Exelixis Inc (EXEL) 2016 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Exelixis fourth-quarter and full-year 2016 financial results conference call. My name is Takeeya and I will be your operator for today. As a reminder, this conference call is being recorded for replay purposes. I would now turn the call over to your host for today, Ms. Susan Hubbard, Investor Relations. Please proceed.

Thank you, Takeeya, and thank you all for joining us for the Exelixis fourth-quarter and full-year 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 Senior 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 December 31, 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 events or results could, of course, differ materially.

We refer you to the documents we file from time to time with the Securities and Exchange Commission 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 referenced times, our dependence on collaboration partners and our ability to maintain our rights under existing collaborations and the level of cost associated with commercialization, research, development and other activities. With that, I'll turn the call over to Mike.

All right. Thank you, Susan, and thanks to everyone for joining us this afternoon. We have a lot to cover on today's call so I'll start with a brief summary of the key events for the fourth quarter and early 2017 and then turn the call over to Chris, PJ, Gisela, and Peter, who will review and provide extensive updates for our Q4 financials, the ongoing CABOMETYX launch and development activities for both cabozantinib and cobimetinib.

Key highlights include first, the strong fourth-quarter commercial performance of CABOMETYX, in advanced RCC, resulting $51.9 million of cabozantinib franchise product revenue. Second, our continued success in monetizing cabozantinib ex-US by achieving $30 million in upfront and milestone payments from Ipsen in the fourth quarter and also receiving an additional $50 million from the Takeda upfront payments in 2017. Third, the expanded development activities for both cabozantinib and cobimetinib including the agreements announced today with BMS and Roche to broadly explore the potential of cabozantinib in combination with immunotherapies.

In addition, three new cobimetinib phase 3 trials were initiated or announced by Genentech in the last nine months, highlighting this important progress. As we look forward, we expect to have an extremely busy 2017 and anticipate filing an sNDA for cabozantinib in first-line RCC as well as data from the CELESTIAL pivotal trial of cabozantinib in second-line HCC.

As you will hear from Chris, we ended 2016 in a sound financial position and we began 2017 with a healthy cash balance and greatly reduced debt. Our success in monetizing cabozantinib ex-US added $340 million in non-diluted cash to our balance sheet over the last year. Coupled with robust CABOMETYX US revenues, we plan to further optimize our balance sheet while supporting the expanded developments of the cabozantinib franchise through I/O combinations and exploring the appropriate strategic investments to expand our pipeline beyond cabozantinib through a measured restart of our in-house discovery efforts and targeted in-licensing activities.

In closing, Exelixis had a strong fourth quarter across all components of our business and is on track for a productive 2017. With that, I will turn the call over to Chris, who will provide more details on our fourth-quarter and full-year 2016 financials.

Thanks, Mike. Total revenues for the quarter ended December 31, 2016, were $77.6 million, compared to $9.9 million for the comparable period in 2015. Total revenues for the year ended December 31, 2016, were $191.5 million, compared to $37.2 million for the comparable period in 2015. Total revenues for the quarter ended December 31, 2016, include $51.9 million of net product revenues, compared to $9.9 million for the comparable period in 2015.

Net product revenues for the year ended December 31, 2016, were $135.4 million, compared to $34.2 million for the comparable period in 2015. The increase in net product revenues for both the quarter and year ended December 31, 2016, as compared to the same period in 2015, primarily reflects the impact of the commercial launch of CABOMETYX in late April 2016.

Total revenues for the quarter ended December 31, 2016, also includes two $10 million milestones achieved for the first commercial sales of CABOMETYX by Ipsen in Germany and the United Kingdom. Total revenues for the year ended December 31, 2016, also include the recognition of $20 million in revenue for milestones from two of our collaboration partners, Daiichi-Sankyo and Merck. Total revenues for the quarter and year ended December 31, 2016, also include $1 million and $2.8 million, respectively, of royalty revenues from Ipsen and Roche and $4.7 million and $13.3 million, respectively, of licensed revenues related amortization of the upfront and approval milestones from Ipsen. In comparison, during the year ended December 31, 2015, we recognized $3 million of contract revenues for a milestone payment received from Merck.

Research and development expenses for the quarter ended December 31, 2016, were $23.8 million, compared to $23.5 million for the comparable period in 2015. Research and development expenses for the year ended December 31, 2016, were $96 million, compared to $96.4 million for the comparable period in 2015.

For both the quarter and year ended December 31, 2016, as compared to the same period in 2015, decreases in share-based compensation and the allocation of general corporate costs were offset by increases in personnel-related expenses resulting from the increase in headcount, predominantly associated with the build out of the Exelixis Medical Affairs organization. For the year ended December 31, 2016, as compared to the same period in 2015, there were also decreases in clinical trial costs from METEOR, our phase 3 trial in RCC.

Selling, general and administrative expenses for the quarter ended December 31, 2016, were $13 million compared to $17.1 million for the comparable period in 2015. Selling, general and administrative expenses for the year ended December 31, 2016, were $116.1 million, compared to $57.3 million for the comparable period in 2015. For both the quarter and year ended December 31, 2016, as compared to the same periods in 2015, there were increases in personnel-related expenses resulting from the increase in headcount connected with the build out of our US commercial organization and outside services to support the launch and commercialization of CABOMETYX.

These increases were offset by a decrease in marketing costs related to losses on our collaboration with Genentech. As we announced in January of this year, Genentech unilaterally changed both retroactively and prospectively the manner in which it allocates promotional expenses of the Cotellic plus Zelboraf combination therapy. As a result, Exelixis is relieved of $18.7 million of disputed cost previously recorded by Exelixis and Exelixis has invoiced Genentech for expenses with interest that Exelixis had previously paid.

Accordingly, during the quarter ended December 31, 2016, we offset selling, general administrative expenses for a $23.1 million recovery of net losses which had been recorded from 2013 through September 30, 2016, including $13.3 million of losses that had been recognized and recorded prior to 2016. During the quarter and year ended December 31, 2016, we also recognized a net gain of $600,000 and a net loss of $4.5 million, respectively, for current US activities in those periods under the collaboration agreement as computed under Genentech's revised cost allocation approach.

