Exelixis Inc (EXEL) 2017 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Exelixis First Quarter 2017 Financial Results Conference Call. My name is LeeAnn, and I'll be your operator for today. As a reminder, this call is being recorded for replay purposes.

I would now turn the call over to your host for today, Ms. Susan Hubbard, Executive Vice President of Public Affairs and Investor Relations. Please proceed.

Thank you, LeeAnn, and thank you all for joining us for the Exelixis First Quarter 2017 Financial Results Conference Call. Joining me on today's call are Mike Morrissey, our President and CEO; Chris Senner, our Chief Financial Officer; P.J. Haley, our Senior Vice President of Commercial; and Gisela Schwab, our Chief Medical Officer, who will together review our corporate, financial, commercial and development progress for the quarter ended March 31, 2017, as well as recent key developments and corporate events. Peter Lamb, our Chief Scientific Officer, is also here with us today and will participate in the Q&A session following our prepared remarks.

As a reminder, we are reporting our financial results on a GAAP basis only, and as usual, the complete press release with our results can be accessed through our website at exelixis.com.

During the course of this presentation, we will be making forward-looking statements regarding future events and the future performance of the company. This includes statements about possible developments regarding clinical, regulatory, commercial, financial and strategic matters. Actual events or results could, of course, differ materially. We refer you to the documents we file from time to time with the SEC, which, under the heading Risk Factors, identify important factors that could cause actual results to differ materially from those expressed by the company verbally and in writing today, including, without limitation, risks and uncertainties related to product commercial success, market competition, regulatory review and approval processes; conducting clinical trials; compliance with applicable regulatory requirements; the availability of data at the reference times, our dependence on collaboration partners and our ability to maintain our rights under existing collaboration; and the level of costs associated with commercialization, research and development and other activities.

Now with that, I'll turn the call over to Mike.

All right. Thank you, Susan, and thanks to everyone for joining us on the call today. We've gotten off to a good start in 2017 with strong operational performance across all components of our business. I'll begin today by providing a brief summary of the key events for Q1 and then turn the call over to Chris, P.J. and Gisela for updates on our Q1 financials, the ongoing CABOMETYX RCC launch and development activities for both cabozantinib and cobimetinib.

Key highlights for Q1 2017 include: first, the strong commercial performance of CABOMETYX in advanced RCC with net product revenues of $68.9 million for the cabozantinib franchise. Second, our use of improved -- the use of our improved cash position to further optimize our balance sheet by paying off the Silicon Valley Bank loan with plans to repay the remaining Deerfield debt by midyear. And third, we continue to make meaningful progress in R&D by advancing development and regulatory activities for both cabozantinib and cobimetinib, reinitiating our internal discovery efforts and exploring potential business development opportunities.

We are pleased to have achieved an important corporate milestone in Q1 by posting our first profitable quarter on an operating basis with diluted earnings of $0.05 per share, driven primarily by substantial growth of cabozantinib product revenues, while at the same time continuing to manage our expenses carefully and further reducing our debt. As we first articulated in July of 2015, we have been strategically focused on running the business to generate positive cash flow through expanding product revenues with the goal of reinvesting the resulting free cash into advancing additional late stage trials for cabozantinib and building a strong product pipeline. It is gratifying for all of us here at Exelixis to have reached this important milestone. We look to expand future R&D initiatives that are balanced with future growth and product revenues while maintaining an unwavering commitment to disciplined expense management.

So with that, I'll turn the call over to Chris, who will provide more details on our Q1 2017 financials.

Thanks, Mike. Total revenues for the quarter ended March 31, 2017 were $80.9 million compared to $15.4 million for the comparable period in 2016. Total revenues include $68.9 million of net product revenues compared to $9.1 million for the comparable period in 2016. The increase in net product revenues primarily reflects the impact of the commercial launch of CABOMETYX in late April 2016.

Our discounts and allowances from gross product revenues increased during the quarter to 11.6%. This increase versus prior quarters is primarily related to increased utilization in our co-pay systems program, which is impacted by our commercial patients starting the year with renewed deductibles, higher Medicare deductions related to patients' passing through the donut hole and, to a lesser extent, higher VA volume. As we see our business continue to evolve, we estimate that our 2017 discounts and allowances will be in the range of 12% to 14% of gross product revenue.

