If anyone else wants to trickle in, then they can, they can do so. I'm Jake Miller with TD Cowen. It's my pleasure to introduce ADC Therapeutics and CEO Ameet Malik here. I'll pass it over. We'll do about 25 minutes for the presentation and five minutes or so for Q&A at the end.
All right. Thank you so much. Welcome. Great to be here with you. My name is Ameet Malik. I'm the CEO of ADC Therapeutics. Just a little bit of an introduction on the company. Overall, we're one of the leaders in the ADC space. We pioneered the space. We've been doing this for over a decade. We have a very robust technology platform and end-to-end capabilities, including a commercialized product. Our portfolio is split into hematology and solid tumor. In hematology, we have an approved product in Xynlonta, which is approved in third line, third line plus DLBCL, with the opportunity to expand into earlier lines of DLBCL, as well as in indolent lymphomas. We also have a phase 1 compound, ADC-602, which is targeting. It's an anti-CD22 compound.
In solid tumors, we have a phase 1 compound targeting AXL, our 601 compound, that's in the clinic, as well as multiple investigational ADCs, which are in the preclinical stage. Our cash runway is into the fourth quarter of 2025, and we have multiple catalysts this year. Just some key business updates from over the past year. Xynlonta Q4 sales are approximately $16.5 million. This is a double-digit increase in Q4 versus Q3. In terms of the pipeline, LOTIS-7, this is a combination study of Xynlonta with the two different Roche bispecific products. We cleared the first two dosing cohorts, no DLTs, and we see early signs of anti-tumor activity in the combination. With our LOTUS-5 study, the enrollment's accelerated quite a bit. We're more than two-thirds enrolled in that study, and that should be completed this year.
ADCT-601 is our solid tumor asset targeting AXL. We reached the recommended dose. We're currently in dose optimization. We've seen early signs of anti-tumor activity in sarcoma and monotherapy in combination, and we're now expanding into pancreatic and then into lung cancer. Then we terminated our program, 901, targeting KAAG1. Balance sheet, as I mentioned, we have about $278.5 million of cash and a cash runway that'll go into Q4 2025. We had a double-digit, just over 20% reduction in OpEx in 2023 versus 2022. Just diving deeper into our portfolio. As I mentioned, we have the hematology side of our portfolio and a solid tumor part of our portfolio. In hematology, we have an approved product, Xynlonta, which is approved in the third-line plus DLBCL setting.
We're doing a confirmatory study right now to expand into the second-line setting. This is our LOTIS-5 study. It's Xynlonta plus rituximab. This is a large phase III study, which we'll complete enrollment this year, we expect. Of course, it's an event-driven trial, but it could read out late 2025 and potentially lead to an approval in 2026. We also have our LOTIS-7 study. This is a combination with Xynlonta plus mosunetuzumab, as well as Xynlonta plus glofitinib. Finally, we have a number of different studies that are going on in the indolent lymphoma population. We have a phase I compound, ADCT-602. This is an anti-CD22. We saw encouraging data that was presented at ASH 2022. We're currently in dose escalation and expect to report some more data later this year on that program.
With solid tumors, we have our ADCT-601 compound targeting AXL. We're studying this as a single agent and in combination in sarcoma, pancreatic cancer, and in non-small cell lung cancer. We also have a whole set of next-generation ADCs, working on a number of different platforms and payloads, linker technology. The most advanced is a differentiated Exatecan-based payload that we're studying with a novel hydrophilic linker. We have IP both on the payload linker combination, as well as on each of the individual molecules. We're targeting, claudin-6, NaPi2b, PSMA, and other undisclosed targets, and we're continuing research on a whole range of, of other new, payload, linker, and conjugation technologies against other molecules that we've not yet disclosed.
