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Exelixis Inc  (NASDAQ:EXEL)
Q1 2019 Earnings Call
May. 01, 2019, 5:00 p.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Good day, ladies and gentlemen, and welcome to the Exelixis' First Quarter 2019 Financial Results Conference Call. My name is Gigi, and I'll be your operator for today. As a reminder, this call is being recorded for replay purposes.

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

Susan Hubbard -- Executive Vice President of Public Affairs and Investor Relations

Thank you, Gigi, and thank you all for joining us for the Exelixis' first quarter 2019 financial results conference call. Joining me on today's call are Mike Morrissey, our President and CEO; Chris Senner, our Chief Financial Officer; P.J. Haley, our Senior Vice President of Commercial; and Gisela Schwab, our Chief Medical Officer, who will together review our corporate financial, commercial and development progress for the first quarter ended March 31, 2019. Peter Lamb, our Chief Scientific Officer, is with us as well and will be joining for the Q&A portion of the call.

During the call today, we will refer to financial measures, not calculated according to generally accepted accounting principles. Please refer to today's press release which is posted on our website for an explanation of our reasons for using such non-GAAP measures as well as tables deriving these measures from our GAAP results.

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 filed 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 steps, market competition, regulatory review and approval processes conducting clinical trials, compliance with applicable regulatory requirements our collaboration partners and the level of cost associated with commercialization, research and development, business development and other activity.

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

Michael Morrissey -- President and Chief Executive Officer

All right. Thank you, Susan, and thanks to everyone for joining us on the call today. Exelixis is off to a strong start in 2019 with important progress from a clinical, commercial and financial perspective. As you will hear from the team, new patient starts, demand, chronic revenue and cash outgrew in the first quarter, as we executed on our strategy to make CABOMETYX the number 1 in TKI in RCC and launching the new second line HCC indication.

We maintained strong momentum to move aggressively throughout 2019 to grow the CABOMETYX business, initiate next wave of cabozatinib pivotal trials and add new agents to our oncology pipeline from internal and external sources. We're pleased to see that the CABOMETYX business grew in the first quarter in the face of anticipated seasonal headwinds from both inventory drawdowns and higher gross to net feeds. Our first quarter results support the projection that cabozatinib's best-in-class TKI profile can drive strong growth in the face of emerging competition from ICI-based combination therapies in RCC and a broad offering of both TKIs and ICIs and HCC. The first quarter results are notable in the context of the RCC competition were first quarter 2019 U.S. revenues for Sutent and Votrient declined compared to fourth quarter 2018 as was the case with most other oral oncology products that have been reported on this quarter.

I'll begin today by providing a brief summary of our key first quarter milestones and then turn the call over to Chris, P.J. and Gisela for details on our Q1 financials, the commercial performance of CABOMETYX and finally, cabozatinib's development activities.

Key highlights for the first quarter 2019 includes first, the significant growth in new patient starts, demand and product revenue in the face of higher gross to net fees, and an inventory drawdown. Net cabozatinib franchise revenue for the first quarter was approximately $180 million. Non-GAAP first quarter net income was approximately $85 million. Non-GAAP diluted earnings were $0.27 per share. And we exited the first quarter with greater than $1 billion in cash and investments. Chris will cover the full first quarter financials shortly.

Second, the continued strong performance of the CABOMETYX business where we maintained its leadership position as the best-in-class TKI for advanced RCC and initiated sales and marketing activities in HCC. CABOMETYX continued to gain additional RCC market share throughout the first quarter. And we're pleased with our initial launch in HCC where we see notable traction in the second and third line study. The depth and breadth of the METEOR and CABOSUN data in RCC and the celestial data in HCC continues to differentiate CABOMETYX from all other TKI's approved in these indications. Notably, CABOMETYX is the only TKI with the pronounced and statistically significant overall survival advantage in both RCC and HCC.

Third, we continue to advance our cabozatinib development program as we aggressively pursue the next wave of cabozatinib late-stage clinical trials. Four pivotal trials highlight important progress in this area, including CheckMate 9ER with cabo, nivo and first-line RCC, COSMIC-311 with single agent cabozantinib and second line DTC, COSMIC-312 with combination in the first-line HCC and with today's announcement COSMIC-313 with the triplet cabo nivo combination in first-line RCC.

And fourth, our integrated discovery development in BD team is employing a combination of internal efforts and external collaborations to build the portfolio development candidates that we can efficiently evaluate in the clinical study.

Our progress throughout the early months of 2019 highlights the team's performance across all compliments of our business, during a dynamic time where both the RCC and HCC landscapes are rapidly evolving.

Operator

Good day, ladies and gentlemen, and welcome to the Exelixis' First Quarter 2019 Financial Results Conference Call. My name is Gigi, and I'll be your operator for today. As a reminder, this call is being recorded for replay purposes.