Total revenues also include $12 million of collaboration revenues compared to $6.3 million for the comparable period in 2016. Collaboration revenues for the quarter ended March 31, 2017, include $4.5 million, $2.7 million and $2.3 million under our collaboration agreements with Ipsen, Takeda and Genentech, respectively, and $2.5 million in collaboration revenues from a milestone payment received from BMS related to the ROR gamma program.

During the quarter, we received a $50 million upfront payment from Takeda upon signing the collaboration agreement. We'll be amortizing this upfront payment over approximately the next 4 years. The $2.7 million of collaboration revenue consists of 2 months of upfront payment amortization equaling approximately $1.9 million and approximately $800,000 of R&D reimbursement. The $2.3 million of Genentech collaboration revenue was exclusively related to royalties on net sales of COTELLIC outside the U.S. in the fourth quarter of 2016 and the first quarter of 2017. Historically, we recorded the Genentech collaboration revenue on a 1 quarter lag, but starting in 2017 we'll be recording these revenues in the quarter in which the net sales occurred.

In comparison, during the 3 months ended March 31, 2016, collaboration revenues include $1.2 million and $100,000 in collaboration revenue under our collaboration agreements with Ipsen and Genentech, respectively, and $5 million in collaboration revenues from a milestone payment received from Merck related to the PI3K-delta program.

Research and development expenses for the quarter ended March 31, 2017 were $23.2 million compared to $28.9 million for the comparable period of 2016. The decrease in research and development expenses were primarily the result of decreases in clinical trial costs for METEOR, the company's Phase 3 trial in advanced RCC as well as decreases in share based compensation. Those decreases are partially offset by an increase in personnel-related expenses resulting from an increase in headcount predominantly associated with the build-out of our medical affairs organization.

Selling, general and administrative expenses for the quarter ended March 31, 2017 were $34.3 million compared to $34.9 million for the comparable period in 2016. The decrease in selling, general and administrative expenses were partially a result of decreases in marketing costs due to a decrease in losses under the collaboration agreement with Genentech and stock-based compensation. Those decreases were almost entirely offset by increases in personnel expenses resulting from an increase in headcount connected with the build-out of our U.S. commercial organization and an increase in legal costs.

Other expense net for the quarter ended March 31, 2017 was a net expense of $3.4 million compared to $10.1 million for the comparable period in 2016. The decrease in other expense net was primarily due to a decrease in interest expenses as a result of the 2016 conversions and redemption of the 4.25% convertible subordinated notes due 2019.

Net income loss for the quarter ended March 31, 2017 was a net income of $16.7 million or $0.06 per share basic and $0.05 per share diluted compared to a net loss of $59.2 million or $0.26 per share basic and diluted for the comparable period in 2016. The decrease in net loss for the quarter ended March 31, 2017, was primarily due to the increase in net product and collaboration revenues and a decrease in operating and interest expenses.

Cash and cash equivalents, short and long-term investments and long-term restricted cash and investments totaled $475.8 million at March 31, 2017, as compared to $479.6 million at December 31, 2016. As we announced in late March, we've prepaid our $80 million term loan with Silicon Valley Bank. This substantially reduced our outstanding debt obligation, leaving Exelixis with only 1 debt obligation outstanding, the Deerfield debt. As we announced last quarter, we intend to pay off the Deerfield debt in the July time frame, and we are reiterating that intent today. After this, Exelixis will be free of any substantial debt obligations, with considerable cash available to fund our growing business.

Now turning to our guidance for 2017. We are reiterating our operating expense guidance that operating expenses for 2017 are estimated to be between $290 million and $310 million. We expect our R&D expense to ramp throughout the year, as the previously announced combination studies of cabozantinib and I-O agents begin.

With that, I'll now turn the call over to P.J.

Thank you, Chris. We are very pleased with the continued progress of the CABOMETYX launch and the Q1 2017 cabozantinib franchise net product revenue of $68.9 million. Q1 CABOMETYX net revenue of $62.4 million compares favorably with the Q4 net revenue of $44.7 million, representing growth of approximately 40% and the third full quarter since the launch.

