Hi everyone. Thank you so much for joining us today. I'm Rafael Amado, Zai Lab's President and Head of Global R&D. Before we begin, we will be making forward-looking statements today, and I ask you to review slide two for further detail. Moving to slide three, here's our agenda. I'll begin with an overview of our global asset portfolio, followed by a detailed presentation of the updated monotherapy phase one dose escalation and dose expansion clinical data for Zoci, that were presented earlier today in a plenary session at the ENA Symposium here in Boston. I'll share what these results mean for the program and our next steps before opening up the line for your questions. Slide four highlights the momentum of Zai Lab's growing global innovation pipeline, which today spans both oncology and immunology, our two core focus areas for global development.
Starting with oncology, at the top left, you can see Zoci, our potential first and best-in-class DLL3-targeted ADC. We have now initiated a global phase three trial in second-line small cell lung cancer, and are rapidly expanding development into first-line small cell lung cancer, as well as other neuroendocrine carcinomas. Beyond Zoci, our pipeline includes several highly differentiated potential first or best-in-class assets in oncology and immunology diseases. For example, ZL-1503, our internally discovered IL-13, IL-31 bispecific antibody, is a next-generation therapeutic for atopic dermatitis. Preclinical data suggests it could achieve broader disease control by targeting both itch and inflammation, potentially leading to faster onset, deeper skin clearance, and rapid relief of pruritus. We have initiated a phase one study and expect to initiate data readout next year.
In oncology, we have ZL-6201, our LRRC15 ADC, which is being developed for sarcoma and potentially other LRRC15 positive solid tumors, including breast and head and neck cancers. This compound has demonstrated strong binding affinity, potent by cellular killing, and a favorable safety profile in preclinical studies, and is expected to enter the clinic next year. We are also advancing ZL-1222, our PD-1 IL-12 immunocytokine, designed to deliver cytokine signaling directly into the tumor macroenvironment while preserving PD-1 checkpoint blockade. We look forward to sharing more data in the coming year. Zai Lab's unique advantage is its seamless integration of speed, quality, and scientific rigor across every stage of drug development. This is powered by our integrated R&D centers in the U.S. and China, with a world-class team of scientists, clinicians, and operational leaders with extensive drug development expertise.
This integration enables us to execute large, complex global trials with agility and excellence. We expect to deliver at least one to two new R&Ds per year, ensuring a continuous pipeline of innovative therapies for patients. Now turning to slide five, Zoci is a great example of how our global R&D model allows us to move with exceptional speed, advancing from phase one R&D to pivotal stage in less than two years. This speed is matched by the compelling nature of the data we're generating. In a notably difficult-to-treat patient population, Zoci has delivered deep and durable responses, achieving a 68% ORR in second-line patients with 1.6 mg per kg. We also observed an impressive 80% ORR among patients with untreated brain metastases, as well as a median duration of response of 6.1 months across all lines and all doses.
We're equally encouraged by the remarkably well-tolerated safety profile, which demonstrated a low rate of grade three treatment-related adverse events, an absence of grade two or higher interstitial lung disease, and zero discontinuations in the 1.6 mg per kg cohort. With this data, Zoci is emerging as a potential best-in-class treatment for small cell lung cancer. Today's announcement marks an important milestone for Zai Lab, as we begin patient enrollment in a global pivotal trial. We're not stopping here. Next year, we plan to initiate our first-line small cell lung cancer registration trial, as well as a registration study in neuroendocrine carcinomas, further extending Zoci's potential across DLL3-expressing tumors. With that, I will turn our attention to the key data that were presented at ENA today.
On slide seven, let me begin by highlighting a few key features of small cell lung cancer because they illustrate why there is such an urgency for new therapies. Small cell accounts for about 15% of all lung cancer, and this translates to more than 370,000 new cases each year worldwide, including over 100,000 in the U.S. and Europe. This is a cancer with a very aggressive biology, growing rapidly, and as a result, about two-thirds of patients are diagnosed at the extensive stage when the disease has spread throughout the lungs and beyond. For these patients, outcomes are dismal, with a median survival time of only about a year. Small cell lung cancer also has one of the highest rates of brain metastasis of any cancer. Up to 70% of patients ultimately develop brain metastasis, which drives significant morbidity and reduces median survival to just about five months.
