Adc Therapeutics SA Aktie

Good morning, ladies and gentlemen, and welcome to the ADC Therapeutics Q2 2026 Earnings Conference Call. [Operator Instructions] This call is being recorded on Thursday, August 13, 2026. 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 our second quarter 2026 financial results and business update. This release and the slides we will use in today's presentation 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 discuss our operational performance and recent business highlights; followed by our Chief Medical Officer, Mohamed Zaki, who will provide clinical and regulatory updates; and lastly, our Chief Financial Officer, Pepe Carmona, who will review our second quarter 2026 financial 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.

Today's presentation also includes non-GAAP financial reporting. These non-GAAP measures should be considered in addition to and not in isolation or as a substitute for the information prepared in accordance with GAAP. You should refer to the company's second quarter 2026 earnings release for information and reconciliation of historical non-GAAP measures to the comparable GAAP financial measures.

I will now turn the call over to our CEO, Ameet Mallik. Ameet?

Thank you, Nicole. We are pleased to share that ZYNLONTA's commercial performance in the second quarter of 2026 continued to be broadly in line with recent quarters. We remain confident in the role ZYNLONTA will continue to play as a differentiated single-agent treatment option for third-line plus DLBCL patients.

Turning to our pipeline progress. As previously disclosed, we announced top line results for LOTIS-5 in June. Based on this data, we held a pre-sBLA meeting with the FDA. And following the meeting, we are assessing the best regulatory path forward. Mohamed will share more details regarding the FDA feedback and our regulatory strategy.

Further to this, the full LOTIS-5 data have now been submitted for presentation at ASH, and we are preparing to submit for publication with compendia submission to follow.

For LOTIS-7, we were pleased to complete enrollment of 100 patients at the selected dose level of ZYNLONTA plus glofitamab as shared in June and have submitted an abstract to ASH for presentation of the data, which we continue to believe demonstrate the most compelling combination data generated to date in second-line plus DLBCL with a safety profile generally consistent with prior LOTIS-7 disclosures.

With these data, we believe that ZYNLONTA plus glofitamab offers an opportunity to take a leading second-line position in the context of the evolving competitive landscape, solidifying ZYNLONTA as a foundational therapy in DLBCL. Beyond this, we are preparing to submit for publication of the LOTIS-7 data with compendia submission to follow. Simultaneously, we are exploring the potential regulatory pathway for this combination and expect to submit for breakthrough designation this year.

With respect to the multicenter investigator-initiated trials of ZYNLONTA in indolent lymphomas, updated marginal zone lymphoma data was submitted to ASH with publication and compendia submission to follow. Presentation of updated follicular lymphoma data is anticipated in the second quarter of 2027 with publication and compendia submission to follow. We also intend to assess potential regulatory pathways for these indolent lymphomas and expect to submit for breakthrough designation for MZL.

Moving now to corporate updates. We announced a strategic reorganization in June. As part of this, we implemented a reduction in our workforce of approximately 17% as well as additional operational efficiencies, resulting in cost savings of approximately $10 million on an annualized basis. As shared at that time, with these changes, we are resourced to deliver on our key clinical, regulatory and manufacturing activities while maintaining the full externally facing footprint to support the continued commercialization of ZYNLONTA in the third-line plus DLBCL setting.

Finally, we ended the second quarter of 2026 with a healthy cash balance of $219.1 million, maintaining our expected cash runway at least into 2028 and enabling us to deliver against our strategy.

Now I'd like to take a moment to remind everyone of our strategy to grow ZYNLONTA. Currently, ZYNLONTA plays a clear role in the third-line plus DLBCL setting. As monotherapy, ZYNLONTA has a well-established profile of rapid, deep and durable efficacy as well as manageable safety with simple and convenient administration. Since FDA accelerated approval in 2021, ZYNLONTA monotherapy has been used in treating approximately 5,000 patients in the U.S. We believe this is just a starting point as we see the potential for ZYNLONTA to reach significantly more patients by expanding use into earlier lines of therapy in DLBCL and into indolent lymphomas.

Now I would like to turn the call over to Mohamed, our CMO, to share more on our pipeline.

Thank you, Ameet. I would now like to share more on our LOTIS-5 and LOTIS-7 studies as we continue to work towards expansion of ZYNLONTA in earlier lines of DLBCL. As a reminder, LOTIS-5 is our Phase III confirmatory study of ZYNLONTA in combination with rituximab versus R-GemOx in patients with second-line DLBCL, which recently read out and met the primary endpoint of progression-free survival.

As noted, we held a meeting with the FDA in early August to present and discuss the totality of the LOTIS-5 data, along with the potential regulatory pathway. During this meeting, the FDA noted substantial concerns regarding the benefit risk or verification of clinical benefit observed in the LOTIS-5 trial. As such, the company is now assessing the regulatory path forward. We plan to provide an update on regulatory strategy and timing in the future. Beyond this, the data has been submitted to ASH. We are simultaneously pursuing publication for LOTIS-5 and potential compendia inclusion starting in 2027.

Turning now to LOTIS-7, our Phase Ib trial combining ZYNLONTA with the highly effective bispecific glofitamab in second-line plus DLBCL patients. We recently announced completion of enrollment of 100 patients at the 150 micrograms per kg dose. Of note, consistent with other glofitamab trials, the protocol for LOTIS-7 recommends prophylaxis, including vaccinations for viral, fungal and bacterial infections, including PJP and herpes virus, which was not part of the LOTIS-5 protocol.

Here, we continue to be encouraged by the promising LOTIS-7 data shared to date, which we believe demonstrates the potential for ZYNLONTA plus glofitamab to be the best-in-class combination. The data on a larger number of patients with longer follow-up has been submitted to ASH for presentation. This data supports the company's belief that ZYNLONTA plus glofitamab demonstrates the most compelling combination data generated to date in second-line DLBCL with a safety profile generally consistent with prior LOTIS-7 disclosures.

Separately, we are preparing for submission of the full LOTIS-7 data for publication and following that, plan to submit to compendia for potential inclusion starting in 2027. In addition, based on this potentially practice-changing LOTIS-7 data, the company plans to submit for breakthrough designation this year and is assessing a Phase III trial for the combination of ZYNLONTA plus glofitamab.

Moving forward, we plan to work closely with the FDA to determine the best path forward to achieve the full approval and advance ZYNLONTA combinations into earlier lines of therapy in DLBCL. In the meantime, we remain confident that ZYNLONTA will continue to play a meaningful role for patients with B-cell malignancies within its currently approved third-line plus DLBCL setting.

With that, I would like to turn the call over to Pepe Carmona, our CFO.

Thank you, Mohamed. On the financial front, ZYNLONTA net product revenues in the second quarter of 2026 were $18.6 million as compared to $18.1 million in the same quarter in 2025. Cost of product sales was $2.3 million and $6 million for the second quarter and 6 months ended June 30, 2026, as compared to $0.8 million and $2.9 million for the same period in 2025. The increases compared to prior year are primarily driven by a change in focus of personnel from research and development clinical supply activities to commercial manufacturing activities.

Total operating expenses were $44.7 million for the second quarter. On a non-GAAP basis, total adjusted operating expenses were $37.2 million for the quarter and were down by 22% over the prior year, primarily driven by lower R&D expenses. As Ameet noted, we expect to save an additional $10 million on an annual basis as a result of the strategic reorganization we announced in June.

On a GAAP basis, we reported a net loss of $16.6 million for the second quarter of 2026 as compared to a net loss of $56.6 million for the same period in 2025. The second quarter of 2026 included a onetime expense related to the strategic reorganization, while the year-ago quarter included restructuring, impairment and related costs from the June 2025 strategic reprioritization and restructuring plan.

On a non-GAAP basis, the adjusted net loss was $16.3 million for the second quarter of 2026 as compared to a net loss of $28.7 million for the same period in 2025. The lower net loss on a non-GAAP basis was primarily due to lower operating expenses. The year-over-year changes on a per share basis were additionally impacted by the higher number of weighted average shares outstanding.

You can find the reconciliation of GAAP to non-GAAP measures for the second quarter in the accompanying financial tables of the press release issued earlier today and in the appendix of this presentation. At the end of the second quarter, we had cash and cash equivalents of $219.1 million as compared to $231 million as of March 31, 2026, a change primarily driven by cash used in operations. This provides us with an expected cash runway at least into 2028.

With that, I will turn the call back over to Ameet. Ameet?

Thank you, Pepe. To close, we are pleased by the commercial performance and the role that ZYNLONTA monotherapy continues to play in third-line plus DLBCL. We look forward to presentation of data from LOTIS-5, LOTIS-7 and MZL before year-end with publication and potential compendia inclusion to follow. Following the FDA pre-sBLA meeting, we are assessing regulatory approaches to determine the best path forward for the LOTIS-5 trial.

At the same time, we believe we have an opportunity for ZYNLONTA plus glofitamab to take a leading second-line position in DLBCL as a potential best-in-class bispecific combination and are actively assessing the potential regulatory path forward. Together, we anticipate we can grow ZYNLONTA beginning in 2027 as we work to make a meaningful difference in the lives of many more patients with B-cell malignancies.

We can now open the line for questions. Operator?

[Operator Instructions] Your first question comes from Eric Schmidt with Cantor.

Appreciate all the updates. Maybe just on the status of the current accelerated approval for ZYNLONTA, given the questions around risk benefit from LOTIS-5. Was there any FDA discussion of maintaining that accelerated approval status?

Yes, great question. So first of all, all the discussions with the FDA were related only to the trial. All their comments were specific to the combination of ZYNLONTA plus rituximab on the trial. So there was no feedback at all about the single agent. So we remain confident that the monotherapy will stay on the market. We'll continue to have accelerated approval. And we're committed to working with the FDA to make sure that we can satisfy the full approval either through LOTIS-5 or through another study.

And then on LOTIS-7 and your characterization of the most recent efficacy data that you guys have seen is compelling and consistent in safety. Have you essentially now seen the final ASH presentation? And do your comments pertain to that? In other words, do you know exactly what you'll present? And is it consistent with that statement?

Yes. So we've already submitted the abstract for ASH, which contains obviously the vast majority of the 100 patients that we enrolled. So the belief that I'm sharing with you about the fact that we think we have very compelling efficacy and safety data is reflective of that ASH abstract. We obviously, for disclosure reasons, you can imagine we don't want to share all the details, but we do believe that we have very compelling data, both from an efficacy and a safety standpoint within the LOTIS-7 data that was submitted to ASH.

And one more question, if I may, with regard to exploring a Phase III pathway for the combination in LOTIS-7. Is that something you're exploring with Roche or by yourselves?

I don't want to comment on that. Obviously, we have a great partnership with Roche, and they've given us great feedback throughout. But what I would say is we've had lots of discussions, but also lots of thought, as you can imagine, even independent of the feedback from the FDA about a potential Phase III design because we know that this data is so compelling that there could be significant upside for the asset by potentially pursuing a Phase III trial. So it's something we've been thinking about for a long time. The team has already been preparing on different design options, and we do plan to file for breakthrough designation this year and to discuss with the FDA potential designs.

Your next question comes from Michael Schmidt with Guggenheim Securities.

This is Sarah on for Michael. Just wanted to follow on quickly on the Phase III plans, whether you could give any color on sort of time line for that now that it appears to be sort of more of the future-looking focus. And then additionally, I had a sort of a question on the LOTIS-5 data. So I know you've mentioned the 105-day period for monitoring adverse events after treatment. I was wondering if you could comment on the timing of the deaths.

So first of all, I just want to emphasize we have a positive study for LOTIS-5. So we still are assessing possibilities to identify the best regulatory approach for LOTIS-5. I mean specifically, we're considering whether additional data risk management options or modifications to the potential label can address the FDA concern. So we are doing that.

In parallel, given that we have, we think, potentially practice-changing data on hand with the LOTIS-7, we're also in parallel going to file for breakthrough designation and explore a Phase III approach there. So it's too premature at this point, as you can imagine, while we're still gathering input from the medical community and obviously have to talk with the FDA on the final design to talk about timing and costs. But I just want to reemphasize that those 2 things are going in parallel.

And then with regards to the 105-day safety window in terms of capturing AEs post the last dose, that's the same, by the way, in LOTIS-7 as well. And one thing I want to emphasize is that as Mohamed mentioned on the call, there was a big difference between LOTIS-5 and LOTIS-7, particularly with regards to the prophylactic measures taken. So in LOTIS-7, consistent with a lot of the other -- with the other glofitamab trials that have been run, LOTIS-7 recommends prophylaxis, including vaccinations for viral, fungal and bacterial infections. That was not part of the LOTIS-5 protocol. So while the time period that we're capturing AEs is very similar, there was a pretty big difference in terms of prophylaxis in the protocol between 5 and 7.

Your next question comes from Maury Raycroft with Jefferies LLC.

This is James on for Maury. Can you provide more detail on the type of Grade 5 infections that were observed in LOTIS-5 and whether those events would have been expected to be mitigated by the prophylactic and vaccination strategies now incorporated in LOTIS-7? Did other infections occur that aren't addressed by those vaccines? And I have a follow-up after that.

Yes. So the primary type of infections were bacterial, which is why we think that prophylaxis could play a role.

Got it. And how do you think about the potential read-through from LOTIS-5 Grade 5 signal to potential NCCN compendia inclusion and adoption of the ZYNLONTA glofitamab combination within the academic community? Could LOTIS-5 impact the NCCN language? And could there be any safety monitoring requirements?

Yes. I don't think there will be any read-through in terms of LOTIS-7 compendia inclusion. Two very different studies, 2 different regimens. As I mentioned, the protocol is different, which we think can help to contribute to some of the safety differences. Just as a reminder, obviously, I can't speak to the data that we have on hand, but I can speak to the prior disclosure that we had. We had a very low percent of Grade 5 events, approximately 4% if you look at our last disclosure we had in December on the 49 patients that we reported. So I do think there's a difference and we don't think there would be a read-through to LOTIS-7 or to any potential NCCN or compendia inclusion.

We now have a question from Leonid Timashev with RBC Capital Markets.

Josh on for Leo here. I was wondering whether or not the FDA in their feedback in response to the Phase III, did they provide any kind of indication of what an effective path forward might look like and what strategies you guys are thinking about at the time being?

Yes. And I think typical in what you have in the pre-sBLA meeting, we share the data results and you're aligning on the package for an sBLA submission. During that, as it is typical with any other pre-sBLA meeting, they share concerns that they have with the data. And so right now, we're basically going through the feedback and assessing whether additional data risk management options or modification to the potential label can help to address those FDA concerns. And that's the basis of which we're evaluating our path forward for LOTIS-5.

[Operator Instructions] Your next question comes from Rob Burns with H.C. Wainwright.

This is Ahmed on for Rob. I was just wondering if you saw Q2 product revenue increase versus Q2 '25. And I was wondering if you've seen any changes in patient starts or unit demand dosing or physician prescribing behaviors since LOTIS-5 disclosure? And then for my second question, I was wondering if in your conversations with the FDA, did they focus on the PFS in patients 75 or older, and if that would influence eligibility criteria or future label?

Yes. So with regard to sales, we haven't seen any impact. If you look at the volume in Q2, very consistent with prior quarters. So -- and we don't think that there will be. If you look overall over the past several quarters, the commercial performance of the monotherapy in the third-line plus setting has been relatively consistent. And that's because ZYNLONTA has an established place in the third-line plus setting, and we don't expect any impact on monotherapy sales.

And then remind me again, I'm sorry, your second question.

No problem. I was wondering if...

Oh, just about patients 75 or older, right?

Yes.

Yes. We don't think it will have any impact on other studies. I think obviously, older patients specifically with infection, we think that the prophylaxis can play a role. And that's also why the protocol, again, I want to stress the LOTIS-7 versus LOTIS-5 are quite different. So I think each study is on its own. I don't think that there's a read-through from this. We certainly learned a lot from LOTIS-5, and we're happy with the differences in the protocol, of course, that we're seeing in LOTIS-7. So we don't see any read-through from LOTIS-5 to either the current indication or other potential combinations.

There are no further questions at this time. So I will now turn the call over to Ameet Mallik for closing remarks. Please continue.

Well, thank you all 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 today's conference call. Thank you for your participation. You may now disconnect.

Good afternoon, ladies and gentlemen, and welcome to the LOTIS-5 Presentation Conference Call. [Operator Instructions] This call is being recorded on Tuesday, June 2, 2026.

I would now like to turn the conference over to Nicole Riley. Please go ahead.

Thank you, operator. Today, we issued a press release announcing results from our Phase III LOTIS-5 pivotal trial. This release and the slides we will use in today's presentation 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; and our Chief Medical Officer, Mohamed Zaki, who will discuss our LOTIS-5 trial 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. Before we get into the details of the LOTIS-5 study, as a reminder, ZYNLONTA is an approved single-agent therapy in third line plus DLBCL. As monotherapy, ZYNLONTA has a well-established profile of rapid, deep and durable efficacy as well as manageable safety with simple and convenient administration. Since FDA accelerated approval in 2021, ZYNLONTA has been used in treating approximately 5,000 patients in the U.

S. Beyond our current indication, we believe in the potential to reach significantly more patients by expanding use into earlier lines of therapy in DLBCL and into indolent lymphomas, offering physicians options that address the unique treatment choices in each disease category. As a reminder, LOTIS-7 is our Phase Ib trial combining ZYNLONTA with the highly effective bispecific glofitamab in second-line plus DLBCL patients. Here, we continue to be encouraged by the promising data shared to date, which we believe demonstrates the potential for ZYNLONTA plus glofitamab to be a best-in-class combination in a highly competitive market.

Today, we will share with you the results of LOTIS-5, our Phase III confirmatory study of ZYNLONTA in combination with rituximab versus R-GemOx in patients with second-line plus DLBCL as well as our planned regulatory next steps.

I will now turn the call over to our CMO, Mohamed Zaki, to discuss these results in detail. Mohamed?

Thank you, Ameet. As noted, LOTIS-5 is our randomized open-label Phase III confirmatory study of ZYNLONTA in combination with rituximab versus R-GemOx in transplant ineligible second-line plus DLBCL patients. The trial enrolled a total of 420 patients randomized 1:1 with 210 patients in each arm. The primary endpoint of the trial was progression-free survival. The key secondary efficacy endpoint was overall survival. Other secondary endpoints included overall response rate, complete response rate, duration of response, duration of complete response, safety, PK parameters, immunogenicity and patient-reported outcomes.

