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

Okay. There's about 4 questions there, so I'll just kind of expand upon that. So yes, we're really excited about the emerging data in metastatic CRPC that's coming out today at ASCO-GU. We had a -- the abstract came out on Monday. We had a press release highlighting the top-line data. There's a long history here of Exelixis and cabo in prostate cancer. I think we've spent a lot of time over the years since the comments read out learning about what some of that data actually meant. That was a trial that failed, looking at overall survival. And understanding the different nuances and different components of that trial, that we could have done better. So we're a learning organization. We've taken the time to dissect all the different pieces and ask the hard questions to understand, really asking the question really is cabo active in that space and how do we maximize the opportunity and the value there. So we've taken a step back and really asked instead of really any further -- going for the home run that we did with cabo, looking at prostate cancer in terms of very specific components of that disease. And it's a complicated disease in terms of the hormonal nature that drives that when those tumors become refractory, the different hormonal agents, chemotherapeutic agents, radiotherapy agents, even IO-type agents that can be brought to bear there. So we've, I think, done a good job of going back, but also looking forward, just understanding where the market is going as the different NHTs, novel hormonal therapies move up in terms of the castration sensitive as well as the M0 nonmetastatic population. So we've done that. The first look is part of the COSMIC-021 trial, and that's a large basket trial looking at 12-plus different tumor types and 24 different cohorts. For cohort 6, which is for CRPC, we really wanted to make that whole question as simple as possible by taking out the controversy and the drama around the bone scan responses that we looked at very carefully back in 2012 and 2013 and 2014. And simply ask the question, what does cabo and atezo do? What does that combination do in patients with RECIST 1.1 measurable disease? So for both selection of patients and then response assessment, we want to use a -- and we have used a very standard noncontroversial, both clinically and regulatorily friendly readout of RECIST. So there's no -- there's really no debate on the viability and the validity of the results that we're talking about this week. The good news is that we see good activity, good tolerability. We're looking in a population that is -- in terms of an entry criteria, that has a single or more NHT, having been either refractory or progressed on by radiographic means, that these patients can have chemotherapy as part of their castration sensitive disease history and about 27%, 28% of those patients actually had docetaxel for that. And the good news is that across the different subtypes of populations of those patients, those that got chemotherapy for their CSPC, those that had one hormonal agents or 2 hormonal agents, all had a similar response rate in that 30-plus or minus percent range with good duration of response. So we're excited about what that means. Again, as you talked about, if you look at some of the competitive data, certainly, chemotherapy with all of the baggage it brings from a tox point of view, can have activity in that kind of same benchmark as well as some of the early IO agents, which are usually much lower, either as a single agent or in combination. So we're excited about that. We've -- as you mentioned, we've increased the actual enrollment size with 2 different cohorts of 50, the second being in January. We've added single-agent cohorts to really demonstrate the contribution of components, which is already kind of out there in terms of both single-agent cabo and atezo, and I think we're very aligned with the agency about what success looks like from the standpoint of a subparty's filings. So our job now is to get all that work done and if I have enough follow-up to feel confident in the data, and then move forward with that package.

And I guess, when can we expect to see the data from the full registration study?

We're guiding to have all that data pulled together in a filing in 2021.

Okay. Great. And then, I guess, there was a little bit of investor debate around the fact that not all patients, as you mentioned, did receive prior docetaxel in the study. I guess I think there's a perception that patients need to be exposed to all available prior therapies to justify an accelerated filing timeline. Can you just comment a little bit more on what the FDA has got to do with -- on this front?

Yes. So it's our clear focus to really provide a treatment option that delays chemotherapy, doesn't replace chemotherapy, doesn't complete with chemotherapy, but actually delays the chemotherapy. And that's a major unmet medical need for patients with late-stage prostate cancer. And I think even some of the data within the demographics of the 021 cohort 6 data that we're talking about this week, underscores that, right? You get 44 patients enrolled in what we're presenting on. Half of those patients came on the study after a single NHT. The other half of those patients came on after a second NHT. So that -- those second half patients, right? Those 22 patients that got 2 NHTs had a choice after they progressed on their first NHT to either get chemo or get a second NHT. And they all basically, from the data, said, "I'll take the second NHT and delay chemo to see how the second NHT does." Then when those patients progressed again, they had the same choice, chemo or clinical trial. And they again chose the clinical trial. So I think it really underscores the fact that you've got elderly gentleman, 75, 80 years old, who had surgery and/or radiation. They've been on ADT for probably 5, 10-plus years. They've had one NHT. Their disease is progressing, and they're choosing to delay the use of chemotherapy. So I think that's a very important goal. And it's one that we really want to reinforce as we go forward in that we think this is an important opportunity for patients as well for investigators and doctors to be able to bring other therapies -- other options to their patients. We're certainly very interested in looking post ADT, post chemo. Cohort 24 actually is targeting that specific population. And it's enrolled quickly. And again, we have the ability to look at that, at the individual cohort, like we did with cohort 6, and add more patients as we think is appropriate. But I think the bottom line is that the notion, at least from our point of view, that you have to exhaust every available therapy before thinking about a Subpart H is just misguided. If you look across the last 40 compounds that have been approved for Subpart H filings in oncology over the last 3 or 4 years, that's just simply not the case and not the case here as well.

