ADC Therapeutics - Q3 2024

Transcript

Speaker 2

Good morning, ladies and gentlemen, and welcome to the ADC Therapeutics Q3 2024 earnings conference call. At this time, all lines are in 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 *0 for the operator. 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.

Speaker 4

Thank you, Operator. This morning we issued a press release announcing our Q3 2024 financial results and business update. This release and the slides we will use in today's presentation are available on the Investor section of the ADC Therapeutics website. I'm joined on today's call by our Chief Executive Officer, Ameet Mallik, who will discuss our operational performance and recent business highlights, followed by our Chief Financial Officer, Pepe Carmona, who will review our Q3 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 Q3 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.

Speaker 5

Thanks, Marcy, and good morning, everyone. Thank you for joining us on today's call. The Q3 of 2024 represented a solid period of continued performance for our company. Throughout the quarter, we continued to focus on execution and delivering on our commercial strategy. Even in a highly competitive market, we have been able to secure our place as a treatment option for third-line plus patients with DLBCL. Our Q3 net product revenues increased to $18 million during the quarter, bringing year-to-date Zynlonta revenues to $52.9 million. We are confident in Zynlonta's profile, with rapid, deep, and durable efficacy, a manageable safety profile, and ease of administration. Beyond our current indication, we believe in the potential to expand the use of Zynlonta into earlier lines of therapy in DLBCL and in the lymphomas through combinations, significantly growing the commercial opportunity.

Enrollment in LOTIS-5, our phase III confirmatory study of Zynlonta in combination with rituximab in patients with second-line plus DLBCL, is nearing completion with full enrollment expected by the end of this year. Data are expected by the end of 2025 once the pre-specified number of events is reached. Interim data, including safety and efficacy in a subset of patients from our LOTIS-7 Part II dose expansion of the Zynlonta plus glofitamab combination arm in second-line plus DLBCL, are expected in December, with additional data anticipated in the first half of 2025. In addition, we are excited that two key investigator-initiated trials conducted at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine studying Zynlonta in indolent lymphomas will be presented at the American Society of Hematology meeting in December.

This includes an oral presentation with updated data from the phase II IIT evaluating Zynlonta in combination with rituximab in patients with high-risk, relapsed, or refractory follicular lymphoma, as well as a poster presentation with updated data from the phase II IIT evaluating Zynlonta for the treatment of relapsed or refractory marginal zone lymphoma. We look forward to the updates from these two studies evaluating the potential of Zynlonta in these lymphomas. The phase I-II clinical trial sponsored by the University of Texas MD Anderson Cancer Center evaluating ADCT-602 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia continues to progress, and dose escalation continues at the 60 microgram per kilogram dose.

Within our solid tumor programs, we have made the decision to discontinue the phase Ib ADCT-601 program targeting AXL as a single agent and/or in combination with patients with sarcoma, pancreatic cancer, and non-small cell lung cancer. Although early signs of antitumor activity were observed during the dose escalation phase, we were unable to demonstrate a favorable benefit-risk profile during the dose optimization and expansion phase. Moving forward, we will prioritize our Exatecan-based platform in solid tumors where progress continues in the IND-enabling studies for the company's Exatecan-based programs for ADCs targeting Claudin-6, PSMA, and NaPi2b, while our ASCT2 targeting ADC is in the drug candidate selection stage. The company has selected one target to move toward IND, which is expected to be disclosed in 2025. At the same time, we continue to explore potential partnership opportunities.

Looking specifically at DLBCL, when you move beyond the front line, cure rates are extremely low. Here, physicians make treatment decisions based on efficacy, safety, and accessibility in the context of individual patient considerations. Zynlonta delivers on all three, which we believe positions it well for use in combination in second-line plus DLBCL. The market has evolved to essentially four modalities: cellular therapies, bispecifics, ADCs, and monoclonal antibodies, as well as chemotherapy, and is moving toward 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 Lotus V and Lotus VII 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 non-systemic 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 and anti-CD19 ADC and Glofitamab and 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 two 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 II dose expansion with Zynlonta at two 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 I and Part II 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.

