ADC Therapeutics SA (ADCT) Earnings Call Transcript & Summary

Welcome to the ADC Therapeutics conference call to review the Lonca Phase II and Phase I/II combination clinical trial data presented at EHA today. [Operator Instructions] I would like now to turn the call over to Amanda Hamilton, Investor Relations at ADC Therapeutics. Please proceed.

Good morning, and welcome to our call. Earlier this morning, we issued a press release with new clinical data for loncastuximab tesirine, or Lonca, which is now available on the Virtual 25th Congress of the European Hematology Association, or EHA25 website. This release as well as the slides we will present today are available on the Investors section of our website at www.adctherapeutics.com. A replay of today's call will also be made available on our website. After our prepared remarks, we will open the call for Q&A. As a reminder, during today's call, we will be making forward-looking statements regarding our financial outlook. On Slide 2 of today's presentation, you can find our legal disclosures. With that, I will turn the call over to Chris Martin, ADC Therapeutics' Chief Executive Officer. Operator, please go to Slide 3.

Thank you, Amanda. Good morning, everyone, and thank you for joining us. It's my pleasure to speak with you today and to provide an update of our significant progress at ADC Therapeutics. If you look at Slide 3, we recently completed the successful initial public offering, providing the company with the capital to execute on our broad clinical development program and earlier stage pipeline. This includes our CD25-targeting Cami program in solid tumors, the CD22 program in Adult ALL and our AXL and KAAG1 programs. In particular, we are pleased with the progress of our Lonca clinical program. In this morning's press release, we highlighted new Lonca data, which is now available on the Virtual EHA Annual Congress website. The presentations include normal presentation of new data from the pivotal Phase II Lonca trial and an e-poster of the Phase I/II combination trial of Lonca plus ibrutinib. The Phase II data presented today shows that monotherapy Lonca demonstrated important anti-tumor activity with an overall response rate of 48.3% and a complete response rate of 24.1% and meaningful durability. These data are very encouraging, and continue to reinforce the significant single-agent anti-tumor activity and manageable toxicity profile of Lonca and its potential to become a foundation for treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. Based on these data, we plan to file the Lonca monotherapy BLA during the second half of this year. Our CMC plans are on track to meet the BLA time line. And we continue to prepare our organization with the build-out of our commercial, market access and medical affairs teams in advance of the anticipated commercial launch next year. The second data presentation is an e-poster of interim results of the Phase I/II trial highlighting the potential to advance Lonca into earlier lines of therapy in combination with other treatments. The data being presented here today show that the combination of Lonca and ibrutinib in a Phase I/II clinical trial of relapsed/refractory DLBCL, and mantle cell patients looks encouraging with an overall response rate of 75% and a complete response rate of 58.3% of the 60 micrograms per kilogram dose used in the expansion cohorts. These data support the growing evidence of the activity of Lonca and leave us even more encouraged by the potential to bring out new treatment option to patients in the relapsed/refractory DLBCL setting. Let me now turn over to our Chief Medical Officer, Jay Feingold, to review today's data in more detail. Jay?

