Good morning, ladies and gentlemen, and welcome to the ADC Therapeutics SA LOTIS- 7 update. At this time, all lines are in listen-only mode. Following the presentation, we will conduct a question-and-answer session. If at any time during this call you require immediate assistance, please press star zero for the operator. This call is being recorded on Wednesday, December 3, 2025. I would now like to turn the conference over to Nicole Riley, Head of Investor Relations and Corporate Communications. Please go ahead.
Thank you, Operator. Today, we issued a press release announcing updated results from our LOTIS-7 clinical trial. This release and the slides we will use in today's presentation are available on the investor section of the ADC Therapeutics website. I'm joined on today's call by our Chief Executive Officer, Ameet Mallik, who will provide a strategic overview and frame the opportunity for ZYNLONTA in DLBCL, and our Chief Medical Officer, Mohamed Zaki, who will discuss our LOTIS-7 clinical trial and updated results. We will then open the call to questions. Before we begin, I would like to remind listeners that some of the statements made during this conference call will contain forward-looking statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995.
These forward-looking statements are subject to certain known and unknown risks and uncertainties, and actual results, performance, and achievements could differ materially. They are identified and described in the accompanying slide presentation and in the company's filings with the SEC, including Form 10-K, 10-Q, and 8-K. ADC Therapeutics is providing this information as of today's date and does not undertake any obligation to update any forward-looking statements contained in this conference call as a result of new information, future events, or circumstances, except as required by law. The company cautions investors not to place undue reliance on these forward-looking statements. I will now turn the call over to our CEO, Ameet Mallik. Ameet.
Thank you, Nicole. I'd like to start by reminding you of our ZYNLONTA strategy. As a single-agent therapy and third-line plus DLBCL, ZYNLONTA has a profile of rapid, deep, and durable efficacy, as well as manageable safety with simple and convenient administration. Beyond our current indication, we believe in the potential to reach significantly more patients by expanding use into earlier lines of therapy in DLBCL with combinations, as well as into indolent lymphomas. The data we've seen across these settings so far has been consistently encouraging, with the potential to be highly differentiating. Today, we are excited to share an update on data from the 49 efficacy-available patients with a minimum of six months of follow-up from treatment initiation in our LOTIS-7 trial. This updated data further supports our belief in the combination of ZYNLONTA plus glofitamab as a potential best-in-class bispecific antibody combination in second-line plus DLBCL.
Looking at the overall DLBCL treatment landscape, whether in the second or third-line setting, there are two main segments. The first segment includes complex therapies, which require unique infrastructure and expertise to handle logistical requirements and patient management. These are primarily limited to the academic centers and more sophisticated community centers and include therapies like CAR-T, transplant, and bispecifics. The second segment comprises more broadly accessible therapies, which all physicians can administer in the outpatient setting and include ADCs, monoclonal antibodies, and chemotherapy. The launch of bispecifics as monotherapy in the third-line plus setting has resulted in an evolution of the treatment landscape, where we estimate there is currently a 60/40 split between complex and broadly accessible segments.
In the second-line setting, where bispecifics have not yet been approved but were recently added to NCCN guidelines for use in combination, we expect that they will continue to gain share and grow the use of complex therapies. While ZYNLONTA is currently approved as a single-agent and third-line plus DLBCL, we believe ZYNLONTA plus rituximab in LOTIS-5 and ZYNLONTA plus glofitamab in LOTIS-7 are complementary approaches to addressing unmet needs in these two key treatment segments. In LOTIS-5, our phase III confirmatory study, we are combining ZYNLONTA with the most widely used agent, rituximab, in second-line plus DLBCL patients. In LOTIS-7, our phase I-B trial, we are combining ZYNLONTA with a highly effective bispecific, glofitamab, in second-line plus DLBCL patients.
When you look at the CR rates among both currently available and emerging therapies in these two treatment segments, we believe the emerging clinical profile of ZYNLONTA plus glofitamab in the LOTIS-7 trial positions us well among complex therapies, and at the same time, the clinical profile of ZYNLONTA plus rituximab in the LOTIS-5 trial has the potential to differentiate us among broadly accessible therapies. We believe these combinations have the potential to double the addressable patient population as we move into second-line and increase the duration of therapy, moving on average from three cycles to five to six cycles. At this point, I'd like to invite Mohamed to share today's update on our LOTIS-7 trial. Mohamed?