ADC Therapeutics was blinded throughout the study. The study utilized both an unblinded independent data monitoring committee to regularly review safety as well as a blinded independent review committee to adjudicate response or progression for each patient. Looking at baseline characteristics, the patient population enrolled was generally balanced between the 2 arms, with the exception of more European patients in the test arm and more rest of world patients in the control arm. Of note, the study enrolled more than 60% primary refractory patients and more than 40% refractory to last therapy across both arms.

Now let's look at summary of the key efficacy results. The study met the primary endpoint of PFS with a statistically significant hazard ratio of 0.73 and a 2-sided p-value of 0.008. No detrimental effect was observed on the key secondary efficacy endpoint of overall survival. The OS hazard ratio was 0.96 and was impacted by the earlier use and higher rate of new anti-lymphoma therapy in the control arm. A higher CR rate was observed in the ZYNLONTA plus rituximab arm. In addition, a longer duration of CRs were seen and importantly, a higher proportion of CRs were maintained at 24 months in the ZYNLONTA plus rituximab arm. Finally, the results seen in the North America region were consistent with the overall study results.

Going deeper into the results. As noted, the study met the primary endpoint of PFS per independent review committee with statistical significance and a hazard ratio of 0.73 and 2-sided p-value of 0.008. Median PFS was 6.1 months for ZYNLONTA plus rituximab versus 4.7 months for R-GemOx. Looking at the Kaplan-Meier curve, you can see good early separation that was maintained throughout the entirety of the curve with a long tail as reflected by the event-free rate. You can see here at 18 months, the event-free rate is 25.1% versus 14.7%. And at 24 months, it is 23.2% versus 9.5% favoring the ZYNLONTA plus rituximab arm.

Looking at PFS by investigator assessment, results showed a hazard ratio of 0.65 with an improvement in median PFS of 5.5 months in ZYNLONTA plus rituximab arm compared to 3 months in the control arm. The difference seen between this PFS assessment and the PFS assessment by IRC is mainly driven by lower early sensoring in the investigator reported data. The main reason for early sensoring were starting new anti-lymphoma therapy without confirmed progressive disease, no post baseline assessment or consent withdrawals. Additional analysis evaluating Time To Treatment Failure or TTF is typically used to mitigate the impact of early sensing. TTF accounts for time to progressive disease, death, new anti-lymphoma therapy or discontinuation from any other reason. This analysis also shows a meaningful difference in ZYNLONTA plus rituximab with a hazard ratio of 0.64 and a median TTF of 5.19 versus 2.76 months.

Turning to the key secondary endpoint of overall survival. There was no detrimental effect observed. The overall survival had a hazard ratio of 0.96 with a median of approximately 12.2 months in both arms and did not achieve statistical significance. The OS results were likely impacted by earlier use and higher rate of new anti-lymphoma therapy in the control arm. Of note, the main cause of death in both arms was progressive disease.

Moving to overall response rate. The ORR was 58.1% in the test versus 45.2% in the control arm. Importantly, the CR rate was 39.5% in ZYNLONTA plus rituximab arm versus 26.7% in the control arm. The median time to best overall response was 44 days in both arms. The median time to complete response was 49 days with ZYNLONTA plus rituximab as compared to 65 days with R-GemOx. Furthermore, the duration of response was 9.2 months versus 7.7 months and duration of complete response was 16.8 months versus 12.3 months, both in favor of ZYNLONTA plus rituximab. Importantly, a higher proportion of CRs were maintained at 24 months, 48.5% versus 16.7% also in favor of the test arm.

Turning now to a summary of the key safety results. The overall Treatment-Emergent Adverse Events or TEAE rates were similar between treatment arms. Similar rates of overall Grade 3 or higher TEAE greater than 5% were observed across both arms. Hematologic TEAEs were higher in control arm where infection, hepatotoxicity and edema effusion were higher in the test arm. SAEs TEAEs leading to study drug withdrawal and Grade 5 events were higher in the test arm. Of note, the majority of Grade 5 TEAEs in the test arm occurred in patients aged 75 years or older.

In this study, TEAE reporting window was defined as 105 days after the last dose of the study treatment or part of a new anticancer therapy, whichever is earlier. The rate of TEAEs were impacted by the longer overall TEAEs observation time in the test versus control arm. This difference was primarily driven by the higher rate of an earlier switching to subsequent therapies in the control arm.

Going deeper now into safety results. The total TEAE rate were similar between the 2 treatment arms. Similar rates of total Grade 3 or higher TEAEs were observed across arms. As noted, SAEs TEAEs leading to study drug withdrawal and Grade 5 TEAEs were higher in the test arm. When it comes to Grade 5 TEAEs, 13.2% were in the test arm versus 4.6% in the control arm. Of these, 6 or 2.9% and 2 or 1% were deemed to be treatment related by investigators in each arm, respectively. The majority of Grade 5 TEAEs in the test arm occurred in patients aged 75 years or older. The highest observed Grade 3 or higher TEAEs more than 5% were hematologic followed by infection and infestation, hepatotoxicity with gamma GT increased as the primary driver and edema infusion. Hematologic TEAEs were higher in the control arm, infection hepatotoxicity and edema fusion were higher in the test arm.

Looking at analysis from the start of treatment to key safety events helps better explain the impact of the safety observation period on the rate of TEAEs reported. This analysis showed the median time to key safety events, including any Grade 3 or higher TEAEs, serious TEAEs or TEAEs leading to study drug withdrawal was longer in the test versus control arm. This showed more event-free time in the test versus control arm. Here, you can also see the rates of TEAEs impacted by the longer overall TEAE observation time in the test versus control arm. Longer overall TEAE observation time led to more reported events with ZYNLONTA plus rituximab. This difference was primarily driven by the higher rate of an earlier switching to subsequent therapies in the control arm.

Looking at overall treatment emergent Grade 5 events, the median age of patients was Grade 5 TEAEs was 76 versus 74 years old in the test versus control arm. Infection was the leading cause across both arms and was higher in the test as compared to the control arm. The main type of infection in the ZYNLONTA plus rituximab arm was bacteria. Of all Grade 5 TEAEs, 59% versus 22% occurred in patients aged 75 years or older in the test versus control arm, respectively. The treatment exposure of Grade 5 treatment emergent adverse events was a median of 4 cycles for ZYNLONTA plus rituximab and a median of 2 cycles R-GemOx. Considering the overall safety profile observed with the combination of ZYNLONTA plus rituximab in patients aged 75 years or older in this study, we expect physicians would consider potential mitigation actions that might include assisting the immune system before treatment, considering prophylaxis and being proactive in treating infection. Taken together, I look forward to discussing these trial results with the FDA in the coming months.

Now I would like to turn the call back over to Ameet.

Thank you, Mohamed. Looking ahead, based on the totality of the LOTIS-5 data shared today, we plan to conduct a pre-sBLA meeting with the U.S. FDA in August with a planned sBLA submission as well as presentation at a medical meeting to follow in the fourth quarter 2026.

Separately, I'd like to share that our LOTIS-7 Phase Ib trial remains on track to be fully enrolled in the second quarter of this year, and we continue to anticipate data readout later this year. In addition, the Phase II IIPs in marginal zone lymphoma and follicular lymphoma are expected to read out between the end of this year and middle of next year.

Before we move to Q&A, we would like to extend our gratitude to the patients, investigators and clinical teams as well as to all our employees who contributed to this important trial.

We can now open the line for questions. Operator?

[Operator Instructions] Your first question comes from Eric Schmidt of Cantor.

I appreciate the very comprehensive update here. In terms of the Grade 5 treatment-emergent adverse events, it looks like in the ZYNLONTA plus rituximab arm, the total rate here is a little more than maybe double what you saw in LOTIS-2 and also higher than what we've seen from LOTIS-7. Is there a rationale in your mind for why we're seeing a higher absolute rate of Grade 5 events? Is it patient selection? Is it combination with rituximab? Is it entry criteria? Any thoughts?

We believe that one of the main reason -- likely reason of higher observed Grade 5 in the test versus control or versus others, but the reporting or the observation period in the control arm was much longer compared to the test arm, that contributed to more -- can you hear me well, sorry?

My question was more just about the absolute rate of Grade 5 events at about 13% here in this study. I think in LOTIS-2, it was much lower at about 6%. And I don't think we've seen anything like that even in LOTIS-7. So wondering what about these patients or this trial has an elevated rate in your mind?

Yes. I think one of the things, and I'll turn it to Mohamed. One of the things is you had a large portion of patients over 40% that were over 75 years of age. Most of the patients with the Grade 5 events happened in that over 75 population, mainly due to infections. Obviously, for LOTIS-2 single agent, it's a different regimen. And for LOTIS-7, to your point, in the first 49 patients reported, we saw quite a low rate of Grade 5 TEAE, only 2 of the 49 patients, so mid-single digit.

In addition, as I mentioned to you also, LOTIS-2 have reported treatment emergent adverse events within 30 days window. This trial have reported into 105 days window. Again, the more time, [indiscernible] the more adverse events you will see in this versus control comparison between trials sometimes hard in order to have single agent, single arm versus randomized trial.

Your next question comes from Maury Raycroft of Jefferies.

This is James on for Maury. We have question. Just going on the Grade 5 imbalance. What gives you confidence that the FDA will be willing to address this through label language with age-based restriction, for example, rather than viewing it as a benefit risk gating issue? And is there any precedent either in DLBCL or broader hem/onc for an age-based label restriction?

And just adding on to the last question, did you see any infection risk in the patients less than 75-year old or with 75 years old? Was there a difference there between treatment and control?

Yes. The majority of Grade 5 TEAEs in the long -- in the elderly patient population. And we believe that the longer overall observation time also have contributed to more reporting in the test versus control, also the difference was primarily driven by higher weight and earlier switching to subsequent therapies. That's why we have shorter reporting in one versus the other. We can't really speculate on what the label will be at this time. However, in hematology, there are several labels that actually address specifically 75 years or older for special warning and precautions on how to manage those. And KOLs typically know how to treat elderly slightly different than the typical patient you will see non-elderly 75 years or older.

And just a quick follow-up. How are you thinking about the read-through from today's update to LOTIS-7? Do you plan to amend the LOTIS-7 protocol at any point? Or you just don't see any read-through there?

No, no. We're not planning to amend the protocol. We've already shared, obviously, 49 patients, as I mentioned, in that the Grade 5 TAEs was quite low. It's only 2 of 49 patients, one on, it's quite low. So there's nothing we're going to do to amend LOTIS-7.

Your next question comes from Michael Schmidt of Guggenheim.

Yes, maybe just one more on the Grade 5 rate being higher perhaps than expected. I guess, how do you think physician will weigh if approved, the positive PFS benefit? The CRs were really durable, it looks like. How will they balance that with the Grade 5 event risk perhaps relative to other therapies? Do you still feel confident in the value proposition of the combination in second-line DLBCL?

Yes. Great question. First, I want to highlight that this is a trial that met the primary endpoint of PFS. Also, there's no different effect [indiscernible] at high CR rate and durable observed, as I mentioned, almost 40% or almost 50% of patients at 24 months kept their CR at that time. It's typically a discussion that we would have with the FDA to plan into the totality of the data and the benefit risk. We will be prepared, of course, to do -- address the [ possible ] risk of this regimen for future weeks.

And given that maybe, Mohamed, you can comment, given that the majority of the Grade 5 is driven by infection, the leading cause of those infections or the leading type of those infections was bacterial, how would a physician manage that or think about how to mitigate that risk?

Typically, prophylaxis antibiotic or use antibiotic during the treatment, also importantly that they evaluate the level of immunoglobulins at baseline before they start the treatment to make sure the patient immune overall and that's easily treatable by IVIg. So there's other methods to address that. Typically, KOLs understand that they're 75-year old and the needs of treatment, and they are able to address that. And as I mentioned, similar label have already addressed separately in the label how to talk about or how to treat 75 years or older in the label for hematology.

Your next question comes from Leonid Timashev of RBC Capital Markets.

I wanted to follow up on this imbalance in the follow-up therapies that patients had. I guess when you say novel anti-lymphoma therapy, I guess what exactly are you referring to there? I mean is there any particular reason there may have been an imbalance there? And I think you mentioned that you tried to adjust for that. Can you just talk a little bit more about that analysis as well?

Yes. In terms of -- you mean follow up for safety, right?

Earlier switching for next available therapy. So basically, look, what we saw in the study, even in R-GemOx, a lot of times, physicians aren't happy with the results and want to switch. And so we observed in this study, as you've seen in other lymphoma studies as well, is there a significantly higher rate of higher rates and earlier levels of switching. That's why you see discordance like, for example, you probably saw in the study, some discordance between the IRC and investigator assessments because in the -- you see basically a lot of that earlier sensing happening because of the much higher rates and earlier switching to next available therapy.

Your next question comes from Sudan Loganathan of Stephens.

This is [ Keith ] on for Sudan. Just a quick one from us. If you could provide your thoughts on how maybe these results have impacted your view and forward strategy within the second line plus DLBCL space, that would be great.

Yes. We're moving forward. We're preparing right now [ brieocrestamine ] with the FDA in June. We intend to have a meeting with them in August, pre-sBLA meeting to discuss the path forward. That's where we'll share the data and get feedback on how to move this forward. So it hasn't really changed our plans in terms of moving LOTIS-5 forward. I'll see how we move that forward and what the label and other things look like will depend on this conversation with the FDA. And we're continuing all the other studies, as I mentioned, LOTIS-7, where we expect to read out later this year, [indiscernible] the studies for marginal zone data by the end of this year and follicular by the middle of next year. So all these other studies are ongoing and moving forward.

[Operator Instructions] There are no further questions at this time. I would hand over the call to Nicole Riley for closing comments. Please go ahead.

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.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation, and you may now disconnect.

Good morning, ladies and gentlemen, and welcome to the ADC Therapeutics Q1 2026 Earnings Conference Call. [Operator Instructions] This call is being recorded on Monday, May 4, 2026. 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 our first quarter 2026 financial results and business updates. This release and the slides we will use in today's presentation 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 discuss our operational performance and recent business highlights, followed by our Chief Financial Officer, Pepe Carmona, who will review our first quarter 2026 financial 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.

Today's presentation also includes non-GAAP financial reporting. These non-GAAP measures should be considered in addition to and not in isolation or as a substitute for the information prepared in accordance with GAAP. You should refer to the company's first quarter 2026 earnings release for information and reconciliation of historical non-GAAP measures to the comparable GAAP financial measures. I will now turn the call over to our CEO, Ameet Mallik. Ameet?

Thank you, Nicole. We continue to make good progress in the first quarter of 2026 as we advance towards multiple important milestones for ZYNLONTA over the remainder of the year, beginning with the expected LOTIS-5 top line readout in the second quarter. From a commercial perspective, we continue to focus on execution and delivering on our commercial strategy, maintaining ZYNLONTA as a differentiated treatment option for third line plus DLBCL patients.

First quarter net product revenues were $20.0 million as compared to the prior year's first quarter net product revenues of $17.4 million. The increase was driven primarily by normal quarter-to-quarter variability in customer ordering with underlying demand broadly stable.

Looking toward the second line plus setting where we believe the largest growth opportunity lies. For LOTIS-5, our Phase III confirmatory trial of ZYNLONTA plus rituximab, we expect to share top line data before the end of June, potentially bringing us another step closer to providing this combination to significantly more patients. While this time line is rapidly approaching, I do want to highlight that we are currently still blinded to the data.

Turning to LOTIS-7. We expect to complete enrollment of approximately 100 patients at the selected dose level of ZYNLONTA plus [indiscernible] in the second quarter with full data anticipated by year-end. In indolent lymphomas, we continue to anticipate data publication between the end of 2026 and mid-2027 from the multicenter investigator-initiated trials ZYNLONTA in combination with rituximab to treat relapsed or refractory follicular lymphoma and of ZYNLONTA as a monotherapy to treat relapsed or refractory marginal zone lymphoma.

We continue to pay close attention in the quarter to managing our cost base and optimizing our balance sheet. On a non-GAAP basis, we've reduced our total operating expenses by 13% versus Q1 2025 and we ended the first quarter of 2026 with a healthy cash balance of $231 million. This maintains our expected cash runway at least into 2028, enabling us to deliver against our strategy.

We are building off the well-established role of ZYNLONTA as a single-agent therapy in third line plus DLBCL where ZYNLONTA has a profile of rapid, deep and durable efficacy, as well as manageable safety with simple and convenient administration. We believe the relative stability we've seen in net product revenues over multiple quarters demonstrates that ZYNLONTA has a clear place in this market.

This is just a starting point as we believe in the potential for ZYNLONTA to reach significantly more patients by expanding use into earlier lines of therapy in DLBCL and into indolent lymphomas. The data we've seen across these settings so far have been consistently encouraging with the potential to be highly differentiating. Through expansion into these settings in DLBCL and into indolent lymphomas, we are confident that ZYNLONTA has the potential to reach peak annual revenues of $600 million to $1 billion in the U.S., assuming both compendia listing and regulatory approval.

The upcoming LOTIS-5 trial readout, if positive, we'll begin to unlock the value of our life cycle management efforts for ZYNLONTA. Taken together with the upcoming data expected from LOTIS-7 and the [indiscernible] lymphoma studies, we expect to accelerate our revenue growth trajectory starting in 2027. Now I would like to turn the call over to Pepe Carmona, our CFO, who will discuss financial results for the first quarter. Pepe?

Thank you, Ameet. On the financial front, ZYNLONTA net product revenues in the first quarter of 2026 were $20 million as compared to $17.4 million in the same quarter in 2025. Licensing revenues and royalties were lower this year due to $5 million milestone we received from our partner in the prior year period.

Cost [indiscernible] sales increased by $1.6 million to $3.6 million for the 3 months ended March 31, 2026. This increase reflects a shift in the allocation of certain personnel costs due to a change in focus from research and development activities to commercial manufacturing activities. Total operating expenses were $46.1 million for the first quarter. On a non-GAAP basis, total adjusted operating expenses were $42.9 million for the quarter. Total adjusted operating expenses were down by 13% over the prior year period, primarily driven by lower R&D expenses.

As Ameet noted, when managing our costs carefully, and we remain disciplined in our capital allocation towards potential value creation while driving efficiency. On a GAAP basis, we reported a net loss of $33 million for the first quarter of 2026 or $0.21 per basic and diluted share as compared to a net loss of $38.6 million or $0.36 per basic and diluted share for the same period in 2025. On a non-GAAP basis, the adjusted net loss was $19.7 million for the first quarter of 2026, as compared to a net loss of $24 million for the same period in 2025.