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

Susan Hubbard -- Executive Vice President of Public Affairs and Investor Relations

Thank you, Gigi, and thank you all for joining us for the Exelixis' first quarter 2019 financial results conference call. Joining me on today's call are Mike Morrissey, our President and CEO; Chris Senner, our Chief Financial Officer; P.J. Haley, our Senior Vice President of Commercial; and Gisela Schwab, our Chief Medical Officer, who will together review our corporate financial, commercial and development progress for the first quarter ended March 31, 2019. Peter Lamb, our Chief Scientific Officer, is with us as well and will be joining for the Q&A portion of the call.

During the call today, we will refer to financial measures, not calculated according to generally accepted accounting principles. Please refer to today's press release which is posted on our website for an explanation of our reasons for using such non-GAAP measures as well as tables deriving these measures from our GAAP results.

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 filed 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 steps, market competition, regulatory review and approval processes conducting clinical trials, compliance with applicable regulatory requirements our collaboration partners and the level of cost associated with commercialization, research and development, business development and other activity.

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

Michael Morrissey -- President and Chief Executive Officer

All right. Thank you, Susan, and thanks to everyone for joining us on the call today. Exelixis is off to a strong start in 2019 with important progress from a clinical, commercial and financial perspective. As you will hear from the team, new patient starts, demand, chronic revenue and cash outgrew in the first quarter, as we executed on our strategy to make CABOMETYX the number 1 in TKI in RCC and launching the new second line HCC indication.

We maintained strong momentum to move aggressively throughout 2019 to grow the CABOMETYX business, initiate next wave of cabozatinib pivotal trials and add new agents to our oncology pipeline from internal and external sources. We're pleased to see that the CABOMETYX business grew in the first quarter in the face of anticipated seasonal headwinds from both inventory drawdowns and higher gross to net feeds. Our first quarter results support the projection that cabozatinib's best-in-class TKI profile can drive strong growth in the face of emerging competition from ICI-based combination therapies in RCC and a broad offering of both TKIs and ICIs and HCC. The first quarter results are notable in the context of the RCC competition were first quarter 2019 U.S. revenues for Sutent and Votrient declined compared to fourth quarter 2018 as was the case with most other oral oncology products that have been reported on this quarter.

I'll begin today by providing a brief summary of our key first quarter milestones and then turn the call over to Chris, P.J. and Gisela for details on our Q1 financials, the commercial performance of CABOMETYX and finally, cabozatinib's development activities.

Key highlights for the first quarter 2019 includes first, the significant growth in new patient starts, demand and product revenue in the face of higher gross to net fees, and an inventory drawdown. Net cabozatinib franchise revenue for the first quarter was approximately $180 million. Non-GAAP first quarter net income was approximately $85 million. Non-GAAP diluted earnings were $0.27 per share. And we exited the first quarter with greater than $1 billion in cash and investments. Chris will cover the full first quarter financials shortly.

Second, the continued strong performance of the CABOMETYX business where we maintained its leadership position as the best-in-class TKI for advanced RCC and initiated sales and marketing activities in HCC. CABOMETYX continued to gain additional RCC market share throughout the first quarter. And we're pleased with our initial launch in HCC where we see notable traction in the second and third line study. The depth and breadth of the METEOR and CABOSUN data in RCC and the celestial data in HCC continues to differentiate CABOMETYX from all other TKI's approved in these indications. Notably, CABOMETYX is the only TKI with the pronounced and statistically significant overall survival advantage in both RCC and HCC.

Third, we continue to advance our cabozatinib development program as we aggressively pursue the next wave of cabozatinib late-stage clinical trials. Four pivotal trials highlight important progress in this area, including CheckMate 9ER with cabo, nivo and first-line RCC, COSMIC-311 with single agent cabozantinib and second line DTC, COSMIC-312 with combination in the first-line HCC and with today's announcement COSMIC-313 with the triplet cabo nivo combination in first-line RCC.

And fourth, our integrated discovery development in BD team is employing a combination of internal efforts and external collaborations to build the portfolio development candidates that we can efficiently evaluate in the clinical study.

Our progress throughout the early months of 2019 highlights the team's performance across all compliments of our business, during a dynamic time where both the RCC and HCC landscapes are rapidly evolving.

Our overall strategic goals remain the same. We seek to grow revenues, manage expenses carefully and reinvest free cash into the business to build long-term sustainable growth. Through focus, determination and team work we strive to deliver on our goals every single day for patients and shareholders.

So with that, I'll turn the call over to Chris, who will provide more details on our first quarter 2019 financials.

