Good morning, ladies and gentlemen, and welcome to the ADC Therapeutics Third Quarter 2024 Earnings Conference Call. [Operator Instructions] This call is being recorded on Thursday, November 7, 2024. I will now turn the call over to Marcy Graham, Investor Relations Officer for ADCT. Marcy, please go ahead..

Thank you, operator. This morning, we issued a press release announcing our third quarter 2024 financial results and business update. This release and the slides we will use in today's presentation are available on the Investors section of the ADC Therapeutics website.

I'm joined on today's call by our Chief Executive Officer, Ameet Mallik, who will discuss our operational performance and recent business highlights; followed by our Chief Financial Officer, Pepe Carmona, who will review our third quarter 2024 financial results. We will then open the call to questions.

Before we begin, I would like to remind listeners that some of the statements made during this conference call will contain forward-looking statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995.

These forward-looking statements are subject to certain known and unknown risks and uncertainties, and actual results, performance and achievements could differ materially. They are identified and described in the accompanying slide presentation and in the company's filings with the SEC, including Form 10-K, 10-Q and 8-K.

ADC Therapeutics is providing this information as of today's date and does not undertake any obligation to update any forward-looking statements contained in this conference call as a result of new information, future events or circumstances, except as required by law.

The company cautions investors not to place undue reliance on these forward-looking statements. Today's presentation also includes non-GAAP financial reporting. These non-GAAP measures should be considered in addition to and not in isolation or as a substitute for the information prepared in accordance with GAAP.

You should refer to the company's third quarter earnings release for information and reconciliation of historical non-GAAP measures to the comparable GAAP measures. I will now turn the call over to our CEO, Ameet Mallik.

Ameet?.

cellular therapies, bispecifics, ADCs and monoclonal antibodies as well as chemotherapy and is moving towards combinations that offer rapid, deep, durable responses with manageable toxicities, which can be administered in the outpatient setting.

Given the improvement expected in the clinical profile with bispecifics and ADC-based combinations, we believe these regimens have the potential to grow at the expense of cell therapy and chemotherapy use. Here, we see the promise of our LOTIS-5 and LOTIS-7 combination studies.

With LOTIS-5, we are combining ZYNLONTA with rituximab, a therapy that community physicians are comfortable using and is a backbone of DLBCL therapy. We feel this combination offers competitive second-line plus efficacy with favorable safety and a convenient dosing schedule, well suited for use across care settings.

In addition, this is a nonsystemic chemo regimen that avoids the irreversible toxicities associated with chemotherapy, a class that is still widely used in second-line plus DLBCL.

With LOTIS-7, we are combining ZYNLONTA, an anti-CD19 ADC, and glofitamab, an anti-CD20, CD3 T-cell engaging bispecific antibody and have completed dose escalation where the combination demonstrated no dose-limiting toxicities and early signs of antitumor activity.

Our hypothesis with this study is that combining these 2 powerful approved single-agent drugs is expected to have additive or synergistic efficacy along with a manageable safety profile given no overlapping non-hematologic toxicities.

In addition, we believe ZYNLONTA used prior to glofitamab may debulk the tumors and reduce peripheral B cells, leading to lower CRS rates and severity. This would open up the use of this combination in earlier lines of therapy across care settings.

We saw encouraging data in the Phase Ib dose escalation and are currently enrolling patients in Part 2 dose expansion with ZYNLONTA at 2 dose levels in combination with glofitamab in second line plus DLBCL. We anticipate sharing safety and efficacy data on 15 to 20 patients in December.

This includes all DLBCL patients from Part 1 and Part 2 dosed with glofitamab plus ZYNLONTA at the 120 and 150 microgram per kilogram doses where scans are available. We expect to share data on additional patients with longer follow-up in the first half of 2025.

Beyond DLBCL, we also see the potential to expand into the second-line plus settings of indolent lymphomas based on data from investigator-initiated trials at the University of Miami exploring ZYNLONTA plus rituximab in high-risk relapsed or refractory follicular lymphoma and ZYNLONTA monotherapy in relapsed or refractory marginal zone lymphoma.

Early data from these studies demonstrate the potential for rapid, deep and durable efficacy with a fixed duration of therapy and a manageable side effect profile.

Based on the high complete metabolic response rates seen thus far in these studies, we believe there is the potential to provide marginal zone and follicular lymphoma patients with years of remission. We are looking forward to the lead investigators sharing more on these studies at the ASH meeting in December.

