Johnson & Johnson (JNJ) Earnings Call Transcript & Summary

Great. Well, great. Good morning, everybody. Thanks for joining us. I'm Terence Flynn, the biopharma analyst at Goldman Sachs. And we're very pleased to have Johnson & Johnson with us. Joining us from the company this morning is Mathai Mammen, who is Global Head of R&D. Mathai, thank you so much for joining us. I really appreciate your time today.

It's my great pleasure, Terence. Happy to be here.

Great. Maybe just to start a couple of high-level questions. The first one I had is just as you think about your capabilities on the R&D side, what do you think really differentiates J&J's approach? And again, as we think about kind of the implications of COVID, any changes to R&D that you're making as a result coming out of the epidemic here?

Yes. So just to step back and think about how we're organized as an R&D organization, it's quite distinctive. The way it works is we're, I think, the only company to have truly end-to-end therapeutic area structures as a prominent -- featuring prominently in how we operate, meaning there's a therapeutic area head, say, David Lee for immunology or Peter Lebowitz for oncology that covers all aspects of that area, from early discovery and target selection through the last labeled indication of that medicine prior to loss of exclusivity. So it can be a couple of decade kind of span of control. And that makes so much of what we do easier relative to other experiences I've had in other companies. So that's one big one. And it enables us to think differently, and I decided to keep it that way to reinforce it. The other is the heavy leaning in, in recent years into use of data and analytics, data science. That's really distinguishing how we operate. And you asked about the COVID-19 experience. I would say, how we were able to execute on our vaccine trial was very much because we had invested heavily in data science. And that sort of the first domino to fall, I would say, in changing us, maybe like other companies, too. And that has led to a culture change in how we operate and make use of emerging data sets to fundamentally change how we define disease, identify patients, diagnose patients to sites. All sorts of things that are practical and executable, we're doing right now. So it's our org structure and data science that I would put upfront. There are all these other elements too on how we're regularly beating up our portfolio and knocking down programs that we believe can't make a world of difference for patients so that is a cultural feature of Janssen that I'm really proud of and we've reinforced. So everything, that normal progression seeking that sometimes happens in companies doesn't happen here. And I'd say that's a patient-centric, very important element to how we operate.

Great. One other thing that I think has been a distinguishing feature is the ability to kind of balance internal and external innovation. And I think you guys have done a great job there, especially on the therapeutic side. So maybe just talk to us about some of the forward outlook there. How are you thinking about that here? Has -- again, similarly has COVID led to any changes about how you're thinking about that balance? And then any therapeutic areas of interest or new ones that, again, you guys are focused on here on the forward?

Yes. So the therapeutic areas that we're in cover a lot of web medicine covers right now. So I don't see the need to change those fundamentally in how we're arranged. There are individual diseases that we'll lean into more heavily. We have our disease area stronghold and path area stronghold structures that sit underneath the therapeutic area structure. An example of a new area that we're going to invest in heavily going forward is bladder cancer. And it's motivated by some of the work that we've talked about publicly with BALVERSA and the TARIS acquisition. But we have so many more ideas and programs in that space that we'll continue to work on. And we want to make bladder cancer something that goes from 95% non-survival rate in 5 years to something that looks like prostate and headed in the direction of multiple myeloma today where we just give it a go and create the right regimens. With regard to external innovation, you're right, like J&J as a whole and Janssen specifically, we are completely agnostic as to where innovation comes from. We've opened the door through some terrific capabilities on our discovery side to being a partner of choice when we offer certain capabilities that are unique to discovery-stage companies and true complementation as possible. And of course, on the development side, we're agnostic as to a source of a medicine that we think is going to make, again, a transformational medicine and treatment for a patient. I'd say, with COVID, it's interesting -- or maybe it's not even COVID per se, but it's just all the resource, the funding that's moved into the biotech arena, it's done a couple of things. On the caution side, it has floated some companies that may not have otherwise been -- it wouldn't have been possible and we have to be especially discerning. But on the other side, it's given life to some high-risk, high-reward opportunities. So we invest a fair bit of time, continuously scouring, creating the right connections, relationships. A lot of this comes down to inference and trust. So it's a machine that we have right now that look at the world and we situate ourselves within it, not above it, but within it as a participant in this ecosystem. And I think that served us well, and we'll continue to do that.

