ADC Therapeutics - Earnings Call - Q2 2025

Executive Summary

• Q2 2025 total revenue was $18.84M, up 8.2% year over year; net product revenue was $18.09M, while adjusted net loss was $28.68M; GAAP EPS was $(0.50) versus $(0.38) in Q2 2024 as restructuring and higher R&D lifted operating costs.
• Against Wall Street consensus, ADCT posted a revenue beat and an EPS miss: Revenue $18.84M vs $17.86M consensus; EPS $(0.50) vs $(0.48) consensus; the top-line beat was driven by price and volume variability, while bottom line was pressured by $13.1M restructuring and impairments and higher LOTIS-5/7 and PSMA IND activities (*Values retrieved from S&P Global).
• Clinical momentum continued: LOTIS-7 (ZYNLONTA + glofitamab) showed ORR 93.3% and CR 86.7% across 30 efficacy-evaluable patients with manageable safety; enrollment expansion to 100 patients at 150 µg/kg is underway; FDA engagement and a second-half update are planned.
• LOTIS-5 remains on track to reach prespecified PFS events by year-end 2025 with top-line data to follow; sBLA submission anticipated in H1 2026; compendia inclusion targeted in H1 2027.
• Liquidity strengthened via a $100M PIPE (net $93.1M), extending expected cash runway into 2028—a key stock catalyst alongside LOTIS-5 top-line and LOTIS-7 updates in H2 2025.

What Went Well and What Went Wrong

What Went Well

• LOTIS-7 efficacy and tolerability: ORR 93.3%, CR 86.7%; 25 of 26 CRs remained at cutoff; CRS/ICANS largely Grade 1–2 with lower CRS at 150 µg/kg; supports expansion to 100 patients and potential compendia strategy.
• Solid revenue execution: Net product revenue of $18.09M (+6.2% YoY); total revenue $18.84M (+8.2% YoY), aided by higher sales price and volume variability; CFO reiterated revenue growth opportunity tied to expansion trials.
• Strengthened balance sheet and runway: $93.1M net proceeds from PIPE financing extended cash runway into 2028, enabling pursuit of clinical catalysts and commercialization readiness.

Management quotes:

• “We recently shared impressive efficacy data from our LOTIS-7 study… and have additional key clinical milestones anticipated through 2026.” — CEO Ameet Mallik.
• “Overall we believe we have multiple value driving catalysts within our cash runway which is expected to extend into 2028.” — CFO Jose Carmona.

What Went Wrong

• Elevated operating expenses and GAAP loss: Q2 total operating expenses were $62.99M; GAAP net loss widened to $(56.65)M, driven by $13.1M restructuring/impairment and higher R&D related to LOTIS-5/7 and PSMA IND enabling activities.
• EPS miss vs consensus: GAAP EPS of $(0.50) fell short of $(0.48) consensus as restructuring and R&D outweighed the revenue beat; adjusted net loss rose to $28.68M from $24.37M in Q2 2024 (*Values retrieved from S&P Global).
• Business rationalization: Discontinuation of early preclinical programs and planned UK facility closure (≈30% workforce reduction) reflect strategic refocus but near-term execution risk and severance/impairment costs.

Transcript

Speaker 6

Morning, ladies and gentlemen, and welcome to the ADC Therapeutics FA ADCT Q2 2025 earnings conference call. At this time, all lines are in a listen-only mode. Following the presentation, we will conduct a question-and-answer session. If at any time during this call you require immediate assistance, please press star zero for the operator. This call is being recorded on Tuesday, August 12, 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.

Speaker 5

Thank you, Operator. Today, we issued a press release announcing our second quarter 2025 financial results and business updates. This release and the slides we will use in today's presentation are available on the Investor section of the ADC Therapeutics website. I'm joined on today's call by our Chief Executive Officer, Ameet Mallik, who will 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, Jose Carmona, who will review our second 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 second quarter earnings release for information and reconciliation of historical non-GAAP measures with the comparable GAAP financial measures. I will now turn the call over to our CEO, Ameet Mallik. Ameet?