Other income and expense net for the quarter ended December 31, 2016, was a net expense of $3.8 million, compared to $9.9 million for the comparable period in 2015. Other income and expense net for the year ended December 31, 2016, was a net expense of $42.1 million, compared to $40.3 million for the comparable period in 2015.

The decrease in other income and expense net for the quarter ended December 31, 2016, as compared to 2015 was primarily due to the reduction in interest expense as a result of the conversion and redemption of $287.5 million in aggregate principle amount of our 2019 notes. For the year ended December 31, 2016, the reduction in interest expense was offset by $13.9 million of loss associated with the conversion our 2019 notes for approximately 54 million shares of our common stock.

Net income for the quarter ended December 31, 2016, was $35.1 million, or $0.12 per share, compared to a net loss of $41.6 million, or $0.18 per share, for the comparable period in 2015. Net loss for the year ended December 31, 2016 was $70.2 million, or $0.28 per share, compared to net loss of $161.7 million, or $0.77 per share, for comparable period in 2015.

The decrease in net loss for the quarter and year ended December 31, 2016, was primarily due to increases in net product revenues, decreases of collaboration revenues, the recovery of net losses previously recorded under our collaboration agreement with Genentech and a decrease in interest expense, partially offset by increases in personnel expenses associated with the increase in headcount connected to the build out for our US commercial and medical affairs organizations and other costs associated with the launch of CABOMETYX. For the year ended December 31, 2016, the decrease in net loss was also partially offset by a loss associated with the conversion of the 2019 notes.

Cash and cash equivalents, short- and long-term investments and long-term restricted cash and investments totaled $479.6 million at December 31, 2016, as compared to $253.3 million at December 31, 2015. The December 2016 cash balance does not include the $50 million upfront payment received from Takeda in February 2017.

As you will see in the 10-K we filed earlier today, we have classified the Deerfield notes as a current liability because we have the ability and the intent of retiring the Deerfield notes in the July 2017 time frame, which is approximately one year prior to their maturity date. This will save the Company approximately $12 million net of the termination fee over the remaining life of the notes. As we look to the future, with the maturing of the Silicon Valley Bank term loan in May 2017 and the early retirement of the Deerfield notes, we will be substantially de-lever our balance sheet in 2017, which positions the Company with significant amount of cash to support our growing business and virtually no leverage.

Now turning to our 2017 financial guidance, the Company is providing guidance that total costs and operating expense for the full year will be between $290 million and $310 million. This guidance includes approximately $25 million of non-cash costs and expenses related primarily to stock-based compensation expense and includes our portion of funding to initiate additional mid- and late-stage cabozantinib I/O combination trials that we announced earlier today. We will not be providing revenue guidance at this time, as CABOMETYX is still relatively early in its launch phase, having just completed its second full quarter since approval.

In closing, 2016 was a year in which we significantly enhanced our financial position. We added over $200 million in cash to our balance sheet. We converted approximately $287 million of debt to equity, we significantly de-levered the balance sheet and the same time maintain our goal of aggressively managing our expenses while successfully launching CABOMETYX in the US. With that, I will turn over the call to PJ.

Thank you, Chris. We are very pleased with the progress of CABOMETYX launch and the Q4 cabozantinib franchise net revenue of $51.9 million. Q4 CABOMETYX net revenue of $44.7 million compares favorably with the Q3 net revenue of $31.2 million, representing growth of approximately 45%.

The success of the launch underlying this revenue growth is being driven by two key factors. First, demand trends are robust in terms of both volume of units shipped and new patient starts. Second, the breadth of the demand, as measured by growth in prescribers and ordering outlets such as hospitals and oncology clinics is encouraging. Demand for CABOMETYX increased by approximately 40% in Q4 relative to Q3 in terms of units shipped. During the same time period, we saw an increase of new patient starts of approximately 20%.

We are also pleased with the trends that demonstrated the breadth of this demand increased in Q4 relative to Q3. In Q4, the prescriber base of CABOMETYX increased by approximately 60% through the specialty pharmacy channel. Additionally, we are very encouraged by 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 50% in Q4. This growth is coming from dispensing community oncology practices, hospitals, and academic institutions, as well as government facilities. We are particularly pleased with the growth in community oncology -- excuse me, community oncology dispensing clinics, as we have deployed tactics and resources to drive growth in 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 relatively small number of high-volume prescribers and beyond that, there are a large number of low-volume RCC prescribers.

Early in launch, we focused more of our promotional efforts on thought leaders and clinicians who treated a high-volume of RCC and we saw rapid adoption among this cohort. After the first few months of launch, we shifted our efforts to broadening the prescriber base and promoting CABOMETYX to the community oncology segments. In Q4, we saw increasing adoption which was driven by community oncologists, indicating that our promotional efforts are broadening the prescriber base, which continues to be a strategic focus for the team.

More than 70% of our growth in Q4 was from community oncologists. This trend is encouraging and confirms feedback from market research that CABOMETYX is being well received not only by KOLs but also by the community as we continue to promote to this larger segment with a variety of sales and marketing tactics. The rapid new prescriber adoption and the increased demand that we are seeing confirms our conviction that CABOMETYX addresses a significant unmet medical need in advanced RCC.

Furthermore, we know from both market research and direct customer feedback that oncologists familiar with the METEOR data will prescribe the drug. This is encouraging as there are still a large number of oncologists who have yet to prescribe CABOMETYX, underscoring opportunity for future growth.

The increase in demand from Q3 to Q4 is also reflected in the 23% increase in our second-line plus new patient market share, which increased from 22% to 27%. It is also consistent with our internal quarterly tracking studies that monitor the market share of new patient starts. This market research indicated increase in CABOMETYX new patient market share in both the second- and third-line settings.

In the second-line, CABOMETYX took share from nivolumab as well as other oral agents. In the third line, share gains were primarily at the expense of oral agents. This is 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.