Great. Great. Well, as we think about -- again, another kind of high-level question here, you guys are hosting a Pharm Day in November. I think the last one was a couple of years ago here. But anything that we should pay attention to here? What are you excited about? Maybe give us some early insights of what to expect or a little bit of a preview.

Sure. No, there's a lot going on in our portfolio, as you know. And so what we've done -- we'll have an opportunity to talk a lot more about this. But the portfolio has been changing quite a bit over the last few years, and we'll have an opportunity to talk about some of the new disease areas that we're in, in full. I mentioned bladder cancer. I haven't talked about lung cancer yet, but these are areas that are new to Janssen and where the products that are emerging right now are spectacular. Like the amivantamab, especially right now in -- for exon 20 characterized lesions of non-small cell lung cancer is going to be really interesting. But in combination with lazertinib, we believe this can be a truly transformational product in -- for lung cancer and something that actually is the preferred product among, well, EGFR-characterized lung tumors. So this is a big deal, and we have multiple other programs behind that in lung cancer. And lung cancer is still 25% of cancer. So this is one of those big areas that we'll unveil more in full, but we've already talked and you know about amivantamab, especially in combination with lazertinib. Bladder cancer, we believe what we have is going to be really, really big, probably bigger than the environment really understands in full today. We're going to combine it with various agents, both our original TARIS, which is gemcitabine slow release in the bladder; BALVERSA, eventually switching to BALVERSA in that TARIS device combination with our PD-1, atezolizumab. These regimens that we'll create and many that I haven't mentioned right now behind it, we believe, can completely change how bladder cancer is treated today and the outcomes that folks unfortunate enough to have bladder cancer might come to expect. Those are a couple. One other I'll mention just before leaving that, I'm happy to elaborate on more is the vaccine space. We're not -- we don't have commercial vaccines today. It's not a business for us. But we've been working away for the past 5 and 10 years on a vaccine portfolio. Apart from COVID-19, we'll be really excited to talk about our RSV program, which we believe is both first-in-class and best-in-class. This is for older adults and a really exciting program that protects against sepsis with E. coli. So gram-negative vaccines aren't really a thing right now. And I'm truly excited about what we'll be able to do protecting patients from E. coli infections and lets -- maybe enables us to look beyond that and other gram-negatives. So then there's others. So we have an HIV vaccine cooking. So the vaccine space in full is something that we'll begin to emphasize as we approach the business review later this year.

Okay. Great. And I think we'll come to amivantamab in a little bit here in terms of some of the cancer assets. But I guess the vaccine discussion, it's a good segue to kind of the next topic I wanted to touch on. Congratulations on the EUA for your COVID-19 vaccine. I know you guys worked very rapidly to bring that to the market and to patients here. As you think about the manufacturing guidance and the outlook there, are you guys still comfortable with being able to supply 1 billion doses this year? I know there's been some back and forth on the Emergent facility, but maybe just give us an update on kind of where you stand on the manufacturing side.

Yes. So just taking a step back, we are very proud of this vaccine. It's -- we believe -- like there will be actually a fair bit of data that gets rolled out in the coming month or 2. That's a follow-up on the EUA data set, the data set that afforded the EUA. And I think we're going to be able to show that our vaccine is especially durable, like it's a long-lasting effect. And that's likely a result of a lot of memory T cells being induced by the vaccine. So that does make a difference to how the vaccine will likely be used and where it will be used in the future. And the other key feature that we already knew about but will be reinforced in a big way is the broad-based activity against the virus regardless of which way the virus kind of pivots. So I don't think we'll be needing to chase particular variants because there's underlying, again, cell-mediated immunity coverage for all the variants that we know of right now equally, equal to the original Wuhan strain. So on the manufacturing side, as you know, we're working very hard with the facility -- the Emergent facility in Maryland. And -- but we're not only dependent on that. We have a number of other facilities in the world that are making both vaccine drug substance and filled vials drug product, and these will come online very shortly. And we remain really confident that, that pacing of 1 billion doses by year-end should be there. And if there's any change to that, we'd obviously update. The Emergent situation is an ever-evolving kind of situation. But we're working extremely closely with health authorities, FDA, and close collaboration to get that facility in the state that we're proud of and create lots of vaccine for the world.

Great. Great. Well, maybe one follow-up. Obviously, the duration of protection is a key question. Everyone is focused on here for your vaccine and the other vaccines. So how are you thinking about the duration of protection here? Do you think this will last more than a year? Again, it sounds like your comments, you feel pretty comfortable there. But maybe give us your best outlook for how long we'd expect that duration to last here and how frequently we might need a booster shot.

