Good day, and thank you for standing by. Welcome to the Ziihera GEA investor webcast conference call. I would now like to turn the call over to your speaker for today, John Bluth, Head of Investor Relations. Please go ahead. Thank you, operator, and thank you all for joining us. We are excited to discuss the FDA approval and U.S. commercial launch of Ziihera in first-line HER2-positive metastatic gastroesophageal adenocarcinoma, or GEA. The slide presentation accompanying this webcast is available on the investor section of our website, and you can also reference the press release we issued regarding the FDA approval of Ziihera. Also on our website, you can find a link to the approved label. On slide two, I would like to remind you that today's webcast includes forward-looking statements, such as those related to our future financial and operating results, growth potential, and anticipated development, regulatory, and commercial milestones, which involve risks and uncertainties that could cause actual events, performance, and results to differ materially from those contained in these forward-looking statements. We encourage you to review the statements contained in our slide deck and the risks and uncertainties described in our SEC filings. We undertake no duty or obligation to update our forward-looking statements. Joining the call today are Dr. Rob Iannone, Global Head of R&D and Chief Medical Officer, who will discuss the approved label; Chumi Khurana, Head of our Oncology Franchise; and Sam Pearce, our Chief Commercial Officer, will discuss our commercial launch strategy. Then we will open up the call for Q&A. The approval of Ziihera is a pivotal moment for Jazz and represents a paradigm shift for the treatment of first-line HER2 metastatic GEA. This approval is a powerful demonstration of our corporate strategy in action as we continue to transform Jazz into a highly innovative, rare disease-focused biopharmaceutical company. Ziihera demonstrated an unprecedented survival benefit, with median overall survival surpassing two years, and is the first and only bispecific HER2-targeted antibody combined with a PD-1 inhibitor and chemotherapy approved for all HER2-positive advanced GEA patients, regardless of PD-L1 status. These results give us high conviction that the Ziihera combination is positioned to significantly improve outcomes and be established as the new standard of care for this patient population. Importantly, the approval marks a major step forward in establishing Ziihera as a multibillion-dollar foundational asset in our oncology portfolio. Backed by robust clinical data and our plans to expand the zanidatamab development program, we are updating our view of the Ziihera peak sales potential to a range of $3 billion-$5 billion. This updated range reflects our confidence in Ziihera's clinical profile, its potential as a foundational therapy across multiple HER2-expressing tumors, and supports our plans to expand zanidatamab's development into new tumor areas. With that, I'll turn the call over to Rob to discuss the approved Ziihera label and the meaningful impact we believe Ziihera can have for patients with GEA. Thank you. I'll begin on slide seven. The FDA approval of Ziihera represents a transformative shift in treatment options for patients with GEA and their families, who now have access to a therapy that delivers a median overall survival of more than 26 months when combined with tislelizumab and chemotherapy. These data from the HERIZON-GEA-01 trial demonstrates the remarkable advance in patient care and survival benefit that Ziihera provides. It's based on these clinical outcomes, along with the FDA approval, that we believe every eligible HER2-positive first-line metastatic GEA patient should receive Ziihera in combination with chemotherapy plus a PD-1 inhibitor, regardless of PD-L1 tumor status. These are the outcomes that drive our motivation and dedication at Jazz. I will now quickly speak to the label and supporting data. Ziihera is indicated irrespective of tumor PD-L1 status in combination with tislelizumab and fluoropyrimidine and platinum-containing chemotherapy as first-line treatment of adult patients with unresectable, locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma for patients with either IHC 3+ or IHC 2+ and ISH-positive disease, as detected by an FDA-authorized test. In addition, Ziihera is indicated with fluoropyrimidine and platinum-containing chemotherapy for patients with HER2-positive IHC 3+ disease as first-line treatment of adult patients with unresectable, locally advanced, or metastatic GEA, as detected by an FDA-authorized test. Ziihera is administered as an IV infusion in combination with chemotherapy, with or without tislelizumab. Dosing is weight-based, with patients weighing less than 70 kg receiving 1,800 mg of Ziihera every three weeks or 1,200 mg every two weeks. Patients weighing 70 kg or greater will receive 2,400 mg of Ziihera every three weeks or 1,600 mg every two weeks. The optionality of Q2-week dosing aligns to FOLFOX administration, as the flexibility allows for physicians to choose the best chemotherapy for their patients. The efficacy results from the phase III HERIZON-GEA trial that appear in the label are outlined on Slides eight and nine. Both investigational treatment arms containing Ziihera demonstrated a statistically significant improvement in PFS, corresponding to a median PFS exceeding 12 months, reducing the risk of disease progression or death by 35% compared with the trastuzumab control arm. Likewise, both combinations containing Ziihera exceeded two years of median overall survival, setting a new benchmark for survival in this disease. The Ziihera, plus tislelizumab and chemotherapy arm demonstrated a clinically meaningful and statistically significant improvement in OS, with more than seven months improvement in the median OS, reaching 26.4 months and a 28% reduction in the risk of death versus the trastuzumab control arm. Nearly 40% of patients treated with the triplet regimen were estimated to be alive after three years. The benefit was observed irrespective of tumor PD-L1 status. In the intention-to-treat population, and as published in the New England Journal of Medicine, Ziihera plus chemotherapy showed a clinically meaningful survival benefit with a median OS of over two years, with a strong trend towards statistical significance at the time of the first OS interim analysis. The top-line results from the second interim overall