As you know, there are six large pharmaceutical companies promoting and co-promoting 11 therapies in the RCC market. The inroads that CABOMETYX is making in this competitive and dynamic space can be seen in recent earnings reports that have detailed the decline of products such as everolimus and sorafenib, partially attributed to competitive pressure in renal cell carcinoma. In Q4, CABOMETYX NRX grew by 26% relative to Q3, while at the same time axitinib NRX were down 10%. US net revenue for axitinib, which is only indicated for RCC, was down 38% in Q4 of 2016 relative to the same time period in 2015.

Also, lenvatinib US revenue in Q4 had no growth over Q3, despite receiving approval in advanced RCC in May last year. This was attributed to significant competition in the RCC market place. 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 hope to accomplish this by highlighting the points that differentiate CABOMETYX from the competition.

Although it is still early in the launch to quantify duration of therapy, we closely monitor our refill and persistence rates. We are pleased with the data that we have analyzed so far. Additionally, there may be the potential for improvement in persistence over time as we see more CABOMETYX used in the second-line setting relative to later lines of therapy.

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 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. That said, we fully recognize that there is significant opportunity to increase demand of CABOMETYX by differentiating from the competition to increase our market share, particularly in the second-line 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. Additionally, our team is preparing for potential future launches for CABOMETYX in the scenario where we get a label for either first-line RCC or second-line HCC.

We have always taken the approach that we will scale of the organization commensurate to the commercial opportunity that we are pursuing. Were we to get additional indications, the investment and infrastructure required to optimize these opportunities would only be incremental relative to the resources we have in place as we leverage the capabilities of our existing team. With that, I will turn the call over to Gisela.

Thank you, PJ. I will provide an overview of the development and regulatory progress in the quarter and cover progress towards a regulatory filing for first-line RCC on the basis of cabozantinib, the status of CELESTIAL and important new development for combining cabozantinib with immune checkpoint inhibitors that have been announced earlier today.

Let me 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 NCI-CTEP.

The trial met its primary endpoint of significantly improving progression-free survival as assessed by investigator 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 the trend in survival, a secondary endpoint in the study. With this positive outcome of the study, we are intentionally focused on all activities supporting a planned supplemental NDA filing for cabozantinib in first-line RCC as our highest priority.

As a reminder, given that this was an externally sponsored study, much of the work we would typically have underway in advance of receiving the final endpoint analysis was only started upon our receipt of all of the relevant data, so we are working on such aspects that are needed to support a filing, including source data verification and preparation of the data sets we have now received from the Alliance, consistent with expectations for the regulatory filing. This requires extensive programming work before we can perform the analyses with these prepared data sets. I want to remind everyone that this is work that we would normally do at study startup and while the study's accruing patients before any study we intend to file on, if successful.

An additional important effort is the collection of all imaging scans from Alliance sites after we have secured individual IRB approvals and all legal and contractual aspects were in place with the Alliance cooperative group and individual sites. We are making good progress here, with the majority of sites now having obtained IRB approval enabling such a scan collection and transmitting the images to the independent radiology facility for the central independent radiology read. With all of these activities and different workstreams underway, we're working toward an sNDA filing in the third quarter of 2017. We will provide additional updates on progress toward this important goal as appropriate.

Now into brief update on CELESTIAL, our phase 3 study in second-line HCC. The randomized placebo-controlled study is designed to enroll patients who have previously received sorafenib with a total of two prior systemic therapies allowed per protocol. The primary endpoint of the trial is overall survival. The trial continues to enroll patients globally. The next interim IDMC review will take place when 75% of the events have occurred and we remain on track to have data in 2017.

Lastly, I would like to turn now to the third important topic in today's development update, the broader development and lifecycle management plan for cabozantinib. As recently announced, we are very excited to start 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 showed 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 pre-clinical and preliminary clinical evaluation, cabozantinib treatment has been shown to affect tumor cells and the tumor microenvironment in a manner that would potentially make them more sensitive to immune mediated attack. In vitro and in vivo employing a murine colon carcinoma cell line demonstrated that cabozantinib treatment altered immune modulation and immune subset conditioning.

Specifically, treatment of tumor cells with cabozantinib in vitro lead into increased tumor cell expression of major histocompatibility complex class I, or MHC class I, antigen and greater sensitivity of tumor cells to T-cell mediated killing. In a mouse tumor model, cabozantinib treatment led to increased peripheral CD8 positive T-cell count, decreased regulatory T-cells and myeloid-derived suppressor cells and decreased Treg suppressor activity. Further, substantial increases in CDH positive T-cell infiltration into the tumor were observed.

In the clinical setting, reductions in immunosuppressive Treg lymphocytes following treatments with cabozantinib were observed in the phase 2 study of subjects with advanced refractory urothelial cancer. In a phase 2 study in metastatic triple-negative breast cancer, cabozantinib-treated subjects experienced a persistent increase in the fraction of circulating CD3 positive T lymphocytes and a persistent decrease in the CD14 positive monocytes, possibly reflecting activation of systemic anti-tumor immunity.

In addition to regulating cells of the adaptive immune system, cabozantinib may impact innate immune cells as well. The TAM kinases AXL, MER, and TYRO3 are potently inhibited by cabozantinib and are believed to play a role in maintaining tumor-associated macrophages in an immunosuppressive state. We are exploring the possibility that cabozantinib might promote a switch in microphage phenotype to a more immune permissive state that could promote anti-tumor immune response.

Further, a phase 1B trial combining cabozantinib with nivolumab or nivolumab and ipilimumab has shown encouraging results in patients with advanced genitourinary cancers. Results for the cabozantinib and nivolumab combination were presented by Andrea Apolo at ESMO 2016. The objective response rate was 43% among 23 evaluable patients with various genitourinary cancers and four of six patients with urothelial cancer, 67% achieved a response.

