Welcome to the 44th annual TD Cowen Healthcare Conference. I'm Yaron Werber from the biotech team, and it's a great pleasure to have with us Mike Morrissey, President and CEO. Mike, good to see you.
Yaron, always a pleasure. Good to see you.
Yeah, my pleasure. So lots to talk about, between CABO, you know, obviously a lot going on between castration-resistant metastatic prostate cancer and neuroendocrine tumors, and then obviously the MSN case, and then obviously a lot of pipeline.
Right.
Let's maybe start by, you know, the guidance for the year contemplated 1%-7% growth.
Mm-hmm.
and, there's obviously a little bit of a price increase, but then there's gonna be a next leg of growth with prostate cancer and neuroendocrine tumors. Give us a sense of your latest thinking on when you can file those, both of those new indications.
Okay, a lot there. Well, first of all, good morning and thanks again for having us back. It's always fun to get to Boston, talk to you guys. I'll be making forward-looking statements today, so just as a reminder, please see our SEC filings for a description of the risks that we face in our business. So yeah, CABO, you know, it's kind of a plateau year for us in terms of revenue. You know, obviously, we're excited and proud to be able to post the kind of numbers we had in 2023. You know, it's CABO is the number one TKI in RCC for both monotherapy second line and as the TKI combination partner in first line. We think we have room to run with new indications.
So we had a strong year last year with top line data for both metastatic CRPC from CONTACT-02 as well as CABINET from the Alliance in a mixed population of both pancreatic NET as well as extrapancreatic or epNET. So the way we framed 2024, we're three years after the launch of CABO nivo and 9ER, which more than doubled revenues. Super pleased to see that growth over you know over 12 consecutive quarters. So it's not surprising we're going to flatten out. The IRA did us no favors in terms of in terms of price increases. So we were you know kind of you know had to stick to the rules there and subsequently the 2024 price increase was only 2.2% based upon the inflation caps that are built into that law.
So, we're looking to again see accelerating growth in 2025 and beyond, based upon the success of the CRPC trial as well as CABINET and the NET population. NETs will probably get filed first. A little bit simpler approach there from a filing point of view. Excited about that data. Really great feedback at ASCO GI or I'm sorry, at ESMO where the data was first presented and then a variety of ad boards this year including at ASCO GI. Excuse me. You know, clear unmet medical need for patients with NET. Lots of moving pieces with Lutathera. The NETTER-2 data came out at GI. That will most likely move up into the front line setting, leaving you know, second and later lines pretty open.
You know, available therapies include chemo, include everolimus, includes depending upon the location of those tumors and the origin of those tumors. We're, we're getting lots of good feedback. Again, the, the GI docs that use those drugs also know CABO well from either liver and/or thyroid or the community docs with renal. So, so we, we feel we're getting great feedback that CABO could really be a, a mover here. So we have big, big expectations in the NET space. Our number one priority this year is to get both, both NET and prostate filed and moving forward towards approval and, and a great development team. Amy Peterson joined at the end of last year and certainly, you know, has tremendous energy and experience here that, you know, we're capitalizing on. So, so lots to do but lots of momentum and lots of excitement.
Obviously getting the ANDA resolved with certainty is of primary importance. All the briefs are done now and in. So it's in the hands of the court. Again, have a lot of confidence here in what we've shown, the evidence, the data that supports that. The team did just a phenomenal job. So looking forward to getting that all done.
Yeah, so let's go maybe just on the end. I'll just get that out of the way. So the briefs were filed, I think it was late, late February or so. It didn't seem like there was anything as expected terribly new in the briefs, the final briefs.
There shouldn't be, right?
Shouldn't be. Yep. Any sense from the judges to when he's planning on ruling?
So he, at the closing arguments when those were all done, at the trial in the fall said he'd hope to have a ruling out in the springtime. So however you want to define that, California spring, Boston spring, but yeah, yeah.
How does one define spring in your view? Spring is what?
Spring is sprung. Exactly. Yeah. Yeah, usually, usually that second quarter.
July is not spring, right?
Yeah, July is not spring. Yeah, not in my book. Yeah.
Do we know when he's gone on vacation or we can work backwards?
Yeah, I haven't checked his vacation schedule yet, so yeah.
We can just call his admin and figure it out. Okay. Neuroendocrine tumors, you'll file for second line. This is a, as you said, it's cooperative, it's a group study, which you've had experience with group studies and using them for filing purposes, obviously. Do you have all the data or do you need to clean some of the data yourself?