Moving to slide eight, the typical patient journey in small cell lung cancer begins with platinum-doublet chemotherapy, plus an anti-PD-L1 or PD-1, followed by maintenance. While this treatment has shown high response rates of 60%- 70%, it is accompanied by considerable toxicity. More than 60% of patients experience grade three or higher treatment emergent adverse events. The median duration of response is only about five months, owing to the fast replicative potential of this tumor. Once patients progress, treatment options are very limited. Topotecan or other chemotherapies may be used, but they provide limited benefit and come with high morbidity. IMDELLTRA, or Tarlatamab, represents an important step forward, and it's a significant improvement over existing standard of care. However, challenges remain with a serious adverse event rate of 51%, the need for dose hydration, and the management of CRS and ICANS, all of which complicate its use in practice.
The reality is that despite incremental progress, this remains a disease with poor long-term outcomes. There is a pressing need for new therapies that can improve outcomes across all treatment settings, whether that is on efficacy, safety, or accessibility. Next slide. Delta-like ligand 3 is one of the most promising targets in small cell lung cancer. It's known to be a driver of neuroendocrine tumors, and it is aberrantly expressed in over 85% of small cell lung cancers, and is minimally expressed in healthy tissue, which makes it an ideal target. Zoci, as I'll refer to going forward, is a DLL3-targeted antibody-drug conjugate. It was purposefully engineered with several unique characteristics that may portend potential best-in-class treatment for recurrent small cell lung cancer.
This includes a high-affinity antibody with a relatively long half-life, which allows for durable and targeted tumor engagement, and a cleavable linker with a drug-to-antibody ratio of eight, which enables a potent bystander effect. Together, these characteristics give Zoci the ability to drive deep and consistent responses across a broad range of DLL3 expression levels, as you will see. Turning to the next slide, this phase one study is designed to evaluate the safety and efficacy of Zoci monotherapy in patients with recurrent extensive stage small cell lung cancer following at least one platinum-containing regimen. We included patients with asymptomatic brain metastases, both treated and untreated, and also allowed patients who failed prior DLL3-targeted therapies. This is a very difficult-to-treat population. The highest dose tested was 2.8 mg per kg, and the maximum tolerated dose was not reached.
Considering the totality of the data, expansion cohorts of 1.2 mg, 1.6 mg, and 2 mg per kg were open to optimize dose selection for pivotal studies. We highlight the 1.6 mg per kg dose to draw your attention, as this is the cohort with the largest sample size to characterize the efficacy and safety of Zoci in slides going forward. Next slide. Here are the baseline and disease characteristics. This is a global study with patients enrolled across the world, including the U.S., Europe, and China. Multi-center and geographic trials obviate the inherent biases of trials involving single countries with a small number of institutions. As of September 15, 115 patients were enrolled across the six dose cohorts. The majority of patients were heavily pretreated, with 56% receiving study drug at second line, and the remaining 44% of patients at third or fourth line, which is known to confer poor prognosis.
Over 90% of patients received prior anti-PD-L1 or PD-1 therapy, and we also enrolled patients who had failed on other DLL3-targeted therapies, including Tarlatamab. Nearly 1/3 of patients also had brain metastases, including 13 who had never received prior brain radiotherapy. This challenging patient population makes the results all the more compelling, as they approximate real-world results. Now let's start with safety results on slide 12. With longer follow-ups, Zoci continues to stand out with a remarkably well-tolerated safety profile. I would like to focus your attention on the treatment-related adverse events in the 1.6 mg per kg cohort. Only three patients required dose reductions, all for grade one events, and no patients discontinued treatment.
Results are even more impressive when you look at grade three or higher treatment-related adverse events, which occurred in just 13% of patients, far lower than the 35%- 50% rate seen with other ADCs in this setting. Pneumonitis and interstitial lung disease, which are notable concerns for some other ADCs, were rare, low-grade, and manageable. In the 72 patients treated at 1.2 mg- 1.6 mg per kg dose levels, there were only two cases, and both were grade one. This differentiated safety profile is important not only because it allows patients to remain on therapy to derive benefit, but also because it positions Zoci as an ideal candidate for combinations in the first-line setting where tolerability is critical. Turning to the next slide. Here you can see the waterfall plot on the 102 patients who had at least one post-baseline scan.
