ADC Therapeutics SA (ADCT) Earnings Call Transcript & Summary

Good morning, ladies and gentlemen. Welcome to the ADC Therapeutics EHA 2025 LOTIS-7 Conference Call. [Operator Instructions] This call is being recorded on Thursday, June 12, 2025. I would now like to turn the call over to Marcy Graham, Investor Relations and Corporate Affairs Officer for ADC Therapeutics. Marcy, please go ahead.

Thank you, operator. Today, we announced an update to the data in our LOTIS-7 trial, which will be presented at the European Hematology Association Congress, or EHA. The press release and the slide presentation we will use on today's webcast are available on the Investors section of the ADC Therapeutics website. I'm joined on today's call by our Chief Executive Officer, Ameet Mallik, who will provide an overview of our corporate strategy and our ZYNLONTA franchise, including our plans for expansion. Our Chief Medical Officer, Mohamed Zaki, who will discuss the progress made with our LOTIS-7 clinical program and provide trial updates. Also joining us on today's call is Dr. Juan Alderuccio, Associate Professor of Medicine and Hematology at the Sylvester Comprehensive Cancer Center at the University of Miami, who specializes in the study and treatment of patients with lymphoma and is a principal investigator on the LOTIS-7 trial. Dr. Alderuccio will take us through the details of the EHA presentation. We will then open the call to questions. Before we begin, I would like to remind the 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, Marcy. As an approved single-agent therapy in 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 ZYNLONTA has the potential to reach significantly more patients while growing the commercial opportunity by expanding use into earlier lines of therapy in DLBCL and indolent lymphomas. Our ongoing Phase III LOTIS-5 study in second line plus DLBCL patients is a confirmatory trial of ZYNLONTA in combination with rituximab, a drug community physicians are comfortable using and one that is considered a backbone of DLBCL therapy. Not only does this combination offer the potential of competitive efficacy and a favorable safety profile, but it is also a nonsystemic chemo regimen that avoids the irreversible toxicities associated with chemotherapy, a class that is still widely used in second-line plus DLBCL. LOTIS-7 trial is a Phase Ib study in patients with relapsed or refractory B-cell non-Hodgkin lymphoma and is the focus of today's discussion. Today, we will review updated results from the study being presented at EHA with a subsequent oral presentation at ICML. ZYNLONTA is also being evaluated outside of DLBCL with compelling data from Phase II investigator-initiated trials in both follicular lymphoma and marginal zone lymphoma recently presented at ASH. Additional data from the Phase II IIT in relapsed or refractory marginal none lymphoma will be presented at ICML next week with the abstract going live on June 15. Looking at the overall DLBCL treatment landscape, whether in the second or third-line setting, there are 2 main segments. The first are complex therapies, which require unique infrastructure and expertise to handle logistical requirements and patient management. This includes therapies like CAR-T, transplant and bispecifics. The second are more broadly accessible therapies, which all physicians can administer in the outpatient setting, including therapies like ADCs, monoclonal antibodies and chemotherapy. Bispecifics have already been approved in the third-line plus setting as monotherapy, and there's currently a 60-40 split between the complex and broadly accessible segments, respectively. In the second line, where bispecifics have not yet been approved, but were recently added to NCCN guidelines for use in combination. The split is closer to 25-75. We believe the emerging clinical profile of ZYNLONTA plus glofitamab in the LOTIS-7 trial positions us well among complex therapies. At the same time, the clinical profile of ZYNLONTA plus rituximab being in the safety run-in portion of the LOTIS-5 trial can differentiate us among more broadly accessible therapies. ZYNLONTA has the potential to disrupt the relapsed or refractory DLBCL market and unlock significant growth in both segments. We believe the initial LOTIS-7 efficacy data give us the opportunity to be highly differentiated to bispecific monotherapies and emerging bispecific combinations. The initial LOTIS-5 data demonstrated a 50% complete response rate, which is double that of our monotherapy data in third line plus DLBCL. Although only 20 patients, we believe that the full trial data are consistent with the safety run-in portion, this positions us well against other broadly accessible therapies. ZYNLONTA combinations have the potential to unlock significant growth by doubling our addressable patient population by expanding into the second line, capturing higher market share with differentiated efficacy and increasing the average duration of therapy. While ZYNLONTA is currently approved as a single agent in third line plus DLBCL, we believe ZYNLONTA has the potential to be the backbone therapy for combinations, raising the bar for efficacy in second line plus DLBCL. ZYNLONTA is a systemic chemo-free option, which can be combined with the highly effective bispecific glofitamab and the most widely used agent rituximab. We believe ZYNLONTA plus glofitamab in LOTIS-7 and ZYNLONTA plus rituximab in LOTIS-5 are complementary approaches to addressing unmet needs in the 2 key treatment segments. At this point, I'd like to invite Mohamed to share a bit more with you about our LOTIS-7 trial. Momahed?