The lower net loss on both GAAP and non-GAAP basis was primarily due to reduced R&D expenses. The year-over-year reductions on a per share basis were additionally impacted by the higher number of weighted average shares outstanding. You can find the reconciliation of GAAP to non-GAAP measures for the first quarter in the compounding financial tables of the press release issued earlier today and in the appendix of this presentation.

At the end of the first quarter, we had cash and cash equivalents of $231 million as compared to $261.3 million as of December 31, 2025. This provides us with an expected cash runway at least into 2028.

Turning to upcoming milestones. We expect to have multiple data catalysts during the remainder of 2026 across the ZYNLONTA program. First, we expect to share the top line data for LOTIS-5 before the end of June with publication of full results anticipated by the year-end. As Ameet noted, we're currently blinded to the data. And to the top line data has been presented, will remain in a blackout period, which means we may need to cancel our participation in any conferences as well as meetings with investors and analysts.

Assuming the results are positive, we plan to submit a supplemental biologics license application to the FDA by year-end, with [indiscernible] publication and compendia inclusion in the first half of 2027 and confirmatory approval to follow thereafter.

With LOTIS-7, we are on track to complete enrollment in the second quarter. We plan to share the next update with full data at a medical meeting by the end of 2026. In addition, assuming positive results, we plan to pursue [ competing ] inclusion as well as assess our regulatory strategy.

With [indiscernible], we expect the lead investigator to share additional data at medical conferences between the end of 2026 and mid-2027 and we plan to assess regulatory and competing strategies once sufficient data are available. I will now turn the call back over to Ameet.

Thank you, Pepe. To close, I am pleased with our start to 2026. We have achieved solid commercial performance while maintaining our strict capital discipline as we look forward to multiple anticipated value-creating catalysts, beginning with the expected LOTIS-5 readout. We are excited about delivering on our strategy and confident we can drive significant potential long-term growth starting in 2027. We can now open the line for questions.

[Operator Instructions] Your first question comes from Maury Raycroft with Jefferies.

Congrats on the progress. You mentioned on the call that you remain blinded to the data. Can you clarify if the database is locked at this point and when you reach the 262 events? And from a process standpoint, can you say what's happening currently? And what are the drivers that will allow you to unblind the data?

Yes. Thanks for the question. So what I can tell you is we're on track to be able to read the data. So the we're completely binded to the data side. I don't know any information yet. But as soon as the database [indiscernible] and we do the statistical analysis, we'll then be able to disclose top line data. So we're not at that point yet. On track to basically to share the data this quarter.

Got it. Okay. And for when you reach the 262 events, is there anything more on that you're saying? From a timing perspective?

Yes, we're not commenting on exactly where we're hitting the events. But what I can tell you is we're on track to hit the to basically to get to the top line results this quarter in the second quarter.

Okay. Understood. Maybe one other quick question. Just following the site level interventions you implemented to address the early dropout in censoring, do you have any perspective potentially from the IDMC to provide any indication that sensoring rates improved after those changes? I guess any -- any more color on that could be helpful.

I can't comment further. What I can tell you is the last IDMC look, which is from a safety standpoint, was last fall. And again, that recommendation wants to proceed as is there have been any other looks from the IDMC at the data.

Next question comes from Michael Schmidt with Guggenheim.

I have a couple. Maybe first commercially. The $20 million in 1Q, it's about 15% growth annually. I know you mentioned ordering pattern, but it just seems more growth than we've seen in recent quarters. And just curious if there's anything else going on in terms of driving more volume perhaps in the approved indication in the market? And then the other question I just had on LOTIS-5, so great to hear that the data is still on track for this quarter. Could you just comment on how much of the result, you'll be able to disclose in the top line announcement. Will you be able to share things like median PFS or perhaps asset ratios, et cetera, in the top line release.

Yes. Thanks, Michael. So first, on sales, as you recall, Q3 was quite low and the Q4 was quite strong. So we had $15.8 million, the $22.3 million, now we're at $20 million. I think it's too soon to call a change in trend to as right now. But I think what we're seeing is definitely very good execution. We're happy that we've been able to maintain our share despite a very competitive environment.

And there is quarter-to-quarter vary. As we saw in the Q3 was one of the lowest quarters in the Q4 is one of the higher quarters in the last couple of years. But I think after 2 quarters in that $20-plus million range, it's encouraging, but too soon to call the trend. So I think if this continues, that may cause it to sort of change where we think the range is going to be.

But I think at this point, just given the variable that we've seen in the last couple of years, I think -- we think it's -- we're still in the range of normal demand within the content of custom order variability -- with regards to [indiscernible] primary endpoints, of course, it can be [indiscernible] ratio point as well.

Your next question comes from Eric Schmidt with Cantor.

A couple of questions for me also on LOTIS-5. First, with regard to procedures. Do I take that base comments to mean that you're now entering the quiet period? Is that starting after today?

We started actually a quiet period, we have to do earnings, of course, but we haven't been engaging with analyst -- investors since April 1 for the whole quarter until we disclose the data.

And then Ameet, on the information that you'll be able to disclose with regard to the top line data for LOTIS-5 this quarter. Will we get some thoughts on how survival is trending? I know the trial's primary endpoint is PFS and you're well powered there. But wondering if you'll be able to provide color on OS trends. And then if you know at this point, how many OS events or how mature the OS data might be at the time of the PFS top line look?

Yes. So in addition to TFS, which obviously will be mature, we will give the gaps that we have on overall survival. So whether it's mature or it's a trend, we will provide the information that we have on overall survival as well as the other key secondary endpoints as well in response rate, duration of response.

So we plan to share all the fat we have. I can't comment right now on how many events we have with regards to [indiscernible] survival. But what I can tell you is it will be -- with whatever restoration we have, we will make a part of the disclosure.

And then maybe just one modeling it for Pepe. The change that we saw from personnel from R&D into cost of goods. Is that an ongoing transition? Are we expecting COGS to be inflated in subsequent quarters as well.

It is going to continue throughout all quarters from now on. So it's a reallocation of those expenses into cost of goods, and we capitalize on time inventory, but the cost of goods are going to increase because of this fixed cost and now it's getting allocated.

[Operator Instructions]. Your next question comes from Sudan Loganathan with Stephens.

My first one, I wanted to ask what -- what you believe the immediate impacts post the LOTIS-5 top line results in the second quarter could be -- for instance, if it is positive, good PFS readout, how this may change of ZYNLONTA is prescribed reviewed in the second half of this year, even prior to complete listing?

And then secondly, I just wanted to ask, even push over to the IITs, how does that add some incremental value over the next year or 2?

Sure. Yes. So once we get to the top line readout assuming it's positive, we then would work to kind of go down too fast. One is to prepare the sBLA submission that typically 4 to 5 months, we expect to have that certainly before the end of this year. And then that could lead to our approval thereafter next year.

And then in addition, we plan to submit to a medical congress and publication by the end of this year. to share the full details as a result, that would be the basis that we would submit to [ Compendia]. So we expect that we could get companion inclusion sometime in the first part of next year and then an approval sometime thereafter in 2027. So we don't expect any revenue impact this year. We expect this year to be largely in line with what the previous years are and only see revenue trajectory increase next year as we'll only start promoting the product once we have a formal approval sometime around the middle of next year. And your second question was around the IT, correct?

Yes. Yes.

Okay. So with the [ IoTs], we have both marginal [indiscernible]. Both of those -- let's call it the data on the full study will be disclosed sometime between the end of this year and the middle of next year. We expect publications to happen around that same time and then to be submitted for company inclusion after that. In addition, we're evaluating the regulatory approach for , but we would take it in a smash we move toward in parallel.

There are no further questions at this time. I will now turn the call over to Ameet Mallik for closing remarks.

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

Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.

Welcome to our fireside chat with ADC Therapeutics. I'm Robert Burns, the Managing Director and Senior Biotech, H.C. Wainwright and I'm joined now by Ameet Mallik, the CEO of ADC. Ameet, thank you for joining us today.

Thank you so much. It's a pleasure to be here.

So why don't we just dive in. So for those who may be unfamiliar with ADC, could you please provide a brief overview of the company?

Sure. Yes. So ADC Therapeutics is a commercial stage company focused on antibody drug conjugates, obviously, 1 of the pioneers. And the focus of our company is really on our CD19 directed approved product ZYNLONTA. ZYNLONTA is currently approved as a third-line -- in the third-line plus DLBCL setting. But beyond our current approval, we have multiple studies to move into earlier lines of DLBCL as well as to move into indolent lymphomas. And that's the strategy of the company is really maximizing the value of ZYNLONTA.

In particular, we have our LOTIS-5 study, which is our Phase III confirmatory of ZYNLONTA in combination with rituximab. That's actually in a readout in the second quarter of this year. So it's coming soon. And then we also have our LOTIS-7 study, which is a study looking at sin plus glofitamab in second-line plus DLBCL as well. That study will read out by the end of this year. And then, of course, we also have indolent lymphoma studies as well.

Before we get into LOTIS-5 and LOTIS-7, why don't we talk about the sort of sales trajectory over the past 4 quarters? And how you envisage the potential sales growth of ZYNLONTA in 2026?

Yes. So we don't provide any annual net revenue guidance, but we do expect that the ZYNLONTA sales in 2026 to be broadly in line with what we've seen in recent quarters. As you know, we have a third-line plus label as a monotherapy, and our sales have been relatively stable over the last couple of years. So we expect that to be the case in 2026. We think the real growth opportunity starts when we move into the second-line setting. And following the approval, the anticipated approval of LOTIS-5 in 2027, we think we'll start seeing growth in 2027 and even more substantial long-term growth starting in 2028 and beyond.

When we think about Q4 of last year, obviously, there's $22.3 million sales of ZYNLONTA versus $15.8 million in Q3 and $18.1 million in Q2. Obviously, there's a little bit of variability in there. Can we expect to see that variability as we move into 2026?

Yes. You can -- I think with this product, we've seen quarter-to-quarter about our variability. What's it driven by? I think it's really driven by 2 things. One is in -- particularly in academic centers or large community centers, because we're a relatively low-volume product, and it's a rare disease, you may be ordering -- you may get an order from a big academic center and then nothing in the next quarter and then you get an order in the next quarter because they're ordering a set of aisle. So there's a little bit of that kind of inventory fluctuation.

The other thing is it's just patient variability, particularly in the community where a community doctor may see 1, 2, 3, third-line plus patients in a year. And they could see 2 in 1 quarter and then not see any for the next 2 quarters at all. So there's a little bit of variability that we've seen in the brand. We're averaging around $18 million a quarter. That's what we've been averaging in the last couple of years, but that does vary. As you just mentioned, the last 3 quarters were going like $18 million, $16 million and $22 million. So we're kind of -- I think we do expect this to continue to see variability. But for the overall annual sales to be roughly in line with what we've seen in a couple of years.

All right. Well, why don't we move -- so obviously, as the ZYNLONTA approved in the third-line plus setting, you got LOTIS-5, LOTIS-7, which are going into the second-line. So why do we talk about the treatment paradigm in that second-line setting? And how does that differ between community and academic medical centers?

Yes. So I think when you look at the overall treatment landscape, whether it's the second-line or the third-line call setting, there's really 2 main segments that exist. And I'll tell you how they different in terms of use in the academic community settings. The first is there's more complex therapies. These are therapies like CAR-Ts and transplant bispecifics. And these are therapies that require more unique infrastructure and expertise to handle the logistical requirements for example, to do a CAR-T, it could be a CAR-T administer side, there's about 150 in the country. To administer bispecifics, you need access to a hospital. So you need capabilities to administer these therapies that not all centers have. Now typically, these therapies are available on all the academic centers, but the majority of the community does not have access to the therapies.

Then you have more broadly accessible therapy is the second segment, which are therapies like antibody drug conjugates, monoclonal antibodies, chemotherapy. These are simple outpatient therapies that really anyone can give, whether it be in the academic center or the community setting.

So academic centers have access to both of these therapies. The community largely has access to the broadly accessible. There is a portion of the more sophisticated or larger community centers that have access to bispecific based therapies. But for the majority of the community, they're really focused on broadly accessible therapies.

Okay. Obviously, there are a few trials for these competitive agency C19 targeted CAR-Ts as well as CD25 bispecifics that are being evaluated in the frontline setting, right? Alpha-1 is a great example of that. ZUMA-23 or the SKYGLO trial. So when we think about those specific trials, if those regimens were to be approved in that frontline setting, how does that affect the market opportunity for ZYNLONTA in the second-line context?

Yes. So there's more and more going on in the frontline line setting. I would say many are R-CHOP or R-CHP regimens outside of CAR-T. So we can talk about that separately. So most things are adding on the standard of care. We know in the frontline setting that 60% to 70% of patients are cured. So the frontline treatments are quite effective and work quite well. The only approval we've had within the last 20 years in the frontline setting is the POLARIX study, which prepared to or chip to R-CHOP, right, and had a modest PFS improvement, not really overall survival improvement. And that was a big breakthrough. So I would say the bar is high in frontline because these therapies work extremely well.

If you look at what's being studied though, in terms of the bispecifics or Monjuvi, other things, I think it's possible that they play a role. Most of those regimens are being extended in the high IPI population sort of where the POLARIX extending we've also studied, that's about 2/3 of patients. Polivy has already captured about 35% share in that frontline setting. So they already captured about half of the total addressable market of the IPI patients.

I think the bispecific based therapies, we'll have to see what the outcome is, what's the efficacy look like, what's the safety profile. If it's positive and can get approved. There's certainly take some of that share. But I think it's unlikely that the majority of patients are going to get access to that, and that it's obviously breakthrough therapy like a breakthrough clinical profile. So the reality is the majority of patients are still going to need access to these therapies in the second-line. But we also like having the benefit of having LOTIS-5 and LOTIS-7, because, for example, if a patient was exposed to a bispecific upfront, they could get a LOTIS-5 regimen. If they weren't, then you could get a LOTIS-7 regimen. So we like having multiple regimens in that second-line post setting.

When you look at CAR-Ts, most of the CAR-T studies are looking at only high -- the IPI definition is different. So whereas for the bispecific based therapies, it's IPI 3 to 5. This is only 4 to 5, which is about 20% of patients. And so the majority of patients, I would say, are unlikely to get a CAR-T in the frontline. We already see a second-line and third-line where you see more patients being treated in academic center than the frontline setting. Only 20 kind of patients in either of those settings gets access to a CAR-T. In this case, because they're being studied mostly in that higher IPI, the 4 and 5 patients, that's only about 20% of patients that could get access to our CAR-T. So we think, again, the majority of patients will not get access to our CAR-T frontline and it won't significantly change the patient population for the second-line plus opportunities that we're studying.

Okay. One of the competitive threats that I've taken a note of is Lyell's Ronde-cel. Now that targets both CD19 and CD20. And it's not really demonstrated any Grade 3 CRS in the trials that we've seen previously. And it's also been evaluated in the second-line setting. So I wanted to get your thoughts as to the uptake of an agent like that in the academic center and how it might erode like physician preference for that agent versus the combination of, let's say, glofitamab and ZYNLONTA in the second-line setting?

Yes. Look, I think Ronde-cel, as you said, it's a CAR-T that targets CD19 supports the rationale for combinations we're setting. Obviously, CD19 is CD20-based therapies, both of which we see in LOTIS-5 and LOTIS-7, I think those -- that combination makes a lot of sense. I think it sort of supports what we're doing with our combinations. I think the reality is when you look at the CAR T market, about 20% of patients in that second-line plus sending have access and are getting -- receiving a CAR-T. It hasn't changed in the last few years. It's been relatively stable. So while there's been share movement between products, there hasn't been actually a fundament of growth in the class. And so we think even that trial is positive, which most likely wouldn't happen before 2030, it's going to compete primarily with the CAR-T class and be limited to the academic centers. I don't think it's going to broadly impact the spaces that we're going after with LOTIS-7 and LOTIS-5.

Okay. Obviously, we've seen more Americans of these trispecific T-cell engagers. I wanted to get your thoughts as to, let's say, you were to see a CD19 trispecific or C19, C20, CD22 agent move into that second line setting as well. How would you view that competitive threat?

Yes. It's hard to speculate without real, I think, robust clinical data. there's a lot of theory that sounds good. I think at the end of the day, it's what efficacy are you offering? Are you getting to a high rate of CRs are they durable? And is it with a manageable safety profile in a fixed duration nonchemotherapy regimen. I mean I think that's essentially what physicians really want. And speculate on early-stage compounds. I think what we would -- what I would say is if I look at the competitive landscape today or what's emerging in the next few years, I think LOTIS-5 and LOTIS-7 are very well positioned in that kind of landscape.

Okay. Obviously, you noted earlier that top line data from LOTIS-5 trial, which is evaluating the combination ZYNLONTA plus Rituxan versus Rituxan Gevo the treatment of second-line plus transplant and eligible BSLs we expected by mid-2026. So given that upcoming data set, can you remind us of the safety running results that you presented at EHA last year? And how far expectations or investors regarding this upcoming release.

Sure. Yes. So LOTIS-5, as a reminder, is our Phase III confirmatory study of ZYNLONTA plus rituximab. It's -- the comparator arm is our GEMOX. So that's what we're going against. The initial safety results because we got approved as an accelerated pathway as a monotherapy. We had to do first a 20-patient safety Ronan before we started this randomized Phase III study. In those 20 patients, with this combination, we saw an overall response rate of 80% and a complete response rate of 50%. Also, we saw that the durability look really good. The median duration of CR was reached even after 2 years of follow-up for those patients. And we didn't see any new safety signals and the safety profile was overall well manageable. So we think that's a really good starting point. Of course, now we have a 420-patient randomized study that's ongoing, and that sudden it's going to read out in the second quarter this year.

In that second quarter, we plan to be able to share, obviously, PFS, which is our primary endpoint of the trial, and that's what the study is powered for. But we also will share all secondary endpoints that are mature as well as key safety tables -- so I think investors will be able to get a good view of what this data is. So we're going to be as transparent as we can without compromising obviously, publication and medical congress that we expect by the end of this year.

So what do you need to have a positive study for instance, Rio, can you talk a little bit about the powering of this study with regard to PFS? And what would success look like in terms of meaningful clinical differentiation for you guys?