Speaker 0

Thanks, Nicole, and hello, everyone. Thank you for joining us on today's call. The second quarter of 2025 represented a period of continued solid performance for our company, as well as the presentation of promising key data. Throughout the quarter, we continued to focus on execution and delivering on our commercial strategy, maintaining our place as a treatment option for Third Line Plus DLBCL patients. Net product revenues were $18.1 million and $35.5 million in the second quarter and first half, respectively, both of which were slightly higher as compared to the same periods in the prior year. During the second quarter, we were pleased to have LOTIS-7 data presented at EHA, the European Hematology Association Congress, and at ICML, the International Conference on Malignant Lymphoma.

We are encouraged by the promising data, which we believe demonstrates the potential for ZYNLONTA plus glofitamab to be a best-in-class combination in a highly competitive market. Data as of the April 2025 cutoff date shows ZYNLONTA in combination with glofitamab was generally well tolerated with a manageable safety profile. In addition, we believe the combination demonstrated clinically meaningful benefit with an overall response rate of 93.3% and a complete response rate of 86.7% across 30 efficacy-evaluable LBCL patients. Of note, 25 of the 26 patients achieving CR remained in CR as of the data cutoff. For reference, we have seen complete response rates in other bispecific combination trials in the range of 47% to 62%. We are currently expanding enrollment to 100 patients at the selected 150 mcg/kg dose, which will support regulatory discussions and is in line with recent examples of bispecific combination therapies added to Compendia.

We expect to share an additional update on LOTIS-7 in the second half of 2025. Once sufficient data with longer follow-up is available, we plan to discuss the path forward for ZYNLONTA and glofitamab with regulatory authorities and to pursue a Compendia strategy. LOTIS-5 remains on track to reach the pre-specified number of progression-free survival events by the end of 2025. After the pre-specified number of PFS events is reached and data are available, we expect to provide top-line data on this Phase III confirmatory trial evaluating ZYNLONTA in combination with rituximab in patients with Second Line Plus DLBCL. Lastly, updated data presented at ICML from the Phase II IIT in marginal zone lymphoma, being led by the Sylvester Comprehensive Cancer Center at University of Miami, showed an overall response rate of 85% and a complete response rate of 69%, with safety consistent with the known profile of ZYNLONTA.

Moving beyond ZYNLONTA, we are on track to complete IND-enabling activities for our exotic and based prostate-specific membrane antigen, or PSMA-targeting ADC, by the end of the year. From a corporate perspective, as part of our strategic plan to focus resources on ZYNLONTA commercialization and expansion opportunities and on our preclinical PSMA-targeting ADC, we discontinued early development efforts for all other preclinical programs in solid tumors. As research and development efforts and related programs are closed out, we plan to shut down our UK facility, reducing our global workforce across functions by approximately 30%. These changes are expected to help position our company for long-term growth with significantly reduced operating expenses. At the same time, we completed a $100 million private placement. Taken together, our expected cash runway now extends into 2028. I'm excited about the multiple upcoming catalysts ahead within this extended cash runway.

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 while growing the commercial opportunity 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 differentiating. Within our current indication, our commercial strategy is focused on relapsed and refractory DLBCL patients who need a treatment with a fast, durable response and a manageable safety profile which can be administered in the outpatient setting. We believe LOTIS-5 has the potential to take ZYNLONTA to $200 to $300 million in peak sales as we expand into the second-line setting.

