ADC Therapeutics SA

Welcome to the ADC Therapeutics fourth quarter and full year 2023 Financial Results Conference call. My name is Norma, and I'll 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. During the question and answer session, if you have a question, please press star 1-1 on your touchtone telephone. I will now turn the call over to Nicole Riley, head of communications. Nicole, you may 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, Amit Malik, Chief Executive Officer, Kristen Harrington-Smith, Chief Commercial Officer, Mohammad Zaki, Chief Medical Officer, Patrick VanBurkel, 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 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 today's press release, in the accompanying slide presentation on slide two, 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, Amit Malik. Amit?

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 de-risked asset in Zynlanta, 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 Zynlanta 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 Zinlanta franchise and have the potential to generate annual peak sales in excess of half a billion dollars. The second pillar of our strategy is grounded in our emerging solid tumor pipeline. Our most advanced asset is ADCT601, 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 externally, supported by non-dilutive funding from partners. Across each of our presenters today, you will hear about how we are putting this strategy into action, whether through enhancing our commercial execution, prioritizing and accelerating our most promising pipeline assets, advancing high potential early stage research programs, or through our capital allocation strategy. Now I'd like to expand briefly on the substantially larger potential opportunity that I just mentioned for Zymanta in earlier lines of DLBCL therapy and indolent lymphomas. Pending the results of the LOTUS 5 and LOTUS 7 studies, our goal is to expand usage of Zymanta into second line and second line plus DLBCL. Furthermore, if data supports expansion into the second line and second line plus settings of follicular lymphoma, and marginal zone lymphoma, we believe this would further increase the potential for this product. Now I'd like to share a snapshot of the business updates you'll hear about today. I'm pleased to confirm that Zanlanta achieved double-digit sequential sales growth in the fourth quarter with revenues of $16.6 million. Importantly, we saw a resumption of growth both in the community and in academic centers. We were also delighted to share positive pipeline news at the start of this year. For our Lotus 7 study of Xanlanta in combination with bispecifics, we shared early data from the first dosing cohort. Since that time, we have successfully cleared the second dosing cohort in both arms with no dose-limiting toxicities. We are encouraged by what we have observed with ADCT601, our novel axle-targeting ADC in sarcoma, and a recently initiated screening in pancreatic cancer patients. Lastly, we disclosed that we are advancing an early-stage portfolio of investigational ADCs, which utilize a novel Exotecan-based platform. Turning to our financial position, we ended 2023 with close to $280 million of cash. Together with our business plans and strict cost discipline, this provides us with an expected cash runway into Q4 2025. which will support us through multiple value-generating catalysts this year and next. So taken together, we enter 2024 with great confidence, having repositioned and refocused the company, and with some encouraging early data emerging from our pipeline. With that, I would like to turn the call over to Kristen for a commercial update. Kristen?

Thanks, Amit. Today, our strategy is to grow Zinlanta 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 T's or by specifics or who have progressed following treatment with these complex therapies. Our strategy is supported by real world data as presented at the recent TANDA meeting. which demonstrated Zinlanza's efficacy pre and post CAR T. Execution against our strategy was a fundamental driver for our commercial restructuring and resulted in higher Zinlanza 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 Zinlanta. We are confident we have the right team and the right strategy to maximize Zinlanta in the current approved indication. Now I want to turn to the future market landscape and the important role we expect Zinlanta 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, an 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 relapsed refractory setting is unlikely. With our confirmatory phase three trial, Lotus 5, our plan is to expand the Zinlanta label to the second line, second line plus. We have a tremendous opportunity to build share in this broader patient population if this study continues to deliver the competitive efficacy that we have already observed with Zinlanta in combination with rituximab in the 20 patient safety run-ins. These data, coupled with the potential advantages of accessibility, ease of use, and manageable tolerability, lead us to believe the results from Lotus 5 will help to cement Zinlanta as a standard of care in the Second Line, Second Line Plus among community centers where R-based regimens are commonly used across all lines of therapy. In addition, these data have the potential to expand the use of Zinlanta in both the Second Line and third-line, third-line plus academic settings when an alternative to CAR-T and or bispecifics is needed. Moving to Lotus 7, our Phase 1b trial evaluating Zinlanta in combination with bispecifics. As we progress this development program forward, our objective is to demonstrate that the combination can deliver enhanced efficacy compared to bispecifics alone, which could significantly expand Zinlanta use. In addition, we hope to demonstrate that Zinlanta, when compared with bispecifics, can reduce levels of CRS and eliminate the need for hospitalizations, expanding accessibility in the community. Ultimately, if successful, this combination has the potential to transform the treatment paradigm in the second line across both settings and substantially enhancing the patient and commercial opportunity for Zinlanta. And now, I would like to turn the call over to Mohamed for a clinical update.

