Jazz Pharmaceuticals plc ($JAZZ)

Hi, everyone. Good afternoon again, and thank you for joining us at the 2026 TD Cowen Biotech Oncology Innovation Summit. I'm Joe Thome, one of the biotech analysts here and the team at TD Cowen. It's my pleasure to have with me today 2 members of the Jazz Pharmaceuticals team. We have EVP Global Head of R&D and CMO, Rob Iannone and we have the Head of Investor Relations, John Bluth. So thanks guys for joining us today. Maybe to kick things off...

Joe, just really quickly. Little housekeeping. Rob and I going to make some forward-looking statements today. So please do refer to our SEC filings to reference those. We also may refer to earnings and guidance, if we do. We're referring to our most recent guidance as of our first quarter update and the same is true of any non-GAAP financial measures. You'll find a reconciliation in our first quarter earnings report. Thanks, Joe. And happy to be here with you.

Yes. Maybe just to start things off, obviously, a lot of progress at Jazz over the past year. Maybe kind if you want to give us a brief update on kind of what we've seen with the business, where we're headed? And maybe specifically over the next 3 to 5 years, where do you see the oncology business headed for Jazz.

John, would you like me to start? Or would you... .

Yes, Rob, why don't you dive in there as the oncologist.

Sounds great. Thanks for the question. Incredibly exciting times for us at Jazz, It's now my seventh year at Jazz, and it's been quite a journey, building a pipeline, building R&D and increasingly having an important stake in oncology across a number of different programs. For zanadatumab, starting with the approval in second-line BTC. This is a major accomplishment. We also saw an approval in from [ Odeso ] in high-grade glioma, an area of extremely high unmet need and also expansion of Zepzelca into the frontline for extensive stage small cell lung cancer where we think Zepzelca will be the most impactful. In terms of our pipeline beyond the most recent approvals, I would emphasize zanidatamab and the incredible opportunity that, that provides. You've seen the top line data for the GEA trial, frontline GEA trial. We're expecting publication in a top-tier journal, hopefully, in the very near future and our process for submissions globally are underway. We have breakthrough designation in the U.S. as well. as real-time oncology review and priority review giving us a PDUFA date of August 25, and we are expecting approval on and before that date. We are also expanding out in other areas for zanidatamab. We have a trial in later-line breast cancer post in HER2, which is accruing very well, and we said expected to complete its accrual midyear next year with results as early as late 2027. We also have an opportunity from a basket trial that we're conducting with Zanidatamab, where we potentially could get a pan-tumor or tumor-agnostic indication and that continues to progress as well. An early pipeline also that continues to grow and progress. And so for oncology, really exciting times for us.

Great. Excellent. Well, maybe just because it's been such a large investor focus, we can start off with first-line GEA. I guess first we have to ask, are there any sort of updates on the progress of the regulatory review for frontline GEA and maybe what's the team doing now to make sure that you're ready for a potential launch given that it is under RTOR and it could essentially come any day.

Sure. Yes. So without commenting on details of regulatory actions, which we don't do, there has been a steady flow of information that we have put into the public. We said we had [indiscernible] if you back calculate from an August 25 PDUFA date for a priority review, we would have completed that submission at the end of February, with real-time oncology review, we would have had the opportunity to provide data sets ahead of that to enable the FDA's review. Now we only had data through the end of November. So it was a pretty rapid and very proud of our team for so quickly mobilizing to get these critical data and information to the FDA. So we didn't have a lot of time in there. But nonetheless, we were able to leverage our RTOR to facilitate even the FDA's review even ahead of our completing this submission at the end of February, which is what set the PDUFA date. We were pleased to get breakthrough designation and of course, pleased to get priority review. So we think we're on track for an approval by or even ahead of that PDUFA date. We're expecting a publication in a top-tier journal. And as soon as we have that publication, we will update NCCN, and there is a possibility of NCCN adoption even ahead of...

And when we think about a potential label, maybe can you go into maybe some of the data specifics that give you confidence that you can get a broad PD-L1 positive and PD-L1 negative label? Is that your expectation? And maybe when you think about in a triplet regimen potential combination partner, do you think you'll be agnostic to combination partner in real-world practice? Or how will that kind of factor in when you think about the PD-1?