This is driven by doubling the patient population, extending the duration of therapy, and improving the clinical profile versus our current indication as a monotherapy. With LOTIS-7, we estimate we can expand the total opportunity for ZYNLONTA in DLBCL to $500 to $800 million in peak revenue with regulatory approval and Compendia listing. If the data persists, we believe ZYNLONTA plus glofitamab has the potential to transform the future lymphoma treatment paradigm by becoming the preferred bispecific combination in the Second Line Plus DLBCL setting. Additionally, in indolent lymphomas, there is a clear unmet need in both the relapsed or refractory marginal zone lymphoma and relapsed or refractory follicular lymphoma settings. We are encouraged by the initial data seen in the Phase II IITs, suggesting the ZYNLONTA regimen could provide significant benefit for these patients.

We believe the indolent lymphomas opportunity could provide additional peak revenue of $100 to $200 million with regulatory approval and Compendia listing, primarily driven by MZL. Taken together, we believe ZYNLONTA has the potential to reach peak revenues of $600 million to $1 billion in the U.S. Looking at the overall DLBCL treatment landscape, whether in the second or third-line setting, there are two main segments. The first are complex therapies which require unique infrastructure and expertise to handle logistical requirements and patient management. This includes therapies like CAR-T, transplant, and bispecifics. The second are more broadly accessible therapies, which all physicians can administer in the outpatient setting, including therapies like ADCs, monoclonal antibodies, and chemotherapy. Bispecifics have already been approved in the Third Line Plus setting as monotherapy, and we estimate there's currently a 60/40 split between the complex and broadly accessible segments, respectively.

In the second line, where bispecifics have not yet been approved but were recently added to NCCN guidelines for use in combination, the estimated split is closer to 25/75. We believe the emerging clinical profile of ZYNLONTA plus glofitamab in the LOTIS-7 trial positions us well among complex therapies, 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. While ZYNLONTA is currently approved as a single agent in Third Line Plus DLBCL, we believe ZYNLONTA has the potential to be the backbone therapy for combinations, raising the bar for efficacy in Second Line Plus DLBCL. ZYNLONTA is a systemic chemo-free option which can be combined with the highly effective bispecific glofitamab and the most widely used agent, rituximab.

We believe ZYNLONTA plus glofitamab in LOTIS-7 and ZYNLONTA plus rituximab in LOTIS-5 are complementary approaches to addressing unmet needs in the two key treatment segments. Now, I will turn the call over to our Chief Medical Officer, Mohamed Zaki, who will share more on our ongoing trials. Mohamed?

Speaker 3

Thank you, Ameet. Initial data from the safety lead-in portion of LOTIS-5, our Phase III confirmatory study of ZYNLONTA in combination with rituximab in patients with Second Line Plus diffuse large B-cell lymphoma (DLBCL), 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. Enrollment is now complete, and we expect to reach the pre-specified numbers of events by the end of 2025 and will provide data once available. A supplemental BLA submission to regulatory authorities is anticipated in the first half of 2026, with potential confirmatory approval in Second Line Plus DLBCL in the first half of 2027.

With LOTIS-7, we are exploring the combination of ZYNLONTA and ADCT-601 with glofitamab, an anti-CD20 Series III T-cell engaging bispecific antibody. These two highly potent single-agent drugs offer important and complementary mechanisms of action in DLBCL, which target two different B-cell 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 two agents. By dosing ZYNLONTA prior to glofitamab, it is our hypothesis that this dosing schedule has the potential to debulk the tumor and to lower CRS rates and grades. The design of the trial includes two parts. Part one, dose escalation, was conducted across non-Hodgkin lymphoma patients at three dose levels of ZYNLONTA with glofitamab or mosunetuzumab in the Third Line Plus.

Part two, dose expansion, was conducted in the Second Line Plus large B-cell lymphoma with ZYNLONTA at two dose levels, 120 micrograms per kg, and the currently approved monotherapy dose of 150 micrograms per kg combined with the approved monotherapy dose of glofitamab. Based on this initial dose optimization, we selected the 150 microgram per kg dose for expansion to 100 patients at this dose level. ZYNLONTA is being given prior to glofitamab to potentially debulk the tumor in the first cycle, and then both agents are given together in subsequent cycles. The primary endpoint is safety and tolerability, and the secondary endpoint of efficacy, PK, and immunogenicity. Baseline characteristics in this study, including being refractory to prior therapy as well as number and types of prior therapies, are representative of the second line DLBCL patient population and similar to other studies in this space.