So the data cleaning is done by the cooperative group. We provide oversight there since the filing is ours and we have to make sure that the data integrity and quality meets our standards for filing. We're obviously doing that. Great collaboration. The Alliance team also did CABOSUN. So different PIs, different, if you will, kind of indication GI versus GU, etc., but they just do a phenomenal job. So, and in this case, based upon the experience with CABOSUN, we actually for cooperative group pivotal trials that we're involved with, we based upon that CABOSUN experience, we had a few more bells and whistles built in. So they were already doing an internal blinded independent review. They were collecting scans.
They were doing all those kinds of important enhancements to the trial to give us that kind of momentum to be able to file and submit if the data was good. So, again, I don't want to get into the details, except to say that we're very pleased with how that collaboration has gone since the top line data was released back before ESMO. The data at ESMO looks solid. The KOL feedback and market research continues to look very promising, and we're doing a number of ad boards with that data, and again, we're getting very strong support there.
So, we're feeling good about that and this is an area that, you know, with CABO with Zanza, we think we can double down on and really make something of it because it's got that it's kind of not exactly like renal in a lot of ways, but it has that same kind of intuitive feel, at least to me, from the standpoint that, you know, it's a pretty good-size incidence population. The prevalence population is, you know, 40,000 or so patients. These patients live for a long time, so they need durable, effective therapies. Some of the radionuclide, you know, Lutathera, for example, you know, there's, it's used and certainly has done very well. In the U.S., I think its 2023 numbers were probably in the $400 million+ range in the second-line therapy.
So it's an effective therapy, but it comes at a cost, right, in terms of, you know, I mean, patients when they take that are essentially radioactive. They have to change how they live, how they, you know, some patients, you know, it impacts where they work, impacts, you know, how they operate at home. So it's not, you know, it's not a trivial impact on their lives. It's effective, which is great, but it comes at a cost, right? You know, there's downstream concern about, you know, other secondary malignancies, MDS, AML that can pop up. So having other options for these patients is super important and the encouragement we've gotten at ad boards from KOLs, from patient advocacy groups has just been fantastic. So, yeah.
Can you just remind us the data from CABINET, what was the PFS or duration of therapy and then how many patients do you think are there in second line?
So the incidence for second line is about 8,000, right? The prevalence pool is really interesting too. Patients, again, can live a long time with slow-growing tumors, so how much of the prevalence pool can you pull into that number, and address? It's TBD, but certainly on our market research and analytics, we're looking at that very carefully to get a sense on just, you know, how big that could be. It's obviously label dependent, you know, blah, blah, blah. Sorry, other question you asked?
The duration of therapy.
Duration of therapy, between, you know, regular NET, pNET and epNET, it goes between 8 and 11 months, right, in terms of PFS benefits. So, that's a, it's a significant, you know, it kind of feels like, you know, like kind of like renal, kind of like thyroid, right? So, that's, you know, we know how that works and, you know, we know how effective dose reductions can be to keep patients on drug for a long time and that's important here. You know, the success of 9ER starting at 40 can't be underscored. That really changed the equation in terms of not only the clinical benefit, you know, PFS response rate, overall survival, but quality of life had a huge impact as well, especially compared to either lenvatinib or axitinib.
We know how to nuance that and I think, I think physicians are becoming much more comfortable about using the lower doses with confidence going forward.
Do you need to expand the sales force or can you handle it?
Well, it would be an incremental build for both prostate and/or NET. We're talking about maybe a handful of additional reps, and we have the ability, right, to be able to mix and match as we need to too because a lot of our reps are calling on community physicians, right? So, and they would be very well tuned. I will say right now, based upon kind of early looks at prescribing patterns, we're already covering about two-thirds of the NET prescribers with our GI sales force. So, it's again, incremental build. It really if we're successful here, best case is that this is a huge impact on top line growth without much additional expenses, from a commercial marketing point of view, which is great.
So we can then, you know, use that extra cash if it's there to, you know, invest wisely, give more back to shareholders, continue to build the business as we go forward.
Yeah. Let's move to CONTACT-02, CRPC. The PFS looked good. I think we'll ask a question about safety. The overall safety was interesting. We'll talk about some of the trial design, but I guess the question is when do you expect survival and do you need to have survival, at least the latest cut of survival to file?
