Welcome to the ADC Therapeutics Fourth Quarter and Full-Year 2023 Financial Results Conference Call. My name is Norma and I will be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. [Operator Instructions]. I will now turn the call over to Nicole Riley, Head of Communications. Nicole, you may now begin.

Thank you, operator. This morning, we issued a press release announcing our fourth quarter and full year 2023 financial results and business updates. This release is available on the ADCT website at ir.adctherapeutics.com under the Press Releases section. On today's call, Ameet Mallik, Chief Executive Officer; Kristen Herrington-Smith, Chief Commercial Officer; Mohamed Zaki, Chief Medical Officer; Patrick van Berkel, Chief Scientific Officer; and Pepe Carmona, Chief Financial Officer, will discuss recent business highlights and review our fourth quarter and full-year 2023 financial results before opening the call for 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 US 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 today's press release and the accompanying slide presentation on slide 2 and in the company's filings with the SEC, including Form 10-K, 10-Q and 8-K. ADCT is providing this information as of the date of today's conference call 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 after the date hereof, except as required by law or otherwise. The company cautions investors not to place undue reliance on these forward-looking statements. Today's presentation also includes non-GAAP financial measures. These non-GAAP measures have limitations as financial measures and 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 information contained in the company's fourth quarter earnings release for definitional information and reconciliations of historical non-GAAP measures to the comparable GAAP financial measures. It is now my pleasure to pass the call over to our CEO, Ameet Mallik. Ameet?

Thanks, Nicole. And thank you all for joining us today. 2023 was a year of prioritization and focus for the company. We made some tough decisions and firmly believe we are well positioned for success in 2024 and beyond. With enhanced talent in place, we implemented a new corporate and capital allocation strategy, focusing our resources and energy on our most advanced and highest potential clinical value drivers. As you can see here, we enhanced commercialization efforts, prioritized our pipeline, expanded our research platform and reduced organizational costs. This reset in 2023 was critical to enable our strategy moving forward. There are two core pillars to the strategy which we believe will unlock the tremendous value we see in this company. Our first pillar, and primary focus, is hematology. Within this, we have a derisked asset in ZYNLONTA, the key product in our prioritized portfolio, which we expect to carry the company through to profitability. We are deploying the majority of our capital to the ZYNLONTA franchise to commercialize our existing third line and third line plus DLBCL indication and to pursue the substantially larger potential opportunity in earlier lines of DLBCL therapy and indolent lymphomas. We believe these potential opportunities will help expand the ZYNLONTA franchise and have the potential to generate annual peak sales in excess of $0.5 billion. The second pillar of our strategy is grounded in our emerging solid tumor pipeline. Our most advanced asset is ADCT-601. And behind this, we have a number of exciting next generation antibody drug conjugates, which potentially address significant unmet patient needs. Driven by our novel platform, we see the potential to advance a broad portfolio of differentiated ADCs against solid tumor targets of interest. To capture this opportunity, our ambition is to progress multiple assets in parallel, internally and…

Thanks, Ameet. Today, our strategy is to grow ZYNLONTA in the community, where the third-line, third-line-plus DLBCL setting continues to be fragmented with no standard of care, and to maintain our position in the academic centers for patients who are not eligible for CAR-Ts or bi-specifics or who have progressed following treatment with these complex therapies. Our strategy is supported by real-world data as presented at the recent Tandem Meetings, which demonstrated ZYNLONTA's efficacy pre and post CAR-T. Execution against our strategy was the fundamental driver for our commercial restructuring and resulted in higher ZYNLONTA demand in November and December, similar to the levels in the first half of 2023. We delivered a 17% increase in net revenue in Q4 compared to Q3, with growth in both the community and academic settings. I am especially proud of our performance, given the competitive dynamic with the recent approvals of two bispecifics in the same third-line, third-line-plus setting as ZYNLONTA. We are confident we have the right team and the right strategy to maximize ZYNLONTA in the current approved indication. Now, I want to turn to the future market landscape and the important role we expect ZYNLONTA to play. Within the DLBCL market, a true standard of care only exists in the front line, with R-CHOP and recently pola R-CHIP, as well as in the academic setting in the second line with CAR-T and autologous stem cell transplant. However, accessibility to most patients treated in the community remains a challenge. The market is evolving towards highly effective combinations with off-the-shelf agents as a cornerstone. As polatuzumab moves to the front line, we expect this will create an unmet need in the market as re-treatment in the relapse/refractory setting is unlikely. With our confirmatory Phase 3 trial, LOTIS-5, our plan is to expand…