Among the 41 patients evaluated for safety, there are certain characteristics that are important to highlight. The median age in this study is 71, with a range of 26 to 85 years of age. The study enrolled patients with large B-cell lymphoma, including de novo DLBCL, transforming follicular lymphoma, high-grade B-cell lymphoma, and grade 3B follicular lymphoma, all considered to be DLBCL. Median prior lines of therapy was two, with a range from one to five. The study includes a number of difficult-to-treat large B-cell lymphoma patients. Nearly 20% of patients presented at double or triple hit. 19.5% of patients received prior CAR-T, which is in line with other trials done with bispecific combinations.

Patients refractory to prior therapy were well represented in the study, with 51% of patients refractory to primary therapy and 49% refractory to last prior therapy, both of which were slightly higher in the 150 microgram per kg compared to 120 microgram per kg dose. Safety was analyzed in the 41 large B-cell lymphoma patients who received at least one dose of ZYNLONTA plus glofitamab. Most notably, as mentioned during the presentation of this data at S, when looking at grade CM4 treatment emergent adverse events occurring in more than 5% of patients, neutropenia was the most common at 24.4%, which is similar to the rate of neutropenia reported in the prescribing information of each drug separately. No additive effects were observed. Beyond that, the type of treatment emergent adverse events observed are consistent with the known safety profile of each drug separately.

The rate of serious treatment emergent adverse events was similar across both doses. Only three of the 20 patients experiencing serious treatment emergent adverse events discontinued treatment. As of the data cutoff, the combination has shown a manageable safety profile and no new safety signal was observed. A total of six patients discontinued due to adverse events, three of which were serious treatment emergent adverse events. For ZYNLONTA, we saw one case each of pericardial effusion, generalized edema, and pleural effusion. For glofitamab, we saw one case of ICM, polyneuropathy, and febrile neutropenia. This is consistent with the known profile of each drug separately. As of the data cutoff date, we can see that overall rates and grades of CRS are higher at the 120 microgram per kg dose compared to the 150 microgram per kg dose.

The 120 microgram per kg dose had 55% any grade CRS, primarily grade 1 to 2, with one case of grade 3. The 150 microgram per kg dose had 23.8% any grade CRS, all of which was grade 1. Grade 1 and 2 CRS were managed using standard of care therapies without ICU admittance or pressor support. The grade 3 CRS was managed with standard of care therapies and included ICU admittance. ICMs were seen in two patients treated at the 120 microgram per kg, and one ICM was observed at 150 microgram per kg dose. These ICMs were low grade and primarily managed with corticosteroids. All patients had a complete resolution of symptoms, with one patient electing to discontinue treatment and two patients resuming treatment and ultimately achieving a complete response.

Of the 41 treated patients at the time of the April data cutoff, 30 patients have reached the initial disease assessment and were efficacy evaluated. In this study, we have seen 93.3% overall response rate and an 86.7% complete response rate. Median duration of response was not reached at the time of data cutoff. The results observed across those levels were consistent in the terms of ORR, CR, and PR. Looking now at the swimmer's plot, the green bars show all patients in complete response, and the length of these bars shows the durability of each response. The gray bars represent who have not yet made it to the first disease assessment, so are not yet available for response. Most responses were observed at initial assessment, which occurred at day 42.

25 out of 26 patients who achieved a complete response have maintained that response as of the data cutoff, and 12 patients converted from stable disease or partial response to complete response over time. At the data cutoff, the longest response in the study is more than a year. Complete responses were observed regardless of prior therapy. Of the six patients previously treated with CAR-T and undergoing response assessment, five achieved a CR. The impressive efficacy and manageable safety profile seen with the combination of ZYNLONTA and glofitamab is encouraging. The data reinforces our belief in the potential for this regimen to change the treatment paradigm for patients with aggressive lymphoma. Now, I will turn the call over to Jose Carmona, our CFO, who will discuss financial results from the second quarter. Jose?