The safety and tolerability profile of the combination was acceptable in a dose of 40 milligrams cabozantinib daily and three milligrams per kilogram every two weeks of nivolumab was identified as the recommended dose for ongoing indication-specific expansion cohorts in RCC and bladder cancer. Updated results for this part of the study, along with results from the triple combination of cabozantinib, nivolumab and ipilimumab were presented at the recent ASCO GU conference in Orlando and continue to show anti-tumor activity in heavily pre-treated patients for the duplet of nivolumab and cabozantinib and now also for the triplet of nivolumab, ipilimumab and cabozantinib in patients with various advanced genitourinary malignancies, with encouraging response rates of 38% and 18%, respectively. Both the doublet and the triplet combinations were generally well tolerated and the recommended dose for the triplet combination is 40 milligrams of cabozantinib daily combined with three milligrams per kilogram nivolumab and one milligram per kilogram of ipilimumab.

With this background information and rationale, we're very pleased to enter into clinical collaboration with BMS combining cabozantinib with nivolumab alone or both nivolumab and ipilimumab in a phase 3 study in first-line RCC, with plans to also study the combination in other indications, including in additional trials and bladder cancer in HCC. BMS and Exelixis will be sharing cost for these trials.

Furthermore, we have also entered into a collaboration with Genentech/Roche to evaluate the combination of cabozantinib and atezolizumab in an initial dose ranging study with planned cohort expansion in four 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 for this evaluation.

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 and we'll have access to the results to support potential future regulatory submissions in their territory. Ipsen will have the opportunity to participate in future combination trials in accordance with the collaboration agreement. Takeda will also have the opportunity to participate in these global trials per the collaboration agreement between Exelixis and Takeda. We look forward to these trials that will be executed by ourselves or our clinical partner in the near term, starting in the first half of 2017 and 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. As always, we will keep you updated on the progress of all these programs at the appropriate time. With that, I will hand the call over to Peter to provide an update on cobimetinib.

Thanks, Gisela. I will turn to cobimetinib, or cobi for short, the Exelixis-discovered MEK inhibitor that's being developed by our partner Genentech. 2016 was a very active and exciting year in terms of the evolution of cobi development and resulted in three new phase 3 trials being initiative or announced, all based on encouraging signals from earlier phase trials. All of these studies incorporate a combination of cobi with an immunotherapy, namely Genentech's PDL1 antibody, atezolizumab, so I start with an overview of the preclinical rationale that supports this approach.

Inhibition of MEK has positive effects with respect to the immune microenvironment on both tumor cells and immune cells, notably T-cells. On tumor cells, MEK inhibition leads to an increased expression of class 1 MHC on the cell surface, rendering the cells more visible to immune system. Increased MHC class 1 expression facilitates presentation of tumor-specific antigens to immune cells and increases the vulnerability of tumors to immune-mediated killing. This effect has been documented in a tumor from a patient taking cobi with the pre-treatment biopsy sample showing low levels of MHC class 1 but the post-treatment biopsy showing significantly elevated levels.

Second, MEK inhibition increases the number of affected T-cells in tumors by protecting them from death as a result of chronic stimulation. Repeat tumor biopsies from patients enrolled in cobi clinical trials have also shown an increase in CD8 positive T-cells following cobi treatment. Consistent with this, in a preclinical tumor model, the combination of a MEK inhibitor and a PD1 antibody was more effective than either agent alone.

These data supported the initiation of a phase 1B trial combining cobi and atezolizumab that enrolled patients into one of four expansion cohorts following the establishment of an appropriate combination dose. Each cohort was initially intended to enroll 20 patients and comprised colorectal carcinoma, metastatic melanoma and non-small cell lung carcinoma cohorts, as well as an advanced solid tumor cohort primarily intended to allow the collection of biopsies. Data from two of these cohorts were reported at major medical meetings last year and resulted in the advancement of additional phases 3 trials.

Data from the metastatic CRC cohort, which enrolled predominantly KRAS mutant patients who had failed at least two prior lines of chemotherapy, was presented at ASCO and updated at ESMO. 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. The microsatellite stable, or MSS, phenotype accounts for 95% of CRC, with the microsatellite instability high, or MSIH, phenotype, which is highly responsive to immunotherapy, comprising the remaining 5%.

No unanticipated safety signal has emerged from the trial. These results provided the rationale for initiating the currently ongoing phase 3 trial that compared cobi combined with atezolizumab to atezolizumab alone or regorafenib alone in the third-line setting of CRC. The trial will enroll 360 patients and the primary endpoint is overall survival.

For reference, median overall survival for patients taking regorafenib is 6.4 months and the objective response rate is 1%. The trial initiated in the second quarter of last year and involves over 100 sites worldwide. Of note, a recent update to the trail listing on clinicaltrials.gov shows that the status of the majority of the sites is now active but no longer recruiting, suggesting that enrollment of those sites is complete.

In the context of metastatic CRC, I also want to highlight another ongoing trial, which initiated in the third quarter of last year. This is a phase 1B trial testing the combination of cobi with atezolizumab and bevacizumab in patients who have received at least one prior line of chemotherapy and whose tumors are microsatellite stable. The study has a safety running cohort to be followed by an expansion cohort and a biopsy cohort and will enroll up to 33 patients.

Results from the metastatic melanoma cohort of the phase 1B study of cobi in combination with atezolizumab were presented at the Society for Melanoma Research meeting in November last year. This cohort enrolled both BRAF mutant and BRAF wild-type patients. Notably, in the BRAF wild-type patient, there was a 50% overall response rate and a preliminary progression-free survival estimate of 15.7 months. Duration of response was encouraging, with the median duration not yet reached after 18.9 months of follow-up.

No unanticipated safety signals emerged. As a result, Genentech has announced plans to initiate a phase 3 trial comparing the combination of cobi and atezolizumab with pembrolizumab in previously untreated patients with metastatic or unresectable locally advanced BRAF wild-type melanoma. The study will enroll 500 patients and has co-primary endpoints of PFS and OS. The first patient is anticipated to enroll in the second quarter of this year.

