Jazz Pharmaceuticals PLC Ziihera Investor Webcast Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Jessica Fye - J.P. Morgan Securities LLC - Analyst : Hey, guys. Good afternoon. Thanks for taking my questions. A couple just to help me size the opportunity here. For the 3,000 US HER2-positive BTC patient number on slide 29, is that incidence or prevalence? And how many of those 3,000 patients are second line? And then just cutting that in the next step further, is the mix of IHC 2+ and 3+ in the trial reflective of the HER2-positive BTC patient population overall? Thank you. Abizer Gaslightwala - Jazz Pharmaceuticals PLC - Senior Vice President, Jazz Oncology & Head of US Hematology and Oncology Hey, Jess. Good to talk to you. It's Abizer. I'll go ahead and start answering the first question. I might refer to Rob on some of the demographics, the IHC 3 trial versus real world. In terms of the -- this is an incidence of BTC patients, HER2-positive, that 3,000 number is both first-line and second-line patients. We don't break that out any further than that. So I think that was your first set of questions. I think your second was around whether IHC 3+ in our trial corresponds to real world. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. DECEMBER 11, 2024 / 9:30PM, JAZZ.OQ - Jazz Pharmaceuticals PLC Ziihera Investor Webcast Robert Iannone - Jazz Pharmaceuticals PLC - Executive Vice President, Global Head of Research and Development, Chief Medical Officer I do think roughly it is real world, Jess. And you know that the great majority are 3+. And I would remind you that while we didn't have a particularly large sample size in the 2+ patients in the first-line BTC trial, we are allowing enrollment there, and that, of course, would be in combination with chemotherapy and immunotherapy. And we'll have an opportunity to study that population further.

Question: Jason Gerberry - BofA Global Research (US) - Analyst : Hey, guys. Thanks for taking my questions. Can you just remind me the proportion of the 3,000 US patients that you envisioned kind of fall into eligibility for second-line treatment, and how you're thinking about a duration of treatment assumption in BTC? And then lastly just any evolving thoughts in GEA, the proportion, the split of PD-L1-positive versus -negative subjects. Anything come out of the September FDA Ad Comm that maybe from those pooled analysis that maybe makes you think a little bit differently about the split? Thanks. Abizer Gaslightwala - Jazz Pharmaceuticals PLC - Senior Vice President, Jazz Oncology & Head of US Hematology and Oncology Yeah. Hey, Jason. It's Abizer. I'll maybe start to address some of your first questions. Again, just to reiterate, we don't really break out the 3,000. There's a lot of assumptions that go into that. And so we just want to kind of leave it at the 3,000 annual incidence. We feel good about that number based on some public databases. And so that is the incident population across front line, second line and beyond. In terms of, I think, your question around how to think about the rate -- or treatment responses, et cetera, I would probably refer to the data Dr. Pant presented in terms of some of the data on clinical efficacy and use that. And that's how we think about modeling, the potential use of therapy over time in patients, appropriate patients. So I'll just refer to that data Dr. Pant presented earlier in the presentation. Rob, I don't know if you want to outline a little bit around the GEA question. Robert Iannone - Jazz Pharmaceuticals PLC - Executive Vice President, Global Head of Research and Development, Chief Medical Officer Sure. Yeah, I do have a few thoughts on the GEA PD-L1 question. So certainly, we don't think that the breakdown in the KEYNOTE-811 necessarily represents the epidemiology. Probably patients who were tested PD-L1 positive may have been over-enrolled in that trial. I think that the prevalence

Question: Annabel Samimy - Stifel, Nicolaus & Company, Inc. - Analyst : Hi, thanks for taking my question. I want to ask -- I guess zani is or Ziihera is in a relatively unique position given it's the only one that's approved for second-line BTC. There are others on the -- that are listed in the compendia listing but through a pan-tumor trial or a basket trial. So I'm just curious from a price sensitivity perspective -- maybe Dr. Pant can answer that -- how do you think about the different options that you have given the several recommendations and the compendia listing and then the price sensitivity? How much does that play into it? And then I have a couple of follow-ups. Shubham Pant - The University of Texas MD Anderson Cancer Center - Professor, Department of Gastrointestinal Medical Oncology and Department of Investigational Cancer Therapeutics Yeah, thank you. Hi, this is Dr. Pant here. So price compendia, I'm not sure about. But I can tell you as a clinician -- so again, there are two kind of FD approved. If you look at it, one basket is trastuzumab deruxtecan and the second one is zanidatamab, right? And this is -- again, it's a personal choice by physicians treating. For me, the patients get GemCis and durva or GemCis and pembroluzimab front line. And that's chemotherapy with biliary tract cancer patients. So these patients, when they kind of get into the second-line setting, they're a little bit -- they've been through chemotherapy. Their bone marrow is a little burnt out. So they may be feeling the effects of chemotherapy. So for me, specifically, I would more think about doing second line and if they progress, then doing trastuzumab deruxtecan after that, but that's just me. And the reason for that is that I think that they get this kind of chemo-free interval in the middle before we introduce the next one. But again, it might -- it's a very personal choice amongst physicians. There are different choice available. But I think, that's the way I would use these two drugs that, zani and trastuzumab deruxtecan as far as sequence is concerned. Did that answer your question?