Now, diving deep into Xynlonta, where we're playing today, if you can see this chart, DLBCL, follicular, and marginal zone, we're playing in that lower left box, the third-line plus DLBCL market. Right now, sales last year are approximately $70 million. We expect this as an $80-$100 million peak opportunity, but the big opportunity to grow the asset comes as we expand into earlier lines of therapy in DLBCL, as well as as we expand into more indolent lymphomas. Both our LOTIS-5 and our LOTIS-7 study have the opportunity to move into earlier lines of therapy in DLBCL. Our LOTIS-5 study, this is the confirmatory Phase III study, with Xynlonta and rituximab.
We shared data last year at ASH, which is the 20-patient safety running data, which showed an overall response rate of 80% and a CR rate of 50% with no new safety signals versus the monotherapy. We've accelerated enrollment, and I said we expect to complete the enrollment of the study this year. LOTIS-7, this is a combination study with both of the Roche bispecific products. We are escalating Xynlonta at three different dosing levels, so the approved dose of Xynlonta is 150 micrograms per kilogram, but we're escalating it at 90, then 120, and then 150. We've now cleared the first two dosing cohorts of the combination in both arms, the Columvi arm and the Lunsumio arm.
We're currently enrolling patients into the last dose level, and we expect to complete dose escalation in the second quarter of this year and then move to dose expansion. We also have a number of IITs in indolent lymphomas, one of which was shared at ASH in December of this past year. This is an IIT of Xynlonta in combination with rituximab in high-risk follicular lymphoma patients, the majority of which were POD24 patients. The data looked really interesting. We had 96% overall response rate, 85% CR rate. That study is continuing and being expanded to 100 patients, and that continues to enroll. It's a multicenter study now. We also have an IIT that's ongoing right now in second-line MZL. This is a single-agent study of Xynlonta. We expect to share data this year in MZL.
There's a significant unmet need in both of these populations, especially when you talk about high risk for FL or in MZL, and we're assessing based on the data that would be generated from this, both a regulatory pathway as well as compendia strategy. We're also looking at the combinations. The LOTIS-7 study is not only looking at DLBCL, but also looking at the combination with bispecifics in follicular lymphoma and in MCL as well. So looking into the DLBCL, now just diving deeper into DLBCL, what's clear is the frontline, you have a pretty common standard of care, whether you're treated in an academic center or in a community. Patients are typically going to receive R-CHOP or Polivy R-CHOP, given the recent approval that happened with Polivy. And that's pretty standard.
When we move into the second-line, if you're in an academic center, CAR-Ts are the preferred agent. More than half of the 35 patients that are treated in an academic center are gonna get a CAR-T. Other patients, a smaller portion, will get transplant, some will get move into clinical trials, and an even smaller percentage will get other novel therapies. But when you get into the second-line community setting and you get in the third-line plus setting, in both settings, there is no real standard of care. So there's a real opportunity to shape DLBCL. Although there's a lot of new trials, there's a lot of new competition, there's still no clear standard of care.
As Polivy is moved in the front line, also, it's opening up an opportunity because most physicians tell us they're not gonna retreat with Polivy across multiple lines of therapy. So as it's really getting embedded more and more pretty quickly in the front-line setting, that opens up an opportunity in the later line setting. So there's really a need for novel combinations in that second-line community setting and in the third-line plus setting in both academic and community settings. Our LOTIS-5 study has the opportunity... When you look at the second line opportunity, particularly in the community, there's a lot of R-based, rituximab-based combinations that are used still in the community today. So this, if you look at the efficacy data we've generated thus far, I think it'll be a very competitive profile with a safety profile that's well understood by community doctors.
We think it has the opportunity to be the standard of care, not only in second-line community, but in the third-line plus setting across the board. Whereas Xynlonta is already being used quite a bit, but Xynlonta rituximab, we expect, can have a better profile than single-agent Xynlonta. The bispecific combinations offer an even bigger breakthrough opportunity for the company. We have the opportunity to increase the efficacy versus bispecifics alone. We know that Columvi, just like Epco, as bispecifics approved in DLBCL, along with Xynlonta, have the highest single-agent efficacy rates outside of CAR-T. So combining these highly potent agents have the opportunity to be better in terms of efficacy than a bispecific alone. That'll help not only in the second-line community setting, but potentially even in the academic center. We know that not everyone's gonna get a CAR-T.