Well, let me start by just telling you what I think the data showed. The study was -- the experiment was designed to test head-to-head zanidatamab versus Herceptin. And those results are clear zanidatamab [indiscernible] Herceptin how you looked at the data, which endpoint you looked at that and Herceptin really should be a historical regimen. And I think that's the most important thing. For these patients, the first decision tha doc faces is, how do I address the HER2-driven disease. And now there's a new standard of care, I believe, is Zanidatamab in front line GEA. The next question is, would patients benefit from a PD-1 inhibitor. Lots of prior data with PD-1 inhibitors in gastric cancer broadly, clearly established, although only in the PD-L1 positive subgroup, all of the labels have that limitation of [indiscernible] PD-L1 negative patients. And certainly in HER2-positive gastric cancer, KEYTRUDA demonstrated a benefit again in PD-L1 positive patients. So lots of prior data that a PD-1 inhibitor is effective in gastric cancer, HER2-positive or HER2 negative. And so this trial was designed to look at that as well. As you know, with third experimental arm where we added tislelizumab. And I think the data are also definitive across PFS, landmarks as well as overall survival that adding a PD1 inhibitor and tislelizumab in this case, it's adding benefit. The study wasn't powered to show a difference between the 2 experimental arms, but it certainly is definitive when you look at Arm c with tislelizumab compared to Herceptin chemo with a 26-plus month median overall survival versus a little less than 2 months. So clear that tislelizumab is adding benefit. And importantly, in both populations of PD-L1 positive or negative. I think the data are clear there. They contrast all prior data, and you might say, well, would that be the case? How do you explain this? We think the differentiated mechanism of action that Zanidatamab has is explaining this. We know as has been published in Nature Communications that the mechanism for Zani different than even giving to the combination of 2 antibiotics like Herceptin and Perjeta. And the reason is that Zani binds to 2 different receptors. Once the antibody binds to 1 receptor, the other open binding site can't reach around on the same receptor. It has to grab another receptor. And that causes receptor clustering internalization. It also creates an opportunity importantly for complement to be fixed and the complement cascade to be triggered. So that, in addition to a highly active Fc fragment, which recruits NK cells, so for ADCC and recruits macrophages called ADCP, we think we're creating inflammation at the tumor site that then synergizes with this. So we think the data support a broad label around PD-1 tell. And ultimately, the study was done with tislelizumab that's where we generated the data. I think there's a lot of information that PD-1s broadly work in gastric cancer. We are generating data as well through an investigator-initiated trial with KEYTRUDA as well. However, really no obstacle to use tislelizumab.

Great. And how large of an opportunity do you think the frontline GEA opportunity, I guess, is in the U.S. and ex U.S.? And maybe has that changed at all after you've seen the full data from the trial in your mind?

Well, our estimates are there about 8,000 HER2-positive patients with GEA in the U.S. And sometimes those data could be refined. But I think importantly, because the results of the zanidatamab trial are so definitive there's a real impetus for docs to ensure that they know the HER2 status of their patients, and they have the opportunity to give Zanidatamab with tislelizumab or another PD-1 inhibitor. We are -- you mentioned about are you ready to launch. Sorry, I didn't answer that question and you mentioned it earlier, but we certainly are ready to launch by the time we get approval. And there are a number of things that have facilitated that. As you know, we are approved in second-line biliary tract cancer. Zanidatamab is approved in second line biliary tract cancer. These are the same community and academic treaters, gastric cancer. And so we're already out there in the market. We have the opportunity for an early NCCN adoption. And we are already able with our MSL force. Obviously, we're not promoting, but we're able to do critical education that's necessary to sort of prepare the launch. So we do feel confident that it will be a strong launch.

Maybe on the -- how rapid, I guess, do you expect the launch to be? Is it going to kind of rolled out at physicians at targeted centers first before expanding? Or kind of how do you think this will be incorporated in terms of that? And second, the company does a really good job at kind of breaking out the narcolepsy in IH population with Xywav, you can kind of see the contributions from each indication in that therapy. Is that possible with Ziihera where you'll be able to see this portion is BTC, this portion is GEA. Or how will we know how the launch is going?

Yes. I'll be careful to stay in my swim lane. So as the R&D guy, I won't comment on things that I'm not familiar with, John, may be able to help me out there. . So again, it's not -- it's I'm not in a position to comment on the projected speed and adoption. But I'll just reiterate that the data. It's the first time we've seen survival data over 2 years, for the median of over 2 years. And this is a very poor prognosis disease. Half the patients don't make it to second line. And so we certainly will be out there, our medical affairs group educating on the importance of doing the testing and adopting this therapy in front line, zanidatamab with a PD-1 inhibitor in order to ensure the best option. And I think 1 thing to facilitate that, as I mentioned this, the data are consistent across PD-L1 subgroups. So there's no need to wait that test result to come back to make a treatment.