survival analysis from the HERIZON-GEA-01 trial doublet regimen are expected this quarter. As outlined in the label, the subgroup of patients treated with Ziihera plus chemotherapy, whose tumors were IHC 3+ for HER2, showed a median overall survival of 25.5 months and a hazard ratio of 0.74, with an upper bound of the 95% confidence interval that did not cross one. We are very pleased with the approved label, and we believe the unprecedented survival benefit supports the use of Ziihera as the new HER2-targeted agent of choice in HER2-positive, first-line metastatic GEA. We expect that Ziihera in combination with tislelizumab and chemotherapy will become the new standard of care for these patients, irrespective of PD-L1 tumor status. Turning to Slide 10, I will review the important safety information. Ziihera has a box warning for diarrhea and embryo-fetal toxicity. Ziihera in combination with fluoropyrimidine and platinum-containing chemotherapy, with or without tislelizumab, can cause severe diarrhea, including life-threatening cases. Physicians should prescribe antidiarrheal prophylaxis during the first cycle when Ziihera is given in combination with these drugs, and supportive measures should be implemented during treatment as clinically indicated. Before modifying the dose of Ziihera, it is recommended to evaluate, modify, or discontinue drugs contributing to diarrhea in accordance with their respective prescribing information. Treatment-related diarrhea that led to Ziihera discontinuation in the HERIZON-GEA-01 clinical trial was uncommon, occurring in less than 5% of patients across both experimental arms. Based on clinical trial experience and input from treating physicians and patients, we view these AEs as manageable with prophylaxis and active management, considering the significant antitumor and survival benefits of Ziihera. In addition, physicians have the option to use FOLFOX in combination with Ziihera, a chemotherapy regimen more widely used in the U.S. relative to CAPOX, which was primarily chosen as the chemotherapy backbone in the HERIZON clinical trial. Other warnings and precautions related to Ziihera administration include left ventricular dysfunction and infusion-related reactions. The most common AEs with Ziihera in combination with tislelizumab and chemotherapy were diarrhea, nausea, decreased appetite, hypokalemia, vomiting, fatigue, peripheral neuropathy, rash, and infusion-related reactions. The most common adverse reactions with Ziihera in combination with chemotherapy were diarrhea, nausea, vomiting, peripheral neuropathy, decreased appetite, fatigue, hypokalemia, infusion-related reactions, and rash. I will cover zanidatamab's unique mechanism of action on Slide 11, which gives us conviction to expand our development program into areas where we think zanidatamab can outperform historical benchmarks for HER2-targeted agents. As described in the Nature publication illustrating zanidatamab's mechanism of action, we believe its design is fundamentally different from other HER2 antibodies. By binding two distinct sites on the HER2 receptor simultaneously, zanidatamab crosslinks neighboring HER2 proteins, leading to receptor clustering. The unique geometry and binding effectively blocks HER2-dependent cancer growth signaling. Additionally, zanidatamab activates the immune system to attack the tumor, including activation of ADCC, ADCP, and CDC. We believe complement cascade activation is unique to zanidatamab among HER2-targeted therapies. Subgroup data from the HERIZON-GEA-01 trial presented at ASCO GI shows PFS and OS benefits were consistent in patients across PD-L1 positive and PD-L1 negative disease. We believe the complement and other immune activation induced by zanidatamab further enhances the efficacy of immunotherapy and explains the efficacy we see irrespective of PD-L1 status. We believe the combination of its unique mechanism of action, along with impressive clinical efficacy and a manageable safety profile for this molecule to date, are supportive of investing further in zanidatamab. Sam will discuss our expanded view on the value zanidatamab may offer to HER2-expressing cancer patients later in the call. I will now turn the call to Chumi for a discussion of our commercialization plans. Thanks, Rob. The FDA approval of Ziihera is a landmark achievement, and our team is ready to deliver this transformative therapy for GEA patients. I will start by outlining the significant unmet need for GEA patients on slide 13. GEA, which includes cancers of the stomach, gastroesophageal junction, and esophagus, is the fifth most common cancer worldwide. Almost all GEA patients, about 90%, are symptomatic and usually present to a primary care provider or in the ER with complaints such as difficulty swallowing, painful swallowing, unexplained weight loss, blood in cough, or abdominal pain. Because the vast majority of GEA patients are diagnosed at an advanced stage, immediate intervention is critical. Approximately 20% of patients are diagnosed with HER2-positive disease, which translates to an annual incidence of about 8,000 cases in the year. HER2-positive GEA is associated with high morbidity and mortality, and there remains a high unmet need for new treatment options. The overall prognosis for patients with GEA remains poor, with a five-year survival rate of less than 10% for metastatic GEA. This combination of high morbidity, mortality, poor prognosis, and limited first-line treatment options underscores the urgent need for new therapies for these patients. The annual incidence of 8,000 HER2-positive GEA cases translates to a highly defined treatable patient population. When we look to patients who have unresectable disease, those who are eligible to receive treatment in the first line, and those who receive HER2 testing, we reach a market of 3,000-4,000 patients on an annual basis who are excellent candidates to receive Ziihera. Our commercial investment strategy is focused on patient identification in GEA, ensuring no patient is left behind. On slide 14, I will highlight how we expect the treatment paradigm to evolve beyond legacy standards of care and reshape the management of HER2-positive GEA. For more than a decade, trastuzumab-based therapy has been the foundation of treatment for HER2-positive GEA, and Ziihera represents a meaningful advance for these patients. In prior standards of care, which are shown on the left side of the slide, patients would need to be tested for PD-L1 status. Those