Christopher J. Senner -- Executive Vice President and Chief Financial Officer

Thanks Mike. I'm very pleased to share with you our strong financial results for the first quarter of 2019. The company reported total revenues of $215.5 million in the first quarter 2019. Total revenues for the quarter included cabozantinib net product revenues of $179.6 million. Total revenues also included the recognition of $35.9 million in collaboration revenues from the company's commercial collaboration partners Ipsen and Takeda.

On a sequential quarter basis, CABOMETYX net product revenues increased by approximately $4.3 million. This result included increases of approximately $4.5 million in CABOMETYX product volume and $9.2 million due to the first quarter price increase and was offset by a decrease in trade inventory of approximately $2.3 million and deductions from gross sales, which increased to 19.8%. The increase in deductions from gross sales for the first quarter was $7.2 million, and was 2.4 percentage points higher when compared to the fourth quarter of 2018, which was 17.4%.

The CABOMETYX wholesaler inventory at the end of the first quarter 2019 was approximately 2.6 weeks on hand, as compared to approximately 2.9 weeks on hand at the end of fourth quarter 2018. The increase in our deductions from gross sales is primarily related to increases in our Public Health Services, or PHS, utilization. CABOMETYX had higher growth in PHS utilization that experienced an overall patient demand.

A segment of our payer mix which is subject to much higher discount requirements than other payer segments. Additionally, our Medicare coverage gap liability increased significantly when compared to the fourth quarter 2018, which can be attributed to both the relative increase in Medicare patient utilization and the increase in the Medicare Part D discount from 50% in 2018 to 70% in 2019.

Taking into consideration these various components of our payer mix, we project that are CABOMETYX deductions from gross sales will be between 19% and 20% for the full year of 2019.

Total revenues also include collaboration revenues of $35.9 million for the quarter ended March 31, 2019. These collaboration revenues include the recognition of $9.4 million of a $10 million milestone from our commercial collaboration partner Takeda for their CABOMETYX filing in Japan for advanced RCC.

Collaboration revenues also include $14 million of royalties earned from approximately $63 million of cabozantinib sales by Ipsen. $2.5 million of profit share and royalties earned under the cobimetinib collaboration with Genentech, Roche and $10 million of additional license, research and development and product supply revenues that were recognized from the company's collaborations.

Our total cost and expenses for the first quarter of 2019 were $130.9 million compared to $117 million in the fourth quarter of 2018. Within total cost and expenses, R&D expenses increased by $6 million and is primarily the result of increases in our clinical trial spend as we invested in the next wave of CABOMETYX pivotal trials and to a lesser degree, increases in licenses and royalty spend primarily from an Invenra project B.

Selling, general and administrative costs increased by approximately $7.8 million. The increase in SG&A expense was primarily related to increase in expenses for corporate giving, personnel, branded prescription drug fee and marketing.

Income taxes for the quarter ended March 31, 2019, was $14.9 million, and our effective tax rate for the quarter was approximately 16.4% compared to $2.5 million and 2.1%, respectively, for the comparable period in 2018. The 16.4% income tax rate in the first quarter is below our guidance range for 2019 and was favorably impacted by certain discrete deduction that occurred in the quarter.

The company reported GAAP net income of $75.8 million, or $0.24 per share on a fully diluted basis for the first quarter 2019. The company reported non-GAAP net income of $85.5 million or $0.27 per share on a fully diluted basis. Non-GAAP net income excludes the impact of approximately $10 million of stock-based compensation net of the tax effect.

Cash and cash equivalents, short and long-term investments and long-term restricted cash and investments totaled approximately $1 billion at March 31, 2019, compared to $851.6 million at December 31, 2018. The increase in our cash reflects approximately $90 million of cash flow from operations, the receipt of $60 million of milestone payments from a collaboration partner Ipsen, and approximately $18 million of royalty and reimbursements from our collaboration partners.

Now turning to our financial guidance. The company is maintaining its financial guidance for 2019. Cost of goods sold is expected to be between 4% and 5% of net product revenues. Research and development expense is expected to be between $285 million and $315 million and includes non-cash expenses related to stock-based compensation of approximately $20 million.

Selling, general and administrative expense is expect to be between $220 million and $240 million and includes non-cash expenses related to stock-based compensation of approximately $35 million.

Guidance for the effective tax rate in 2019 is between 21% and 23%. And finally, overlap several quarters we have experienced increasing variability in our deduction from gross sales and wholesale inventory levels that should be considered when modeling future revenue trends.

As I mentioned earlier, we project that our detections from gross sales for CABOMETYX will be for 19% and 20% for the full year 2019. Also, we expect increased quarterly variability in wholesaler buying patterns, which can lead to variability and how much inventory wholesalers hold, as we and other by biopharma experienced in the second half of 2018. Some of these inventory variability can be attributed to the implementation of new price transparency regulations and can provide wholesalers opportunity by extra supply in advance for anticipated price increases.

