Zai Lab 2026 ESMO Investor Call - ZAI LAB LTD

Hello, everyone, and thank you for joining us for the presentation of the results from our Phase I study evaluating SOZI, our DLL-3-targeted ADC in combination with atezolizumab with or without carboclatin in small cell lung cancer. The results we're sharing today strengthen our confidence in SOZIs' potential and support her global development strategy in frontline. Please refer to our forward-looking statements in slide 2. Here on slide 3 is our agenda. I'm very pleased to have Dr. Pedro Rocha join me today. He's a medical oncologist and clinical researcher specializing in thoracic malignancies, including small cell lung cancer, at Valdebron University Hospital in Barcelona. I will start with brief comments on our global portfolio and the characteristics of SOSI. Dr. Rocha will then take us to the highlights from and we will end with a question and answer session. Please see slide four for Dr. Rocha's disclosure information. Before heading into the data, here's a snapshot of our global pipeline in oncology and immunology. Our lead oncology asset is SOSI, and we're entering a pivotal period in SOSIs development with three registrational trials expected to be underway by the end of the year, namely the ongoing second-line trial in small cell lung cancer DELEVATE, second-line extrapulmonary NEC, and first-line small cell lung cancer. Our focus is on strong clinical execution and generating the data needed to realize dose's full potential. In immunology, our long-acting IL-13, IL-31 receptor alpha by specific, called ZL-15L3, is approaching its first clinical data readout next month. We believe this combination of dual pathway inhibition and potentially extended dosing intervals could offer meaningful differentiation in atopic dermatitis and potential other inflammatory diseases. Turning to SOCI, SOCI is a DLS-3-targeted antibody drug conjugate with high picomolar binding affinity, a potent topoisomerase-1 inhibitor payload, and a drug-to-antibody ratio of 8. The linker is cleavable, which means that the payload can be released not only inside the tumor cells, but also in the surrounding tumor microenvironment, resulting in a strong bystander effect. This design allows DOSI to have potent tumor killing while maintaining a favorable safety profile, and we're seeing this translate into meaningful clinical activity. Now, we recognize that small cell lung cancer is an increasingly competitive field, but when you look at the totality of the data, we believe DOSi has important clinical properties that make it an agency of choice in this disease. As a monotherapy in second-line plus small cell lung cancer, SOSI has demonstrated high response rates with good durability, as well as robust intracranial activity, including in patients with untreated brain metastases. ADCs have a narrow therapeutic window, and that is why it is important to emphasize SOSIs safety. We believe it has the potential for best in class tolerability and even among ADCs in this space and therefore allows monotherapy and combination development approaches. This is particularly important as we move into the frontline setting where the future of treatment will be built on new combination regimens. Tolerability will be a critical determinant of which ADC can become the backbone of choice whether with IO or other agents including diesel engagers. We are already working with our partners VI and Amgen to realize the potential of these combinations as the standard of care in small cell lung cancer continues to evolve, thereby developing SOSI as a key product that will further differentiate it from others in the class. And with that, I will hand it over to Dr. Rocha for the clinical data. Thank you, Rafael. And now I will be presenting results from the phase one study evaluating SOSi in combination with ATISO plus or minus carboplatin, what we call it doublet or triplet cohort. So on this slide, we can see our study design, which includes dose escalation and backfill and expansion cohorts for the doublet combination. So we see plus ATISOs. And as you can see also here, we will focus on this, what we have in the red squares on the backfield expansion for the doublet, and we also present some results on the triplet. On the next slide, we can see the baseline characteristics for the population included. three-quarters at stage four disease at initial diagnosis. Most were ECOG1, and this perhaps reflects that usually these patients are symptomatic and need treatment that can reduce the tumor burden. And also highly important will be the presence of brain metastasis that, that, as a reminder, this study includes the patients with untreated brain metastasis. The doublet population was predominantly Asian, while the triplet was more balanced, and this was related perhaps with the initial study that includes a lot of patients from Asia. It is true that if we take into account the study and also the efficacy on second and plus lines from DOSI, we have not observed a difference in efficacy or safety between Asian and non-Asian patients. And also here highlighting that for the first 15 patients treated with 1.6 mg SKEG doublet, the median follow-up was 10 months. At the 1.2 milligram kick dose level, the median follow-up was 12.6 months. And with that context, the next slide, we can see the waterfall plot for the doublet-first-line combination. And as you can see here, this slide shows the efficacy from SOC plus a T-cell isomalase-first line. overall, the confirmed objective response rate was 81.4%, and nearly all patients had a response of stable disease. In particular, among the 33 patients treated with OSI at 1.6 mg Kg in combination with a TISO, 27 patients achieved a confirmed response, an objective response rate of 81.80 percent and taking account the standard of care chemoplasm immunotherapy this compares favorably which for the standard-of-care we can think about