As there remains significant unmet need across these lymphomas with sufficient data, we plan to discuss the path forward with regulatory authorities as well as seek inclusion in compendia. With that, I would like to turn the call over to Pepe..

Thank you, Ameet. In the financial front, we remain well capitalized, ending the third quarter with $274.3 million in cash and cash equivalents, which is expected to fund operations into mid-2026 based on current plans.

ZYNLONTA net product revenues were $18.0 million for the third quarter and $52.9 million for the first 9 months of 2024 as compared to $14.3 million and $52.4 million for the same periods in 2023. The third quarter growth versus prior year is primarily driven by volume increase together with a net price increase.

Throughout the year, we have maintained our disciplined capital allocation strategy and decreased operating expenses for the first 9 months of 2024 by 12% year-over-year on a non-GAAP basis, which excludes stock-based compensation.

In the third quarter, our non-GAAP operating expenses increased versus prior year by 5% due to investment in ZYNLONTA LOTIS-5 trial and acts as Phase I clinical program, partially offset by efficiencies in other operating expenses.

We will continue to take a very disciplined approach to our capital allocation through the remainder of 2024 and into the coming year. You can find a reconciliation of GAAP measures to non-GAAP measures in the accompanying financial tables of the press release issued earlier today and in the appendix of this presentation.

On a GAAP basis, we reported a net loss of $44.0 million for the quarter or $0.42 per basic and diluted share as compared to net loss of $46.7 million or a net loss of $0.57 per basic and diluted share for the same period in 2023.

On a non-GAAP basis, adjusted net loss was $29.4 million or an adjusted net loss of $0.28 per basic and diluted share as compared to adjusted net loss of $32.4 million or $0.39 per basic and diluted share for the same period in 2023.

The decrease for the 3 months ended September 30, 2024, is primarily related to higher revenues, while the decrease year-to-date is primarily due to lower operating expense. With our strong balance sheet, we believe we're well financed to continue to pursue our corporate strategy.

As a reminder, hematology continues to be a primary focus of our capital allocation. And within this, our key objective is to create value by expanding the use of ZYNLONTA beyond our current indication. We expect to achieve this by fully supporting our commercialization efforts in the U.S. directly and through our partnership ex U.S.

and by investing behind potential expansion into earlier lines of DLBCL and indolent lymphomas. In solid tumors, our aim is to pursue multiple ADC candidates in parallel and increase our shots on goal through our novel exatecan-based research platform.

In addition to the candidate we are taking forward to IND, we will determine on a case-by-case basis whether we wish to progress additional candidates internally or seek to partner in order to share the development and financial risk. With that, I will turn the call back to Ameet..

Thanks, Pepe. As we've illustrated today, we made significant progress in the third quarter, maintained our disciplined approach to capital allocation, and are excited about what is ahead for the remainder of 2024. We have key potential value-driving milestones, which we expect before the end of this year.

These catalysts include expected completion of enrollment in LOTIS-5 and initial efficacy and safety data from LOTIS-7, Part 2 dose expansion in December as well as the presentation of updated indolent lymphoma Phase II IIT data at ASH.

Looking ahead with a strong balance sheet to execute our strategy, I am confident that ADC Therapeutics is well positioned to drive value creation for all our stakeholders. We can now open the line for questions.

Operator?.

[Operator Instructions] Your first question comes from Michael Schmidt of Guggenheim..

Could you comment a little bit more about the commercialization of ZYNLONTA in its approved indication? I know it's not expected to grow dramatically, but when we look at some of the recent CD20 bispecific antibody launches, I mean, they seem to be experiencing some meaningful uptake in a similar category.

And so I'm just curious, what are you seeing in terms of utilization right now and potential incremental growth opportunities from the current run rate, again, in the approved indication? And then I had a follow-up..

Okay. Sure. Thanks, Michael. Appreciate the question. As you said, there has been increased competition from bispecifics. Since they launched over a year ago, they obviously had penetrated pretty significantly in the academic setting in the third-line setting as well as made some inroads into the community.

One thing we see is more referrals going on between the community and academic for patients to get access to bispecifics. So they've certainly taken over probably close to about 1/3 of the overall third-line plus market share.

I think what I'm excited about with the team is if you look at our overall volume, it's pretty much in line despite all that competition. So we continue to maintain a relatively stable mix of demand between the community and academic setting. So it's still about 50-50.