Thanks, Kristen. It's my pleasure to provide an update on our clinical stage pipeline. Starting with LOTIS-5, our Phase 3 confirmatory trial with ZYNLONTA and rituximab, we significantly accelerated the pace of enrollment in 2023, and we reported encouraging updated safety lead-in results in September. While we have been pleased with the increase in patient enrollment, our clinical team recently observed higher than expected sensory in the trial, which was confirmed with the IDMC. As a result, we may need to expand enrollment beyond the planned 350 patients to achieve the required number of pre-specified progression free survival events. Based on the current pace of enrollment, we do not expect this to affect our target to complete enrollment in 2024. Importantly, the IDMC noted no safety concerns and recommended the study to proceed at its most recent meeting held on the 16th of January 2024. Moving to LOTIS-7, this is our Phase 1b study to explore ZYNLONTA in novel combinations. We are focusing on the combination in two bispecifics arm, Roche's glofitamab and mosunetuzumab. Enrollment started in each arm in July 2023. Part 1 is a 3 plus 3 dose escalation and third line plus heavily treated patient, with ZYNLONTA doses starting at 90 microgram per kilogram, and then proceeding to 120 and 150 micrograms. As we discussed in January, we dosed the first three patients in each arm with the 90 microgram dose and cleared the dose limit to 60 period. Since that time, we have cleared the 120 microgram dose for both arms, with no DLTs and we are currently enrolling the 150 microgram dose. Once dose escalation is complete, we plan to expand at the appropriate dose levels. After the first investigator assessment, we have seen evidence of antitumor activity among the majority of patients dosed at…

Thanks, Mohamed. It's a pleasure to update you all on our research activities. As we disclosed at the start of this year, as part of our broad toolbox, we're now developing ADCs utilizing a differentiated payload based on the topoisomerase I inhibitors, exatecan, together with a novel hydrophilic linker. Compared with commercially available toxins such as the DXD platform, our innovative and proprietary approach has shown evidence in preclinical studies for greater potency, stronger bystander activity and excellent tolerability. Initially, we are conducting research utilizing our exatecan-based platform against four highly attractive targets and indications with high unmet needs. The first is Claudin-6, which is a novel target that is highly expressed in ovarian, endometrial, testicular and non-small cell lung cancer. The second target is NaPi2b, a validated ADC target, which is also highly expressed in ovarian, endometrial, and non-small cell lung cancer. The third is PSMA, which is a validated ADC target, highly expressed in metastatic castrate-resistant prostate cancer. We intend to select a clinical candidate based on a novel optimized PSMA-specific antibody. Lastly, we are applying this platform to an undisclosed target. What I can say is that the target is a novel transporter protein, which is highly expressed in multiple hematological and solid tumor malignancies. For Claudin-6, NaPi2b, and the undisclosed target, we have completed in vivo pharmacology and dose range-finding studies in cynomolgus monkey. In each case, we've seen strong antitumor activity with an attractive therapeutic index and no evidence of interstitial lung disease. Based on the encouraging initial data from these three investigational candidates, we believe we have a differentiated ADC platform that can be applied to multiple tumor targets of interest. In terms of next steps, we will share data for Claudin-6 and NaPi2b at AACR next month. The abstracts are available on the AACR website, and I would encourage you to review them. Following AACR, we plan to share additional information on our differentiated research platform at an investor event in the second quarter. With that, I would like to hand over to Pepe.

Thank you, Patrick. Before I get into the financials and outstanding catalysts, I want to remind everyone of our corporate business development strategy. Hematology continues to be our primary focus. And within this, our key objective is to drive the value of ZYNLONTA. We will achieve this by fully supporting our commercialization effort in the US directly and through our partnership ex-US. In solid tumors, our aim is to pursue multiple ADC candidates in parallel and increase our shots on goal. We will determine on a case-by-case basis whether we wish to progress candidates internally or seek to partner in order to share the development and financial risk. Turning to our fourth quarter performance, we're now reporting our results under US GAAP as we became a US domestic filer starting January 1st, 2024. Starting with our balance sheet, as of December 31st, we had cash and cash equivalents of approximately $278.6 million or a $32 million decrease from the end of Q3. Moving to the P&L, as you already heard, ZYNLONTA net sales were $16.6 million in the quarter, a decrease of 16% versus prior year, primarily driven by higher gross-to-net due to discounted drug rebate and slightly lower volume, partially offset by higher gross price. Our total operating expenses on a non-GAP basis, which excludes stock-based compensation, were down 24% compared to the fourth quarter of last year. This mainly reflected our focus on driving operating efficiencies, together with reduced R&D expenditure due to focused investment in our clinical studies and lower selling and marketing expenses. For 2024, we will continue to take a very disciplined approach to our operating expenses. This is crucial to funding the development of our key pipeline programs and maintaining our expected cash runway into the fourth quarter of 2025. You will 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. Moving to the bottom of the P&L, on a GAAP basis, we reported a net loss of $85 million for the quarter or $1.03 per basic and diluted share. This took our full year 2023 net loss to $240 million or $2.94 per basic and diluted shares. My final slide highlights the multiple potential value driving milestones which we expect in 2024. With that, I will turn the call back to Ameet.

