Half Year 2025 ADC Therapeutics SA Earnings Call
Speaker #3: Good morning, ladies and gentlemen. And welcome to the ADC Therapeutics FA/ADC TQ2 2025 earnings conference call. At this time, all lines are in a listen-only mode.
Operator: Good morning, ladies and gentlemen, and welcome to the ADC Therapeutics SA 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 12th, 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 #3: 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.
Speaker #3: 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.
Speaker #3: Nicole, please go ahead.
Speaker #4: 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 Investors section of the ADC Therapeutics website.
Nicole Riley: 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 am 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.
Speaker #4: 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, will discuss our clinical programs and updates.
Speaker #4: Followed by our Chief Financial Officer, Pepe Carmona, who will review our second quarter 2025 financial results. We will then open the call to questions.
Speaker #4: 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.
Speaker #4: 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.
Nicole Riley: 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.
Speaker #4: 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 accepted as required by law.
Speaker #4: 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.
Speaker #4: You should refer to the company's second quarter earnings release for information and reconciliation of historical non-GAAP measures, for the comparable GAAP financial measures. I will now turn the call over to our CEO, Ameet Mallik.
Nicole Riley: 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 #4: Ameet?
Speaker #5: 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.
Ameet Mallik: 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.
Speaker #5: 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 PLBCL patients.
Speaker #5: Net product revenues were $18.1 million and $35.5 million in the second quarter and first half, respectively. Both figures were slightly higher compared to the same periods in the prior year.
Speaker #5: During the second quarter, we were pleased to have Lotus7 data presented at EHA, the European Hematology Association Congress, and at ICML, the International Conference on Malignant Lymphoma.
Speaker #5: We are encouraged by the promising data which we believe demonstrates the potential for Zilanta plus Clofidomab to be a best-in-class combination in a highly competitive market.
Ameet Mallik: 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%.
Speaker #5: Data as of the April 2025 cutoff date shows Zilanta in combination with Clofidomab 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.
Speaker #5: 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%.
Speaker #5: We are currently expanding enrollment to 100 patients at the selected 150 micrograms per kilogram dose, which will support regulatory discussions and is in line with recent examples of bispecific combination therapies added to Compendia.
Ameet Mallik: We are currently expanding enrollment to 100 patients at the selected 150 microgram per kilogram 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 3 confirmatory trial evaluating ZYNLONTA in combination with rituximab in patients with second-line plus DLBCL.
Speaker #5: We expect to share an additional update on Lotus7 in the second half of 2025. Once sufficient data with longer follow-up is available, we plan to discuss the path forward for Zilanta and Clofidomab with regulatory authorities and to pursue a Compendia strategy.
Speaker #5: Lotus5 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 3 confirmatory trial evaluating Zilanta in combination with Rituximab in patients with second-line plus PLBCL.
Speaker #5: Lastly, updated data presented at ICML from the phase two IIT in marginal zone lymphoma, being led by the Sylvester Comprehensive Cancer Center at the 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 Zilanta.
Ameet Mallik: Lastly, updated data presented at ICML from the phase 2 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 PSMA-targeting ADC program 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 program, 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%.
Speaker #5: Moving beyond Zilanta, we are on track to complete I&D enabling activities for our exothecan-based prostate-specific membrane antigen, or PSMA, targeting ADC by the end of the year.
Speaker #5: From a corporate perspective, as part of our strategic plan to focus resources on Zilanta, commercialization, and expansion opportunities, and on our preclinical PSMA-targeting ADC, we discontinued early development efforts for all other preclinical programs in solid tumors.
Speaker #5: 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%.
Speaker #5: 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.
Ameet Mallik: 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 am excited about the multiple upcoming catalysts ahead within this extended cash runway. 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 while growing the commercial opportunity by expanding use into earlier lines of therapy in DLBCL and into indolent lymphomas. The data we have seen across these settings so far has been consistently encouraging with the potential to be highly differentiating.
Speaker #5: 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 and third-line plus PLBCL, Zilanta has a profile of rapid, deep, and durable efficacy, as well as manageable safety with simple and convenient administration.
Speaker #5: 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 PLBCL and into indolent lymphomas.
Speaker #5: 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 PLBCL patients who need a treatment with a fast, durable response and a manageable safety profile which can be administered in the outpatient setting.
Ameet Mallik: 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 million to $300 million in peak sales as we expand into the second-line setting. This is driven by doubling the patient population, extending the duration of therapy, and improving the clinical profile versus our current indication as a monotherapy. With LOTIS-7, we estimate we can expand the total opportunity for ZYNLONTA in DLBCL to $500 million to $800 million in peak revenue with regulatory approval and Compendia listing. If the data persists, we believe ZYNLONTA plus glofitamab has the potential to transform the future lymphoma treatment paradigm by becoming the preferred bispecific combination in the second-line plus DLBCL setting.
