Exelixis, Inc. (EXEL) Earnings Call Transcript & Summary

Yes. So 312 is, again, as you said, it's cabo, atezo in the frontline studying versus sorafenib. Very similar to the IMbrave study that looked at bev/atezo versus sorafenib that read out positive for, again, response rate, PFS, overall survival. And it was approved in this summer in the U.S. and now being approved really around the world. It really changed the entire dynamic. It's the first I/O regimen that showed success in beating sorafenib head-to-head. And that was a really important first step. And it's really starting to dominate the first-line setting. So the 312 study is very similar to the IMbrave study, except we basically replaced bevacizumab, Avastin, with cabo. And again, it's -- in my mind, it's a great and potential enhancement. Cabo has single-agent activity in liver cancer survival benefit from the CELESTIAL study. We've seen, I think, really interesting data, say, cabo combined with other I/Os as well in liver cancer in a mixed first-line, second-line population that we talked about back at ASCO GI earlier in the year. So we're very excited about that trial. We think it's -- again, it's probably that indication. Liver cancer is probably one of the more underserved indications in all of oncology, just due to the fact that there haven't really been a lot of new drugs and newly effective drugs that have been introduced over the last decade or so. So we're excited about that. And again, based upon all the data that's out there, we think we're really encouraged by what we could see, absolutely have to do the experiment, have to see the top line data, but we're excited about having that kind of on the horizon. So that -- again, that fully enrolled this year. Again, middle of COVID, lots of challenges there, but the team did a great job in making sure we got that done on time and got drug to patients and tracked their progress, et cetera. We had initially planned, based upon our event modeling work, to expect to see that readout this year. But events have come in slower, which happens sometimes when we modeled. So we think that will be a first half 2021 event. So we're tracking events. We'll have more clarity on that as time goes on, but we're very excited about that and certainly very interested to see how this compares when we see the data.

And you can see how everything is teeing up for next year. One of the other studies is looking at cabo in differentiated thyroid cancer. It's already approved in medullary thyroid cancer. Obviously, a smaller indication here, but I think we could get a first interim look by year-end. So maybe just a quick comment on that study and that opportunity.

Yes. So it's -- that's the COSMIC-311 trial. That's looking at single agent, cabo versus placebo, in second-line patients who progressed on a first TKI. It's a trial. It's kind of a trial within a trial design. The first look at data is for the first 100 patients looking at response rates for the 2 arms. If that's successful, we -- based on feedback with the agency, we can file on that. If not, we go to the full 300 patients looking at PFS. So -- but again, we've guided to expect to have the response rate readout for the first 100 patients in Q4 of 2020. So we hope to see that over the next month or so.

Awesome. Looking forward to it. So I'm going to switch gears here a little bit because I remember back when you started COSMIC-021, which is a Phase II study. This study just sounded like such a good idea to me to really cast the net wide to see where you were going to be able to combine cabo and atezo and get the best bang for the buck. And so many of these label expansions that we're talking about have really emerged from that. So the one I'm going to start with is cohort 6, which is in prostate cancer. Again, I know you for a long, long time, Mike, and I know, coming back to prostate cancer probably means a lot. And again, I think you're going to be able to actually file next year based on cohort 6. So maybe catch us up on all of that. You're also conducting CONTACT-01, which is a Phase III study. So tell us what's the latest in prostate cancer.

Yes. So it's -- we could spend an hour on 021 in prostate cancer and what we've learned from that and how we're moving forward. The 021 trial has been just an incredible opportunity to profile cabo/atezo across a wide variety of indications, have the flexibility to kind of follow the data, add patients where we see compelling activity early on, publish that as we have now numerous times for different cohorts. Prostate, as you know, I'm sure everybody knows, we had a lot of prior efforts there back in the 2012, 2013 time frame when I first took over as CEO. We've learned a lot from that experience and from the COMET studies. And I think what we did in the context of 021 in cohort 6 was really designed a better set of experiments based upon what we learned from the COMET experience and how to ask really a better set of questions, right? So looking at patients with only measurable disease by RECIST 1.1, we took the response assessment question and drama from the COMETs completely out of the equation. We're using both clinically and, I would say, regulatorily relevant and meaningful response assessment criteria. So there's no debate. A response is a response. We're using RECIST 1.1, no issue. We've learned a lot about dosing as well, obviously. And that was one of the big issues back with COMET-1, was we had these elderly, heavily pretreated frail patients who just couldn't tolerate significant dose.

