The afternoon sessions of the first day of the BofA Health Care Conference. My name is Geoff Meacham. I'm the senior biopharma analyst here at BofA, and Charlie Yang from my team is on stage as well. So we're thrilled today to have Johnson & Johnson, and with us on stage here is John Reed, who's Executive VP, Innovative Medicine, from the R&D side. So John, thanks a lot for joining us. Thank you, Geoff. Great to be here. What we'll do is just, if you wanna give us a high level, kind of set up the stage here for, you know, what, what to expect here from a, you know, sort of a pipeline perspective, and then we have- Right Lots of questions. Yeah. Well, I have to say, the pipeline has just been like a rocket ship. We enjoyed last year a 90% success rate across all stages of the pipeline, and in the first quarter this year, about 85%. So really kind of industry leading success rates, and the the momentum has just gotten so strong in oncology, immunology, even in neuroscience now. We see a lot of opportunity just in the recently launched medicines. If you look in myeloma, where we're number one, and we're number one and number two overall in hematologic malignancies, you've got TECVAYLI, TALVEY, CARVYKTI, so first-in-class T- cell redirector bispecifics, as well as the best-in-class CAR-T cells that, you know, have recently been getting additional line extension approvals, building on our success with DARZALEX, the CD... You know, the first biologic for myeloma, the CD38 targeting molecule. So really exciting momentum there as we move these into earlier lines of therapy and in combinations. In prostate cancer, where J&J is also number one, recent data in the early space, with adjuvant therapy, they were looking really interesting and more readouts to come. But in the late stage, in metastatic, we have four new mechanisms in the clinic: radiopharmaceuticals, T-cell engagers, ADCs, CAR-T cells, so really exciting momentum there. And then in lung cancer with RYBREVANT, the world's- Yeah first bispecific for a solid tumor indication, targeting two growth factor receptors, really what we think is the new standard of care for EGFR receptor mutant lung cancer. So that's just in oncology, and then in immunology, we'll be sharing next weekend our data in inflammatory bowel disease with TREMFYA, our selective IL-23 biologic. And, and then SPRAVATO, the first new mechanism for depression in more than half a century, continues to gain market share and acceptance. We just had a monotherapy set of data. They're beautiful. Best effect sizes seen in that space, so really transformational therapy. So those are even the things that have just recently been approved. And then the pipeline of, you know, new modalities that are seeking their first approval has really been, really exciting. So maybe we can get into some of that during the- Yeah. Yeah during the interview. Well, let's talk about myeloma first. Okay. So obviously, a huge contributor to you guys. Maybe I guess the question is, like, where are we for DARZALEX as a foundational therapy in myeloma, obviously foundational in your P&L? But you know, give us a perspective on what's ahead and, you know, in terms of share opportunities, lifecycle management opportunities. Yeah, DARZALEX continues to grow. It's actually now our largest-selling product, having displaced, STELARA, which, went off patent recently. And we've been getting more and more, traction in the front-line setting as, we release data like the PERSEUS study that we showed at the ASH Meeting in the American Society of Hematology. We're added on to the most, prevalent or common backbone regimen. We've, you know, had progression-free survival at unprecedented. I think the hazard ratio was, you know, 0.3 something. Actually, no, it was 0.58. So, you know, reducing the risk of progression by more than half. And, so we're getting more and more traction there. Plus, you know, in myeloma, there's this kind of pre, cancerous, if you want to call it, state, smoldering myeloma- Yep where patients have not yet met the diagnosis. So we're going to have data on that in combination with REVLIMID pretty soon. That could open up that, which is a big space. And then, you know, going forward, we're doing combos of DARZALEX with our TECVAYLI and TALVEY, our T-cell engagers, so that's looking more and more promising too. And even have collaborations with academic investigators who are taking those again into smoldering myeloma, trying to intercept disease early and even into MGUS, which is an even more prevalent, even earlier- Yep sort of pre-neoplastic state. So I think there's still a lot of opportunity with Dar. It's still the only sub-Q option for CD38 therapy out there, and it's, you know, become more and more a backbone of almost every regimen out there. Sounds great. Yeah, and then the next, you know, conversation obviously will shift to cell therapies with CARVYKTI. Right. So, fantastic data in last line and then moving up the paradigm. Maybe just help us, John, with where we are in the manufacturing, you know, capacity. Yep. That tends to be a rate-limiting, you know, step. Mm-hmm. Is 2025 the year that you think we'll be more free and clear of capacity, and kind of what does that mean for the paradigm? Yeah. So it's certainly been a journey. Autologous CAR-T is, it's a steep hill to climb. But fortunately, I mean, CARVYKTI has been such an effective product that it certainly gives us the motivation to do what's necessary. You know, you if you saw in the second line, where we just recently got the approval. T he CARTITUDE-4 data, you know, hazard