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 2 highly potent single-agent drugs offer important and complementary mechanisms of action in DLBCL, which target 2 different B cell surface antigens 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 nonhematologic toxicities between the 2 agents. By dosing ZYNLONTA prior to glofitomab, it is our hypothesis that this dosing schedule has the potential to debulk the tumor and lower CRS rates and grades. The design of the trial includes 2 parts. In Part 1 dose escalation was conducted across non-Hodgkin's lymphoma patients at 3 dose levels of ZYNLONTA with glofitamab or mosunetuzumab in the third line plus. In Part 2, dose expansion moved forward in second-line large B-cell lymphoma with ZYNLONTA at 2 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. We have dosed the initial 40 patients, 20 in each cohort for the dose optimization and selection. 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. The primary endpoint is safety and tolerability with secondary endpoints of efficacy, PK and immunogenicity. As of the cutoff date of April 14, initial data suggests the combination of ZYNLONTA plus glofitamab is generally well tolerated with a manageable safety profile in large B-cell lymphoma with no DLTs at either 120 or 150 microgram per kg dose during dose escalation. Dr. Alderuccio will provide more details here. But it is important to note that neutropenia and known adverse event of each drug was the most common treatment-emergent adverse events of grade 3 or higher. We have not observed an additive effect when it comes to neutropenia. The overall rate of neutropenia was approximately 24% in this study, which is similar to the average reported in the approved prescribing information of each drug separately. In addition, we observed lower rates of CRS compared to glofitamab monotherapy label. All CRS and ICAN events observed were low grade with the exception of one Grade 3 CRS event at 120-microgram per kg dose. Importantly, no Grade 5 treatment emergent adverse events have been observed. Turning to efficacy. We observed an overall response rate of approximately 93% and an unprecedented complete response rate in this setting of approximately 87% per Lugano criteria. Of note, 25 out of 26 patients with complete response remained in CR as of the data of cutoff. In addition, we observed conversions over time with 12 patients converting from stable disease or partial response to complete response in the study. Based on the scientific evidence available and in alignment with the Data Safety Monitoring Committee, we have selected the 150-microgram per kg dose for expansion to 100 patients. Of note, 150-microgram per kg is the approved starting dose of ZYNLONTA for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy. As I mentioned a moment ago, in this study, safety was manageable in both doses. However, we observed a lower rate of CRS of any grade at the 150-microgram per kg dose compared to the 120-microgram per kg dose. In addition, both doses showed high level of efficacy. However, the median time to complete response was shorter at the 150-microgram per kg dose at 42 days as compared to 80 days at the 120-microgram per kg dose, which is an important factor in treating aggressive lymphoma. Finally, from a clinical pharmacology perspective, we observed an increased predictive probability of having a high complete response with the 150-microgram per kg dose compared to the 120-microgram per kg dose. The impressive efficacy and manageable safety profile seen to date in this trial with the combination of these 2 potent anticancer agents with unique mechanisms of action is encouraging. The data reinforce our belief in the potential for this regimen to change the treatment paradigm for patients with second line plus DLBCL. With that, it is my pleasure to pass the presentation over to the principal investigator on the LOTIS-7 study, Dr. Juan Alderuccio.

