Good morning, everyone. Welcome to our next panel discussion with Gilead Sciences. We have a couple of important members of the executive team from Gilead here up with us. To my left, Dietmar Berger, who's the new CMO, and I like to say running the hot seat of R&D in front of Wall Street to talk about, obviously, everything going on in the pipeline, as well as Cindy Perettie. She's Executive Vice President of Kite and runs everything at Cell Therapy, which is obviously a very important part of Gilead as well. We are going to talk about both of those organizations. Maybe I just first thought we could start with Dietmar. You've now been at the role for six months. I'd like to think at this other broker conference in January in San Francisco where we first got introduced to you.
It's an important role at Gilead to oversee everything in the pipeline. Maybe you could just tell us a little bit about, in your first six months, how you're thinking about Gilead's pipeline in the near and the midterm. Obviously, HIV is a part of that, but also non-HIV. How should we think about Gilead's R&D pipeline now that you've been in the seat?
Yeah, great. Thanks a lot for having us and really happy to be here and to speak about the pipeline. What I've seen over the last six months is really the story is coming together very nicely. The focus is on virology, oncology, and immunology. Those are the key therapeutic areas that are at the center of what we're doing. I very much agree to that focus. This is really where we want to double down. In all of those areas, you see the pipeline nicely progressing, right? On the virology side, we have lenacapavir as kind of the biggest event coming, especially in prevention for HIV. The PDUFA date for that is June 19th. We are really looking forward to that.
Yeah, as you said, it's a holiday, so maybe June 18th.
Yeah, maybe June 18th, but let's see how this turns out. Exactly, June 18th is a holiday. We have on the oncology side, most recently, we had positive data with TRODELVY in the first-line setting for triple-negative breast cancer. That, of course, gives us really good validation on the oncology side. The first-line triple-negative setting is a setting of large unmet medical need. This is the most severe setting of breast cancer. Going from second-line to first-line really gives us access to about double the patient population, really gives us a possibility to serve those patients in need. Duration of therapy is also longer in the first line. That gives us a real opportunity. We have other studies coming for TRODELVY. That story is also nicely coming together. On the oncology side also, you've got Anito-cel, right?
We can talk more about that from the Kite perspective in myeloma. We have an emerging, and I believe really interesting immunology portfolio with an oral alpha-4 beta-7, with an IRAK4, with a STAT6 degrader. I believe that's also a really important piece of the portfolio. Overall, if you look at the portfolio, in my view, there's a lot of opportunity. The focus on virology, immunology, oncology is the right focus for us. You'll see us build and grow in all of those three areas.
Perfect. Okay. With HIV, since that is, as you said, quite timely, counting down the days to June 19th, Marty McHerry will be here later this afternoon. Maybe you could just talk to the audience about how FDA interactions are going on lenacapavir. You have breakthrough therapy on this program, but it has been a review process certainly over the last few months during the new administration. People are a little bit nervous about review. Maybe just tell us a little bit about how that's been going. You fully expected an approval in just a few weeks?
Yeah. The interactions that we had with FDA on lenacapavir have been going absolutely as planned. No surprises, no irregularities or concerns. So we are reassured, right? We're sticking with the PDUFA date this time. We have no other information. Really looking forward to bring that opportunity to the prevention setting, to the community. We're ready for that launch. And it's a really important component also of our overall approach to virology, where we have the potential to have up to nine additional launches, right, before 2033, which really is an important piece of the portfolio, adding more optionality both on the prevention side and on the treatment side. So really think from a longer-term perspective. There's a lot of opportunity there.
Talking about that broader interaction also from a development perspective, also when we think about clinical trials and clinical trial interactions, all of those with FDA have been going well.
Okay. Okay. We'll find out in a few weeks. Hopefully, that's all settled away. Now, to just add on that, obviously, again, very important this year is that Gilead and Johanna have been quite bullish, at least that's our perception of the potential launch of this drug post-June 19th. What should the messaging be for investors in terms of how you think or how Gilead is expecting the launch of this important new PrEP drug to be?