Question: Andrea Newkirk - Goldman Sachs & Co. LLC - Analyst : Hi, everyone. Thanks for taking the question. Two for us, please. Now that Ziihera is commercially available, just curious how much disease or drug education you believe will be required to drive prescribing. And then also just wondering if there are any launch analogs you would point us to help us think about the cadence of uptake in 2025 and beyond for second-line BTC here. Thanks so much.

Question: Gregory Renza - RBC Capital Markets (Canada) - Analyst : Great. Good afternoon, everyone. Congrats on the approval. Thanks for taking my question. Renee, maybe a question for you as you definitely noted just this being Jazz's third launch in oncology since 2020. And as you and Abizer and the team have discussed, the overlap in the call universe. just curious what this means in terms of validation and in your interest to really build the armamentarium in the solid tumor and oncology place to arm your field force with more products and more options for commercial and for patients. And maybe just touch on how validating this is with maybe Jazz's more recent business development approach with zanidatamab a few years ago, what the approval means for that strategy. Thanks so much.

Question: Joel Beatty - Robert W. Baird & Co. Incorporated - Analyst : Hi. Thanks for taking my questions. The first one is on the 3,000-patient incidence, is that 3,000 unique patients, or is there some patients that are

Question: Ami Fadia - Needham & Company, LLC - Analyst : Hi. Good evening. Thank you for taking my question and congrats on the launch. My first question is just about -- maybe for Dr. Pant and Abizer -- how do I think about these disbursement of patients across the academic and community setting? And with the recommendation added on to the NCCN guidelines, can you at least qualitatively talk about the adoption curve we should see across the two settings? And then just the one thing we noticed on the NCCN guidelines, the wording indicates that zani is added in Category 2A but useful in certain circumstances, recommendations. So I didn't know what to make of that. So if you could address that, that would be helpful. Shubham Pant - The University of Texas MD Anderson Cancer Center - Professor, Department of Gastrointestinal Medical Oncology and Department of Investigational Cancer Therapeutics I can take the first question. As far as uptake, what I've seen over the last decade, actually in cholangiocarcinoma or biliary tract cancers is that there has been a lot of -- testing has become fairly standard across -- because at Anderson, we get a lot of patients from outside. There are big cholangio center patients come self-referred or we get patients sent from other physicians to look for trials. And I can tell you that I've really seen an uptake in sequencing and testing for these patients. So I think that kind of pool of patients that are already tested, and they're looking at it, and that target is growing. So I think it's definitely there because, again, like I think somebody mentioned before about HER2 testing and -- in a community, they've been doing it for a long time, right, for other -- like for breast cancer and other. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. DECEMBER 11, 2024 / 9:30PM, JAZZ.OQ - Jazz Pharmaceuticals PLC Ziihera Investor Webcast And I've seen like a lot of testing because of FGFR inhibitors and H1 inhibitors, other targets in biliary tract cancer. That uptake definitely seems -- so it's fairly -- we're able to see that in the community as well as in academics, at least the testing part of it. The second question, maybe somebody else could answer on the NCCN. I'm not sure about the category thing. Robert Iannone - Jazz Pharmaceuticals PLC - Executive Vice President, Global Head of Research and Development, Chief Medical Officer Could you just repeat the question, Ami? Make sure I understand.

Question: Mohit Bansal - Wells Fargo Securities, LLC - Analyst : Great. Thank you very much for taking my question. And again, thank you for this update. I have a question regarding GEA. So do we know in the first-line setting, what percent of patients are taking herceptin combination with the checkpoint inhibitor versus herceptin plus chemo combination? And then when you see your first-line GEA data, how would you think about the PD-1 plus zani plus chemo arm? Do you think that one should compare it to 811 trial? Obviously, it's a cross-trial comparison but -- or it will be just like the benefit of checkpoint on top of zani. How would you think about it? Thank you. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. DECEMBER 11, 2024 / 9:30PM, JAZZ.OQ - Jazz Pharmaceuticals PLC Ziihera Investor Webcast Robert Iannone - Jazz Pharmaceuticals PLC - Executive Vice President, Global Head of Research and Development, Chief Medical Officer Sure. So similar to the answer I gave before, it's clear now from the data that it's only patients who are clearly expressing PD-L1 are likely to benefit from a PD-1 inhibitor. What proportion of patients is that? And the literature is a little bit varied on this point, but it may be sort of 60-40 -- so still a fairly large proportion of patients who would be getting -- for whom the standard of care would still be considered to be herceptin and chemotherapy. And the way we're looking at this is zanidatamab is going to be positioned to be the HER2 therapy of choice. We now have data, as we've mentioned in the presentation, across tumor types, across lines of therapy as monotherapy, and combination, in patients who are refractory or naive, [HER2] therapies really differentiating zanidatamab as the best-in-class monoclonal antibody and the only bispecific, biparatopic, monoclonal antibody. So we think it's going to be the HER2 agent of choice in front-line GEA regardless of the PD-L1 status, which doesn't predict at all response to HER2 therapies. For those patients who are expressing PD-L1 or are likely to benefit from a PD-1 inhibitor, they could get zanidatamab potentially in combination with the PD-1 inhibitor. Ultimately, based on the results of the ongoing Phase 3 trial, where we have two experimental arms: zani plus chemo or