Speaker #5: We believe Lotus5 has the potential to take Zilanta, the 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.
Speaker #5: The Lotus7 we estimate we can expand the total opportunity for Zilanta and PLBCL to 500 to 800 million in peak revenue with regulatory approval and Compendia listing.
Speaker #5: If the data persists, we believe Zilanta plus Clofidomab has the potential to transform the future lymphoma treatment paradigm by becoming the preferred bispecific combination in the second-line plus PLBCL setting.
Speaker #5: 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.
Ameet Mallik: 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 2 IITs, suggesting a ZYNLONTA regimen could provide significant benefit for these patients. We believe the indolent lymphomas opportunity could provide additional peak revenue of $100 million to $200 million with regulatory approval and Compendia listing, primarily driven by 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.
Speaker #5: We are encouraged by the initial data seen in the Phase Two IITs, suggesting a Zilanta regimen could provide significant benefit for these patients. We believe the indolent lymphomas opportunity could provide additional peak revenue of $100 million to $200 million.
Speaker #5: With regulatory approval and Compendia listing, primarily driven by MZL. Taken together, we believe Zilanta has the potential to reach peak revenues of 600 million to 1 billion dollars in the U.S.
Speaker #5: Looking at the overall PLBCL 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.
Speaker #5: 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.
Ameet Mallik: 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 is 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 guideline 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.
Speaker #5: Bispecifics have already been approved in the third-line plus setting if monotherapy and we estimate there is currently a 60/40 split between the complex and broadly accessible segments, respectively.
Speaker #5: 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.
Speaker #5: We believe the emerging clinical profile of Zilanta plus Clofidomab in the Lotus7 trial positions us well among complex therapies and at the same time the clinical profile of Zilanta plus Rituximab in the Lotus5 trial has the potential to differentiate us among broadly accessible therapies.
Speaker #5: While Zilanta is currently approved as a single agent in third-line plus PLBCL, we believe Zilanta has the potential to be the backbone therapy for combinations raising the bar for efficacy in second-line plus PLBCL.
Ameet Mallik: While ZYNLONTA is currently approved as a single agent and 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 a 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 #5: Zilanta is a systemic chemo free option which can be combined with the highly effective bispecific Clofidomab and the most widely used agent, Rituximab. We believe Zilanta plus Clofidomab in Lotus7 and Zilanta plus Rituximab in Lotus5 are complementary approaches to addressing unmet needs in the two key treatment segments.
Speaker #5: Now, I will turn the call over to our Chief Medical Officer, Mohamed Zaki, who will share more on our ongoing trials. Mohamed?
Speaker #6: Thank you, Ameet. Initial data from the safety leading portion of Lotus5, our phase three confirmatory study of Zilanta, in combination with Rituximab in patients with second-line plus PLBCL, showed an overall response rate of 80% and a complete response rate of 50% with no new safety signals.
Mohamed Zaki: Thank you, Ameet. Initial data from the CST lead-in portion of LOTIS-5, our phase 3 confirmatory study of ZYNLONTA in combination with rituximab in patients with second-line plus 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 and ADCT-602 CD3 T-cell engaging bispecific antibody.
Speaker #6: The administrating 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 number of events by the end of 2025 and will provide data once available.
Speaker #6: A supplemental BLA submission to regulatory authorities is anticipated in the first half of 2026 with potential confirmatory approval in second-line plus PLBCL in the first half of 2027.
Speaker #6: With Lotus7, we are exploring the combination of Zilanta and ANCI C19 ADC with Clofidomab and ANCI CD20 CD3 T cell engaging bispecific antibody, this too highly potent single agent drugs offer important and complementary mechanism of action in PLBCL.
Mohamed Zaki: These two highly potent single-agent drugs offer important and complementary mechanisms of action in DLBCL, which target two different B-cell separate 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 in the third-line plus.
Speaker #6: We target two different B cell surface antigens while delivering a potent payload and activating T cells. Given this, we expect to see additive or synergistic efficacy.
Speaker #6: In addition, there are no known overlapping non-hematologic toxicities between the two agents. By dosing Zilanta prior to Clofidomab, it is our hypothesis that this dosing schedule has the potential to debulk the tumor and to lower CRS rates and grades.
Speaker #6: The design of the trial includes two parts. Part one, dose escalation was conducted across non-Hodgkin lymphoma patients at three dose levels of Zilanta, with Clofidomab or most antizumab in the third-line plus.