And with that, I'll turn the call over to P.J.

P.J. Haley -- Senior Vice President, Commercial

Thank you, Chris. I'm very pleased to discuss in detail with you today the strong performance of CABOMETYX in the first quarter. In Q1, CABOMETYX built on the position of being the number one TKI for new prescriptions in RCC and became the leading TKI in total prescriptions or TRx in RCC.

Additionally, the approval and launch of CABOMETYX in HCC is off to an encouraging start across a variety of metrics that I will touch on in these remarks. In Q1, we saw positive trends in the business in terms of demand, new prescriptions, and expansion of the CABOMETYX's prescriber base.

Patient demand grew by 33% year-over-year and 3% quarter-over-quarter. And this growth was driven by both RCC and HCC.

New prescriptions or NRx were up by 17% in Q1 relative to the fourth quarter of 2018. The growth in new prescriptions in Q1 was driven equally by RCC and HCC. We're pleased to see the growth in demand and new prescriptions coming from both of the new tumor types for which CABOMETYX as indicated.

This underscores healthy fundamentals for both parts of the franchise and I'll go into more detail for each momentarily. Additionally, the prescriber base grew by 10% quarter-over-quarter and 53% year-over-year from 2018. This growth was driven by new community prescribers for both RCC and HCC as well as new academic prescribers within HCC.

CABOMETYX's net revenue grew to about $176 million, representing an increase of 36% year-over-year and 2.5% quarter-over-quarter. As Chris mentioned, net revenue in Q1 was impacted by increased PHS utilization, increased Medicare doughnut hole expenditures, and a drawdown of inventory following two successive quarters of inventory build.

Inventory is now on the low end of the range that we historically observed for CABOMETYX. Furthermore, inventory was built across the industry in Q4 last year and that appears to be the case for the RCC oral, tyrosine kinases inhibitor market as well.

I will now turn to more specifics of the RCC marketplace, which continues to become increasingly competitive. We have long anticipated approval of PD-1 TKI combinations in RCC. And very recently, the combination of pembrolizumab and axitinib was approved in the first-line setting.

To get a better sense for the evolving competitive dynamics through Q1, we analyze the IQVIA data for RCC oral TKI inhibitor or TKI market comprised sunitinib, pazopanib, axitinib, and CABOMETYX.

As you can see from this analysis of publicly available data, CABOMETYX became the leading TKI in total prescriptions in Q1, surpassing Votrient, and gaining three share points for a TRx market share of 34%.

We're pleased that CABOMETYX continued to grow in Q1 despite the competitive marketplace. This represents significant progress and a share point increase of 3% relative to the last quarter and a growth rate of 8% in TRx relative to Q4 2018. Additionally, these data show that CABOMETYX became the number one TKI for total prescriptions in the RCC market.

Turning to NRx, you may recall that CABOMETYX became the leading TKI in RCC for new prescriptions in Q4 and the CABOMETYX NRx share continue to increase in Q1 to 36%.

Also encouraging is the NRx growth trend in Q1, relative to Q4, showing that CABOMETYX NRx grew 17%, outpacing the TRx growth rate of 8% Q-over-Q. Both growth rates were higher in Q1 relative to Q4.

The RCC market will continue to be driven largely by the sequencing of therapeutic options, and we feel good about CABO's place in the market as sequencing evolves. Most patients will have the opportunity to receive either CABOMETYX followed by ICI therapy or an ICI combination followed by CABO in sequence.

The number of second-line patients who have progressed on the combination of nivo/ipi increased again in Q1 and we expect this gradual trend to continue in the coming quarters as there are many frontline nivo/ipi patients that have yet to progress.

CABOMETYX is well-positioned to be the treatment of choice for these patients as well as patients who progress on pembro/axi.

Market research continues to indicate that approximately 90% of key opinion leader survey would chose CABOMETYX as their therapeutic option after a first-line ICI combination, whether it is NivoIpi or PD-1 TKI. The RCC business has strong momentum heading into Q2. According to data from IQVIA brand impact, CABOMETYX new patient market share was stable in the first line and increased in the second line in Q1.

Furthermore, since the approval of NivoIpi in April, the vast majority of the patients who have progressed on this combination have received CABOMETYX as their second line treatment. In fact, data from IQVIA brand impact suggest that CABOMETYX captured the vast majority of market share patients in Q1 who have progressed on NivoIpi, consistent with our market just mentioned.

We continue to see broad utilization across academic and community settings, lines of therapy and clinical risk groups. Given the patient flow dynamics and the strength of the CABOMETYX data, we expect RCC demand to continue to grow in 2019. In addition to the continued momentum of CABOMETYX and RCC, we're excited to also drive growth in the newly received indicating in HCC, representing a third tumor type and fourth indication for the cabozantinib franchise. Our team began executing on the launch immediately upon receiving approval for the second line HCC indication on January 14th, and we're pleased with the progress made.

