Exelixis Inc (EXEL) 2016 Q3 法說會逐字稿

Good day ladies and gentlemen, and welcome to the Exelixis third-quarter 2016 financial results conference call. My name is Sayed, and I will be your operator for today. As a reminder, this conference call is being recorded for replay purposes. I would now like to turn the call over to your host for today, Miss Susan Hubbard, Investor Relations. Ma'am, you may perceive.

Thank you Sayed, and thank you all for joining us for the Exelixis third-quarter 2016 financial results conference call. Joining me on today's call are Mike Morrissey, our President and CEO, Chris Senner, our Chief Financial Officer, PJ Haley, our Vice President of Commercial, Gisela Schwab, our Chief Medical Officer, and Peter Lamb, our Chief Scientific Officer, who will together review our corporate, financial, commercial and development progress for the quarter ended September 30, 2016, as well as recent key developments and corporate events.

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 results or events 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 the applicable regulatory requirements, the availability of data at reference times, our dependence on collaboration partners, and our ability to maintain our rights under existing collaborations, and the level of costs associated with commercialization, research and development, and other activities.

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

Thank you Susan and thanks to everyone for joining us on the call today. I'll provide a short overview of the key events for Q3 and then turn the call over to Chris, PJ, Gisela, and Peter, who will provide a more detailed review on our financials, the ongoing CABOMETYX launch, and updates on development activities for both cabozantinib and our partnered compounds.

Key events from the third quarter include, first, our strong first full quarter of CABOMETYX revenues, reflecting the momentum of the launch driven by the strength of the METEOR data and the skill and energy of our commercial and medical affairs teams; second, the EU approval of CABOMETYX on September 9 for the treatment of advanced RCC patients following prior anti-VEGF therapy; third, the presentation of 15 abstracts featuring Exelixis-discovered compounds cabozantinib and cobimetinib at ESMO, including the first presentation of the CABOSUN data; and fourth, the strong Q3 P&L performance from both a revenue and expense perspective, coupled with our improved balance sheet with the conversion of the 2019 notes.

Exelixis remains in a solid financial position to pursue our mission of bringing innovative medicines to patients with cancer.

We are pleased with the progress of our US CABOMETYX launch. Total Q3 net product revenue for the cabozantinib franchise was $42.7 million. As PJ will highlight later in the call, CABOMETYX continues to be prescribed for advanced RCC with increased frequency and rapidity by healthcare professionals in both the academic and community setting. We continue our broad efforts to maximize the impact of CABOMETYX within its labeled indication by educating physicians on the appropriate use of the drug.

Meanwhile, Ipsen is in the final stages of preparing for the EU CABOMETYX launch following the recent EMA approval, and first sales should occur this year, triggering additional financial milestones. In fact, we were notified today by Ipsen that the first sales in Germany were recorded yesterday, triggering a $10 million milestone to be recorded this quarter.

We had a very productive meeting at ESMO in Copenhagen which included the highly anticipated presentation by Dr. Toni Choueiri of the CABOSUN data for cabozantinib versus sunitinib in previously untreated patients with intermediate or poor risk RCC. The data, which Gisela will describe in a moment, were well received by oncology experts across the globe, and we intend to file a supplementary new drug application, or sNDA, for this indication.

Also presented at ESMO were posters describing the initial clinical experience with cobimetinib in combination with chemo or immunotherapies. These results are driving additional late stage development activities for the drug by Genentech.

In addition, another of our partnered compounds, CS-3150, has advanced into a Phase 3 pivotal trial in Japanese patients with hypertension that is being conducted by Daiichi Sankyo, as Peter will describe later.

On the financial side of our business, Q3 was a strong quarter with growing revenues along with continued financial discipline across the entire organization. As you will hear from Chris, we've earned approximately $4 million in Q3 when compared to our cash position at the end of Q2, a notable achievement in the face of an ongoing US launch, and recorded a net loss of $0.04 per share. We intend to exercise continued financial discipline moving forward while making prudent and thoughtful strategic investments to help us compete in the marketplace and advance the cabozantinib development program.

In addition, we are looking closely, carefully, to invest in both internal and external oncology assets at the appropriate time and as attractive opportunities become available.

In closing, Exelixis had a strong third quarter across all components of our business and is on track for a productive finish to 2016.

So, with that, I'll turn the call over to Chris, who will provide more details on our Q3 financials.

Thanks Mike. Before I start, I want to note that I will be speaking to the financial data referenced in Slides 8 through 13 in our earnings presentation. These slides include comparisons to both the third quarter of 2015 and the second quarter of 2016 for your reference.