Yeah, yeah. So we expect to have the final survival output this year. Not going to give too much clarity or specifics around that. Obviously it's all event-based. When we get it, we get it. PFS with no decrement in survival is an approvable endpoint. There's plenty of precedence for that in prostate cancer, outside of prostate cancer. But the actual details around how much or how mature survival needs to be is something that we're working out with the agency right now. So I guess I don't want to speculate on that. I don't want to break into jail and say more than I should, but you know, it's a discussion, and there's two different work streams.
One is a dialogue with the regulators on a global basis and the other is really around, you know, getting, getting the events we need. But again, as you said, right, so we went on PFS. Hazard ratio was, was 0.65, in the, in the in the PFS ITT population. Overall survival had a hazard ratio of 0.79, with, I think an information fraction of, of, of 49%. So relatively early. So yeah, so we're excited. We're certainly, you know, others, others in this space are starting kind of with their backs against the wall, you know, with, with, with, you know, hazard ratios for OS greater than one, which is a place you don't want to be, obviously. So we're feeling pretty good about what we've got so far.
The subgroup analysis that we had at ASCO GU I thought was pretty impressive, around, you know, the liver met population, the hazard ratio in the 0.4 range, which was exactly analogous to what Pluvicto saw in PSMAfore. Again, similar population, different overall modalities, but similar efficacy in that. We had 25% of our patients had liver mets. They had like 5%. So very different overall kind of distribution but similar activity. Prior chemotherapy, CABO Tecentriq did really well as well compared to the second NHT and then the overall population looking at patients with both visceral mets and bone mets did really well too.
So, we're excited about that overall profile, you know, 50% improvement in PFS for what was probably the most stringent population studied in the second line, first second line setting with all measurable disease, lots of liver met patients, lots of prior chemotherapy. I think our level of lymph node metastasis was in the 75% range, which is just unheard of. So very, very poor prognosis population. I was surprised that didn't get a lot of play in ASCO GI or ASCO GU. There was so much noise around the second NHT as a comparator, which I just didn't get because everybody does that. It kind of missed the mark in terms of just the population that we studied was so far advanced and had such bad disease and we did so well.
So, we're hoping all that momentum goes forward and, you know, certainly excited about being in that space and I have ideas for Zanza there, obviously, based upon the success of CABO, and lots to do for sure.
Let me ask you a question because at the end you're totally correct about everything you said, obviously. In the KOL feedback, they're in love with radiopharmaceuticals and they're not in love with the second NHT as a control. But you have a positive study in a tough population, but the community is sort of, you know, not as enamored as they need to be. How do you change that?
Well, that was the case with, with CABO and RCC after METEOR came out as well. It's kind of like, you know, another PFS win. Yeah, survival, you almost hit. Yeah, so what? And obviously, through the data evolving to have survival and then having, you know, really great focus in terms of educating docs on the benefits, on the differences, on essentially how CABO, in RCC, second line RCC as the first kind of first solvo, you know, changed standard of care for patients with RCC and that's, that's been our goal, across the board. Everything we do is focused on that. Just getting over the goal line isn't good enough. You if you're going to be successful commercially, and that's the ultimate kind of lens from which we've learned through CABO, you have to change.
You have to improve standard of care if you expect to move the needle for patients and if you do that effectively, then you will be successful in terms of driving revenue growth and driving the business. So, so I think we can do the same thing with, with CRPC, with CABO Atezo. You know, the, you know, when I think about the second NHT debate, you know, there are 11, 11 either existing or already completed phase 3 pivotal trials in CRPC that have used a second NHT, as the control arm, right? And those include the PARPs, those include chemo, those include the radiotherapies, and those even include the latest and greatest kind of third gen NHTs, say that Merck is doing, through their, their, collaboration with Orion, right? Those all involve using those trials, enrolling thousands of patients, maybe even more, have a second NHT.
So, you know, SPLASH, for example, the discussant, right, he was a PI for SPLASH. What did SPLASH use as a control arm? A second NHT. So it was a bit disingenuous and it was a bit academic and that's fine. That's what these things are for. End of the day, if we get a label, I think we're very confident based upon the CABO experience and certainly in RCC, we can compete and we've competed and we've done more. I mean, we've been able to move to a position where we're one of the dominant players in this space. So we can do it again.
So where do you ultimately see CABO at the center getting used? You failed an NHT and this is pre-Pluvicto? Is it post-Pluvicto, pre-second NHT?