Speaker 1

Thank you, Mohamed. On the financial front, ZYNLONTA net product revenues in the second quarter of 2025 were $18.1 million as compared to $17 million in the same quarter of 2024. The first half net product revenue was $35.5 million compared to $34.9 million during the first half of 2024. In connection with the strategic reprioritization and restructuring plan announced in June 2025, the company incurred $13.1 million in restructuring and impairment costs in the second quarter of 2025, which consisted of $6.7 million in employee severance and related benefit costs and $6.4 million in non-cash impairment assets in connection with the close down of the UK facility. Total operating expenses for the quarter were $47.8 million on a non-GAAP basis, representing an 8% increase over the prior year, primarily driven by higher R&D costs, mostly related to LOTIS-5 and LOTIS-7, as well as PSMA IND-enabling activities.

The expenses on the ZYNLONTA LOTIS-5 trial, which is the largest investment we are making, are expected to decrease as we complete the trial going into 2026. On a GAAP basis, we reported a net loss of $56.6 million for the second quarter of 2025, or $0.50 per basic and diluted share, as compared to a net loss of $36.5 million or $0.38 per basic and diluted share for the same period in 2024. The increase in net loss for the quarter is primarily attributable to one-time restructuring and impairment costs and higher R&D expenses. You can find the reconciliation of GAAP to non-GAAP measures in the accompanying financial tables of the press release issued earlier today and in the appendix of this presentation. As of June 30, 2025, cash and cash equivalents were $264.6 million compared to $194.7 million at March 31, 2025.

This change was primarily driven by the net proceeds received in the company's private placement, partially offset by our use of cash in operating activities for the quarter. Across the LOTIS-5, LOTIS-7, and marginal zone lymphoma ZYNLONTA programs, we expect to have multiple data catalysts in the remainder of 2025 and 2026 with potential LOTIS-5 approval and compendia listing for all of this in the first half of 2027. For LOTIS-5, we expect to reach the pre-specified number of progression-free survival events by the end of this year, with top-line results and potential supplemental BLA submission in the first half of next year. With LOTIS-7, we intend to share fewer, more mature data toward the end of this year and expect to complete enrollment of 100 patients at the 150 microgram per kg dose in the first half of next year.

We plan to engage with regulatory authorities starting later this year. With sufficient data, we will pursue publication and a potential compendia strategy. With indolent lymphomas, we expect additional data to be shared at medical conferences this year and next by the lead investigators. Beyond ZYNLONTA, we are excited to see the advancement of our exatecan-based PSMA-targeting ADC with potential completion of IND-enabling activities toward the end of this year. Overall, we believe we have multiple value-driving catalysts within our cash runway, which is expected to extend into 2028. I will now turn the call back to Ameet.

Speaker 0

Thank you, Patrick. I am pleased with how we are executing against our strategy and continue to be encouraged by the consistently promising ZYNLONTA data we are generating across our ongoing trials. We believe our revenue growth opportunity comes with expanded use of ZYNLONTA through regulatory approvals as well as inclusion in guidelines, and we are confident in the multiple pathways we have to achieve our peak revenue goal. We can now open the line for questions. Operator?

Speaker 6

Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star followed by the one on your touchtone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press star followed by the two. If you are using a speakerphone, please lift the handset before pressing any keys. One moment, please, for your first question. Your first question comes from Michael Schmidt with Guggenheim. Your line is now open.

Speaker 4

Hi guys, good morning. Thanks for taking my questions. I had two bigger picture questions, I guess. One is on the Roche complete response letter recently on glofitamab in second line DLBCL. I'm just curious what your view is, how you think this may affect the overall DLBCL market in a second line setting, and then perhaps also, you know, any impact of that on your trial collaboration or potential next steps. The second question was really around LOTIS-5, and I know you've sort of reaffirmed timing of the PFS analysis by year end, and I'm just wondering if you had a sense of how mature overall survival is by the end of this year, and presumably there will be an interim OS analysis as well. Just wanted to confirm that. Thank you.