End customer demand increased by approximately 40% in Q1 relative to Q4. This encouraging trend was driven by robust increases in new patient starts, refills for patients already on therapy and broad expansion of the CABOMETYX prescriber base. The number of prescribers who have written CABOMETYX through the specialty pharmacy channel increased in Q1 by nearly 40%. We are also pleased with the growth we have seen in the specialty distributor channel of our business. In addition to strong volume growth in this segment, the number of outlets that have ordered CABOMETYX increased by 20% in Q1. This growth is coming from dispensing community oncology practices, hospitals and academic institutions as well as government facilities. We're particularly pleased with the growth in the community oncology clinics as we have focused on these key practices. Taken together, these data depict solid fundamentals and momentum of the CABOMETYX business.

We are gratified to see that our strategy and approach to the RCC marketplace are producing impactful results. RCC is a mature market with a relatively small number of high-volume prescribers. And beyond that, there are a large number of low-volume prescribers. Our data would suggest that we have been competing effectively in the high-volume segment of the market. So the continued growth we saw in Q1 adoption was driven primarily by community oncologists, indicating that our promotional efforts are broadening the prescriber base, which continues to be a key strategic focus for the team. Approximately 80% of our growth in Q1 was from the community segment.

The increase in new patient demand from Q4 to Q1 is also reflected in our second-line plus new patient market share of approximately 30%. Our data points to an increase in CABOMETYX new patient share in both the second and third line settings and competing effectively with both oral and IV agents. The data are also confirmatory of feedback we are receiving from customers that they are moving CABOMETYX forward in their treatment algorithm as they gain more experience using it.

CABOMETYX continues to take market share in the competitive and dynamic RCC space. This can be seen in prescription data from Q1 where CABOMETYX NRx grew by 31% relative to Q4, while at the same time, axitinib NRx declined 11%, continuing its downward trend. In fact, CABOMETYX was the only oral agent approved for renal cell carcinoma that exhibited growth in total prescriptions in the first quarter of 2017.

We believe that opportunity remains to grow our market share in both the second and third line settings by increasing the breadth of new prescribers and driving incremental utilization from our current prescribers where we focus on the second-line patient opportunity. We plan to accomplish this by highlighting the points that differentiate CABOMETYX from the competition. Our experienced team has generated a very competitive, if not market-leading, share of voice and is executing at a very high level as we work to ensure the appropriate patients with advanced RCC has the opportunity to benefit from CABOMETYX. We have great data, a strong label and solid momentum. That said, we continue to believe that there is significant opportunity to increase demand of CABOMETYX by differentiating from the competition and that this will translate to an increase in our market share, particularly in the second line RCC setting.

We believe there is also opportunity for growth as we continue to expand our promotional efforts in order to reach more physicians who have yet to prescribe CABOMETYX. We are motivated to compete in this dynamic market to bring the benefit of CABOMETYX to every eligible patient as we continue to build on the positive momentum of our launch.

With that, I will turn the call over to Gisela.

Thank you, P.J. I will provide an overview of development progress in the quarter and cover our activities in support of a regulatory filing for first-line RCC on the basis of CABOSUN; the status of CELESTIAL, our randomized Phase 3 study in second-line HCC; and our progress on the important new development plans for combining cabozantinib with immune checkpoint inhibitors; and then I will close with a brief update on cobimetinib.

First, I'll start with CABOSUN, the randomized Phase 2 trial that compares cabozantinib and sunitinib in the first-line treatment of intermediate or poor risk RCC patients. Results of this trial were presented at the ESMO conference last September and published in the Journal of Clinical Oncology later in 2016. This study is being conducted by The Alliance for Clinical Trials in Oncology in collaboration with NCI-CTEP. The trial met its primary endpoint of significantly improving progression-free survival as assessed by investigators in the cabozantinib arm compared to sunitinib. The results showed a clinically meaningful and significant improvement for cabozantinib as compared to sunitinib in PFS and objective response rate and a trend in overall survival, a secondary endpoint on the study. With all activities and different work streams in support of the planned supplemental NDA well underway, we are making good progress and are on track towards an sNDA filing in the third quarter of 2017. We will provide additional update on progress towards this important goal as appropriate.

Second, I'll provide a brief update on CELESTIAL, our Phase 3 study and second-line HCC. The randomized placebo-controlled study is designed to enroll patients who have previously received sorafenib with a total of 2 prior therapies allowed per protocol. The primary endpoint of the trial is overall survival. The trial continues to enroll patients globally, and we're tracking events closely and are getting closer to the number of events required for the second interim analysis. We anticipate that the review will occur in the second half of 2017. If the second interim analysis reads out positive, we would expect to submit a supplemental NDA in the first quarter of 2018, given that for this in-house-run study, all the preparatory work has been ongoing while the study is enrolling and maturing. A final analysis, if needed, will be in 2018.