Also presented last year at ESMO were the results from a separate phase 1B trial studying the combination of cobi with vemurafenib and atezolizumab in patients with BRAF mutant metastatic melanoma. In the 29 response evaluable patients, there was an objective response rate of 83%, including 10% complete responses. 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 cobi, vemurafenib and atezolizumab compared to cobi, vemurafenib and placebo in previously untreated patients with metastatic or unresectable locally advanced BRAF mutant melanoma was initiated in January and is planned to enroll 500 patients with the primary endpoint of PFS.

Finally, data were presented from the phase 1B dose ranging stage of the COLET study in triple-negative breast cancer patients combining cobi with paclitaxel. 8 of 16 patients, or 50%, achieved a tumor response to paclitaxel and cobi and the combination was tolerable, with new safety signals emerging. The randomized phase 2 stage of the trial, comparing paclitaxel to cobi, paclitaxel to cobi plus paclitaxel, is now fully enrolled and two new cohorts have been added to the study, testing the combination of cobi with paclitaxel and atezolizumab or cobi with nab-paclitaxel and atezolizumab.

As is evident from the activity in the last nine months, the evolving development path for cobi is focused on exploring its potential to be a broadly applicable combination partner for atezolizumab. This includes testing the ability of cobi to improve clinical outcomes in tumor types that are somewhat sensitive to atezolizumab, such as melanoma, as well as those that have historically been refractory to single-agent immunotherapies, such as microsatellite stable CRC. In principle, this approach could be applied to many additional tumor types and we look forward to updating you with respect to future cobi development as it evolves.

We also note that a trial sponsored by BMS was initiated late last year testing the combination of cobi with nivolumab and ipilimumab in a colorectal carcinoma patient population, demonstrating that interest in this approach is not restricted to Genentech. I'll now turn the call back to Mike.

All right. Thank you, Peter. In closing, 2016 was an important year for Exelixis and proved to be an inflection point for the entire organization. As pleased as we are with our progress, we remain steadfast and focused on the critical opportunities that are ahead of us.

On a personal note, I am most proud of the amazing team we have here at Exelixis. Both individually and collectively, we work hard every minute of every day to help patients with cancer. This is a tough business where success is never taken for granted. We continue to strive to push both our science and our business forward with a great deal of urgency as we tackle the challenges that we face going forward.

The achievements and financial results from 2016 highlight the significant progress we have made towards driving the business to positive cash flow. We look forward to the opportunity to reinvest in cabozantinib's 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 forward in 2017 and beyond.

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)

Eric Schmidt, Cowen and Company.

Thanks for taking my questions and congrats on the progress. Maybe for Gisela or Mike, it sounds like you have got a little bit greater confidence in the filing for CABOSUN in the front-line RCC indication, yet it was not clear, to me at least, what's driving that confidence. I do not think you have done much to complete your independent reviews. Is that correct or could you clarify?

Yes. Absolutely. This is Gisela. We are working very hard. It is a high-priority, the highest priority, really, for the entire organization to complete the filing on the timeline that I've specified, which is foreseen in the third quarter of 2017.

We are working as one of the work streams on collecting the images from the Alliance sites to enable an independent radiology read. That has not been completed but we have made good progress towards collecting the images and continue to work along those lines. There are also other works streams that are ongoing. I mentioned source data verification programming efforts and preparing the datasets for a regulatory filing. We are certainly pleased with the results that we have seen from the study as they were presented at ESMO and also published in the JCO and so we're really focused now on pulling everything together for the sNDA filing in the third quarter.

Okay and --

Eric, it's Mike. Let me add a little bit more color here. Again, our confidence in the filing has not changed at all since the Q3 call. Again, at ESMO in 2016, we gave at our investor briefing very clear guidance that we intended to file an sNDA and that is still the case. Obviously, we've had more time, we have generated the additional data since we've gotten the datasets in-house and the data in-house, so we're talking more today and providing more clarity on our progress and the timelines for submission, but our confidence has been and remains high.

Okay. Thank you. For PJ, on sales trends, clearly you're optimistic for additional share gains, maybe even optimistic for some duration gains. We have seen that you have been able to add about $10 million to $50 million on a quarter-over-quarter basis to aggregate sales of CABOMETYX in the US. Is that a reasonably steady kind of outlook for the drug in 2017 in the absence of any real guidance?

Yes. Thanks for the question, Eric. What I will say is we are very pleased with the quarter that we just had and Q4 and the growth that we had relative to Q3, as we had net revenue growth of approximately 45% over Q3 and the demand growth was approximately 40%.

I guess sort of beyond that, we are really pleased with the breadth of the business metrics that we saw around that, seeing 60% new prescribers through our SP channel, seeing 50% increase in outlets in our special distributor channel and we really do see opportunity for continued growth moving forward as we continue to differentiate CABOMETYX from the competition, particularly in the second-line setting and also with the numerous prescribers who have yet to prescribe CABOMETYX.

Maybe I'll ask the question differently. You really did not mention any challenges or potential concerns with your future outlook for the drug. Should we take it to mean that there is not any restriction on the steady growth that you have projecting?

Eric, this is Chris. The way I would look at it is this. We are very happy with what we have seen so far from a revenue point of view but we're definitely not satisfied. We are going to continue to invest in the product for the future growth but it is still really early in the launch phase.

As I mentioned, we just completed our second full quarter and to a large degree there is still a lot of competition out there. There are 11 products, as PJ mentioned, and three of those products have all launched in the last -- essentially the last 12 months, so we are confident where we are and we're confident where we are going but we're not going to provide you guidance with it at this point in time.

Okay. That's fair, Chris. One quick one for you then and I'll hop off. In terms of the OpEx guidance for 2017, can you give any kind of a breakdown between SG&A and R&D? I assume that guidance includes a healthy level of investment around the nivo collaboration, maybe also the atezolizumab collaboration, as well as the change in COTELLIC accounting going forward?

Yes, it does. I will it out for you little bit here. If you look at where we ended 2015, you've got to remember also that on an as-reported basis, our 2016 expenses were lower because we had the $23 million of Genentech expenses we took back through the P&L.