Speaker 0

Okay, thank you so much, Michael, and thanks for both of your questions. The first one was around StarGlo, the complete response letter that they received, and any impact that we see that could happen for us. The second question was around LOTIS-5 and what the status of overall survival or interim overall survival analysis would be when we get to top-line results. I'll turn it to Mohamed first to talk about the complete response letter with StarGlo, and maybe also highlight some differences between how we've conducted some of our trials like LOTIS-5 and the StarGlo study.

Speaker 3

Sure, thanks Ameet, and thanks for the question, of course. The complete response letter that was received by Roche from the FDA, we don't really know the details of that, so it's really hard to comment on that specific letter. However, we remain confident that there is an unmet medical need in the Second Line Plus diffuse large B-cell lymphoma landscape, and also we remain confident that the LOTIS-5 and LOTIS-7 is well positioned to address the unmet medical need in that sense, specifically for people who cannot or are not suitable for complex severe therapy. I want to highlight also what is in LOTIS-5, the design that makes us comfortable. First of all, it's a large study, 420 patients. In addition, also it's randomized one to one, and how are the 90% with the assumption that large animals will give about four months?

All the study is required to show two months difference, six months in the test arm to the study to be successful. Also, we're very comfortable with the data shared with the early safety run-in with a 50% complete response and 8% RRM at progression-free survival of 8.3 months in that disease setting. That's for our comfort regarding the differences. Also, I think we shared before that our enrollment in Asia was significantly lower than what the StarGlo study was. In terms of interim, of course, at the final analysis of progression-free survival, there are always FDA usually asked and looks for how much data on overall survival is available, and we will get there. We'll be able to talk more about that when we reach the final progression-free survival.

Speaker 0

I just may follow up. Is your expectation that OS at that point in time is mature enough to potentially show a difference, or is it just too early in terms of the event rates by the end of this year?

Speaker 3

It's hard to speculate on that for now. To be honest with you, it's hard to tell.

Speaker 0

Yeah, and then basically, Michael, just so you understand the timing, what we said is we believe we'll hit the pre-specified number of PFS events by the end of this year. Obviously, we need to clean the data off the database. Once that happens, we would share sort of top-line, meaning if the data is positive or negative, but the full results of the trial would obviously get published and go to a medical congress, and that's when the full data will come out. In parallel, obviously, we'll be engaging as a parent with the supplemental BLA submission with the FDA. Thank you.

Speaker 6

Your next question comes from Kelly Shi with Jefferies. Your line is now open.

Speaker 2

Hi, good morning. This is Jenna on the line for Kelly. Thanks for taking our questions. Could you please give us some updated thoughts on durability with these, you know, impressive high CRs seen from LOTIS-5 and LOTIS-7? How much incremental durability benefit would you expect, maybe versus glofitamab alone for LOTIS-7, and, you know, for these two trials? How may that compare with other rituximab or glofitamab combos? For the LOTIS-7 update coming in the second half, what kind of early read into durability may we expect there? Thank you so much.

Speaker 0

Yeah, thanks for the question. You're asking, I think, about not only the high CR rates that we've seen with LOTIS-7, but you're asking about the durability and what gives us confidence in the durability and what measures of durability we will start to see over time to demonstrate that durability of the CRs. I'll turn it to Mohamed to talk about, one, why we believe we will see good durability, but also what metrics we'll be able to show over time to demonstrate that durability of the CRs.