who tested positive for PD-L1 were eligible for the newest regimen known as pembrolizumab, which added an IO to the ToGA regimen, while patients who tested negative for PD-L1 would continue to receive the trastuzumab-based ToGA regimen. Now, with Ziihera, once patients have confirmed HER2 positivity, the treating physician is able to begin treatment with the HERIZON regimen without testing for a patient's PD-L1 status and without delay. Given the unprecedented survival outcomes seen from the HERIZON-GEA trial, we expect the Ziihera IO chemotherapy regimen to rapidly become the preferred clinical choice for eligible HER2-positive GEA patients. Moving to slide 15, our launch strategy is built on rapid execution and operational leverage designed to swiftly establish Ziihera as the definitive HER2-targeted backbone. Critically, our success in BTC serves as a powerful commercial foundation for our next major growth phase in GEA. Because there is a significant direct overlap between existing BTC and GEA treating accounts, our commercial infrastructure is fully primed and highly optimized. With over 90% target position overlap, our team will rapidly generate clinician excitement and demand. This enthusiasm is rooted in zanidatamab's exceptional clinical data, specifically an unprecedented median overall survival exceeding two years. Due to the high overlap across our solid tumor counts, our field force has already established relationships with the highest volume prescribers. Our team is right-sized to capture the larger GEA market without requiring commercial expansion. The key components of our launch strategy leverage Jazz's strengths as a rare disease company, including identifying specific patient populations and building a precise commercial infrastructure to serve them. Our launch model is based on the blueprint for how Jazz successfully commercializes therapies for rare and complex diseases. The key component of Ziihera launch is identifying the right patient at the right time to accelerate adoption of Ziihera. The HER2 testing infrastructure is already mature, with 80%-90% of patients undergoing biomarker testing at diagnosis. Anywhere from 60%-80% of HER2-positive patients go on to receive a HER2-targeted therapy, depending on where the patient is being treated. While academic centers lead in adopting biomarker-driven therapies, we are actively closing this gap in the community settings. Our launch in second-line BTC established a foundation for us to rapidly increase our presence in these community accounts and accelerate Ziihera's adoption in GEA. We are executing our high-touch commercial model across academic and community networks, deploying specialized peer educators and dedicated support systems to ensure seamless treatment initiation and long-term patient adherence. To complement direct engagement, our non-personal promotion and digital campaigns will increase awareness of Ziihera as a new treatment option. To support immediate clinical adoption at launch, we have submitted this data to key oncology pathways. Ordering is available for customers through leveraging our established permanent J-code and is also backed by our robust JazzCares patient support program. Rounding out the foundational components of our strategy is an emphasis on creating exceptional patient initiation and treatment experiences, which I will describe on the next slide. We have made strategic investments that support sustained patient adherence to treatment, including the nurse educator program and patient starter kit. Details on these programs are outlined on slide 16. The nurse educator program is comprised of oncology-certified nurses who provide peer-to-peer proactive education on the dosing and administration of Ziihera. The patient starter kit include educational resources around adverse event management with common over-the-counter loperamide. By supporting education around long-term adherence, we can help patients achieve the best possible outcomes. These materials were developed with feedback from patients, caregivers, and advocacy groups, and are designed to improve patient safety, comprehension, and satisfaction. We remain committed to empowering patients and caregivers through every step of the treatment journey, and are so excited to bring a therapy with such dramatic survival improvement to them. I'll now turn the call over to Sam to review the commercial opportunity for Ziihera. Thank you, Chumi. This approval is transformational for patients with HER2-positive GEA and marks an important inflection point for Ziihera. With approvals now in both BTC and GEA, Ziihera has evolved from a promising pipeline asset into a commercially launched medicine with the potential to become a foundational HER2-targeted treatment across multiple tumor types. Our previous $2 billion+ peak sales potential was based on the foundational indications of first-line and second-line BTC, first-line metastatic GEA, metastatic breast cancer, and our pan-tumor program. We worked diligently over the last two years to launch the registrational clinical trials that you can see outlined on slide 18. One of the most exciting areas is breast cancer, the largest HER2-positive solid tumor market. We believe zanidatamab has the potential to play an important role following progression on ENHERTU. We're evaluating this opportunity in our ongoing EmpowHER-303, which we expect top-line data from late next year or early 2028. At the same time, we are actively expanding our ambitions into earlier stage breast cancer, where the opportunity is substantially larger through the EmpowHER-BC-208, which was initiated over a year ago, and the I-SPY program. We're also actively engaged in combination strategies that could further enhance the value of zanidatamab. These include collaborations such as our ongoing study with Boehringer Ingelheim, zongertinib, as well as continued development in our registrational pan-tumor program across multiple HER2-expressing cancers. With the zanidatamab clinical development program well underway, the question is: Where will we take zanidatamab next to unlock its full potential? Which I'll cover next on slide 19. We have greater confidence in the molecule's ability to deliver meaningful outcomes across a much broader set of HER2-driven cancers, including earlier lines of therapy and larger tumor types. The HERIZON-GEA results significantly strengthen our conviction in zanidatamab's potential. Demonstrating unprecedented survival outcomes in