Total revenues for the quarter ended September 30, 2016 were $62.2 million compared to $9.9 million for the comparable period in 2015. Revenues for the third quarter of 2016 include $42.7 million of net product revenue compared to $6.9 million for the comparable period in 2015. The increase in net product revenues for the three months ended September 30, 2016 as compared to the same period in 2015 reflects the impact of the first full quarter of CABOMETYX revenues since its commercial launch in late April 2016, as well as an increase in COMETRIQ revenues. Net product revenues of CABOMETYX and COMETRIQ were $31.2 million and $11.5 million respectively.

Total revenues for the quarter ended September 30, 2016 include the recognition of $15 million of contract revenue from the Daiichi Sankyo CS-3150 milestone, $3.8 million of license revenues recognized under our collaboration and license agreement with Ipsen, and $700,000 of royalties on ex-US net sales of COTELLIC. During the comparable period in 2015, there was $3 million of contract revenues for a milestone payment received from Merck related to the worldwide license of our PI3K-delta program.

Research and development expenses for the quarter ended September 30, 2016 were $20.3 million compared to $26.1 million for the comparable period in 2015. The decrease was primarily related to decreases in share-based compensation, clinical trial costs, and the allocation of general corporate costs. Those decreases were partially offset by increases in personnel related expenses resulting from an increase in headcount predominantly associated with the buildout of the Exelixis Medical Affairs organization.

Selling, general, and administrative expenses for the third quarter -- for the quarter ended September 30, 2016 were $32.5 million compared to $17.8 million for the comparable period in 2015. The increase was primarily related to an increase in personnel related expenses resulting from the increase in headcount connected with the buildout of Exelixis US commercial organization and marketing and outside services to support the launch and commercialization of CABOMETYX.

Other income and expense net for the quarter ended September 30, 2016 was a net expense of $18.5 million compared to $9.8 million for the comparable period in 2015. The increase in net expense is primarily due to the $13.8 million of loss associated with exchange and conversion through September 30, 2016 of $285.3 million in aggregate principal amount in the Company's convertible senior subordinated notes due 2019 for approximately 53.7 million shares of our common stock. The net expense also includes interest expense, including $3.9 million of non-cash expense related to the accretion of the discounts on both the 2019 notes and the Company's indebtedness under secured convertible notes due 2018 held by entities associated with Deerfield for the quarter ended September 30, 2016 as compared to $6.9 million for the comparable period in 2015.

Net loss for the quarter ended September 30, 2016 was $11.3 million, or $0.04 per share, compared to $45.5 million, or $0.21 per share, for the comparable period in 2015. The decreased net loss for the quarter was primarily due to increases in net revenues and decreases in research and development expenses which were partially offset by increases in selling, general, and administrative expenses and other income and expense net.

Turning to our financial guidance for 2016, given where we are in the year, we are refining our previously provided guidance, and we are now projecting that total operating expenses for the full-year 2016 will be approximately $245 million, including approximately $25 million of non-cash items primarily related to stock-based compensation expense.

And with regards to our cash in 2016, at the end of the third quarter of 2016, we had cash and cash equivalents, short and long-term investments, and long-term restricted cash and investments totaling $379.6 million. This represents an increase from $253.3 million at December 31, 2015.

As we look to year-end 2016, we expect to receive at least $85 million in milestones from our collaboration partners, Ipsen and Daiichi. When this is coupled with our growing revenue from product sales and continued vigilant expense management, we expect that, at year-end, we will be in a very healthy cash position.

Additionally, after aggressively retiring our outstanding convertible debt obligation, we ended the quarter with approximately $200 million principal amount of debt outstanding. We continue to evaluate our balance sheet to ensure that we have the capital structure that best supports our business requirements today and into the foreseeable future.

And with that, I will turn the call over to PJ.

Thank you Chris. We were very pleased with the progress of the CABOMETYX launch and the Q3 cabozantinib franchise net revenue of $42.7 million. Q3 CABOMETYX net revenue of $31.2 million compares favorably with the Q2 net revenue of approximately $11 million after adjusting for the initial build of channel inventory.

I would like to sincerely thank the entire commercial team for their tireless efforts and dedication to RCC patients and to Exelixis.

Since approval, CABOMETYX is experiencing rapid and broad uptake in the advanced RCC marketplace. According to IMS' BrandImpact September Report, CABOMETYX has achieved approximately 20% share in terms of new patients in the second line RCC setting.

If we focus on just the TKI market in the second line setting, CABOMETYX has garnered 40% share, which is the highest of any TKI. In the third line setting, CABOMETYX has become the market leader with 35% of new patient share and 55% of new patients within the TKI market. Based on these data, CABOMETYX is now the most commonly used oral therapy for previously treated advanced RCC patients.

We believe that significant opportunity remains to grow our market share in both the second and third line RCC settings by increasing the breadth of our prescriber base and driving incremental utilization from our current prescribers. We hope to accomplish this by focusing on the points that differentiate CABOMETYX in this crowded marketplace.