Thank you, Ameet. Let's take a deeper look into our rationale for exploring the combination of ZYNLONTA and anti-CD19 ADC with glofitamab and anti-CD20/ CD3 T-cell engaging bispecific antibody. These two highly potent single-agent drugs offer important and complementary mechanisms of action in DLBCL, which target two different B-cell surface engines while delivering a potent payload and activating T-cells. Given this, we expect to see additive or synergistic efficacy. In addition, there are no known overlapping non-hematologic toxicities between the two agents. By dosing ZYNLONTA prior to glofitamab, it is our hypothesis that this dosing schedule has the potential to debulk the tumor and to lower CRS rates and grades. The design of the trial includes two parts. In part one, dose escalation was conducted in non-Hodgkin lymphoma patients at three dose levels of ZYNLONTA with glofitamab or Mosunetuzumab in the third-line plus setting.
In part two, dose expansion moved forward in second-line plus large B-cell lymphoma with ZYNLONTA at two-dose levels, 120 micrograms per kg, and the currently approved monotherapy dose of 150 micrograms per kg combined with the approved monotherapy dose of glofitamab. Based on the scientific evidence available and in alignment with the Data Safety Monitoring Committee, we selected the 150 micrograms per kg dose and are currently enrolling approximately 100 patients at this dose. ZYNLONTA is being given prior to glofitamab to potentially debulk the tumor in the first cycle, and then both agents are given together in subsequent cycles. ZYNLONTA is administered for up to eight cycles and glofitamab for up to 12 cycles. The primary endpoint is safety and tolerability with secondary endpoints of efficacy, PK, and immunogenicity.
As Ameet noted, today we are sharing safety and efficacy data on all efficacy-available patients with a minimum of six months of follow-up from the time of treatment initiation. This is an important view of the data as we believe it provides the most stable, meaningful update on safety as well as depth and durability of response in a way that is most representative of the overall data. As of the data cutoff date of November 17, safety data continue to show the combination is generally well-tolerated with a manageable safety profile, and the updated efficacy data continue to support the combination of ZYNLONTA plus glofitamab in the second-line plus DLBCL.
It is important to note that neutropenia, a known adverse event of each drug, continues to be the most common treatment-emergent adverse event of grade three or higher, and it's similar to the average reported in the approved prescribing information of each drug separately. Grade five adverse events occurred in two patients, and one was treatment-related per the investigator. In addition, we continue to observe lower rates of CRS compared to the glofitamab monotherapy label. ICANS rates observed continue to be low, and all were grade one or two. Turning to efficacy, best overall response rate was 89.8% as assessed by Lugano criteria and based on investigator assessment. We observed a complete response rate of 77.6%. Of note, 33 out of 38 patients achieving CR remained in CR as of the data cutoff.
In addition, we observed conversions of 14 patients from stable disease or partial response to complete response over time. Of the eight patients previously treated with CAR-T, six achieved a CR. Baseline characteristics in this study are representative of the second-line plus DLBCL patient population. Our goal for the full study is to have baseline characteristics which are similar to other bispecific combination studies in this space. Among the 49 efficacy-available patients, there are few characteristics that are important to highlight. The median age in this study is 70, with a range of 26- 85 years of age. The study enrolled patients with large B-cell lymphoma, including de novo DLBCL, transformed follicular lymphoma, high-grade B-cell lymphoma, and grade 3B follicular lymphoma, all considered to be DLBCL. Median prior lines of therapy was one, with a range from one to five.
The study includes a number of difficult-to-treat large B-cell lymphoma patients. 16.3% of patients received prior CAR-T, which is in line with other trials conducted with bispecific combinations. Patients refractory to primary or last therapy were all represented in this study, both of which were significantly higher in the 150 microgram per kg compared to the 120 microgram per kg dose. Turning to safety, most notably, when looking at grade 3 or 4 treatment-emergent adverse events occurring in more than 5% of patients, neutropenia continues to be the most common at 32.7%, which is similar to the rate of neutropenia reported in the prescribing information of each drug separately. Grade 5 adverse events occurred in two patients, or 4.1%.