a large phase III randomized clinical trial provides important validation of both the molecule and its underlying biology, reducing development risk as we expand the program. Based on the strength of the HERIZON-GEA data and the growing body of evidence supporting zanidatamab's unique mechanism of action, we're increasing our peak sales expectation for Ziihera to $3 billion-$5 billion, up from our prior estimate of $2 billion+. Beyond breast cancer, we are advancing registrational opportunities in colorectal cancer and evaluating potential pathways in non-small cell lung cancer. Early clinical data have been highly encouraging, and we look forward to progressing the program. Taken together, we believe Ziihera has the potential to become a foundational HER2-directed therapy across multiple tumor types. Our updated peak sales range reflects both the progress we have made and the significant long-term opportunity we see ahead as we continue to expand the clinical and commercial potential of this asset. I will conclude on slide 21. As we look ahead to the next decade and beyond, we see significant opportunity for growth, driven by Ziihera's potential to redefine what is possible across HER2-expressing cancers. The approval of Ziihera in GEA proves our ability to identify, develop, and bring highly differentiated, high-value assets to market, driving both clinical progress and long-term shareholder value. In addition, it is a validation of our vision to build a leading biotechnology company focused on innovative, life-changing medicines for rare diseases. As we expand the zanidatamab development program, we will explore both Jazz-sponsored and collaborative clinical trials to realize the full potential of this unique medicine. We are laser-focused on delivering a strong launch in GEA and realizing the increased Ziihera peak sales opportunity of $3 billion-$5 billion through continued data generation, thoughtful global expansion, and disciplined commercial execution. I would like to take a moment to acknowledge and thank the patients, physicians, caregivers, and Jazz team members for their commitment and dedication to bring Ziihera to this point. It has been an incredible effort over many years to reach FDA approval for GEA patients. With that, I will turn the call back to the operator to begin the Q&A session. Thank you. Our first question today is coming from the line of Jessica Fye of JPMorgan. Please go ahead. Hey, guys. Good afternoon. Congrats on the approval and thanks for taking our question. I am curious, of the new $3 billion-$5 billion peak projection for Ziihera, how much of that is accounted for by BTC and GEA, and how much of that is from additional indications? If I can ask for forgiveness in advance on asking a second question, can you talk about how you get to that 3,000-4,000 eligible frontline patients in the U.S. for Zani? What cuts do you take to get to that number? Thank you. Hi, Jess. It's Sam. Thanks for your question. Yes, obviously over the last couple of years, we've learned a lot about the potential for Ziihera, and we're very excited now with the approval of GEA to upgrade our peak potential for Ziihera to $3 billion- $5 billion. As you may recall, the original estimate of $2 billion+ included both first-line BTC, the GEA approval, as well as the metastatic breast cancer in cancer tumor. The new $3 billion - $5 billion range obviously goes beyond that now with the approval of GEA. We're excited about taking Ziihera into other HER2-expressing cancers such as colorectal cancer, non-small cell cancer, early-stage GEA, and early breast cancer. While we're not providing a split between those indications that makes up the $3 billion- $5 billion peak, what I can say is that the BTC and GEA are a significant contributor to that. We're obviously now with the label. We're really excited to get going in GEA and start to deliver on the potential there. Just to the second part of your question, we've obviously talked about the 8,000 patients before. Now as we look at the FDA-approved label, we're able to provide more specificity on what the exact kind of addressable patient population is of those 8,000. To get to the 3,000- 4,000, we're obviously looking at the unresectable disease patient population, as well as those that are eligible to receive treatment in the first-line setting and those who receive HER2 testing. So from that, we go from the 8,000 to the 3,000 - 4,000. Thank you. One moment for the next question. Our next question is coming from the line of Marc Goodman of Leerink. Please go ahead. Anything on the label that was a surprise to you? The commentary around the diarrhea, probably not. What about the IHC 3+ doublet kind of restriction? Anything there or that commentary? Thanks. Hi, Marc. This is Rob. Thanks for your question. To me, the label is very, very favorable. We were really pleased to have approval of zanidatamab as now the preferred regimen for HER2 GEA approval with tislelizumab and irrespective of PD-L1 status. We really feel that the triplet is appropriate for every patient, unless there is a specific contraindication. On the diarrhea, it has been addressed already. This is a known toxicity of zanidatamab when combined with certain chemotherapy. We found in the conduct of the clinical trial that it is very manageable with very few patients actually discontinuing Ziihera due to diarrhea. Chumi touched on the education that is planned around this, which will be very important. We think that some of that diarrhea is driven by capecitabine and may even be more manageable with FOLFOX in the U.S. when given appropriate prophylaxis, and attending to onset of diarrhea. We are very pleased that the triplet is approved again, irrespective of PD-L1 status. Of course, that is for both IHC 2+ and IHC 3+. Again, I think that this is a very poor prognosis disease. Many patients do not make it to second-line therapy. It is clear that the addition of tislelizumab benefited patients, which is consistent with prior PD-1 therapies in gastric cancer. We think the triplet is really the new standard of care. With regard to interpretation of data on IHC 2+, that is a very small subset. It is true from an epidemiology perspective, most patients who are HER2-positive or IHC 3+ in the trial was a very small subset. We think that the data are probably confounded by other factors, as is evidenced by overperformance of the control arm, where even in the control arm, IHC 2+s did better than IHC 3+s. Overall, very