Thank you, Mohamed. Baseline characteristics in this study are representative of the second line plus diffuse large B-cell lymphoma patient population and similar to other studies in this space. Among the 41 safety evaluable patients, there are a few characteristics that are important to highlight. The median age in this study is 71 with a range of 26 to 85 years of age. The study enrolled patients with large B-cell lymphoma, including de novo diffuse large B-cell lymphoma, transformed follicular lymphoma, high-grade B-cell lymphoma and Grade 3b follicular lymphoma, all considered to be diffuse large B-cell lymphomas. Median prior lines of therapy was 2 with a range from 1 to 5. This study includes a number of difficult-to-treat large B-cell lymphoma patients. Nearly 20% of patients presented as double or triple hit, 19.5% of patients received prior CAR-T, which is in line with other trials done with bispecific combinations. Patients refractory to prior therapy were well represented in this study with 51% of patients refractory to primary therapy and 49% refractory to last prior therapy, both of which were slightly higher in the 150-microgram per kilo compared to 120-microgram per kilo dose. Safety was analyzed in the 41 large B-cell lymphoma patients who received at least 1 dose of loncastuximab plus glofitamab. Most notably, as Mohamed mentioned earlier, when looking at the Grade 3, 4 treatment emergent adverse events occurring in more than 5% of patients, neutropenia was the most common at 24.4%, which is similar to the rate of neutropenia reported in the prescribing information of each drug separately. So we are not seeing any additive effect here. Beyond that, to date, the type of TAEs observed are consistent with known safety profiles of each drug separately. The rate of serious TAEs were similar across both doses. Only 3 of the 20 patients experienced serious TAEs discontinued treatment. To date, the combination has shown a manageable safety profile and no new safety signal was observed. A total of 6 patients discontinued due to adverse event, 3 of which were serious TAEs. Overall, the numbers are small with 3 each for loncastuximab and glofitamab. For loncastuximab, we saw one case each of pericardial effusion, generalized edema and pleural effusion. And for glofitamab, we saw one case each of ICANS, polyneuropathy and febrile neutropenia. It is important to consider the profile and management of cytokine release syndrome and ICANS when using bispecific therapies. In this study, we can see that overall rates and all grades of CRS are higher at the 120-microgram per kilo dose compared to the 150-microgram per kilo dose. The 120-microgram per kilo dose had 55% any grade CRS, primarily Grade 1 and 2 with 1 case of Grade 3. The 150-microgram per kilo dose had 23.8% any grade CRS, all of which was Grade 1. Grade 1 and 2 CRS cases were managed with tocilizumab, corticosteroids, acetaminophen and our fluid bolus, without ICU admission or pressor support. The Grade 3 CRS case was managed with tocilizumab, acetaminophen, dexamethasone, norepinephrine and included ICU admission. ICANS were seen in 2 patients treated at a 120-microgram per kilo and 1 ICANS was observed at the 150-microgram per kilo dose. These ICANS were low grade and primarily managed with corticosteroids. All patients had a complete resolution of symptoms with 1 patient electing to discontinue treatment and 2 patients resuming treatment and ultimately achieving a complete response. Of the 41 treated patients at the time of the April data cutoff, 30 patients have reached the initial disease assessment and were efficacy evaluable. The results of observed across dose levels were consistent in terms of overall response rate, complete response and partial response. In this study, we have seen a 93.3% overall response rate and an 86.7% complete response rate. Median duration of response was not reached at the time of data cutoff. Looking now at the swimmer plots. The green bars show all patients in complete response and the lengths of these bars show the durability of each response. The gray bars represent patients who have not yet made it to the first disease assessment, so are not yet evaluable for response. Most responses were observed at initial assessment, which occurred at day 42. 25 out of 26 patients who achieved a complete response have maintained that response after the data cutoff. And 12 patients converted from an assessment of a stable or partial disease to complete response over time. At this point, the longest response in this study is more than a year. Complete responses were observed regardless of prior therapy. Of the 6 patients previously treated with CAR-T and undergoing response assessment, 5 achieved a complete response. The median time to complete response was shorter in the 150-microgram per kilo at 42 days compared to median time to complete response in the 120-microgram per kilo dose at 80 days. Median time to complete response along with the safety differentiation and pharmacokinetics modeling supported the recommendation of the DSMC, of which I am a member to move forward with the 150-microgram per kilo dose of loncastuximab for further expansion. While still early, these data are highly encouraging. I would now like to turn the call back to Ameet.