Speaker #6: Part two, dose expansion was conducted in the second-line plus large B cell lymphoma with Zilanta at two dose levels 120 micrograms per keg, and the currently approved monotherapy dose of 150 micrograms per keg combined with the approved monotherapy dose of Clofidomab.
Mohamed Zaki: 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.
Speaker #6: Based on this initial dose optimization, we selected the 150 micrograms per keg dose for expansion to 100 patients at this dose level. Zilanta is being given prior to Clofidomab to potentially debulk the tumor in the first cycle and then both agents are given together in subsequent cycles.
Speaker #6: The primary endpoint is safety and tolerability, and second 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 representatives of the second-line PLBCL patient population and similar to other studies in this space.
Speaker #6: Among the 41 patients evaluable for safety, there are 13 characteristics that are important to highlight. The median age in this study is 71 with a range of 26 to 85 years of age.
Mohamed Zaki: 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 biospecific combinations.
Speaker #6: The study enrolled patients with large B cell lymphoma, including durable PLBCL, transforming follicular lymphoma, high-grade B cell lymphoma, and grade 3B follicular lymphoma all considered to be PLBCL.
Speaker #6: Median prior lines of therapy was 2 with a range from 1 to 5. The study includes a number of difficult-to-treat large B cell lymphoma patients.
Speaker #6: Nearly 20% of patients presented as double or triple hits, 19.5% of patients received prior CAR-T, which is in line with other trials done with bispecific combinations.
Speaker #6: 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.
Mohamed Zaki: 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 micrograms per kg compared to 120 micrograms 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, when looking at grade CM4 treatment emergent adverse event 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.
Speaker #6: Both of which were slightly higher in the 150 micrograms per keg compared to 120 micrograms per keg dose. Safety was analyzed in the 41 large B cell lymphoma patients who received at least one dose of Zilanta plus Clofidomab.
Speaker #6: Most notably, as mentioned during the presentation of this data at ASH, when looking at grade 3 and 4 treatment-emergent adverse events occurring in more than 5% of patients, neutropenia was the most common at 24.4%. This percentage is similar to the rate of neutropenia reported in the prescribing information of each drug separately.
Speaker #6: So, 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.
Speaker #6: 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.
Mohamed Zaki: The rate of serious treatment emergent adverse events was similar across both doses. Only 3 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 ICANN 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.
Speaker #6: 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.
Speaker #6: For Zilanta, we saw one case each of pericardial effusion, generalized edema, and pleural effusion. And for Clofidomab, we saw one case of ICAMs, polyneuropathy, and febrile neutropenia.
Speaker #6: 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 micrograms per kg dose compared to the 150 micrograms per kg dose.
Speaker #6: The 120 microgram per kg dose had 55% any grade CRS, primarily grades 1 and 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.
Mohamed Zaki: 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. ICANNs were seen in two patients treated at the 120 microgram per kg, and one ICANN was observed at 150 microgram per kg dose. These ICANNs 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.
Speaker #6: Grade 1 and 2 CRS were managed using standard of care therapies without ICU admittance or pressure support. The grade 3 CRS was managed with standard of care therapies and included ICU admittance.
Speaker #6: ICAMs were seen in two patients treated at the 120 micrograms per kg dose and one ICAM was observed at the 150 micrograms per kg dose. These ICAMs were low grade and primarily measured for TB steroids.
Speaker #6: 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.
Speaker #6: Of the 41 treated patients at the time of the April data cutoff, 30 patients had reached the initial disease assessment and were efficacy evaluable.
Mohamed Zaki: Of the 41 treated patients at the time of the April data cutoff, 30 patients had reached the initial disease assessment and were efficacy-evaluable. 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 show 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.
Speaker #6: In the study, we have seen 93.3 overall response rates and an 86.7% complete response rate. Median duration of response was not reached at the time of data cutoff.
Speaker #6: The results observed across dose levels were consistent in 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.
Speaker #6: 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 20 six patients who achieved a complete response have maintained that response as of the data cutoff.
Mohamed Zaki: 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 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. Pepe?
Speaker #6: 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.
Speaker #6: 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 Zilanta and Clofidomab is encouraging.
Speaker #6: 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 Pipi Carmona, our CFO, who will discuss financial results from the second quarter.
Speaker #6: Pepe?
Speaker #7: Thank you, Mohamed. On the financial front, Zilanta net product revenues in the second quarter of 2025 were 18.1 million, as compared to 17 million in the same quarter of 2024.
Jose Carmona: 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 liberalization and restructuring plan announced in June 2025, ADC Therapeutics SA 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.