This includes one grade 5 non-treatment-related adverse event of sepsis due to gastric ulcer and one grade 5 treatment-related adverse event of generalized edema per investigator, which occurred more than 105 days after the last dose of study treatment. Of note, this patient completed eight cycles of ZYNLONTA and discontinued glofitamab after 11 cycles. To date, the types of treatment-emergent adverse events observed are consistent with the known safety profiles of each drug separately. Thus far, the combination continues to show a manageable safety profile, and no new safety signal was observed. When it comes to drug discontinuation, 6.1% or three of the 49 patients could discontinue both therapies due to treatment-emergent adverse events. Six patients or 12.2% discontinued ZYNLONTA only, and three patients or 6.1% discontinued glofitamab only due to treatment-emergent adverse events.
Based on study protocol, patients who discontinued one treatment could continue to receive the other. It is important to consider the profile and measures of cytokine release syndrome and ICANS when using bispecific therapies. In this study, we can see that overall rates of CRS are higher at 120 microgram per kg dose compared to the 150 microgram per kg dose. The 120 microgram per kg dose had 52% any grade CRS, primarily grade one or two, with one case of grade three. The 150 microgram per kg dose had 25% any grade CRS, all of which grade one or two. Grade one and two CRS cases were managed with tocilizumab, corticosteroid, acetaminophen, and/or fluid bolus without ICU admittance or pressure support. Grade three CRS case was managed with tocilizumab, acetaminophen, dexamethasone, norepinephrine, and included ICU admittance.
ICANS were seen in two patients treated at the 120 microgram per kg dose. These ICANS were grade one and two and primarily managed with corticosteroid. Both patients had complete resolution of symptoms and resumed treatment, ultimately achieving a complete response. At the 150 microgram per kg dose, one patient experienced ICANS, however, this patient discontinued treatment prior to the first assessment and was not efficacy evaluable. Moving now to efficacy, the results observed across both dose levels were broadly consistent in terms of ORR, CR, and PR. In this study, we have seen 89.8% overall response rate and a 77.6% complete response rate. With a larger data set, we are now sharing for the first time an efficacy analysis for both primary refractory and relapsed patients. Primary refractory is defined as no response or progression on or within six months after initial response to front-line therapy.
Relapse is defined as progression following an initial response as well as disease refractory to last prior therapy. As you can see, we saw strong efficacy in both the relapsed and primary refractory populations across both dose levels. In the 24 relapsed patients, we observed an ORR of 100% and a CR rate of 91.6%. In the 25 primary refractory patients, we observed an ORR of 80% and a CR rate of 64%. Looking now at the swimmers plot, the green bars show all patients in complete response, and the length of these bars shows the durability of each response. Most responses were observed at initial assessment. 33 out of 38 patients who achieved a complete response have maintained that response as of the data cutoff. 14 patients converted from an assessment of stable disease or partial response to complete response over time.
At this point, the longest response in this study is more than 18 months. Complete responses were observed regardless of prior therapy. Of the eight patients previously treated with CAR-T and undergoing response assessment, six achieved a CR. These overall updated results are highly encouraging. I would like to remind you that what is important when treating patients with relapsed refractory DLBCL is the rate and durability of CRs with a manageable safety profile. We continue to be encouraged by the results of this study and believe these data continue to demonstrate compelling efficacy, including deep and durable responses, as well as manageable safety in the second-line plus relapsed refractory DLBCL patients treated with ZYNLONTA plus glofitamab. Now, I would like to turn the call back to Ameet. Ameet.
Thank you, Mohamed, for walking us through the LOTIS-7 trial update.