Well, you know, with the incidence population in the first and second line of metastatic CRPC of 70,000+ patients annually, you know, we can carve that up. It'll be defined by our label to a certain degree, and it'll be defined by others' labels if, if and when they get them, and then how we, you know, how we market that. But what's clear, at least in the U.S., and this has been done. It's been published for the last few years now, is that if you look retrospectively at real-world data, right, patients, 5,000+ patients, right, patients choose to right now use a second NHT over chemo on the order of 5-to-1, 6-to-1 if you look at the actual data.
Plus, if you look at that real-world data, it appears and there's lots of caveats here, but it's just data that overall survival for a second NHT is actually better than docetaxel. So in some ways, patients are the ultimate they get to vote with what they choose to take. It's not the doctor's choice. It's the patient's choice. And if we have a better approach than a second NHT because everybody wants to avoid using chemo until they absolutely have to, then we think that can really move the needle.
Questions from the audience before we go into the rest of the pipeline? Let's talk about Stellar-305, the phase 2/3. This is specifically in head and neck. Zanzalintinib, Keytruda versus Keytruda alone. When you look at this, this is first line, obviously. When you look at the prior CABO Keytruda study, it's an IST, 52% response rate, about 15 months PFS, right, 22 months survival. So you compare that to LEAP-010, that looks pretty good. That was the Merck and Lenvima Keytruda.
Yep, yep. Just came out last week. Yeah.
CABO, which had 36% response rate, eight months PFS. That was discontinued. When you think about the bar for you, what's the bar here?
A bar is to win, right? No doubt. And that's, that's a statistical game that, that we have to win. Again, the, the study, at least as I understand it, LEAP-010 was stopped because survival was trending the wrong way. I think the response rate cut was, just to correct, at least my perception, I think it was 46% for LenPem versus about 25% for PEM. The interesting thing there is the, the duration of response was, was the other way around, right? So it was about 10 months for LenPem, not, the median was 10 months for LenPem, not reached for PEM. If you look at the 12-month split, it was actually about 60/40 favoring PEM. So those curves really separate dramatically and you have, you know, 50% more patients who have, you know, a duration of 12 months or more with PEM than you do with LenPem.
So, I think this is actually presenting as a pretty typical phenotype of what you see with LenPem in pivotal trials, especially when you start at the full dose of lenvatinib. And I think that's somewhat phenocopied with head and neck, with melanoma, with second line lung, and a few others where the toxicity of lenvatinib gets in the way of using that chronic and dosing that combination chronically.
At least from all the feedback I'm reading from our MSLs and everybody else who's been, you know, just on the prowl, look trying to understand what's going on there kind of from the KOL community, I think the general sense is that a more tolerable TKI like CABO, like Zanza, has the opportunity to have that extended duration of therapy for the combination, which then can bring benefit beyond just response rates and PFS. So in some ways, LEAP010 actually validates, you know, you can have an impact on the disease in terms of response rates. We're double. PFS doubled. It went from 2.8 to like 7 months, at the second interim. That benefit, if you will, "benefit," couldn't translate to improved survival because of the toxicity of that combination, namely around lenvatinib. So that's been the goal.
That was the goal with CABO and 9ER and RCC frontline RCC was to drop the dose, play that game, take a little bit off the activity, but have it be a more chronically tolerable therapy, which it is, and certainly the quality of life data supports that. And we think lenvatinib potentially is even better from the standpoint of some of the early data we've got out there right now within RCC. So I would say confidence is as high as it can be based upon where we're at. It's a phase two, three design. So we'll get an early look at the first couple hundred patients and understand how it's going. If we have to resize or reevaluate after that, that's the goal. But you know, this is a, it's an important population.
You know, Andrew Peters, our head of strategy, likes to frame it as, you know, kidney RCC, head and neck today is kind of where kidney cancer was a decade ago. He says it better than I do, but that's, that's kind of the analogy. So, so we think with effective therapies and maybe XB002 plays here, others, you know, building a franchise in head and neck could be really interesting, right? So.
Okay. Yeah, interesting. Let's go to non-clear cell RCC and before we talk about STELLAR-304, with Zanza, do you have any sense how much CABO is being used right now in, in CC?
Yeah, hard to say. Yeah. Our market research is, I would say, minimal there and certainly from a script point of view, they don't discriminate between clear cell and non-clear cell. Yeah, yeah.
But is it considered standard or not necessarily?
Well, it is. It is. So there's about 20% of the of the overall RCC population is non-clear cell. We and others have a label for all advanced RCC, both clear cell, which includes both clear cell and non-clear cell. So it's not discriminated, but there have been no, no pivotal trials looking at a non-clear cell population by itself. So again, if we're successful, we can educate and market on that, on that really anomaly that could be a really, I think, beneficial way to go, right? So.