Our team continues to compete and focus on building market share by targeting prescribers with patients who would have historically received other oral agents in the second and third lines. CABOMETYX has the attributes to become the oral agent of choice in this setting, where the market share for other oral agents is approximately 45% in the second as well as the third line settings. This represents a large growth opportunity for CABOMETYX.

While we are focused on building on the leadership position of CABOMETYX among TKIs, we continue to compete directly with immunotherapy, which represents an opportunity of 38% of the second line RCC market. The key to this will be continuing to differentiate CABOMETYX by reinforcing that it is the only single agent that offers statistically significant and clinically meaningful improvements in the trifecta of efficacy endpoints of overall survival, progression-free survival, and objective response rate in a large global pivotal trial.

Importantly, CABOMETYX is also the only oral agent that first has preferred status in the NCCN guidelines in the setting, and second, addresses the important resistance pathways of MET and AXL in addition to VEGF.

Our sales and marketing efforts are focused on promoting the METEOR data and elucidating these key points of differentiation, which market research indicates compels oncologists to prescribe CABOMETYX. Our approach has already led to encouraging trends in prescriber adoption. The number of unique CABOMETYX prescribers increased by approximately 150% in Q3 relative to Q2. This increase was driven predominantly by community oncologists indicating that our promotional efforts are broadening the prescriber base, which is a key strategic focus for the team.

As we discussed last quarter, we saw rapid adoption among the academic oncologists. In fact, nearly all of the KOLs already have prescribed CABOMETYX in the commercial setting. The rapid new prescriber adoption that we are seeing confirms our conviction that CABOMETYX addresses a significant unmet medical need in advanced RCC.

We continue to evolve our channel in order to optimize customer and patient access to CABOMETYX. Recently, we signed the Federal Supply Schedule Agreement and CABOMETYX is now broadly available at VA and Department of Defense facilities and through TRICARE.

Payor coverage and our conversations with payors continue to be positive and encouraging. In fact, we now have secured favorable coverage for more than 224 million covered lives and are not encountering any coverage barriers for appropriate patients. Similar to physician feedback, payor feedback has been positive based on the clinical value of the METEOR data.

With regards to our business outside of the US, we are certainly pleased with the progress and collaboration of our partner, Ipsen. ESMO was an extremely successful meeting for both Exelixis and Ipsen, which you will hear more about from Gisela. They provided the ideal venue for the launch of CABOMETYX in Europe on the heels of the EU approval.

Finally, we continue to expect COMETRIQ to return to the stable level of demand in medullary thyroid cancer that was observed previously before the recent ramp due to RCC utilization prior to CABOMETYX approval.

The RCC market has been very dynamic over the last year as there are now 11 treatments approved for advanced RCC. There are six large pharmaceutical companies promoting and co-promoting these therapies. Many of them have been in this competitive market since 2006.

The dynamic RCC market and inroads that CABOMETYX is making can be seen in the recent Q3 earnings reports that have detailed the decline of products such as everolimus, which is down 19% in the US, attributed to competitive pressure in breast cancer and renal cell carcinoma. In addition, sorafenib was down 13.5% year-over-year in the US, and axitinib declined 26% year-over-year and 20% quarter-over-quarter in the US, both attributable to competitive pressure in RCC. In this context, we are pleased that our deeply 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 appropriate patients with advanced RCC have the opportunity to benefit from CABOMETYX.

We have great data and a superior label and are off to a solid start with market share of approximately 20% in the second line and 35% in the third line. That said, we fully recognize that there is significant opportunity to increase our market share by differentiating CABOMETYX and growing our prescriber base. 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 now turn the call over to Gisela.

Thank you PJ. I will start with a brief regulatory update where we continue to make good progress.

CABOMETYX was approved in the European Union on September 9, 2016. This followed an accelerated review by CHMP and we are pleased to report that our partner Ipsen is now launching CABOMETYX in the first countries in the EU.

In today's development discussion, I will cover key data presented at ESMO 2016 in Copenhagen, in particular speak in more detail about the results and next steps for two clinical studies, CABOSUN, the randomized Phase 2 trial in previously untreated patients with intermediate or poor risk RCC, and the Phase 1b combination study of cabozantinib and nivolumab in GU malignancies, data from which was also featured prominently at ESMO. At this year's ESMO conference, 15 presentations featured Exelixis discovered compounds. There were eight presentations on cabozantinib and seven presentations on cobimetinib data. Most notable was the oral presentation in the presidential symposium by Dr. Toni Choueiri of the CABOSUN results showing significant improvement in progression-free survival and objective response rate in first-line RCC.

CABOSUN is a randomized Phase 2 study comparing cabozantinib and sunitinib in the first-line treatment of patients with advanced intermediate or poor risk RCC. This trial was performed by the Alliance for Clinical Trials in Oncology under our CRADA with NCI-CTEP. CABOSUN enrolled 157 patients. Patients were stratified by the IMDC risk category, intermediate versus poor risk, and the presence of bone metastases, yes versus no. Progression-free survival was the primary endpoint of the study.