Speaker #7: Total 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 revalorization 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.
Speaker #7: Total operating expenses for the quarter were 47.8 million and a non-GAAP basis representing an 8% increase over prior year primarily driven by higher R&D costs.
Jose Carmona: 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-targeting ADC program 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.
Speaker #7: Mostly related to Lotus5 and Lotus7, as well as PSMA, I&D enabling activities. The expenses on the Zilanta Lotus5 trial which is the largest investment we are making is expected to decrease as we complete the trial going into 2026.
Speaker #7: On a GAAP basis, we reported a net loss of 56.6 million for the second quarter of 2025, or 50 cents per basic and diluted share.
Speaker #7: 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, as well as higher R&D expenses.
Speaker #7: You can find the reconciliation of GAAP to non-GAAP measures in the comparing financial tables of the press release issued earlier today and in the appendix of this presentation.
Jose Carmona: You can find the reconciliation of GAAP to non-GAAP measures in the compelling 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 ADC Therapeutics SA's private placement, partially offset by our use of cash in operating activities for the quarter. Across the LOTIS-5, LOTIS-7, and MZL 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 PFS events by the end of this year, with top-line results and potential supplemental BLA submission in the first half of next year.
Speaker #7: As of June 30, 2025, cash and cash equivalents were 264.6 million compared to 194.7 million at March 31st, 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.
Speaker #7: Across the Lotus5, Lotus7, and MZL Zilanta programs we expect to have multiple data catalysts in the remainder of 2025 and 2026 with potential Lotus5 approval.
Speaker #7: And Compendia listing for all of these in the first half of 2027. For Lotus5, we expect to reach the pre-specified number of PFS events by the end of this year with top-line results and potential supplemental BLA submission in the first half of next year.
Speaker #7: With Lotus7, we intend to share fuller more mature data toward the end of this year and expect to complete enrollment of 100 patients at the 150 micrograms per kilogram dose in the first half of next year.
Jose Carmona: 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 kilogram 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 exotic and based PSMA-targeting ADC program, 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 Mallik.
Speaker #7: 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.
Speaker #7: Beyond Zilanta, we are excited to see the advancement of our exothecan-based PSMA targeting ADC with potential completion of I&D enabling activities toward the end of this year.
Speaker #7: Overall, we believe we have multiple value-added catalysts within our cash runway which is expected to extend into 2028. I will now turn the call back to Ameet.
Speaker #5: Thank you, Pepe. I am pleased with how we are executing against our strategy and continue to be encouraged by the consistently promising Zilanta data we are generating across our ongoing trials.
Ameet Mallik: Thank you, Pepe. 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 #5: We believe our revenue growth opportunity comes with expanded use of Zilanta through regulatory approvals, as well as inclusion in guidelines. We are confident in the multiple pathways we have to achieve our peak revenue goal.
Speaker #5: We can now open the line for questions. Operator?
Speaker #8: 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 touchstone phone.
Operator: Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star followed by the one on your 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 speaker phone, 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 #8: You will hear a prompt at your hand has been raised. Should you wish to decline from the polling process, please press star followed by the two.
Speaker #8: If you are using a speakerphone, please let the handset before pressing any keys. One moment, please, for your first question. Your first question comes from Michael Schmidt with Guggenheim.
Speaker #8: Your line is now open.
Speaker #9: 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 Glofidomab in second-line PLBCL.
Michael Schmidt: 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 am 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, any impact of that on your trial collaboration or potential next steps. The second question was really around LOTIS-5, and I know you have reaffirmed timing of the PFS analysis by year end. I am 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. I just wanted to confirm that. Thank you.
Speaker #9: I'm just curious what your view is, how you think this may affect the overall PLBCL market in a second-line setting, and then perhaps also, you know, any impact of that on your trial collaboration or potential next steps.
Speaker #9: And then the second question was really around Lotus5 and I know you've sort of reaffirmed timing of the PFS analysis by your 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.
Speaker #9: Just wanted to confirm that. Thank you. Okay. Thank you so much, Michael. And thanks for both of your questions. So the first one was around star glow, the CRL that they received.
Ameet Mallik: Okay. Thank you so much, Michael, and thanks for both of your questions. The first one was around glofitamab, 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 will turn it to Mohamed Zaki first to talk about the complete response letter with glofitamab and maybe also highlight some differences between how we have conducted some of our trials like LOTIS-5 and the glofitamab study.
Speaker #9: And any impact that we see, you know, that could happen for us. And the second question was around Lotus5 and what the status of OS or interim OS analysis would be when we have, when we get to top-line results.