Yes. So the primary endpoint of the study, which was discussed and agreed to with the FDA is PFS. So in Lotus, the PFS is powered at 90% to show a hazard ratio of 0.67. So in other words, we need to show up hazard-ratio 0.67 or less to have a positive primary end point. If you look at R-GEMOX, which is the standard of care in the cycle setting is why the used comparator really across almost every Phase III study in relapsed/refractory DLBCL, including those 5. When you look at across the data from our GEMOX as a comparator arm across most of the recent studies, it's really anywhere from 2.3 to 5 months. When you look at the most recent study, it's typically between 3 and 4 months. So you look at the 2 most recent Phase III studies are in that 3- to 4-month range. So what this means is if Remo, for example, delivered a form of median PFS, ZYNLONTA plus rituximab would have to deliver 2mordifference to be positive with a hazard ratio of 0.67. In the context of our primary endpoint, that's positive. With no detrimental effect on overall survival and a positive benefit risk profile, we think we have a very good submission to the FDA.

Ability, I think, is differentiating because Rob, like outside of CAR-T and chemotherapy, there's no full approvals in second line. Monjuvi has an accelerated approval, which could turn into a full approval to their frontline trial gets approved. But right now, there's very few full approvals in second line. So getting a full approval is in and itself differentiating.

Yes. Given the sort of benchmarks that you cited for R-GEMOX from a PFS perspective as well as what we've seen in that safety run in and all the previous assets, it seems like there's really high confidence behind this trial being successful. Would you take me to agree with that statement?

We're confident. I mean, I think we ran the study -- we're confident for really 2 reasons. I would say. One is the design of the study. If I think about other setbacks from competitors. One is you want to have a really good clinical trial design and conduct of the study. And I think we feel quite confident about that. This is a sufficient size with 420 randomized patients. It's powered at 90% with 1 to 1 randomization and so that gives us a lot of confidence. The other thing I'd take it as confidence is we know how [indiscernible] performed, which is typically, as I mentioned, that 3- to 4-month range. we saw in our safety run in a median PFS of 8.3 months. And so with a CR rate of 50%. And so I think that's what gives us confidence that even if you saw some erosion essential you're keeping rituximab the same in both arms, you're preparing our ADC, Talanta to GEMOX. And based on the data that's motion other studies as well as the data we saw in the safety run and that's what gives us confidence.

I think the other thing is that there was an interim futility analysis that was conducted in the second quarter of 2024. We have an independent data monitoring committee that is looking -- we are all blinded -- completely blinded to the data, but they're able to look at the data unwinded from an efficacy and safety standpoint. And even in the interim futility announcement, which was an efficacy look at the data there's a prespecified efficacy boundary that had to be met, that was passed and the IDMC to us to kick in. In addition, they've looked at the safety of this multiple times, including most recently, last fall, and again, told us to continue without any modifications as it is. So those are the data points we have, we're blinded to the study, but I think just based on the information that we know, those are the things that give us confidence.

Okay. Obviously, PFS is an event-driven endpoint. So is there any possibility of slippage for this data readout to go into like third quarter or potentially longer.

No, we're confident that we're going to have a top line readout in the second quarter.

So assuming the top line data readout comes out positive, talk to me a little bit about the regulatory strategy that you tend to pursue with regard to the LOTUS 5 data set?

Yes. So assuming a positive study happens in Q2, it typically takes about 4 to 5 months to file the BLA followed by what we expect to be a 10-month review period. That gets you to an expected approval sometime in the middle of 2027.

Let's say, were to be approved for the LOTIS-5 trial. What sort of incremental market opportunity would you expect to see from the LOTIS-5 trial dataset alone, excluding LOTIS-7?

Yes. I think when you look at it today, we basically are playing in the third line plus market. So there's about 6,000 patients in the third month market. We have about a 10% share and with an average of 3 cycles that translates to $70 million to $75 million. That's basically where our sales have been. If you look at the second line -- if you add the second line opportunity and the third line opportunity, cycline adds an additional 12,000 patients. So if we're able to just maintain that same 10% train the third line in the second-line setting with the expected increased number of doses. So in the safety on we saw patients were getting 5 cycles versus monotherapy 3 cycles. So with the extra patients keeping the same share but with a longer duration of therapy, that would get you to $300 million just with the same share. So conservatively, I think we've guided to -- even if you only get 5% to 10% share in second line, and maintain the same temperature in the line with a longer duration to get to $200 million to $300 million. We think that's very doable.

Design to [indiscernible] listings from, let's say, LOTIS-7?

No, no, that would be all incremental on top of that. The low to 7 and in lymphoma opportunity is on top of that. We think the total opportunity with approvals and perpetuals things for ZYNLONTA could be anywhere between $600 million to $1 billion in peak sales. So LOTIS-5 is only a portion of that total opportunity that we believe we could have.

Okay. Talk to me a little bit more about the trial design here as well. Because obviously, we know that gross silver can affect various survival endpoints. Is there a crossover in this trial?

There's no crossover.

Okay. Perfect. Why don't we shift gears now to the combination with glofitamab and that's being evaluated in react/refractory NHL in the low-7 trial. You recently presented updated data at ASH 2026. So can you give us a high-level overview of those results?

Yes. So I mean LOTIS-7, we're looking -- it's a Phase Ib trial, and we're combining ZYNLONTA with highly effective bispecific glofitamab in second line plus DLBCL patients. We know that outside of CAR-T, the only products that have ever been approved as single agents in any line of therapy in DXL the 2 bispecific products, acretivam and glofitamab and ZYNLONTA. So we're combining 2 of the only products that are ever been approved to single agents together. So these are 2 of the most potent molecules and we're very pleased so far with the initial results. We have in the first 49 efficacy evaluable patients, which all had a minimum of 6 months of follow-up, we were to demonstrate a 90% overall response rate and a 78% complete response rate across those 49 patients. So -- and then -- so that means 38 of the patients achieved a CR. Of those 3 of those 38 remain a CR of the data cutoff. We had all patients with at least 6 months of follow-up. We have patients going out to almost 2 years. And in that population, we also had about 8 patients. We had 8 patients that were previously treated with CAR-T. 6 of those patients achieved a CR. So we really believe that this combination can provide clinically meaningful benefit for patients data showed that the combination, in addition to having very strong efficacy, continue to be generally well tolerated with a manageable safety profile and the safe side effects that we're seeing were known side effects with either 1 of the agents. We didn't see any new side effects. And so taken together, we think together with LOTIS-5 we think that also having LOTIS-7, we really can provide multiple options to physicians depending on what's accessible and suitable for patients in that second-line plus setting and that these 2 approaches are very complementary for us to play a meaningful role in that second-line plus WCL setting.

Yes. Given the data that we've seen with the CD25 specifics in us large piece of lymphoma, what sort of CR delta relative to those historical controls would you want to see in order to pursue these regulatory or compendia pathways?

Yes. So if you look at there's 3 different biospecific accommodations that are preferred right now in NCCN guidelines, and they all have set rates anywhere between 51% and 61%. And what physicians have told us that if you're in the 6 already differentiate yourself on the pack, right? If you get to 7% or above from a CR standpoint, it can be transformative. But that's obviously our goal is to be transformative both in terms of the depth of response, but we also want to make sure the durability of those responses is very meaningful tangible safety profile. So that's the, I would say, the scenario we're going for. But I think we -- given that we showed a 78% complete response rate in 49 patients, I think we feel quite confident with where we can land with the 100-patient result that we expect to share by the end of this year.

Yes. I know that there was a paper that was published last year by Hutchinson colleagues in the JCO and presented results for glofitamab plus poison the second line plus DLBCL setting and in that paper, we saw a 78.3% objective response rate, 59.7% CR rate with an MPFS and MOS of 1.3 and 33.8 months, respectively. Now when I compare that data set to what we saw at ASH. Obviously, your DAS set looks better from an efficacy statement of a cross-trial comparison basis. But we do note that there were more third line plus patients in that trial than in LOTIS-7. So I'm curious to get your thoughts as to how you see the combination of vofinamab plus polatuzumab stacking up against Elantascofinumab on whether there's an opportunity here to particularly move into the frontline setting as well.

Yes. So actually, first of all, we're well balanced. If you look at the data cost of [indiscernible] patients between second-line patients and third-line prostates are very well balanced, like most other studies, I would say we have -- it's almost 50-50 between patients who had 1 prior line of therapy versus 2 or more. So it's pretty balanced between the second line and the third line cost settings. I think what's unique about obviously, glofitamab is 1 of the 2 most potent bispecific products, right? It's a very, very good product. Combining with Polivy though, is a product that doesn't have a strong single-agent activity, which never approved as a single agent drug as opposed to ZYNLONTA, which has very strong single-agent activity. So we think it's a more active drug, and that's why this combination is so powerful.

The other thing I think to note is that Polo is playing a very important role in the frontline setting. It's -- the POLARIX data led to a 35% share in that frontline setting. So a lot of patients are getting exposed to poll to be upfront. I think most of the business don't want to retreat for patients that progress on the therapy in the next line of therapy. So again, I think the fact that we have very equipment single-agent activity, the data so far looks best-in-class from a biospecific combination standpoint. And we're not being used in that frontline setting. I think those are all advantages.

In terms of could we move to the front line, there's a lot of physicians that are excited about it because they ask if you can get to CR rate in the second line cross setting where you have heavily pretreated patients. We have high-risk groups. We have high-grade B-cell lymphoma. We have high IPI patients, post CAR-T patients. We have a lot of high-risk groups, a lot of time are refractory. We looked at our data, a lot of primary refractory patients in our study and yet we still have a strong aggregacy, what could it be in frontline, could you get to significantly more. So that's something we'll consider in the future. I think right now, what we're focused on is how do we make sure that we can deliver on these studies and really create a very meaningful commercial opportunity in that second-line plus setting.

Yes. One of the things that I'm calling logs I remember a data set that you guys presented, where it showed that the efficacy in ZYNLONTA host CD19 CAR-T isn't really affected by the prior CD19 CAR-T usage. So do you really expect any sort of erosion in market opportunity if the senior 1 CAR-Ts go into the frontline setting? Yes. Obviously, the ipi score, the IPI classifications , it's much more stringent for the cars, but just based on that data set alone, it doesn't seem like you would have much erosion just from CD19 CAR T going to the front line.

I think it could be an opportunity because we get a lot of our use special again centers, post CAR-T or post-CAR-T that correct? We get a lot of our use today in that setting. And so if CAR T sort of move up front, again, they're playing in that IPI4 and 5 population, which is about 30% of the population that could be eligible for CAR-T. So even if all 20% were to get a CAR T, those same patients, remember the chair that CAR-T has in second line and third line plus is also only 20%. So if a lot of patients get treated in frontline, I think that will reduce the number of patients that get it in the second line of potline app, it's actually an opportunity for us. And we know that the product today is being used pretty extensively in that post-profit biospecific setting.

Yes. One of the questions that I get a lot is how do you see the utilization of LOTIS-7 versus LOTIS-5 in that second-line setting? Like if physicians didn't have -- if they got just like the POLARIX trial regimen, how -- which reset do you think a physician would sort of reach to LOTIS-5 or LOTIS-7?

I think it all depends on what's accessible and what's suitable for the patient. Obviously, the LOTIS-7 regimen is likely to be much more powerful, potent, right? I mean efficacy, we haven't seen efficacy like this from any of these combination regimens. So it's definitely a more potent combination. But not everyone has access to or suitable bispecific based therapy. So if you look today in the second-line setting, about 10% of patients get a bispecific based product. In the third-line setting, cost selling, it's about 35%. So I think it depends how this market shapes up between complex therapies and broadly accessible therapies. Right now, the split between those 2 settings in the second line is 35% complex therapies like CAR Ts and bispecifics, 65% broadly accessible. In the third line setting, it's actually 60% complex every versus 40% broadly accessible. I think what we like is that between LOTIS-5 and LOTIS-7, we're playing in both of those segments and depending on what the physicians have access to and depending on what's suitable based on also the comorbidities and patient characteristics. What's the most suitable therapy, we can play in both of those segments. Every 10 share points in that second-line plus setting with our product is worth about $300 million. So if we get to 10% sure, that will be 30 we're going to get to 20% share between the 2 therapies, that $600 million. So depending on the share we can get across both therapies, you can see how this can be a significant opportunity for us between LOTIS-5 and LOTIS-7.

Yes. Obviously, when we think about that frontline setting again, Allogene's approach is differentiated relative to ZUMA-23 and some of the other CAR T trials in the frontline setting. Is there any specific impact from the way that Allogene is conducting their trial? And like is there any direct read through as to the opportunity for you guys in that second setting?

Look, I'd say -- so far, what we've seen is that when new CAR T products come out, they tend to cannibalize each other. We've seen a lot of share movement between products, but the class hasn't really grown. For the last several years, really, it's been kind of stuck at that roughly 20% penetration. The more outpatient they get, the more accessible they could be in the community. I think you're still competing with then bispecific based combinations, which are how deep are the response is, how durable. That's always been the question on some of the allogeneic CAR-T around durability I think it's dependent on the clinical profile. I think we feel very good on the data that we've shared so far with LOTIS-7 on both the depth of response and the durability of response and the potential even for this to go outpatient, if you remember like the CRS, or GLOFIT on its own, if you look at the label has about a 70% all-grade CRS. Most of that was Grade 1 and 2, but there was even some grade 3 4. And those 49 patients that we showed we significantly are able to reduce the CRS. In fact, at the 150 dose of ZYNLONTA, which is our approved dose, that's the dose we're expanding and moving forward with, we were able to reduce the CRS to 25% all grade. So that could be a substantial improvement versus other bispecific based therapies. So we think we have a chance to differentiate on doubt the response, durability of response and safety profile. And so where the CAR-Ts are going to have to compete against to, suppose the allogenic CAR-Ts.

Yes. I completely agree with you there with regard to differentiation, both from an equity perspective, but also a CRS perspective with these ZYNLONTA combinations. Just a high level, I want to get your thoughts on in vivo CAR T and whether you see any potential impact on you guys from that next wave of CAR-T ingenuity?

Yes, I don't want to expect. I think it's all going to depend on the clinical efficacy. And what I said is so far outside of the autologous CAR-Ts, we haven't seen -- we've definitely seen more convenience. I think it's all going to come down to the durability. And it's too soon to tell, I'd say, because I think what's so good about the autologous part is that for 30% of patients they're still in a CR 5 years later, essentially, they call it punctually care, right? And I think that's going to always be the question about any of these newer PRT platforms is can you get to that same level of durability and long-term response that you see with [indiscernible]. I think it's still just an open question right now.

Okay. Why don't we shift gears a little bit to MCL and follicular lymphoma. Obviously, we've seen some data from these investigator-initiated files provide an overview of those data sets is how are you thinking about pursuing or whether you're pursuing potential registrational trials in either of those indications?

Yes. So we have really promising Phase II data from both 2 different multicenter IITs. One is Enanta in combination with rituximab in a relapsed or refractory follicular lymphoma. We also have another study with ZYNLONTA as a monotherapy to treat relapsed/refractory marginal zone lymphoma. The data was presented at medical congresses for both of these last year. We're encouraged that, for example, in follicular lymphoma, there was data presented from 55 advocacy valuable patients, and these are in high-risk relapsed/refractory FL patients. The overall response rate is 98% with a complete response rate of 84%. When you look at it versus competitive benchmarks, it's really outstanding data. Similarly the data presented on the first 26 advocacy evaluable patients last year at ICML, showed an overall such rate of 85% and a CR rate of 69%. Both of these also combinations combination of Poland the monotherapy and MCL had a very manageable safety profile. So we think these can be highly differentiating. But the pathway right now is a 100-patient study with molecular 50 patients studied with marginal zone. We expect that both of these studies to read out and be presented at Medical Congress as sometime between the end of this year and the middle of next year, we think that can form the basis for a companion inclusion after the publication. In addition to the competition strategy that we are evaluating regulatory strategies, in particular, for MCL, where -- when you look at the data sets that led to the approval, for example, R-squared or BTK inhibitors, it's on the basis of 70 patients or less, typically 60 to 70 patients. And so we already have a 50-patient study ongoing. We will discussed with the FDA about potential pathways for accelerated approval or what the regulatory pathway could be for the into [indiscernible].

Yes. Obviously, you mentioned both potentially pursuing regulatory pathways with the FDA as well as compendia listings. Could you sort of help frame what the incremental benefit would be, not just from Compendia but also from FDA approval. Like can you say you get a company listing for MZL or for the low 7 regroom right? Maybe you'd see 5% uptake. What sort of incremental uptick would you see with an FDA approval?

Yes. So I mean, obviously, if it's only in compendia not yet approved, that's an off-label indication. And although it would be reimbursed, we will not promote off-label. So your ability to educate on the regimen, if it's not approved, you're not going to promote the product. And so the uptake generally is less with Compendia than it would be with the full approval, we could promote, particularly in the community set. Academic physicians tend to be very aware of it tend to be very knowledgeable. And it's up to them to decide what they think is best for their patients to treat. Of course, as I said, we're not going to promote it. But it's up to them. Where is the community they tend to be less aware. And so although companion strategies can provide a point of access for business to use a product if it's in the patient's best benefit because of no promotion, they tend to be used less. So I don't want to give you an order of magnitude. But when you look to say an MDL, for example, there's 2 main regimens that are approved, 2 main regimens that are compendia. The 2 main regimens that are approved have the majority of the market. So it definitely helps to get approval. But data matters as well. So when you look at the square and the BTK inhibitors, the CR rates are typically around 30% or less. And what we've seen, again, with our study is 69% CR rate. So I think the clinical profile matters as well, and we feel good about the data we're generating right now and plan to continue to finish out these monies to get into competitive but also then we'll discuss with the other regulatory bots about potential approval pathways as well.

Okay. Last month, you announced an amended health care royalty financing agreement. Could you sort of discuss the name what that provides to the company.

Yes. So we have a relative agreement with Healthcare Royalty where initially, they gave the invested $300 million into the company in exchange for a royalty strip. That royalty right now is at 7%, but could go up to, depending on where the revenue is up to 10%. So that's what the essence the basic agreement is. Also in that agreement, there was a change of control provision that would be $750 million, should there be a strategic transaction. And so what we negotiated is to reduce that change in control payments from $750 million to $150 million, if something were to have between now and the end of 2027, thereafter, it would be $200 million. And then in the event of a change in control in exchange for that, health care at will continue to receive the same royalties that they were up to this point, that 7% to 10% until the original royalty cap is reached. And of course, that $150 to $200 million are change in control would also contribute to the royalty rumors. So they don't get more money in total, but that will happen. And in addition, we granted HCR warrants to purchase approximately $9.8 million of common shares with an exercise price of $3.81. So these are exercisable through the end of 2030, but there are subject to a lockup through the end of 2027. So that's the basic provision of this I think for us, it just provides the company more strategic flexibility. And I think it shows the great partnership we have with ACR and also the confidence that they have in ZYNLONTA long term to be able to restructure this deal like this.