We know that even some patients getting a CAR-T are elderly, sometimes, consolidating off of a PR, not a CR. So there's an opportunity, I think, to even take some of the share from CAR-T if you have a combination therapy that's offering really high levels of CR rates with a, you know, very durable level of efficacy. We also have the opportunity to improve the CRS profile, which is one of the Achilles heels right now of the bispecifics in terms of being used in the community setting.
Bispecifics are growing rapidly right now in the third-line plus academic setting, but in the community, the requirements around hospitalization and particularly the high levels of CRS, for example, with Columvi, there's about 70% CRS rates and a small portion that have Grade three and Grade four, but even that deters a lot of community physicians from wanting to use bispecifics despite the good efficacy. So if we can improve on the efficacy profile and reduce the CRS levels with bispecifics, I think that's a really compelling combination. Now, turning to our solid tumor portfolio, our lead compound in the clinic is ADCT-601, targeting AXL. It's a novel compound. We're using a PBD-based payload with a lot of novel linker and conjugation technology to make sure that this is highly stable.
We know that AXL is expressed not only in sarcoma at high levels, and which is where we tested it first as a proof of concept, but also in pancreatic and non-small cell lung cancer. Sarcoma is a good proof of concept because you don't need to use a biomarker-driven approach. You can. In an unselected patient population, we know that roughly 90% of patients with sarcoma have expression levels of AXL on the cell surface membrane, and the key is AXL is expressed both intracellularly as well as on the cell surface of tumor cells, so we need to make sure it's the expression on the tumor cell. We also developed a biomarker assay, an IHC-based assay, that will be used in a more biomarker-driven approach, both in pancreatic cancer and non-small cell lung cancer.
We have generated data already in sarcoma on the dose escalation and reached the recommended dose of 13 mg. We're now currently in dose optimization in sarcoma, both as monotherapy as well as in combination with gemcitabine. We saw anti-tumor activity, including responses in very late-line patients, which most physicians would say when you get to third, fourth line soft tissue sarcoma patients and you're seeing responses, that's clinically meaningful. So we want to see more of that, obviously, as we expand the data in sarcoma, but we're also now the next priority is to move into pancreatic. We've recently started screening in pancreatic cancer, and we'll be generating data in pancreatic cancer over the course of this year, and then we'll move into non-small cell lung cancer afterwards. Beyond our ADCT-601 compound, we also have a growing technology platform.
We know with ADCs, a lot of the space has evolved from companies going after particular payloads or particular technologies and developing molecules based on that, to an approach that's more based on the biology. We know we have to go after targets that are highly expressed on tumor cells, but not on healthy cells that allow for internalization. And that requires, if you want to go after a broader set of biological targets, also a broader set of technology tools to go after. So we've really expanded the set of antibodies, payloads, linker conjugation technologies, that help us to go after a much broader set of biological targets. One of the more advanced ones is using exatecan.
I think everyone's probably aware of the DXd platform from Daiichi Sankyo, which produced really, I'd say, outstanding results with HER2 and is being used in a number of other molecules. So it's, it's clearly it's a proven platform to go after topoisomerase I inhibitors. But there are some drawbacks, and there's still potential to improve upon that platform. Exatecan is highly hydrophobic, so it's very hard to work with. And so we developed a novel linker technology, which we have, IP pending right now on the linker payload technology combination, which is highly hydrophilic and allows for stability and use of the full exatecan molecule. We know there's a lot of advantages to this. For example, better potency, better bystander effect.
And also, we've tested now in three different monkey models, three different molecules, we've seen no signs of ILD, which is one of the safety drawbacks of the DXd platform. We are seeing a very, very high therapeutic index also with this platform, in the neighborhood of 12-15. We know that we can dose up to 40 mg/kg in monkeys without seeing toxicity, and we're seeing efficacy in the low single-digit mg/kg level, so a very high therapeutic index. We now have 4 different molecules that are using this, that are at or near the clinical candidate selection stage. Once you get to that stage, as we move forward, it's roughly 18 months to get to IND from once you get to clinical candidate selection. So we're going after a number of, I think, very interesting targets.