Thanks, Kristen. It's my pleasure to provide an update on our clinical stage pipeline. Starting with Lotus 5, our phase 3 confirmatory trial with Zinlanta and rituximab, we significantly accelerated the patient 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 Routes 7, this is our Phase 1b study to explore Zanonta in novel combinations. We are focusing on the combination in two biospecific ARB, Roches, Grafittimab, and Mucinthizumab. Enrollment started in each arm in July 2023. Part one is a three plus three dose escalation and third line plus heavily pre-treated patient with the long-term 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 periods. 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 those escalation is complete, we plan to expand at the appropriate dose levels. After the first investigator assessment, we have seen evidence of anti-tumor activity among the majority of patients, those at the first two level, with mixed histologists including DLBCL, follicular lymphoma, and marginal zone lymphoma. We expect to share additional data once a larger and more mature data set is available. While we are excited about what we have seen, we recognize that it is early And once those expansion in second line is complete and assuming data are promising, we plan to approach regulatory agencies to discuss our strategy and potential path forward. Beyond our own studies, there is a significant amount of interest from investigators to explore Zalanta in additional indications and combinations. At ASH in December 2023, There was an oral presentation from the University of Miami on their investigator-initiated phase two study of the Lanta and rituximab in patients with high-risk relapsed or refractory follicular lymphoma. There's a unique population not served well by the current standard of care. Initial results from the 33 patients were very encouraging. including a best overall response rate of 96% and a complete response rate of 85%. In terms of safety, the majority of adverse events were primarily grade 1 and manageable. The presentation was extremely well received by the physician community, and the trial is now being expanded to other centers with a target enrollment of 100 patients. The University of Miami is also conducting another investigator-initiated Phase II study of the long-term interlapsed refractive marginal zone lymphoma, an indication with significant unmet needs. The study is designed to enroll 50 patients, and a futility analysis is expected to be conducted in the second quarter of this year. We anticipate the investigators will present the data from both studies at upcoming medical meetings. If these investigator-shared trials are positive, we would move quickly to determine the regulatory and or compendia path forward. I want to turn now to our solo tumor candidate, ADCT601 targeting Axel, which we are investigating in a phase one study in sarcoma, pancreatic cancer, and non-small cell-line cancer. While others have explored Axel as a therapeutic target, We are especially excited by the potentially differentiated profile we see with the 601D2, its innovative design of incorporating a PBD toxin. Axel is expressed in multiple tumor types, and it has been shown that high expression of Axel is correlated to worse patients overall survival across many cancer types, including non-small cell line cancer, pancreatic, and sarcoma. Our phase one trial includes monotherapy as well as combination arms with gemcitabine in sarcoma and pancreatic cancer. Giving the high level of action expression sarcoma is serving as the proof of concept. In January, we disclosed that we reached the recommended dose of 13 milligrams. In addition, we also share that ADCT601 was well tolerated at the doses tested, and we have been encouraged by the early signs of anti-tumor activity in both monotherapy and combination. The study is currently in part two, which includes dose optimization and expansion. We plan to share additional data from the trial in a presentation at ACR next month for which abstract is now available online. With regard to the other indications, I am pleased to report that we have initiated screening in the pancreatic cancer monotherapy arm based on an enriched patient population. We also plan to initiate dosing in the non-small cell line cancer preselected patients once we have optimized the assay for non-small cell line cancer. I am encouraged by the progress we are making with our pipeline and look forward to sharing more in the future. I would now like to hand over to Patrick.

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-1 inhibitor exotecan, 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 of greater potency, stronger biocenter activity, and excellent tolerability. Initially, we are conducting research utilizing our exotecan-based platform against four highly attractive targets and indications with high unmet needs. The first is Chlordon-6, which is a novel target that is highly expressed in ovarian, endometrial, testicular, and non-small cell lung cancer. The second target is NEPI-2B, 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 CLAUDON6, NAPI2B, and the undisclosed target, we have completed in vivo pharmacology and those range-finding studies in cinnamogus monkeys. In each case, we've seen strong anti-tumor 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 Chlorbent6 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 wishes 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 upcoming catalyst, 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 Zin London. We will achieve this by fully supporting our commercialization effort in the U.S. directly and through our partnership ex-U.S. 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 U.S. GAAP as we became a U.S. 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, the long-term net sales were $16.6 million in the quarter, a decrease of 16% versus prior year, primarily driven by higher gross net due to discarded drug rebate and sliding lower volume, partially offset by higher gross price. Our total operating expenses on a non-GAAP 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 gap measures to non-gap 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 a $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 Amit.