So can you talk about the STELLAR-304 Zanza study and this maybe the design? I believe data is going to be in 2025 or so.
Yeah, we haven't given guidance on data. It's a pretty straightforward study. It's Zanza Nivo, versus Sutent in frontline, non-clear cell, RCC. Very similar design, if you will, to what we had for 9ER for the overall population. So I would probably be willing to say the probability of success is pretty high here. Sensitive tumor type, the IKCS data we had with Zanza, at the end of last year, pretty compelling in terms of response rates, pre and post, CABO, you know, that continues to look really encouraging from the standpoint of a late line population. So yeah, so it's, we're off to the races there for sure.
The primary is PFS, so it's a combined PFS and a secondary survival?
Yeah, yeah, exactly.
It's not a co-primary?
No.
Okay. Let's move to the ADCs. Maybe next you have two different tissue factor ADCs. You know, as you said, 002, the JEWEL-101 study is ongoing and now you have an IND next year with a 371. The first one is a microtubule, the second one is a topoisomerase inhibitor.
Right. Exactly. Exactly.
Can you talk about what's the reason to have 371 and the different slightly different mechanism?
Simply trying to be able to simply focusing on matching traditional tumor sensitivity to chemotherapy with the payload from the ADC, right? You know, not one payload is not going to service every tumor type equally or potentially effectively. Just getting it there might not be enough if that tumor the way that tumor's built and it's, you know, redundancy in terms of pathway activation and resistance mechanisms may make one over the other less effective. So we like the idea of having two different approaches going in the Venn diagram view, going after different tumor types or going after similar tumor types that could allow us to be even more effective. So it's purely an empirical game, if you will, based upon prior precedents for really tumor sensitivities to chemotherapy. So and we're surprised. It's kind of a no-brainer to us.
We're surprised more people don't do this because it's a good way to recycle, if you will, a known effective binder with the right chemotherapy for the right tumor type, maybe in the right combination at the right time. It's just making that targeted therapy, that much more specific. So.
It's the same binder and it's the same underlying affinity antibody?
Same, same, same antibody. Exactly. Same binder, same epitope, everything. It's just a different linker warhead, right? Which, and now today that's so they're so readily available, you know. It didn't involve us inventing anything. It just really kind of making the construction work and then getting it into talks, right? So the data looks good. Dana had some just phenomenal data back in December. Yeah, yeah.
As you think about your pipeline, you've really filled it out both into phase one, you know, four different compounds and pre-IND you have another five. Do you have more room to bring in more pipeline?
So again, part of the part of the refocusing, at the end of last year, earlier this year, was really an acknowledgment and kind of statement of the obvious that we don't need more development candidates, pre-INDs and INDs. The pipeline is actually really, really full there with a lot of exciting molecules. So our, our focus is really late stage now, right? And we've been looking at late stage over the last few years, haven't found anything that we're, we have a lot of conviction in, but that continues, right?
If we can bring in a molecule that has the appropriate level of data supporting a pivotal trial or in a pivotal trial, that would be very, very attractive to us and we would push a transaction because for us, it's really the vision is multiple products, across the continuum of solid tumors, in GU, GI, you know, thoracic, if you will, head and neck and lung, and then and then women's tumors, breast, gynecologic. But that's the that's the sweet spot for us. And if we're effective there, then with a if there's a late stage molecule that can fit in, then it's, it's very attractive to us for sure.
You know, with the downturn and I think hopefully we're beginning to emerge from, especially in oncology, there are several mutational best programs that are now moving into pivotal. I think they've these companies have all become victims of, well, these are not going to be mega blockbusters. They're going to be smaller drugs and can you survive as thin alone? But a lot of them have some proof of concept data that's fairly reasonable. They're not going to be, you know, $500 million-$750 million programs. Are you open to bringing in things that could do $200-$300 or do you want to do things that are bigger?
Well, you know, if it's if it's $200-$300, if we can if we can get convicted on that, sure. If it's if it's $25-$50, probably not. And that's see, that's the issue. The confidence intervals are so big at this stage, and that's the learning from the last decade of going after these, you know, hyper-targeted therapies is that it's often, you know, $80 or $100. It's not $300. It's less. So you've got to have the conviction that, you know, it's going to be big enough to be able to move the needle, right? So.
Yeah. Well, Mike, terrific. Thanks for joining us. Always good to see you. We appreciate it.
Yeah, you bet, man. Good job. Thank you.
Thank you.