Yes. So I'm not going to be able to be very specific right now because we're looking at data right this minute, and we will publish it in the coming couple of months or a month or 2. But I'll tell you like the key to durability is the induction of memory T cells, right? And we see extremely good levels of memory CD4 and memory CD8 T cells and better than what other manufacturers have reported by quite a bit. And we see corresponding downstream components of the immune system, meaning both effector CD8 cells and antibodies that have a kinetics that is comfortably flat. And so we'll be able to talk more specifically about what that interval should look like as we get more data published in the coming month or 2. But I'm feeling really good, Terence, about the durability of our vaccine. And I don't know whether it would be required once yearly or even less frequently than that, and we'll be able to speak to that shortly.

Okay. Great. Good to hear. I guess one other follow-up is that data -- the new data coming out, is that from the second Phase III trial that you guys are running with the booster schedule? Or this is just follow-up data from the first kind of Phase III trial or maybe it's some real-world experience?

Yes. It's multiple sources. We have actually Phase I and II studies also running where we do a lot of sampling from the participants there to further characterize their immune response with time. So it's that, plus the 3001 study. This is ENSEMBLE, which is the first big Phase III study. We have more data coming out in the July time frame there where we'll have lots of data built on durability and on activity against variance. The one you're referring to, the 2-dose study, was -- I think I'd characterize that right now as a bit of a backstop that we had in case our data were not broad-based or were not durable. And in which case, maybe a booster shot within a couple of months or at 2 months would be necessary. We'll see all that data too in July. But with the emerging data on the single shot, I'm feeling really good that the single shots are actually a really good vaccine.

Okay. Okay. Great. Well, again, in the interest of time, I want to move on to your cancer portfolio. We're on the heels of ASCO right now. Obviously, this has been a big growth driver for the company, particularly in multiple myeloma and CLL where you have 2 cornerstone franchises here. Obviously, you're developing a number of new myeloma agents as well targeting some of these new antigens. You have a CAR-T, you have some bispecifics. Maybe just walk us through kind of as you think about the portfolio here, how do you see the paradigm in myeloma evolving? And then we'll dig into some of the specific assets here. But just if you step back kind of 10,000 feet, if we look out 3 to 5 years, how does the paradigm evolve here on the myeloma side?

Yes. So we have our eyes squarely on heading towards cure. And we understand that every patient kind of enters the system at a slightly different place. They may have different tumors. They're in different circumstances with different access. So what we want as Janssen is to create the right regimens for a broad spectrum of patients so as to head towards cure. And we want to work towards these combination sequencing, in the right way, agents to be able to do exactly that. And I see that in that 3- to 5-year time frame as fundamentally evolving, and we as a serious leader in the space with multiple tools for all of these different patients. So I'll highlight a couple of things. The Cilta-cel program, this is our BCMA CAR-T program, it's -- I just speak very personally for me, I don't think I've ever seen in my professional career data that I'm as excited by as this program is producing. Like in CARTITUDE-1, we see -- so first, who was in CARTITUDE-1? These are patients with multiple myeloma that have received a median of 6 prior lines of therapy, like 85% of them were triple refractory. And their life expectancy was quite short. And what we see right now is 18 months after dosing, 81% of these patients are alive. And that's pretty phenomenal. We have a 92% MRD negativity rate. And the way we define MRD negativity is you can't detect a myeloma cell in 10 to the 5 or 100,000 cells. So it's a very, very high bar for response. And 92% of our patients who have a single shot of Cilta-cel are MRD negative. And then this was their background coming in. So this is phenomenal. That said, we're going to continue to move that to earlier lines. We're of the philosophy in our cancer space that hit the patients with the best possible therapy as early as possible, and that will lead to the best outcome. So we'll be looking -- even the CARTITUDE-1 results were incredibly good, we'll be moving down the lines as we go. We have, as you suggested, other therapies, the CD3 redirectors. So teclistamab and talquetamab are very important products to us. This is a lot less burdensome for the patients. And what we've been able to demonstrate so far -- and both of these, by the way, have breakthrough -- teclistamab has breakthrough designation, and both of them were moving forward very aggressively. We see just excellent data. We see the tolerability as particularly good. We see the outcome as particularly good relative to other CD3 redirectors. And I want to mention one thing that's very important here is the -- going back to what I said at the beginning, we're creating regimens. So we have running right now a combination of the BCMA CD3 teclistamab with DARZALEX. And if you recall, DARZALEX not only has activity, obviously, against multiple myeloma, but it has immune-modulating activity. It does clear out some -- like some myeloid-derived suppressor cells. It increases clonality. So we believe that combination where we've already yielded data that it's really effective and works better together. We're going to really hammer on that and see how far we can take that as a regimen. And depending on how that goes, we may move those combination concepts to -- with DARZALEX to other CD3 redirectors as well. So we get the question sometimes coming back, like do you have to choose between CAR-T and the CD3 redirectors? I believe there's different cohorts of individuals in the real world that come in that have different circumstances. Some are particularly ill and need urgent attention. They're not going to be able to -- they're not going to be great candidates for Cilta-cel. They may be ideal candidates for a CD3 redirector program, maybe following a treatment with DARZALEX or in combination. So we have these various ways of constructing our regimens that we believe, just from what I said, in 3 years is going to make a world of difference to patients with multiple myeloma, and then we have other therapies that might address multiple myeloma by other mechanisms. Talquetamab is another example of a different antigen, GPRC5D, that's also found on multiple myeloma cells, plasma cells. And if, for some reason, BCMA, we hit a wall or the patients hit a wall, we can use talquetamab either by itself in combination following other therapies so as to rescue these patients that they get in trouble, and there are others beneath that as well. So I don't know -- I think we're a company right now that's incredibly, strongly committed to heading towards cure in multiple myeloma.