Thank you, Dr. Alderuccio, for walking us through the LOTIS-7 trial update. We are encouraged by the data and look forward to expanding enrollment to 100 patients at the selected 150-microgram per kilogram dose. Within our current indication, our commercial strategy is focused on relapsed or refractory DLBCL patients who need a treatment with a fast durable response and a manageable safety profile, which can be administered in the outpatient setting. We believe LOTIS-5 has the potential to take ZYNLONTA to $200 million to $300 million in peak sales as we expand into the second-line setting. This is driven by doubling the patient population, extending the duration of therapy and improving the clinical profile versus our current indication as a monotherapy. With LOTIS-7, we estimate we can expand the total opportunity for ZYNLONTA in DLBCL to $500 million to $800 million in peak revenue with regulatory approval and compendia listing. If the data persists, we believe ZYNLONTA plus glofitamab has the potential to transform the future lymphoma treatment paradigm by becoming the preferred bispecific combination in the second line plus DLBCL setting. Additionally, in indolent lymphomas, there is a clear unmet need in both the relapsed or refractory marginal zone lymphoma and relapsed or refractory follicular lymphoma settings. We are encouraged by the initial data seen in the Phase II IIT suggesting a ZYNLONTA regimen could provide significant benefit in these indolent lymphomas. We believe the indolent lymphomas opportunity could provide additional peak revenue of $100 million to $200 million with regulatory approval and compendia listing, primarily driven by marginal zone lymphoma. Taken together, we believe ZYNLONTA has the potential to reach peak revenues of $600 million to $1 billion in the U.S. Across the LOTIS-7, LOTIS-5 and marginal zone lymphoma ZYNLONTA programs, we expect to have multiple data catalysts in the remainder of 2025 and 2026, with potential approval or compendia listing for all of these in the first half of 2027. With LOTIS-7, we intend to share fuller more mature data toward the end of this year and expect to complete enrollment of 100 patients at the 150-microgram per kilogram dose in the first half of next year. We plan to engage with regulatory authorities starting later this year, while we simultaneously pursue publication and a potential compendia strategy. For LOTIS-5, we expect to reach the prespecified number of PFS events by the end of this year with top line results and a potential BLA submission in the first half of next year. With indolent lymphomas, we expect additional Phase II IIT data to be shared at medical conferences this year and next by the lead investigators. And beyond the use of ZYNLONTA, we are excited to see the advancement of our exatecan-based PSMA targeting ADC with potential completion of IND-enabling activities towards the end of this year. Overall, we believe we have multiple value-driving catalysts within our cash runway. We can now open the line for questions. Operator?

[Operator Instructions] And with that, our first question comes from the line of Kelly Shi with Jefferies.

Congrats on strong data. I have a couple of questions to Dr. Alderuccio. Maybe firstly, based on this durable complete remission rate -- I mean complete response rate at approximately 6 to 7 months of a median follow-up time, would you be able to predict overall survival benefit based on previous clinical trial experience? Do you see a good correlation of complete response rate to overall survival for lymphoma therapies?