Thanks, Pepe. To close, we enter 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?

Thank you. As a reminder, to ask your question, you'll need to press star 11 on your telephone. To withdraw your question, please press star 11 again. Please wait for your name to be announced. Please stand by while we compile the Q&A roster. One moment for our first question. Our first question will come from the line of Noreen Cabrera with Capital One Securities. Your line is now open.

Hi, good morning. Thanks for taking my question and questions, actually. And congrats on the progress. So actually, I was just curious about Lotus 7. You know, can you talk about the safety data with bispecifics, you know, in combination to date and, you know, what's been seen with other therapies? And relative to that, you know, can you speak to your expectation for Lotus 7, you know, your level of confidence for this combination? And just on the same topic, you know, you mentioned... on the press release, that you have a larger data set, you present when you have a larger data set, you know, can you just talk about sort of the size and scope of that data set that you would expect to release, you know, is it after the 120 microgram data? Appreciate some great hilarity. Thank you.

Thanks, Noreen. I really appreciated it. 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?

Sure.

Thanks, Amit. Thanks for answering the question. With regard to RUCA7, as you know, it's a dose escalation study of combination of the LONTAP plus two different bispecific agents, pitonap and centuzanap, in three different disease types, marginal zone, DLBCL, and follicular. in third line plus. We are very encouraged by the fact that we have cleared the first two of those levels, the 90 microgram per keg and the 120 microgram with no DLTs. And all we've seen so far is either no CRS or low-grade CRS that resolved very quickly. We are very encouraged by the anti-tuber activity we keep seeing in this study today. 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's pretty much it. answers to your question. I hope I didn't miss exactly, kind of multiple points, Noreen, so I hope I didn't miss anything.

Yeah, Noreen, and maybe just one thing to add. Thanks, Mohamed. You know, we're now currently dosing the 150 microgram per kilogram dose in both the glufidamab and the mosentuzumab arm. Once those are cleared, we'll move right into the dose expansion in second line plus DLBCL with glufidamab, 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.

Perfect. And I guess I have one for Kristen, and then I'll hop back in the queue. I'm just curious in terms of, you know, the penetration levels with the Zedlanta 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?

Sure. Thanks, Noreen. So we don't share exact numbers of penetration. What I can tell you is that we had a strong foundation in the first a 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 in Lhasa, but actually we also saw an increase in volume in the academic centers as well. post the entrance of two biospecifics. 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 Sinlanta with this refined strategy.

Great. Thank you so much. I'll hop back in with you. Thanks.

Thank you. One moment for our next question, please. Our next question comes from the line of Brian Chen with JP Morgan. Your line is now open.

Hey, guys. Thanks for taking our questions this morning. Just a couple. On Lotus 5, can you talk 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 Lotus 5, and how much of that is due to safety-related withdrawal? And I have a couple of questions left. Thanks.

Thanks, Brian. Appreciate it. So, Mohamed, do you want to talk about Lotus 5 and censoring?

Yes. So, thanks for the questions, Brian. And I just want to highlight that it is not uncommon for initiatives, the need for increased enrollment in a global open-label phase 3. It's also not uncommon to see a bit higher censoring when you are dealing with the less refractory diseases. The main reason, we believe, for the higher than average surgery is the lack of convenience from physicians and patients with relations to the control arm, possibly. And that's usually because the physician doesn't 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 DNC 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 statistical analysis plan to reach the end of the study. So it's a replacement procedure that many, is due in order to make sure they get that on time. The good news is that even with possible increase in the size of the 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 enrollment per month compared to month before.

Great. And then going back to your comment related to commercial brand profitability later this year, what does that actually entail? You know, can you talk about the growth that we should expect in our model? And, you know, related to SG&A expenses, how should we model that, you know, for the rest of the year? Thanks.

Okay. Yeah, thanks, Brian. Pepe, do you want to take that in terms of gross and net evolution, what commercial brand profitability means and the evolution of SG&A?

Yeah. Thank you, Brian, for the question. On brand profitability, what we expect this year is that the revenues coming out of Zinlonta in the U.S. will be able to pay for all the expenses directly related to commercializing Zinlonta, 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, the commercial items in LONTA is not a uses of funds. It's more like a sources of funds to start funding the pipeline. For modeling purposes, gross net, if you heard our messages in 2023, from the first half to the second half of the year, our gross net increased a high single digit percentage point. we expect that 2024 will have a similar gross net ratio that we have 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 cycling over higher gross remit than what we saw in the first half of 2023 by that same percentage point. 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 of 2023. From an expenses perspective, we will continue to drive productivity measures. We're 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 models five. which we expect full enrollment this year. So after full enrollment happens and then the trial winds down into 2025, we expect a decrease of RMB expenses due to a lot of style. All that depends obviously on the success of the other trials, but that's the biggest driver of the expenses this year, which will decrease as we go on to 2025.

