa Kirin. Early signs of activity we're seeing as early as a proof-of-concept Phase I study in patients with moderate to severe atopic dermatitis, where various improvements in disease markers and clinical symptoms were observed. In February of this year, Kyowa Kirin announced positive Phase II results from a double-blind, placebo-controlled study of 274 patients with moderate to severe atopic dermatitis, a study that was conducted in the U.S., Japan, Canada and Germany. The primary endpoint was successfully met with a statistically significant improvement in the percent change from baseline in the Eczema Area and Severity Index, often called the EASI score, at 16 weeks compared to placebo. There was also improvement in various secondary endpoints, such as the EASI-75, which represents an improvement of 75% or greater from baseline; and the Investigators Global Assessment Score, or IGA, of 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 III program. And with our partners at Kyowa Kirin, that will be the first order of business for us. We believe KHK4083 represents a significant opportunity in atopic dermatitis alone. And that, of course, is our immediate focus. 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 begun 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, Murdo and I will now transition to provide a brief perspective on the LUMAKRAS launch. Of course, we had FDA approval last Friday. For those of you following along, I'm now on Slide 9. LUMAKRAS 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 mission statement. LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer as determined by an FDA-approved test who have received at least 1 prior systemic therapy. The FDA took advantage of various accelerated review pathways to bring LUMAKRAS 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 960 milligrams once daily, which can be taken with or without food. Turning to Slide 10. As I 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 and a frequency of 1% to 3% in a variety of other solid tumors. LUMAKRAS 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 LUMAKRAS clinical development program across 5 continents, and have, of course, many combination therapies in development at this time. On Slide 11, you can see -- on our next slide, you can see that KRAS G12C is one of the most prevalent driver mutations in lung cancer. As I mentioned, it occurs in about 13% of individuals, roughly comparable to the frequency of EGFR mutations. That translates to about 20,000 to 25,000 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 LUMAKRAS. On the next slide, you can see that, until today, there have been no therapies available for patients. Consumers bear the G12C mutation. Chemotherapy is most commonly used in this setting but historically has had relatively low response rate and a 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 LUMAKRAS 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 LUMAKRAS. We've been happy to work with Guardant on a liquid biopsy kit, which is the first FDA-approved test using next-generation sequencing in the liquid biopsy setting. National Medicare coverage is already established for non-small cell lung cancer testing. We also worked with QIAGEN on their therascreen RGQ PCR assay, which is a tissue-based assay. This kit is well established in the marketplace, where it is used in colorectal cancer to actually select wild-type patients who are available for anti-EGFR antibody therapy, such as Vectibix. This single gene test is well-covered by Medicare as well as commercial insurers. As part of the development program, we've also done concordance studies and found very strong concordance between the liquid biopsy and tissue biopsy assays. 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 and G12C mutational status, and we intend to obviously expand that testing. And with the advent of the approval of LUMAKRAS and the now actionability of the KRAS G12C mutation, we think that, that will rise fairly rapidly. The other thing just to note is that the majority of non-small cell lung cancer patients are treated in a community oncology setting. 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 copayment 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 LUNGevity Foundation to build awareness with our customers and with patients to understand that LUMAKRAS is now available and that they may be eligible for treatment if they have progressed on their frontline therapy. Lastly, Amgen Assist offers other financial support options for any insurance-type referrals, and we've been extending the Amgen Assist Program across the entire portfolio of Amgen products. On the next slide, basically, we are very focused on providing value to patients, oncologists and, of course, the health care system at large. And we believe that having LUMAKRAS available at the U.S. list price of $17,900 per month represents, indeed, good value. The first part of our value story is that you do have a targeted precision oncology therapy biomarker, which narrows the treatable population to 13% non-small cell lung cancer. That reduces the exposure of patients to a therapy that they may not benefit from. We also believe that we have 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 demonstrate the safety and efficacy profile of LUMAKRAS with additional clinical work that's underway. Then on the next slide, you can see that really our strategy, as outlined by Dave Reese, has been exemplified by LUMAKRAS' launch. There are many, many people who should feel extremely proud of this. Our investigators, the patients that volunteered for our early clinical trials. And I'd be remiss if I didn't thank David Reese and his entire R&D organization for working so hard, so diligently, through a pandemic, over the last 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're prepared for this day. Everyone here at Amgen is extremely energized and we'll be putting everything we can into ensuring that patients who are eligible for this product are able to access it and able to afford it. 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&A.

[Operator Instructions] Your first question comes from the line of Michael Yee with Jefferies.

Can you hear me?

Yes. Can hear you just fine, Mike. Go ahead.

My question was around the commercial launch for KRAS. And just trying to compare and contrast to other target therapies that have launched over the past few years. Maybe you could talk about either tailwinds or headwinds. I think about maybe better testing and increased testing and awareness. 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.