Thanks, Kelly, for the question. So Dr. Alderuccio, I think the question, Kelly, you're asking is really about the durability of the CRs and the potential for that to translate over time into overall survival benefit and what the correlation between CRs and OS is? So Dr. Alderuccio, could you handle that?

Yes. Thank you for the question. This is a critical question about large B-cell lymphoma. Yes, the high number of CR seen in the trial in LOTIS-7 is encouraging. And we know that complete response by the Lugano criteria that was the criteria used in this study is a strong surrogate of durability. As the current data cutoff, 25 out of 26 CR patients remain in CR. In addition, CRs have been shown to be durable with each drug individually in the heavily pretreated third line plus single-agent langastuximab and glofitamab. So I agree that we need longer follow-up, but the current results are encouraging. And I think it's high encouraging of that these complete responses will translate in a survival benefit.

And also a follow-up is on efficacy, this initial data showing the efficacy actually could a surplus CAR-T. But could you also comment on overall tolerability profile, including CRS, ICANS, but also neutropenia, thrombocytopenia, those immune cell-related to tox of ZYNLONTA, glofitamab combo and make a comparison to other therapies in lymphoma. How would you assess the possibility for this combo regimen to be broadly used at community centers?

So yes, these...

Yes, that's an important question.

I'm sorry.

No, no go ahead Dr. Alderuccio, please.

Yes, so these agents independently has been in the -- have been approved for already a few years and people is more and more comfortable dealing with the unique toxicities. What is important to highlight is that the toxicities of this combination were not higher than the single-agent toxicity report on each trial independently. So we didn't see any addition on -- or a cumulative effect or higher effect of this combination on the rate of neutropenia, ICANS or CRS. So I think that's the first point that is important to remark that they had the current follow-up and with the current number of patients enrolled. Regarding the question about if these patients will be adopting community centers. We think that -- I think that while broad accessible therapies have traditionally been used in community centers, uptake of bispecific is already occurring in more sophisticated community centers. And over time, I expect to see bispecific combinations more broadly adopted in community centers as they have shown a better clinical profile as in this trial. So I think the initiation of loncastuximab before glofitamab was a decision in the study schema because this appears to have decreased the toxicity of glofitamab.

One more, if I may. Could you help us to understand the rationale of the synergy between ANTI-CD19 ADC in the CD20 T-cell engager, why this combination can achieve efficacy better than CAR-T? Is it due to like different modalities, different mechanism of action and the broader epitope coverage? Could you help us to understand like the reasons behind?

Yes. So maybe I'll -- Mohamed, you could first talk mechanistically about the 2 molecules and how they fit together. And then Dr. Alderuccio, if you have anything else to add, that would be great as well.

Sure. In terms of the mechanism of action of each drug separately. First, I want to highlight there are 2 potent agents. Each one is approved an accelerated approval. The second part that is important here, they actually target 2 separate antigen expressed in the B-cell. One is the CD20 and other one of CD19, which could bring a complementary mechanism of action. More importantly, the activation of immune system by each drug, typically, of course, the glofitamab activate the immune system, possibly creating adaptive immunity with memory cells. Also, ZYNLONTA kills the cell through immunogenic cell death by apoptosis that also activates the immune system, creates adaptive immunity and memory cells. Now earlier, as we've shown by each drug separately, the median duration of complete responses have not been reached after 2 years for ZYNLONTA and after 3 years for glofitamab with limited duration of cycles used. So it tells you that the resistance of CRs without treatment could possibly be dated actually by the immune system activation that lasts for much longer than the actual treatment itself. So that's pretty much, Dr. Alderuccio please feel free to add if you would like.

Yes. No, I agree. These are highly effective agents independently that has been shown in Phase II studies and the mechanism of action is independently of one or the other loncastuximab has -- is an ADC with a cytotoxic payload and glofitamab and ANTI-CD20/CD3 T-cell engaging. So I think it's a synergistic effect between both agents that is the one that triggers the efficacy and the results that we have seen in the current presentation.