CABOSUN met its primary endpoint of significantly improving progression free survival compared to sunitinib. Median PFS was 8.2 months with cabozantinib and 5.6 months with sunitinib for an HR of 0.69, and a one-sided P value of 0.012, representing a 31% reduction in the rate of disease progression or death. Consistent results were seen across subgroups by stratification factors, all favoring cabozantinib.

The objective response rate was also significantly improved with cabozantinib as compared with sunitinib with 46% versus 18%. Overall survival results were immature with a minimum follow-up of about 16 months. The median overall survival for cabozantinib was 30.3 months and, for sunitinib, 21.8 months, for an HR of 0.8. This result did not reach significance and future analysis of overall survival with longer follow-up is planned.

The safety profiles of cabozantinib and sunitinib were similar and consistent with what has been previously reported for VEGFR TKIs in this indication, and no new safety signals were identified for either compound. Based on these results, Exelixis plans to submit a supplemental new drug application, or sNDA, for cabozantinib as a treatment of first-line advanced renal cell carcinoma, and it's working with the Alliance to transfer the complete CABOSUN clinical database to Exelixis.

Additionally, we are working with the Alliance on collecting all images for an independent radiology review. The timing of an sNDA submission is dependent on various factors, and we are not providing guidance on timing today.

Preparations for an sNDA are the top priority for Exelixis, and we will update you when we are further along in the process.

Other presentations at ESMO for cabozantinib included a subgroup analysis for METEOR, our Phase 3 study in previously treated patients with advanced RCC which showed consistent benefit for all three endpoints -- overall survival, progression free survival and objective response rate -- in all subgroups regardless of tumor burden and spread of disease or geographic region.

An additional presentation showed that quality-of-life was similarly maintained throughout the course of treatment for patients receiving cabozantinib as for patients in everolimus. However, when a patient's disease progressed, quality of life decreased substantially, illustrating the importance of extending progression-free survival as was seen with cabozantinib. Time to disease deterioration was significantly longer with cabozantinib compared to everolimus.

And lastly, an important Phase 1b trial presented by Dr. Apolo showed results of the first part of the ongoing Phase 1b study evaluating the combination of cabozantinib plus nivolumab in 24 patients with genitourinary cancers. This trial enrolled patients with various heavily pretreated GU malignancies. The median number of prior therapies was three, and 10 patients had received four or more prior therapies. An objective response rate of 43% was reported across all patients in the study and four of six, or 67%, of patients with urothelial cancer and two of two patients with squamous cell cancer of the bladder achieved a response.

The combination of cabozantinib and nivolumab was generally well tolerated in a dose of 40 milligrams daily of cabozantinib with 3 milligrams per kilogram of nivolumab every two weeks as the recommended dose for the now ongoing expansion cohorts in bladder cancer and RCC.

In parallel with the doublet expansion cohorts, Part 2 of the 1b study evaluates a range of doses for the triplet combination of cabozantinib and both nivolumab and ipilimumab. This dose ranging part of the study is now fully enrolled and we look forward to the data from Part 2 at a future conference.

Data on the tolerability and antitumor activity of the combination studies in this early phase trial could set the stage for a later phase evaluation, not only in the genitourinary setting, including RCC and bladder cancer, but in other areas as well like non-small cell lung cancer and histologies that appear sensitive to both agents. Development plans are under discussion with key opinion leaders and with our partner, Ipsen, and we are working towards implementation of further trials for cabozantinib in the months to come.

And lastly, let me briefly turn to the development of cabozantinib in liver cancer. Our ongoing Phase 3 study in second line treatment of HCC continues to accrue patients globally. The trial, called CELESTIAL, is a randomized, placebo-controlled study evaluating cabozantinib versus placebo in patients with advanced HCC who have received prior sorafenib. The primary endpoint of the trial is overall survival. We continue to expect results for this study in the 2017 time frame.

And with that, I will hand the call over to Peter to speak about our partnership programs with Daiichi Sankyo for CS-3150 and Roche for cobimetinib.

Thanks Gisela.

First, our partner, Daiichi Sankyo, recently initiated a registrational Phase 3 trial of our mineralocorticoid receptor antagonist, CS-3150, or esaxerenone, in Japanese patients with essential hypertension. Mineralocorticoids play an important role in regulating blood pressure, primarily through controlled sodium reabsorption in the kidney, but also via effects on other tissues. Steroidal mineralocorticoid antagonists such as spironolactone and eplerenone have been used as antihypertensive agents for some time but suffer variously from poor selectivity, low potency, short half-life, and potential for inducing hyperkalemia and are not indicated for patients with diabetic nephropathy.