Speaker 3

It's important to highlight that the high number or maybe unprecedented number of CRs observed within LOTIS-7 so far is very encouraging and very important also to highlight that we all know that the CRs are a good surrogate biomarker for durability. Both drugs, each one separately, are showing significant durability in Third Line Plus with the median duration of response in the CR patients not reached for glofitamab for three years and for LOTIS for two years. We're also looking forward to continuing looking at the data and will be sharing more updated data by the end of this year. It is also encouraging to share that based on the durability we're looking at so far, it's important to highlight that the median CR rate that has been seen by other combinations of bispecifics is ranging between 47% and 62%. We know that our numbers are higher than that.

The initial response of 12 months for those studies ranged in between 63% to 75%. It's important to highlight that our focus in our benchmarking on the durability at 6 and 12 months and more, of course, as we get more data. We keep monitoring this data, but it's very encouraging right now. As I mentioned before, 25 out of 26 CRs remain in CRs at the time of data cutoff, with the longest of them reaching more than a year.

Speaker 0

Yeah, in the future data updates, you're going to see, obviously, updated swimmer's plot. That's obviously a great indication of durability when you see individual patients, so how durable those CRs are. Like other studies, we'll be able to talk about the median duration of the CRs at 6 and 12 months as the data matures, and we have sufficient data to share on that. You'll see more durability data as we kind of give future updates.

Speaker 6

Thank you, super helpful. Your next question comes from Eric Schmidt with Cantor. Your line is now open.

Speaker 4

Thanks for my question. Congrats on the progress in Q2. Maybe just a quick one with regard to LOTIS-7 and your discussions with the FDA. What is it that you're hoping to get asked and answered, and how might you communicate that result, and maybe also how might you communicate the LOTIS-7 data later this year? Would that be at a conference or company-sponsored event? Thank you.

Speaker 0

Yeah, so maybe I'll start, and then I'm going to pass it to Mohamed. First of all, with LOTIS-7, as you're aware, and we've communicated, we currently have expanded the trial to enroll 100 patients at the 150 microgram per kg dose of ZYNLONTA, plus the full dose of glofitamab. That's well underway. We've seen the enrollment do quite well. It's accelerated. That path towards being able to get published and get into compendia is a strategy that's kind of ongoing. In parallel, obviously, as the data matures, we want to engage with the FDA on potential path forwards, what that could be, whether it be in Second Line or Front Line. I think we can explore different options with the FDA. That's one of the things we want to test.

Maybe Mohamed, you could talk more about what we want to do with the FDA in those discussions about potential regulatory approaches.

Speaker 3

Yeah, definitely, when you have some data with sufficient follow-up, the discussion of the age of sequence range between how to bring such an effective regimen to patients quickly and also what is the future development plan, more than just having it quicker on the bigger picture, on bigger studies for Second or Front Line, as Ameet mentioned. Of course, there's a discussion about what doses, other things like that could come into the conversation. Essentially, the timing to do that will depend on how the data and the amount of follow-up that we have and to really have a fruitful discussion with the agency.

Speaker 0

Yeah, in terms of the data update we share later this year, we haven't disclosed if it'll be a company update or medical congress. Obviously, we want to share as much data as we can. As you know, that's one of the considerations, the data cutoffs sometimes for medical congresses are much, much earlier. That's one of the things we're considering in that choice of how we can make sure that we could show a robust update that goes beyond what we shared in June. Got it. Thank you.

Speaker 6

Your next question comes from Leonid Timashev with RBC Capital Markets. Your line is now open.

Speaker 0

Yeah, thanks for taking my question. I just want to ask on some of the indolent lymphomas. I guess, given the encouraging marginal zone lymphoma data you've seen, can you just remind us how you see ZYNLONTA fitting into these more indolent indications, given that there's, you know, it's not like different benefit risk calculus there? What you're thinking the bar is for NCCN inclusion in these indolent lymphomas, both in terms of what you'd want to show in efficacy and also the number of patients. Maybe just a quick follow-up on that, I guess. Would you also consider looking at bispecific combos in these? Thanks.