And your next question comes from the line of Michael Schmidt with Guggenheim.

Yes, congrats, really nice data update here at EHA. Yes, I thought the sort of conversion to CR over time is quite interesting sort of from either PR or even SD. Is that something that's unique to this combination? Or is that seen with glofitamab as well? And then I know it's a fixed duration regimen, but what -- for modeling purposes, what is a good duration of treatment assumption for this if you account for this, the need to perhaps treat longer to convert patients to CR over time?

Okay. Thanks, Michael. So 2 parts to your question. One was about the conversion of to CR over time. You saw in the swimmer slot that 12 of the patients converted, 1 from SD, 11 from PR, so just why that happens. And the second question was about the fixed duration and how many cycles. So I'll answer the second part first, and I'll turn it to Mohamed and Dr. Alderuccio for the first question. So in terms of the fixed duration of cycles, typically with ZYNLONTA monotherapy, what we're seeing in the third-line setting is an average of 3 cycles. What we've seen in this trial for the patients who have got treatment is an average of 6 cycles of ZYNLONTA and also an average of 6 cycles of glofitamab. So it is a fixed duration therapy, and yet we see durability continuing beyond that. But maybe, Mohamed, do you want to start and then Dr. Alderuccio, you can chime in as well, just on why there can be conversions from patients who are initially assessed with the PRSD, but over time can convert to a CR.

Yes. As I mentioned in the previous question, the mechanism of action of each drug separately with the acquisition of immune response maintains the disease control without the need for continuation of treatment. So that is very encouraging in treating a lymphoma patient with a fixed duration treatment and the response is maintained. If you see how this happened in each drug separately, when we got accelerated approval, the CR median duration response was not reached for 2 years by ZYNLONTA in spite of the median duration of number of cycles used was about 3 and for glofitamab, the same phenomena with CRs median duration response not reached as of 3 years with the median number of cycles for that study is about 5. In the current study, the median duration of cycles for each drug separately was 6 cycles of ZYNLONTA and 6 cycles of glofitumab. So we are predicting this to be the same phenomenon. The CRs is lasting already and the conversion at the earlier data cut when we showed that in December was 5 conversions. Now we have 12 conversions. So it's actually going exactly where we expect it to go. Dr. Alderuccio, if we would like to please add anything you would like to add.

Yes. No, I agree with your statement, Mohamed. I think also it's important to remember that glofitamab as other bispecific may produce an initial tumor flare. And we base the response on the Lugano criteria, which is nuclear medicine, a PET/CT based response criteria. So it's possible that the higher uptake that we see in the lymphoma area is compatible with a partial response or a stable disease because of the T-cell infiltration, but the inflammatory reaction that this drug produced and that subsequently, the response improved from the stable disease or partial response to a complete response. I think that's also something that can partially explain the reason for these conversions.

Okay. And then I mean, when we talk to physicians just earlier this week, I think they really like to see this combination approved ultimately, FDA approved. And so yes, I'm just curious, so this 100-patient cohort now that you're expanding into. Do you think this could potentially support an FDA filing? Or is there the plan perhaps to conduct a larger study subsequent to completing this expanded cohort?

Yes. Great question, Michael. So yes, the plan, as you said, is to expand the 150-microgram per kilogram dose in this LOTIS-7 study to 100 patients in total. We know that, that will help to serve 2 key purposes. One is based on different precedents when you look at 3 different bispecific combinations were added in the first quarter of this year to preferred NCCN guidelines, it was based on about 100 patients. And we think that's a sufficient number upon publication to be able to submit and hopefully get accepted as a preferred regimen in NCCN guidelines. But the other benefit of 100 patients is it produces a much larger safety database, which is helpful for regulatory discussions. And so there's 2 reasons why we're doing it. Mohamed could speak about -- we do plan to engage with the FDA in the second half of this year to explore possible regulatory approaches. It's not clear if we're going to do that, but we are going to have engage in discussions on what potential approaches can be. So Mohamed, do you want to talk how we're thinking about the regulatory approach?