The vast majority of patients, including those who had untreated brain metastases at baseline, showed target tumor regression, with many being deep and durable responses. Half of the responders in the overall population, including half in the 1.6 mg per kg dose cohort, are still ongoing at the data cutoff. Turning to slide 14. With longer follow-up and a larger sample size, the overall response rate remains consistent with earlier reports. The response is higher in patients who received the study treatment as second-line therapy, with a best overall response of 60% across all doses. In the 1.6 mg per kg cohort, the dose emerging as potential randomized phase III dose achieved an overall response rate of 68%. We also continue to observe high systemic responses in patients with brain metastases, including an 80% ORR in patients who did not receive prior brain radiotherapy.
Intracranial disease affects up to 70% of small cell lung cancer patients and remains a key contributor to morbidity and mortality. Rapid onset of efficacy and tumor debulking allows for potential clinical benefit and future combinations with chemotherapies and immunotherapy. Beyond high response rates, durability is also important. Here again, Zoci is showing very encouraging signs. The median duration of response across all dose levels reached 6.1 months, and many patients are still on therapy after data cutoff. On slide 15, we see the spider plot showing the response being fast and patients having substantial clinical benefit. The median PFS across all patients was 5.4 months, a strong outcome in this heavily pretreated setting compared to other agents in second line, especially accounting for all doses and lines of therapy.
In conclusion, on slide 16, we believe that Zoci has the potential to be both the first and best DLL3-targeted ADC for small cell lung cancer, and ultimately to become an important treatment choice in this disease where patients desperately need better options. Zoci is delivering the right combination of efficacy, durability, and tolerability. We're seeing deep and durable responses in a very tough-to-treat, heavily pretreated population, including patients with brain metastases and those previously exposed to other DLL3-targeting therapies. Importantly, this profile holds up across multiple geographies and with longer follow-up, giving us confidence in the robustness of this data. Safety remains best in class with no treatment discontinuations due to toxicity and very low rates of serious adverse events at 1.2 mg- 1.6 mg per kg.
Looking ahead, a randomized phase two study is ongoing to optimize dose selection, and we have already initiated a phase three startup activity towards a registration trial versus investigator's choice. Next slide. We're executing this program with remarkable speed. In less than two years, we have advanced from the start of global phase one to pivotal phase. This is due to the remarkable dedication by an outstanding team, which keeps the momentum on this program, not only in second line, but in first line and NEC, which will be the subject of upcoming updates. This pivotal study will compare Zoci against investigator's choice of therapy, with overall response rate and overall survival as the primary endpoints. Secondary endpoints include duration of response, progression-free survival, time to response, safety, and quality of life.
We will soon start enrolling patients into this registrational enabling study with a planned interim readout in early 2027, which could potentially set the stage for an accelerated approval submission, a major milestone for patients and for Zai Lab. As stated on slide 19, beyond second-line small cell lung cancer, we're also pursuing indications in earlier lines of treatment where the opportunity is even larger. Given its efficacy to date and favorable safety profile, Zoci is particularly well-suited for use in the first-line setting, either to enhance maintenance treatment or as a potential replacement for chemotherapy. We are currently evaluating Zoci in combination with anti-PD-L1 and chemotherapy in the phase one study, with the goal of augmenting or replacing chemotherapy. Escalation for the doublet combination cohort in first-line small cell lung cancer is complete, and it's ongoing for the triplet cohort.
We expect to share data in the first half of next year. As this data matures, we plan to move quickly into a pivotal study in the front-line setting in 2026. We're also exploring novel combination strategies with additional agents to further unlock Z oci's potential. We will be able to disclose more next year when we initiate a phase one combination trial. We're executing this program with both speed and quality, with the goal of fundamentally reshaping the treatment paradigm for patients with small cell lung cancer. Next slide. Beyond small cell lung cancer, Zoci is also being evaluated in neuroendocrine carcinomas, or NECs, an area of high unmet need with over 350,000 patients globally and a prognosis that remains poor. Five-year overall survival across multiple tumor types stands at a dismal 5%- 15%.