Speaker #9: So I'll turn it to Mohamed first to talk about the CRL with star glow. And maybe also highlight some differences between how we've conducted some of our trials like Lotus5 and the star glow study.
Speaker #5: Sure. Thanks, Ameet. And thanks for the question, of course. The CRL that was received by Roche from the FDA we don't really know the details of that.
Mohamed Zaki: Sure. Thanks, Ameet, and thanks for the question, of course. The complete response letter that was received by Roche from the FDA, we do not really know the details of that, so it is really hard to comment on that specific letter. However, we remain confident that there is an unmet medical need in the second-line plus DLBCL landscape. Also, we remain confident that the LOTIS-5 and LOTIS-7 are 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 is a large study, 420 patients. In addition, also, it is randomized one to one. And how are the 90% with the assumption that large amounts will give about four months?
Speaker #5: 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 PLBCL landscape.
Speaker #5: And also we remain confident that the Lotus5 and Lotus7 is well positioned to address the unmet medical need in that sense. Specifically for people who cannot or not suitable for complex severe therapy.
Speaker #5: I want to highlight what is in Lotus5, the design that makes us comfortable. First of all, it's a large study for 120 patients.
Speaker #5: In addition also, it's randomized one to one. And how are the 90% with the if the assumption that large amounts will give about four months, all the studies required to show two months difference, six months in the test arm to the study to be successful.
Mohamed Zaki: All the studies required to show two months difference, six months in the test arm for the study to be successful. Also, we are very comfortable with the data shared with the early safety running with the 50% complete response and 8% overall response rate and a PFS of 8.3 months in that disease setting. That is 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 PFS, there are always FDA usually asks and looks for how much data on OS is available. We will get there. We will be able to talk more about that when we reach the final PFS.
Speaker #5: Also, we're very comfortable with the data shared, with the early safety running with the 50% complete response and 8% to our PFS of 8.3 months in that disease setting.
Speaker #5: 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 Star Glow study was.
Speaker #5: The in terms of interim, of course, at the final analysis, of PFS, there always FDA usually asks and looks for how much data on OS is available.
Speaker #5: And we will get there. We will be able to talk more about that when we reach the final PFS analysis.
Speaker #3: It 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 a too early in terms of the event rates, you know, by the end of this year?
Ameet Mallik: If there's any 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 #9: It's really hard to speculate on that for now. So to be honest with you, it's hard to tell. Yeah. And then basically, Michael, just so you understand the timing, I mean, what we said is we believe we'll hit the pre-specified number of PFS events by the end of this year.
Mohamed Zaki: It is really hard to speculate on that for now. To be honest with you, it is hard to tell.
Ameet Mallik: Yeah. Then, basically, Michael, just so you understand the timing, what we said is we believe we will hit the pre-specified number of PFS events by the end of this year. Obviously, then you have to clean the data off the database. Once that happens, we would share 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. That is when the full data will come out. In parallel, obviously, we will be engaging and preparing for the supplemental BLA submission with the FDA.
Speaker #9: Obviously, then you have to clean the data and lock the database. Once that happens, we would share sort of top-line, meaning is the data positive or negative.
Speaker #9: 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.
Speaker #9: In parallel, obviously, we'll be engaging and preparing for the SBLA submission with the FDA.
Speaker #3: Thank you.
Operator: Thank you. Your next question comes from Kelly Shi with Jefferies. Your line is now open.
Speaker #8: Your next question comes from Kelly Xu with Jeffries. Your line is now open.
Speaker #10: 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?
Jenna: Hi, good morning. This is Jenna on the line for Kelly Shi. 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 #10: With these, you know, impressive high CRs seen from Lotus5 and Lotus7, how much incremental durability benefit would you expect maybe versus Clofidomab alone? For Lotus7 and, you know, for these two trials, how may that compare with other Rituximab or Clofidomab combos?
Speaker #10: And then for the Lotus7 update coming in the second half, what kind of early read into durability may we expect there? Thank you so much.
Speaker #9: Yeah. Thanks for the question. So you're asking, I think, about not only the high CR rates that we've seen with Lotus7, but you're asking about the durability and what gives us confidence in the durability and what measures of durability will we start to see over time to get to demonstrate that durability of the CRs.
Ameet Mallik: Yeah. Thanks for the question. You are asking, I think, about not only the high CR rates that we have seen with LOTIS-7, but you are asking about the durability and what gives us confidence in the durability and what measures of durability will we start to see over time to demonstrate that durability of the CRs. I will turn it to Mohamed Zaki to talk about, one, why we believe we will see good durability, but also what metrics we will be able to show over time to demonstrate that durability with CRs.
Speaker #9: So 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 #9: It's important to highlight that the high number or maybe unprecedented number of CRs observed within Lotus7 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.