I'd like to turn now to the third important topic in today's development update, the broader development and lifecycle management plan for cabozantinib. We are very excited about the progress on multiple initiatives evaluating cabozantinib in combination with immune checkpoint inhibitors in collaboration with BMS and Genentech/Roche. Cabozantinib and the immune checkpoint inhibitors, nivolumab, ipilimumab and atezolizumab have all shown efficacy and are approved in various cancer indications. The combination of such active compounds with different mechanisms of action provides a very compelling opportunity for the next wave of late-stage trials for cabozantinib moving forward.

We have discussed previously that there is a strong rationale for combining cabozantinib with immune checkpoint inhibitors as cabozantinib treatment has been shown to result in a more immune permissive tumor environment. Through preclinical and preliminary clinical evaluation, cabozantinib treatment has been shown to affect tumor cells and the tumor microenvironment in a manner that could potentially make them more sensitive to immune-mediated attacks. This could potentially mean that cabozantinib makes tumors more sensitive or even re-sensitizes them to immune checkpoint inhibitors.

With this background information and rationale, we are very pleased to be working in a clinical collaboration with BMS, combining cabozantinib with nivolumab alone or both nivolumab and ipilimumab in a Phase 3 study in the first-line RCC setting, which is expected to start midyear of 2017, with plans to also study the combinations in other indications, including an additional trials in HCC and bladder cancer. BMS and Exelixis will be sharing costs for these trials. Furthermore, we have made progress with our collaboration with Genentech/Roche to evaluate the combination of cabozantinib and atezolizumab in an initial dose ranging study with planned forward expansion in 4 different settings, including patients with previously untreated advanced RCC, patients with previously treated bladder cancer and patients with previously untreated, both cisplatinum eligible and ineligible, bladder cancer. Genentech/Roche will be providing atezolizumab free of charge for this evaluation. This trial is also expected to start mid-2017.

Our partner, Ipsen, has opted in to participate and co-fund a Phase 1b trial with atezolizumab, and the Phase 3 first-line RCC trial with BMS checkpoint inhibitors as well as access to the results to support potential future regulatory submissions in their territories. Both Ipsen and Takeda will each have the opportunity to participate in future combination trials in accordance with the terms of their respective collaboration agreements. We look forward to these trials that will be executed by ourselves and our clinical partners in the near term, and we are on track for starting the first trials in the first half of 2017. We will provide further details on the specific trials when they are being initiated.

In addition to our internal and clinical partner efforts, there are also multiple study proposals going through advanced review at NCI-CTEP and our investigator-sponsored trial program of Phase 2 trials combining cabozantinib with immune checkpoint inhibitors in various indications, including non-small cell lung cancer, triple negative breast cancer, endometrial cancer and other tumor types.

And lastly, our partner, Genentech, continues to advance cobimetinib in a broad development program that includes 3 Phase 3 trials. The IMblaze 370 trial is comparing the combination of cobimetinib with atezolizumab, with atezolizumab alone or regorafenib alone in the third-line setting of colorectal carcinoma. Roche recently announced that this trial had reached full enrollment during the first quarter of the year. Second, the IMspire 150 TRILOGY trial, comparing cobimetinib and vemurafenib to cobimetinib plus vemurafenib plus atezolizumab in BRAF mutation-positive advanced melanoma patient began enrolling early this year. And finally, a Phase 3 trial comparing cobimetinib plus atezolizumab to pembrolizumab and BRAF wild-type advanced melanoma patients with IMspire 170 is anticipated to begin enrolling this quarter. We look forward to updating you on these trials as data become available. And as always, we will keep you updated on the progress of all these programs at the appropriate time.

And with that, I will hand the call over to Mike.

All right. Thank you, Gisela. I'll close by saying that we made significant progress across the organization and achieved our first quarter of profitability on an operating basis in Q1 2017. We look forward to the opportunity to reinvest in cabozantinib development and to rebuild our pipeline through internal R&D efforts as well as to potentially in-license and/or acquire compounds where appropriate.