Now, if you look at it, about half of our increase on an as-reported basis will come from R&D and a lot of that will -- a lot of that increase, or much of that increase, is coming from the investments that we are assuming from cabozantinib I/O combination trials and those will ramp. As we look at the back end of the year, those expenses will start to ramp up. It will be slow in the first part of the year but they will ramp up in the second part of the year. When you look at it SG&A expense, which is the other half, essentially, that will come back to, I would say, earlier 2016 levels in the first quarter and then they will grow as we get into the second, third and fourth quarter.

Great. Thanks and congrats on the progress once again.

Great. Thanks.

Thank you. Stephen Willey, Stifel.

Yes, thanks for taking the questions and congrats on all progress here. Just maybe a question for Mike. Just wondering if you can maybe elaborate a little bit on the strategic decision-making process behind the collaborations that you announced this morning. There was obviously a lot of overlaps/redundancy in the GU malignancies front between Roche and Bristol, so just kind of wondering if there was maybe an exclusive option that was on the table or if this was just kind of a strategy whereby the Company wanted to kind of get its chips spread across the table.

Yes, Steve, thanks for the question. I would frame it as we have talked about publicly in the past. Again, we're looking at, I would say, the broad opportunity to combine cabozantinib across arguably sensitive tumor types to both single-agent cabo and single-agent PD1 PDL1 molecules that has been shown in the past and then also across the different I/O opportunities.

I talked about that previously as a matrix, if you will. Sensitive histologies on the X axis and the different I/O opportunities on the Y axis and our goal ultimately is to fill in as much of that real estate as we can in a P&L-friendly fashion. I think today's announcements with both BMS and Roche really I think are the first step in that regard in terms of working with two of the leaders in the I/O space in tumor types that we think are sensitive and important and certainly have some important under-met medical need that we'd like to be able to address.

On the RCC side, and I think that is the simplest when you look at the phase 3 profile for both cabo and nivo in the second-line space. Those are the only two agents that have improved overall survival in a global pivotal trial, so really begs the question to combine those and ask the question of what that can do and then with the idea of adding even ipi on top of it. Again, we are agnostic in terms of where we are going to go from here. We would like to work, again, across that matrix as much as we can to continue to build value for patients and for our shareholders as we move those trials forward.

Okay. Maybe just a follow-up on the Bristol collaboration. We just saw refractory data with -- in combination with nivo in the refractory bladder setting. Just wondering if you're comfortable enough, I guess, with the activity of the drug at this point to think about initiating a front-line bladder study as part of the Bristol collaboration, specifically a registrational study.

Yes. Fair question. I'll pass it over to Gisela.

Yes, I think the bladder cancer space is certainly evolving, as we speak, with approvals for various agents coming through in bladder cancer and we feel there is certainly remaining unmet medical need, both in the front-line setting in different patient populations as well as is in the later line of therapy and as we are moving forward with formulating our thoughts on the design of these trials, we'll certainly provide updates and share our thoughts with you.

Okay. Maybe just another one for either Mike or Chris, just with respect to the ongoing arbitration with Genentech. You have obviously cleared up things on kind of a cost sharing side. I know that there was some prior mention around a discussion regarding pricing and just wondering if you'd provide us an update as to maybe where that conversation stands and when we may be able to anticipate some kind of resolution there. Thanks

Yes, Steve, fair question. You are correct. We certainly made some progress on the cost allocation variable of that complex equation in January. I am really not in a position to provide any more details around the overall process. That is a confidential process, one that we are certainly pursuing very seriously but we want to maintain that confidentiality going forward.

It is not possible to speculate on timing for overall parts of that process either, so unfortunately I just cannot provide a lot more information for you today except to say that as we get definitive feedback, we will be able to share that with you then, okay? So fair question, stay tuned.

All right. Thanks for the color.

Thank you. Michael Schmidt, Leerink Partners.

Hey, guys. Congrats on a good quarter and thanks for the detailed update. I had a couple follow-on questions, maybe one on the Bristol collaboration. It sounds like you are in pretty advanced stages in terms of ramping up or getting ready for the front-line RCC trial. Just wanted to confirm that you said you anticipate to start that in the first half of this year. The follow-up question is what is the gating factor to initiating the other planned trials with Bristol? Is there additional phase 1 work that is necessary or are you basically ready to go?

This is Gisela. Regarding the first-line RCC effort, we are hoping to see that initiated in the first half of the year of 2017 and there certainly active work on going towards that and we will provide updates as we proceed along those lines. We are also looking obviously at other tumor types and those are discussions that are ongoing at this point. We mentioned bladder cancer. We also mentioned hepatocellular cancer, where both cabozantinib and also nivolumab have showed single-agent activity where both agents are being evaluated in phase 3 studies and where an initial study could evaluate the preliminary activity and safety intolerability of the two agents. Those are the near-term goals for this collaboration and there's certainly opportunity for other tumor types as well where single-agent activity has been seen for both agents.

Okay. It sounds like you will have the front-line combination study initiated by the time you will submit the sNDA with the CABOSUN trial. I guess the follow-up question is, where do you stand with conducting additional survival analysis in the CABOSUN study and would you be able to include that in the sNDA filing, potentially?

The Alliance and specifically the PI for the study Dr. Apolo had mentioned at ESMO and after that, that the Alliance would eventually conduct additional analyses for overall survival. We do not have any timing guidance at this point regarding the filing. We will submit the most up-to-date data that we are in the possession of at the time.

Okay. Thanks. Then a housekeeping question on the CABOMETYX quarter. Did you see any changes in growth net adjustment an/or an inventory channel changes?

Yes, Michael, thanks. It's Chris. We did not see any change in inventory. It is still in the three- to four-week range which has been -- which was consistent to the way we ended the third quarter. On a gross-to-net basis for CABOMETYX, we didn't see a big change. We are still in the 10% or so, 10% to 11% range of gross-to-net on CABOMETYX and we see that as the percentage going forward as of now.

Okay. One more if I may. You did provide several metrics, market uptick metrics and it seems like you have a focus, a strong focus on addressing or targeting community physicians. I guess my question is can you provide us with some information? What percentage of the overall target in the prescriber base has prescribed cabo at this point?