favorable label from our perspective, and we think zanidatamab is now a HER2 agent of choice in this setting, and the triplet really should be the standard of care for everyone who is eligible. Thank you. One moment for the next question. Our next question is coming from the line of Gregory Renza of Truist Securities. Please go ahead. Greg, good afternoon, Jazz team. Let me add my congratulations on the approval as well. For Rob and Samantha, just circling back to the change in your belief in the peak sales opportunity. Certainly, a decisive statement on going from, as you noted, Samantha, the IHC 2+ to $3 billion-$5 billion. We appreciate the color you have provided. Just to add on that, just curious if you could comment a bit on how you are characterizing perhaps any change in the time horizon to peak or the time to getting to that peak potential to the $3 billion-$5 billion. Also, are there any alterations in how you are looking at the geographic spread that has also informed your conviction today on those numbers? Thanks so much, and congratulations again. I can first of all comment on the peak sales potential. We had already always said $2 billion +, and now we are being more concrete around what that plus actually represents. Obviously, with this GEA approval, it discharges some of the risk around some of the other studies that we have ongoing. We know that we have our development program in breast cancer, which is obviously one of the largest opportunities that we are now very excited about. Rob can speak a little bit about some of the timings associated with that. And obviously moving into early breast cancer as well, which will be a significant contributor to the overall peak potential for the program. So maybe, Rob, if I hand over to you to say a little bit about the time horizon for some of those study readouts. Yeah, happy to. And I will just very quickly maybe give a broad description. So remember, we are approved in second-line BTC, but we have a front-line BTC that is ongoing and progressing very well, where there is no HER2 therapy approved in that space. So combining with PD-L1 in that setting, we think the prospects of that being a positive study are very, very high. We now have the definitive new standard of care in front-line GEA. We are very interested in exploring other aspects of gastric cancer. I think there is the potential in early-stage gastric cancer where, again, there is no approved HER2 therapy. As Sam mentioned, we have made meaningful progress on a phase III trial in a later-line breast cancer setting post ENHERTU, which was kind of an obvious first place to go with zanidatamab in breast cancer given how ENHERTU is changing that treatment landscape. And this will really be the only pivotal trial that looks specifically post ENHERTU. And there again, it is a head-to-head comparison with Herceptin. But we had broader ambitions in breast cancer. As Sam mentioned, we have ongoing phase II work in neoadjuvant breast cancer in our EmpowHER-208, as well as collaborations with I-SPY and MD Anderson Cancer Center. And we will look to interpret those data and potentially move to a pivotal trial in neoadjuvant breast cancer. We have collaborations with both Boehringer Ingelheim as well as Iambic Therapeutics on novel TKI combinations with zanidatamab, starting in breast cancer, but potentially in other settings. And the importance there is that that combination could be quite powerful, allow us to get to even earlier lines in breast cancer and difficult to treat populations such as brain mets. And then we have aspirations beyond that. You may have seen that we have breakthrough designation now in colorectal cancer. We will be working with FDA to define a path to approval with colorectal cancer. We have an ongoing pan-tumor trial, which ultimately could give us a tumor-agnostic indication. That trial is also enrolling non-small cell lung cancer patients who are overexpressing HER2, and there may ultimately be a path there as well. A lot of opportunity now given the results that we have so far with zanidatamab. Thank you. One moment for the next question. Our next question is coming from the line of Annabel Samimy of Stifel. Please go ahead. Hi, thanks for taking my question. It was good to see the broad label. I was curious about the extent to which Ziihera could be used with pembrolizumab rather than tislelizumab. Do you think there is going to be any kind of interchangeability in the marketplace, and how do physicians approach when they have been using pembrolizumab? Just some curiosity about that. Also, the 3,000- 4,000 eligible patient population, is there an opportunity moving it towards the 8,000, or is the 3,000- 4,000 quite set? Thanks. Yeah. The study was conducted with tislelizumab, which is already approved in the U.S. We think there is little obstacle to combining with tislelizumab. However, as you said, multiple other PD-1s have shown efficacy in gastric cancer. We do have an ongoing trial combining with pembrolizumab, which should provide some, let us say, safety and preliminary efficacy, such that if there were some compelling reason to use a PD-1 agent other than tislelizumab, we think zanidatamab would certainly be compatible. Hi, Annabel. It's Sam. The three to four patient population. This patient population that we're talking about here, that is reflected in that $3 billion-$5 billion peak estimate that we've provided. Within that, obviously, we're looking at the kind of unreflectable disease. There's also those that get a test. We will be focusing on ensuring that patients that are tested, first of all, that they're tested for HER2-positive, that's obviously routine, but those patients that are tested and are positive for HER2, then they are treated with zanidatamab. So these are all the areas that we'll be focused on during the launch phase. Thank you. One moment for the next question. Our next question is coming from the line of Jason Gerberry of Bank of America. Please go ahead. Hey, guys. Thanks for taking my question. Mine was just, would you expect physicians to prioritize the doublet in elderly patients? Some of the language in the label seem to suggest that the diarrhea profile, more severe cases, was less with the doublet. So curious, it's a meaningful size subgroup within GEA, if you think the doublet would get traction there. And how you think community docs will navigate some of the prophylactic measures with the diarrhea, and if there's any analogs you can point us