We're still in the early days of the launch, but the key metrics indicate that we're exceeding our expectations. As we have stated for some time, HCC is a market that will need to be built, as new therapies become available for these patients. This is consistent with the external market research, which indicates that the HCC market will grow in the coming years.

Our market research indicates that CABOMETYX is already achieving significant awareness relative to the other TKIs in HCC. If aware of the celestial data, the majority of physicians indicate that they intend to prescribe CABOMETYX consistent with its approved labeling. Initial market research indicates that cabo will be the TKI of choice in pretreated HCC patients and we're seeing this in the market as cabo is already taking share from regorafenib.

We view these collective observations as encouraging and consistent with the initial HCC market trends we're seeing in terms of both new prescriptions and demand. As I mentioned earlier in my remarks, we're seeing HCC contribute to approximately half of cabo's demand growth and half of the brand's growth in new prescriptions in the first quarter.

We're pleased that HCC and RCC are growing with regards to both of these metrics. Based on the fact that CABOMETYX has demonstrated a survival benefit in a second tumor type, the HCC indication seems to have generated additional confidence in Cabo among the physician community and other synergies for the CABOMETYX brand. Importantly, the HCC approval has increased account access for our sales force and facilitated not only productive HCC discussions, but has increased the number of meaningful RCC discussions and interactions with prescribers as well. In fact, our pre-approval RCC sales footprint covered approximately 95% of the combined RCC and HCC market potential. And we began calling on the remaining HCC-specific prescribers immediately following approval.

While early days, external share of voice data is validating our strategic approach to the market, as CABOMETYX has the leading share of voice in second line plus HCC, while maintaining the leading share of voice in the RCC market. Our established footprint in community oncology and community physician familiarity with CABOMETYX is aiding the uptake within HCC.

Our market research had indicated that there would be an increased interest in prescribing CABOMETYX for HCC, if the physician had previous experience using cabo and RCC. This is playing out in the market as approximately 80% of HCC prescribers in Q1 have previously return cabo and the other 20% are largely academic-based. We're pleased to see this uptake for HCC in both the academic and community segments of the market.

We're also pleased with the results of Q1, but believe that many more RCC patients and now, HCC patients, could benefit from CABOMETYX. CABOMETYX grew in Q1 in terms of new prescription and demand in both RCC and HCC. The HCC approval continues to augment the overall positive perception of the brand and gives our customers more options as they strive to help patients with difficult-to-treat cancers.

CABOMETYX is now the number one prescribed TKI in RCC, and we look forward to building on this momentum in RCC, HCC and other potential future indications as the cabozantinib development program expands. Our team is focused and motivated to compete every day to bring the benefit of CABOMETYX to every eligible patient as we continue to build the franchise.

With that, I'll turn the call over to Gisela.

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Thank you, P.J. I am pleased to provide an update on the progress of the cabozantinib development program and will start with an overview of our combination trials of cabozantinib with immune checkpoint inhibitors. Our clinical collaboration with BMS, combining cabozantinib with nivolumab alone or cabozantinib with nivolumab and ipilimumab is making great progress.

The ongoing Phase 3 CheckMate 9ER study in treatment-naive RCC patients comparing cabozantinib in combination with nivolumab versus sunitinib hence completed enrollment recently with the last few patients in Japan, going through the screening period before randomization.

This study is sponsored by BMS and co-funded by ourselves and our partner Ipsen and Takeda, together with BMS. We are very pleased with it's progress and are expecting result from this study early next year as BMS commented on their recent quarter call. We look forward to be event-driven analysis and will provide further update when available.

Also, as announced today, we are initiating a further Phase 3 trial, COSMIC-313, evaluating the treatment of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in the first line RCC. We are independent sponsor and BMS is collaborating with us and providing nivolumab and ipilimumab free of charge.

The primary endpoint of 676 patient trial of PFS and secondary endpoint includes overall survival and objective response rate. Despite a significant progress in the treatment of RCC during the last few years, further improvements are needed. This study further builds on the positive outcome on cabozantinib study in first line RCC from cabozantinib demonstrated superior PFS compared to sunitinib in patients with intermediate RCC as well as the positive CheckMate 214 trial that's demonstrated superior overall survival with the combination of nivolumab and ipilimumab when compared to sunitinib. Also these trials have led to regulatory approval from the respective compound.

So we are excited to move these agents with proven activity in first line RCC forward in combination as we believe that cabozantinib target profile, resulting in more immune permissive environment with immune checkpoint inhibition may result in further improvement of important outcomes in the first line RCC, including the depth of response as well as duration of PFS. This is the first trial to compare a TKI checkpoint inhibitor combination to be approved in checkpoint inhibitor combination of nivolumab and ipilimumab in the first line RCC.