Mohamed Zaki: It is important to highlight that the high number, or maybe unprecedented number, of CRs observed in LOTIS-7 so far is very encouraging. It is 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 ZYNLONTA for two years. So we are also looking forward to continuing looking at the data and would be sharing more updated data by the end of this year. It is also encouraging to share that based on the durability we are looking at so far, it is important to highlight that the median CR rate that has been seen by other combinations or by bispecifics is ranging between 47% and 62%.
Speaker #9: 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 Glofidomab for three years and for Lonca for two years.
Speaker #9: So we're also looking forward to continuing looking at the data, and we'll 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, the important to highlight that the median CR rate that have been seen by other combination of bispecifics is ranging between 47 and 62%.
Speaker #9: I surely know that our numbers are higher than that. And the initial response of 12 months for those studies ranging between 63 to 75%.
Mohamed Zaki: We know that our numbers are higher than that. The initial response of 12 months for those studies is ranging between 63% to 75%. Also, it is important to highlight that our focus in our benchmarking is on the durability at 6 and 12 months and more, of course, as we get more data. So we keep monitoring this data, but it is very encouraging right now. As I mentioned before, 25 out of 26 CRs remain in CRs at the time data cutoff, with the longest of them reaching more than a year.
Speaker #9: Also, it's important to highlight that where our focus in our benchmarking on the durability at six and 12 months and more, of course, as we get more data.
Speaker #9: So 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 #9: Yeah. So in the future data updates, you're going to see obviously updated swimmers plot. That's obviously a great indication of durability when you see individual patients show how durable those CRs are.
Ameet Mallik: Yeah. So in the future data updates, you are going to see, obviously, updated swimmer's plot. That is, obviously, a great indication of durability when you see individual patients, so how durable those CRs are. But like other studies, we will 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. So you will see more durability data as we kind of give future updates.
Speaker #9: But like other studies, we'll be able to talk about the median duration of the CRs at six and 12 months as the data matures.
Speaker #9: And we have sufficient data to share on that. So you'll see more durability data as we kind of get future updates.
Speaker #8: Thank you. Super helpful. Your next question comes from Eric Schmidt with Cantor. Your line is now open.
Jenna: Thank you. Super helpful.
Operator: Your next question comes from Eric Schmidt with Cantor. Your line is now open.
Speaker #9: Thanks for my question. Congrats on the progress in Q2. Maybe just a quick one with regard to Lotus7 and your discussions with the FDA.
Michael Schmidt: 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 are hoping to get asked and answered, and how might you communicate that result? 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 #9: 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 Lotus7 data later this year?
Speaker #9: Would that be at a conference or company-sponsored event? Thank you. Yeah. So maybe I'll start, and then I'm going to pass it to Mohamed.
Ameet Mallik: So maybe I will start, and then I am going to pass it to Mohamed. First of all, with LOTIS-7, as you are aware, and we have communicated, we currently have expanded the trial to enroll 100 patients at the 150 microgram per kilogram dose of ZYNLONTA plus the full dose of glofitamab. That is well underway. It is actually, we have seen the enrollment do quite well. It has accelerated. That path towards being able to get published and get into Compendia is a strategy that is 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 is one of the things we want to test.
Speaker #9: So, first of all, with Lotus 7, as you're aware and we've communicated, we currently have expanded the trial to enroll 100 patients at the 150 microgram per kilogram dose of Zilanta.
Speaker #9: Plus the full dose of Glofidomab. That's well underway. Actually, we've seen the enrollment do quite well; it's accelerated. So that path towards being able to get published and get into Compendia is a strategy that's kind of ongoing.
Speaker #9: In parallel, obviously, as the data matures, we want to engage with the FDA on potential paths forward. What that could be, whether it be second-line or front-line, I think we can explore different options with the FDA.
Speaker #9: So that's one of the things we want to test. And maybe Mohamed, you could talk more about what we want to do with the FDA in those discussions about potential regulatory approaches.
Ameet Mallik: Maybe, Mohamed, you could talk more about what we want to do with the FDA in those discussions about potential regulatory approaches.
Speaker #5: Yeah. Typically, when you have some data with sufficient follow-up, the discussion of the agency could range between how to bring such an effective regimen to patients quickly.
Mohamed Zaki: Yeah. Typically, when you have some data with sufficient follow-up, the discussion with the agency could range between how to bring such an effective regimen to patients quickly. 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 Mallik mentioned. Of course, there is discussion about what doses, other things like that could come into the conversation. It is actually the timing to go there will depend on how the data and the amount of follow-up that we have and to maybe even have a fruitful discussion with the agency.