Yeah, we are ready. We worked a lot on that launch. Obviously, Johanna would be much better to answer those questions. We are approaching the launch in a very cross-functional way as well. We are really building capabilities around the prescribers and the sites. All the way from coming from a sales perspective, from a medical perspective, reimbursement perspective, nurse coordinators, really thinking about the different aspects that are necessary to have a successful launch with a once-every-six-month subcutaneous prevention approach, right? The feedback that we're getting from the community, from both the people who receive the prevention, but then also the prescribers, has been really positive, both with regards to the data, but then also with regards to how we're approaching this space. We feel we're ready.
That actually leads to a second question with which you're overseeing, which is the other developments within PrEP. If the once-every-six-month injection is successful, then you are still working on actually a broader portfolio in PrEP. We'll get to treatment in a second, which includes a once-every-year injection. It's not once every six months. You got a once-every-year injection. That actually, I learned recently, has already started phase three. Is that another plan to start? You tell me.
Hasn't started yet. Just to be very clear, right? For the current launch, what's important to also note is, I mean, it will, of course, take some time, just to be clear about that, right? Because you will need reimbursement, and you will need to reach out to all of those different sites. We're basically saying within the six-month period, we're going to have access then to roughly about 75% of the sites. I think that will take some time, just to be very clear about that. Talking about the broader prevention space, we had at CROI, that's the big retroviral conference in San Francisco earlier this year, we had data with a once-every-year injection of lenacapavir. That's an intramuscular injection. The study that we presented, the data that we presented is largely pharmacokinetic data.
It shows us that coverage at that level from a PK perspective is actually even stronger than what we've seen with a six-monthly subcutaneous injection. We are very confident that we can offer the same prevention benefit with a once-every-year intramuscular injection. Again, hearing back from the community, hearing from prescribers, having a once-and-done shot once a year is actually what people are really waiting for. That will be an additional option that we bring to that community.
It's all about adding more options.
The phase three will start later this year.
Will start. Okay. Will start. Teaser. Okay. Now, interesting about that one, too, is because as I think back at the development of PrEP programs, even going back to DESCOVY, that was interesting because the endpoint on DESCOVY was obviously infections. It is unique because these are prevention, so you have to look for HIV cases. With lenacapavir, that was also a unique trial design, and it was comparing to expected natural case history as well. Without getting into all the details here, they can take years. It can take years from starting enrollment and then finishing out. Now, is this a program that you could actually bridge PK data to the lenacapavir once every six months, or you need to have FDA discussions, but that is not completely out of the way.
Yeah, absolutely quick.
Could be quicker than expected.
You're absolutely right. There are opportunities for different types of study design, especially in a case where you have lenacapavir. We know lenacapavir. We know the efficacy. We know the pharmacokinetics. We are, of course, in discussions around what's the right study design. The possibility of a PK bridging design is there. We're going to communicate that as we start the phase three, really, what type of design we've chosen.
Last question on HIV before we get to oncology is the idea that the company is quite bullish on the new opportunity for treatment. Now, just to be clear, treatment of HIV is the vast majority of the HIV commercial market. My estimate is 80% of the business, certainly for you guys as well. You guys are trying to transition to also offering options that are coming soon for longer-acting treatment options, not PrEP treatment. Tell us about your maybe top two or three most important ones. That starts with a long-acting pill. You also have longer-acting injections that could be for the treatment of HIV.
Yeah. We think also in treatment, optionality will be really important, right? We have efficacy at this point. We have safety. Optionality for the community is really important with regards to dosing frequency, with regards to what kind of tablet or what kind of approach do they have. We are working on basically daily, weekly, monthly, and every six-month approaches. That is just four different types of patient populations, right? Different types of people with HIV. For example, also at CROI, we had data with a combination of lenacapavir plus two broadly neutralizing antibodies that would be a once-every-six-month therapy, right? We will not compromise on the quality of the response, right? BIKTARVY is really the measure that we have to live up to, right, with no resistance development, et cetera. We want to see that type of efficacy. We have presented the data.
That is another program that we will move forward, obviously, into later-stage studies. That would be for those people, just to give you that example, for those people who want to come to a site once every six months. There is still a lot of stigma associated with the pills, with carrying the pills around, with going to the physician frequently, et cetera, et cetera. Having a once-every-six-month possibility, go to the site, get your infusions, be done with it, is really attractive for part of the population, right? We are working on these other possibilities as well. We are working, for example, on an oral combination of bictegravir and lenacapavir, two-drug combination for people who are currently on really complex regimens where they already developed some resistance and they need different drugs in combination.