I would just like to remind everyone why LOTIS-7 is important to our strategy and to highlight the catalysts we have over the coming year. Looking at potential peak revenue, the largest opportunity is from the combination of ZYNLONTA plus glofitamab in second-line plus DLBCL with LOTIS-7. Together with ZYNLONTA plus rituximab and LOTIS-5, we estimate we can expand the total opportunity for ZYNLONTA in DLBCL to $500 million-$800 million in peak revenue, with regulatory approval and compendia listing. Overall, we believe ZYNLONTA has the potential to reach peak revenues of $600 million-$1 billion in the U.S. as we expand into earlier lines of DLBCL and into indolent lymphomas. We expect to have multiple data catalysts in 2026 across the ZYNLONTA programs, supported by a cash runway that extends at least into 2028.
For LOTIS-5, we expect to provide top-line data in the first half of 2026, once the pre-specified number of PFS events is reached and data are available. Assuming positive results, a supplemental biologics license application submission to regulatory authorities will follow, with potential confirmatory approval in second-line plus DLBCL, as well as publication and compendia inclusion in the first half of 2027. With LOTIS-7, we plan to share the next update with full data at a medical meeting and submit for publication by the end of 2026. In addition, assuming positive results, we will assess regulatory and compendia strategies. With indolent lymphomas, we expect additional data to be shared at medical meetings by the lead investigators, and we plan to assess regulatory and compendia strategies once sufficient data are available.
Overall, I continue to be excited by the consistently encouraging ZYNLONTA data we are generating across our ongoing trials and by the potential for ZYNLONTA to change the treatment paradigm for second-line plus DLBCL patients. We can now open the line for questions. Operator.
Thank you, ladies and gentlemen. We will now begin the question and answer session. Should you have a question, please press star, followed by the one on your touch-tone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press star, followed by the two. If you are using a speakerphone, please lift the handset before pressing any keys. Your first question comes from Eric Schmidt with Cantor. Your line is now open.
Thanks, guys. Good morning, and I appreciate you taking my question. Maybe the first question is on efficacy.
You laid out, I think it was slide seven, some of the benchmarks and metrics for other regimens in terms of response rates in this setting. Now that we have a good chunk of durability data from this trial, how do we think about that 33 out of 38 CRs being durable as of last cutoff relative to, say, other regimens that might have been tested in this setting?
Yeah, thanks for the question, Eric. You know, I think we feel good about our durability, and that's one of the reasons we want to share data with at least six months of follow-up because there's a much better look at durability right now. Typically, when you look at other trials, you want to look at the duration of CR over time. So there's metrics for duration of CR at six months or 12 months.
You can basically look at the Kaplan-Meier curve. We're a little bit too early to have that mature data right now in terms of durability. But I think importantly, when you look at these 33 CRs that are still remaining in CR, we can get through a little bit detail of the other five because actually of the five, only two progressed. Two patients had grade five AEs while they were still in a CR, and one patient was censored because of getting a solid tumor cancer and having to get chemotherapy, and so we were lost to follow-up. So actually, even in the 33 of 38, there were only actually two progressors within that. So we feel really good about the durability.
I think when we give the next update, final update, we'll be able to provide more details on duration of CR, and I think that'll be able to give good comparisons to other trials over time.
Thanks, Ameet. That's helpful. As a follow-up, we have seen in the last couple of updates that the CR rate tweaked down a little bit. Obviously, 78% still extremely impressive, still looks like a best-in-class therapy. But it's not lost on us that you've now treated a lot more patients than the 49 that have shorter than six-month follow-up. With that in mind, what kind of gives you confidence that the CR rate could stabilize around these levels as opposed to continue to tweak downward?
Thanks. Yeah. So I would also say that if you look at the updates, it was 72% the first update, then went to 87%, now 78%.
I think that's a natural flow of patients. I mean, the intent of the study is to have a balanced population. We want to make sure that it's representative of all second-line plus populations and all the different subpopulations. So whether it's relapsed, refractory, second-line, third-line plus, post-CAR-T, not exposed to CAR-T. So we're really trying to have a very balanced population. Our goal is to make sure that the baseline characteristics are similar to other bispecific antibodies in the space. There's a couple of things that we're doing, and I'll turn it to Mohamed to just kind of comment on how we're making sure that we can achieve this intent of having a similar balanced population to other big bispecific antibody trials.
Yes. There are several initiatives that we took, actually, talking to all investigators and explaining the intent of the protocol is to be second-line plus.
