Good day, and thank you for standing by. Welcome to the Zai Lab 2026 ESMO Investor Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one and one again. Please be advised that today's conference is being recorded. I will now like to hand the conference over to our speaker today, Rafael Amado. Please go ahead.
Hello, everyone, and thank you for joining us for the presentation of the results from our phase I study evaluating zoci, our DLL3-targeted ADC, in combination with atezolizumab, with or without carboplatin in small cell lung cancer. The results we're sharing today strengthen our confidence in zoci's potential and supports our global development strategy in frontline. Please refer to our forward-looking statements on slide two. Here on slide three 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 Vall d'Hebron University Hospital in Barcelona. I will start with brief comments on our global portfolio and the characteristics of zoci. Dr. Rocha will then take us through the highlights from ESMO, 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 zoci, and we're entering a pivotal period in zoci's 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 in DLLEVATE, second-line extra-pulmonary NEC, and first-line small cell lung cancer. Our focus is on strong clinical execution and generating the data needed to realize zoci's full potential. In immunology, our long-acting IL-13/IL-31 receptor alpha bispecific, called ZL-1503, 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 zoci.
Zoci is a DLL3-targeted antibody drug conjugate with high picomolar binding affinity, a potent topoisomerase 1 inhibitor payload, and a drug-to-antibody ratio of eight. The linker is cleavable, which means that the payload can be released not only inside the tumor cell, but also in the surrounding tumor microenvironment, resulting in a strong bystander effect. This design allows zoci to have potent tumor killing while maintaining a favorable safety profile, and we're seeing this translate into meaningful clinical activity. We recognize that small cell lung cancer is an increasingly competitive field. But when you look at the totality of the data, we believe zoci has important clinical properties that make it an ADC of choice in this disease.
As a monotherapy in second-line plus small cell lung cancer, zoci 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 zoci's safety. We believe it has the potential for best-in-class tolerability, 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 T-cell engagers.
We are already working with our partners BI and Amgen to realize the potential of these combinations as the standard of care in small cell lung cancer continues to evolve, thereby developing zoci as a key product that will further differentiate it from others in the class. With that, I will hand it over to Dr. Rocha for the clinical data.
Thank you, Rafael. Now I will be presenting results from the phase I study evaluating zoci in combination with atezo ± carboplatin, what we call it doublet or triplet cohort. On this slide, we can see our study design, which includes dose escalation and backfill and expansion cohorts for the doublet combination, zoci plus atezo. As you can see also here, we will focus on what we have in the red squares on the backfill 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. About three-quarters at stage 4 disease at initial diagnosis. Most were ECOG 1, and this perhaps reflect that usually these patients are symptomatic and need treatment that can reduce the tumor burden.
Also, highly important will be the presence of brain metastasis, 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. 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 zoci, we have not observed a difference in efficacy or safety between Asian and non-Asian patients. Also here, highlighting that for the first 15 patients treated with 1.6 mg/kg doublet, the median follow-up was 10 months. At the 1.2 mg/kg dose level, the median follow-up was 12.6 months. With that context, the next slide, we can see the waterfall plot for the doublet first-line combination.
As you can see here, these three slides show the efficacy from zoci plus atezolizumab 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 zoci at 1.6 mg/kg in combination with atezo, 27 patients achieved a confirmed response, an objective response rate of 81.80%. Taking account the standard of care, chemo plus immunotherapy, this compares favorably with, for the standard of care, we can think about a 60%-68% 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.
Importantly, as you can see with some arrows, those responses are still ongoing. If we put it, again, in context of the standard of care that we have currently, usually the patients with small cell lung cancer, the disease progress 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 mg/kg, the duration of response was 8.3 months. For the first 15 patients at 1.6 mg/kg with a minimum of 10 months of follow-up, the median duration of response was not reached. So this is very encouraging results. The progression-free survival for 33 patients at 1.6 mg/kg cohort, the six months progression-free survival was 81.9%, which is a very promising result.