We believe that has the possibility to give them a much simpler regimen and, again, to make therapy better for them, basically. We are working on the weekly. We are working on the monthly. We feel moving that forward is really going to be important for the patient.
I'm particularly excited about the once-every-three-month and once-every-six-month injection with the longer-acting integrase to go along with your capsid. That's a real big development if you can get a long-acting integrase.
Exactly.
With that. So those are more earlier, but they are in the clinic.
They are in the clinic.
We'll track that. Okay. That would bridge us then to if you're excited about the potential blockbuster of PrEP that's coming, hopefully after June 19, and that launch goes well, then you've got treatment options that you guys are working on. We have oncology. Let's talk about oncology, near-term, medium-term. First, I'm going to give Cindy an opportunity to talk about this before I get to TRODELVY because we were both at ASCO. Obviously, in a couple of weeks, you are going to have new updated data for Anito-cel. This is the Arcellx BCMA CAR-T. It looks as compelling, more compelling than CARVYKTI from Legend, but they're ahead. Tell us about your view of Arcellx Anito-cel BCMA program, what data is coming at EHA in a couple of weeks, and is this a compelling option versus CARVYKTI?
Thanks for the question. Maybe I'll start with the data, and then I'll talk about our market preparation. With the data that we're going to share next Saturday, it is, I think. Yep.
Next Saturday.
Yeah.
At EHA.
What we've been able to show is an improvement on our complete response rate. The last data cut we shared was at ASH of last year. This data cut is about six months more mature. We have a 97% overall response rate. We're seeing 68% of patients having a complete response rate, which is maturing over time. We expect that that will continue to mature. We have a 93% minimal residual disease. We're excited about the data. We're slightly better than what we saw with CARVYKTI at the exact same time point. From a safety perspective, we continue to see a differentiated safety profile. For grade three and above, CRS or ICANS were at 1% for both. Below that, we're in the low single and double digits, which is perfectly leaning itself towards an outpatient therapy.
We do not see the onset of CRS and ICANS until day four. As I think we have shared previously, that 72-hour window in which patients can remain out of the hospital, those patients who end up having a CRS event or an ICANS event that would need to go to the hospital, we are not observing that for four days. It lends to a really nice therapy that could be delivered in the community. We have not seen any of the long-term or delayed neurotoxicities, so no Parkinsonism, no Guillain-Barré, no cranial nerve palsy. The other piece that we have not observed, which is now something that is being looked at a little more closely from regulators, is enterocolitis. Those are the differentiators as I think about the safety profile overall.
Safer product, no long-term delayed neurotoxicities in that later onset of the CRS and ICANS allows us to think about this therapy as an outpatient therapy. As we move forward, we are getting ready for launch, just as we talked about lenacapavir as well. Today, the Kite footprint around the globe is in 30 markets. In the U.S., as an example, we have 160 authorized treatment centers. We continue to grow that number every year. Globally, we have 550 authorized treatment centers. We would continue to grow that between now and launch. We have the largest footprint of centers that can deliver CAR-T. We are excited about that.
Is that significantly greater than J&J CARVYKTI footprint?
We don't comment on that, but I'd encourage you to look at it.
Okay.
Okay.
It's bigger.
The second component is as it relates to our manufacturing. We have begun manufacturing. We completed the tech transfer late last year. We are now manufacturing out of our Maryland facility for the clinical trials. For the material necessary for iMMagine- 3, as an example, it is coming out of our Maryland production facility. What we are observing in that is that we have turnaround times that are equivalent to what we see with our commercial products today in lymphoma and leukemia. That 14-17 day turnaround time globally. It is early days, and we will continue to monitor.
Which you think is faster than the competitor?
Which is faster than the competitors. We also have a higher reliability rate. Of course, it's early days for us. We'll continue to look at that. We're again on par with what we see in leukemia lymphoma, which is that 96% reliability in our manufacturing. Coupling the manufacturing efficiency and our ability to serve a number of markets and our footprint, we feel really great about the launch coming up. We're really excited about the data that we're going to share at EHA. Stay tuned.
When are you filing or what's the timing of the next steps if this data at EHA is good?
We are continuing to monitor those patients on iMMagine- 1. We will do one more final data cut before filing. We will share that data at a congress later this year. Our goal is to file this year and to launch in 2026.