Our unwavering focus on disciplined expense management, where new R&D initiatives are aligned with robust growth and product revenues, will continue to be our guiding principle as we move the company forward in 2017 and beyond. Simply stated, we are 1 team with 1 mission: To advance medicines to treat patients with cancer, giving them and their families hope for the future. I am incredibly proud of the Exelixis team, who, individually and collectively, work tirelessly to deliver on this mission. We have much more to do, and I am confident that we have all the elements in place to advance both our science and business with a great deal of focus and urgency as we tackle the challenges that we will face in the future. We look forward to updating you on our progress. Thank you for your continued support and interest in Exelixis.

We're happy to now open the call for questions.

(Operator Instructions) Your first question comes from Eric Schmidt with Cowen and Company.

Maybe a couple quick ones. First, just to clarify on CELESTIAL. Gisela, are you still committed to having the data, the final data, one way or another in 2017? Or if the trial doesn't stop at its second interim, might we need to wait until 2018 for the final?

Yes, Eric, we'll have the interim analysis, the second interim analysis in the second half of 2017. And if we have to go to the final analysis, that would be a 2018 event.

Okay. And then for Chris, you didn't mention royalties from Ipsen. I think they reported, I think, EUR 7.6 million. What's going on with your part of those profits?

Yes, Eric. Thanks for the question. So as you may recall, the first $50 million is at a 2% royalty. So you're talking, I think, $135,000, $140,000 of royalties which are not that -- that are in our numbers, it just wasn't broken down.

Okay. And I'm wondering if you might want to make any predictions on future profitability. Obviously, you achieved a landmark in turning profitable from an operations standpoint this time around.

Eric, it's Mike. I'll take that one. Again, we're certainly pleased with the Q1 performance. We think there's more upside there. So we're not satisfied with Q1 but certainly started the year off on the right foot. Our stated goal previously has been to generate free cash and reinvest that free cash in the business. That goes back to the last financing that we did in 2015 and that's still the operational strategy going forward. Obviously, we want to focus on growing the top line through cabo, additional cabo indications, new compounds, internal, external, whatever. But that's the real focus going forward, is to really build the business based upon using free cash that we can generate through product sales.

Your next question comes from Stephen Willey with Stifel.

Just so I guess a couple of CELESTIAL questions. I know enrollment into the study was kind of a bit of a nonlinear exercise. So I guess I'm just trying to figure out if the extension of a potential final read into '18, is that a byproduct of the patient enrollment kinetics? Or is that a byproduct of, I guess, the slower-than-expected event rates?

Well, it's an event-driven study. And so as I said earlier, we are tracking events very closely, and are now approaching the event number required for the second interim analysis. And looking at the trajectory of the events, we would expect the final analysis to occur in 2018.

Okay. And then I know the study actually allows for, I think, more than 1 prior systemic therapy. And I guess just curious if you're seeing many patients who have both prior exposure now to sorafenib and maybe regorafinib as well post that Phase 3 win?

Yes, patients are required to have seen and been treated with prior sorafenib and they could have had 1 additional other systemic therapy and we haven't specified what that is, so we would expect reporting that out when results become available.

Okay. And maybe just a last question for Chris. It doesn't look like there was really any material inventory shift per the Quarter, but just wanted to make sure that there was no stocking benefit in the $62 million cabo number.

Thanks, Steve. So it's Chris. So no, we're around 3 weeks' inventory and we ended last quarter with around 3 weeks' inventory for CABOMETYX. So there was no stocking.

And your next question comes from Michael Schmidt with Leerink Partners.

I had a few additional question regarding the label expansion activities that you're doing for CABOMETYX. And 1 question on the CELESTIAL trial I had was I know you're doing a subgroup, or maybe it's a post hoc analysis by MET expression status in the study and I was wondering if the study is actually powered to show a benefit in that subgroup should the overall analysis be negative potentially?

Well, the MET analysis is foreseen in the protocol, and accordingly, we're collecting the tissue and the analysis is ongoing. But the power of the study is really dedicated to the overall study.

Okay. And then a question on your future planned studies with Bristol combining cabo with Opdivo, potentially also in HCC. And I was wondering if -- what the gating factor is to starting additional studies in HCC. Do you need to see the TEP1 inhibitor Phase 3 trial results? Or do you need to see the CELESTIAL Phase 3 trial result before starting additional studies? Or is it independent of that, of these data points?