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 ALT, are. So if you get a lung panel today, KRAS G12C may not be on the front page of that path report. That's what we're working on with pathology, with pathologists and with oncologists. 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 [ ROS ] products or even ALK at the very beginning of the XALCORI's approval and launch, where ALK testing was relatively low. The fact that we've been campaigning for over a year now in creating awareness of KRAS G12C affecting about 13% of patients, the fact that we have very good reimbursement programs assisting commercially insured patients and other programs assisting a broader population of patients, both with biomarker testing and with out-of-pocket expenses related to the 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, salespeople 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 health care professional website was up and running and providing information to them. So this is a well-oiled machine that's running extremely effectively. But 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 are 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.

Our next question comes from the line of Terence Flynn with Goldman Sachs.

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.

Thanks, Terence. Yes, we can't really go into more detail on the efficacy profile now until those data are presented publicly. And obviously, we're 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 point, for it to be 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?

Yes. Maybe I'll take the first part of that question and then ask Peter or Murdo to comment on the second, or Arvind. Yes. Terence, I think your supposition regarding the onset of action is correct, probably related directly to the mechanism of action. As I noted, we believe this has a dual mechanism, both blockade of OX40 signaling, but then also depletion of critical OX40-bearing T cells over time. 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 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, do you want to take the second part on royalties?

Yes, Dave. Thank you. Matthew, we're going to make a $400 million upfront payment to Kirin Kyowa, as we mentioned, future milestone payments potentially worth up to an additional $850 million. 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.

Congrats on the early approval and deal . On the LUMAKRAS 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?

Yes, Geoff, 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 said before, in 30 years of drug development in this field, this is one of the best-behaved molecules we've seen. The monitoring for liver function test is quite common with small molecules and is something that oncologists do, of course, routinely. We don't really think that's going to be an issue at all. The pneumonitis you mentioned. I should point out that there's a background rate of pneumonitis of between 0.5% and 1% in patients with non-small cell lung cancer. Some of the patients with pneumonitis, for example here, also had confounding factors, such as immediate pretreatment with checkpoint 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 LUMAKRAS, and I'm quite confident in what the safety profile will look like there.

Your next question comes from the line of Yaron Werber with Cowen.

Great. David, for you, if you don't mind, just a couple of quick ones. On LUMAKRAS, the LFT rate was low double digits in the label. So I think it's 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 KHK4083. I mean, to your point, is the thinking here, I know you're testing 2 different dosing regimens, the half-life is 29 days. Should we assume this is monthly dosing?

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 by some of the clinical data, one could envision that reasonably infrequent dosing will be a target here. More on that when the clinical data are presented a little bit later by our investigators.

Your next question comes from the line of Ronny Gal with Bernstein.

Congratulations on the approval and the deal. Just a quick question for Murdo. If you can discuss the prevalence pool versus the incidence pool for LUMAKRAS. It seems that there must be a lot of patients out there who are currently diagnosed and could be waiting for this ahead of you 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 inhibitor. 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 LUMAKRAS. 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.

I had 2 today, if I may. One, perhaps on -- well, 1 on each, if I may put it that way. So on OX40, what were the dose levels in Phase II? And can you characterize the safety profile? Because that was a big question heading into that Phase II. And I ask because there's a lot of fever, chills and even oral sores observed in Phase I 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 240 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 960 is taken as a function of multiple pills of lower strength, I'm just trying to understand how you guys intend to present and price the lower doses such that, if there were to be a lower dose approved, the price integrity stays intact.

Great. Thanks, Umer. I'll take the first question on OX40 on the safety profile and then turn it over to Murdo for LUMAKRAS pricing. As we mentioned in our opening remarks, we were obviously impressed with the safety profile. As you pointed out, fevers and chills were not uncommon, as reported in the Phase I study. Typically, for -- as with many antibodies, it tends to be a first dose phenomenon. Our belief is that, in 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 LUMAKRAS. And as you rightly point out, there are ways of preserving a price point in the market that we think represents good value for the product. 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 dose 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.

Congratulations on really significant news. Just with respect to LUMAKRAS. Murdo, could you talk a little bit about your expectations in the market for the proportion of patients that will be second line and third line? And then how do you think the duration of treatment is likely to play out in the real world between those 2 different populations?

Yes. Thanks for the question, Geoffrey. 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 LUMAKRAS to target KRAS G12C, some of the persistence with frontline therapy might diminish in terms of you see a little bit of PD-1 recycling between first line and second line. If you're a KRAS G12C patient, that may not be a choice that you want to make. You may work with your oncologist to look at something like LUMAKRAS before you would do that. 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 LUMAKRAS.

Your next question comes from the line of Salim Syed with Mizuho.

Great. Congrats on the approval in the OX40, guys. Just one on LUMAKRAS 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 SHP2 collaboration. You're now taking control of when you're going to release that data, et cetera. I presume you may think there's the problem with the therapeutic index there. So I'm curious if there is something there in general that you can speak to that would allow you to partner with other SHP2s outside of Rev Med. And then just a quick one on the pricing question. Was the mechanism, Murdo, that you guys were speaking to here potentially pulling the 960-milligram dose from the market if the 240 mg looked similar?