How should we think about the regulatory endpoints for that? What is the hurdle for approval given what has been seen as a precedent, obviously, through CARVYKTI and also, I guess, by specifics as well? On the other hand, FDA, or specifically Vinay Prasad, has commented about BCMA CAR-T and MRD negativity. How does that commentary align with your confidence on being able to get approved? The head of CBER has made comments in the past.
Yeah. So obviously, many of us have taken the time to read the publications. I think we did on TRODELVY as well, as well as listen to the podcast. I think what we're observing from the FDA is honestly no change in the interactions that we continue to have with them. We did just recently change our primary endpoint to a co-primary endpoint on the iMMagine- 3 study, incorporating minimal residual disease and received FDA and global approval at that dual endpoint. We'll continue to move forward with that. With the iMMagine- 1 study, of course, we'll have progression-free survival. We'll have a different set of data that we file on. The minimal residual disease becomes really important in iMMagine- 3 and as we move into the newly diagnosed population.
Because as you know, in multiple myeloma, what we're seeing from CAR-T is that those patients can actually have a single dose of CAR-T and not progress for, let's say, seven or eight years. Progression-free survival, you wouldn't want to wait that seven or eight years to have the data to file. Minimal residual disease is really important as an endpoint. I believe the agency recognizes that. There have been comments, as you know, in the public domain from interviews on how the regulators are thinking about that. We have a chance in a week or so to have informal interactions with the agency per the industry. I forgot what he's calling it, but the.
The listening tour.
The listening tour.
The listening tour. Okay. So in other words, you believe that there's been no change and that ultimately a lot of the provocative stuff in the past needs to ultimately be more pragmatic now that they're in the seat. You're confident about no major changes.
We haven't observed any, is what I want to share. We'll obviously continue to have dialogue with the agencies.
Okay. Can we talk also about your $2 billion YESCARTA franchise? If you are going to be bullish on Anito-cel and launching and you think there's differentiation there, you are currently the leader in CD19 CAR-T. The products have actually been, as I'm a financial analyst, declining either sequentially or year over year. Why would that be? Are these going to grow? Consensus numbers have these at billions of dollars.
Yeah.
They're declining. They were declining.
What we've shared is that we continue to face headwinds with YESCARTA and TECARTUS. And that's from both in-class and out-of-class competition. There was a number of new approvals last year, the second half of last year, for both YESCARTA and TECARTUS in-class competition. And then certainly the bispecifics is out-of-class. The piece that we're looking at with YESCARTA and TECARTUS is not that different from what I described with Anito-cel. It's about how do we get into the community. Today, we know in lymphomas, one or two out of 10 patients are seen in the community. In myeloma, it's greater. Sorry, eight out of 10 patients are seen in the community. In myeloma, it's nine out of 10 patients. Our ability to unlock the community is something we've been really focused on.
We have continued to message that with the in-class and out-of-class competition, this year, we think we will be roughly flat. I think the piece we are pretty excited about is we have just shared data at ASCO this year of one of our three next-generation constructs for lymphoma and leukemia, which is the Kite 363, where we have been able to show a much improved in a phase one, quite ill population. These are very late-stage and aggressive patients. We were able to show a 78% complete response rate in that study. We are showing safety that we believe will be in line with being able to move therapies like this closer to where patients are in the community. We are excited about what is coming. We have three different constructs. We are going to be making a decision on which one we advance into pivotal studies in the next two months.
We look forward to sharing more of that data at a congress later this year.
All right. So flattish, but can resume growth after that based on getting more into the community. Okay. What about let's shift to TRODELVY. So we're at ASCO. I think it's safe to say that one of the more consensus positive presentations was a lot of the commentary in the presentation, but the commentary and discussion around the ASCENT-0 4 study with first-line triple-negative breast cancer with TRODELVY, a very strong survival benefit. They called it potential standard of care now. You have also announced in a press release that the PD-L1 negative population also read out positive. That's going to be presented. You basically have covered the space here. What does that mean for TRODELVY growth? Because TRODELVY also has had some slowing. You have a new opportunity for growth here with triple- negative. There is also competition coming.
What do you see are the push pulls for TRODELVY in triple- negative breast cancer and in HR positive breast cancer too? Want to do the round?