In 2006, Exelixis and Daiichi Sankyo entered into a partnership to identify and develop novel mineralocorticoid antagonists with improved properties, which led to the discovery of CS-3150, a highly potent and selective nonsteroidal mineralocorticoid receptor antagonist with a long half-life that is highly active in preclinical models of hypertension and diabetic nephropathy.

Daiichi Sankyo subsequently conducted an extensive Phase 1 and 2 clinical trial program testing CS-3150 in Japanese patients with hypertension and in patients with diabetic nephropathy, but examined the effects of different doses of the CS-3150 on blood pressure, urinary albumin creatinine ratio and rates of hyperkalemia.

In the Phase 2b study in hypertensive patients, there was a clear dose dependent antihypertensive effect with 2.5 to 5 ml daily of 3150 providing similar blood pressure control to 100 ml daily of eplerenone, while, in a Phase 2b study in patients with diabetic nephropathy, a significant reduction in urinary albumin creatinine ratio was observed versus placebo at all doses of CS-3150 tested. The induction of hyperkalemia was low in all studies.

The recently initiated pivotal Phase 3 registrational trial will enroll 930 Japanese patients with essential hypertension to one of three arms -- CS-3150 2.5 ml, or 5 ml daily, or eplerenone 50 ml daily. The trial has a noninferiority design with a primary endpoint of change in sitting systolic and diastolic blood pressure from baseline and a safety end point of hyperkalemia incidence. Topline data from the trial are anticipated to be available in the second half of next year.

In addition to the pivotal trial, Daiichi Sankyo is currently sponsoring a series of smaller trials examining the effects of CS-3150 in specific patient populations with hypertension and in combination with other antihypertensive medications.

Hypertension is highly prevalent in Japan and impacts approximately 43 million patients, only 30% to 40% of whom are adequately controlled by current antihypertensive therapies.

Finally, initiation of the trial triggered a $15 million milestone payment to Exelixis which we received in the fourth quarter.

Now, let me turn to cobimetinib, the Exelixis-discovered MEK inhibitor that is being developed by our partner, Genentech. Cobimetinib was featured in seven presentations at ESMO, including additional analyses based on the pivotal coBRIM trial and other earlier studies in melanoma.

I'll briefly highlight three presentations that describe the activity of cobimetinib in combination with immuno- or chemotherapy that are driving additional late stage development of the drug.

First, data were presented from the 1b dose ranging stage of the COLET study in triple negative breast cancer patients combining cobimetinib with paclitaxel. Eight of 16 patients, or 50%, achieved a tumor response with paclitaxel and cobimetinib, and the combination was tolerable with no new safety signals emerging. The randomized Phase 2 stage of the trial comparing paclitaxel to cobimetinib plus paclitaxel is now enrolling.

Also presented was an update of the Phase 1b trial combining cobimetinib with atezolizumab in colorectal carcinoma patients who have failed two prior lines of chemotherapy. The 20 KRAS mutant patients enrolled in the study showed an objective response rate of 20%. Notably, responses were seen in patients whose tumors were microsatellite stable, a phenotype that responds very poorly to single agent immunotherapy agents. These results provided the rationale for initiating the current ongoing Phase 3 trial COTEZO that compares cobimetinib combined with atezolizumab to atezolizumab alone, or regorafenib alone, in the third line setting of colorectal carcinoma.

And lastly, for the first time, results from a 1b study of cobimetinib in combination with vemurafenib and atezolizumab were presented showing an objective response rate of 83%, including 10% complete responses among 29 response evaluable patients with advanced BRAF mutant melanoma. No new safety signals were identified in this trial. On the basis of these results, a pivotal placebo-controlled Phase 3 trial evaluating the combination of cobimetinib, vemurafenib and atezolizumab compared to cobimetinib, vemurafenib and placebo was recently posted on clinicaltrials.gov. Sponsored by Roche, this trial is scheduled to start enrolling in the first quarter of next year.

Taken together, emerging data suggests that there may be a broad role for cobimetinib in combination with both chemo and immunotherapy in a range of underserved tumor types, and we look forward to providing additional updates as they become available. In this context, we also note that two new trials sponsored by BMS are now recruiting testing the combination of cobimetinib, nivolumab and ipilimumab in multiple solid tumor patient populations.

Finally, at the upcoming Society for Melanoma Research Conference to be held in Boston between November 6 and 9, seven abstracts will be presented featuring cobimetinib, including updates on long-term survival from the coBRIM trial and combination data for cobimetinib plus atezolizumab in BRAF wild type and mutant metastatic melanoma.

So I'll now turn the call back to Mike.

Thank you Peter. In closing, I could not be more pleased with our progress over this year-to-date and we remain focused on the opportunities and significant milestones that are ahead of us. The Exelixis team consistently demonstrates our passion, urgency and commitment to help patients with cancer, whether that is through further development of our compounds in areas of significant unmet medical need or by ensuring there are no barriers for the patients who could potentially benefit from access to our medicines.