Obviously, there's -- like we said last quarter, there can be normal order-to-order -- quarter-to-quarter ordering variability. But we see relatively strong advocacy for the use of ZYNLONTA by academic physicians and use in the community. So I think the trend that we've been seeing, we anticipate to continue to see.

And we continue to see the possibility for an $80-plus million peak sales potential in the current indication..

Okay. Great. And on the LOTIS-7 data later this year, I know you said you expect to present data on about 15 to 20 patients with glofitamab.

So what is a positive result here? What are you looking for in this initial data for LOTIS-7?.

Yes, I think it's a great question. So I mean, if you look at other bispecific combinations, and there's been a number of bispecific combinations that have come out with data. And obviously, our data won't be mature enough to look at PFS or overall survival. What we'll have is overall response rates and CR and PR rates.

If you look at that, they tend to be in the 50% to kind of 60% range. I mean, if you look at the majority of the bispecific combinations, they're in that range when you look at the second-line plus setting.

So of course, we want to be competitive from an efficacy profile, but also to hopefully continue to show what we saw in the dose escalation, which is continued improvement in the overall rates and severity of CRS. And so that's the goal for the profile.

Obviously, we have to let the data mature and we'll show it in December, but those are the 2 things we hope to be able to share. One thing I would just note also in terms of efficacy is that when data is reported by competitors or in other trials, it's always about best overall response rate and best CR. That matures over time.

And so we expect to be able to share preliminary data on the scans, but also, I think data matures over time, and we'll continue to share updates not just this year, but as we go into next year as well..

Your next question comes from Eric Schmidt of Cantor..

Appreciate the update, Ameet and Pepe. Maybe just coming back to AXL601 and sort of the solid tumor opportunity.

Is there anything you learned from your decision to give this a quick hook with regard to, I don't know, PDV payload or linker or safety or maybe it was just the target that was in the go here?.

Yes. I mean, I think what's interesting is when we did the dose escalation, you're obviously giving more limited dose duration. And when you're doing the dose escalation, we did see some initial clinical activity, which we had shared in sarcoma, both as monotherapy and combination.

That basically led to the investment to say, let's do the dose expansion optimization. We knew with the payload and target combination, there was a limited therapeutic index. And so one of the things we wanted to look at was different dosing schedules, for example, 3 versus 4 weeks.

Or what we've done in other programs start with a higher dose and then down dose. And so we played with that during the dose optimization and expansion phase. But unfortunately, we weren't able to sustain the level of efficacy we want to see with a favorable tolerability profile.

And so the benefit risk that we saw during that dose optimization expansion phase just wasn't there. It's hard to speculate how much is target versus payload. But I would just say that some of the side effects that we saw as we were continuing to dose at high levels and -- were more limiting to get to the efficacy we want to see.

So the reason we made the call is we wanted to have a specific endpoint. You remember, we said we're going to dose up to 80 patients, we're going to either see a strong efficacy signal and a strong profile that we think we can go out and do a BD deal or we're going to stop the program.

And so we had very disciplined go/no go criteria that we stuck with, and we just made a decision that it wasn't worth pursuing any further..

Appreciate the discipline.

Can you be a little bit more specific on time lines for a next solid tumor IND filing and/or partnership conclusion discussion?.

Yes. So as you know, we've really shifted the whole solid tumor strategy towards newer payloads. So as you know, exatecan is the most advanced, and we have 4 different programs in that. We will give an update in the future. I mean, as you know, we've picked one program that we're already progressing on our own towards IND.

We haven't given the timing expectation on that. We will give that in a future update. And we continue to be in discussions with partners around potentially research collaboration for some of the other programs. I don't anticipate that's going to happen this year, just to set expectations. I think it's more of a 2025 event..

Eric, so between the drug candidate selection until you get to an IND, in average, it takes about 18 months. It can fluctuate, but that's roughly the time line on that. And we obviously, as Ameet said, we already selected the drug that's going to move to [indiscernible]..

Okay. And a quick one for you, Pepe, on ZYNLONTA sales. I think you mentioned net pricing gains.

Could you quantify the magnitude or percent increase in net pricing?.

Yes. We take twice a year price increases in low single digit. So compounded annually, is mid-single digit roughly..

Your next question comes from Kelly Shi of Jefferies..

So for LOTIS-7 trial, what kind of synergy you expect from this combo, particularly on durability front? And also just curious, are there any community centers are involved for this ongoing trial?.