Last question for me. It's actually a 2-part question. In the past, we've seen some preclinical data for some of your earlier stage assets, I know you don't really talk about that much anymore. But how are you thinking about potential BD opportunities moving forward? And then the second part of the question is, what's your current cash position and what sort of runway does it provide?

Yes. So I think in terms of BD right now, we're really focused on executing these ZYNLONTA trials and really helping to translate that into a significant opportunity for ZYNLONTA starting with growth in 2027. That's the core focus of the company. But as a company eventually transitions to a profitable P&L with our current indications that can allow us to continue to invest, to some combination of either more life cycle management for ZYNLONTA, but also potentially complementary hematology assets. And those are the things that we'll explore as we get into a positive cash position as a company. Again, right now, we're focused on executing and delivering on what we have. And then in terms of our cash position, we have a very strong cash position. We raised last year about $160 million. So we ended the year with a cash balance of $261 million. That will give us an expected cash runway to at least into 2028. And so together with all the milestones that we have this year, where we have LOTIS-5 and LOTIS-7 data coming this year, the inland data coming in between the end of this year and middle of next year. And the ability, we think, to compendia through regulatory approvals for this asset to get to $600 million to $1 billion, we think we're really well financed to be able to do that. And as the data gets unlocked this year, and we think it will significantly de-risk the growth opportunity that we see starting next year.

Awesome. So is there anything we haven't touched on today, they sort of want to highlight for investors?

No, I would just say, look, this is an exciting year. This is really, as I mentioned, a year where the -- the data gets unlocked and it's going to open up an opportunity to start the growth of ZYNLONTA and then that growth can be further accelerated through additional life cycle management or to potentially complementary new assets. And we think this is a key year. Last year it was key for us to execute finance the company well, and we think this is a key unlocking year across from a data standpoint.

Well, so we look forward to all the data that's going to be presented later this year. Ameet, thank you so much for joining us today.

Thank you, Rob. I really appreciate it.

Good morning, ladies and gentlemen, and welcome to the ADC Therapeutics Q4 2025 Earnings Conference Call. [Operator Instructions]

I will now turn the call over to Nicole Riley, Head of Investor Relations and Corporate Communications for ADC Therapeutics. Nicole, please go ahead.

Thank you, operator. Today, we issued a press release announcing our fourth quarter and full year 2025 financial results and business updates. This release and the slides we will use in today's presentation 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 discuss our operational performance and recent business highlights, followed by our Chief Financial Officer, Pepe Carmona, who will review our fourth quarter and full year 2025 financial 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.

Today's presentation also includes non-GAAP financial reporting. These non-GAAP measures should be considered in addition to and not in isolation or as a substitute for the information prepared in accordance with GAAP. You should refer to the company's fourth quarter full year 2025 earnings release for information and reconciliations of historical non-GAAP measures to the comparable GAAP financial measures.

I will now turn the call over to our CEO, Ameet Mallik. Ameet?

Thanks, Nicole, and hello, everyone. Thank you for joining us on today's call. We are pleased to share an update on our achievements in 2025 and our excitement for the future. Before I get into the details, I'd like to take a moment to reflect on the progress we've made over the past few years and why we believe this positions us strongly for the future.

We have implemented a strategic plan to focus on ZYNLONTA with optimized life cycle management. This includes advancing LOTIS-5 as well as initiating the bispecific combination study, LOTIS-7 and IITs in indolent lymphomas. By focusing the company, we reduced our operating cost structure by approximately 50%. At the same time, we refined our go-to-market model, which resulted in strengthened KOL advocacy, and a sustained market position in the third-line plus DLBCL setting despite the entry of the bispecific class. Central to these achievements, we upgraded leadership and talent across the organization which resulted in improved execution. Lastly, we strengthened our balance sheet through equity and BD and improved our strategic flexibility with an amended HCR agreement.

Having set the strategic course for our company, we see 3 horizons for potential value creation. These are centered around final data disclosures, approval and compendia inclusion and ultimately delivering growth. As we advance across these horizons, our vision is to first establish ZYNLONTA as a backbone therapy with a differentiated clinical profile across combinations in second-line plus DLBCL. Second, provide significant patient benefit in indolent lymphoma, including follicular lymphoma and marginal zone lymphoma. And third, achieve potential annual U.S. peak revenue opportunity of $600 million to $1 billion, assuming compendia inclusion and regulatory approval with a highly leveraged cost structure providing us with broader opportunities to invest in complementary hematology assets.

2025 was a year of substantial progress for our company. We further derisked our portfolio with multiple exciting milestones achieved for key ZYNLONTA trials in both second-line plus DLBCL and through the indolent lymphoma IITs. We undertook a strategic reprioritization to focus resources on ZYNLONTA expansion opportunities, positioning the company for long-term growth with significantly reduced operating expenses, and we significantly strengthened our balance sheet, providing us with the ability to deliver against our objectives. Among our accomplishments from a commercial perspective, we continue to focus on execution and delivering on our commercial strategy, maintaining ZYNLONTA as a differentiated treatment option for third-line plus DLBCL patients.

Building off an unusually low Q3. Performance was strong in Q4 with net product revenues of $22.3 million, primarily driven by variability in customer ordering patterns, as well as activation of some new accounts. Sales for the year were $73.6 million and remained roughly stable in line with our expectations in the third-line plus setting.

Looking toward the second-line plus setting, where we believe the real growth opportunity lies, with LOTIS-5, we expect to share top line data in the second quarter of 2026, potentially bringing us another step closer to providing this combination treatment to significantly more patients. With LOTIS-7, we expanded target enrollment to approximately 100 patients at the selected dose level and shared updated safety and efficacy data on 49 efficacy evaluable patients in December, which we believe continues to support the potential for this regimen to be a best-in-class combination in a highly competitive market.

Indolent lymphoma's promising Phase II data was also shared in 2025 from the multicenter investigator-initiated trials of ZYNLONTA in combination with rituximab to treat relapsed or refractory follicular lymphoma and of ZYNLONTA as a monotherapy to treat relapsed or refractory marginal zone lymphoma with presentations at the International Conference on malignant lymphoma and the international workshop on non-Hodgkin lymphoma. We anticipate publication of data across these IITs between the end of 2026 and mid-2027.

Most recently, we were pleased to have entered into an amendment to our royalty purchase agreement with HealthCare Royalty. This update to the terms of our agreement is a reflection of ACR's conviction and the long-term value of ZYNLONTA, and we believe these new terms give us greater strategic flexibility.

Finally, from a corporate perspective, through strict capital management in 2025, including a strategic reprioritization and multiple financings, we ended the year with a cash balance of $261 million with an expected cash runway at least into 2028. With this significant progress, we are confident in our path ahead as we work to make an impact for more patients moving forward.

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 and into indolent lymphomas. The data we've seen across these settings so far has been consistently encouraging with the potential to be highly differentiated. We continue to believe that through expansion into these settings, ZYNLONTA has the potential to reach peak annual revenues of $600 million to $1 billion in the U.S. Our current indication, as I noted earlier, has shown relative stability in net revenues over multiple quarters demonstrating ZYNLONTA has a clear place in the market as a monotherapy. We believe LOTIS-5 has the potential to lift peak annual revenue for ZYNLONTA to $200 million to $300 million as we expand into the second-line setting. Not only would this double the addressable patient population, but with an improved clinical profile versus our current indication of the monotherapy, we expect to gain share in the second line offsetting and improved duration of therapy. With LOTIS-7, we estimate we can expand the total opportunity for ZYNLONTA in DLBCL to $500 million to $800 million in peak annual revenue with both regulatory approval and compendia listing. If the data continues to be compelling, we believe ZYNLONTA plus glofitamab has the potential to transform the future of lymphoma treatment paradigm by becoming the preferred bispecific combination in the second-line plus DLBCL setting.

On top of this, we see additional potential for ZYNLONTA in relapsed or refractory marginal zone lymphoma and relapsed or refractory follicular lymphoma. If the encouraging initial data in the Phase II IITs are maintained in larger patient numbers, we believe these indolent lymphomas could provide additional peak annual revenue for ZYNLONTA of $100 million to $200 million with both regulatory approval and compendia listing, primarily driven by MZL.

Let's drill down a little more into the specifics of the DLBCL treatment landscape to explain why we believe ZYNLONTA has the opportunity to play a significant role. In both the second and third-line plus 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 confined to the academic centers and more sophisticated community centers and include therapies like CAR-T, transplant and biospecifics.

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 is monotherapy in the third-line plus study 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 or added last year to NCCN guidelines for use in combination, we expect that they will continue to gain share and grow the use of complex therapies. Through LOTIS-5 and 7, we believe ZYNLONTA combinations have the potential to raise the borrowing efficacy in second-line plus DLBCL in their respective treatment segments, establishing ZYNLONTA as a backbone therapy with a differentiated clinical profile across combinations and offering complementary approaches to addressing unmet needs.

In LOTIS-5, our Phase III confirmatory study, we are combining ZYNLONTA with the most widely used agent rituximab in patients with second-line plus DLBCL. As a reminder, initial data from the safety lead-in portion showed an overall response rate of 80% and a complete response rate of 50% with no new safety signals demonstrating that this combination has the potential to provide competitive second-line plus efficacy with a favorable safety profile, allowing broad accessibility.

In LOTIS-7, our Phase Ib trial, we are combining ZYNLONTA with a highly effective bispecific, glofitamab in second-line plus patients. In December, we reported updated data from the trial, which demonstrated a 90% best overall response rate and a 78% complete response rate across 49 efficacy evaluable patients with a minimum of 6-month follow-up. Not only did this support a clinically meaningful benefit for patients, but the data also showed the combination continues to generally be well tolerated with a manageable safety profile. Taken together, we are encouraged by the expanding data set, which we believe demonstrates the potential for ZYNLONTA plus glofitamab to be a best-in-class combination in a highly competitive market.

When you look at the CR rates across these 2 treatment segments, we believe the emerging clinical profile of ZYNLONTA plus glofitamab in LOTIS-7 positions us well among complex therapies. And at the same time, the clinical profile of ZYNLONTA plus rituximab in LOTIS-5 has the potential to differentiate us among broad-based sensible therapies. Together, 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 3 cycles to 5 to 6 cycles.

We have established a place for ZYNLONTA monotherapy today in later lines because it works quickly. CRs, when achieved, are durable, and it has manageable safety and a convenient dosing schedule. As compared to our current indication as a monotherapy, we believe an improved CR rate in a broader patient population with LOTIS-5 will makes ZYNLONTA more relevant among both academic and community treaters, especially for patients who cannot access, are not suitable for or progress on a CAR-T or bispecific based therapy.

When you take into account the fact that there are approximately 12,000 patients in the second line, in addition to the approximately 6,000 in our currently addressable third-line plus patient population and the average number of cycles in ZYNLONTA will increase from approximately 3 to 5. We believe that once in the second-line setting, we will be positioned to reach more patients with additional cycles and we'll capture share accordingly.

In the second line setting, every 10 points of share translates to approximately $200 million in revenue and every 10 points of share in the third-line plus setting to approximately $100 million based on the expected longer duration of therapy for this combination. We have already achieved an approximately 10% share in the third-line plus setting as a monotherapy with a CR rate lower than that of competitive combination-based therapies. Therefore, if we maintain a 10% share we have today in the third-line plus setting, achieving only 5% to 10% share in the second-line setting, would translate to roughly $200 million to $300 million in peak sales opportunity for the ZYNLONTA plus rituximab combination alone. Taken together with the DLBCL bispecific combination and indolent lymphoma opportunities, we believe we could deliver on our vision of a combined potential peak annual revenue of $600 million to $1 billion in the U.S. assuming compendia listings and regulatory approvals.

Now I will turn the call over to Pepe Carmona, our CFO, who will discuss financial results for the fourth quarter. Pepe?

Thank you, Ameet. On the financial front, ZYNLONTA net product revenues in the fourth quarter of 2025 were $22.3 million as compared to $16.4 million in the same quarter in 2024. On a full year basis, net product revenues were $73.6 million versus $69.3 million in 2024 with an underlying volume broadly flat. Total operating expenses were $41 million and $202.9 million for the fourth quarter and full year ended December 31, 2025, respectively. On a non-GAAP basis, total adjusted operating expenses were $39.4 million and $181.3 million for the quarter and full year ended December 31, 2025, respectively. Total adjusted operating expenses were down over prior year by 15% and 6%, respectively. The reduction in total adjusted operating expenses for the fourth quarter was primarily driven by lower R&D expenses. The decrease in total adjusted operating expenses for the full year was across all major lines of the income statement.

We continue to be disciplined in our market allocation towards potential value creation while driving efficiencies across the portfolio. On a GAAP basis, we reported a net loss of $6.4 million for the fourth quarter of 2025 or $0.04 per basic and diluted share as compared to a net loss of $30.7 million or $0.29 per basic and diluted share for the same period in 2024. Net loss for the full year ended December 31, 2025 was $142.6 million or a net loss of $1.12 per basic and diluted share as compared to a net loss of $157.8 million or a net loss of $1.62 per basic and diluted share for the full year ended December 31, 2024.

The lower net loss over both periods was primarily due to a higher cumulative catch-up adjustment gain associated with our deferred royalty obligation and reduced R&D expenses partially offset by a restructuring impairment and related costs incurred in connection with the strategic realization and restructuring plan. You can find the reconciliation of GAAP to non-GAAP measures for the fourth quarter and year-to-date in the compounding financial tables of the press release issued earlier today and in the appendix of this presentation.

At the end of the quarter, we had cash and cash equivalents of $261.3 million compared to $250.9 million as of December 31, 2024. We significantly strengthened our balance sheet in 2025 by entering into a $100 million PIPE financing in June 2025 and a $60 million PIPE financing in October 2025, providing an expected cash runway at least into 2028.

We expect to have multiple data catalysts in 2026 across the ZYNLONTA program. For LOTIS-5, we expect to provide top line data in the second quarter of 2026. We expect to publish full results by the year-end. Assuming the results are positive, we will file a supplemental biologic license application submission to the FDA with potential publication and compendia inclusion in the first half of 2027 and confirmatory approval to follow in mid-2027. With LOTIS-7, we plan to share the next update with full data at a medical meeting and through publication by the end of 2026. In addition, assuming positive results, we plan to pursue competing inclusion as well as assess a regulatory strategy.

Within indolent lymphomas, we expect additional data to be shared at medical conferences by the lead investigators between the end of 2026 and mid-2027 and we plan to assess regulatory and competitive strategies while sufficient data are available.

I will now turn the call back over to Ameet.

Thank you, Pepe. To close, we achieved meaningful progress across our ZYNLONTA clinical program in DLBCL and through investigator-initiated trials in indolent lymphomas this past year. And we believe we have laid the foundation for multiple anticipated value-created catalysts ahead, as Pepe just highlighted. With our strengthened cash runway, we are confident we will drive significant potential long-term growth beginning in 2027.

We can now open the line for questions. Operator?

[Operator Instructions] Our first question comes from Maury Raycroft from Jefferies.

Congrats on the priors. I'm going to ask one on LOTIS-5. At a high level, how are PFS events tracking relative to the 262 events required to trigger the top line analysis? Is there any chance the readout could get bumped into third quarter? And then wondering if you can clarify what will be included in the top line and whether CR durability could be included in that update? Or is that more likely to be reserved for a later medical conference?

Yes. Thanks so much for the question. So we are confident in the Q2 timing of the top line readout. So we expect to be able to hit the events in time, and we will be able to share top line data in Q2. We're very confident in that.

In terms of what we expect to share, we're going to share the primary endpoint, which is PFS for the trial. That's what the study is powered to show. In addition, we're going to share all the secondary endpoints that are mature as of the time of the top line data as well as key safety tables. So we want to make sure that we're as transparent as possible with the market without compromising obviously, publication that we expect to happen by the end of the year.

Your next question comes from Michael Schmidt from Guggenheim.

Another one on LOTIS-5. And so just thinking about your market projections in second-line DLBCL. I think you spoke about an incremental $200 million to $300 million opportunity, assuming maintaining sort of a 10% share in that setting. And I was just wondering if that is perhaps too conservative. I'm just curious how you think about the market, especially now that we've seen Monjuvi perhaps moving into first-line, we see some of the bispecific antibody data reading out, perhaps below expectations. And so I'm just curious if there's upside perhaps to your LOTIS-5 opportunity assessment? And then I had a follow-up question.

Yes. I mean, I think based on the profile we saw in the safety run and if the final results look similar, obviously very highly confident that we can play a meaningful role in second-line plus DLBCL with this combination.

To your point, we've already achieved an approximately 10% share in the third-line plus setting as a monotherapy. And I would say it has some attributes that physicians really like the fact that it works very quickly, very durable CRs, manageable safety profile, convenient dosing.

One of the drawbacks right now is we have a less than competitive CR rate because we're competing against combination. So of course, now with the combination, we expect to have competitive and potentially been differentiating CR rates with a positive Phase III study. So we do feel confident we should be able to maintain that share in the 10% range in the third-line plus setting. And if we're able to maintain that same 10% in second- line, that would translate to $300 million.

The exact, I would say, peak sales opportunity, we're going to know when we know the clinical profile because we think we can achieve this even with a competitive profile relative to other competitors. If we have a more differentiated profile, potentially we could do more. But we'll revisit the peak sales opportunity once we know the final clinical profile of the combination.

Yes. That makes sense. And then just another question on LOTIS-5. So just curious whether you've allowed crossover in this study? Especially as it pertains to getting an early look at overall survival, whether that's something that could perhaps be achieved?

And then the other question related to that, I had is how are you thinking about potential use of bispecific antibodies post-progression perhaps impacting OS. Obviously, that could happen in either arms of the study. But I'm just curious, in general, perhaps how meaningful or how important you think OS could be as a differentiator in the setting, which obviously was not achieved by some of the other programs in second-line.

Yes. So we obviously don't know whether and how the subsequent therapies are between the different arms. So that's -- whether there were CAR-T bispecifics, as you said, or any other therapies, we're not obviously certain, we're completely blinded in terms of the study. Obviously, subsequent therapies can affect overall survival.

I think the way we look at this is if we have a positive PFS without any detrimental effect to overall survival and overall a positive benefit risk profile, we think that we'll have a very good submission for the FDA.

Your next question comes from Eric Schmidt from Cantor.