Thank you, Chris. Good morning, everyone. Let me start by reviewing the data from our pivotal LOTIS 2 trial. As shown on Slide 5, this trial was a single-arm, multicenter, open-label Phase II study that evaluated the safety, efficacy and pharmacokinetics of Lonca as a monotherapy in patients with relapsed or refractory DLBCL. Patients received 30-minute intravenous infusions of Lonca once every 3 weeks at a dose of 150 micrograms per kilogram for the first 2 cycles, followed by 75 micrograms per kilogram for subsequent cycles or up to 1 year or until disease progression, unacceptable toxicity or other discontinuation criteria, whichever occurred first. A total of 145 patients participated in the study. As you can see on Slide 6, the study included patients with very poor prognosis, such as double hit and triple hit and transformed disease. The study also included patients who never responded to first-line therapy and patients who were refractory to all prior lines of therapies as well as patients who had high-grade B-cell lymphoma and high-risk genetics. Patients in this study had a median of 3 prior lines of therapy. Turning to the next slide. As Chris mentioned earlier, monotherapy Lonca demonstrated important anti-tumor activity, an overall response rate of 48.3% and a complete response rate of 24.1% in the overall study population. Patients refractory to first line or all prior lines of therapy had an overall response rate of 38% and 36%, respectively. This data reflects the significant activity Lonca can achieve even in these difficult-to-treat patients. If you turn to Slide 8, we are pleased to see that as data has matured, we have seen an increase in duration of response with a meaningful median duration of response of 10.25 months. On Slide 9, you can see that toxicities were manageable and no new safety concerns were identified. Bone marrow suppression was common but manageable, and the rate of febrile neutropenia was only 3.4%. The most common non-hematologic grade 3 and higher treatment-emergent adverse event was elevation of the liver enzyme, GGT, seen in 16.6% of patients. It's important to note that this laboratory abnormality was not associated with any abnormal liver function. In conclusion, on Slide 10, the anti-tumor activity seen in these patients who have failed a meeting of 3 prior lines of therapy represents an opportunity for patients with limited treatment options to benefit from Lonca and in patients with a complete or very deep partial response the possibility of undergoing a stem cell transplant, which is considered the best option for long-term survival. And now turning to the data presented in the e-poster on Slide 11. The LOTIS 3 trial is evaluating the combination of Lonca and ibrutinib in the Phase I/II trial of relapsed/refractory DLBCL and mantle cell lymphoma patients. Lonca is administered as a 30-minute intravenous infusion, using a standard 3+3 dose escalation design at doses of 60 or 90 micrograms per kilogram. Patients receive Lonca every 3 weeks for the first 2 cycles with concurrent fixed-dose ibrutinib, 560 milligrams per day given orally up to 1 year. On Slide 12, as of the April 6 data cutoff, 25 patients were enrolled, 23 with DLBCL and 2 with MCL. These patients received a median of 2 cycles of Lonca, with 19 patients at the 60 micrograms per kilogram dose and 6 patients at the 90 microgram per kilogram dose. Slide 13 shows that early clinical data is promising and an overall response rate of 75% and a complete response rate of 58.3% at the Lonca dose of 60 micrograms per kilogram in combination with ibrutinib in patients with non-germinal symptoms, DLBCL and mantle cell lymphoma. The patients with only DLBCL in that cohort had an overall response rate of 73% and a complete response rate of 64%. The protocol has been amended to include GCB DLBCL patients. On the next slide, you will see that 2 dose-limiting toxicities were observed in a 90 microgram per kilogram cohort. One DLT was possibly related to ibrutinib, and the other was probably related to both drugs. No DLTs have been observed in patients receiving the selective regimen for Phase II. The 2 most frequent grade 3 and higher treatment-emergent adverse events have been thrombocytopenia and anemia. We chose the regimen of 60 micrograms per kilogram of Lonca with 560 milligrams ibrutinib for a cohort expansion and new regimen that will be used in the forthcoming Phase II portion of the study. Turning to Slide 15. In summary, we are pleased with the early data for Lonca in combination with ibrutinib. The combination had promising anti-tumor activity and a manageable toxicity profile. The study continues to enroll MCL and GCB DLBCL patients in the expansion phase, and we anticipate opening the Phase II portion of the study soon. In summary, the data presented at EHA for Lonca monotherapy will be the basis for the BLA that we intend to submit in the second half of 2020. The encouraging early data of Lonca in combination with ibrutinib suggest that the combination can be safely administered and that there are significant anti-lymphoma activity. The benefit/risk profile provides the strong basis for the continued development of this combination. With that, I will now turn the call back over to Chris for closing remarks.

Thank you, Jay. As you can see, we've made excellent progress with the Lonca clinical program. We're excited by these data and pleased to be preparing the BLA for submission in the second half of this year. The Lonca program illustrates the potential of the PBD and ADC platforms and the remarkable productivity of both the preclinical and clinical R&D teams. We are pleased to be moving forward not only with Lonca but with our earlier-stage pipeline as well. Before we take your questions, I'd like to thank you for joining the call especially in these extraordinary times. I trust you and your families are safe and well. We will now open the call for questions. Operator?