Heavy dose, yes.

And now we're using the 40-milligram dose, which we've seen across the board, has much better tolerability when combined with ICIs. And really importantly is that doing that trial back in 2013, 2012, most investigators didn't have the experience with cabo that they have now, right, especially in prostate cancer where TKIs aren't normally used. So it's just a very different environment. We had the first publication of some of the data back at ASCO GU in the spring.

Fantastic.

Very compelling data, great 30-plus percent response rates in heavily pretreated patients. Tolerability was exceptional in terms of low discount rates. Good PFS, good signal of activity. And so that data, coupled with what was emerging in the space, prompted a discussion with the agency about would an accelerated approval approach be viable here. We got good feedback there. So we're off to the races, right? So what we've done in between then and now is we've added another close to 100 patients, so we're above the 130-patient threshold. And we're now just wrapping up the single-arm cohorts to be able to really define the contribution of components in the context of the doublet cabo/atezo versus single-agent cabo, single-agent atezo. So that's all ongoing. But again, we're excited about the opportunity. We have a long-term interest in this space with all the success of the NHTs moving into M0, the M0 population, a castration-sensitive population. There's really a very important opening for new modalities that don't involve chemotherapy. So we're excited about what that -- what this could mean for patients, for the company, for the cabo story and certainly between the cohort 6 efforts and now CONTACT-02, which is the pivotal trial, the confirmatory trial. We've got a lot of irons in the fire here, and we're just excited to be working with Roche and Genentech on this, too. So we've got a lot of momentum and obviously we've got to get it done and we got to get the data and do all the work. But it's been a very productive year in terms of advancing that program forward.

[Technical Difficulty] types of cancer prostate. Another example to now is cohort 8, again, from [Technical Difficulty] cancer. And now you're conducting the CONTACT-01 trial. So maybe you can tell us about the opportunity in lung.

Absolutely. So we had a lot of interest in -- historically in non-small cell lung cancer with cabo. Cabo, by itself, as a single agent, combinations. Certainly, the state of the art in 2019, 2020 is ICI's frontline, either single-agent ICI/ICI combinations. Now I/O-I/O combinations as well. So lots of frontline I/O being used and, therefore, you have -- it's a large bolus of patients who become refractory to I/O frontline who are in need of better therapy. So we designed one of the cohorts, that's cohort 7, to look at this I/O refractory population in 021. And again, we had data at ASCO, which showed, I think, really compelling signs of activity and near 30% response rate per RECIST 1.1. So again, no debate about the activity there. Again, good tolerability, low discount rates, et cetera. So that's prompted us to, again, continue to enroll patients both in the cohort 7 arm, which is the combination arm as well as a single agent cohort arm, but then also start the CONTACT-01 trial, which is looking at the same population in a global randomized pivotal trial against those attacks. So again, exciting times. It's a big population. It's one that we think we've got some real insight into and some real traction into. So that's enrolling well, and we're excited about having that opportunity to work with Roche on this very important trial.

And I'm going to skip CONTACT-02 right now because we've talked a lot about frontline kidney cancer because I really want to get back into some of the discovery efforts. I love that Exelixis is back into discovery. I'll start with XL092 where you're really building on that cabo clinical experience. So tell us about this compound and what your plans are.