ratio, what was it? 0.26, the best- Yeah - hazard ratio ever produced with any therapy in myeloma. I mean, my goodness! So yes, we've been expanding the number of sites. We recently built and opened a new facility in Ghent, Belgium, to supply the European market. We've been expanding our sites in New Jersey, partnerships with other companies to expand into their excess capacity to give us more slots. On the lentivirus, which had often been kind of a rate-limiting component of these, we've really mastered that technology now and have now gotten FDA clearance on a 50-liter scale. So we don't see that being a rate-limiting step anymore for us. And then, you know, behind the scenes, we're working on all kinds of ways of automating and roboticizing this process so that it can be even more high throughput and higher scale. We announced a partnership last year with a U.K.-based engineering company called Cellular Origins. And then we're leveraging all those scores of engineers we have in MedTech at J&J, and have got them also in our labs, helping us to figure out how to make more of this an automated closed system process that we can do at scale. So, you know, it's a journey, but- Yeah feel good about the progress we're making. As you move it, CARVYKTI, to earlier lines of therapy, I know that, you know- Mm-hmm. FDA recently updated guidance for MRD negativity that should- Yeah help with trials and development. But what are the, you know, the challenges of moving up the paradigm, and obviously, the benefits are, you know, a huge number of patients and, you know, long duration- Right - therapy or long benefit. Yeah, I think so. Regardless of the therapy, indeed, as you move to earlier lines, you're gonna have to wait longer for definitive clinical readouts. So the FDA pronouncement that they would allow the minimal residual disease as a potential approval endpoint is a really nice opportunity then to, you know, to be able to, frankly, justify the investment of going into these really early spaces. But that will, you know, won't solve the problem in other countries unless they get on board with this at some point. At this point, they're still requiring the usual progression-free survival, overall survival types of endpoints. So our studies so far are still designed with those classic endpoints, but we are looking at whether MRD negativity in very, very early, like smoldering or things like this, could be a way to go in the future. In terms of CAR-T in these earlier lines, I think that's really interesting because, you know, the standard of care for patients who can tolerate it is to go through an autologous bone marrow transplant, which is not trivial, right? There's a high, pretty, pretty significant mortality rate associated with that, high risk of secondary malignancies. So if we can offer as an alternative to that, to try to get that residual disease under control with a CAR-T therapy, I think that could be a complete paradigm changer for early-stage myeloma. I guess last question on myeloma. When you think about bispecifics, lots of exciting assets that, you know, are coming up the paradigm at J&J. Yep. How does it all play out? You know, do you see DARZALEX maintaining its first line, and then you sort of have this wave of cell therapy, CAR-Ts, middle of the paradigm, and then bispecific? How do they-- How does it- We're frankly trying to move everything in the front line. Okay. So we're doing combos of Dara with Tec or Tal, and seeing if we could move that into the front line. Then, as I said, as an alternative to bone marrow transplant in the front line, having the CAR-Ts then to sort of polish it off. So that would be the dream, is to bring these all into the front line. Gotcha. Okay. Charlie, you want? May I follow up on that just quickly? Just in terms of how, like, the big cells potentially thinking about for the bispecifics, right? Is the base pilot, base case for them to be used in a front-line setting? You know, I think we see that as a potential for the future. We have to generate the data to, you know, prove it. Currently, it's more in the later lines. And for patients that maybe CAR-T is not the right solution for them, this turns out to be a, you know, a very good way to come in and, in a different way, engage the immune system. Particularly popular outside the U.S., where CAR-T is not usually reimbursed in most countries. So we really see it as, you know, a couple different ways to solve the problem for patients. We also find some patients just have preferences. Like, we've talked to some patients who love the prospect of going on a CAR-T, where then they could have long remissions and not have to worry about taking a medicine every day or every week. And then we have others who, you know, when they've relapsed, they go: "I, I don't want to wait because the CAR-T cells take a few weeks to prepare. I don't wanna wait. I want something I can just jump to now." And so they prefer the bispecifics. So it's nice to have different, different ways of trying to crack the problem for patients, depending on their preferences and their circumstances. Got it. How about from, like, the competitive dynamics kind of standpoint, just within your own kind of bispecif- bispecifics versus CAR-Ts or potentially kind of other CAR-Ts in place in terms of kind of taking out the, you know, the best, taking out the infusion spot? You know, how, like, how impacting, how your, kind, progression this year, and then maybe, you know, just to follow to that, kind of think about other potential competitors coming up in, in potentially in a