This is Alexa on for Eric. And congrats on a great year. So one question for me. So R&D spend was down about $10 million from the previous quarter. So do you expect what we're seeing in Q4 to be the current run rate going forward?

Thanks, Alexa. I appreciate the question. So Pepe I'll turn that question to you around R&D spend in Q4 and what we expect going forward.

Yes. Thanks for the question. So we expect that as we move to 2026 and 2027, R&D expenses should go down, assuming we maintain the current number of trials and the current pipeline that we have as the LOTIS-5 trial will continue to wind down and then LOTIS-7, we'll get to a peak, but then will go down. So R&D expenses are expected to fluctuate quarter-over-quarter, but in general, for '26 and '27 to be going down.

Your next question comes from Sudan Loganathan from Stephens.

The first one, given the amended health care royalty agreement, they expect the cash flow weigh into 2028. How should we think about the capital allocation priorities between commercial investment behind ZYNLONTA or advancing combination strategies and then the potential business development angle, especially considering the remaining deferred royalty and term loan obligations?

Yes. I'll start off, and then Pepe, feel free to add. So I would say that right now, we feel pretty confident with our cash runway guidance that even with relatively stable revenues until we get to the new indications, which we expect to happen in 2027 with LOTIS-5 and as well as with the cost guidance that Pepe just mentioned, for all the activities that we have currently planned, our current LOTIS-5, our current LOTIS-7, our current IITs, all of our current ongoing activity as well as investing more prelaunch in both commercial and medical affairs activities. That's -- those are all the assumptions that we have in our current guidance. Obviously, if we were to do any additional life cycle management or new activities that would not be currently based within our cash runway guidance that we have right now.

We think the ACR agreement provides strategic flexibility now because, obviously, by reducing the change in control payment just allows more strategic flexibility and optionality for the company going forward. And so we're really pleased by that. In exchange, of course, they continue the royalties, which given that our COGS is low to mid-single digit, when you add on the royalty agreement, the gross margin is still quite good for this product even when you add both of those things then.

But Pepe is there anything else you would add to what I just said?

Yes. I think you gave all the details. It's -- at the end of the day, we are solely focused on driving ZYNLONTA growth, and that's by completing the LOTIS-5 and LOTIS-7 and indolent lymphoma trials. That capital has been allocated and is part of our cash runway as well as all the prelaunch activities and launch activities of ZYNLONTA in 2027 in the second-line setting. It does also cover some of those expenses related to a loan. So it's all included. We believe we have a really strong cash position right now to execute on our plan.

And if I could, just a second one real quick. I wanted to ask about if you can give any details on maybe your market strategy as you get some of these last final data readouts this year and looking -- going towards the regulatory -- compendia and regulatory inclusion pathway first half of next year. Could you give us any details on how your marketing strategy could change to get into the DLBCL space, the second-line space?

I mean the good thing is we have a very good footprint. So our field force already covers about 90% of the potential of DLBCL. We have a full MSL team as well. and a strong headquarter team. So we will make some incremental increases, both on the commercial and MSL footprint as well as some additional expenses in terms of A&P and other expenses from a headquarters basis. But I would say incremental because we think we're already pretty well covered. Obviously, when you do a prelaunch and launch activities, and we can expand into a much bigger population, the second-line population, which we think also with a better profile than we have today. Those incremental investments are going to help us to make sure that we drive education around the product use, particularly with -- when we anticipate a LOTIS-5 approval sometime in the middle of next year.

We think LOTIS-5 obviously, is also key because once we get to the top line readout next year, it really actually unlocks the total value of the life cycle management plan for ZYNLONTA because that is our full approval. And we think that the total opportunity that we have for ZYNLONTA, not just with LOTIS-5, but assuming we can have regulatory approvals and compendia for the other indications, it could take the total peak revenue opportunity for ZYNLONTA to $600 million to $1 billion. So we think ZYNLONTA LOTIS-5 readout to Q2 is really a key unlocking event to start driving the value of the total asset potential.

And your last question comes from Leonid Timashev from RBC Capital Markets.

I just wanted to ask on sort of the current commercial run rate for ZYNLONTA. I guess you've had a couple of stronger quarters. I guess at what point do you think that becomes a trend where you're actually seeing genuinely more enthusiasm and use from investigators in the current labeled indication? Or is there still seasonality? And maybe what does that tell you about potential future launch of ZYNLONTA as you expand the indication?

Yes. I mean I think we're pleased that over the last couple of years, since bispecifics have launched, we've basically been able to maintain our share within a space that's gotten a lot more competitive. So I think we feel really good about that. If you look more broadly at 2025 versus 2024, volumes are roughly stable. There's some slight increase in sales mainly driven to slight increases in net price. So as you know, we don't provide any annual net revenue guidance, but we still -- we expect this year, sales again to remain broadly in line with what we've seen in the recent years. And the real inflection point will start when we get the approval for LOTIS-5 next year where we think we can really significantly increase the potential sales opportunity for ZYNLONTA.

Thank you. As there are no further questions at this time, we may proceed with the conference.

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.

Ladies and gentlemen, this does conclude your conference call for today. We thank you very much for your participation. You may now disconnect. Have a great day.

Good morning, everyone. My name is [Mary Lou], and I'm one of the associates on the healthcare investment banking team at JPMorgan. It's my pleasure to introduce our next presentation from ADC Therapeutics. I'm joined by the company's CEO, Ameet Mallik, who will give a presentation on the business, followed by a Q&A session. Thank you very much for being here. And with that, I'll turn it over to you.

Thank you very much. It's a pleasure to be here with all of you today, and I'm very happy to introduce our company, ADC Therapeutics. So overall, we're in the ADC space. We have an approved product in ZYNLONTA that we're currently working to expand in combination in earlier lines of DLBCL and into indolent lymphomas. Over the course of 2025, we made significant accomplishments, most notably progress with all of our key trials where we will again demonstrate key data, which we believe is derisking the portfolio of trials for ZYNLONTA, but also to strengthen our capital position, both through restructuring the company and through significant equity raises. If you think about where are we as a company going forward now, this is a year of final data disclosures for a lot of our key studies.

So this is a year where the data is going to get derisked. And as we go into 2027, we'll get approval and compendia inclusion for multiple new uses, which can lead to growth starting in 2027 and continuing into 2028 and well beyond. Now just taking a step back, ZYNLONTA, our approved asset, is a CD19 directed ADC using a PBD-based warhead. It's approved currently in the third line plus DLBCL setting. That has a few attributes that are very unique and differentiating versus other molecules. First, it works very quickly. The median time to response is first disease assessment, 1.5 months. Patients are getting a response, most times even best response if they're going to get to a CR within that time frame. Even as a single agent, and there's very few single agents approved within relapsed/refractory DLBCL, we have a 48% overall response rate and nearly a 25% CR rate.

The median duration of response when you get to a CR wasn't reached even 2 years later. So when you get to a CR, you're going to get there quickly and they tend to be very durable. The side effect profile is manageable. We don't have any ICANS, CRS or any cumulative irreversible toxicities like you see with many of the other therapies in the field. And a simple Q3-week dosing, physicians typically administer for a fixed duration, no REMS or inpatient stay. Now overall, where we're approved in a relatively small indication as a single agent in the third line plus setting, the strategy is really, one, to move in combination in earlier lines of DLBCL as well as to move into indolent lymphomas. Across all of these settings, we've seen very differentiated data that I'm going to walk through today, which we think can expand the opportunity significantly within the lymphoma space.

Now if you deep dive into what is happening within the market within DLBCL, when patients get treated in the frontline setting, they're getting pretty standard therapies. Typically, their R-CHOP or Polivy R-CHP. But when you move to that second-line plus setting, that relapsed/refractory setting, Treatments really fall into 2 main categories. You have more complex therapies like CAR-Ts and transplant and bispecific-based therapies that require unique patient management and infrastructure requirements to administer these therapies. So for patients who have access to these therapies and are suitable for these therapies, they tend to get these complex therapies. But we know many patients, particularly in the community, either don't have access or not suitable for these therapies, and you also see broadly accessible therapies.

These are typically ADC-based monoclonal antibody-based or chemo-based therapies. And so these 2 segments coexist right now. If you look at the third-line setting where we play today, in the complex therapy market, bispecifics were approved about 2.5 years ago and we gained significant share. So together, complex therapies are now at about 60% and broadly accessible about 40% share. We have 10% share of the total market. So roughly 10 of those 40 share points is where ZYNLONTA plays today. Now in the second-line therapy, where bispecifics have not yet been approved, but were added last year to guidelines, we see complex therapies at about 35% share. So 65% of patients are still getting a broadly accessible therapy in that second-line segment. We expect that complex therapies will grow driven by bispecific-based combinations in that second-line setting. But nonetheless, these 2 segments will continue to coexist going forward.

And our strategy is really to be able to win in both of these segments to have leading efficacy potentially in both of these segments. With our LOTIS-7 trial, this is the combination with ZYNLONTA plus the approved product, glofitamab, the approved bispecific product glofitamab. And then in the broadly accessible segment, our ongoing Phase III study, which we expect to read out in the second quarter of this year with ZYNLONTA plus rituximab. Now when you look at the data that's been generated up to this point and put it in line with what's going on in the competitive landscape, starting first with complex therapies, the bispecific monotherapies were approved with roughly a 40% CR rate, which is actually quite good for a monotherapy. Then you get to bispecific combinations.

There's 3 different combinations that have been added to compendia. They have CR rates ranging between 51% and 61%. And then, of course, CAR-T, the approvals were in that 65-ish range for CR rate. What we were able to demonstrate in the first 49 patients, and I'll go through this data with ZYNLONTA plus glofitamab is a 78% CR rate. So very encouraging data that we've seen so far in this trial. Now going to the right-hand side of the page, the broadly accessible segment, chemotherapy is still a mainstay in use quite often, particularly in the community in that second-line plus setting. The CR rate is typically around 25%, which is very similar to what we see with the monotherapy for ZYNLONTA. The combinations in this space, which are typically ADC or monoclonal antibody based have a roughly a 40% CR rate.

What we were able to show in the first 20 patients, the safety run-in portion of our Phase III study was about a 50% CR rate. So we think we have a chance, again, to be very competitive and even differentiating potentially in both of these segments. Now as you move to second line, you don't -- only add twice as many patients in the second-line segment as you have in the third-line plus segment. We also have an ability, we think, to capture higher market share with a more differentiated clinical profile. And then finally, the duration of therapy, where we see, on average, 3 cycles with ZYNLONTA monotherapy. In the combination studies, we're seeing about 5 to 6 cycles. So all of these factors can help to drive a significantly higher revenue growth opportunity than what we see in the monotherapy. Now deep diving into our Phase III study. This is our LOTIS-5 confirmatory study. This is a randomized study with 420 patients, 1:1 randomization, 90% power, where we're looking at ZYNLONTA plus rituximab versus R-GemOx.

Overall, the primary endpoint is PFS and key secondary endpoints like overall survival, ORR, CR and other key secondary endpoints. As I mentioned before, before we went into the randomized portion of the study, there was a 20-patient safety run-in on which the basis of the data I shared where we demonstrated an 80% overall response rate, 50% CR rate and over an 8-month PFS. This study completed enrollment in the -- by the end of 2024. We need to hit a prespecified number of PFS events of approximately 262 in order to stop the study and read it out. We expect to be able to have that and read top line results for this study in the second quarter of this year and then full results to come at a medical congress by the end of this year.

Now if you look at the profile of our compound, as a monotherapy, we have some distinct differentiating points. One is it works very quickly. As I mentioned, you're typically getting to a response, oftentimes the best response already at the first disease assessment. So it works very quickly. And when you get a CR, they tend to be very durable. The other thing that's very good about the product profile is its manageable safety. There's no irreversible toxicity. So through down dosing or stopping treatment, the patient can -- those side effects resolve, also convenient dosing schedule. Physicians are administering this typically with a fixed duration, and it's a Q3-week dosing with a 30-minute infusion. So very easy to give, very easy to add on to other therapies as well.

Now the limitations right now of the profile as a monotherapy is that we have a limited indication with only third line. Most other combinations are being playing in the second line plus. So why does that matter? If you're a community physician, for example, you may only see 1, 2 or 3 patients in a year than in the third-line setting because you tend to refer out much more to academic physicians as you get to later lines of therapy, whereas in the second-line setting, you may be seeing these patients every month. So it becomes a little bit less relevant for some of the community physicians. And then we also have a CR rate that's around 25%. When we move into LOTIS-5, not only are you moving into a broader patient population, which is significantly more patients is more relevant for community physicians because they see those patients much more often. But also the efficacy from a CR standpoint, we believe can be competitive and even potentially differentiating.

It doesn't take a lot just with this first opportunity to transition this from what was roughly a $70 million opportunity. We ended last year with roughly $73 million of sales to get this to $200 million to $300 million opportunity. We already have, if you look at the left-hand side, 6,000 patients in the third line plus setting. We have roughly a 10% share with 3 cycles that translates in that roughly $70 million. With LOTIS-5, when you add an additional 12,000 patients in the second line, even with only a 5% to 10% share with increased number of cycles, that takes the opportunity to $200 million to $300 million. With every additional 5 share points in the second-line setting, that's an additional $100 million opportunity. So we believe this really already in this one indication can significantly increase the revenue opportunity for the product. Now I'll turn to the other combination in DLBCL that we're very excited about, which is our LOTIS-7 study. This is looking at the combination of ZYNLONTA plus glofitamab, both approved products as single agents with complementary mechanisms of action.

We, of course, as I mentioned, our anti-CD19 ADC and glofitamab is an anti-CD20, CD3 T-cell engaging bispecific antibody. Now we had a hypothesis that we could see additive or synergistic efficacy, but of course, you need to test the safety as well. And so we did a dose escalation first, looking at the full dose of glofitamab as well as 3 different doses of ZYNLONTA, 90 micrograms per kilogram, 120 micrograms per kilogram and the approved dose of 150 micrograms per kilogram. There were no DLTs in the dose escalation, so we moved on to dose expansion. Within the dose expansion, we approved -- we looked at the 2 higher doses of ZYNLONTA with the fully approved dose of glofitamab. Again, I'll share data on both of those looked good, and we're continuing now to expand with 100 patients at that approved dose of ZYNLONTA, 150 micrograms per kilogram plus the approved dose of glofitamab.

One of the unique things about the dosing sequence around this is glofitamab already has Obinutuzumab given on day 1 before the step-up dosing of glofitamab. This is typically when patients have to be hospitalized because of the risk of CRS and ICANS that can occur during that step-up dosing. But glofitamab on its own, when you look at the monotherapy data, still has about a 70% all-grade CRS rate. What we did is after obinutuzumab on day 1, we give the first cycle of ZYNLONTA on day 2. So before you do the step-up dosing of glofitamab on day 8 and day 15. And then these cycles are given -- these products are both given on the same day every 3 weeks. They both are Q3-week dosing, where ZYNLONTA is given for up to 8 cycles and glofit is given for up to 12 cycles.

We believe that by doing that, we could debulk and hopefully reduce the rate and grade of CRS, which you'll see in the data coming forward. Overall, we are pleased with the safety profile that we saw with this combination. The most common Grade 3 event for both products actually is grade 3 or higher neutropenia, roughly 30% in the label of each product. We were happy to see that we didn't really see additive toxicity on the overall grade 3 neutropenia was about 33%, which is very similar to what you see with either product alone. The other grade 3 and higher events that we saw were very, I would say, typical to what's known in the profile of either product. We didn't see any new side effects and the levels were very similar.

CRS, as I mentioned, was able to improve. So whereas you see 70% with the monotherapy of glofitamab when we used the 120 dose of the -- dose that's below the approved dose of ZYNLONTA, that went down to 52%. At the approved dose, which is where we're currently expanding, CRS went down to 25%. So significant reduction versus what's seen in the label, and that was all grade 1 and 2. ICANS is about 4.1%, only grade 1 and 2, again, similar to the profile of glofitamab. From an efficacy standpoint, again, very encouraging.

In the first 49 patients that were tested, roughly a 90% overall response rate and close to a 78% complete response rate. So this data, when you look at it in the competitive landscape is, we believe, can be highly differentiating. Of the 38 patients that were in CR, 33 remained in the CR as of data cutoff. I'll show you the swimmer's plot, so you can see the duration of therapy. Most of the patients achieved a CR at the first disease assessment, but about 14 of those 38 CRs converted over time from an initial assessment of either PR or stable disease. 8 patients were treated previously with CAR-T, 6 of which achieved a CR.

So again, encouraging data in a tough-to-treat population. When you look at the efficacy across both the relapsed population and the primary refractory population, again, we saw very strong efficacy in both populations. You can see overall in the relapsed population, nearly a 92% complete response rate and in the primary refractory, 64% CR rate. So overall, very encouraging results. As you all know, not only in the post CAR-T population, but primary refractory, these are much tougher to treat patient population. So we're happy to see that across these different segments, we're seeing strong efficacy. Here's a look at the swimmer's plot. The green bars represent the CRs. And you can see when you look at that day 42, roughly that 6-week point, the first disease assessment, you see a lot of white either triangles, stars, those are PRs or CRs that are happening right at the first disease assessment.

When you see the black stars, those are ones that convert to CRs over time. And you can see again, as I mentioned, the majority of the CRs, 33 of the 38 remain in CR as of the data cutoff. All of these patients had a minimum of 6 months of follow-up and the longest patient was nearly 2 years of follow-up. So we're seeing encouraging again, early durability data, which we will continue to progress as this trial enrolls. Now I'll turn to marginal zone lymphoma. Marginal zone lymphoma, although being an indolent lymphoma still has high unmet need. There's very few therapeutic options. BTK inhibitors are still the mainstay for most patients. There's roughly 3,000 to 4,000 patients in the U.S. that have relapsed/refractory marginal zone lymphoma. And outside of the recently approved CAR-T product where typically CAR-Ts are not used very significantly in the indolent setting.

You see CR rates only of up to 29% right now. And for therapies, oftentimes, the BTK inhibitors where patients have to keep on the therapy until they progress, so they can be on sometimes for quite a long period of time. We're running an IIT, multicenter IIT driven by the University of Miami, Dr. Lossos, with 50 patients right now. This is data that was presented last year at ICML in June in the first 26 efficacy evaluable patients, overall response rate of 85%, complete response rate of 69%. And the safety profile was consistent with the known profile of ZYNLONTA. This is again, single-agent use of ZYNLONTA, fixed duration. patients are getting, again, on average, like 5 to 6 cycles.