The current standard of care is chemotherapy, which offers limited response and high toxicity, with no targeted therapies available despite high DLL3 expression across NEC subtypes. We initiated a global phase I-II study in May of this year, and data are already looking promising, potentially supporting advancement into a registrational cohort next year. We plan to present detailed data at a medical conference in the first half of 2026. In conclusion, Zoci is emerging as one of the most exciting opportunities in small cell lung cancer and potentially in neuroendocrine carcinomas. Over the next year, we will be reaching several important milestones, including pivotal trial initiations and early combination data that will continue to build momentum for this program using innovative registration trials. We look forward to keeping you updated as we work hard to deliver on Zoci's promise for patients.
Now, operator, please open the line for questions and answers.
Thank you. As a reminder, to ask a question, please press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. Once again, please press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. Please stand by while we compile the Q&A results. Once again, please press star one and one on your telephone and wait for your name to be announced. We are now going to proceed with our first question. The first question has come from the line of Jonathan Chang from Leerink Partners. Please ask your question. Your line is opened.
Hi guys. Thanks for taking my questions. First question, can you discuss how you're thinking about the timelines for Zoci development and how that positions Zoci in the competitive landscape?
Hi, Jonathan. It's Rafael. As I mentioned in the prepared remarks, we are starting the phase three study at the moment. This study is slated to continue until 2027. The accelerated approval opportunity remains viable to us after discussions with the FDA. We expect to file in 2027 for accelerated approval based on response, as well as durability of response. The approval will depend on the exact timing on filing and review, but it could be as early as the end of 2027, early 2028. That's how we're thinking about the pivotal trial, the first approval for Zoci.
Got it. Thank you. Just second question, what is your latest thinking on the positioning of IMDELLTRA in the treatment paradigm, and how does that impact your development strategy and thinking around the commercial opportunity for Zoci? Thank you.
Yeah, this is a really interesting question. Of course, IMDELLTRA has a very broad development program. You obviously know the data that was presented at ASCO and then published. It is in second line, but they have an extensive program in front line as well, and combinations as well will follow. My sense, and this is just my own opinion, is that eventually IMDELLTRA will become more of a front-line agent. It will obviously be given to patients that receive other agents in front line, like potential ADCs as well. How the patient segmentation will take place, I think it'll depend on the results of the trials and also the patient characteristics as well. I think it remains to be seen. There's a maintenance study that they have. There's a quadruple study that they have.
ADCs, particularly our product, at the moment, we're thinking about positioning as a chemotherapy-sparing product as well. With its characteristics of rapid onset of action and rapid onset in patients with metastases, particularly untreated metastases, and really good safety profile, I think it will compete well in front line as well. I think time will tell. It's still early. This study still needs to be executed and read out. Stay tuned. I think it's a good time for this disease that there are active agents that are all in development.
Got it. Thanks for taking my questions.
Thank you. We are now going to proceed with our next question. The next question has come from the line of Li Watsek from Cantor Fitzgerald. Please ask your question.
Hey guys, thanks for taking our questions. Maybe just two. First, can you talk a little bit about, you know, how should we interpret DOR versus PFS, which metric is most relevant to look at in this setting? Then, you know, second, can you just comment a little bit on what you're seeing in the front line landscape, which is evolving quite rapidly? What can you say about your front line trial strategy and timeline, given your competitors are also moving to front line very aggressively?
Yeah. The first question is duration of response versus PFS, which is a great question. In single arm trials, one has to be very careful comparing outcomes in general, because the studies can be very different geographically. The number of patients that are enrolled can vary. The number of months of follow-up can vary. That means the number of patients that are censored. A lot of care has to go into comparing studies across each other. More to the point of duration of response versus PFS, duration of response is really a more valid endpoint than PFS in single arm trials. Duration of response is only calculated in patients that respond, and it's really a reliable measure of patient benefit in a single arm trial, because it measures how long patients are benefiting from the drug using the surrogate endpoint of response. This is strictly as a result of treatment.