Yes. So we had data at the Triple meeting about a month ago, and we talked about it extensively on the Q3 call. So anybody who wants to dive into the details and slides and transcripts, go forward or talk to Susan, and she can get you information. The whole 092 story, I think, again, it's a very focused, elegant plan to take the 15 years of learnings that we had and, in some ways, false starts and mistakes and restarts that we have with cabo. Any new approach is bound to have that kind of drama and trauma built into it. But take those learnings and then apply them to what we think is a better molecule, right? So we like the activity profile. We love the clinical profile. Cabo is a very unique molecule. When you look at the survival data as a single agent in RCC, the survival data that we see in HCC, the only molecule that we're aware of as is a single agent and has a survival data in both RCC and HCC. The data in prostate and lung and blah, blah, blah, I mean, it's just -- it's a very active molecule. But we had to learn how to use it, and we had to learn from all that experience then how to make a better molecule. So we think that with 092, we've been able to phenocopy cabo's activity profile based upon all the important targets that hits that drive tumor growth, tumor survival, tumor progression, if you will, in terms of resistance as well as the key cell types in the tumor micro environment. And then apply that learning to a molecule that's been engineered to have a shorter half-life. Because I think a shorter half-life is much more user-friendly for a clinician when these kind of molecules almost always have to be dose-adjusted based upon individual patient sensitivities, right? So it's easier to do that with a molecule that's got a 24-hour half-life than a 4-day half-life. So simple enhancements, but potentially very high impact in terms of how it would be used clinically. So we've done that. We've -- again, the data that we had at Triple meeting shows this clinical half-life being between 20 and 28 hours. So that's fantastic. And now we're embarking on a very broad development program, some single agent work, but mostly as combinations across, again, a variety of I/O combination partners, molecules, a variety of clinical collaborators, a variety of indications as well as lines of therapy, doublets, triplets, et cetera, that will allow us to really explore the I/O white space in a way that's never really been done before with a small molecule as a way to enhance the activity of various I/O singlet -- single molecules and doublets that could really expand the opportunity to raise the bar in terms of standard of care for a variety of different indications. So there's a lot there. It's hard to go into that in like 5 minutes or less. But we're excited about where we're going there and certainly have a lot of momentum and a lot of interest from various pharma partners who have I/O assets that they'd like to be able to combine with 092 because the cabo story is so compelling as an activity profile. And if you could just tweak the molecule a little bit to make it a little bit more user-friendly like we'd have with 092, it could really be a very important advance. So we're excited about that. Going to be hitting that really hard in the years to come.

Really exciting. And I got to just hats off and say a testament to you and the team, Gisela and Peter have been at it for a long, long time to advance this pipeline. I know we don't have time to talk about all of these, but you have the ambitious goal of filing 4 INDs in like the next 6 months or something. So maybe you can just touch on a couple of those and tell us what to keep our eyes open for.

Yes, for sure. Well, the near-term molecules are the iconic Tissue Factor antibody, which we're super excited about. It's been a great collaboration with them. And again, we're dotting the i's and crossing the t's to get that done this year. Again, they've done a great job of finding what we think is potentially a better binder in terms of a noncompetitive binder for Tissue Factor with Factor VII as well as kind of a potentially better next-gen linker and warhead, which they published on recently in terms of the ability to have tumor killing with this enhanced warhead approach. So combined, we think it's a very interesting molecule. Certainly behaves great preclinically. We've got to do the right experiment now on the right -- in the right species, obviously. But we certainly have that momentum now to be able to start doing that Phase I work in 2021. The other molecule I'll highlight is the CDK7 inhibitor from Aurigene, another collaborative effort. They've been great to work with. We've got a whole cadre of program that's kind of coming up behind it. CDK7 is an important self-signaling molecule in the cell cycle cascade. So lots of strong biology there, which supports kind of the single agents and combinations.

Yes, a great biology.

So we're super jazzed to be back in the discovery game. It's in our blood, man. We're just -- that's who we are. We're drug discoverers at heart. And we've done, I think, some great clinical work and getting things over the goal line, regulatory-wise. And now the commercial organization has certainly exceeded -- achieved great things. But now our challenge is to do this again and again and again. And I think we have the momentum and the balance sheet and the culture to really be able to make a lot of progress in 2021 and beyond. So we're super jazzed.

Great. Well, Mike, I think that's a great place to end it. Exelixis is available for one-on-ones during Piper Sandler's Healthcare Conference taking place from December 1 through the 3. Please contact your Piper Sandler representative to schedule meetings. Thanks, Mike.

Thanks, Ted. See you.