The preliminary activity and total ability of both the combination of cabozantinib and nivolumab and the triplet culmination including ipilimumab has been previously evaluated in Phase Ib study shared by Dr. Andrea Apolo.

In this Phase Ib trial conducted in previously treated patients with advanced GU tumors, including RCC, a total overdose of 40 milligrams of daily oral cabozantinib together with either three milligrams per kilogram of nivolumab alone or three milligrams atezolizumab with nivolumab plus one milligram of atezolizumab with ipilimumab for every three weeks for the first blood administration.

We are also making great progress in our collaboration with Genentech Roche, our combination Phase 1b trial of cabozantinib and ipilimumab, the COSMIC-021 Phase 1b trial is actively enrolling patients across 20 expansion cohorts in various setting. And our Phase 3 trial COSMIC-312 in patients with previously untreated advanced hepatocellular cancer, and then growing patients in United States and abroad.

For our COSMIC-021 and COSMIC-312, we are collaborating with Genentech Roche who are providing atezolizumab and our partner Ipsen is co-funding the study. Further late stage checkpoint inhibitor combination study and indication, including potentially bladder cancer and non-small cell lung cancer and promising tumor types from the COSMIC-021 trial are also anticipated, and we will provide more details as we get ready to initiate these trials.

And separately, on the regulatory side for cabozantinib and late breaking news announced just a few days ago, Takeda, our partner for cabozantinib in Japan saw an NDA for cabozantinib for the treatment of advanced RCC with the Japanese regulatory authority.

In addition to the very active cabozantinib development program, we are working on expanding our development pipeline. Late in quarter four 2018, we have new IND for a next-generation tyrosine kinase inhibitor targeting VEGFR and MET, and the Phase I trial for XL092 is now actively involving patients. Data dependent, we plan on advancing this compound quickly through dose-finding and disease-specific, single agent forward expansion, as well as combination approaches, setting the stage for late-stage development.

I'll close with a brief update on cobimetinib, two Phase III pivotal trials in previously untreated melanoma has been involved fully last year. These include IMspire150 or TRILOGY evaluating cobimetinib, vemurafanib plus atezolizumab in BRAF mutant-positive patients, locally advanced for metastatic disease and IMspire170 that values cobimetinib and atezolizumab in BRAF wild-type metastatic melanoma. Per Roche full year 2018 results call in January of 2019, potential regulatory filings later this year if data is supportive.

And finally, we're busy preparing for the annual ASCO conference, starting at the month of the month in Chicago. We're looking forward to the conference with nine cabozantinib and two cobimetinib related to ASCO will be presented and to the opportunity to connect in person key with opinion leaders and partners.

So in summary, I'm very pleased with the progress made in our development program and reported milestones reached during the quarter and look forward to updating you in the future.

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

Michael Morrissey -- President and Chief Executive Officer

All right. Thanks, Gisela. I'll close by saying that Exelixis maintained strong momentum in the first quarter of 2019. And we're excited about the growth potential of our company across all aspects of our business. Notably, our Q1 results highlight that we continue to grow the business quarter-over-quarter and year-over-year due to the strength of the CABOMETYX launch, our deals with Ipsen and Takeda in disciplined expense management.

Cabozantinib is vectoring toward $1 billion per year of global run rate and has helped literally tens of thousands of patients with RCC and now HCC, live longer and recover stronger. The strength of our business provides a compelling opportunity for potential long-term growth, as we continue to invest in R&D with future additional cabozantinib late-stage trials and new product candidates through both internal and external R&D efforts.

I want to thank the entire Exelixis' team for their dedication and commitment as we navigate the opportunities and challenges that lie ahead of us. As I said previously, we have a team and culture that is focused, energized and extremely resilient. And we remain committed to making every day count as we discover developing commercialize the next generation of our medicines for cancer patients to meet the better and more effective therapies. We look forward to updating you on our progress.

Thank you for your continued support and interest in Exelixis. And we're now happy to open the call for questions.

Questions and Answers:

Operator

(Operator Instructions) Your first question comes from the line of Andy Hsieh from William Blair. Please proceed.

Andy Hsieh -- William Blair -- Analyst

Great, thanks for taking my question and congratulations on the quarter. So impressive 70% NRX growth rate, I'm just wondering, is there any among patients who have previously been treated with in front-line setting, are you seeing any kind of pattern there in terms of patients going on cabo? Are they rapid progessers? Are they stable disease, patients who have failed after the short period of time? Any sort of trend line that you can provide there?