Thanks, Pepe. To close, we entered 2024 with a clear strategic roadmap and the capabilities to drive value creation for all our stakeholders. My team and I are excited about the company's prospects and look forward to keeping you updated on our progress. Now we will be available for questions. Operator?

[Operator Instructions]. Our first question will come from the line of Naureen Quibria with Capital One Securities.

Congrats on the progress. Actually, I was just curious about LOTIS-7. Can you talk about the safety data with bispecifics in combination to date, and what's been seen with other therapies? And relative to that, can you speak to your expectation for LOTIS-7, your level of confidence for this combination? And just on the same topic, you mentioned on the press release that you have a larger data set. You present – I mean, you have a larger data set. Can you just talk about sort of the size and scope of that data set that you would expect to release if it's after the 120 microgram data? Appreciate some granularity.

Maybe I'll turn it over to Mohamed to answer both those questions on the safety profile and what we're hoping for and what we've been seeing as well as on – yeah, so, Mohamed, do you want to take it?

With regard to LOTIS-7, as you know, it's a dose escalation study of combination of the ZYNLONTA plus two different bispecification, glofitamab and mosunetuzumab in three different disease types, marginal zone, DLPCL, and follicular in third line plus. We are very encouraged by the fact that we have cleared the first dose levels, the 90 microgram per kg and the 120 microgram with no DLTs. And all we have seen so far is either no CRS or low-grade CRS that resolves very quickly. We are very encouraged by the anti-tumor activity we keep seeing in the study to date. It's an open-label study and we see things live. However, it's early days, and we would like to wait until we have more mature data to be able to share more mature cohorts later this year. I think that pretty much answers your question.

Maybe just one thing to add. We're now currently dosing the 150 microgram per kilogram dose in both the glofitamab and the mosunetuzumab arm. Once those are cleared, we'll move right into the dose expansion in second line plus DLBCL with glofitamab. And that'll be the focus. That's where I think we're going to get a better representation of efficacy when we have a broader number of patients, longer follow-up, and in a single histology. And that's really the focus of part two of the study, which we will start as soon as we clear the dose escalation.

I guess I have one for Kristen, and then I'll hop back in the queue. Just curious in terms of the penetration levels with the ZYNLONTA in the academic and community settings, what are those? Can you comment on that, number one? And number two, can you talk about what you saw in terms of how were you able to increase growth in academics, just out of curiosity?

We don't share exact numbers of penetration. What I can tell you is that we had a strong foundation in the first couple of years of launch and within the academic setting. In 2023, starting in Q2, we really refined our strategy to focus more on the community. Our strategy of driving adoption with the community played out well, and we started to see the impact of that in Q4 2023. So not only did we see more community sites adapt ZYNLONTA, but actually, we also saw an increase in volume in the academic centers as well, post the entrance of two bispecifics. So we see this increased demand, and I would say in November and December, we started to see our demand levels come back to what we saw in the first half of 2023, and we look forward to driving progressive growth with ZYNLONTA with this refined strategy.

Our next question comes from the line of Brian Cheng with J.P. Morgan.

Just a couple. On LOTIS-5, can you talk about a little bit more about the censoring that you mentioned on the call? Specifically, what is the reason for the higher than expected censoring in LOTIS-5? And how much of that is due to safety-related withdrawal? And I have a couple questions left.

Mohamed, do you want to talk about LOTIS-5 and censoring?