Speaker #5: 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.
Speaker #5: Of course, there's discussion about what dose is, other things like that could come into the conversation. So it's actually at the timing to go there will depend on how the data and the amount of follow-up that we have and to be able to have a fruitful discussion with the agencies.
Speaker #9: Yeah. And in terms of the data update we shared later this year, we haven't disclosed if it'll be a company update or a medical congress.
Ameet Mallik: Yeah. In terms of the data update we share later this year, we haven't disclosed if it will be a company update or medical congress. Obviously, we want to share as much data as we can. As you know, that is one of the considerations; the data cutoffs sometimes for medical congresses are much, much earlier. That is one of the things we are considering in that choice of how we can make sure that we can show a robust update that goes beyond what we shared in June.
Speaker #9: Obviously, we want to share as much data as we can. And so as you know, that's one of the considerations is the data cutoff sometimes for medical congresses are much, much earlier.
Speaker #9: And so that's one of the things we're considering in that choice of, you know, how we can make sure that we can show a robust update that goes beyond what was shared in June.
Speaker #5: Got it. Thank you.
Michael Schmidt: Got it. Thank you.
Speaker #8: Your next question comes from Lonid Timeshev with RBC Capital Markets. Your line is now open.
Operator: Your next question comes from Lonid Temeshev with RBC Capital Markets. Your line is now open.
Speaker #3: Yeah. Thanks for taking my question. I just want to ask on some of the indolent lymphomas. I guess given the encouraging MZL data you've seen, can you just remind us how you see Zilanta fitting into these more indolent indications given that there's slightly different benefit risk calculus there?
Ameet Mallik: Yeah. Thanks for taking my question. I just want to ask on some of the indolent lymphomas. I guess, given the encouraging MZL data you've seen, can you just remind us how you see ZYNLONTA fitting into these more indolent indications, given that there's somewhat 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? And then maybe just a quick follow-up on that, I guess. Would you also consider looking at biospecific combos in these? Thanks.
Speaker #3: And then 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?
Speaker #3: And then maybe just a quick follow-up on that. I guess would you also consider looking at bispecific combinations in these? Thanks.
Speaker #9: Yeah. So yeah, I agree. We are very encouraged by the indolent lymphoma data we've generated both in the relapsed sed refractory setting of MZL and follicular.
Michael Schmidt: Yeah. So, yeah, I agree. We are very encouraged by the indolent lymphoma data we have generated both in the relapsed refractory setting of MZL and follicular. Specific to your question around MZL, there is a study that is ongoing. The phase 2 IIT 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 guideline was perdebrutinib, 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. So we think 50 is about the right number. We are well on our way to enrolling that number of patients.
Speaker #9: Specific to your question around MZL, there's a study that's ongoing, the phase two 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 perdebrutinib, which is a BTK inhibitor based on 36 patients.
Speaker #9: The most any trial has ever enrolled, which is a clinical trial, is about 62 patients. So we think 50 is about the right number.
Speaker #9: We're well on our way to enrolling that number of patients. In terms of what you need to show, you know, right now when you look at the CR rates in that relapsed refractory setting, the highest CR rate is about 29%.
Michael Schmidt: In terms of what you need to show, you know, right now, when you look at the CR rates in that relapsed refractory setting, the highest CR rate is about 29%. So, you know, we are well above that, obviously, with the data we are 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, you know, we are really pleased about the safety profile right now that we are seeing with ZYNLONTA. At this point, we do not see the need to combine with a bispecific because we are seeing such high efficacy with the single agent.
Speaker #9: So you know we're well above that obviously with the data we're sharing right now. Clearly, I think 40% or above would be significant improvement over any of the standard of care.
Speaker #9: In terms of risk benefit, which is one of the other things you mentioned, you know we're really pleased about the safety profile right now that we're seeing with Zilanta.
Speaker #9: 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. And particularly in the indolent lymphomas, thinking about the safety profile for, you know, knowing the patient's can be treated and can be, you know, on on treatments and in a disease setting for multiple years oftentimes.
Michael Schmidt: And particularly in the indolent lymphomas, thinking about the safety profile for, you know, knowing that patients can be treated and can be, you know, on treatments and in a disease setting for multiple years, oftentimes, the tolerability profile is obviously much more important than even in more aggressive lymphomas like DLBCL. So we feel quite comfortable with our approach as a single agent ZYNLONTA in marginal zone lymphoma, and that is the approach we will take going forward.
Speaker #9: The tolerability profile is obviously much more important than even in more aggressive lymphomas like PLBCL. So we feel quite comfortable with our approach as a single agent Zilanta.