Great. Well, obviously, really, really exciting and lots of progress. I guess 2 follow-ups is on the competitive landscape. So as you think about the profile, Cilta-cel, your CAR-T BCMA, how do you think that stacks up as -- I know these cross-trial comparisons are difficult, but as you think about the profile there, maybe just give us your perspective. And then the other area where there's been maybe some forward progress is the allogeneic CAR-Ts. And so as you guys think about that, is that something you're also focused on? Do you have any internal programs there to kind of take that off-the-shelf approach and move it forward? Or is the bispecifics kind of the way you get there with an off-the-shelf?

Yes. Great questions. So with the BCMA CAR-T, Cilta-cel, as you just said, the big caveat is cross-trial comparisons. But we are looking at some pretty phenomenal data that I believe are best in class. They're best in class to what's seen, the 18-month survival that I mentioned of 18 months, the very high degree of progression-free overall, that kind of durability. So both the depth of the response and the durability of response, I believe, are best in class. And it's interesting to think of why that might be. And we've offered a number of suggestions, hypotheses, and we're going to continue to explore that. And depending on what we find, we will translate it to other CAR-T cells, NK cells, off-the-shelf technology were those insights. One of the special features of Cilta-cel is it has a dual binder. So this is, you can imagine, a biparatopic thing that binds its target BCMA as a [ vice might ]. Instead of just one spot, it grabs hold of it as a [ vice ]. And that's a particularly high-affinity interaction. And you could easily imagine why that's helpful. Like if the tumor cell, for example, has lower levels of that targeting antigenomic surface, this might be a way of not losing hold, so low density on surface of cells. But we believe that in addition to that, there are other good reasons. This -- the way the cell is manufactured and the CAR is installed in the T cell makes also other very interesting features. For example, the time to any degree of cytokine release syndrome seems narrowly in that 7- to 9-day window. There too, what that might provide is the potential for patients to be treated in the outpatient setting. That's going to be huge from an access standpoint as opposed to a very burdensome state for patients. So not only are our data excellent as you're asking and I think strongly differentiated, but some key features and a mechanistic explanation might make it particularly an accessible CAR-T.

Okay. Great. Maybe we'll touch on amivantamab now. Congrats on the FDA approval. You mentioned this earlier in your remarks. Maybe just remind us where this fits in the treatment paradigm right now for the current population. And then as you think about that sequencing question, I guess, what percentage of patients in the U.S. are already receiving NGS for their tumors and kind of would already know their status for this specific mutation?