Speaker 4

Yeah, I agree. We are very encouraged by the indolent lymphoma data we've generated both in the relapsed refractory setting of marginal zone lymphoma and follicular. Specific to your question around marginal zone lymphoma, there's a study that's ongoing. The Phase II IAT is expected to enroll 50 patients. We think that number is clearly sufficient because when you look at the numbers, actually the last compound that was added to NCCN guidelines was pirtobrutinib, which is a BTK inhibitor based on 36 patients. The most any trial has ever enrolled, which is a clinical trial, was about 62 patients. We think 50 is about the right number. We're well on our way to enrolling that number of patients. In terms of what you need to show, right now when you look at the CR rates in that relapsed refractory setting, the highest CR rate is about 29%.

We're well above that, obviously, with the data we're sharing right now. Clearly, I think 40% or above would be a significant improvement over any of the standard of care. In terms of risk-benefit, which is one of the other things you mentioned, we're really pleased about the safety profile right now that we're seeing with ZYNLONTA. At this point, we don't see the need to combine with a bispecific because we're seeing such high efficacy with the single agent. Particularly in the indolent lymphomas, thinking about the safety profile for knowing that patients can be treated and can be on treatments and in a disease setting for multiple years, oftentimes, the tolerability profile is obviously much more important than even the more aggressive lymphomas like diffuse large B-cell lymphoma.

We feel quite comfortable with our approach as a single agent ZYNLONTA in marginal zone lymphoma, and that's the approach we'll take going forward.

Speaker 6

Ladies and gentlemen, as a reminder, should you have a question, please press star one. Your next question comes from Sudan Loganathan with Stephens. Your line is now open.

Speaker 0

Hi, Ameet, Mohamed, and Patrick. Congrats on the strong progress in the quarter, and thank you for taking my questions. First, can you walk us through your Salesforce growth plan and timeline as you expect to unlock a much larger TAM with the strong response data outcomes of the LOTIS trial? How will marketing responsibilities of the combination with glofitamab be split, if any at all, with Roche? When do you anticipate the earliest opportunity the MSLs will have to start talking about the LOTIS trial data to prescribing physicians? Lastly, real quick, post the complete response letter of ZYNLONTA, do you anticipate LOTIS-5 confirmatory Phase III study, if granted full approval for the glofitamab plus polatuzumab-R-CHP combo, can we quickly change the landscape for treatment of second line DLBCL, akin to how glofitamab plus GemOx was expected to, or be more of the same?

Okay, you asked a few different questions. One was around the commercial and medical affairs approach that we're going to use. Two, you said is there going to be any collaboration with Roche on that? Three, you asked a little bit about LOTIS-5, and the LOTIS-5 would be the confirmatory study. Let's answer each of those questions. From a field force and medical affairs standpoint, we think we have the right footprint. We're already, if you look at our commercial footprint, we're covering 90% of the potential of DLBCL, so we think we're well covered in that setting. Similarly, if you look at our MSL force, it's very competitive where we're able to cover all the academic centers and all the large community centers. We think our footprint is where it needs to be.

Obviously, we would add some resources on the marketing and medical side as you would pre-launch and in the early launch phases as we kind of expand the potential use of ZYNLONTA. With regards to any collaboration, as you know, we'll be launching, we believe, with a successful approval of LOTIS-5, we would be then promoting that and be successfully launching that. LOTIS-7 is a bit different because what we expect the first step to be is in compendia, and as you know, we won't promote anything off-label, and our commercial teams won't be actively discussing LOTIS-7. MSLs obviously will be there to respond to questions that physicians have around the LOTIS-7 data, and at this point, there's no planned collaboration commercially or medically with Roche on that. With regards to the frontline study with glofitamab polatuzumab-R-CHP, it's hard to know.

We don't want to speculate beyond what Roche has said, obviously. I think their intention is that that could be their confirmatory study, but we're waiting like you are to see if that gets confirmed by the FDA.

Speaker 6

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

Speaker 0

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.

Speaker 6

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