P.J. Haley -- Senior Vice President, Commercial

Yes, Andy, thanks for the question. This is P.J. We're certainly pleased with what we're seeing in the market research data the brand impact data is that we're getting the vast majority of the patients the last couple of quarters progress think of nivo. We're really what we're seeing because it is kind of 90% range. We're really getting all types of patients who are progressing on NivoIpi across the board and that's been approved, as you know, now for over a year. We see the kinetics of kind of those patients progressing continue to increase, which is I think logical given the timing and given their data.

And furthermore, our market research continues to indicate that we should really capture the vast majority of those patients progressing on either NivoIpi or PD-1 TKI. So we're seeing that broadly. We're pleased with that. And certainly, we'll continue to really ensure that those patients have the opportunity to benefit from CABOMETYX.

Andy Hsieh -- William Blair -- Analyst

Great. That's helpful. So moving on to HCC, I'm just wondering, based on the conversations you have on the field with physicians, following the setback with KEYNOTE-240, are you seeing a decrease or I guess, hesitancy in terms of prescribing checkpoint inhibitors for HCC patients there?

P.J. Haley -- Senior Vice President, Commercial

Yes. Thanks for the question, Andy. P.J., again. Definitely interesting, sort of, times and data in HCC, as that markets expanding and new options are becoming available. I'd say it's kind of early days to really understand any potential impact of that announcement of the keynote data.

But what we really are seeing, and I think every tumor type is different, is that the prospect of physicians treating HCC is quite positive toward TKI's. And I think with cabo coming to market here, we're seeing really good feedback on the CELESTIAL data.

We're seeing excellent uptake with regards to taking market share in both the second and third lines, predominantly, if at the expense of regorafenib. And I think that momentum and the demand growth and new prescription share growth, I think, really sets us up with good momentum heading into the rest of 2019.

Andy Hsieh -- William Blair -- Analyst

Great. Okay. And regulatory question in terms of HCC. I guess, the question is for Gisela. What other studies or conversations does Takeda need to have in order to have that approved in Japan? Obviously, that's very, very large market there for HCC?

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Yes. I won't comment for Takeda. Obviously, I don't have to address these questions and just suggest to address of (Indiscernible) partners. And typically what one would do in indications for a positive Phase 3 study data and this is conducted internationally, averaging 30% sort of been conducted. But I won't address Takeda's question.

Andy Hsieh -- William Blair -- Analyst

Got it. Okay. Awesome. That's all for me. Thank you answering all my questions.

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Andy, Thank you.

Operator

Thank you. Our next question is from Yaron Werber from Cowen. Your line is now open.

Yaron Werber -- Cowen -- Analyst

Yeah. Great. Thanks so much for taking my questions. So a couple of things. Number one, maybe I don't know who wants take one on. When I look at -- I'm trying to get a handle of how the long-term HCC is going so far, in terms of maybe a little bit more absolute numbers. So when you're referring to about half the growth of the brand coming from HCC, are you referring sort of on a quarter-over-quarter basis? Let's say, over the 5-sort-of-million quarter-over-quarter, is that sort of way we should think about that, maybe half of that?

P.J. Haley -- Senior Vice President, Commercial

Yeah. Hi, Yaron. This is P.J. Let me take that. So with regards to the growth, I was referring to, kind of, the new prescription growth and the demand growth are approximately half-and-half RCC, HCC. But with respect to your question and trying to talk about the overall business, what we saw in Q1 is approximately 4% to 5% of the business was driven from HCC.

And what I'll say about that is, as is often the case in oncology, prior to Q1, there was some unsolicited off-label utilization of CABOMETYX and HCC. This is something we've seen years ago, with regards to COMETRIQ being used in RCC. Certainly, some thing we didn't promote -- don't promote off label. But that's how you get to kind of 4% to 5% of the business being HCC in Q1.

Yaron Werber -- Cowen -- Analyst

Got it. Okay. So maybe kind of 7 to 8 roughly is -- that's a absolute sales in HCC, but maybe of that $2 million to $3 million is the growth quarter-over-quarter in HCC?

P.J. Haley -- Senior Vice President, Commercial

Yeah. We're not going to address specific numbers. But I think hopefully that helps you kind of frame it with all the other data we provided.

Yaron Werber -- Cowen -- Analyst

Yeah. Thank you. And then, just moving to 9ER and the powering of the study and both PSF, but more importantly on survival. So the study is now about 650 patients and certainly unquestionably well powered for PSF. Just comparing it to some of the other studies that have been done recently, they're sort of in the 850 range. I'm talking about 101 and obviously Keynote-426. How are you -- how did you arrive with Bristol about study size from a several standpoint and then a powering standpoint as you can give us a sense to how you got there? Thank you.