Obviously, the ADC space, there's a lot of competition around targets like HER2 or Trop-2 and others. But I think some very interesting targets where we're one of the early companies going after are compounds like targets like NaPi2b, Claudin-6, PSMA. We also have an undisclosed target where we believe we may be first in class as well. So there's a number of opportunities that we're going after with this exatecan-based payload approach. The overall strategy, if you think of our capital allocation, a lot of our capital allocation is going towards hematology, particularly in the US. We know that with LOTIS, with our current indication with Xynlonta, this can be an $80 million-$100 million peak opportunity. With LOTIS-5, our confirmatory study, moving into second line, we've talked about, that should roughly triple the size of our opportunity in total.
That could take us to $250+ million in peak sales. That gets the company with our current cost base towards break even or profitability. LOTIS-7 can help to expand even further. So we're putting a lot of our capital allocation towards hematology, which we believe is a more de-risked pathway towards profitability for the company while we play out multiple solid tumor bets. Given the number of bets we have in solid tumors, partnerships and collaborations will be part of the strategy to progress multiple programs forward. That doesn't mean we don't want to have a significant economic interest. That doesn't mean we don't want to do some programs on our own, but we know that the number of programs that we're generating and as well as others behind it, we won't be able to do everything on our own.
So partnership would be part of the strategy in order to finance a broad set of solid tumor targets. Overall, this year, we have multiple different data catalysts. So with Xynlonta, we'll achieve commercial brand profitability this year. What that means is the sales that we generate more than offset the whole commercial organization, the field force, the A&P cost, the whole MSL team, all of our IT. So everything to do with the commercialization efforts and medical affairs efforts related to the product are more than paid for with Xynlonta sales already in third line. LOTIS-5, our confirmatory study, will complete enrollment this year. LOTIS-7, we will complete dose escalation in the second quarter of this year, and we expect to have expansion data updates in the second half of this year.
For follicular data and marginal zone, the IITs I mentioned will have updates at medical conferences this year and next year. Our 602 compound, our anti-CD22, we expect to have additional data updates from the dose escalation of the phase 1 program this year. Our AXL program, we're generating more data in sarcoma, and we expect to have a clinically meaningful number of patients in pancreatic tested that we will be able to share later this year. May have a small amount of lung cancer this year, or going into next year. Preclinically, we continue to advance the set of ADCs, and you can expect to see more data coming out in terms of the differentiation of these molecules at upcoming congresses as well.
Then finally, as I mentioned, you know, we have a cash runway into the fourth quarter of 2025. Obviously, we'll have a lot of value-generating milestones within that timeframe... and we'll continue to finance the company, you know, through a combination of dilutive and non-dilutive ways as we continue to progress the pipeline, and partnerships and licensing will be part of that strategy. So with that, I guess, Jake, should we move to the Q&A part?
Yeah, absolutely. I can start us off too with a couple here. On the ADC front, the next-gen ADCs, when do you expect to move any of those four into the clinic, and does that depend on any partnerships or anything of the like?
Yeah, I mean, so we, because a lot of our capital allocation is going towards hematology, we believe we have a really de-risked pathway with Xynlonta, especially with LOTIS-5 and LOTIS-7. That's where a lot of our funding is going. So we are progressing solid tumor assets forward, but certainly to progress the portfolio forward, that will require some level of non-dilutive financing. We're also-- we can always have to look at, as we progress these compounds forward, what's the valuation from the markets versus from Partners? And to the extent that early-stage assets get valued by the markets, we can progress more forward. So it, it depends on that combination. But for any of these assets, we're about, you know, 18 months away from the clinic when you get to that clinical candidate stage.