Speaker #9: In marginal zone lymphoma, and that's the approach we'll take going forward.
Speaker #8: Ladies and gentlemen, as a reminder, should you have a question, please press star one. Your next question comes from Sudan Logan Than with Stevens.
Operator: 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 #8: Your line is now open.
Speaker #9: Hi, Ameet, Mohamed, and Pepe. Congrats on the strong progress in the quarter. And thank you for taking my questions. First, can you walk us through your sales force growth plan and timeline as you expect to unlock a much larger TAM with the strong response data outcomes of the Lotus trials?
Ameet Mallik: Hi, Ameet, Mohamed, and Pepe. Congrats on the strong progress in the quarter, and thank you for taking my questions. First, can you walk us through your sales force growth plan and timeline as you expect to unlock a much larger TAM with the strong response data outcomes of the LOTIS-5 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-5 trial data to prescribing physicians? Lastly, real quick, post the complete response letter of glofitamab, do you anticipate glofitamab confirmatory phase 3 study, if granted full approval for the glofitamab plus polyVR CHAP combo, to typically change the landscape for treatment of second-line DLBCL, akin to how glofitamab plus Genmox was expected to, or be more of the same?
Speaker #9: How will marketing responsibilities of the combination with Glofidomab be split if any at all with Roche? And when do you anticipate the earliest opportunity the MSLs will have to start talking about the Lotus trial data to prescribing physicians?
Speaker #9: And then lastly, real quick, you know, post the CRL of star glow, do you anticipate sky glow confirmatory phase three study if granted full approval?
Speaker #9: For the Glofidomab plus poly VR chap combo, can we change the landscape for treatment of second-line PLBCL, akin to how Glofidomab plus GemOx was expected to, or be more of the same?
Speaker #9: Okay. So you asked a few different questions. One was around the commercial and medical affairs approach that we're going to use to use that is there going to be any collaboration with Roche on that?
Ameet Mallik: Okay. So you asked a few different questions. One was around the commercial and medical affairs approach that we are going to use. Two, you said is there going to be any collaboration with Roche on that? Then three, you asked a little bit about SkyGlo, and the SkyGlo would be the confirmatory study. Let us answer each of those questions. From a field force and medical affairs standpoint, we think we have the right footprint. We are already, if you look at our commercial footprint, we are covering 90% of the potential of DLBCL, so we think we are well covered in that setting. Similarly, if you look at our MSL force, it is very competitive where we are able to cover all the academic centers and all the large community centers. So we think our footprint is where it needs to be.
Speaker #9: And then, three, you asked a little bit about sky glow and if sky glow would be the confirmatory study. So let's answer each of those questions.
Speaker #9: 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.
Speaker #9: So we think we're well covered in that setting. Similarly, if you look at our MSL force, it's very competitive. We are able to cover all the academic centers and all the large community centers.
Speaker #9: So we think our footprint is where it needs to be. Obviously, we would have some resources on the marketing and medical side as you would pre-launch and in the early launch phases.
Ameet Mallik: 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 will 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. As you know, we will not promote anything off-label, and so our commercial teams will not be actively discussing LOTIS-7. MSLs, obviously, will be there to respond to questions that physicians have around the LOTIS-7 data. At this point, there is no planned collaboration commercially or medically with Roche on that. With regards to the front-line study with glofitamab, polyVR CHIP, it is hard to know.
Speaker #9: As we kind of expand the potential uses of Zilanta, with regards to any collaboration, as you know, we'll be launching we believe with a successful approval of Lotus5, we would be then promoting that and be successfully launching that.
Speaker #9: Lotus7 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.
Speaker #9: And so our commercial teams won't be actively discussing Lotus7. MSLs obviously will be there to respond to questions that physicians have. Around the Lotus7 data.
Speaker #9: And at this point, there's no planned collaboration commercially or medically with Roche on that. With regards to the front-line study with Glofid, poly VR chap, it's hard to know.
Speaker #9: 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 you know we're waiting like you are to see if that gets confirmed by the FDA.
Ameet Mallik: We do not want to speculate beyond what Roche has said, obviously. I think their intention is that that could be their confirmatory study, but you know, we are waiting like you are to see if that gets confirmed by the FDA.
Speaker #8: There are no further questions at this time. I will now turn the call over to Ameet for closing remarks.
Operator: There are no further questions at this time. I will now turn the call over to Ameet Mallik for closing remarks.
Speaker #9: 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.
Ameet Mallik: 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.
Speaker #9: Operator, you may now end the call.
Operator: Ladies and gentlemen, this concludes your conference call for today. We thank you for participating with us. Please disconnect your lines.