a 60 to 68 percent of response rate on the next slide we can also see a spider plot where we are seeing those responses occur early this is also something that is clinically relevant of 35 responders 34 achieved their response at the first post baseline tumor assessment so what we are seeing is a very rapid onset of response with this combination and importantly as you can see with some errors that those responses are still ongoing And if we put it, again, in context of the standard of care that we have currently, usually the patients with small cell cancer, the disease progresses quickly within the first five months. So this is something that is very positive from this combination. For the 10 patients treated with 1.2 milligram KIG, the duration of response was 8.3 months. And for the first 15 patients at 1.6 mg KIGS with a medium of 10 months of follow-up, the medium duration of response was not reached. So, this is very, very encouraging results. The progression-free survival of all 33 patients at the 1.5 mg Kig cohort. The six-month progression-free survival was 81.9%, which is a very promising result. For the first 15 patients with longer follow-up, medium progression- free survival has not yet been reached, and two-thirds of those patients have not progressed as a DAT of cutoff. The 18 additional patients in the expression cohort demonstrated an encouraging early progression- progression-free survival consistent with the initial 15 patients. For reference, the six-month progression- free survival with chemoimmunotherapy in the EMPOWER-133 was around 30%. And clearly, these results could change how we think about the first-line small cell and cancer treatment. On the next slide, we also evaluate the SOCI as a triplet in combination with a TISO plus carboplatin and despite the small sample size we can see a very notable anti-tumor activity with a confirmed objective response rate of 92.3 percent and as you can see a important tumor reduction right with patients achieving almost a complete response And this is, again, as in the doublet, this tumor reduction is quite important in our patients that most of the times are very symptomatic at diagnosis. Again, if we look at the durability of this tumor rejection with a triplet, we can also see this is observed within the first tumor assessment. So very rapid, deep, and again, with a sustained tumor reduction with a triplet. On the next slide, also important is the safety as a doublet, as a first-line therapy. So if the febrile durability we have observed with OCM monotherapy previously in patients with second and plus lines is continuing to be encouraging in this first- line doublet. are no dose-limiting toxicities observed during dose escalation. And at 1.6 milligram kick in 33 patients, only 9.1 percent of patients experience grade 3 or higher adverse events attributed to ZOSIC. We only observed one case of grade 1 ILD, and this is relevant in the context of other ADCs in the field in small cell and cancer that we are seeing higher rates of ILD and there were no socio-related treatment discontinuations or treatment related deaths reported in this court and this is something that deserves to be highlighted compared with other drugs currently being explored in small cells. Although it's also true that these data are still maturing but I believe that the ZOSI safety profile will be consistent with what we have seen in ZOSIMONI therapy where we have a longer follow-up. So, the conclusions in the doublet part seems that adding a T-zoosimab does not seem to change the safety profile of ZOSi. On the next slide, we have the safety of the triplet as first-line therapy, and in comparison, And in comparison, while the triplet demonstrated higher antitumor activity, as we've seen before, it also resulted in substantially more toxicity than the doublet. Serious drug-related adverse events and grade 3 or 4 toxicities were more common with the triplets than with the doublets. So we acknowledge that the addition of carboplatin is bringing more toxicity to our patients. and we also saw more frequent treatment interruptions primarily in the context of increased hematological toxicity this is something that we expect with carboplatin what we think in normal current clinical practice and the next slide i guess with this tornado plot clearly shows the difference between the adverse events on the safety profile from the doublet and and the triplet and And as you can see, the most common treatment-related events with the doublet were anemia, nausea, and lycopenia, although mainly grade 1, 2. And with addition of carboplatin, we saw greater hematological toxicity, particularly neutropenia and trobacitopenia, which is consistent, as I was saying before, consistent with what we would expect from adding a platinum-based chemotherapy, and it's very similar to what we are seeing in clinical practice. Again, the numbers are small, and longer follow-up remains important, but the low severity of the events observed with the doublet thus far is encouraging. And this is my last slide as a conclusion. In summary, our data demonstrated Zosie at 1.6 mg Kg in combination with atezolizumab has shown high response rates, rapid onset of this response, and encouraging durability in the first-line treatment of extensive stage small cell lung cancer. Overall, these findings provide a strong clinical rationale for further evaluating ZOZ-plus immunotherapy as a potential first-time treatment option for patients with extensive stage, small cell, and cancer. And I guess with that, I would like to pass it back over to Rafael. Thank you. Thank you, Dr. Rocha. Now let me put this resource into the context of how first-line small cell lung cancer treatment is evolving. Today's standard of care is platinum etoposide chemotherapy plus immunotherapy with LURVI maintenance approved, but not very commonly used. The emergence of Tarlatamab maintenance introduces another