Yes, this is PJ. I'll take that question. We are really focusing on expanding our business by broadening the prescriber base in the community. We have talked about previously there's really a small number of really high-volume KOLs or academic prescribers and that is really on the order of hundreds of prescribers, whereas there is a broader opportunity among the community oncologists where there is thousands of oncologists that do see RCC patients of the metastatic diagnosis on yearly basis.

So really it is a small percentage that are sort of the high-volume academic KOL and really a much bigger percentage in the community and we believe we have continued opportunity to increase that, which is why we are deploying tactics across sales, marketing, non-personal promotion, digital marketing, GPO group purchasing organization tactics to really continued to get out our message in many ways in a community oncology setting.

Okay. Well, great. Thank you and congrats on the progress.

Thanks, Michael.

Thank you. Ted Tenthoff, Piper Jaffray.

Great. Thank you very much. I have a couple quick questions, if I may. First, for Chris, I just want to make sure I'm getting this right. The way you described it, in the fourth quarter you actually had a net gain from COTELLIC and Roche, so is that what was included the royalty line?

No, Ted. This is Chris, obviously. From Roche, the royalty we received from COTELLIC is only for ex-US. Any of the profit share or loss, and we had a loss for the year of around $4.5 million, runs through the SG&A expense; however, I will say that when we looked -- and I think Eric asked this question, too. When we look at 2017, the expense guidance assumes that the COTELLIC profit and loss P& L will be a profit in 2017 and therefore we'll be recording that as collaboration revenue as we look to 2017.

Great. Excellent. That's helpful. Cool. One for Gisela, with respect to CELESTIAL, do we have any clearer timing on data about when that may come this year? Also, any comments on kind of current duration of therapy for cabo?

The CELESTIAL, as you know, is a blinded study and it is ongoing enrollment. As I mentioned earlier on, it's continuing. We are expecting data in 2017. We have not really guided towards any specific time in the year. We'll certainly update you as we get closer. Given that it is a blinded study, we're not looking at cabo duration on treatment.

I am sorry, so cabo in RCC, any update on --

I am sorry. I did not hear you.

Yes, Ted. This is PJ. I can discuss that with regards to duration. For duration in the commercial setting, it is a bit early to get sort of enough data to have a retrospective look at duration of therapy. We are really closely monitoring our refill rates and the persistence of therapy and we're really pleased with the data that we are analyzing at this point.

As we are moving forward into Q4, we had more second-line patients which are healthier, which could potentially have a better persistency rate than later-line patients relative to earlier in the launch, so we do believe that as that trend continues and we see more early line of therapy patients, aka, second line we could have a little bit of upside in the persistency.

Okay. Cool. It would be great to get clarity on that if you can ever share it. Thanks so much.

Thanks, Ted.

Thank you. Andy Hsieh, William Blair.

This is Andy Hsieh on for John Sonnier. Congrats on the progress and the very successful quarter. We have two questions. First question is for Mike. Would you mind coming out for us the Company's growth strategies in the mid and longer term?

Second question is for PJ. As you are changing the commercial initiatives, were you able to correlate what you are doing, i.e., focus on doctors who have not prescribed cabo and changes in script trends, especially given the fact that there seems to be an apparent acceleration starting in January. Thank you.

Okay. Why don't I start. Give you some sense of kind of our aspirational goals as we go forward.

Look, we are very focused on building value, again, for patients and shareholders. We made a decision five or so years ago to focus on cabozantinib to really help catalyze the transition from a development-stage company to commercial company. Again, that was not a strategy, per se. We did not wake up one morning and say let's be a cabo-only company because that is a good strategy. It was a tactic to be able to really advance the Company forward to, if successful, be able to generate free cash that we could then organically invest in the business and grow the business based upon that free cash flow really driving our investments going forward.

That, I think, is starting to happen now. Certainly, we see growth potential in cabozantinib and certainly the announcements today I think would start to lay the foundation for that, how we then generate the next wave of pivotal trials. Obviously first-line RCC would come first but we're certainly excited about the possibility of doing more in the short to midterm as warranted by data.

Beyond that, certainly cobimetinib is going to play an important role potentially in driving the growth of our business. Again, as we talked about previously, we do not pay for any development that is going on with that compound. Obviously, with the discussion that Peter had today and you've heard from our friends at Genentech and Roche about what they are doing, how they are investing in different cobi combos, especially cobi/atezo combos. There is a big program going there that we are excited about and certainly would benefit from success from a commercial point of view if those different trials in colon, in melanoma, maybe others, were successful. Beyond that, as we talked about today several times, we are looking very closely at either generating a pipeline of compounds through our restart of internal discovery, which Peter is leading, and/or through in-licensing and/or acquisition efforts around early-stage clinical compounds that we can then develop broadly and move into product.

Again, it's a pretty broad strategy. I think it is one that we are excited about. It is one that we think we have really made that transition from development stage focused to a commercial focus and come back full-circle around internal discovery BD to allow us to build a portfolio of products that our very well-trained, experienced sales team then can go and sell at the appropriate time. Lot of work to do, but we certainly like our momentum going forward.

Okay. PJ?

Yes, thanks, Andy. I will address your question to me. With regards to broadening sort of our prescriber base in the community, limit my comments to kind of what we saw in Q4. With regards to that, what we know is the data, the METEOR data from market research advisory boards, et cetera, are very compelling and when physician see it, they do want to prescribe the drug.

As it's really the second quarter of the launch and really early sort of the early innings of the launch, so to speak, we're just really starting to get our marketing tactics out to the broader community base, so I think a lot of those physicians do not see as much renal cell carcinoma but as they hear the message, that is what kind of led to that 60% increase in prescriber growth that we saw in Q4 and there are still many physicians who have yet to prescribe the drug. I think it is really good data and a good strategy and marketing mix that's getting the data out there more broadly in the second half of the year and as we continue to differentiate from the competition through our trifecta of efficacy with the only drug in a global pivotal phase 3 trial that is yielded overall survival benefit, progression-free survival benefits and objective response rate benefit, that really resonates with physicians and gives us hope that we can continue those trends as we continue to get more physicians to prescribe the drug and broaden our prescriber base, as well as grow our market share, particularly in the second-line setting.