Question: Jeff Hung - Morgan Stanley & Co. LLC - Analyst : Thanks for taking my questions. In the past, you've said that there's overlap with your existing solid tumor footprint from Zepzelca. How many additional reps -- sales reps did you hire for Ziihera? How many reps in total are now detailing the drug and what proportion of second-line BTC physicians and patients can you cover with the sales footprint? And then, for Dr. Pant, what proportion of your BTC patients would be eligible to be treated with Ziihera? And can you just talk through how you see the pace of adoption in your Ziihera treatment naive patients playing out over the next 12 months? Thanks. Abizer Gaslightwala - Jazz Pharmaceuticals PLC - Senior Vice President, Jazz Oncology & Head of US Hematology and Oncology Sure. So I'll take the first question. In terms of our commercial footprint, we won't get into specifics about numbers and size. That was just proprietary in how we think about our commercial model. What I'll say is that we leverage -- there's a high level of synergy with what our team currently does in the lung cancer space with Zepzelca for how we think about launching Ziihera in BTC and eventually GEA. I mean, as I mentioned earlier, a lot of solid tumor drugs are treated in the community oncology setting. Community oncologists, by definition, generally treat many types of solid tumors. They have multi-group specialties that have special tumor focus. But then within that same umbrella, they treat a wide variety of tumors. And so we feel that construct serves as well for lung cancer, as we know GI cancers, across the specifics, which are really good. And it's been an incremental add but a really incremental add and a really good synergy in terms of what we're doing in the solid tumor space. I'll let Dr. Pant take the second question. Shubham Pant - The University of Texas MD Anderson Cancer Center - Professor, Department of Gastrointestinal Medical Oncology and Department of Investigational Cancer Therapeutics And could you repeat that question for me, please? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. DECEMBER 11, 2024 / 9:30PM, JAZZ.OQ - Jazz Pharmaceuticals PLC Ziihera Investor Webcast

Question: Joon Lee - Truist Securities - Analyst : Hey, thanks for taking our question. In the ongoing trials for first-line BTC, GEA, and breast cancer, do you also expect 3+ HER2 expression would be needed to show clinical benefit. Or are there other nuances that we should be considering? Thank you. Robert Iannone - Jazz Pharmaceuticals PLC - Executive Vice President, Global Head of Research and Development, Chief Medical Officer Yeah. So remember, we had a relatively small sample set in the single-arm monotherapy BTC trial that led to the accelerated approval. The other trials you mentioned, for example, in the front-line BTC or front-line GEA as well as the later-line breast cancer trial are all in combination with other chemotherapy agents and in indications, where there is maybe a clear track record for the value of HER2 therapies. And so I wouldn't necessarily read through a restriction in those indications to just the 3+. We are evaluating 2+ and 3+, and we're optimistic that the benefit will be broad.

Question: Joseph Thome - TD Cowen (Research) - Analyst : Hi, there. Good evening. Thank you for taking my questions. Maybe the first one for Dr. Pant. I guess, is there any IHC 3+ HER2-positive BTC second-line patient identified that you would not treat with Ziihera for any reason, and what would be that reason? And then a little bit of a follow-on to Joon's question maybe, in the GEA study, are there prespecified subset analyses for IHC 3+ population and those that are IHC 2+, ISH+? Thanks. Shubham Pant - The University of Texas MD Anderson Cancer Center - Professor, Department of Gastrointestinal Medical Oncology and Department of Investigational Cancer Therapeutics Yes. So I'll leave the second one to Rob. I'll answer the first one. It would be rare. As somebody who's actually treated patients on Ziihera in the Phase 1 trial and now in the Phase 2, it's very well tolerated. These patients -- it's a non-chemo option. These patients that go about their day, really side effects are very easily manageable. So the one -- if I had to guess, would be maybe somebody with a low ejection fraction that I wouldn't want to give it -- congestive heart failure or something that I think could be a challenge. That's the main one that comes to mind. But GEA, I'll let Rob answer that one or somebody else from Jazz Robert Iannone - Jazz Pharmaceuticals PLC - Executive Vice President, Global Head of Research and Development, Chief Medical Officer Yeah. Do you mind just repeating the second part of the question?