to that give you a high degree of comfort how that would be managed by community oncologists. Thanks. Sure. So with regard to the older population, I do think that every eligible patient, unless there's a specific contraindication, should get the triplet. Remember, this is still a very lethal disease. It's clear that tislelizumab added to the benefit irrespective of PD-L1 status. You can even see as you look toward the latter parts of that curve, that there's some encouragement there that that might persist. We believe that the mechanism of action potentially synergizes with the PD-1, and this is a disease where you don't want to sequence the therapies. You really want to give these best therapies up front where there may be synergy, and you get the full benefit. In terms of toxicity as it was observed in younger than 65 or older than 65, interpret that with some caution. You start to get to small subgroups where other factors may be at play. I would just point out specifically with regard to diarrhea, these are easily distinguished. The zanidatamab diarrhea comes on early, whereas tislelizumab diarrhea is more immune-related and tends to be more delayed. There are diagnostic evaluations that really can distinguish the two. I will let others comment potentially on differences in community practice. But as I said, we conducted a very large global trial where we think the diarrhea is managed very well. There is needed education around starting with prophylaxis, ensuring the patients alert doctors promptly if they have onset of diarrhea, because more can be done in terms of supportive care, in terms of upping the anti-diarrheal therapy. The label pretty clearly says to first modify chemotherapy so that you can maintain exposure to Ziihera, which is really critical for the survival benefit. These various things that we know about how to manage will be subject of education for any new prescriber, whether that be tertiary care centers or in the community. I think everyone will be well-equipped to manage this well. But maybe Sam or Chumi would want to add to that answer. I would just add that, of course, the benefits of using Ziihera in this patient population are clear from the data that we have, that we are familiar with now. In the clinical trial, discontinuation rates of Ziihera due to diarrhea was low, less than 5%. What we want to do now is ensure that those results can be replicated in the real world. We will be investing significantly to ensure that our patient doctors are supported, to ensure that patients can stay on treatment and get the full benefit of Ziihera. Maybe I will just ask Chumi to comment here a little bit around some of the investments that we are making to achieve those goals. Thank you, Sam. So we have invested in education around management of diarrhea, and we made some strategic investments that support sustained patient adherence, which is obviously important. We have a clinical nurse educator team that will provide support to nurses on patient initiation and management so that they have a first great experience. We are doing peer-to-peer education speaker programs that are targeted specifically at the community and will proactively educate on the evolving treatment paradigm, as well as the compelling efficacy and data. By supporting this education around long-term adherence, we can help patients achieve the best possible outcomes. We are prepared to do that. Thank you. One moment for the next question. Our next question is coming from the line of Leo Timashev of RBC. Please go ahead. Hey, guys. Thanks for taking my question and congrats on the approval. I wanted to ask more broadly on the development strategy. You guys are running the basket study for potentially, and you talked about how it would potentially be registrational for tumor agnostic label, but you are also exploring a potential registrational study in colorectal and in non-small cell, and I guess those would also be included in the basket study. I guess what I am asking is, how are you thinking about the differences that specific studies in colorectal non-small cell could add to the opportunity? I guess how you are thinking about what those clinical trials would be enrolling in terms of patients, and just any sort of differences in future labels that you would be aiming for or patient segments. Thanks. Sure. I am happy to take that question. The basket study or the pan-tumor trial was really meant to allow us to enroll the patients that we would needed ultimately to get a tumor agnostic label. We are progressing toward that goal. We continue to think that that is potentially a pivotal trial for that purpose. It is a place where we can get additional data in refractory colorectal cancer patients as well as non-small cell lung cancer patients, in addition to any patient across a whole range of rare tumors who overexpress HER2. There may be an opportunity for a tumor agnostic indication, in addition to having enough patients in any one indication, such as colorectal or even non-small cell lung cancer, where you may get a specific label in that regard as well. Remember, for colorectal cancer patients, we had some phase I data. I think there were 28 patients in the phase I. We are adding to that in the Study 206 pan-tumor. On the basis of the combination of those from phase I and from the 206 study, we received breakthrough designation. The next step now is to agree with the FDA on path to an approval for colorectal cancer. But you are right, it is an opportunity for a pan-tumor or tumor agnostic indication, as well as to generate data that could give us specific indications. Then, of course, there is the opportunity to go beyond that. That would be in a refractory setting, but there is always the possibility of then expanding into earlier lines as well. Thank you. One moment for the next question, please. Our next question is coming from the line of David Amsellem of Piper Sandler. Please go ahead. Hi. Good afternoon. Thanks for taking our question. This is [Allie] on for David. Looking beyond the U.S., you've cited a combined annual incidence of, I believe, 63,000 across the U.S., EU, and Japan. Can you please provide more color on the EU specifically and the number of annual cases there, and just a general broad refresher on how you're thinking about the EU opportunity? Thanks. Yes. Thanks for the question. Yes. We've said 63,000 patients, GEA, and that reflects globally the U.S., Europe, and Japan. We are excited about taking