important advancement, but we believe there is an opportunity to go further. Rather than treating patients with chemotherapy and IO induction and give maintenance for those who haven't progressed, What if we could bring the most active modalities together and replace chemotherapy to deliver higher efficacy and better tolerability from the beginning to all these patients, not just the ones not progressing, with a longer duration of therapy? Our vision is to replace chemotherapy with ZOZI as the ADC backbone in combination with IO and potentially ATCE. This could allow us to treat patients earlier, remove the attrition between induction and maintenance, and deliver a continuous front-line treatment. And we are already testing that vision with global partners. We believe these mechanisms are highly complementary. SOSI delivers direct cytotoxicity activity independent of T cell fitness, while Tarlatamab recruits T cells to attack TLS-3-expressing tumor cells. This creates the potential for deeper and more durable disease control while replacing the conventional chemo backbone. Turning to our global development, a global phase III in second-line plus small cell lung cancer is ongoing, and our potential registrational study in extrapulmonary NEC is fully enrolled. But we are extending beyond that. We're also exploring opportunities in other DLL3-expressing cancers, including immediate stage small cell cancer, large cell neuroendocrine carcinoma, and brain tumors where DLL-3 is expressed. we're very excited by what is to come. Over the next 12 to 18 months, we are expecting multiple important data readouts for our key programs, as well as our first potential USBLA submission next year. And with that, I'm happy to take your questions. As a reminder, to ask a question, please press star 1 1 on your telephone and wait for your name to be announced. To answer your question please press star one on one again. We will now take our first question from the line of Michael Yee from UBS. Please go ahead. Thank you. Two questions from us. Congratulations on the data. Very exciting as you get through second line and then first line. So maybe just with Second line, can you just confirm the timelines for the enrollment, the data timeline readouts, and then your ability to file in second line to get this drug on the market and your ability to file just on the interim analysis later next year? And as it relates to today's data, maybe you could just clarify for us, is the goal to replace chemo and be the dominant standard first-line regimen to replace chemos, or also the idea to be in combination with a TCE with Amgen, and you would attempt to run also a maintenance study in combination. Maybe just clarify how you're thinking about the competitive position in a first-liner. Maybe you're going to try and do both. Thank you. Thanks, Michael. This is Rafael. To your first question, the second-line study is ongoing. It's agreeing well. We still intend to have accrual next year, analysis of the data and file next year. We are enrolling patients both in second line and also making more efforts to enroll patients, but so far the timelines have not changed. With regards to the goal of the first line in light of this data, we plan to start a doublet study with SOZI plus checkpoint inhibitor against chemotherapy plus IO, and potentially LRBI will be allowed as well as maintenance. There is the potential of combination with a TCE in the future, it was mentioned in the prepared remarks, and, you know, we'll just have to see how the ongoing studies with our partners shape up. Perhaps I will ask Dr. Rocha to tell us a little bit more about how he sees the future of small cell lung cancer treatment. Sure. Hi, Michael. Thank you for your question. So I guess if you asked me this question a couple years ago, I would say it's crazy to chemotherapy from frontline because we are need to deep response and quick response nowadays and in light of results of different ADCs where you can see that the response rates are there they are quick so the question will be more I guess which ADC you will choose for frontline and I guess we will remove chemotherapy from front line definitely so if you need to choose an ADC I guess you probably go for the one that you can tolerate for longer time perhaps and here most likely safety toxicity quality of life from our patients will take a important role in our decision and that's my vision and i yeah i guess the goal should be replace chemotherapy front line big goal thank you congrats Thank you. We will now take the next question from the line of Yigal Nokumovitz from Citi. Please go ahead. All right. This is Caroline on for Yigall. Thanks for taking our question. Where do you think XoC's largest opportunity for differentiation lies? Is it durability, CNS activity, tolerability, or the ability to support future combos? Thank you Well, in general, you know, we've shown all those aspects that you just mentioned. Clearly, the response rates both in monotherapy, second line, and beyond are high when second line is 68% with durability of six months, and now you've seen our data in front line with 82% response rate and, you now, good durability with a six-month BFS of 82% of patients. So clearly activity is paramount and I think SOCI is showing results that are, you know, pretty much state-of-the-art. It's also combinable because of, as Dr. Rocha just said, the safety is among the best of ADCs. And also I think, you, know, intracranial activity is important for many physicians, patients present with intracranial disease, they may need to suspend treatment initially for local regional therapy, and a SOC can address intracrannial disease as we've shown before in over 60% of patients with dedicated analysis of brain metastases. So I think it's a mixture of single agent activity and safety, which will allow combinability and that positions us really well to have the drug in both second line as well as first line. Maybe if I can add something here, and thank you for your question. So, and here, from my perspective, right, that I'm working in a university hospital where we have different clinical trials. So from last year, just to give you a background from where I'm talking about, right, because we include more than 100 patients with extensive stage small cell cancer in different clinical trials. So that means that we also have a clear vision on other drugs that are being developed, and I will not talk about that. But again, I do think that clinically, this is an important part that can you achieve a brain response? 