Speaker 3

Thank you, Ameet. On the financial front, we remain well capitalized, ending the Q3 with $274.3 million in cash and cash equivalents, which is expected to fund operations into mid-2026 based on current plans. Zynlonta net profit revenues were $18.0 million for the Q3 and $52.9 million for the first nine months of 2024, as compared to $14.3 million and $52.4 million for the same periods in 2023. The Q3 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 nine months of 2024 by 12% year-over-year on a non-GAAP basis, which excludes stock-based compensation.

In the Q3, our non-GAAP operating expenses increased versus prior year by 5% due to investment in Zynlonta LOTIS-5 trial and AXL 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 the 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 three 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 the 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.

Speaker 5

Thanks, Pepe. As we've illustrated today, we made significant progress in the Q3, 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 Lotus V and initial efficacy and safety data from Lotus VII, Part II 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?

Speaker 2

Thank you. Ladies and gentlemen, we will now begin the question-and-answer session. If you have a question, please press star followed by the number one on your touch-tone phone. If you wish to be removed from the queue, please press star followed by the number two. If you are using a speakerphone, you may need to pick up the handset first before pressing the numbers. Once again, if you have a question, please press star, then one on your touch-tone phone. One moment, please, for your first question. Your first question comes from Michael Schmidt of Guggenheim. Please go ahead.

Speaker 6

Questions. Could you comment a little bit more about the commercialization of Zynlonta and 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.

Speaker 5

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 and 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 academics for patients to get access to bispecifics. So they've certainly taken over probably close to about a third 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 settings, so it's still about 50/50. Obviously, there's, like we've 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.

Speaker 6

Okay, great. And on the Lotus VII data later this year, I know you said you'll 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 Lotus VII? Thanks so much.

Speaker 5

Yeah, 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 two 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.

Speaker 6

Thank you.

Speaker 2

Your next question comes from Eric Schmidt of Cantor. Please go ahead.

Speaker 0

So thanks for taking my questions. Appreciate the update, Ameet and Pepe. Maybe just coming back to AXL 601 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, PBD payload or linker or safety, or maybe it was just the target that was a no-go here?

Speaker 5

Yeah, I mean, I think it'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 in 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, three versus four 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 was 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 were more limiting to get to the efficacy we wanted 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-criteria that we stuck with, and we just made the decision that it wasn't worth pursuing any further.

Speaker 0

I appreciate the discipline. Can you be a little bit more specific on timelines for a next solid tumor IND filing and/or partnership conclusion discussion?

Speaker 5

Yeah, because we've really shifted the whole solid tumor strategy towards newer payloads, so as you know, Exatecan is the most advanced, and we have four 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 toward IND. We haven't given a timing expectation of 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.

Speaker 6

I'm just comparing to Eric, so between the drug candidate selection until you get to an IND, on average, it takes about 18 months. It can fluctuate, but that's roughly the timeline on that. And obviously, as Ameet said, we already selected the drug that's going to move to IND.

Speaker 0

Okay. And a quick one for you, Pepe, on Zynlonta sales. I think you mentioned net pricing gains. Could you quantify the magnitude or % increase in net pricing?

Speaker 6

Yeah, we take twice-a-year price increases in low single-digit. So compounded annually is very mid-single-digit, roughly.

Speaker 0

Thank you.

Speaker 2

Your next question comes from Kelly Shi of Jefferies. Please go ahead.

Speaker 7

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

Speaker 5

Yeah, so we hope to see synergy, obviously. That's what we're testing, right? It's 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.

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.

Speaker 7

Thank you very much.

Speaker 2

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

Speaker 1

Hi, this is Greg. Thanks so much for taking our questions. On LOTIS-7, I mean, one of the key value propositions here is the potential to reduce side effect profile such as CRS. I'm just curious, what would that data need to look like in the initial update to be considered as a meaningful improvement from bispecific or bispecific plus chemo? And then I have a follow-up.

Speaker 5

Yeah, 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.

I think we're looking to hopefully improve on both dimensions versus the bispecific monotherapy.

Speaker 1

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

Speaker 5

Yeah, sure. So you probably saw the abstracts that were released on Tuesday. 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 to 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 up 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 be able to with data that's also had 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 three 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 with, remember, we're doing a 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.

Speaker 1

In terms of the timeline, when do you expect to have enough data?

Speaker 5

Yeah, I mean, I guess what I would say is you'll see a further update at ASH now. That'll 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's 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.

Speaker 1

Got it. Thank you so much.

Speaker 2

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.