Yeah. Let's first talk about the triple negative breast cancer setting, which is where we had the data exactly as you said, right? ASCENT-0 4 was here. ASCENT-0 3 is going to be at a meeting later this year. This gives us access to the entire first-line triple negative breast cancer setting, right? This is a setting of high unmet medical need, not a lot of change over the last 20 years. This was very clearly voiced as a potential new standard of care in that setting. What that does for us is the patient number between second-line going to first-line roughly doubles. About half of the patients who are treated in first-line never get to second-line because the disease is so progressive, rapidly progressive, and because patients are doing really poorly. Moving into first-line roughly doubles the number of patients.
It also leads to a longer duration of therapy, which then further adds to the opportunity. Also, we have additional studies coming for TRODELVY in breast cancer. As you said, right, we have a study in first-line hormone receptor positive breast cancer coming. And that's ASCENT-07. We also have a study that's in the adjuvant setting, ASCENT-05, in the adjuvant setting of triple negative breast cancer. Overall, we feel we are well set up for more growth in the breast cancer setting. In addition to that, we have a study in non-small cell lung cancer, the first-line setting, PD-L1 high. We have a study in small cell lung cancer. We're based on strong phase two data. We've received breakthrough therapy designation from the FDA. We have a study in endometrial. Overall, the program for TRODELVY should enable additional growth.
In the near term, clearly in the first-line setting.
Is Dato-DXd a competitor in triple negative? Because they are coming as well. They have a TROP2 construct from AstraZeneca. They are also approved in HR breast cancer now. Their triple- negative data is coming. Are you expecting more?
Yeah. The study is coming. That's very true. At this point in time, it's important to think about the differences between the molecules, right? For example, we have overall survival benefit, significant overall survival benefit in the second-line setting, which Dato-DXd has not demonstrated. We believe the molecule is differentiated. We believe the data that we have demonstrated and you've seen ASCENT- 04 really clinically meaningful progression-free survival benefit and a trend also in overall survival, I think that sets up really well for that.
In the last two minutes, maybe just two more R&D questions. Inflammation. You mentioned inflammation at the beginning of this talk. You mentioned STAT6. I believe you have an IRAK4 as well. You have an alpha-4 beta-7, sorry for the alphabet soup. These are psoriasis and atopic derm products, potential orals. Kymera had some data this week in STAT6. Where is your STAT6? What are the inflammation programs that you guys have that pretty much nobody's talking about right now? You have been building and brewing in that space.
Yeah. Yeah. The inflammation portfolio is earlier, very clearly. It is important for me to mention because it is one of our focus areas. It is an area where I believe we are making good progress building it, right? The alpha-4 beta-7, the oral, is currently in phase two. That is the one that is furthest ahead.
When will we get data on that one?
Sorry?
When could we get data on that one? Alpha-4 beta-7 oral,[Lily-bar MAb ].
It's currently in phase two, right? It will take a little bit of time to see the data. Having an oral alpha-4 beta-7, the pathway is de-risked. It can be a really good basis for combinations in inflammatory bowel disease. That is where we are moving to combinations. There are other orals that would be good combination partners. You have the IRAK4. There is an inhibitor and a degrader. The inhibitor is in the clinic at this point in time. The IRAK4 degrader is moving into the clinic. The STAT6 is also moving into the clinic. We are not in the clinic yet. We feel we have announced the deal, right, earlier this year around JPM.
For STAT6?
It's for STAT6. It's basically with Liaopharma. We believe the molecule has a really good preclinical profile. We're currently preparing it to enter into the clinic. That, of course, gives us a strong opportunity in type 2 inflammation, which at this point is, I would argue, partially de-risked based on the data that you've seen.
What was it specifically? You see a greater potency, just a greater molecule than the Kymera program?
We looked very carefully at the different programs. We feel this is a program that, from a potency perspective and from what we've seen as preclinical characteristics, is a differentiated program.
Kymera is still, I think, holding out. You looked at all these programs.
We did.
Very good.
We're also moving our CAR-T 363, our BCMA one.
Also in inflammation. Can you talk about that?
In rheumatology. We will be filing in neurology.
I.e., CAR-T for lupus, etc.
Lupus, myositis, scleroderma on the rheumatology side.
Fantastic. Thank you guys very much for the time together. Great.