Just want to highlight that it is not uncommon for initiate the need for increased enrollment in a global open label Phase 3. It's also not uncommon to see a little bit higher censoring when you are dealing with the relapsed/refractory diseases. The main reason we believe, or for the higher than ever censoring, is the lack of convenience from physicians and patients with relation to the control arm, possibly. And that's usually because the physicians usually want to be in the active arm, of course. So, you can expect to see a little bit higher than usual. And there was no concerns by the DMC that met in January with regard to any safety issue that is not related to any safety reason or anything related to do. But it is very important, this is simply replacing possibly missing events to reach the required number of events, clear the [indiscernible] to reach the end of the study. So, it's a replacement procedure that many Phase 3s do in order to make sure they get that on time. The good news is that, even with possible increase in the size of this trial, we do not anticipate to have a delay on finishing enrollment, which we have communicated to be within 2024. The reason for that is, recently, we have observed an acceleration of enrollment and we've seen really a quite high number of enrollments per month compared to month before.

Going back to your comment related to commercial branded profitability later this year, what does that actually entail? Can you talk about the gross-to-net we should expect in our model? And related to SG&A expenses, how should we model that for the rest of the year?

Pepe, do you want to take that in terms of gross-to-net evolution? What commercial brand profitability means and the evolution of SG&A?

On brand profitability, what we expect this year is that the revenues coming out of ZYNLONTA in the US will be able to pay for all the expenses directly related to commercializing ZYNLONTA, which means all the sales force, marketing team, medical science liaison, and all discretionary spending, which would include A&P, cost of goods, IIT, and other related expenses. So, basically, from a capital allocation perspective, commercializing ZYNLONTA is not a usage of fund. It's more like a source of funds to start funding the pipeline. For modeling purposes, gross to net, if you've heard our messages in 2023, from the first half to the second half of the year, our gross to net increased a high single digit percentage point. We expect that 2024 will have a similar gross-to-net ratio that we had in the second half of 2023. So, we don't expect further increases, but as you model it in the first half of 2024, we'll be fighting over a higher gross to net than what we saw in the first half of 2023, like that same percentage points. So, high single digit increase in the first half of 2024 compared to prior year, but it will be more even in the second half of 2024 compared to the second half 2023. From an expenses perspective, we will continue to drive productivity measures. We are not providing exact guidance on all OpEx levels, but we will keep driving productivity across the board. Importantly, this year, the highest investment level that we have is in LOTIS-5, [indiscernible] trial for ZYNLONTA, which we expect full enrollment this year. So as the full enrollment happens and then the trial winds down into 2025, we expect a decrease of R&D expenses due to LOTIS-5. All that depends obviously on the success of the other trials, but that's the biggest driver of R&D expenses this year, which will decrease as we launch 2025.

And our next question comes from the line of Gregory Renza with RBC Capital Markets.

Congrats on the progress. Maybe just building on the commercial strategy. Amet, it's helpful to hear the color of the pull through from the fourth quarter. Just curious if the CD20 bispecific combination was within those expectations and any factors that we should be thinking about going beyond what Kristen and Pepe had indicated on the dynamics of uptake for 2024. And maybe just related to that, if I may, as we think about the longer term opportunity for late line, just curious if you have any updated thoughts on ZYNLONTA's positioning just relative to ADC based combinations and third line. I certainly saw the ECHELON-3, et cetera, triplet meeting its OS endpoint improvement regardless of CD30 expressions. Just curious if you had any updated thoughts on those evolving dynamics as well.

I'll start and then I'll pass it on to Kristen and Mohamed in case they have additional comments. But, yeah, I would say overall bispecifics are definitely gaining ground in that third line setting post CAR-T. You saw there was strong growth. While CAR-Ts are basically kind of flattening out right now when you look at – out of the sales of all the CAR-T [Technical Difficulty] in Q4 versus Q3 is kind of flattening out. Bispecifics continue to grow dynamically and the uptake, particularly in the academic setting, continues to grow. In the community setting, while they've been used in more sophisticated centers, the uptake there is much more limited. I think what we found though is that there's a clear place for ZYNLONTA, either for patients where a bispecific is not suitable, where a patient may need even faster responses for ones that progress post their bispecifics because it doesn't work for every patient. So I think academic positions have sort of figured out how to best use ZYNLONTA around a dynamic where there is a new competitor and when bispecifics are growing. So we saw part of that rebound because I think, in Q3, where there was a big push towards just bispecifics, in Q4 we saw that ZYNLONTA continued to be used with those that progressed or those who were not as suitable as doctors sort of figure out the best patients to go to a bispecific post a CAR-T. In terms of the competitive landscape, I think the whole space is moving towards combinations. I think one of the advances we have is that we're approved as a single agent and we have strong single agent activity. Not many drugs that have been approved as a single agent. In fact, the bispecifics and ZYNLONTA are two of the only drugs [Technical Difficulty] that have been approved as single agents. And so, I think our combination strategy with both LOTIS-5 and LOTIS-7 position us really well. I think we'll have competitive profiles with those two combinations that, in spite of an evolving landscape, will position us really well for growth not only in the third line setting where we are today, but also in the second line setting where we will move with those trials. Kristen and Mohamed, is there anything else that I missed that you would add?