This is not a salvage therapy for fourth and fifth line, nor a protocol design for primary refractory patients. Yes, primary refractory will be included. However, it has to be balanced. So also in conjunction with the steering committee of the study, and we're all aligned. In addition, there are parameters in the protocols, actually, that will eventually make sure for this population to be stabilized by the end of the study. In the 150 dose, we're only looking at 28 patients. There are 72 more patients to be enrolled. So there is quite an opportunity for this to stabilize and be able to be balanced over time.
Your next question comes from Michael Schmidt with Guggenheim. Your line is now open.
Hey, good morning. Thanks for taking my question and congrats on the data update. Yeah, I just had a couple of follow-ups. One on efficacy.
I think you did a great job on slide 16, sort of outlining some of the differences in relapsed and primary refractory patient responses. And obviously, the primary refractory patients are much harder to treat. And it looks like there were more of those at the higher dose. But I'm just curious what your expectation would be in the real world in terms of the distribution of those categories and how that compares to the approved therapies in second line.
Yeah, it's a great question, Michael. Good observation. I think the difference in % of primary refractory in the 150 versus the 120 obviously drives some of the efficacy difference when you look at overall numbers. But clearly, we're very pleased with the 150 because we see 90% relapse, 90% CR in the relapsed population, and almost a 67% CR rate in the primary refractory patient population.
That data is outstanding. When you look at the real world, patients are pretty balanced between the two populations. It's pretty evenly split. When I look at the other trials, the other big bispecific antibody trials that are listed in compendia, they're also anywhere from 52%-58% of the study is primary refractory. So we're indexing a bit higher right now at that 150 dose. But again, the goal is that over the course of the study, we'll have a pretty balanced study that's more in line with the real-world population.
Okay. Super helpful. And then, obviously, great to see the enrollment trajectories of trending towards completion of the 100-patient cohort in the first half of next year. And sort of just stepping back and thinking about your bigger picture strategy.
I was just curious in terms of future commercial uptake in the second-line DLBCL setting based on compendia listing alone, how much upside could that drive in terms of sales relative to perhaps pursuing a formal regulatory approval in second-line DLBCL in the future?
Yeah. Certainly, with compendia, you would only expect to capture a portion of the total revenue potential. Obviously, for anything that's in compendia where we don't have regulatory approval, we will not promote. So it would be up to the decision of compendia to list it, and then, of course, for physicians to make an independent decision. One thing I will note, at this point, there are no bispecific antibody products in the second-line setting that are approved. There are three different antibodies that are in compendia. Now, that, of course, could change over time, but as of now, that's the case.
So at least with where the landscape sits today, we'd be entering sort of at parity where everything would be a compendia. So I can't tell you exactly the percentage that it's going to be, but it would be certainly a portion of the total because you're not going to promote. So regulatory approval and doing a phase III study would generate additional revenue opportunity.
Great. Thank you so much, and congrats on the update.
Yeah. Thanks, Michael.
Your next question comes from Clara Dong with Jefferies. Your line is now open.
Hi. Good morning. Thanks for taking our question. Congrats on the update. So two questions from me. One, can you first maybe clarify the differences in the patient populations between the previous update and today's update? I think you mentioned today's update, you have a minimum of six months of follow-up time.
So just trying to understand, were all patients in the earlier update included in the new data set today and any differences in terms of the efficacy population? And then secondly, can you also help us understand maybe qualitatively the durability of complete responses among patients with prior CAR-T therapy and those with primary refractory and relapsed? The response data in those two populations are quite impressive. So just also wondering what could be the clinical implications to physicians as well from the data from those populations.
Yeah. So maybe starting with your second question about the CAR-T and the primary refractory, I think we're pretty pleased to see that the CR rates are quite high. So obviously, not as high as in the relapsed population, but we continue to see very high CR rates.
And we're not breaking out durability for each one because you get to small populations. But I think what you can see is of the 38 CRs, only two progressed. So that kind of shows that there's very little progression in any population right now. And so I think we feel pretty comfortable with this early data right now that the durability looks quite good. And then in terms of your first question around the difference between the last update, if you remember, we had 41 safety-available patients, but only 30 were efficacy-available. That's because only 30 of the patients had at least achieved the first assessment, disease assessment. The other 11 had only been dosed, but not yet reached the first assessment. So this update includes all of those patients plus an additional, obviously, set of patients to get to the 49.