couple of years. Now, how, how is J&J thinking about that? Well, it's certainly becoming competitive. J&J has the advantage that we were first in class with these mechanisms, first in class with CD38 Darzalex, first in class with the BCMA targeting, first in class with GPRC5D, which is actually an antigen we discovered in our own labs. You know, others, once they see something works, they try to copy it and come in behind you, so it will be competitive. But I think the combinations, the, you know, the fact that we have such a diversified portfolio, that we can bring combinations together, that others, maybe have one of the assets, but not all the assets. So, and then, you know, we never stop inventing. Like, we've got an early development right now, a molecule I'm super excited about. It's a trispecific that gets BCMA and GPRC5D in a T-cell engager. So you have the CD3 arm to grab the T cell, and then two targets on the myeloma. And that way, if the myeloma becomes smart enough to try to, you know, downregulate one of the targets to try to escape, the other one's still there, so much less, you know, resistance problems. The early data are still coming in, but, you know. So, yeah, we just keep moving on. We try to disrupt ourselves rather than have somebody else do it. Yeah. Great. John, would you view, you know, JJ's capabilities and CAR-T and cell therapy, you know, as a broadly strategic, you know, advantage? I know in myeloma, clearly, you know, the partnership with Legend, but you look at other liquid tumor types, is that something that you would rather—a modality you'd rather go after or a bispecific, or is it all of the above? Yeah, I guess, you know, we've taken more of a multiple approaches approach. If you look at what we're doing in B-cell malignancy, where, you know, our kind of entry point there was the BTK inhibitor, IMBRUVICA, the first BTK inhibitor, which has been an amazing molecule, and we've even been building on that with, you know, the data we just shared at the last ASH meeting in frontline CLL in combo with venetoclax. Yep. The new standard of care, IMBRUVICA plus venetoclax. But we have in the clinic now, a CD19, CD20 Bi-CAR for lymphoma, and then we have a tri-specific for lymphoma, with CD20 and CD79b and CD3, and we have a co-stim with CD28 and CD19. So we're, you know, we're again, building up both the, you know, multifunctional biologics and, you know, the kind of multifunctional CAR-Ts to see if we can break through to the next wave of innovation in that space. And then, we're trying to do some of this in solid tumors. You know, in prostate cancer, you know, we've got, a CAR-T targeting a thing called KLK2, which is the most selective prostate cancer marker out there. It's expressed prostate only, not, unlike PSMA and some of those, it spill into other tissues. We have a radiopharmaceutical targeting that, an alpha emitter. We have a T-cell engager targeting that, and then we, on the bispecific PSMA side, we've got an antibody-drug conjugate and a CD28 bispecific. So really using multiple approaches, 'cause it's gonna take combinations to win the war against cancer, and- Yep so we're trying to bring all the weapons we can bring to bear for those areas where we really commit. Just along those lines, I mean, let's switch gears to bladder cancer and the TARIS platform. So, you guys had recent data at the, you know, AUA meeting, but maybe just take a step back and just give us a bit of a history here of- Yep you know, what gives you the conviction and the platform and, you know, what makes you excited about this Yep as a new strategy? Yeah, and I think, so this, for those who don't know, this is a drug device combo that is inserted in the bladder for early bladder cancer, which is a huge problem. 600,000 new cases a year of early bladder cancer. It's the most expensive oncology indication today to manage, 'cause it's kind of like whack-a-mole, where they have multiple tumors popping up in the bladder, and the urologists are in there with the scopes, et cetera, and try to chop them out and catch them. Most patients, though, end up losing their bladder, which, as you can imagine, what that does to the quality of life that patients suffer through without a bladder. So to have a bladder-sparing option is really a game changer. So, you know, by having the drug device combo, we've been able to really achieve unprecedented levels of complete responses. Now, the journey started with the acquisition of TARIS, which had made a prototype version of this device that releases gemcitabine, good old chemotherapy, with a, you know, controlled pharmacology, so it just comes out at a nice, steady rate, and it can sit there for weeks. But that was not optimized, and they were building those one at a time by hand. So our engineers whipped that into shape, got it ready for mass manufacturing, optimized elements of it. We put that in the clinic, and we've got breakthrough designation on that now. And the data we showed at the AUA, it's just single-arm data, but it's so compelling, with 83% complete response. Of the responders, 85% still in remission, best in disease, activity. So we're gonna file on that using the breakthrough designation while we do more advanced studies. And then on top of that, again, the engineers with our process chemists and came up with another one with a targeted therapy, erdafitinib, our FGFR receptor inhibitor, and made an entirely new device, different technology. Uses a barrier diffusion technology rather than an osmotic technology. That releases the drug with consistent pharmacology, not for