And Joe, in terms of differentiating BTC sales from GEA sales, they are different dosing regimens, but the GEA population is much larger. So we expect the growth that we see in Ziihera. It would be really driven by GEA uptake. It's very hard for us. Rob mentioned the overlap between the physicians. So it's hard for us to see sort of differences in prescriptions, BTC versus GEA. We'd expect it to be driven by and really revenue is the biggest metric to look at as we start to see the launch unfold.

Perfect. And maybe we'll turn over to the breast cancer indication. I guess, can you just highlight a little bit what gave you the excitement to go into the breast cancer study? And relatedly, with GEA, it was pretty "easy" to kind of guess what the comparator arm was going to do because we had a couple of trials to go off of. Post an HER2 in the breast cancer setting, I think data is still kind of developing there. What do you think the comparator arm is going to show? Or kind of what did you power the trial for that comparator arm in breast cancer?

Yes. So just to start with here, I go into breast cancer. Well, especially as we turned over more and more cards and that started with the second-line BTC trial that led to the approval, additional data in breast cancer frontline, later line with chemo combination with novel agents like CD-47 combination with non-chemotherapy agents in the ER-positive group, all of this has been published. . With palbociclib and fulvestrant, for example, demonstrating that there's activity despite the fact that patients would have received multiple prior HER2 therapies sometimes including not only Herceptin and Perjeta, but then T-DM1, [ ospitucatanib ], and in many cases in HER2. So the differentiated mechanism of action, giving us confidence that would be active even in later line breast cancer. We also saw an emerging gap in the data as in HER2 moves to the frontline. Many breast cancer oncologists approached us about this to say as it HER2 gets to the front line, there will be a gap in the data as to what to use. And you alluded to the fact that how do you know how trastuzumab will perform in the setting because the treatment landscape has evolved. And the fact is that we had to make some assumptions, but it probably is evolving over time, we'll have more data to substantiate that. So this was an opportunity for us to get into that later line HER2 space. As an initial foray into the breast cancer, not necessarily the only thing that we'll do in breast cancer, especially as we gain conviction around [indiscernible]. And specifically to your point, I won't say what our protocol assumptions were to not share that level of detail. However, we use the data that are out there, and we do recognize that, that's probably evolving as we see real-world databases coming out post HER2.

And maybe to wrap up the zanidatamab part of the discussion. The company historically had put out this sort of $2 billion potential for the asset. I guess now that we have more clinical trial data, I guess when do you think the company might be in a place to revisit that number? Or do you think that's still the right number when you include BTC, GEA and breast cancer? I guess how do you see that kind of peak potential evolving?