This quarter's achievements and financial results represent significant momentum toward delivering on our commitment to investors to drive the business to positive cash flow. Future financial success would give us the opportunity to reinvest in our business, invigorate our organic R&D efforts, as well as to potentially in-license and/or acquire compounds, where appropriate, to provide new treatment options to patients with cancer. We are fully committed to this vision while maintaining a strong, extensive, disciplined expense management where new R&D initiatives are aligned with robust growth and product revenues.

We look forward to updating you on our progress as we go forward. Thank you for your continued support and interest in Exelixis. And we are happy to now open the call for questions.

(Operator Instructions). Eric Schmidt, Cowen and Company.

Just a few questions, maybe starting on CABOMETYX, and congrats on a good quarter. It sounds like there was no stocking in Q3. Is that correct?

This is Chris. Thanks for the question. There wasn't significant stocking at all. What we are looking at now is the inventory being in the range of three to four weeks in the trade, and that's where we are expecting it to remain as we go forward.

And Chris, I think, last quarter, you kind of commented that you didn't think there was a bolus of initial patient demand, and you were seeing sort of steady growth throughout the initial launch period. It certainly looks like that reflected itself in very, very strong Q3 numbers. But when you look forward, do you see any slowing of growth? And I ask because there are third-party sites like IMS that suggest that the growth has decelerated.

This is PJ. Thanks for the question. A couple of things. We are certainly very pleased with the start to the launch. Certainly, the $42.7 million in cabozantinib franchise revenue in Q3 was very encouraging, and we are pleased with that.

The third-party sources of data that you guys look at and we look at definitely have a lot of questions where they sort of bounce around early in the launch phase as they kind of learn how to optimize their methodology and really track in on it. So we see a lot of data internally. We are very confident in the data that we do see and see a lot of signs in demand. I would certainly look at the CABOMETYX brand revenue, Q3 over Q2, after you account for the initial channel inventory fill, and you see that nearly tripling, which is I think a good sign.

And certainly what I would point to is our market share growth. Seeing approximately 20% share in the second line, 35% share in the third line we view as a very encouraging sign. And what we really look at there is there's a lot of opportunities as we go forward. We think we have opportunity to compete and gain market share relative to the other oral TKIs, which have about 40% -- or excuse me, 45% share in the second and third lines, and also immunotherapy in the second line setting where there is an incremental 38% share we can go after. And we feel that continuing to differentiate CABOMETYX with the trifecta of efficacy that we have, we can continue to make progress in the marketplace.

Great, thanks for that. Maybe just one last one, Mike. I think I heard you speak more on this call about in-licensing and building your pipeline maybe through external asset acquisitions. Obviously, there's a lot of competition in oncology these days. What makes you think that you are maybe better positioned as a buyer versus a seller?

Yes, I think it's all around our ability to navigate the assets that are available from a variety of sources. We have to be I think very in tune with both our capabilities, our pipeline, our record of success in doing discovery in the past, which was significant, about 20 INDs over about an eight-year period. So, I think that insight and that record of just knowledge allows us to operate in a way where we think we can uncover assets and compounds that may be asymmetrically valued as we go forward.

So, again, we're going to take our time and do this right. We are not going to rush into doing anything that doesn't make sense. And as we make progress there going forward, we will be sure to update you and other investors as we go.

Thanks. Congrats on the quarter.

Stephen Willey, Stifel.

Thanks for taking my questions and congrats on the quarter as well. I guess -- so can you maybe just speak to the timing of the VA, the DoD and the TRICARE access coming online, and I guess just what fraction of the 224 million lives on the coverage that represents?

Yes, happy to talk. This is PJ. So that recently came online I think in the last five or six weeks, but we did, I would just say, importantly, we had seen purchases from the VA before that. So the important thing though is we think we have significant opportunity there and upside with that in place, certainly as it provides more access for our team to continue to get into those accounts and work with those healthcare professionals. It represents, I believe, about 6% to 8%, give or take, of the lives, but I'd have to really double-check that.

But what I look at across the board is really the feedback has been favorable and the share is growing.

When I think about kind of overall payor situations of the broader picture, certainly very pleased with the 224 million covered lives at this point, and the fact that we haven't had any significant barriers, so we really are having the opportunity to get CABOMETYX to the patients who can benefit from it.

Okay. That's helpful. And then, Gisela, I know you talked about there being several variables that are driving the timing of the sNDA submission for CABOSUN, and I think we are kind of all aware of the independent radiology review that needs to occur. But can you maybe just speak to some of the other variables that require some box-checking before this process can be undertaken?

Absolutely. I think, clearly, we need to transfer (technical difficulty) transfer of the database from the Alliance into Exelixis, and subsequent to that, we can begin to prepare data sets in accordance with what is expected for regulatory filings, and also factoring, as you mentioned, the independent radiology review, which requires collection of all the images from the sites and central read. So there are a number of things to accomplish, and we are certainly working hard on it. It's a top priority for us and we will certainly update as we move along and are clearer on the timing.