It's a really good interpretable efficacy endpoint for assessing activity as well as durability. When you look at PFS, PFS without a control arm is very difficult to interpret. There are differences between, as I mentioned before, regions versus global accruals, between patient baseline factors. PFS also includes stable disease patients, and some stable disease patients may have very aggressive disease versus others that may have very stable disease that is not growing very fast, and maybe it's not a reflection of the drug. It's just a reflection of the natural history of the disease. That is not the case for duration of response, for instance. Also, PFS is calculated using Kaplan-Meier methodology, which is different from duration of response. Duration of response is just a median. A lot of censoring will exaggerate PFS.
If you have a short follow-up where a lot of patients are censored, that is, they haven't met either progression or death, they will tend to have a longer PFS than they will when the data matures. One has to interpret PFS with caution when the follow-up is short. In general, the regulatory endpoint for a surrogate endpoint such as response will follow response as well as duration of response rather than PFS. The second question is the first-line strategy, given the competition. As I said before, there are two agents that have followed the strategy of maintenance, and then IMDELLTRA also is in first line. There's really no strategy at the moment of chemotherapy sparing, and we think that that is an important strategy, because many patients cannot get more than four to six cycles of platinum, etoposide, and maintenance PD1.
When you look at many of the ADCs, they're all moving to front line. PET/CIF, for instance, is a good example where chemotherapy was eliminated by combining it with PD1. Some of the breast cancer ADCs are also going into front line. There is also already a history of being able to spare chemotherapy, or at least reduce the chemotherapy burden, and synergize with PD1 agents. This is exactly what we're testing now. We have completed the combination with Atezolizumab, and now we are in first line with Carboplatin and Atezolizumab. Data accrual is going very well. The tolerability of our drug lends itself really well to this combination, because the treatment-related AEs is relatively low. It's only 13%, which is actually the lowest of many of the ADCs that are out there.
We think that it will be a good agent to combine in first line, but to spare some of the side effects of full-dose chemotherapy. As I said in the prepared remarks, we will finish this. We will present some of the data or the data up to the follow-up time next year in the first half of the year, and we plan to start a study looking exactly at that setting. I think there will be options for patients, either standard chemotherapy combinations, maintenance therapy, or chemotherapy sparing with ADC. I think physicians will have a choice for their patients, which is really what we want to do with the development of these drugs.
Thank you. We are now going to proceed with our next question. The next question has come from the line of Linhai Zhao from Goldman Sachs. Please ask your question.
Thanks for taking my question. This is Linhai from Goldman Sachs. A little bit more on the recent registration of the phase three trial in second line. Can you share a little bit more on the latest timeline? I found that the current timeline for the early 2027 to file the AA approval is kind of delayed compared to our initial timeline. Also, in the clinicaltrials.gov description, it said that the patient enrollment also includes second-line tobacco treatment. Can you help us understand if the patients with second-line tobacco treatment would be considered still as second line or third line? How much % of such patients do we intend to enroll in this phase three trial?
Thank you for the question. We are including IMDELLTRA in the control arm because it's got accelerated approval, but obviously, it's got a definitive trial. The use of Tarlatamab in second line in the U.S. is a clear standard at the moment. We, in a way, have the advantage of not having started it yet. We're pretty advanced with regards to other products, but we are going to compare it to contemporary therapy, rather than therapy that was really salvaged with very little activity. As a result, because Tarlatamab prolongs survival and it's an active drug, we have increased the sample size of the study to retain the power of the study and the treatment effect. That extra accrual may lead to slight delay, and we're trying to mitigate that by increasing the number of sites.
We still think that we will get accelerated approval or data to file for accelerated approval in 2027. The issue of including Tarlatamab, I think, is important, and it'll reflect real-world usage in the U.S. The % of patients that receive Tarlatamab, I think, will vary, but it will reflect, again, what is the usage in the U.S. As you know, that use will change with time. It is included as a physician choice, so we are not forcing which agent the physician should choose, but if they choose to use Tarlatamab, they will. With regards to Tarlatamab in third line, some patients may have failed Tarlatamab, and they could enter the study. Likewise, those patients that have not received Tarlatamab when they go into the treatment arm, they could receive Tarlatamab upon progression. That would attenuate any treatment effect of Tarlatamab as well.