Yes. Thanks, Ameet, and thanks for the question, of course. It is important to highlight that the high CR rate, unprecedented seen in this study with the manageable safety profile is very encouraging. And with the 100 patients enrolled going to the agency and discussing what's the potential o bring in this regimen quicker to patients in an ethical trial, meaning the control arm has to be a good decision. Now it is not clear what the control are could be at the moment because of the [indiscernible] are not popular anymore in the U.S. and maybe Western countries and becoming very hard to enroll patients if that's the control among others, nothing rises to the level of this number of CR. So during the CAR-T approval, there was a synthetic control arm used in order to approve CAR-T in a single-arm trial with 100-plus patients. So that could be a discussion or typically, we could land into a control arm, what's called investigator best choice between whatever available therapy in a global study, have to make choices whether the control arm is available not just in the U.S. and other countries as part of the trial. So as Ameet mentioned, we are going later this year to discuss the regulatory path with the agency among other things, we'll discuss.

Yes. And then Michael, with the financing that we announced also this morning, we're funding the full 100-patient expansion as well as we announced the extending the cash runway to 2028. Any further regulatory discussions, I think, would also probably have to be in conjunction with the partners that we have also in the study? Operator, go ahead.

Your next question comes from the line of Eric Schmidt with Cantor.

Congrats also on the data update. Maybe 2 questions. One for Dr. Alderuccio and one for the company. Dr. Alderuccio, if you look forward to a time when you have access to both this combination as well as CAR-T therapy in the second-line DLBCL patient population, are there subsets of patients that you think would be better served by one or the other treatment paradigm? And then for the company, actually, Ameet, you just kind of touched on this. How should we think about we think about [indiscernible] future participation in a development program for this combination? What would be a good result for ADCT?

Okay. So Dr. Alderuccio, do you want to start with how you would think about this in your future treatment paradigm if this becomes accessible as well as CAR-T and other therapies?

Yes. That's a good question that I have been doing myself after starting seeing the data. I think if the data persists, the combination of loncastuximab plus glofitamab will be the preferred bispecific combination option in patients without access or not suitable or who progress after CAR-T. Right now, defining the one population or the other is difficult with preliminary data, but I think it's highly promising. I think also it's important to recall that the current CAR-T that are in the -- are approved, require a process of catheter insertion and a process that will take a few weeks until the product is ready for the patient to receive it. And patients that are quickly progressing, there are risk of further progression and deterioration, potential death if they are not treated promptly. So I think this combination that is off the shelf and the patient can start quickly once the following day, if needed, is very attractive in that population, patient that require treatment right away, and this a common scenario in relapsed/refractory B-cell lymphoma.

Yes. And then with regards to Roche, as you know, since the start of the study, we've worked very closely with them, and we really appreciate the collaboration, Roche is obviously one of the leaders within the lymphoma space. And we benefited not only by them providing supply of the product as a clinical trial, but also really valuable insights, both clinical and regulatory insights based on their experience. So we really appreciate the collaboration. And I can't comment or speculate on what the future will be, but we do look forward to continuing to collaborate and assessing different ways in which we can continue to partner to bring this combination to as many patients as possible going forward and look forward to keeping you updated as that progresses.

Your next question comes from the line of Sudan Loganathan with Stephens.

This is Felix for Sudan. Thank you very much for the data, and we are impressed. I have 2 questions. What was the reason for the discontinuation rates? And what was the discontinuation rate as at the last time of data cutoff? And number two, the ORR looks very impressive, but we wanted to understand which ORR benchmark that you are looking to beat or be on par with?

Okay. Well, 2 great questions. So maybe Dr. Alderuccio, I'm going to actually have you start with both of these. So the first question, Dr. Alderuccio, was what are the reasons for discontinuing treatment within LOTIS-7?