For the first 15 patients with longer follow-up, median progression-free survival has not yet been reached, and two-thirds of those patients have not progressed as of cutoff. The 18 additional patients in the expansion cohort demonstrated an encouraging early progression-free survival consistent with the initial 15 patients. For reference, the six months progression-free survival with chemo immunotherapy in the IMpower133 was around 30%. Clearly, these results could change how we think about the first-line small cell lung cancer treatment. On the next slide, we also evaluate the zoci as a triplet in combination with atezo plus carboplatin. Despite the small sample size, we can see a very notable anti-tumor activity with a confirmed objective response rate of 92.3%. As you can see, important tumor reduction with patients achieving almost a complete response.
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 you look at the durability of this tumor reduction with a triplet, we can also see this is observed within the first tumor assessment, so very rapid, deep, 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 the favorable tolerability we have observed with zoci monotherapy previously in patients with second-and-plus lines has continued to be encouraging in this first-line doublet. There are no dose-limiting toxicities observed during dose escalation. At 1.6 mg/kg in 33 patients, only 9.1% of patients experienced Grade 3 or higher adverse events attributed to zoci.
We only observed one case of Grade 1 ILD. This is relevant in the context of other ADCs in the field in small cell lung cancer that we are seeing higher rates of ILD. There were no zoci-related treatment discontinuations or treatment-related deaths reported in this cohort. This is something that deserves to be highlighted compared with other drugs currently being explored in small cell. Although it is also true that these data are still maturing, I believe that the zoci safety profile will be consistent with what we have seen in zoci monotherapy, where we have a longer follow-up. As the conclusions in the doublet part, it seems that adding atezolizumab does not seem to change the safety profile of zoci. On the next slide, we have the safety of the triplet as first-line therapy.
In comparison, while the triplet demonstrated a higher anti-tumor activity, as we have seen before, it also resulted in a substantially more toxicity than the doublet. Serious drug-related adverse events and Grade 3 or 4 toxicities were more common with the triplet than with the doublet. We acknowledge that the addition of carboplatin is bringing more toxicity to our patients. 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. 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 the triplet. As you can see, the most common treatment-related events with the doublet were anemia, nausea, and leukopenia. Although, mainly Grade 1/2.
With addition of carboplatin, we saw greater hematological toxicity, particularly neutropenia and thrombocytopenia, which is, as I was saying before, consistent with what we would expect from adding a platinum-based chemotherapy and is 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. This is my last slide.
As a conclusion, in summary, our data demonstrate that zoci 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 zoci plus immunotherapy as a potential first-line treatment option for patients with extensive-stage small cell lung cancer. I guess with that, I would like to pass it back over to Rafael. Thank you.
Thank you, Dr. Rocha. Now let me put these results 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 lurbi 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 zoci as the ADC backbone in combination with IO and potentially a TCE.
This could allow us to treat patients earlier, remove the attrition between induction and maintenance, and deliver a continuous frontline treatment. We're already testing that vision with global partners. We believe these mechanisms are highly complementary. Zoci delivers direct cytotoxicity activity independent of T-cell fitness, while tarlatamab recruits T-cells to attack DLL3-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 potentially registrational study in extrapulmonary NEC is fully enrolled. We are extending beyond that. We're also exploring opportunities in other DLL3-expressing cancers, including limited-stage small cell lung cancer, large cell neuroendocrine carcinoma, and brain tumors where DLL3 is expressed. In closing, we're very excited by what is to come. Over the next 12-18 months, we are expecting multiple important data readouts for our key programs, as well as our first potential U.S. BLA submission next year. With that, I'm happy to take your questions.
As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and 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. 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. 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 chemo, 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 line, or maybe you're going to try and do both. Thank you.
Thanks, Michael. Rafael. To your first question, the second line study is ongoing. It's going well. We still intend to have accrual next year, analysis of the data on file next year. We are enrolling patients both in second line and also making more efforts to enroll patients for zoci as well. But so far, the timelines have not changed.
With regards to the goal of first line in light of this data, we plan to start a doublet study with zoci plus checkpoint inhibitor against chemotherapy plus IO, potentially lurbi 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 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. I guess if you asked me this question a couple years ago, I would say it's crazy to remove chemotherapy from front line because we need a 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 front line. 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 a longer time, perhaps. And here, most likely, safety, toxicity, quality of life from our patients will take an important role in our decision. That's my vision. And 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 Nochomovitz from Citi. Please go ahead.
Hi, this is [Caroline] on for Yigal. Thanks for taking our question. Where do you think zoci's largest opportunity for differentiation lies? Is it durability, CNS activity, tolerability, or the ability to support future combos? Thank you.