Yes. So this is a fantastic question. Actually, I haven't decided to answer it. So first of all, with amivantamab, the -- right now, we have accelerated approval. We call it RYBREVANT, so amivantamab for the treatment of patients with locally advanced or metastatic non-small cell lung cancer. And these are of the category where the EGFR has an exon 20 insertion mutation in it. So exon 20 somewhat messes up the tyrosine kinase binding site. So other tyrosine kinase inhibitors would have trouble getting at tumors of this type. So amivantamab, just as a reminder to everyone listening, does not bind the tyrosine kinase site. So it is a dual-binding bispecific that instead engages EGFR on the top of the -- like the extracellular domain, so is oblivious irrespective of what's going on within the tyrosine kinase domain. So that's very different and very special. Plus the other specificity that it carries is it binds cMET. And cMET is often, in response to EGFR inhibition, is one of the important resistance mechanisms where it comes up. So taking advantage of this alternate engagement mechanism for EGFR and getting in front of any workaround the tumor might have is part of the reason RYBREVANT and amivantamab, we believe, is very special. And so the way that will work now going forward is we'll look at it in combination with lazertinib, which is a next-generation tyrosine kinase inhibitor. And so beyond these exon 20 insertion mutations, we're going to move into the broader EGFR mutation class where not only will amivantamab provide an alternate engagement mechanism and better response as a result, but we're using like a best-in-class, late -- next-generation tyrosine kinase inhibitor and lazertinib. You asked about sequencing, and this is important. So it is still a minority of people that have NGS sequences that would understand their tumor. This is going to be an issue across the board for many mutation-specific treatments, precision medicine that's coming in our industry. What we're doing -- I mentioned the importance of data science before, what we're doing is we're working on a methodology where we can use histopathology slides to infer an EGFR mutation of the right type. And that's a big deal because everyone has a biopsy. And everyone gets slides [ domain ]. And so that's not a done deal, and we're going to update on that as time goes on. But I just want to give a heads up of the kind of thing we think about. And it's patient access that's the most important. So if we can get everyone to understand that they are a candidate by practically understanding that not everyone is getting their tumors fully sequenced, the patients will be better off.

Great. And maybe just one last one before we move on to another program is I know you're running the head-to-head trial. You referenced this versus TAGRISSO. Is there an opportunity for -- I think ClinicalTrials.gov suggests data 2024 time frame. Is there a possibility that data could have an interim analysis before that time frame and we might see data before then?

We do have planned interim analyses, but right now, we should just expect it in full as ClinicalTrials says. But we do have opportunities depending on how good the combination is to take a look. And if it's supportive, then come forward quicker.

Okay. Okay. Great. Another -- outside of oncology, another interesting program in Phase II that I think has been more below the radar maybe is this Factor XIa inhibitor that you're working on with your partner, Bristol-Myers. There's 2 Phase II trials going on. I think we're expecting data from the total knee replacement study here this year and then the stroke prevention study next year. Maybe just talk to us about the robustness of the genetic preclinical and clinical data that validate Factor XIa as a target. And then what are you hoping to see from these Phase II trials to give you and your partner confidence in moving into a broader Phase III program?

Yes. Great question. Super excited about this program. We and our partner, BMS, are both really excited about this program. So just as a reminder, this is a Factor XI inhibitor -- Factor XIa inhibitor. And so it's not a very old discovery. It's fairly recent that there's a kind of hemophilia, called hemophilia C, out there that's not even really recognized until recently as a form of hemophilia where people are deficient in Factor XI. And so what that yields is -- and there aren't a lot of these people. So there is genetic evidence here, but it's not like there are hundreds of thousands of these people. But from what we could discern among groups of patients that are deficient in Factor XI is they do have sometimes mild like nose bleed or brushing your teeth kind of bleed, but they don't have bleeds per se that are clinically concerning, the kind that one would have with other forms of hemophilia. There isn't enough evidence from the genetics alone to understand that they're protected against ischemic strokes. But that's our hypothesis that we're largely testing in the study, whether we can have efficacy with the promise of genetic -- the genetics from a bleeding perspective, not having as much bleeding as a Factor X or other ways of stopping clots. And so this is our big task. As you said, there's the axiomatic total knee replacement study of -- in the product called milvexian. So that's what we're -- the name of the Factor XI inhibitor. So axiomatic total knee replacement will read out a little bit later this year. And the secondary stroke prevention, another axiomatic study, will read out after that. Both of these are really important. The first one compares milvexian to enoxaparin. So -- and enoxaparin is a standard of care following total knee replacement. And so that's going to be a really important study. We'll look -- we'll judge the results based on adequate efficacy relative to enoxaparin, but hopefully, reduced clinically relevant bleeding rates. And we think there's enough signal there that we'll be able to tell the difference. Axiomatic secondary stroke protection is -- prevention, sorry, is different. Milvexian's added to aspirin and clopidogrel, which is the standard of therapy in secondary stroke prevention. There, we began recruitment in 2018. It's ongoing. It's very much on track. Particularly proud of the teams, by the way, on both these studies that they kept everything running through heroic measures through COVID. So we remain more or less on track to report results as we've said for some time. And when there's data, we'll talk about it more. But this could be a game changer depending on exactly what we see.