[Operator Instructions] Our first question comes from the line of Matthew Harrison at Morgan Stanley.

So I guess two for me. So one on Lonca monotherapy, on durability. Can you just, I guess, clarify for us how many patients at risk did you have out on the curve? I didn't see the numbers at the bottom. And I guess what I'm trying to make sure we understand is how robust is the tail of this data set at this point compared to the data set that you had previously presented. And then second on the combo. I guess talk about the dose response and why you picked the lower dose. And I think more importantly, what do you need to do to maybe accelerate that into a potential pivotal study for earlier lines?

Thank you, Matthew. I'll ask Jay to address both of those questions. Please, Jay?

Sure. Matthew, in terms of durability of response, when we first showed the first data set at ASH, which was 52 patient futility, we announced that the patients furthest out had -- were about 8 months. Currently, on the slide that was shown today, the furthest outpatients are about 15 months. Obviously, this data will continue to mature, but this is the data that we have with us today. In terms of the dose response in the combination trial, the patients with 90 micrograms per kilogram certainly responded, but the 2 DLTs made that dose unacceptable from a safety profile point of view. Therefore, we chose to expand the cohorts of 60 micrograms per kilogram and due to the fact that the first 3 patients treated with 60 micrograms per kilogram all went into remission, complete remission, by 6 weeks. So that was a dose we chose to take forward into the expansion cohorts. We have amended the trial so that we can start the Phase II portion of the study in the same trial, and that will be initiated in the near future.

We have one further question in the queue so far. [Operator Instructions] The next question comes from the line of Boris Peaker at Cowen.

Congratulations on the excellent data. My first question, in the pivotal study, you enrolled fairly sick patients with poor prognosis and baseline characteristics. So you said you had double hit, triple hit, transformed disease, nonresponders to frontline therapy, and some of these were excluded by some of your competitors. I'm just curious, how can you capture this kind of distinction for patient enrollment in the product label so you could market that element of your pivotal study?

Jay, again, I'll ask you to address that, please. Jay?

For us, obviously, the eventual label will be dependent upon discussion with FDA. We would anticipate that FDA would follow the usual policy and give us the indication to a broad population of DLBCL patients who have held at least 2 prior lines of therapy. That was the population that was studied in this study. We can't obviously, compare ourselves to what other labels will look like and -- nor are we in a position to discuss the differences in the population. I think they speak for themselves in terms of patients we included and the patients they've included in some of the more recent competitive studies.

Okay. And my last question on the duration of response, obviously, you showed a significant increase here. Curious if there is a specific patient subgroup that drove the increase relative to the prior update, or is it just longer follow-up? What is the key?

At this time, what I can tell you that it appears to be longer follow-up. But we're still doing analysis of the data, and we don't have all the subset analysis completed yet.

And we've had one further question joining the queue so far. That's from the line of [ James Eason ], who's a private investor.

I was wondering when you applied for the Lonca BLA, do you apply for the -- its breakthrough designation at the same time? Or is that totally separate? And typically, how long does the FDA take to come back with yes or no on the breakthrough designations?

Thank you for that question. We haven't disclosed our approach to breakthrough designation. We haven't applied the breakthrough designation yet for the Lonca program. But as you'd imagine, we've been having regular discussions with the FDA as we develop this agent, and we'll be looking to file for accelerated approval when we file the BLA.

[Operator Instructions] Okay. That seems to be the final question coming for you. So I'll hand back to our speakers for the closing comments.

Thank you very much, and thank you, everybody, who's joined this call. As I say, we're very pleased with this data. And I think the ibrutinib combination study does show the potential to move Lonca into earlier lines of therapy and the broad single-agent activity, as Boris Peaker pointed out, across patient population that included hard-to-treat populations, even patients that have never responded to any prior line of therapy. And we saw responses across that population. So yes, we're excited to be moving toward Lonca and look forward to announcing the filing of the BLA in due course. So thank you very much, everyone.