The reason we went to a minimum of six-month follow-up is it provides a much more mature way to look at the data. We can start to see, do the PRs convert to CR, or do they progress? Are the CRs durable? AEs, we know, can accumulate over time. So it gives a better picture of the AEs. So we want to give the most mature view of what the data would look like and the most representative view of the data. We could do that, obviously, in earlier data cuts, but now that we have a larger sample set with nearly 50 patients with a minimum of six months of follow-up, I think this is a pretty robust update that we're able to provide now.
Thank you. Very helpful.
Yep. Thank you.
Your next question comes from Leonid Timashev with RBC Capital Markets. Your line is now open.
Hey, thanks, guys. Thanks for taking my question. I wanted to ask on the safety profile. I guess I'm curious. It seems as though this was just only in the efficacy-evaluable population, so some patients are not being included. I wonder if you can just talk about the safety profile in totality. I mean, obviously, we've dosed additional patients now. If there were some events that were readjudicated, I know it looks like the ICANS patient was in the safety population, not in the efficacy population. So that number looks like it improved. And then related to that, it looks like the edema and effusion rates are maybe higher than what's currently on label for ZYNLONTA. I'm wondering if that's just due to small numbers in this trial or if there's maybe some kind of interaction going on with the bispecifics. If you have any thoughts around that. Thanks. Okay.
You're asking about the safety population. First of all, I'll say we won't comment on additional patients beyond the 49 we're showing, other than to say I think everything we're seeing is pretty consistent. I don't think we're seeing anything as an outlier. One of the reasons we, again, want to show safety with at least six months of follow-up is because some AEs can accumulate over time, can occur not just at the initial dose, but can happen over time. I think this provides a very good view of the AE profile. We feel pretty comfortable that it's consistent with the known profile. We didn't see any new safety signals that weren't known with either one of the drugs.
And even in the case of, let's say, neutropenia, which is one of the known toxicities that's seen with both agents, we saw a level of about 32%, which is very similar to what's seen with either ZYNLONTA or with glofitamab individually in the label. So we didn't see really additive toxicity. So we feel pretty comfortable with the toxicity profile, and we think it's held. Again, with longer follow-up, you can accumulate more events. So we think this is a pretty accurate view of where the safety profile looks like.
Your next question comes from Sudan Loganathan with Stephens. Your line is now open.
Hi. Good morning. Thank you for taking my questions. I'll add another one here on just the safety profile. Just wanted to understand better the CRS rates or any other treatment-related adverse events when looking at this combination, ZYNLONTA plus glofitamab.
How does that compare to the CAR-Ts or other bispecific monotherapy or combinations? I'm curious as this kind of matures out with more patients, what do we want to see in the CRS rates to have confidence that it could be best in class?
Yeah. I mean, I think, first of all, CRS with a CAR-T, I think, is even much more severe than with a bispecific. So I think bispecific CRS is definitely more manageable than with a CAR-T. But nonetheless, what you see with glofitamab on its own is about a 70% CRS rate, all grades. Now, most of that's low grade. There are some small percentage which are higher grade. So I think we feel pleased.
I mean, this is something that was done intentionally to dose the ZYNLONTA before the step-up dosing of glofitamab after the obinutuzumab in order to debulk the tumor and to try to reduce the CRS rates and grades because we know, again, glofitamab is a very potent compound, and that was the goal of the way we approached the product. So I think it's good to see that, again, consistently, what we're seeing in terms of CRS is much lower. And you can see there's some dose dependence that's been consistent with the prior updates. So whereas we saw at the 120 dose, lower dose, 52% any grade CRS, mostly low grade. We had one case of grade 3. But in the 150 dose, it was only 25% in all grade 1 and 2. So we do feel like that debulking seems to be working. Again, it's a hypothesis.