Well, in general, we've shown all those aspects that you just mentioned. Clearly, the response rates, both in monotherapy, second line and beyond are high. Second line is 68%, so its durability is six months. Now you're seeing our data in front line with 82% response rate and good durability with a six-month PFS of 82% of patients. Clearly, activity is paramount, and I think zoci is showing results that are pretty much state-of-the-art. It's also combinable because, Dr. Rocha just said, the safety is among the best of ADCs.
Also, I think, intracranial activity is important for many physicians. Patients present with intracranial disease, they may need to suspend treatment initially for local regional therapy, and zoci can address intracranial disease, as we've shown before in over 60% of patients with dedicated analysis of brain metastases. 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. Here from my perspective, that I'm working at university hospital where we have different clinical trials. From last year, just to give you a background from where I'm talking about, because we include more than 100 patients with extensive-stage small cell lung cancer in different clinical trials. That means that we also have a clear vision on other drugs that are being developed, and I will not talk about that. Again, I do think that clinically, this is an important part that c an you achieve a brain response?
80% of our patients will present brain mets during the evolution of their disease. This is clearly important. Can we maintain that treatment for longer? This is also something important in maintaining the quality of our patients. That is also related with toxicity, and that's something that I think is quite important and should differentiate how we choose our first line, at least.
Thank you.
Thank you.
We will now take our next question from the line of Anupam Rama from JPMorgan. Please go ahead.
Hello, this is [Brooke] in for Anupam. Thank you so much for taking our question. What are the gating factors to initiating the global first-line ES-SCLC study by year-end 2026? Have you met with regulators on the design of the study? Thank you.
Thanks for the question. We are standing up the study now. It requires, obviously, a lot of operational work. 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 they've reviewed the study. Obviously, we have their green light to proceed. We're pretty excited that this will be our first front-line 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 Li Watsek from Cantor. Please go ahead.
Good morning. This is [Mobina] for Li. Question about brain mets. It seems like at baseline, some of your patients had brain mets. 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. With such a high response rate, I think the inference would be that the response rate in the brain remains high, like what we saw in second line. But still early for us to know this. The study is still accruing, 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. Will this be part of your phase III trial as well?
Yeah. Patients will be allowed to enter the study with brain metastasis, as we did in this trial, as well as the second- line plus[supplies] study. Yes.
All right. Thank you.
Thank you. As a reminder, to ask a question, please press star one and one. We will now take our next question from the line of Ziyi Chen from Goldman Sachs. Please go ahead.
Thank you for taking my questions, and congrats on the data. Just one question on the phase III design. We are definitely looking forward for the first phase III front-line study to get initiated. Now in this study, from the protocol being published, you are evaluating the doublets instead of the triplets. Now I think companies moving forward with front line combined with PD-L1 and also combined with a TCE. What about those triplets? Given the data, it still looks pretty good. Also from safety perspective, frankly speaking, compared to other ADC peers, it is not worse, right? Your doublet is much better. I am 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. Rocha alluded to, the PFS was not reached at 12 months. The median survival with chemotherapy and IO is in the order of or so. We are approaching PFS rates that are similar to OS with chemotherapy. We think this is really quite an active regimen that deserves to be tested in phase III. Testing it together with a TCE. We are collaborating with Amgen and BI, we said before, and those studies are still ongoing. They are early, and we clearly think that this is a combinable drug, and we will make a decision once we see the data. As you mentioned, as you are forecasting, a pretty promising and, I think, interesting proposition that could lead to activity and safety. Now, Dr. Rocha, if you want to comment further.
Thank you. Yeah, I guess from the triplet, as I can see right now, if we plan a phase III trial, I guess I will be more favorable to not include chemotherapy in doing a chemo-free regimen in front line. We still have chemotherapy for the next lines, right? We still know that some patients will progress somehow. I will keep the chemotherapy for the next lines, and I will be very comfortable to just keep the zoci in front line. Combined with a T-cell engager, probably, yes.
As we were saying before, the brain mets, this is an important thing. 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-cell engager. I will be much more comfortable to give an ADC in front line.
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.
I'd like to thank Dr. Pedro 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.
This concludes today's conference call. Thank you for participating. You may now disconnect