And so we think this, again, could be a real important opportunity for us. We're in the process -- the study is now in the process of enrolling the 50 patients in this setting. And then we plan to not only once the study is completely enrolled and reads out, submit to compendia, but also we're evaluating potential regulatory strategies as soon as we have sufficient data from these 50 patients. Now turning to follicular lymphoma. There is still -- there's many more therapeutic options in follicular than there are in marginal zone, but nonetheless, especially when you get to high-risk groups, there's still quite a bit of high unmet need. So this is a study that's looking at the combination of ZYNLONTA plus rituximab. This is the same combination that's being used in our Phase III confirmatory study in DLBCL. And again, looking at high-risk patients, many of which are POD24 patients.

In the 55 efficacy evaluable patient population, the trial was able to demonstrate 98% overall response rate and nearly an 84% complete response rate, again, with no new safety signals and a profile that was very consistent with the known profile of ZYNLONTA. So again, we think this is very, very encouraging. Right now, the study, again, is a multicenter study on track to enroll 100 patients. And then again, we'll assess both regulatory and compendia strategy as soon as the study is completed with sufficient data. Now if you take a look at the overall opportunity, we're playing in that small box on the lower left, that roughly $70 million-ish opportunity with third line plus monotherapy. As I walked through the data already before, we have a chance to take that opportunity just with LOTIS-5, the Phase III study that's going to read out in the second quarter of this year to a $200 million to $300 million opportunity.

We can take that to $500 million to $800 million with the combination with glofitamab with regulatory approval and compendia inclusion. And then with those indolent lymphomas that I mentioned with marginal zone and follicular lymphoma that could provide an additional $100 million to $200 million with regulatory approval and compendia inclusion. So overall, we think the potential of this product can grow from where it is today to a $600 million to $1 billion peak potential in the U.S. alone. When you take a step back and look at the milestones and the key value-driving catalysts coming forward, we plan to for LOTIS-7, complete enrollment of the study in the first half of this year. We expect to have a readout of that study by the end of this year and then to be able to pursue both compendia strategy, which should happen soon after and then regulatory strategies in parallel.

We think, again, the publication and potential inclusion in compendia can happen in the first half of 2027. With LOTIS-5, we plan to share top line results from the Phase III study in the second quarter of this year. And then again, would file the sBLA and in parallel, share the full data at a medical congress, and that can lead to an approval, we believe, in mid-2027. For marginal zone and follicular lymphoma, the idea is to finish these studies, and we will share that data as early as the end of this year, but sometime between that and the middle of next year to have final results from both of these studies. So we have a lot of data coming on our molecule across these different settings over the course of this year and into early next year. So I want to thank you. I appreciate the opportunity to share the story with you, and I think we'll open up to questions.

Thanks very much for the presentation, and we'll open the floor to questions now.

Maybe I can start with the first one. You've covered a lot today, and it's clear that ADC Therapeutics strategy is centered on ZYNLONTA, DLBCL. Can you share a little bit more about the current treatment landscape and where ZYNLONTA fits in and where you believe ZYNLONTA has the opportunity to play a significant role?

Sure. So patients are treated in DLBCL either in the academic setting or in the community setting. And when you're in the front line, the treatment options are very similar. Patients are typically going to get either R-CHOP or Polivy R-CHP. Those are really the standards of care. And when you look at it, roughly 35% of patients are treated in the academic settings and about 65% in the community. When you move to second line, the treatment options start to again change because now you start getting the segments that I mentioned before of complex therapies, which are more driven by academic institutions and then broadly accessible therapies. These 2 segments exist. And as you get to later lines of therapies, physicians tend to refer out more to academic centers in the community because they don't always have access or the capability to deal with these more complex therapies.

So when you get to second line, it's roughly a 40-60 split between academic and community. It gets to about 50-50 by the time you get to third-line setting. So you see this increasing trend of referring from community to academic. Nonetheless, as I mentioned, within each of these segments, complex therapies, despite having very strong efficacy, patients have to both have access to it, but also be suitable for it. And there's comorbidities that can also preclude a patient from getting access to some of these therapies. So that's why our strategy is really to win in both segments. It's critical to have options for all patients regardless of their patient characteristics or regardless of the treatment setting in which they get treated for the DLBCL. So that's where, again, LOTIS-7 is well positioned, we believe, to be differentiated within that complex therapy segment. And our LOTIS-5 combination, we believe, is very well positioned to be differentiated within that broadly accessible segment.

And what has your current experience been for the third-line plus DLBCL with ZYNLONTA? And how do physicians feel this product?

Yes. I think physicians really like the fact that it works fast, CRs are durable and it's really safe and convenient to give. So I think that those are the attributes that physicians really like. And despite bispecifics, which were launched about 2.5 years ago and in that third line plus setting, gained about 35% share, we were able to maintain our 10% share of the total market despite the market getting much more competitive. And again, we're playing as a single agent in a field of mainly combinations. So we feel like the attributes we have are already playing quite well. As we move into these combinations in earlier line settings, not only do you become more relevant, but the clinical profile, we think can be much more differentiated, and that will open up a significantly bigger opportunity for ZYNLONTA as we expand beyond the third-line setting into earlier lines.

Sales have been essentially flat for ZYNLONTA over the past few years. Where do you see the opportunity to grow with this product?

Yes. I think because we played in a small segment in the third-line plus setting. And as I mentioned, where competition gained a lot of share, we were still able to actually hold our own at the roughly $70 million mark by maintaining our roughly 10% share in that third-line setting despite increasing competition. As we move into the earlier lines, that's when we think there's going to be a big revenue inflection in the product. So we should be getting into compendia for many of these combinations and uses potentially as early 2027. That will lead to some growth. But the real big inflection point will come in the middle of the year when we have the approval of LOTIS-5. And we think that's when you can have significant growth starting in mid-2027 going through 2028 and beyond.

That's great. You have 2 important trials in the second-line plus DLBCL. What is the strategy in this line? And how do these 2 trials play together?

Yes. As I mentioned, I mean, there's -- the reason that these 2 segments exist is, for example, if you think of CAR-T, which is one of the more tougher to administer products in that complex therapy segment, has great efficacy, but not all patients can get access to it. Only about 20% of patients get a CAR-T in second line, third line despite the strong efficacy. So we know that there's still a need for other therapies. Even bispecific products, which again have strong efficacy, many community physicians can't administer those products. They don't have the capability to manage CRS or ICANS.

And so the core of our strategy is really to make sure that we can offer great complementary solutions and be a backbone therapy for what's used most commonly in DLBCL. So we think bispecifics will be the backbone therapy within the complex therapy segment. And again, we're adding on instead of chemo or other ADC products. And in the broadly accessible therapy, our based therapies, Rituxan-based therapies are the most commonly used therapies, typically Rituxan and chemo. We're replacing that with ZYNLONTA and again, can kind of fit in with the way physicians think about the treatment. They think about, I'm using a bispecific-based therapy or Rituxan-based therapy. We're replacing the chemo with an ADC where we think we can deliver a significantly better clinical profile.

What do you need to see in LOTIS-5 to be competitive, assuming a positive trial, what is the potential source of business for LOTIS-5?

Yes. So I think to be competitive, as I mentioned, there's already some attributes that are really differentiating about the product. The fact that it works fast, the CRs are so durable, it's safe and convenient. In addition, we think by moving to the second line, you become much more relevant, especially for community treaters, where we think that will be the biggest opportunity to expand ZYNLONTA with LOTIS-5 in the community where broadly accessible therapies are still the mainstay.

And then also having a more competitive CR rate, where right now, we're at 25%, where most of the other therapies are around 40% CR rate. So if we're at or above that level, you're competitive to differentiating on efficacy as well. So we think those elements are what's going to help to drive the use of ZYNLONTA should we have a positive study with LOTIS-5. Now the sources of business will come from the main broadly accessible therapies. So chemo is one of the biggest ones, but also, of course, Monjuvi, Polivy, other targeted therapies that are used in that second-line plus setting. Those would be the sources of business, the currently approved products in that broadly accessible segment.

And what gives you confidence you will be able to achieve the noted peak revenue with LOTIS-5?

What gives me confidence is that even with a complete response rate that's below that of the combinations we're competing with as a single agent and despite bispecifics gaining so much share in that third line plus setting, we've been able to maintain roughly a 10% market share. If we achieve that same market share in the second-line setting with a better profile in combination, that would lead to a $300 million opportunity. So I think just simply put, even with the suboptimal clinical profile, we've been able to do it in the third-line setting because of the other attributes. When you improve the CR rate in the clinical profile and you get into a population where you add an additional 12,000 patients to the 6,000 patients we're planning today, you get to about a $300 million opportunity. So that's what gives us the confidence is we've been able to do it, and I think we can continue to execute and deliver on that with the profile that we expect.

What can we expect from the next update on LOTIS-7.

Yes. So we shared a couple of interim looks at LOTIS-7 most recently in December, where we showed data on the 49 patients that I shared with the 78% CR rate. So the next update will be the final data on all 100 patients with at least 6 months of follow-up. That we expect to happen at the end of this year at a major medical congress and publication. We think that can be the basis for submitting to guidelines as well as for any regulatory discussions with the FDA and other agencies.

How does the opportunity for LOTIS-7 change if you're listed rather than pursuing the full approval?

Yes. So obviously, if we're just listed before any potential approval, we won't promote the product. So that does affect the amount you could do. What we said is that LOTIS-7 with a regulatory approval in compendia beyond the $200 million to $300 million with LOTIS 5 could be an additional $300 million to $500 million opportunity. But of course, if you're not promoting the product, you're going to capture a portion of that. What we know now in the landscape is that all the bispecific combinations that are currently being used in the second-line setting are all in compendia.

So if we had a compendia -- if we're only in compendia initially, we'd be at a level playing field. So again, we won't promote the product. That's not something we would ever do off-label. But we have seen that the use of bispecific combinations, just given the data has been there. And physicians tend to be data-driven. So we believe that ZYNLONTA plus glofitamab has the chance to have the most highly differentiating clinical profile within that class.

That's very helpful. Thank you. I think we're at time. Thanks very much again for the great presentation, and thanks, everyone, for joining.

Yes. Thank you very much.

Good morning, ladies and gentlemen, and welcome to the ADC Therapeutics SA LOTIS-7 update. [Operator Instructions] 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 Investors 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 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 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 evaluable patients with a minimum of 6 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 2 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 could 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 in 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 2 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 Ib 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 2 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 3 cycles to 5 to 6 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 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 non-hematologic toxicities between the 2 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 rates. The design of the trial includes 2 parts. In Part 1, dose escalation was conducted at non-Hodgkin lymphoma patients at 3 dose levels of ZYNLONTA with glofitamab or mosunetuzumab in the third-line plus setting. In Part 2, dose expansion moves forward in second-line plus 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.

Based on the scientific evidence available and in alignment with the Data Safety Monitoring Committee, we selected the 150 microgram 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 8 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 evaluable patients with a minimum of 6 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 and non-adverse events of each drug continues to be the most common treatment-emergent adverse events of Grade 3 or higher and is similar to the average reported in the approved prescribing information of each drug separately. Grade 5 adverse events occurred in 2 patients and 1 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 1 or 2.

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 8 patients previously treated with CAR-T, 6 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 evaluable patients, there are a few characteristics that are important to highlight. The median age in this study is 70 with a range of 26 to 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 1 with a range from 1 to 5. 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, 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 2 patients or 4.1%. This includes one Grade 5 nontreatment-related adverse event of sepsis due to gastric ulcer and one Grade 5 treatment-related adverse event of her oedema per investigator, which occurred more than 105 days after the last dose of study treatment. Of note, this patient completed 8 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 3 of the 49 patients could discontinued both therapies due to treatment-emergent adverse events. 6 patients or 12.2% discontinued ZYNLONTA only and 3 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 measure 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 1 or 2 with 1 case of Grade 3. The 150 microgram per kg dose had 25% any grade CRS, all of which Grade 1 or 2. Grade 1 and 2 CRS cases were managed with tocilizumab, corticosteroids, acetaminophen and/or fluid bolus without ICU admittance or pressure support.

Grade 3 CRS case was managed with tocilizumab, acetaminophen, dexamethasone norepinephrine and included ICU admittance. ICANS were seen in 2 patients treated at the 120 microgram per kg dose. These ICANS were Grade 1 and 2 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, 1 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 6 months after initial response to frontline therapy. Relapse is defined as progression following an initial response as well as those 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 swimmer's plot. The green bars show all patients in complete response and the length of these bars show 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 8 patients previously treated with CAR-T and undergoing response assessment, 6 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 in LOTIS-5, 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.

Overall, we believe ZYNLONTA has the potential to reach peak revenues of $600 million to $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 prespecified number of PFS events is reached and data are available. Assuming positive results, the 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?

[Operator Instructions] Your first question comes from Eric Schmidt with Cantor.

Maybe the first question is on efficacy. You laid out, I think it was Slide 7, 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?

Yes. Thanks for the question, Eric. I think we feel good about our durability, and that's one of the reasons we want to share data with at least 6 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 6 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 into a little bit detail of the other 5 because actually of the 5, only 2 progressed, 2 patients had Grade 5 AEs, while they were still in the CR and 1 patient was censored because of getting a solid tumor cancer and having to get chemotherapy. And so we was lost to follow-up.

So actually, even in the 33 of 38, there were only actually 2 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 will be able to give good comparisons to other trials over time.

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 6-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?

Yes. So I would also say that if you look at the update, it was 72% the first update that 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 combinations 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 how we're making sure that we can achieve this intent of having a similar balanced population to other big bispecific combination trials.

Yes. There is 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 factory will be included. However, it have to be balanced.

So also in conjunction with the steering committee of the study, and we're all aligned. In addition, there is parameters in the protocols actually that will eventually make sure for this population to be stabilized by the end of the study. We're -- in the 150 dose, we're only looking at 28 patients. There is 72 more patients to be enrolled. So there is a quite opportunity for this to stabilize and be able to be balanced over time.

Your next question comes from Michael Schmidt with Guggenheim.

Congrats on the data update. 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?

Yes, it's a great question, Michael, and good observation. I think the difference in percent 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% relapsed -- 90% CR in the relapsed population and almost a 67% CR rate in the primary refractory patient population. So that data is outstanding.

When you look at the real world, patients are pretty balanced between the 2 populations. It's pretty evenly split. When I look at the other trials, the other big bispecific combination trials that are listed in compendia, they're also anywhere from 52% to 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 trajectory sort 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. And 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?

Yes. Certainly, with compendia, we'd only expect to capture a portion of the total revenue potential. Obviously, for anything it's in compendia where we don't have regulatory approval, we will not promote. So it would be up to the decision of the 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 combination products in the second-line setting that are approved. There are 3 different combinations 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. And congrats on the update.

Your next question comes from Clara Dong with Jefferies.

Congrats on the update. So 2 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 in today's update, you have a minimum 6 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 doses are primary refractory and relapsed. The response data in those 2 populations are quite impressive. So just also wondering what could be the clinical implications to physicians as well -- of the data from those populations?

Yes. So maybe starting with your second question about in 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 could see is, of the 38 CRs, only 2 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 evaluable patients, but only 30 were efficacy evaluable. That's because only 30 of the patients had at least achieved the first -- reached 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 6-month follow-up is it provides a much more mature way to look at the data. We could 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 AE. So we want to give the most mature and view of what the data would look like and the most representative view of the data. We could do that obviously an earlier data cuts, but now that we have a larger sample set with nearly 50 patients with a minimum of 6 months of follow-up, I think this is a pretty robust update that we're able to provide now.

Your next question comes from Leonid Timashev with RBC Capital Markets.

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 could just talk about the safety profile in totality. I mean obviously, you'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 infusion 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? If there's maybe some kind of interaction going on with the bispecifics, if you have any thoughts around that?

Okay. So you're asking about the safety population. First off, I'd 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. So I don't think we're seeing anything as an outlier. One of the reasons we, again, want to show safety on -- with at least 6 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. So I think this provides a very good view of the AE profile.

And 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.

I'll add another one here on just the safety profile. I 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? Curious as this kind of matures out with more patients, what do we want to see in the CRS rates to still have confidence that it could be best-in-class?

Yes. I mean I think, first of all, CRS with a CAR-T, I think, is even much more severe than with the bispecific. So I think bispecific CRS is definitely more manageable than with the 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 -- was done intentionally to dose the ZYNLONTA before the step-up dosing of glofitamab after 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.

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% and 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 grade CRS will, I think, further -- could further drive the penetration of bispecifics in the community setting.

Got it. 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 you have, it may have taken a year or a little bit more than that. Obviously, in your guidance, you're expecting to have full enrollment of 100 patients by the -- 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 full up the enrollment.

Yes. I mean we've clearly had a lot of interest in the trial since the EHA, ICML update in June, and we saw some acceleration in the enrollment. But we're also -- per what Mohamed said, there's an intent to make sure this is a balanced study and that the baseline characteristics are very well represented. So yes, 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. And congrats on all the progress in the data.

[Operator Instructions] Your next question comes from Robert Burns with H.C. Wainwright.

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 want to get your thoughts on that data set, especially since it seems like they had a little more second line plot, there were more patients with 2 medium prior lines of therapy. And considering the Phase III ongoing SKYGLO trial, I want 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?

Yes. So I think I think the glofit-pola data is strong. I mean it was about a 62% CR rate in some tough-to-treat population. So I think it shows that 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 is -- has done a good job. It's the first agent with the POLARIX trial in over 20 years to change the frontline setting from R-CHOP to Pola-R-CHP. And a decent number of patients, probably somewhere around 1/3, maybe even a little more of patients are getting pola frontline. So I think that agent has definitely advanced the frontline setting.

With regards to the other frontline 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 2 to 5 patients. That's roughly 2/3 of patients in the frontline setting. And obviously, what we've seen -- I think if bispecifics do get approved and show a 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 frontline.

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 frontline to second line, I think it depends probably -- it's hard to speculate, but I think it will 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 frontline and second-line setting.

And in this dynamic environment where bispecifics, we don't know how deep are they going to go to 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 is 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.

There are no further questions at this time. I will now turn the call over to Ameet for closing remarks.

Well, 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.

Good morning, ladies and gentlemen, and welcome to the ADC Therapeutics Q3 2025 Earnings Conference Call. [Operator Instructions] This call is being recorded on Monday, November 10, 2025.

I will now turn the call over to Nicole Riley, Head of Investor Relations and Corporate Communications for ADC Therapeutics. Nicole, please go ahead.