three weeks, but three months, and that has given 90%+ complete response rates in the clinic. So it's just a completely transformational therapy that only a J&J could do with a device and a drug, where we got MedT ech and pharma under one roof. Yep, makes sense. Charlie, you want to? Maybe you want to maybe talk about like some of the. I know you mentioned kind of like the efficacy or the durability. You know, what else do you think is the differentiating factor for the TARIS platform? Kind of especially in light of all this emerging therapies out there. Yeah, I think the tolerability is outstanding, and it's something that just fits so easily in the urologist practice, right? So they, you know, they don't like to give systemic therapies and IV infusions or things like this, but they like to use the scope and the catheters. It's an intravesical treatment. It takes about two minutes to insert it. It takes about one minute to take one out using standard technologies that the urologists use all the time. So we just feel it just fits so well into the practice, well-tolerated, you know, outstanding efficacy. So we feel like we've really got a winner here. Would you say that, you know, this is essentially kind of all the HCP out there, or at least, you know, nurses can also do these procedures as well? Yeah, that's right, and that's probably what will happen, especially outside the United States. But yeah, you know, a really trained nursing staff, it's quite simple. It's not much different than doing, you know, as if you're doing a catheterization just to remove, you know, urinary urine from the bladder or something. It's not that much more complicated than that, frankly. You good? Yeah. So let's switch gears to lung cancer. Okay. The lazertinib, RYBREVANT combo. Maybe just take a step back in the recent MARIPOSA data, you know, how does J&J look at this relative to, say, a standard of care, like TAGRISSO? Can both parties, you know, win? It's not. Usually, these markets aren't a zero-sum game. It's kind of how we think about it, but I wanted to, you know, just get your- Mm-hmm. - your perspective on the approach to moving up the paradigm and- Yep and how you, you see yourself competitively. Yeah, and I mean, you make a good point that there's no shortage of lung cancer, right? It's extremely common, extremely deadly still. But you know, in the head-to-head, the MARIPOSA study, for those who don't know, was osimertinib versus two different ways of attacking the EGF receptor pathway. One was a third-generation lazertinib, which is a third-generation tyrosine kinase inhibitor, oral small molecule that hits a bunch of the resistance mutations and is brain penetrant. Important because very often when patients with lung cancers relapse or end up in dire straits, it's because of brain metastases. And then RYBREVANT, a bispecific antibody that gets the EGF receptor, yes, but also another growth factor receptor, c-Met, which is often involved in resistance to EGF receptors. So we're anticipating the resistance mechanisms and trying to stay ahead of them. The molecule is also fully immune competent, so the, the tail of it, the Fc region, recruits immune cells, and we think that's also an important part of the mechanism that is brought to bear that you would not get in a small molecule, EGF receptor inhibitor. So with this multidimensional way to try to attack, you know, we saw outstanding progression-free survival. The overall survival data are still maturing, but they look very very encouraging. The PFS2, which is sometimes used as a way of kind of predicting where OS might go, those data were outstanding as well. All this in the front line setting. So those have been submitted on a global basis, and, you know, we're waiting for the approvals. But while we were waiting, we started further evolving the regimen, so we now have a sub-Q. So instead of IV, you'll see those data at ASCO. The pharmacology, the efficacy, everything beautiful, but you also have now the convenience of sub-Q, but also better tolerability because the IV preparation had some infusion reaction issues. This one now, very clean. And then we also had in the first studies, probably because we were inducing so much tumor cell lysis, that can lead to venous thrombosis, like. So we now do prophylactic anticoagulants with our XARELTO for four months. Takes care of that. And then EGF targeting therapies always have some skin tox, but we now have a prophylactic use of skin treatments that are ameliorating that to some extent. So all that work is helping to further optimize the regimen, make it more tolerable for patients, more convenient for patients. So we feel really good about that. And then in the second line, you know, we had great data in combination with chemo for a couple different types of EGF receptor mutations. So it's, you know, all the data sets have just been really stellar on the progression-free survival. The regulatory path for sub-Q, is it just sort of a bridging mechanism, or do you have to run a? We have efficacy as well. So we feel like we've got the package that allows us to submit sometime this year. Okay. Perfect. And maybe just on the, I guess, again, like, kind of competitive dynamics, you know, with the first line- Yep You know, versus TAGRISSO or versus TAGRISSO plus chemo. You know, I know this is, like, more of a chemo-free option But kind of what's the feedback from, you know, physician, from docs in terms of how they're thinking about the, the data that they have seen so far? Right versus kind of the patient convenience or? Yeah, as I said, I think