Yes, we're not awaiting additional results to start the work here with combining cabo and nivolumab. As you know, there's published data from Phase 2, both for cabozantinib and nivolumab that is showing activity in this disease. And so certainly encouraged to move forward with it as it is.

Okay. And then I had a question on the Daiichi Sankyo molecule CS-3150 that you have licensed with them. And looking at on a clinical trial graph I noticed their Phase 3 program looks like it's nearing an end in the next few months, and I was wondering if you have - like if you can remind us on economic interest on that molecule and maybe what their time line is regarding data disclosure from the Phase 3 program there?

Yes, this is Peter, I can take that question. So just by way of reminder, CS-3150 is a potent selective nonsteroidal minerocorticoid receptor antagonist that was discovered at Exelixis and which is now partnered with Daiichi Sankyo. Daiichi are responsible for all of the ongoing clinical development activities and will be responsible for any future commercial activities. In terms of the status of the compound, Daiichi moved it into a pivotal Phase 3 trial back in September of last year. This was in Japanese patients with essential hypertension, and we were certainly pleased to see that, that trial reached full enrollment in the first quarter of this year. And I think Daiichi have reported at least that they're expecting top line data from that trial in the second half of their financial year 2017. But obviously, I'll have to refer you to Daiichi for more clarification of exactly when they might be expecting it. In terms of our economic interests, under the contract, we're eligible for a series of clinical regulatory and commercial milestones associated with the advancement of the compound as well as low double-digit royalties on any potential future sales.

And is this molecule aimed at the Japanese market only? Or are they looking to register worldwide potentially?

So the data, all of the development that Daiichi has been doing has been in the Japanese market in terms of what they're planning for the future. Again, I'd have to refer you to them.

And your next question comes from Andy Hsieh with William Blair.

This is Andy Hsieh on for John Sonnier. We have 2 questions. First one is for P.J. I think before, maybe a year ago, I believe you guys talked about the breakdown for subscribers is about 70%-30% community versus academic. Does that ratio still stand? Secondly, just a question on spending. Obviously going forward, the combination trials, there are several parties involved. Are the responsibilities of Takeda and Ipsen, are they geography-based? Or is there a percentage that they're responsible? Maybe structurally, can you walk us through the expense?

Yes, Andy. This P.J. Thanks for the question. I think, kind of going back to my memory bank here to remember what was said a long time ago. I think, typically, oncology markets you see sort of that 80-20, 70-30 split in academic to community. What I could say about CABOMETYX in the current RCC market is that we've talked about is there's a large number -- or excuse me, a small number of high-volume prescribers, many of them academic. We're competing extremely effectively in that market. So if you actually look at our slides, you could see that over time, we've expanded our community base. So we're sort of at a point where we're about, give or take, 60%, 65% in the community. And that's an increasing number, which I view as a very good sign for the business for 2 reasons: One, because we've got rapid adoption among the KOLs in the academic prescribers which is always a good place to start out a launch; and two, because we really have great momentum in the community and we see that expanding again this quarter as we increase our business by 80% of our growth came from the community, and our prescriber growth grew by 40% of new prescribers through the specialty pharmacy channel. So it's about, like I said, 60%, 65% community and increasing as we look over the past few quarters, which I think is a healthy place to be.

So Andy, this is Chris. From a cost-sharing point of view on the R&D side, so if you look at the current ongoing trials, we fund 100% of them, and Takeda reimburses us around 20% for those. If you look at the future trials that we may do, including the BMS trials, which we're sharing the costs in, as Gisela noted in her prepared remarks, Ipsen has opted in for that, and Ipsen will pay 35% of our share of those studies. And as of right now, because it's still new, Takeda hasn't made a decision to opt in or not, but if they do opt in, they would share 20% of our share of the BMS combination trial cost.

And your next question comes from Edward Tenthoff with Piper Jaffray.

Quick question. I apologize if this was asked or if this was something that you can't comment on, but I wanted to get a sense if you know about frontline utilization. I know, obviously, you don't promote it on that especially with the filing coming, and it was easier to interpret earlier when we can kind of see through COMETRIQ sales ticking up. But do you have any sense of whether there is some adoption in the front line?