Thank you, operator. Today, we issued a press release announcing our third quarter 2025 financial results and business updates. This release and the slides we will use in today's presentation 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 discuss our operational performance and recent business highlights; our Chief Medical Officer, Mohamed Zaki, who will discuss our clinical programs and updates; followed by our Chief Financial Officer, Pepe Carmona, who will review our third quarter 2025 financial 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.

Today's presentation also includes non-GAAP financial reporting. These non-GAAP measures should be considered in addition to and not in isolation or as a substitute for the information prepared in accordance with GAAP. You should refer to the company's third quarter earnings release for information and reconciliation of historical non-GAAP measures to the corporate GAAP financial measures.

I will now turn the call over to our CEO, Ameet Mallik. Ameet?

Thanks, Nicole, and hello, everyone. Thank you for joining us on today's call. In the third quarter of 2025, we continue to focus on execution and delivering on our commercial strategy, maintaining ZYNLONTA as a differentiated treatment option for third-line plus DLBCL patients while advancing data across key trials.

Net product revenues were $15.8 million in the third quarter, reflecting variability in customer ordering patterns and were broadly in line with the quarterly run rate over the past 2 years. We continue to progress against our key ZYNLONTA trials in second line plus DLBCL and expect to share additional data in the coming months. We plan to provide an update on LOTIS-7, our Phase Ib trial evaluating ZYNLONTA in combination with the bispecific antibody, glofitamab, before the end of the year. Then in the first half of 2026, we plan to announce top line results from LOTIS-5, our Phase III confirmatory trial of ZYNLONTA in combination with rituximab once the prespecified number of PFS events is reached and data are available.

Within indolent lymphomas, the lead investigator on the Phase II IIT of ZYNLONTA in combination with rituximab recently presented encouraging updated relapsed or refractory follicular lymphoma data at the 22nd International Workshop on Non-Hodgkin Lymphoma. The trial is on track to enroll 100 patients. In addition, the Phase II IIT of ZYNLONTA in relapsed or refractory marginal zone lymphoma continues to enroll to the target of 50 patients. Beyond ZYNLONTA, we continued with IND-enabling activities for our PSMA-targeting ADC, which are on track to be completed by the end of the year.

Lastly, just after the quarter end, we secured a $60 million private placement led by TCGX, including participation from Redmile Group and other existing investors. This financing takes our expected cash runway at least to 2028. With our strengthened balance sheet, I am confident that we are well positioned to further invest in ZYNLONTA as we anticipate advancing into earlier lines of therapy for DLBCL and into indolent lymphomas.

As a 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 in the potential to reach significantly more patients by extended use into earlier lines of therapy in DLBCL and into indolent lymphomas. The data we've seen across these settings so far has been consistently encouraging with the potential to be highly differentiating. We continue to believe that through expansion into these settings, ZYNLONTA has the potential to reach peak annual revenues of $600 million to $1 billion in the U.S.

Our current indication has, as I noted earlier, shown relative stability in net revenues over multiple quarters, demonstrating ZYNLONTA has a clear place in the market as a monotherapy. We believe LOTIS-5 has the potential to lift peak annual revenue for ZYNLONTA to $200 million to $300 million as we expand into the second-line setting. Not only would this double the addressable patient population but, with an improved clinical profile versus our current indication as a monotherapy, we expect to gain share in the second-line plus setting and improved duration of therapy. With LOTIS-7, we estimate we can expand the total opportunity for ZYNLONTA in DLBCL to $500 million to $800 million in peak annual revenue with both regulatory approval and compendia listing.

If the data continues to be compelling, 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. On top of this, we see additional potential for ZYNLONTA in relapsed or refractory marginal zone lymphoma and relapsed or refractory follicular lymphoma. If the encouraging initial data in the Phase II IITs are maintained in larger patient numbers, we believe these indolent lymphomas could provide additional peak annual revenue for ZYNLONTA of $100 million to $200 million with both regulatory approval and compendia listing, primarily driven by MZL.

Let's turn on a little more into the specifics of the DLBCL treatment landscape to explain why we believe ZYNLONTA has the opportunity to play a significant role. In both the second and third line plus settings, 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 confined to the academic centers and more sophisticated community centers and includes 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 includes 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.

Through LOTIS-5 and LOTIS-7, we believe ZYNLONTA combinations have the potential to raise the bar on efficacy in second line plus DLBCL in their respective treatment segments, offering complementary approaches to addressing unmet needs. In LOTIS-5, our Phase III confirmatory study, we are combining ZYNLONTA with the most widely used agent, rituximab, in patients with second-line plus DLBCL. As a reminder, initial data from the safety lead-in portion showed an overall response rate of 80% and a complete response rate of 50% with no new safety signals, demonstrating that this combination has the potential to provide competitive second-line plus efficacy with a favorable safety profile, allowing broad accessibility.

In LOTIS-7, our Phase Ib trial, we are combining ZYNLONTA with a highly effective bispecific, glofitamab, in second-line plus patients. Data presented in June at EHA and ICML based on the April 2025 cutoff showed the combination was generally well tolerated with a manageable safety profile. Furthermore, we believe it demonstrated clinically meaningful benefit with an overall response rate of 93.3% and a complete response rate of 86.7% across 30 efficacy-evaluable patients. We are encouraged by the promising early data, which we believe demonstrates the potential for ZYNLONTA plus glofitamab to be a best-in-class combination in a highly competitive market.

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 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. Together, we believe these combinations have the potential to double the addressable patient population as we move into the second line and increase the duration of therapy moving on average from 3 cycles to 5 to 6 cycles.

Now I will turn the call over to our Chief Medical Officer, Mohamed Zaki, who will share the latest on the Phase II follicular lymphoma IIT data. Mohamed?

Thank you, Ameet. I am pleased to share updated data from the Phase II investigator-initiated trial of ZYNLONTA in combination with rituximab in relapsed/refractory follicular lymphoma. The data were presented in September at the 22nd International Workshop on Non-Hodgkin Lymphoma by the lead investigator, Dr. Juan Pablo Alderuccio, from the Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.

Data presented from the 55 efficacy evaluable patients to date in this trial continues to demonstrate encouraging results with an overall response rate of 98.2% and a complete response rate of 83.6%. After median follow-up of 28 months, median PFS was not reached and the 12-month PFS was 93.9%. In in this trial, no new safety signals were observed and CFT was consistent with the nonprofile of ZYNLONTA. The University of Miami is actively enrolling towards a target of 100 high-risk relapsed/refractory follicular lymphoma patients and is opening the study at additional U.S. cancer research centers. As soon as sufficient data are available, we plan to assess the regulatory and update pathways.

Now I will turn the call over to Pepe Carmona, our CFO, who will discuss financial results for the third quarter. Pepe?

Thank you, Mohamed. On the financial front, ZYNLONTA net product revenues in the third quarter of 2025 were $15.8 million as compared to $18 million in the same quarter in 2024. Total operating expenses for the quarter were $45 million on a non-GAAP basis, representing a 12.1% net decrease over prior year. The reduction was primarily driven by lower R&D expenses with sales and marketing expenses stable year-over-year.

We continue to be disciplined in our capital allocation towards potential value creation while driving efficiencies across the portfolio.

On a GAAP basis, we reported a net loss of $41 million for the second quarter of 2025 or $0.30 per basic and diluted share as compared to a net loss of $44 million or $0.42 per basic and diluted share for the same period in 2024. The decrease in net loss for the quarter is primarily attributable to lower R&D and G&A expenses. You can find the reconciliation of GAAP to non-GAAP measures for the third quarter and year-to-date in the accompanying financial tables of the press release issued earlier today and in the appendix of this presentation.

At the end of the quarter, we had cash and cash equivalents of $234.7 million, which compared to $250.9 million as of December 31, 2024. In October, we entered into a $60 million PIPE financing which, on a pro forma basis, expanded our cash and cash equivalents to approximately $292.3 million as of that date. The strengthening of our balance sheet allows us to execute our strategy with an expected cash runway extending at least to 2028.

Across LOTIS-5, LOTIS-7 and MZL ZYNLONTA programs, we expect to have data catalysts in the remainder of 2025 and 2026. For LOTIS-5, we expect to provide top line data in the first half of 2026 once the prespecified number of PFS events is reached and data are available. Assuming positive results and supplemental biologic license application submission to regulatory authorities will follow with potential confirmatory approvals in second line plus DLBCL as well as publication and compendia inclusion in the first half of 2027.

With LOTIS-7, following presentation of the data at EHA and ICML in June, we observed an acceleration in enrollment in the study at a selected 150-microgram per kilogram dose level. We plan to provide a clinical update on all efficacy-evaluable patients with a minimum of 6 months of follow-up through a corporate announcement before the end of the year. Once sufficient data with longer follow-up are available, we plan to engage with the FDA. In addition, assuming positive results, we plan to pursue publication and compendia inclusion in the first half of 2027.

With indolent lymphomas, we expect additional data to be shared at medical conferences by the lead investigators and we plan to assess regulatory and competitive strategies when sufficient data are available. Beyond ZYNLONTA, we continue to advance our exatecan-based PSMA-targeting ADC with completion of IND-enabling activities anticipated towards the end of this year.

I will now turn the call back over to Ameet.

Thank you, Pepe. Let me close by saying that I'm pleased with how we are executing against our strategy and continue to be excited by the consistently encouraging ZYNLONTA data we are generating across our ongoing trials. We have a clear vision to unlock the true potential of the company with multiple potential value-creating milestones ahead and a balance sheet that enables us to deliver on our strategy.

We can now open the line for questions. Operator?

[Operator Instructions] Your first question comes from Eric Schmidt with Cantor.

Maybe on LOTIS-7, intrigued by Pepe's comments that we're seeing accelerated enrollment post the June data release. Not surprising, of course. Can you frame how many patients we might get later this quarter? And then in terms of your target enrollment out of 100 or so patients, are you adjusting that target? And is it possible that, that target could be achieved sooner rather than later?

Thanks for the question, Eric. Yes, no, we've been pleased that since the EHA and ICML update, we had even greater interest in the trial and enrollment definitely accelerated. We're still targeting the roughly 100 patients that we've been targeting to enroll. It will occur quicker than what we originally anticipated. We're not giving any exact time line. We're still confirming the first half of next year to have that completed.

And then in terms of the upcoming data release, Ameet, are you still targeting 40 or 40-plus?

Well, will give -- as you recall, we have enrolled originally 20 patients in each dose and then we continue to expand at the 150 dose, right? So it will clearly be more than the original 20 and 20, but it won't be fully 100. And also, I want to make sure you heard what Pepe said is that we're going to be sharing update on all efficacy-evaluable patients with a minimum 6 months follow-up. This is because it provides more stable, meaningful updates both in terms of the depth of response, but also the durability of response.

That was, as you may recall, some of the questions we received in the early updates is we have a very limited follow-up. So now we're focused and where the data is more stable, and that's really what takes us with the minimum of 6 months follow-up.

Your next question comes from Clara Dong with Jefferies.

This is Jenna Li on the line. Could you talk about, in the context of the upcoming LOTIS-5 and LOTIS-7 data and the submission time line, when should we expect to see an inflection point for ZYNLONTA sales And could you also give some qualitative comment on the pace of revenue ramp-up once you have those potentially positive data or approval in hand?

So I think you're asking about the milestones and then also the revenue inflection. So first, I would say, for LOTIS-7, we expect to share an interim update on data later this year. And obviously, we expect to have full data sometime by the end of next year or into the first half of 2027, As you can see, what we guided to is publication and/or compendia inclusion sometime between the end of next year in the first half of 2027.

With LOTIS-5, we expect to share top line results in the first half of 2026 and then have approval sometime in the first half of 2027. So if you think of the revenue ramp up for those two, following compendia inclusion and approvals, which we expect for both the first half 2027, we expect revenues to ramp up subsequent to that.

Sorry, just a quick follow-up. Did you also have any comments on the pace of ramp-up following first half '27?

Yes. I mean, I don't want to guide to the exact ramp up. What I will say is if you look at other launches, whether it's the bispecifics or POLIVY in the front line or others I would say the majority of the ramp-up happens during the first 2 years post launch or approval or compendia listing of a new indication. It's typically -- the maturity is going to happen in the first 2 years.

Your next question comes from Michael Schmidt with Guggenheim Securities.

This is Sarah on for Michael. So I just wanted to get your thoughts on with these newer agents moving into frontline DLBCL, is that something that you are or would consider pursuing for ZYNLONTA?

Yes. And I think the front line will be interesting because if you look at the frontline setting, for decades really, R-CHP was the standard of care. And then only a couple of years ago, you saw POLIVY R-CHP get approval. And that was based on a marginal improvement in PFS without the benefit. But of course, safety looked good. And that's been actually pretty widely adopted. So probably, the high bar is my point.

One of the biggest things being studied right now are bispecifics. And I think there are some excitement about. It if those could have potential still to be determined, I think. We're still a little bit of ways away from seeing those readouts. And in terms of our future development, we'll consider how that goes for this combination post the readout of the 100 patients. And obviously, any support would depend on a partner or two. And I don't see us likely finding a Phase III study with this in the front line or the second line setting with this combination purely on our own. Yes, we're watching the space closely.

Your next question comes from Leonid Timashev with RBC Capital Markets.

I just want to ask on sort of the split of community and academic. I know you've talked about LOTIS-5 potentially being more positioned in the broadly applicable therapies and the LOTIS-7 more for the academic. But I guess I'm curious how neat you think those breakdowns actually are going to be and sort of how you're going to balance ultimately where patients are found and how you want to focus your sales force across academic and community to sort of pursue the opportunity where it is.

Yes. So I wouldn't do the breakdown in terms of community. What I'd say is for the more complex therapies, whether it's CAR T or bispecifics, let's just talk about bispecific because that's more applicable to LOTIS-7. They're not only used across all of the academic space. They are used in more sophisticated community centers and that may grow over time. So I wouldn't say statistics are purely community versus academic. It's more all of the academic can administer products and a portion of the community can administer those products. In that universe of institutions that can administer the product, obviously, LOTIS-7 is going to have a critical place.

Then there's other therapies like chemotherapy, ADCs, antibodies, which are more broadly accessible, and those can be ministered across all settings. But they are still administered in the academic centers and they're administered in all the community settings. So I wouldn't differentiate to say LOTIS-7 is going to be purely academic and LOTIS-5 is going to be purely community. The reality is LOTIS-7, when a patient is suitable for it and the facility can administer the therapy, you're going to go with the highest efficacy product and a combination that you can go with. We think LOTIS-7 is really well positioned and that will be used, again, in all the academic centers and a portion of the community. Exactly how much, we'll see over time how bispecifics will adopted by the community.

With LOTUS 5, either because of accessibility of the therapy or because suitability for the patient, remember, there are some patients that have co-morbidities or other conditions, which may prevent that from getting an immune-based therapy. Subsequently, there maybe a post-CAR T patient that's at risk of infection or maybe a patient with autoimmune disease. I mean, there are other reasons why you're not going to want to give a bispecific based therapy. And for other centers in the community, they are going to have access to them. And so for all those reasons, we think LOTIS-5 still plays a big role. We don't see our based chemo regimens having of our share in the relapse/refractory market.

So we think we have a good place, and that's really our strategy, is to hopefully have leading efficacy in both of these segments, both the complex therapies and the more broad accessible therapies.

Your next question comes from Sudan Loganathan with Stephens.

I know you've spoken about the opportunity in the second line, third line plus for relapsed/refractory DLBCL with LOTIS-7, LOTIS-5 outcomes, respectively. But can you give us more details on how you view each percentage increase in penetration in either the second or third line setting would add to the ZYNLONTA revenues to achieve your peak guidance ranges that you've noted?

And then secondly, regarding this ZYNLONTA plus rituximab for relapsed/refractory FL. Data thus far at 84% CRE seems to sit nicely right after the T cell therapeutics and then in line or slightly better than bispecifics. If this holds true, does this mostly take market share away from bispecifics? Or any opportunity to take from the T cell therapeutic options in FL? I'd like to get in your details on those things.

Yes. So I would say to answer your first question about what's the share point worth, so think about -- in the second line setting, I'd say there's about 12,000 patients in the U.S. and in the third line plus setting, there's 6,000 patients. So depending on where you're getting the share is the second line setting or third line plus, every share point obviously multiplied by the number of patients. With monotherapy, we're typically seeing 3 cycles.

Now remember, the first two doses of our product are at 150 micrograms per kilogram and then it drops to 75. So it's weight-based, but oftentimes, it can be two vials for the first 2 cycles and drop to one vial. What we're seeing with LOTIS-5 and LOTIS-7 is somewhere between 5 to 6 cycles. So you can just do the subsequent calculation on vials. And then you know what our net price and our growth price is in the upper $20,000, net price is in the lower $20,000. So if you do the kind of calculation depending on what -- if you're talking about a share point in the second line or third line plus in, that kind of gives you a rough estimate.

Just by way of example, like in the LOTIS-5, for example, if we were able to maintain our roughly 10% share that we have in the third line plus setting and translate that in second line setting but with increased duration of therapy in our net pricing, that would take our product, which is on roughly $70 million run rate, that's what it's kind of been the last couple of years, to just over $200 million. Obviously, we're hoping with efficacy improvements you actually gain share, and that's what leads to the guidance of $200 million to $300 million. You can see more calculation for LOTIS-7.

Now turning to the indolent lymphomas. I think we're excited both about the data that Mohamed spoke about with the relapsed/refractory follicular lymphoma and relapsed/refractory marginal zone lymphoma data that was presented at EHA and iwNHL. I think both right now on outstanding results. I would say, in terms of the opportunity for potential adoption, right now, we're basically funded to try to get for both. So obviously, we won't promote either of these indications. But what I could say is unmet need and the level of competition is probably higher -- the unmet need is higher in MZL and the level of competition is lower in MZL versus follicular lymphoma. That's why we emphasize that one to a bit more.

When you look at the different agents that are approved or in compendia, the SCR rates are 29%, roughly 30%. Even if you look at subsequent data that has come out, maybe a bit higher than that. What we've been showing is closer to 70% CR in the MZL setting. In follicular although the data is outstanding, and we hope to have a place there, it's a lot more competitive. There's literally more than 10 agents that have Phase III trials including the bispecifics and many other agents who have large Phase III studies with overall survival. And it's just a more competitive space. So that's why we think the potential for uptake is just smaller, not because the data isn't excellent, but just because it's a much more competitive space. .

There are no further questions at this time. I will now turn the call over to Ameet Mallik for closing remarks.

Well, I want to thank you all for joining our call today. We really appreciate the questions and we appreciate 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.