In summary, I think we're doing a contemporary trial that incorporates the therapies that are available, and I think it will be more valid with regards to what happens in the real world. It gives physicians options, and we will try to accelerate the trial to try to decrease any potential delay in accrual. Again, we're still guiding towards end of 2027, early 2028 for approval. The last comment I will make is the first approval is based on response. The Tarlatamab response rate is 35% in the first phase three study, as opposed to 68%- 70% for our drug. We're not actually very concerned with the accelerated approval. We just want to make sure that the power for survival is correct.
Thank you. Just to clarify, the second-line Tarlatamab in this trial was considered as the control group, right?
Tarlatamab inclusion of Tarlatamab for patients that are Tarlatamab naive will be in the control group. As I said before, any patient in the treatment arm that had not received Tarlatamab could receive Tarlatamab. I mean, we don't control post-progression therapies.
Got it. Thank you. That's very clear.
Thank you. We are now going to proceed with our next question. The next question has come from the line of Anupam Rama from JPMorgan. Please ask your question.
Hi. This is Joyce on for Anupam. Thanks for taking our questions. For your pivotal study, it looks like clinicaltrials.gov is also showing that you will look at two Zoci doses, assuming that they are 1.2 and 1.6 mg per kg. Could you just talk about what points were discussed with regulatory agencies when aligning on dose selection and your continued confidence in 1.6 as the likely dose for approval? Thank you.
Thanks, Joyce. That's a great question. We have been spending a lot of time trying to hone into the dose and have frequent dialogue with the agency. The FDA agrees that 1.2 and 1.6 are the doses to really look at. We started a randomized cohort in the current study, 001, comparing 1.2 versus 1.6. We actually are close to finishing that cohort. Just in case we didn't have sufficient numbers of patients, we built in a randomization or a running phase into the phase three study. I think as soon as we achieve the number of patients in each one of the arms, which will include patients in the 001 and in the pivotal trial 003, we will choose a dose and then drop the other arm of the pivotal trial. Of course, we will have to have agreement with FDA to do that.
At the moment, our expectation is that 1.6 would be the dose, given its therapeutic index. I think doing that work is really important, because although one could go higher or lower, the therapeutic index of ADCs still remains narrow. As you can see, there's only 0.4 mg/kg difference between these two doses, but they can result in significant differences in efficacy or durability. It behooves us, I think, to have this in the phase three study. We may be able to drop that dose soon if we get clarity from the 001 trial on what the dose is and get agreement from FDA.
Great. Just to follow up, if I could, just zooming out, your registrational strategy positions you about one and a half to two years ahead in this space versus others. Could you just speak to how important that lead time is in terms of competitive advantage, especially with how the landscape continues to quickly evolve? Thank you.
Yeah. I think we, as I mentioned before, we are extremely pleased and proud of the work that the team has done to move this program expeditiously and fast. We studied a lot of doses. We've opened many sites around the world. We think we have a study that really represents real-world patients, and we have excellent data with a response rate in the 70% range with the dose that we believe is going to be the randomized phase three dose. That speed is really important because if one doesn't do this careful work and does it in an expeditious manner, you know, one would pay a price in the phase three study.
I think choosing a dose that was very effective, but at the same time extremely safe as ADCs go, with no discontinuations, only grade one ILD in a couple of cases, 13% grade three plus, mostly hematologic toxicity, I think that is really, you know, best-class type doses that we've been able to achieve and uncover with this product. It also opens the door not just for this disease and line of therapy, but as I mentioned before, for front line combinations and neuroendocrine carcinomas and other tumor types. This is an advantage that allows us to move really fast, and we plan to continue to have dialogue with FDA and potentially obtain drug designations that help us develop this in an expeditious manner. In drug development, one and a half years is really a very long period of time.
It's not just the properties of the drugs, which are excellent in this case, but it's also how it is developed and how quickly do we move. I think in this case, this program is world-class, I think.