The only thing that I would add, two things. One, just to add on to your evolving landscape, we see already with polatuzumab moving up to the front line that it is creating a need for a different mechanism in the second line and third line. So definitely carving out a space for ZYNLONTA, whether it's today or in combination once we get LOTIS-5 and LOTIS-7. The other question was around ECHELON-3. We also saw that. We've been tracking – we always track our marketplace and the dynamics. And one, it's nice to see a win for an ADC. It reinforces the efficacy of ADCs. But, two, we haven't seen any data on that trial other than the headline that Pfizer put out in terms of the overall survival win. R squared is used. It's pretty uncommon use, primarily in the community, but still we'd love to see the data that Pfizer has on their triplet versus the doublet and look forward to that, so that we can better put it into context and understand any impact in the market.

If I may ask, Kristen, also regarding the [indiscernible] story, is that we need to see how the control arm in the trial actually did to be able to better evaluate the data and understand it better. Specifically, this is in third line plus, if I understand the trial correctly. Our target is for LOTIS-5 and the potential to see this to go to second line plus. So it's not directly, but in a very minimal number of patients. And when you get to third or fourth line, there may be some combo. However, we don't know that in details, of course, to be able to understand it better.

Ameet, maybe just a follow up as Patrick has discussed the NextGen platform. Just wondering – and we all look forward to an event later this year, as you mentioned. Just wonder if you could elaborate a bit on just the rationale for selecting NaPi2b, Claudin, and PSMA just for the NextGen ADCs. And do you have a sense at this point which targets or target has the strongest rationale for internal versus the external partnerships that Pepe alluded to?

Maybe, Patrick, do you want to take the first part of the question? And then, Pepe, you can take the second part of the question around partnering.

We have selected these targets because we think that they fulfill all the criteria for good ADC targets. If you look at what's known for them, it's clear that for each and every target, there's a very good level of validation for targeted approach. Of course, they're all expressed in indications with high unmet need. And we also very carefully looked at the competitive landscape for NaPi2b, Claudin-6, PSMA and the undisclosed targets. And we believe that, in most cases, if not all, we're among the first three to four players studying those targets. But, of course, with a differentiated approach using our novel exatecan-based platform. So to us, that means they really are attractive targets to work on.

Let me take the partners discussion. So as we disclosed, the next generation exatecan-based payload and the target earlier this year in January 4th, we did an outreach with several companies and we already started some discussions. These conversations and that potential partnership takes a few quarters. So it's not something that you would do in a short turnaround. But we do see the interest and we will continue to advance those conversations for potential partnerships this year.

[Operator Instructions]. Our next question comes from the line of Kelly Shi with Jefferies.

This is [indiscernible] for Kelly. First question, just wanted to confirm that – is safety the only thing that you need to clear before moving into second line? And when would you expect to have any data available from second line patient? Secondly, for AXL study, can you remind us if you enroll patient based on expression and we have that biomarker data available when the data is presented at AACR?

Yes, in terms of the expectation from LOTIS-7 dose escalation is to clear the dose levels. And based on that, [indiscernible] protocol, we are allowed to move directly to second line for expansion. We're expecting to share information focused on safety in the second quarter and more on the expansion of second line in DLBCL specifically in later in 2024. In terms of AXL, so far our enrollment is not with a pre-selection strategy. However, as of the pancreatic enrollment will be enrichment and for non-small cell lung cancer we will be pre-selecting.

At this time, I'm showing no further questions. I'd like to hand the conference back over to Mr. Mallik for closing remarks.

Yeah, thanks all for your attention and interest in ADC Therapeutics. Between now and our next earnings call, we expect to share some important updates on LOTIS-7, on the futility analysis and top line data of ZYNLONTA as a single agent in marginal zone lymphoma, and on data being presented at AACR which we will follow up with a research investor event. As such, we look forward to multiple interactions with you in the coming months. With that, I would like to close the call. Thank you all.

This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day.