But we're pleased right now with where the CRS rates are because that is one of the barriers. I mean, bispecifics have gotten more adopted in the community, but more sophisticated community centers. And having lower rates and grades of CRS will, I think, could further drive the penetration of bispecifics in the community setting.
Got it. Thanks. Just a quick follow-up also. I think maybe I'm doing the math wrong here, but just curious. I think to get around close to these 50 patients that you have may have taken a year, a little bit more than that. Obviously, in your guidance, you're expected to have full enrollment of 100 patients by probably the first half of 2026. Curious on just what your take is on getting the next 50 patients, what the trajectory looks like as you're looking to kind of ramp up the enrollment. Thanks. Yeah.
I mean, we've clearly had a lot of interest in the trial since the EHAN ICML update in June, and we saw some acceleration in the enrollment. But we're also, per what Mohamed said, there's an attempt to make sure there's a balanced study and that the baseline characteristics are very well represented. So yeah, I think we're on track with what we've always said, which is that this study will be fully enrolled in the first half of 2026.
Great. Thank you, and congrats again on all the progress in the data.
Ladies and gentlemen, as a reminder, should you have a question, please press star one. Your next question comes from Robert Burns with H.C. Wainwright. Your line is now open.
Hey, guys. Thanks for taking my questions and congrats on the data. Two questions from me, if I may.
I guess we recently saw a publication for the combination of glofitamab plus Pola. I wanted to get your thoughts on that data set, especially since it seems like they had a little more second-line plus more patients with two median prior lines of therapy. And considering the phase III ongoing SKYGLOW trial, I wanted to get your thoughts as to how you see the landscape evolving should that trial read out positive and what sort of impact it might have on the utilization of ZYNLONTA plus glofitamab in the second-line setting. Thanks.
Yeah. So yeah, I think the glofitamab Pola data is strong. I mean, it was about a 62% CR rate in some tough-to-treat populations. I think it shows it's a potent combination. Again, I think when you look at this combination, we think it's actually very strong at 78% CR rate. Polatuzumab has done a good job.
It's the first agent with the POLARIX trial in over 20 years to change the front-line setting from R-CHOP to Pola-R-CHP. And a decent number of patients, probably somewhere around a third, maybe even a little more of patients are getting Pola front-line. So I think that agent has definitely advanced the front-line setting. With regards to the other front-line studies and bispecifics, I think there's clearly some excitement around them. We'll see where they get approved. One thing that's important is, like the Pola study upfront, it's being studied in IPI two to five patients. That's roughly two-thirds of patients in the front-line setting. And obviously, what we've seen, I think if bispecifics do get approved to show good agent, they're going to capture a portion of it. So not every patient, I think, is going to get a bispecific or Pola front-line.
But having a non-Pola regimen in the second line is important given how strong Pola has been upfront. And that's, again, where we think the combination of glofitamab plus ZYNLONTA, where you have a different ADC exposure, is good. And then whether there'll be recycling of bispecifics from front-line to second-line, I think it depends probably. It's hard to speculate, but I think it'll depend somewhat on the response of the patient. Are they primary refractory? Do they relapse over time? But they had a good response. We do see that there's recycling, obviously, with rituximab between the front-line and second-line setting. And in this dynamic environment where bispecifics, we don't know how deep are they going to go in the community. Will they get approved front-line? There are some open questions.
This is where we believe our strategy of having both LOTIS- 5 and LOTIS- 7 is so important because we have the opportunity to have potentially a best-in-class bispecific ADC combination in that complex treatment segment where it requires more sophisticated administration of the product, and in the broadly accessible segment where patients can give everything, there's still a lot of chemo use, a lot of ADC and monoclonal antibody use. We have LOTIS- 5. Beyond this update, I think I want to just reiterate also, LOTIS-5 i s going to be a big update that's going to come in the first half of 2026. It is our confirmatory phase III study, and we believe that alone, even beyond LOTIS- 7, can significantly increase the potential of ZYNLONTA versus where we are today.
Awesome. Thanks.
Yeah. Thank you.
There are no further questions at this time.
I will now turn the call over to Ameet for closing remarks.
I want to thank everyone for joining the call today and for your continued support. We look forward to keeping you updated on our progress. Operator, you may now end the call.
Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.