I'll stay with my pattern of doing all the hard questions to John. I'll start and just describe how I see the zanidatamab development program evolving, say, from the time we first made that statement, which was actually a $2 billion-plus statement. So a lot has happened in terms of data that we've generated. We've now been in the marketplace with BTC, and we're confident that it's performing the way you expect based on the data. Our frontline BTC trial is progressing as planned. As John pointed out, that's a smaller population, but very important for frontline BTC patients, again, many of them don't make it to second line. There's no approved HER2 therapy. So our experiment is versus nothing. And it's in combination with a PD-1 or a PD-L1 inhibitor, and we now know, as we discussed earlier, from the GEA trial that we're clearly seeing synergy. So in an opportunity where you're against no other HER2 agent and you have the opportunity to synergize with the new therapy. We think that high probability of success trial, and that will expand our market BTC online and hopefully change practice around identifying those patients. We then saw the GEA data, which we've talked [indiscernible] % I'll speak for myself. I was optimistic about it being a positive trial outcome. I think this even exceeds what I might have predicted it was first [indiscernible]. So the PFS benefit was substantial across both arms. The overall survival benefit is substantial. Of course, it's only the triple that was stat sig. But remember, stat sign is a function of how much alpha against it, and we only put a small amount of alpha the first interim. So [ RMB ] still showed over 24 months median survival compared to less than 2 months. So I think the results are definitive, and I think that probably drives the level of enthusiasm, plus the idea that now this is the whole population in combination with a PD-1 inhibitor, where you would expect the duration of therapy to be longer. We've seen that in the trial. So I think we could be sanguine about the opportunity in front long. Rising tide lifts all boats as I say, certainly, as you accumulate data and you gain confidence and conviction about the drug, and I think you increased your confidence in other areas. So breast cancer is the next area that's very important to us. We talked about the trial that's ongoing. You and other listeners may be aware that we're very interested in early breast cancer. We have a collaboration with IP collaboration with MD Anderson, and we have our ongoing trial, which is a Phase II. And we hope that, that will ultimately lead to a Phase III in the neoadjuvant space. Speaking of neoadjuvant, while we haven't made any definitive plans here. We certainly are interested in are there other areas of gastric cancer where Niara might be used. Again, early extra cancer, no approved HER2 therapy. We now see that IMFINZI is approved there, very similar to front line BTC where we would be against nothing in combination possibly synergizing. And then back to breast answer, I think there's other areas we can explore. We have a partnership with Beringer. We have a partnership with [indiscernible]. As we see these novel TKIs come up and seem to be differentiated good evidence that the combination of an antibody like zanidatamab with TKI could be also synergistic TKI can raise the correction level plays right into the zani's mechanism of action around clustering and immune activation. So we see that combination potentially being studied in other breast cancer set as well. And we'll see as the Phase II data emerge what we'll be able to do there. I think that combination could be relevant in other settings as well. We touched on the basket trial. That's important for a couple of reasons. It is an opportunity to get a tumor agnostic indication, which we know is possible in this area of HER2-positive disease. It's also giving us a chance to further explore tumor types like colorectal cancer and non-small cell lung cancer, for which we had some prior data, but we're looking to extend our observation to understand whether we could get into those areas as well. We published frontline data at ESMO for colorectal cancer. We had previously published later line monotherapy data for colorectal cancer. It's an interesting space that we're following careful. So when we had said $2-plus billion, I think it was really around BTC, GEA and the 1 breast cancer trial that we had started. And I think we really are beginning to put into place plans that could extend the value of basket but we haven't put a number to that. John, what would you add from that?

No, I think you said it well, Rob. It's a $2 billion plus peak sales estimate and now that we have the data from GE and we're in these new areas, it's an area we'll look at and see if it's appropriate to refine going forward.

And I think 1 of the nice surprises to the Q1 financials was Zepzelca's strong performance after moving into the front line. I guess how should we think about continued performance of that asset?

Thanks for asking about Zepzelca. We're really proud of that. We brought that asset in, which was positioned as a second line. We pretty quickly recognized the opportunity in frontline. We saw that patients progress rapidly after finishing their induction chemotherapy and an opportunity to use a drug like Zepzelca, which we felt was very well tolerated. There was some resistance to that because many docs said, coming off of platinum therapy, patients don't want to get another therapy. But we proved that you could do it and you can do it safely and with significant benefit. And also that, that is the time to intervene, the progressions are so rapid. Many patients don't make it the second line, but also to sort of preempt that progression to forestall the progression, that's important from a quality of life perspective as well. Of course, we also saw an overall survival benefit. And part of our rationale in addition to preempting that progression as a maintenance therapy was that we had Phase II data in second line, we had some preclinical data suggesting that there could be a synergy with immunotherapies. So the ASCO abstracts are out now. I don't know if you have had a chance to start to sort through them. but I'll call your attention to 1 on Zepzelca It looks at the impact of tumor-associated macrophages. These are immune cells that cause immune suppression and can interfere with the benefit that you might see from a PD-L1 antagonist cycle tislelizumab. So we looked in the import study. And in fact, it proves what has been known before, tumors with high tumor-associated macrophages don't do as well when they get tislelizumab. On the other hand, the combination arm did quite well. And so clearly, given the combination for those patients who might otherwise be somewhat resistant to immunotherapy is rational based on these data. So again, evidence of synergy, and I think the key message there is Zepzelca going to have its best effect in front line. It's going to have an effect across the populations that were studied. It's not dependent on a biomarker, the way [ DL3 ] might be. And it seems to be synergizing with immunotherapy. So give it upfront with immunotherapy, don't say that and that really has been our focus.

And with that, unfortunately, we are out of time for the session. But thank you both for joining us, and we also didn't get through modezo and the BD activity in oncology potentially this year. So give investors something to wait for next time. But thank you both again and thanks to everyone for tuning in.

My pleasure.

Thank you.