Okay. Great. Yes, looking forward to seeing that data here over the near term. Obviously, one other area that's highly topical right now is Alzheimer's disease given the Biogen aducanumab approval yesterday. I know you guys have been working in Alzheimer's for a long time, and you have a tau program in development. But just would welcome your perspective on kind of what this approval means for the industry, maybe how you think about Alzheimer's drug development and then how we should think about your tau program and when we might see the initial Phase II data.

So Alzheimer's disease and other neurodegenerative conditions, there's probably nothing more serious or more an unmet need right now in the world than that as the population in the world ages, and many, many people suffer the ravages of Alzheimer's disease. So it's a massive area of investigation. It's also a massive area of historically a failure after failure after failure because the biology of how one develops Alzheimer's is still not super clear. So I congratulate my colleagues at Biogen for moving this into the -- now the marketed space, and it's an incredible achievement. I think it does float a lot of boats right now, like that event. We're committed for the long term in this space. And we've been working, as you mentioned right now, on a tau program that's quite different from some of the other tau programs. So tau is a key protein in these tangles that when seeded, kind of spread around the brain and are -- work in conjunction with the amyloid to actually cause the pathology. So it's a critical component, we think, both alone and in combination with amyloid to cause Alzheimer's disease. So our tau program, though, is different in that the antibody binds to a phosphorylated protein in the middle of tau, what we call the mid-domain binder. And the reason that's really important is that the ends of tau where other tau programs have targeted, they disappear because the -- in the processing, sometimes they get ripped away. So it's an incomplete engagement, we feel, to go for a tau that binds to these ends of tau. So it's a very differentiated program that way. We don't think the other approach, in fact, has as high a chance. And so we'll be looking forward to data in the coming year or so on some data, a little bit more than that maybe for looking at some of the preliminary data. And then behind that, we have a strong program, highly committed. We have, through past efforts in Alzheimer's disease, some very specialized ways of identifying patients at different times, different states of their pathology. Our PET biomarker capabilities and impact on this program are huge. And so that's going to be a key element of how we define our patients as we look forward to data from the tau program.

Great. Maybe last question here in the interest of time is the regulatory framework for the JAK inhibitors is another topic that's top of mind for a number of folks here. You guys are developing TD-1473, which is a local acting JAK for IBD. And you're running, I think, a pretty broad Phase IIb study right now. So maybe just would welcome your perspective on risk/benefit here for the category. And then how should we think about what you need to see to advance into Phase III?

Yes. So systemic JAK inhibitors are effective and they offer patients a great deal of benefit. But as you said and as we all know, they come with safety concerns and black box warnings, and ultimately, limit efficacy because there's probably a ceiling on systemic exposure. And the regulators are very focused on that. So the compound you're referring to, 1473, now named is izencitinib. This has got restricted following World administration. So our partners at Theravance have worked on a molecule that when taken orally are absorbed just into the lamina propria and don't really go beyond the relevant portions of the gut where all the immune actions is. So this is in a pretty big study right now. And we're quite hopeful that regulators will consider this kind of drug differently as there isn't -- there really isn't substantial or even much at all systemic exposure. So all the effects that the regulators and clinicians and myself worry about with systemic JAK inhibitors should be avoided entirely. The analogy here, I think, appropriately, is inhaled steroids versus systemic steroids. One is they both can be very effective, but one is a whole lot more tolerable and safer than the other. And the regulators have learned to think about those topical versus systemic therapies quite differently. So we'll see when there's data, like what -- with the more advanced clinical outcomes and pharmacokinetics, we'll have a package that we'll then take to regulators to be able to have this exact conversation.

Okay. Great. Well, thanks so much, Mathai. I really appreciate your time and insights today, and best of luck and stay safe.

Thank you, Terence. Appreciate the opportunity.

Thank you. Take care, everybody.