zanidatamab, obviously more broadly with this GEA indication. We're anticipating an EMA approval before the end of this year. We've also, as part of Project Orbis, there has been the FDA filing has been also simultaneously completed in the U.K. and in Health Canada, so also anticipating approvals there in the foreseeable future. So yeah, excited about the potential for GEA beyond just the U.S. into these major markets soon. Thank you. One moment please for the next question. Next question's coming from the line of Gary Nachman of Canaccord Genuity. Please go ahead. Thanks, and congrats on the approval. So any commentary on what you think uptake should look like for the first few quarters of the GEA launch? How much pent-up demand is there within the 3,000- 4,000 treatable patients that was waiting for this approval? How smooth reimbursement will be using the existing J-code? Based on the GEA approval and label, would you consider modifying anything in the breast cancer and other future studies? Thank you. Thank you very much for the question. We are really excited about the label approval today, very excited about the label itself and the opportunity that gives us with Ziihera in this indication. As you know, we have been established in the field now, with BTC and with our solid tumor team in general, across the Ziihera as well. That gives us a major foothold that was established. Chumi mentioned the strong overlap between prescribers, which means those relationships have already been developed. A lot of the friction that you might anticipate with a new launch doesn't really exist here because of the fact that we have the permanent J-code in place, reimbursement established as well. I will just hand over to Chumi, who can speak a little bit about our plans here to really accelerate the launch of Ziihera. We believe this data is really important for patients, and we believe that it is going to be very important for us to hit the ground running, and ensure that patients can benefit from this treatment as soon as possible. Our plan, and ambition really reflects that. So Chumi, perhaps you can add a little bit more depth and color as to how we plan to do that. Yeah, sure, Sam. We are really, really excited about the label that we have gotten and are ready to go. Our team is right-sized to capture the larger GEA market, without requiring major expansion. We did add some MSLs last year, and so we are ready to go. Not only do we have 90% overlap with BTC, but we have also been, as you know, very successful with Ziihera, and it is the same team that has a strong presence in the community accounts and academic accounts. So we are very established amongst our headline prescribers. So we are ready to go. We have got the payer access. As Sam said, we have the J-code. In addition to that, our state-of-the-art JazzCares support services, along with flexible ordering and fulfillment options, will ensure that providers can access Ziihera efficiently and without delay. Thank you. I think part of the question is also, do we learn anything there that impacts our thinking on breast cancer? I would just say we're satisfied with the design of the breast cancer trial that's ongoing. We certainly learned a lot from the GEA trial, though. One thing was when you put zanidatamab up against Herceptin directly in the context of GEA at least, I think you can infer results in other contexts as well, it beats it definitively. The other is that we think this mechanism action with zanidatamab probably synergizes with immunotherapy. If you think of all the trials that have been done with PD-1 agents, in gastric cancer, they've all had restricted indications to patients whose tumors are PD-L1 positive. This is the first trial showing activity in PD-L1 negative patients, really suggesting that immune activation occurring with zanidatamab due to its unique mechanism of action is probably synergizing with immunotherapy. That does make us think that wherever we can go head-to-head with Herceptin, wherever we can combine with a PD-L1 or PD-1 antagonist like frontline BTC, like early gastric cancer, other settings, that could be a pretty good formula. Perhaps just before we close this question, I think the other element of this, was whether we expect a kind of bolus of patients that would be waiting for treatment. That's not something that we anticipate in this space. Typically, when patients get a diagnosis, they get treated right away. So, yeah, that shouldn't be part of the expectation here. I might also just add that on the previous question when we were talking about the EU, the expectation is that we will make a submission to the EU by the end of the year and not approval. So apologies for that. Just wanted to clarify that. Thank you. One moment please for the next question. Our next question is coming from the line of Sean Laaman of Morgan Stanley. Please go ahead. Good afternoon, Jazz team. Congratulations and hope everyone's well. Obviously, a big ramp to get to the new peak sales, but what early commercial data point do you believe would give investors confidence that the peak sales estimates may prove indeed reasonable? How are you thinking about guiding? What sort of metrics do you think you might unfurl to investors as we go quarter -to- quarter during the launch? Thank you. Yes. Thanks for the question. In relation to the confidence, I think we're very confident about our potential to realize the full potential of Ziihera. We've seen a very strong uptake in BTC achieving standards of care in that space. We've also demonstrated our ability to execute in the community with the launch of Ziihera and IMforte. So we've got strength in this area, we've got experience in this area, and we're very confident about being able to execute here too. In terms of what we'll be reporting here will be quarterly sales. Maybe I'll just hand over to John here just to comment a little bit further on the guidance side of things. Sure. Thanks, Sam. Yeah, Sean, I think the revenue number, as Sam's saying, is really the one to watch as the GEA launch gets off the ground. Then, we'll be looking closely at the metrics and evaluating if there's good information we can provide to the Street to help you assess how the launch is going and how Ziihera is being accepted commercially and clinically. I wouldn't want to commit to anything specific right now, but we want to make sure that you've got good visibility, as we do, to how things are going. We're excited about the GEA launch. Thank