Okay. Then you also announced the expansion of the lung cancer cohort in the signal finding study, around the same time actually as the initial prostate cancer expansion in COSMIC-021. Could you just remind us of the status of this cohort and potential next steps in lung cancer for cabo plus TECENTRIQ?

For sure. So that's the other cohort that we're certainly very excited in, both from the standpoint of expansion within 021, but also as part of our collaboration now -- clinical collaboration now with Roche/Genentech where we will run free pivotal trials in prostate, lung and renal and basically share the costs of those trials. And then our half, both Ipsen and Takeda have the ability to opt into those and further draw down our half. So I like the idea of doing these kinds of large, global, expensive pivotal trials with partners and collaborators to be able to share the costs, so then we can do more and more, both within cabo and then outside of that development plan. In terms of lung, again, there's a very large unmet medical need with all the patients going on to IO frontline, either IO by itself or IO/chemo or sequencing chemo and IO. So again, those are patients who are coming off that either with primary refractive disease or after progression with some level of benefit is large and really focuses us and others around the importance of being able to bring new modalities, single agents combinations into that space. So I would say cohort 7 is just the nonsmall cell. Cohort is about a half step behind where prostate is. We're certainly very interested in pushing this forward. We have a single agent cabo cohort from the summer as well. Again, asking the question around the contribution of components. So that's moving forward aggressively, and with a pivotal trial planned with Genentech, we're certainly ready to move forward there in a very broad sense to be able to profile that further.

Okay. Great. And then maybe a couple of more questions on -- maybe one on IP, which appears to be a concern among investors. So you did receive an ANDA filing last year for CABOMETYX, obviously, challenging the polymorph patent, which expires in 2030, 4 years roughly after the competition of matter that you have on the drug. I guess what gives you confidence in the strength of this patent data?

Again, we talked about this a lot on the last earnings call and at JPMorgan. We're not going to litigate this publicly. It's not surprising that a generic company would come after a compound that's generating $1 billion a year in revenue. The system is built that way. We have very strong data, very strong IP as well as a great team of both internal and external experts who are going to help us litigate this with the ANDA filer, and we're very confident in that. So I won't say more than that, except to say that we're investing in a way that I think is indicative of our confidence based upon all the data that we've got around the polymorphs and in our ability to maneuver there going forward. So we have a lot of confidence. Obviously, we're going to put a stake in the ground here and defend our position very, very aggressively. And I'll let that action go forward without me commenting on that further.

Okay. And then as you mentioned earlier, you have been reinvesting some of the cash that was into the early-stage pipeline, the internal pipeline, and you did recently announce that you will initiate expansion cohort for XL092, your next-gen multi-kinase inhibitor. Maybe just briefly comment on how this molecule maybe compares to CABOMETYX? And how it might be positioned longer term relative to the CABOMETYX franchise?

Yes, for sure. So we -- again, we have a pretty extensive effort right now across different modalities, targets, pathways and cell types within our internal and external network of drug discovery. We have a long history there and certainly have a lot of confidence in our ability to make good molecules, make timely molecules that we think can address important biology and large unmet medical needs. 092 is the first compound out of that effort. We have a decade or more of experience with cabo clinically. We have, I think, a deep appreciation of its strengths and perceived weaknesses that we have now addressed, both chemically as well as biologically to what we think is to make a better next-gen molecule. So that's been profiled now in the clinic since the beginning of last year, and we're moving into combinations. We have ultimate flexibility from all the data we're getting with 021 across the different cohorts as well as, say, even within something like prostate cancer, that's very complex in terms of the different components of that disease where we could slot in 092, where appropriate, based upon kind of a longer-term vision for how to make that molecule work. So stay tuned on the actual details. We haven't talked about that molecule publicly yet, in terms of its biology, it's pharmacology, it's clinical activity and experience yet. We'll be doing some of that later this year, where we start to roll out, again, more information and more data on the compound.

Great. So with that, we'll have to wrap up. But looking forward to a data-rich year ....

That's the plan, yes, for sure...

On CABOMETYX and other 3 NDA filings as well.

Okay.

Thank you, Michael.

Thank you.