Thank you. Andrew Peters, Deutsche Bank.

Hey, guys. Thanks for taking my questions and congrats on the progress as well. I guess I just wanted to focus on a couple of things. I guess first, the language in the Bristol press release earlier today and some of what you have discussed today talks about expanding cabo combinations into other indications beyond RCC and HCC, so just wanted to get a better sense of the limiting steps to getting those studies off the ground. For example, would you likely need to run some kind of phase 1/2 studies for similar to the NCI bladder study or would you potentially go straight into pivotals?

Secondly, as you think about the front-line RCC study, how do you kind of think about the competitive dynamics there as you are thinking about use of capital with kind of many other ongoing large phase 3 front-line RCC trials? How do you think about incremental differentiation of cabo plus nivo or the triple relative to those? Thank you.

Hey, Andrew. It's Mike. Thanks for the question. Why don't we have Gisela take the first one and I'll take the second one.

Yes, I think the combination has been evaluated now in phase 1 through the NCI study of cabozantinib and nivolumab and also cabozantinib, nivolumab and ipilimumab. Doses for recommended phase 2 doses have been established with 40 milligrams of cabozantinib and full dose of the other compounds and so I think we can take those forward into new trials. We have obviously with RCC an indication where both modalities have shown very nice activity, showing the survival benefit in the second-line setting and so here we have a lot to go on and to move forward into phase 3.

We have, as you know, with cabozantinib single-agent activity across a wide variety of different tumor types. We have heard results and we've talked about those previously, for instance in lung cancer generated in a randomized phase 2 study through (inaudible) where cabozantinib, either as a single agent or in combination with erlotinib, more than doubled PFS and overall survival compared to erlotinib. So there's clearly single-agent activity and there's clearly single agent activity for the immuno-oncology compound so in such indications, I think we have a lot to go on to move forward into later-stage trials and certainly more discussions will follow on that.

To follow up on your second question, I think the whole goal behind these cost-sharing arrangements in these pivotal trials, especially, for example, with the first-line renal was to be share the cost and share the risk and then able to do more, broadly speaking, across different tumor types, different I/O combination opportunities. So very consistent with our past discussions on the topic. This is a starting point and it is one we hope to build on as we go forward.

Okay. Thanks. Just to make sure that I understand, you, based on the previous monotherapy activity you have seen before in indications like lung, you would expect to be able to move straight into pivotal trials instead of, say, running a smaller lead-in phase 2, for example? Is that correct?

Yes. I would not go that far, just to clarify. We're not giving any guidance on what our plan is here and I would not want to speculate on any specific trials, combinations, any details until we are ready to announce that. I think what Gisela said is correct. We will look at each situation carefully in the context of the data we have got, what we see as our risk profile and certainly do that in the conjunction of a new collaborator with their views on this topic as well.

I would just say stay tuned, right? We're going to look at this very carefully. We have done a pretty good job of evaluating the risk and moving forward with some pretty good trials in the past and we will continue to do so in these collaborations as we go forward.

Okay. Great. Then just one on the commercial side. I think I heard you correctly, you mentioned you have roughly around a 27% market share right now. Should we think about kind of the quarterly sales run rate as what you would expect with a kind of 27%-ish share of drug in second-, third-line RCC, or how do you think about kind of the way you view market share as it translates to the commercial opportunity? Thank you.

Yes, Andrew, it's Mike. It's a fair question. It's a good question. It's one that gets ultimately to guidance going forward and we're just not comfortable giving that perspective today.

I am sure you can appreciate, it is still relatively early in the launch. As Chris and PJ both said, it is a very competitive space. I can assure you that we are working very, very hard from a commercial sales and marketing, market access point of view to really reach every possible patient that we can. As we go forward, you'll see the numbers as we generate them and from the public sources. Just stay tuned, okay?

Great. Thank you.

Thank you. (Operator Instructions)

Asthika Goonewardene, Bloomberg Intelligence.

Hi, guys. Thanks for taking my question and again, congrats on the quarter. Let me start off with one on cabozantinib. Reimburse -- data that we have for reimbursement of the drug looks pretty good and besides the detailing efforts, I'm curious to know what are the catalysts that you guys have in the year that could help drive volume growth?

Well, thanks for the question. This is PJ. I will say a few things. Obviously, we're pleased as we have discussed today with regards to the growth we have seen going from Q3 to Q4 with regards to revenue, volume, and prescriber growth. I think you mentioned reimbursement. We're actually very pleased. At the last call we had about 224 million covered lives. Now we're up to about 250 million covered lives.

So very pleased with coverage of the drug, working very hard without Exelixis access services program to ensure that the appropriate patients have therapy and we're happy that, that is going very well. I think as we look forward, we have the opportunity to grow as we get more prescribers, many who have not yet written the drug to describe the drug and continue to differentiate in the second-line setting to really drive market share there in that patient published.

Great, PJ. Is there any other data presentations that you are expecting this year, maybe certain conferences that could help stimulate growth a little bit more?

Yes, it's Mike. Look, there is a number of international medical meetings, oncology meetings that we normally are at. It is a little bit too early to prospectively talk about what will have those meetings, so as those abstracts are submitted and accepted, our practice is to get that information out. But there's plenty of opportunity between ASCO and ESMO and things in between to be able to continue to talk about the data, talk about the compound. Certainly the milestone around the sNDA filing is an important milestone for us internally and that we're working towards very carefully. Thanks for the question.

Excellent. Thank you. One last one for Gisela, if I may. Clinical trial say that the CELESTIAL study is still recruited, but the last update on that was, I think, in August. Is that an accurate representation of the trial's recruitment status?

Yes. The study is still recruiting globally. That is correct.

Okay. Lovely. Thank you, guys, and congrats again for the quarter.

Thank you.

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

Okay, great. Thanks, Takeeya. 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 your participation in today's conference. This concludes the program. You may now disconnect. Everyone, have a great day.