Do you have any other questions?

Thank you. One moment for our next question, please. And our next question comes from the line of Gregory Renza with RBC Capital Markets. Your line is now open.

Hey, good morning. I'm meeting the team. Congrats on the progress. Thanks for the updates and for the questions. Maybe just building on the commercial strategy, Amit, it's helpful to hear the color of the poll through from the fourth quarter. Just curious if the CD20 buy-specific competition was within those expectations and, you know, 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 Zolotis positioning just relative to ADC-based combinations and third line. I certainly saw the Echelon 3, etc. triplet meeting its OS endpoint improvement regardless of CD30 expression. So, just curious if you had any updated thoughts on those evolving dynamics as well. Thanks so much.

Yeah, I'll start, and then I'll pass it on to Kristin and Mohamed in case they have additional comments. Yeah, I would say, you know, overall, bi-specifics 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, you know, out of the sales of all the CAR-T, you know, agents in Q4 versus Q3, it's kind of flattening out. Bi-specifics continue to grow dynamically and the uptake, particularly in the academic settings, 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 Xanlanta, you know, either for patients where a bisuic is not suitable, where a patient may need, you know, even faster responses for ones that progress post-bisuic because it doesn't work for every patient. So I think academic physicians have sort of figured out how to best use Xanlanta around where there is a new competitor and, you know, when bi-specifics are growing. So we saw part of that rebound because I think, you know, in Q3 where there was a big push towards just bi-specifics, in Q4 we saw that Synlata 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 bi-specific close to CAR-T. And then in terms of the competitive landscape, I think the whole space is moving towards combinations, you know, I think one of the advantages we have is that we're approved as a single agent and we have strong single agent activities. Not many drugs that have been approved as a single agent. In fact, the bispecifics and Zinlant are two of the only drugs, classes that have been approved as single agents. And so I think our combination strategy with both Lotus 5 and Lotus 7 positioned us really well. I think we'll have competitive profiles with those two combinations. But in spite of an evolving landscape, you know, 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, Amit, two things. One, just to add on to your evolving landscape, we see already with Politizumab 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 Ximanta whether it's today or in combination once we get Lotus 5 and Lotus 7. The other question was around Echelon 3. We also saw that. We've been tracking. We always track our marketplace and the dynamics. 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. You know, 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 add, Kristen, also regarding the African 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 plot if I understand the trial correctly. Our target is for LUTAS 5 and potential facilities 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 . However, we don't know the data yet to be able to, in details, of course, to be able to understand it better.

That's really helpful. And I mean, maybe just a follow-up is Patrick has discussed the next-gen. platform. Just wondering, and we all look forward to an event later this year, as you've mentioned, just wondering if you could elaborate a bit on just the rationale for selecting NAPI 2B, the Quad, and PSMA just for the next-gen 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? Thanks again.

Yeah, so 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.

Sure, Amit. Yeah, thanks, Brian. So 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 a targeted approach. Of course, they're all expressed in indications with high and mid-need. And we also very carefully looked at the competitive landscape for FB2B, CloudN6, 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 extrateam-based platform. So, to us, that means there are attractive targets to work on.

And let me take the partnership discussion. So as we disclose the next generation exotican-based payload and the targets 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 It takes a few quarters, so it's not something that you would do in a short turnaround. We do see the interest, and we will continue to advance those conversations for potential partnerships this year.

Got it. Thanks again, guys.

Thank you. As a reminder, to ask a question, that's star 11, and please wait for your name to be announced. Our next question comes from the line of Kelly Shi with Jefferies. Your line is now open.

Hi. Good morning. Thank you very much for taking the question. This is Yun for Kelly. So first question, this one is 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? And then secondly, for XL study, Can you remind us if you enrolled patients based on expression and we have that biomarker data available when the data is presented at AACR? Thank you.

Thanks for the question. And yes, in terms of the The expectation from Lotus 7 dose escalation is to clear the dose levels and based on that, that per 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 Axel, so far our enrollment is not with a pre-selection strategy. However, as of the pancreatic enrollment, we will be enrichment, and for non-small cell-like cancer, we will be pre-selecting.

I'm showing no further questions. I'd like to hand the conference back over to Mr. Malik for closing remarks.

Thanks all for your attention and interest in ABC Therapeutics. Between now and our next earnings call, we expect to share some important updates and a lot of seven on the fidelity analysis and top-line data of Simlanta as a single agent in margin of zoning format. And on data being presented at AACR, which we will follow up with a research investor event. 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.