80 percent of our patients will present brain mets during the evolution of the uh of their disease this is clearly important can we maintain those that treatment for longer this is also something important and maintaining the quality of our patient and that is also related with toxicity and that's something that i think is quite important and should differentiate how we choose our our first client at least We will now take our next question from the line of Anupam Rama from JPMorgan. Please go ahead. Hello. This is Brooke in for Anupom. Thank you so much for taking our question. What are the gating factors to initiating the global first-line ESSELC study by year and 26, and have you met with regulators on the design of the study? Thank you. Thanks for the question. We are standing up the study now. I mean, it requires, obviously, a lot of operational work, but we are aiming to start the study by the end of the year. With regards to discussions with regulators, yeah, they've seen early cuts of this data and and they've reviewed the study, and obviously we have their green light to proceed. So we're pretty excited that this will be our first frontline trial, and we will endeavor to execute it as swiftly as possible. Thank you. Thank you, we will now take the next question from the line of Lee Wozzeck from Kantor. go ahead. Hey, good morning. This is Moubin Hanfouli. It's a question about brain meds. It seems like at baseline some of your patients had brain meds, have you seen any evidence of intracranial activity in the first line just like what you saw in the second line thank you we actually have not looked by independent review in terms of intracranial responses you know with such a high response rate I think the inference would be that the response rate in the brain remains you know high like with what we saw in second line but I feel early for us you know to know this that is still a growing and we will definitely look to see but we have no reason to think that the drug will behave differently in first line than it did in second line okay and in will this be part of your first free trial as well yeah patient will be allowed to enter the study with brain metastasis as we did in this trial, as well as the second-line PLUS study. All right. Thank you. Thank you, as a reminder, to ask a question, please press star 1 and 1. We will now take our next question from the line of Si Chen from Goldman Sachs. Please go ahead. Thank you for taking my questions and congrats on the data. Just one question on the phase three design. Well, we're definitely looking forward for the first phase three frontline study to get initiated. But now in this study, from the protocol being published, that you're evaluating the duplets, right, instead of the triplets. So now I think companies moving forward with for online combined with PD-L1 and also combined with TCE. But what about those triplets? Given the data, that still looks pretty good. And also from a safety perspective, frankly speaking, compared to other ADC peers, it's not worse, right? Just your duplex is much better. So I'm trying to understand, will the triplets still have a role in specific subgroup population that could potentially benefit from those chemo combinations? Thank you. Yes. We are starting the doublet study based on these results. As Dr. Roach alluded to, the BFS was not reached at 12 months, and the median survival with chemotherapy NIL is in the order of 30%. So we're approaching BFS rates that are similar to OS with chemotherapy, so we think this This is really quite an active regimen that deserves to be tested in phase three. Testing it together with TCE. We are collaborating with Amgen and VI, as we said before, and the studies are still ongoing. They're early, and we clearly think that this is a combinable drug, and we will make a decision once we see the data. But as you mentioned, as you forecast in a pretty promising and I think interesting proposition that could lead to activity and safety. And Dr. Roach, if you want to comment further. Thank you. And yeah, I guess from the triplet, as I can see right now, and if we plan a phase three trial, try i guess i will be more favorable to not include chemotherapy in like doing a chemo free regimen in front line we still have chemotherapy for the next lines right so we still know that some patients will not will progress somehow and and so i will keep it the chemotherapy for the next line and i willbe very comfortable to just keep the nadc in frontline combined with the T cell engager? Probably yes, but as we are saying before, right, the brain mess, this is an important thing, right? But as far as we know from response with T cell engagers are not so good, at least the real world data that we have, few cases, few case reports, but again, responses does not seem the strong effect from the T cells engager. So I will be much more comfortable to give an may be seen from time. Thank you so much. Thank you. Thank you, there are no further questions at this time. I would now like to turn the conference back to Rafael Amado for closing remarks. Yeah, I'd like to thank Dr. Rocha for being with us today and to all of you that participated in the call and we look forward to providing further updates in the future on this program.