Yes. So we hope to see synergy. Obviously, that's what we're testing, right, is to see either additive or synergistic efficacy because obviously, these are complementary mechanisms. ZYNLONTA is, of course, CD19 ADC and glofitamab is a CD20, CD3 T cell bispecific. So we hope to see additive or synergistic efficacy.

And because of the way we're dosing by giving the ZYNLONTA a week before to debulk the tumor, we're also hoping that, that reduces the rates and severity of CRS. So the profile is really to prove on both dimensions of the bispecific monotherapy. In terms of the trial, we are in academic centers and in large community centers.

We're in CAR-T centers as well as centers that don't give CAR-T. So we're really trying to make sure that we're testing this in a representative sample of second-line plus patients because we think it's really important to test across the whole patient sample.

You should expect a patient sample that's very consistent with other large-scale bispecific combination trials..

Your last question comes from Gregory Renza of RBC Capital Markets..

This is [indiscernible] on for Greg. On LOTIS-7, I mean, one of the key value proposition here is the potential to reduce side effect profile such as CRS.

I'm just curious, what would that data need to look like perhaps in the initial update to be considered as a meaningful improvement from bispecific or bispecific plus chemo? And then I have a follow-up..

Yes. I think the most meaningful thing, obviously, what we saw in the dose escalation was in the low 30%. Glofitamab on its own is roughly 70%. So rates of CRS are obviously important, but I think severity is even more important because when you look at Grade 1 CRS, it could be treated as simply sometimes as [Tylenol], Grade 4, you're hospitalized.

So the difference between these grades is very significant. And especially to remove the requirement or even option for hospitalization, I think the important thing is to get rid of high-grade CRS, so Grade 3 and Grade 4. So what we would hope to see like we saw in the dose escalation was no high-grade CRS.

I think that's the most important part from that standpoint. But again, we also want to see efficacy that's strong, too. So I think we're looking to hopefully improve on both dimensions versus the bispecific monotherapy..

Got it.

And as a follow-up, I'm just curious, what should we be -- I mean, can you help us set expectations for the indolent lymphoma update at ASH? And can you also remind us, like what are the sizes of this data set that will be needed for the compendia listing? And maybe help -- if you could help refine the time line, when do you expect to have that sufficient data to pursue that route?.

Yes, sure. So you probably saw the abstracts that were released on Tuesday, and we had a press release just summarizing the abstract data from both the relapsed/refractory high-risk FL study as well as the relapsed/refractory MZL study. So what I would expect in the presentations, FL is an oral presentation, MZL is a poster presentation.

It's just updated data as you see with most things. So when the investigators have to submit data in the summer, they, of course, will update that with more patients and more duration and provide further detail in the presentation. So that's what you should expect at ASH.

And then in terms of the number of patients that are needed, there's more of a precedent, I would say, in MZL, where when you look at patient sample sizes that have gotten the guidelines, it's been as little as 36 patients. The most has been kind of around 50, so -- when there was inclusion. And even for approvals, it's only been to about 68 patients.

So that's kind of the range, I would say. We're doing a 50-patient study. You can see the data that was presented in the abstract was 20 patients. I would expect to see probably a few more when you get to the presentation because there'll be more patients that have been enrolled.

And that's sort of -- we'll have to be in that range, I would say, to get -- to be able to -- with data that also has some level of durability to be able to submit to get into -- potentially to get into guidelines or have discussions with regulatory authorities.

With follicular, there's a little bit less of a precedent because there's a number of Phase III studies that have gone on, head-to-head studies. The unique thing about the patient population we're studying though is it's only a high-risk patient population. Many of these patients are POD24.

So the unmet need, of course, in this population is significantly higher. And so there may be a possibility. Remember, we're doing 100-patient study, which is a pretty large study in this more narrow patient population.

There's a possibility that we would be able to submit and have discussions with the FDA on a more accelerated path in this high-risk patient population..

And in terms of the time line, when do you expect to have enough data?.

Yes. I mean, I guess, what I would say is you'll see a further update at ASH now. That will be the next real update on the data where you'll see more details versus what was in the abstract. In terms of timing, we haven't given any updates because obviously, these are both investigator-initiated trials. So the enrollment is not in our control.

I think you'll just see that versus the updates that we gave earlier this year and prior year, these continue to enroll. There continues to be interest given the high unmet need in both of these settings..

Thank you, ladies and gentlemen. That concludes our question-and-answer session. I will now turn the call back over to CEO, Ameet Mallik.

Ameet?.

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

Thank you for attending. You may now disconnect your lines. This concludes today's conference..