So I guess would you say that the centralized reads are kind of the rate-limiting step at this point?

There are number of activities that are somewhat time consuming. The centralized read is one of them and the collection of the scans is another so that, in aggregate, will continue to be our highest priority.

Okay. And the 3150 data looks pretty interesting, I guess. I'm not necessarily sure there's been much of a public disclosure with respect to the economics of the Daiichi Sankyo collaboration, I think because there's some mention maybe of double-digit royalties. But can you maybe provide some commentary around what the milestone flow might look like beyond just the initiation of the Phase 3? Thanks.

This is Peter. I'm happy to speak to that. So, clearly, we are very excited to see another one of our partnered programs moving into late stage development, and we are extremely happy with the support that the program has been getting from our partner, Daiichi Sankyo.

With respect to the actual agreement, under the terms of the agreement, Daiichi Sankyo was solely responsible for all development, any future or potential commercialization, and Exelixis is eligible for a series of regulatory and commercial milestones. And you're correct, we are also eligible for low double-digit royalties on any sales in the future.

Okay, but there hasn't been any quantification of remaining milestones.

No, there's been no public disclosure of that.

Okay. Thanks for taking my questions.

Michael Schmidt, Leerink Partners.

Good afternoon. Thanks for taking my questions. I had one, a commercial question, just looking at sort of as you monitor the initial launch. What are you seeing in terms of duration of therapy in clinical practice for CABOMETYX?

Thanks for the question. This is PJ. Generally, what I would say with regards to duration of therapy, really far too early to be able to glean any information as we are still very early in the launch.

With regards to the trial, what we saw in the METEOR trial ultimately was a median duration of therapy of 8.3 months. So, again, still too early to say what we saw in the commercial setting.

Previously, what we had talked about with regards to COMETRIQ is we saw, for the RCC patients on COMETRIQ, a duration of therapy that was approaching that in the seven-month range. But you know what I would say is we are really happy with what we are seeing and the feedback we are hearing so far in the launch and really pleased that we've had significant prescriber adoption, adding about 150% more prescribers in Q3 relative to Q2, and broadening that community oncology prescriber base, which is really, I think, encouraging for us as we move forward.

Okay, thanks. And Giesla, a question on the HCC CELESTIAL trial. How is enrollment going there? And have you opened additional sites? I noted that you're still guiding to data in 2017 more broadly, but are there plans to accelerate enrollment in the study for example?

Enrollment in the study is ongoing globally, and we haven't provided any specific numbers, but we are confident in having results in the 2017 time frame. We haven't specified that as yet. We will potentially do so when we get closer.

Okay. Thanks for taking my questions and congrats on a good quarter.

Ted Tenthoff, Piper Jaffray.

Thanks. I had two quick questions and then actually a little bit of housekeeping, if I may. So, the first is on the milestones. How and when will you recognize the $60 million and $10 million milestones from Ipsen? And are these included in that guidance that you mentioned of $85 million in milestones due to that and the $15 million for Daiichi? Maybe you can give us a little bit of color on that.

It's Chris. So, the $60 million milestone from Ipsen was recognized in the third quarter, and will be paid to us in the fourth quarter, so that $60 million is in the $85 million. That $60 million will get amortized over the life of the remaining patent, which is out to 2030.

The $15 million milestone for Daiichi was recognized as revenue in the third quarter. And as Peter mentioned, we already received that $15 million in the fourth quarter.

And then the two $10 million milestones will be recognized as revenue when earned, and so the one, as Mike mentioned earlier, the Germany one, the $10 million will be recognized as revenue in the fourth quarter. And also our expectation is to receive that cash in the fourth quarter. So the $60 million, the $15 million, and the $10 million make up $85 million. Now, there is still another $10 million milestone out there for one of the other EU Big 5 countries launch, and we will provide update on that when that is -- when we (technical difficulty)

Awesome, very helpful. And then a quick question with respect to the number of shares outstanding, if I may. On the 10-Q, on the front, as of October 26, you had 286.456 million shares. However, was there -- how many additional shares were issued from the remaining debt conversion post-October 26?

It's not a big number. We didn't have -- we had less than -- we had about $1 million, $1.5 million or so of debt outstanding. So, I don't know the exact number of the top of my head but it's not a big number.

That's helpful. Excellent. Congrats guys on the progress with the commercial side of things and also on the clinical and regulatory side. I'm looking forward to further updates. Thank you.

(Operator Instructions). John Sonnier, William Blair.

Thanks for taking the question and congrats on a great quarter and all the progress. I guess a longer-term development question for Giesla. There was a lot of interest from your KOLs at ESMO in the idea of doing a frontline RCC study in combination with nivo. How do you think about that? Is that something you might consider if successfully approved in that setting?