We are now going to proceed with our next question. The question has come from the line of Yigal Nochomovitz from Citi. Please ask your question.
Hi. This is Caroline Ong for Yigal at Citi. Thanks for taking our question. We were wondering if you could tell us more about the significance of the brain METS data in small cell lung cancer. What is it about this drug's construct that apparently does a very good job with CNS penetration and activity? Did this exceed your expectations? Thanks.
Yeah. Thank you for the question. As I mentioned before, brain metastasis is a big problem in this disease. When patients develop it, their median survival is very short. Close to 2/3 of patients or beyond can get brain metastasis, and they survive about five months. They're poor candidates for systemic therapy, for instance, and their disease tends to be really fast growing. It's actually an area of relapse, even in patients that have systemic disease control, so they have to come off the drug because of brain metastasis. The numbers that we quote are patients that responded that had brain metastasis. We're now doing an analysis of patients that responded in the brain using RANO criteria, which is a two-dimensional way of measuring CNS tumors, and we plan to present that next year. That data, I think, is even more impressive.
I think the response rate that we've attained, particularly in patients that have never been treated for brain metastasis, is very impressive. If you look at the rest of the studies, they never included this kind of patients. They included patients that were treated and that had stable disease on treatment. They didn't have any new metastasis, and their metastasis was not growing. In our case, if a patient had the novel brain metastasis and didn't have symptoms, we did include those patients. To our surprise, we saw 80% of the patients, 80% of the metastasis responding, and we have accumulated more and more examples of those.
We think this is really important for a patient that comes in that has brain METS and really doesn't have a lot of time to, for instance, go to a neuroradiologist to receive brachytherapy or gamma knife or any of the radiotherapy localized procedures that are used, because that delays systemic therapy. In the meantime, the patient is progressing, whereas being able to give this antibody and control both the intracranial as well as systemic disease is, I think, really important. We hear this from our investigators all the time. Lastly, in terms of why this happens, we think the blood-brain barrier is disrupted, and antibodies can penetrate the brain. More importantly, this is an antibody that has picomolar affinity, so it can bind even low numbers of DLL3 molecules in the surface of the cell.
Because of the bystander effect and internalization, both direct and indirect effect cause very rapid decrease in the size of these brain lesions, to the point that they don't actually get treated with radiotherapy. They only receive this systemic therapy. I think it is a property of the drug that I think will play well in the treatment of the disease, and it's not observed with other agents.
Thank you. As a final reminder, to ask a question, please press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. We are now going to proceed with our next question. The question has come from the line of Clara Dong from Jefferies. Please ask your question.
Hi. Thanks for taking my question and congrats on all the progress. I saw you're planning to initiate a phase one global study of Zoci plus novel combo in 2026. We're wondering, could you share more details about this trial and the design, particularly in light of today's data update and what you see as the potential significance or rationale behind this novel combination? Thank you.
As I mentioned before, we think that this is potentially best in class, particularly based on tolerability and also mechanism of action. Obviously, ADCs are not the only drugs being developed in small cell lung cancer, and we want to position this drug as a cornerstone of potential future combinations that make biological sense. At this point, it's premature for us to disclose what other studies we will be doing. We will explore other indications that we will announce with time. There are other agents that have orthogonal mechanisms of action that could combine well with these therapies. As I mentioned before, immunotherapies are some of those. I think we should just stay tuned and see what time brings. Right now, we're obviously focused on standing up this phase three study and then moving forward rapidly with the first line as well as neuroendocrine carcinomas.
We will explore other combinations to see whether we can find synergy for these patients and then place Zoci as a centerpiece of therapy along lines of therapy and combinations with other agents.
Got it. Thank you. Looking forward to it.
Thank you. We have no further questions at this time. I will now hand back to you, Mr. Rafael Amado, for closing remarks.
Thank you everybody for your great questions today and for joining us. I'm incredibly proud of the team's progress, and I really look forward to sharing our next steps as we advance this program with you, as well as our entire pipeline in oncology, which is moving equally fast. With that, operator, you may disconnect.
Thank you. This concludes today's conference call. Thank you all for your participation. You may now disconnect your lines. Thank you.