the efforts we've been making to make the regimen we have with lazertinib and RYBREVANT, a chemo-free one, to make it better, more tolerable, more convenient, will really help there. I mean, chemo is no walk in the park, as you know. So, I know most of the oncologists we talk to really like to have the chemo in their back pocket for when patients relapse, and they usually do relapse at some point. So if you've already used that, you really don't have much to turn to in the second-line setting, which I think is why the PFS2 data are informative, right? Because if you relapse, if the patient's relapse after RYBREVANT lazertinib, you still have chemo that you can turn to and buy some more time for the patient. You know, if you're doing that up front, you've kind of used all your ammunition and now you're left with nothing. Got it. Are we going to expect to see OS data later this year as well, or? Maybe. It's event-driven. Okay. It could be later this year, but we can't promise because it's event-driven. Got it. Mm-hmm. Yeah. So oral IL-23, there's a- Yes, sir. A lot to talk about J&J, so there's a number of programs we can ask about. But, so, you know, 2113, give us some context for how you think that shapes up to the standard of care today or an emerging standard of care? Right For example, for TYK2s. Yeah. You know, maybe just a little background. So this is a what we call a targeted oral peptide, so to that binds to the IL-23 receptor and inhibits it. And that is really difficult chemistry, but the teams use these complex cyclic peptides that we got a starting point from a collaborator, Protagonist, and then over, I think, a three or four-year journey, just, you know, solve problem after problem till we have now a well-behaved molecule. We can give it orally. So it's very stable and very potent. So we're doing once-a-day dosing and have seen in the, you know, the phase two data in psoriasis just, you know, beautiful efficacy, along with the pristine safety you've come to expect from IL-23 selective inhibitors. So we're in the middle of the phase three campaign for psoriasis, while we're now starting,,we've started phase two studies and some other indications like ulcerative colitis. But just to give you a sense, I think, of how much interest there is in having an oral option on the part of patients, we enrolled the phase three psoriasis studies in one-third the time that it normally takes to do a phase III study in that indication. Patients are just flocking to the protocol. And as we know, when you look at diseases like psoriasis, there's a- Mm-hmm you know, let's say, a relatively low penetration rate in terms of the percentage of patients who are eligible for advanced therapy, who actually take one. Yeah. And that's because of the resistance of some of the. Either there's a resistance to the injections or there's concern about safety, which you have with some of the other oral therapies, where instead of selectively targeting the receptor, you're targeting signal transducing kinases, that, yes, they play a role in your desired receptor, IL-23, but they also play roles in other receptors, too, and then you get this collateral damage in terms of the risk of safety. So, so we've just seen enormous enthusiasm for it, and the molecule's been behaving beautifully. And then the final thing I would say, which is not trivial, is the manufacturing. So, you know, we're not making this like you would a GLP peptide, where you have, like, a solid support, and you add one amino acid at a time. This has been done with a completely non-solid phase, a completely solution phase chemistry using convergent synthesis. We've driven down the cost of goods by 100-fold and have scaled this to multi-kilogram scale. It's really a beautiful piece of process chemistry that the team has done as well. I think the last question here, just to sort of tie everything together, you know, you talked a little bit at the beginning about, you know, J&J's approach and top-down, but from a, say, a BD versus a licensing perspective, there's a lot of in-house innovation that J&J, you know, can push forward, but there's also, you know, opportunities for, you know, partnering as well. So- Sure. How do you think about that going forward, you know, with so many companies and with sort of nifty technologies, but maybe not quite products, right? Right. This is a perfect spot for you guys. Yeah. I mean, look, we have a broad partnering agenda, and I think J&J's been known with that, when they we have these kind of, you know, unique approaches, like innovation centers around the world and JLABS and things like this, where we, you know, try to have scouts out in the four corners of the globe, looking for interesting technologies and assets, and incubating companies. Usually, we'll have, like, 50 companies per JLAB at different eco you know, innovation centers around the world. But we play in both the platform side and the product side. So some things are supplementing the pod pipeline. Like I just mentioned, the Protagonist collaboration that led to the IL-23 inhibitor, 2113. Others are more the platform side. On the, you know, on the CAR-T side, for example, we acquired a company called Serotiny, which has an AI-enabled, high-throughput way of optimizing the CAR construct. And then we partnered with Cellular Origins on the robotics and automation side for the manufacturing. So, you know, we're playing both the platform and the product side, as part of our overall innovation agenda. Gotcha. Okay. Well, John, thank you very much. Oh, thank you, Geoff. Thanks, Charlie. Thank you.