NovaBridge Biosciences ESMO 2026

Please go ahead, Srishti. Welcome, and thank you for joining today's webcast to discuss the updated phase I-B givastomig data presented at ESMO.

A year ago, we were encouraged by the early activity we were seeing with givastomig. Today, with substantially more follow-up, we have a much deeper understanding of the durability, safety, and overall clinical profile of the program. Today's discussion is about more than an updated data cut. It's about how a much more mature dataset has changed our understanding of the program and increased our confidence in the future development. With additional follow-up, the key objectives of the phase I-B study have now largely been accomplished. We have characterized the durability and consistency of the clinical benefit, selected the 8 milligrams per kilogram dose for the registrational development, and used the data generated through this study to inform our phase III strategy.

What is particularly encouraging is that our confidence in the clinical profile of givastomig has increased as the dataset has matured. We continue to see evidence of durable clinical benefit with responses that can persist and, in some patients, deepen over time. The data also continue to demonstrate clinical activity across the CLDN18.2 expression levels, including lower expression tumors, supporting the broad potential of the program. To summarize, this mature dataset has allowed us to better characterize durability, establish the registrational dose, and support a global registrational study protocol that has been approved by the FDA. With that, I'd like to introduce our Chief Medical Officer, Dr. Phillip Dennis, who will review the updated clinical results, discuss the key findings from the mature dataset, and explain how these data inform selection of the 8 milligrams per kilogram registrational dose and support our planned registrational development strategy.

Following Phil's presentation, he will be joined by Dr. Sam Klempner, Associate Professor of Medicine at Massachusetts General Hospital and lead investigator of our Phase I-B study, who will provide an independent clinical perspective on the durability of the findings, the relevance for patients with gastric cancer, and the potential implications for the treatment landscape. Phil, over to you. Thank you, Shristi.

Before getting into the data, it is helpful to step back and consider what a successful therapy needs to deliver in frontline gastric cancer. Efficacy is critical, but so are broad patient applicability, manageable safety, and the ability to integrate into routine clinical practice. Many CLDN18.2 targeted approaches involve trade-offs between these dimensions, and this slide helps put that landscape into context. Against that backdrop, let us turn to givastomig. With the additional follow-up we are presenting today, we can now assess the profile of givastomig with greater maturity, including the depth and durability of response, safety, and activity across CLDN18.2 expression levels. Let us walk through what the updated dataset tells us. Next slide, please. When we initiated this Phase I-B study, we believed that a successful frontline therapy would need to demonstrate four things. First, broad patient applicability. Second, durable clinical benefit. Third, a manageable safety profile.

And fourth, practicality for routine clinical use. Earlier in development, many of these questions remained unanswered because the dataset was still relatively immature. What makes today's update different is the amount of follow-up we now have available. With nearly 18 months of median follow-up in the selected 8 milligram per kilogram cohort, we can now move beyond simply asking whether the drug is active. We can now begin to assess whether responses are durable, whether safety remains manageable over prolonged treatment, whether activity extends across CLDN18.2 expression levels, and whether the overall benefit-risk profile supports broad frontline use. As I walk through the data, I will come back to each of these four attributes because they provide a useful framework for understanding how the program has evolved as the dataset has matured.

But first, it is worth briefly revisiting the mechanism and why we believe this approach had the potential to address those four attributes. Next slide, please. givastomig combines 18.2 targeting with conditional 4-1BB T-cell activation. This design seeks to amplify anti-tumor immunity within the tumor microenvironment while maintaining a safety profile suitable for frontline use. The key question has always been whether that design translates into durable clinical benefit and manageable safety. The updated Phase I-B dataset provides increasing confidence that it does. Of course, mechanism alone does not determine clinical impact. Ultimately, that needed to be evaluated in the Phase I-B study, which was designed to answer several key development questions. Next slide, please. The Phase I-B study was designed to not only establish safety and characterize activity, but ultimately to answer three questions that would be critical for registrational development. First, what dose should advance into registrational development?

Second, is activity observed across a broad CLDN18.2-positive population? Third, does clinical benefit remain durable with longer follow-up? Importantly, the study designed patients across the CLDN18.2-positive spectrum rather than focus exclusively on the high expression cohort. The updated dataset provides important information on dose selection, durability, safety, and patient population that helped inform registrational development planning. With that framework in mind, let's turn to what we've observed clinically, beginning with the breadth of activity across the CLDN18.2-positive population. Next slide, please. One of the most important findings in this dataset is the consistency of activity across CLDN18.2 expression levels. Strong activity was observed in patients with CLDN18.2 expression in greater than 75%, which is where currently approved 18.2 targeted therapy is primarily focused. Importantly, activity was maintained in lower expression tumors.

At the 8 mg per kilogram dose, which we have selected for registrational development, objective response rates were 82% in the claudin high population and 75% in patients with CLDN18.2 expression between 1% and 74%. Disease control approached 100%, and nearly every efficacy-evaluable patient experienced some degree of tumor shrinkage. Activity was also observed across PD-L1 subgroups. Importantly, these findings have persisted as the dataset has matured, with nearly 18 months of median follow-up in the 8 mg per kilogram dose. While these are early phase data, the consistency of activity across expression levels gives us increasing confidence that the opportunity may extend beyond the currently defined high expression treatment segment. Beyond response rates alone, we also wanted to understand the consistency and magnitude of these responses. Next slide, please. Response rate is important, but we also wanted to understand the breadth and depth of activity across the study population.

What we observed was evidence of activity across CLDN18.2 expression levels, as well as PD-L1 subgroups. Beyond the responses themselves, we saw substantial depth of response at the selected 8 mg per kilogram dose, with a median tumor reduction of 62%. Most notably, 68 of 69 efficacy-evaluable patients experienced some degree of tumor shrinkage. That level of consistency suggests the activity we're observing is broadly distributed across the population rather than driven by small subsets of patients. In our view, these findings strengthen the overall response rate signal and provide important context for what comes next. The key question then becomes whether those responses translate into durable clinical benefit over time.

With nearly 18 months of median follow-up in the selected phase III dose cohort, we are now in a position to begin answering that question. The key question then becomes whether those responses translate into durable clinical benefit over time. Next slide, please. If I had to identify the single most important takeaway from this update, it would be durability. Earlier in development, we knew givastomig was generating responses. The key question was whether those responses would translate into durable clinical benefit over time. With nearly 18 months of median follow-up at the selected 8 mg per kilogram dose, we now have much greater visibility into that question. What we're seeing is not merely a response rate story. The median duration of response is now 15.2 months. The median progression-free survival has reached 16.9 months. 14 patients remained on treatment at the data cutoff.

Importantly, responses often continue to deepen after an initial response, and today's dataset looks better than it did a year ago. That is exactly what you hope to see from a therapy intended for prolonged frontline treatment and benefit. What gives us confidence is not simply that we have observed the responses, it is that those responses translated into durable disease control as the dataset has matured. It is also worth noting that despite nearly 18 months of median follow-up, only 13 progression events had occurred, while 18 patients remained censored and 14 patients were still receiving treatment at the time of the analysis. In frontline metastatic gastroesophageal cancer, generating responses is important, but sustaining responses over time is what ultimately matters most to patients and physicians. For us, that is one of the most encouraging aspects of this dataset. The signal became stronger rather than weaker as follow-up matured.