Sure. So, we are certainly very encouraged by the results of the early phase study that I outlined earlier on in the call. It's being conducted by Andrea Apolo at the NCI where we've seen good tolerability of the combination of cabozantinib and nivolumab and also an encouraging 43% response rate in patients with heavily pretreated genitourinary malignancies. So, that is certainly important data.

We are discussing further trials and a late stage trial certainly with our key opinion leaders as well as internally, and we will definitely update you as we get a little closer.

Maybe just a broader question, it might be for Mike as I know, when you're looking for an ex-US partner, one of the criteria you wanted was a partner that had an interest in developing the compound as broadly as possible. With the launch underway and RCC going successfully in a lot of new data, where do you see I guess the next development frontiers for cabo?

You know, we have a lot of opportunities in terms of how we move forward with cabozantinib. And I think we've talked generally over the last few months about doing a very careful analysis in the context of making sure that we are making the right investments as we go forward to be able to really maximize the potential of the asset, build a franchise as best we can while certainly watching how we spend money. So, that analysis is ongoing and has been ongoing for a while.

Certainly, as Giesla mentioned, GU indications look very promising, bladder, renal, etc. Very interested in doing other work, especially where we have data today, if you look at lung as an example, other indications that we think have some traction as well. So, again, it's a wide open playing field for us. We think we've got good data, good momentum. Obviously, the initial data that was at ESMO in terms of the combined ability and the activity with nivo, the first PD-1 that we've looked at was very encouraging in terms of both the tolerability, the safety and the initial signs of activity, especially in bladder. So we are encouraged by that and looking forward to do more. Wouldn't want to speculate on what we will do first, second and third as we go forward, but rest assured that, as we generate that plan and as we get things moving, we will be able to update you guys in a very straightforward fashion.

No, that's fair enough. And just a quick one either I guess for Chris or PJ. With the VA and DoD coming online, does that change materially your gross to net? Should we think about that in terms different than I think you've kind of pointed towards 10% or so?

It's Chris. No, I think we are still guiding in that range. I think 10% is around where we think it's going to get to. As you can see, in the quarter, we were closer to 9% this quarter and a little -- like 9.7% last quarter. So we are in that range. I don't think DoD, with the volume and the discount there, will change it dramatically.

Perfect. Thanks a lot.

One last thing. You sound kind of hoarse there. Were you up late last night in Wrigleyville celebrating?

That is a distinct possibility, here at the home of the world champion Chicago Cubs.

There you go. That's awesome.

Thanks a lot.

Andrew Peters, Deutsche Bank.

Thanks for taking the question and congrats on the quarter, and also thanks for kind of all the detail on utilization. Maybe a question for PJ then on that point. So, you talked about kind of gaining share from the TKIs, both in the second and third line setting, but presumably the I/O agents are doing the same. Do you have any kind of feeling for who is gaining share faster? And as you think about maybe taking some of the share that you described from nivo, what do you think is really going to drive that switch in terms of the decision-making process for the physicians?

Thanks for the question Andrew. I think, first, we're just very happy. We feel we are taking share from all the agents and certainly all the classes of therapy in both lines as this brand impact IMS data has shown over time. So very pleased with the strength of our launch.

Looking at that as well, we're actually seeing, particularly in the second line setting, really second and third line, nivolumab declining. So it really gives us confidence that our approach, our messages of differentiation and efficacy, are really resonating and give us the opportunity to continue to take share from really the orals, the TKIs, as well as immunotherapy. We have a lot of opportunities coming up this weekend. Actually, we are the Kidney Cancer Association in Miami with a lot of the top experts. We've just rolled out our branded campaign this month really focusing on the trifecta of efficacy. So, we really feel good about moving forward our ability to strive and continue to take share from all of the competitors.

Okay, great. And then just I guess a related question to what Eric asked earlier on kind of the relationship between some of the IMS data. Did you see any kind of seasonality in terms of uptake or use over the summer? And was there any kind of change as we got into the fall and people were coming back from vacations? Was there any kind of seasonal effect in the 3Q number, or was it pretty consistent?

With regards to that, I know, in former brands, I've worked on people, I sort of discussed that and asked that. But we are in a launch and I think everything we are seeing Q2 to Q3, obviously the end of Q3 being in the fall is really seeing demand headed in the right direction with regards to any metric we look at, whether it's end demand, revenue, or sort of prescriber adoption and utilization. So, we really didn't see any of that.

Okay, great. Thanks again and congrats on the quarter.

I'm showing no further questions at this time. I'd like to hand the conference back over to Miss Hubbard for closing remarks.

Thank you, Sayed, and thank you all for joining us today. We welcome your follow-up calls with any additional questions you may have that we were unable to address on today's call.

Ladies and gentlemen, thank you for participating in today's event. This concludes our program. You may all disconnect and have a wonderful day.