So the most common reason for this discontinuing both agents during the study was physician or patient decision after achieving a satisfactory response such as a complete response, followed by a few additional cycles of consolidation. Additional reason to stop treatment included reaching the maximum number of cycles of either or both drugs, reaching deep enough responses with intention to bridge to cellular therapies such as CAR-T or transplant that happened in only 2 patients and adverse events. Those were the most common reasons.

And then the second question, which is what do you think would be -- I think you were asking a compelling overall response rate and CR rate for this trial as the study matures.

Yes, that's a great question. I think our profile with -- so I will say that rather than overall response rate in aggressive lymphoma as physician, I am interested in complete response rate. And a profile with a CR rate or complete response rate above -- at or above 70%. And comparable durability to what we are seeing with other bispecific combinations, will be clinically differentiating from other treatment options. In this trial, the complete response rate was 86.7%, with 25 out of 26 patients remaining CR a data graph that gives confidence that -- about the profile of this combination.

Apologies, I was on mute. Your next question comes from the line of Leonid Timashev with RBC Capital Markets.

This is Mitch on for Leonid. Just wondering if you could provide some additional context on the safety profile of LOTIS-7 compared to the safety profile of glofitamab in prior studies? And why do you think that the CRS and ICANS rate are potentially lower at the 150 dose of ZYNLONTA compared to the 120 dose?

Sounds good. We really appreciate it. So maybe, Mohamed, do you want to take this one, which is just comparing the safety profile, particularly with regards to CRS and ICANS of glofitamab monotherapy versus this combination? And why do you think that the 150-microgram per kilogram dose does even better than the 120-microgram per kilogram dose of ZYNLONTA when combined with the full dose of glofitamab?

All right. Thank you, Ameet, and thank you for the question. First of all, I would like to highlight that the label of glofitamab showed 70% any grade CRS with a single agent in the trial that led to the approval. Currently, with the addition of ZYNLONTA ahead of glofitamab to help debulking more than what's already included in the label of [indiscernible] at day 1, we added ZYNLONTA at day 2 and glofitamab for the first time at the 8 and then sequence cycle they are dosed together seems to have helped in reducing the all-grade integrate CRS. And if you see the differential between the 2 doses, the CRS rate observed in the 120 in the range of 55% slightly but still lower than glofitamub alone showed. However, in the 150, it's about 2.4%. So significantly reduction in the recent CRS. In addition, the 120 had three Grade 2s and one Grade 3. The 150 have only Grade 1. And if you know the difference, Grade 1 is simply using [indiscernible] and steroids. Grade 3 is ICU. So we see a very strong benefit from that perspective. The reason the 150 was selected for expansion have 3 main reasons. As I mentioned, the reduction on the rate and grade of CRS as seen by the Data Safety Monitoring Committee who oversee the trial in the escalation and expansion and dose selection. That's number one. Number two, the median time to CR was shorter on the 150 at 42 days compared to 80 days at the 120. In addition, from a clinical pharmacology perspective in the modeling shows that predictable probability of having a deeper response is more when you actually have higher doses in the first 2 cycles compared to 2 lower doses. So pretty much the 3 elements that usually are used for dose optimization and selection have met. And unanimously, that safety committee recommended 150 to be the dose to move to expansion. So I hope that answers explains the things and addresses your question.

Yes. Thanks, Mohamed. And just a reminder, the 150-microgram per kilogram dose of ZYNLONTA is the approved dose. So essentially, what we're moving forward with now in the continued expansion to 100 patients is the approved dose of both agents.

We have no further questions at this time. I would like to turn it back to Ameet Mallik for closing remarks.

Well, I want to thank you all for joining our call today and for your continued support. We look forward to keeping you updated on our progress. Operator, you may now end the call.

Thank you, presenters. And ladies and gentlemen, this concludes today's conference call. Thank you all for joining me now.