you. One moment for the next question. Our next question is coming from the line of David Hoang of Deutsche Bank. Please go ahead. Hi there. Thanks for taking my question, and congrats on the approval. I just wanted to ask about if you have your latest visibility on the NCCN review process and whether we should be expecting Category 1 recommendations for the doublet and the triplet. Is that recommendation in any way a gating factor to see more brisk uptake of Ziihera in GEA? Thank you. I can start by commenting on the process. We obviously don't control the timelines for NCCN. We know they have a regular meeting every year in August. We provided data every step of the way, including at the time of the abstract and post and oral presentation at ASCO GI and then the New England Journal of Medicine paper. Now we have approval, so we're very confident in the label that we have and the data that support that label, and we do think that should come through to a Category 1 on NCCN. This is a drug that has a survival advantage showing more than seven months' difference in the triplet arm at a median level at the first interim analysis. Yeah, I might just add, I think given the strength of the data, we would anticipate NCCN Category 1 listing. Had that NCCN approval come through earlier than the approval, then that might have paved the way for patients to have access sooner than the approval. But now that we have the approval and we have the label that we're thrilled about, we know the strength of this data. We have the J-code already in place. Then we're not anticipating any friction here when it comes to access. In fact, our sales teams have been trained on the label, and they're in front of customers as of this afternoon. Everything is in place for us to be able to execute this launch, I think, extremely well. Thank you. One moment for the next question, please. Next question is coming from the line of Ash Verma of UBS. Please go ahead. Yeah. Hi there. This is Natalie on for Ash. Thanks for taking our question and congrats again on the label. Maybe just to build off of some of the prior questions, could you comment a bit more on the breakdown of patients in the community and what are some of your expectations for community growth? Thank you. Thanks for the question. Yes, perhaps I'll hand to Chumi to talk around our community strategy. Yeah. Thank you, Sam, and thanks for the question. The split between academic and community, about 30% of GEA is treated in the academic centers, and about 70% of GEA is treated in the community. As we launch, a lot of our investment and focus of the team is in the community setting. We have great relationships in the academic setting based on BTC, and a lot of focus of what we're doing is peer-to-peer education, working with the key community centers, and both our MSL teams as well as our sales teams are focused on education in the community and building upon relationships that we have due to Ziihera and BTC. We're ready to go there and focus there. Thank you. One moment, please. The next question's coming from the line of Joseph Thome of TD Cowen. Please go ahead. Hi, this is Jacob on for Joe. Thanks for taking our question. We were just wondering now that the doublet is approved in IHC 3+ disease, what specifically do you think the second interim OS analysis could potentially change on labeling NCCN guidance or maybe even commercially? Do you think a statistically significant OS outcome here could support a label update or a broader treatment recommendation? It seems like you're maybe leaning more toward a triplet right now where possible. Yeah. I mean, as we're reiterating that we're expecting that next interim this quarter, certainly there's the potential for there to be useful information that would then result in a label update. But I would just reinforce that at the first interim, the data were quite mature and the results were quite definitive. It wasn't necessarily stat sig because we put a relatively small alpha against it. But if you look at the hazard ratios for overall survival and even the median compared to the control arm, it was a clinically meaningful difference with pretty narrow confidence intervals there. So I think it definitively showed that zanidatamab beats Herceptin, and I'm not sure that the next interim, even if it's stat sig, changes my view on that. I think it's a favorable result. To your point, we do think that the triplet is going to benefit patients most for all the reasons that we said before. It can be used irrespective of PD-L1 status. It's a very poor prognosis disease where you really want to give your best therapy up front. In this case, we think there's potentially synergy between zanidatamab and a PD-1 antagonist like tislelizumab, so you want to combine them to get the greatest benefit for a population where previously maybe half the patients wouldn't have gotten to second-line therapy. Yeah, I would just reinforce that from the commercial perspective. We do believe that Ziihera in combination with tislelizumab and chemotherapy is the preferred choice for all patients, except those for whom it is not indicated or to whom tislelizumab may be contraindicated. Of course, in that patient population, that is for IHC 2+ and IHC 3+ across PD-L1 status as well. Commercially, that is where our focus will be. That is where patients are going to get most benefit. The arm B OS readout, we have everything in the label that we need right now to be successful. The OS readout to come obviously will be very interesting to see, and we would anticipate that the arm C with the tislelizumab would continue to strengthen as well. We are very excited with the label that we have. We believe that is going to give us every opportunity to really execute well commercially and ensure that patients can really make a really significant, meaningful benefit from this new treatment option. This does conclude today's Q&A session. I would now like to turn the call back over to Sam for closing remarks. Please go ahead. Thank you, operator, and thank you everybody for your questions today. We really hope that this overview of zanidatamab has conveyed our excitement about the potential for Zani to become the HER2-positive agent of choice. I would like to just close by thanking all of our Jazz colleagues for their commitment and dedication to bring Ziihera to GEA patients in need. Thank you all very much. This ends today's programming. Thank you so much for participating. You may now disconnect.