Things right now could already be in the clinic or at the IND stage in 2025, in the second half of 2025.
Then on Xynlonta, can you just provide any more, you know, detailed granularity on commercial performance, particularly in Q4, and then growth potential in third line plus?
Yeah, so I mean, Q4 was a nice rebound for us. Last year, we made a significant change to the commercial strategy and the commercial model. What's clear is, the model we had before was very focused on academic centers, which are still the thought leaders and drive a lot of even the prescribing that happens in the community, because community doctors are often asking for referrals from academic doctors, even when the patients aren't getting referred and treated in the academic center. But we needed to start orienting our commercial model more towards how local healthcare systems were based. And so we reoriented our whole commercial model from, I'd say, more of a one-size-fits-all, which was internally driven, activity-based model, to one that was structured around local healthcare systems.
So, for example, if you look at something like, you know, MSK in New York, they have satellite centers in Long Island, they have satellite centers in New Jersey. Before, that was three different sales reps calling on those territories, no one looking after the whole system of care. Those systems of care exist across the whole U.S. You can look at the systems here in, you know, with Partners and Dana-Farber. They're systems of care where, which blend between academic and community, and which blend outside of a narrow geography. So we've restructured our teams to mirror how healthcare is delivered locally. That was a significant change last year. We changed about 50%. 50% of the team was either new enroll or new to the company. So it was a massive change where we took a hit in Q3.
It's nice to see that in Q4, we rebounded, had double-digit growth, and if you look at the volume that we saw in November, December, it was back to where we were before the restructuring. So we expect to see modest growth. I mean, third line plus, when you see it's about 6,000 patients in the U.S., and our duration of therapy is about three to four cycles, there's a limited amount of growth opportunity, but we'll see some progressive growth. The much bigger opportunity comes as we move into other lines of therapy and into other lymphomas.
Then on LOTIS-7, I guess, to just follow up, can you talk a little bit more about early signs of anti-tumor activity, and then just broad safety profile there?
Yeah, so in the LOTIS-7, we're just to take a step back on the design, we have two different arms to the study. We're combining Xynlonta with glofitinib, and we're combining Xynlonta with mosunetuzumab. In the study, we're escalating Xynlonta, three different dose levels. One of the unique things we're doing in the glofit arm, though, is we're dosing the Xynlonta before glofit. So obinutuzumab is given on day one, we give glofit- we give Xynlonta on day two, and then glofit on day eight, and then every three weeks after, you give both together. The idea there is if you can debulk the tumor, potentially lower the CRS levels. At the 90-milligram dose, that's what we saw. We didn't see any CRS in the glofit arm. We saw only grade 1 in the mosun arm, where we're dosing them concomitantly.
If we can continue to see lower levels of CRS levels, this can help to bring bispecifics from, which predominantly academic use, into the community. So that's what we've seen so far. We haven't seen any DLTs, and we're seeing lower grades of CRS, and we hope that will continue as obviously, as we test more patients. These are very active agents. You know, we know that glofitinib and Xynlonta, as an example, are approved already right now in DLBCL. They're highly active agents, and so we've seen, you know, activity, obviously, in what I'd say is a very heavily pretreated patient population in the dose escalation trial. Once we complete the dose escalation, which we anticipate in Q2, we plan to expand into two different dosing to two different doses, but in the second-line-plus setting.
The protocol allows us to move right into second line, which I think is a more representative population of where we wanna go in terms of testing the efficacy of the combination.
I guess the last one for me, how are you thinking about capital financing needs, and then any timeline you have on that?
Yeah, we haven't provided a timeline. I mean, luckily, we do have a cash runway that goes to late 2025. We have a lot of different data catalysts that are gonna happen, even starting in Q2 this year, and then as the year progresses, we have multiple different data catalysts. So we'll continue to finance the company, I think, through a combination of, you know, dilutive and non-dilutive ways to obviously get our cash runway well into 2026.
Awesome. All set. Thank you very much.
All right.
Appreciate your time.
Thank you so much. Appreciate it.