Ted, this is P.J. Well first, I'll remind you that we certainly only promote CABOMETYX or any of our products within the labeled indication. And with regards to commenting on off-label utilization, by policy, with one exception in the past, we're not doing that now or currently moving forward. What I'll say is we've had really great strength in both the second and third and later line settings. So we've seen good growth there in the prescriber base, in the volume demand up 40%, the revenue up 40%. And we think we still have a lot of opportunity and room to grow by both expanding the prescriber base, a lot of prescribers haven't written yet, as well as moving it more into the second line setting.

Your next question comes from Andrew Peters with Deutsche Bank.

Couple questions for me. I guess first just on the Bristol collaboration. Can you walk through, I guess, what are the limiting steps on getting the bladder and HCC studies started? And as you think about the other potential trials that you talked about, can you just walk through the sort of discussions that you're having with Bristol in terms of what those potential other indications could look like and the extent of those studies? And then just secondly, in the past, you've talked about the potential for multiple deals beyond just say, a Bristol and a Roche, is there the possibility to expect additional collaborations over the course of the year? And how do you think about continued business development in terms of the partnership on CABOSUN?

This is Gisela. Just starting with your first question regarding limiting steps to get the study started, it's really agreement on the study design, development of protocols and the usual startup activities that are associated with new clinical trials. So these are being worked on and are advancing quite nicely. And regarding indications beyond the ones we've named, I cannot comment on this as yet other than to say that there are some discussions ongoing.

Yes, it's Mike. Maybe I'll try and answer your second question. Again, as we said previously, we're really interested in exploring as much, if you will, real estate as possible across both hot and cold tumors in terms of different histologies as well as different I-O opportunities. In that regard, we're talking to everybody in some shape, manner or form. Don't want to give any guidance on that. Don't want to speak with any clarity on that right now. But we're looking to again I think really expand the number of opportunities we have across the board to look at different tumor types with cabo-I-O combination. So stay tuned on that. Certainly, we're very pleased with the initial steps forward with the BMS and Roche collaborations, and there's lots more to do. And we're going to try to get that done as we go forward.

Your next question comes from Chad Messer with Needham & Company.

Crossing that threshold over into operational profitability, it's something only a select few biotech companies ever accomplish. Just wondering now that you're about a year into the launch in RCC with cabo, do you have an understanding of what's sort of driving prescriber decisions to use cabo second line versus later, something about disease characteristics or sequence of other treatments? Or any kind of pattern that you can grab on to that would be driving earlier versus later use?

Yes, great question. Why don't we have P.J. start that off and I'll try and provide some color commentary as needed, okay? P.J.?

Okay, great. Thanks for the question, Chad. I will say, I think that depends on prescribers generally. It's very clear from our market research as well as feedback that we get from customers through advisory boards and other meetings that if physicians, oncologists are aware of the data, really, of the trifecta benefit in overall survival progression-free survival and the response rate, they're willing to utilize the drug. Typically, in oncology often, they will start in the third-line setting or later line settings and move it up. So that's what we're seeing. We're seeing prescribers, as they get some experience with the drug, move it forward from the third line or later into the second-line setting which is certainly an encouraging sign and a sign that they're having a good experience with the drug. That said, I think it's -- there are some potential patient types that could be potentially preferential, patients who might be symptomatic or have rapidly progressive disease, they want a response to their disease quickly. I -- what we hear from customers is that CABOMETYX is a great option for those patients. That said, our label really is broad and we can promote it to all patient types. So it's really encouraging what we're hearing now. As you mentioned, we're a year into the launch, and we think we have a lot more work we can do as we get more prescribers educated on the drug, we'll have an opportunity to it try and continue to grow the business going forward.

(Operator Instructions) And your next question comes from Stephen Willey with Stifel.

Just a quick question on CABOSUN actually. So I know you guys are going to be filing in the third quarter this year. But I guess I'm just curious if there's going to be any opportunity for us to see the centralized review results, I guess, either presented at some conference venue or communicated to us via you guys prior to there being some kind of formal sNDA decision.

Yes, I think the IRC review, obviously, is a critical step. And I think we've said before and reiterate today, that we would expect this data to be made public in a scientific conference, and in that context we would certainly discuss it as well.

At this time, there are no further questions. And so I will turn the call over to today's host, Susan Hubbard. Ms. Hubbard?

Okay, great. LeeAnn, thank you, and thank you all for joining us today. We welcome your follow-up calls with any additional questions that you may have. Thanks again.

Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program, and you may all disconnect. Everyone, have a great day.