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Yes. Just in general, to comment on the 9ER study is designed to Bristol's endpoint, primary endpoint (Indiscernible) secondary endpoint to overall survival. The study, as we said, has enrolled about 650 patients. When you look at other trials in this space the -- they're measured as an event-driven endpoint to see the -- some of these trials achieved with relatively few events and number. And I think our own experience with cabozantinib in the METEOR, just to remind you, the study was 658 patients strong and met with PFS enrolled endpoint.

And maybe lastly, another point to consider is that cabozantinib and also nivolumab individually are single agent, met overall survival endpoints in their respective registration study. Did that help you out

Yaron Werber -- Cowen -- Analyst

Yes, absolutely. Thank you.

P.J. Haley -- Senior Vice President, Commercial

Yaron?

Yaron Werber -- Cowen -- Analyst

Thank you.

Operator

Thank you. Our next question is from Michael Schmidt from Guggenheim. Your line is now open.

Michael Schmidt -- Guggenheim -- Analyst

Hi. Thanks for taking my questions. I just wanted to dig in a little bit more into the 1Q 2019, CABOMETYX sales figures. So, I think, when I look at -- understanding inventory moments and some of the gross to net impact, but looking just the pure volume growth, I think you said, there was about 3% sequential growth in volume.

Some of that driven by HCC, which is obviously less than what you had in the fourth quarter and then the third last year I think you had 4%, 5% and 6% volume growth, respectively, sequentially back then.

Can you just help us understand how we should think about growth dynamics, in particular, in RCC going forward over the rest of the year? Is that a growth rate that we should look at from a forward-looking point of view?

P.J. Haley -- Senior Vice President, Commercial

Yeah. Thanks for the question. Michael, this is P.J. A couple of things, we're not going to provide guidance on specific growth for the remainder of the year. But what I would say is that, we're certainly pleased with the fact that we had growth in Q1 from both RCC and HCC.

And what I'd say beyond that, some of which is industry wide is we saw really nice sort of kinetics in the demand over the course of the quarter, certainly, in the later part of the quarter with regards to that demand and demand growth.

Another thing I would kind of point to here is, as I mentioned, we saw strong growth in NRx new patient starts in Q1. So certainly, pleased with that both on the RCC side and the HCC side, which are both driving that approximately equally.

And then, looking forward, as I've kind of mentioned in my prepared remarks, in RCC, we see continued demand growth over 2019, and that's primarily driven by more patients progressing on ICI combinations and CABOMETYX continuing to capture the vast majority of them in the second line.

And we certainly see the potential for demand growth in HCC, as we're in the very early stages of that launch and all the metrics are very positive. So, I think that's what I'd say with regards to that on the overall perspective.

Michael Schmidt -- Guggenheim -- Analyst

Okay. And then, you said that, more growth than historically it was driven by patients, any government reimbursement channel, which contributed to the increase in gross to net?

Just wondering if this is something that's driven by disease type or maybe -- could you maybe comment on how compares between RCC and HCC and if this is a trend that we should keep an eye on going forward?

Christopher J. Senner -- Executive Vice President and Chief Financial Officer

Yeah this is -- Michael, this is Chris. Thanks for the question. So, like I mentioned, we did see increased utilization in PHS, which is greater than demand as you pointed out. And I said, that phenomenon has been going on for the last couple of quarters.

We do continue to see a significant portion of our business on the commercial side. And we do see that, we increased utilization on the Medicare Part D side. And also that utilization was coupled with the higher discount rate that we had to take, which is legislated at the beginning of 2018.

Michael Schmidt -- Guggenheim -- Analyst

Okay. Thanks. And then last question. We saw there was an ASCO presentation actually from investigative on the study. I am just wondering if you could help us with some more comments your own expectations for how big is the study. Is this something that could potentially end up in NCCN guidelines, so any guidance that would be helpful?

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Yeah. This will be presented at ASCO. This study is a Phase II trial conducted and will be presented by Patrick at this financial result, but it is a regular size Phase II study and results are forthcoming so, happy to talk about that at ASCO.

Michael Schmidt -- Guggenheim -- Analyst

Okay, great. Thank you.

Operator

Thank you. Our next question is from Silvan Turkcan with Oppenheimer. Your line is now open.

Silvan Turkcan -- Oppenheimer -- Analyst

Well thanks for taking my question and congrats on the quarter. Could you tell me little bit more about the new COSMIC-313 trial that you initiated? How do you -- what is the importance of that trial compared to 9ER?

Are you confident in both trials? And what would be the timeline? Will it be to almost same patient number as 9ER, would it be kind of just same timeline here?

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Yeah, we're very excited. Obviously, to start in the study. I think it's an important study in the first-line stage in RCC and its -- as the first triplet combination of cabozantinib, nivolumab, and ipilimumab going into the Phase 3 comparison versus the approved nivolumab and ipilimumab combination, that set apart from other trials in this space.

I think it spoke earlier to the scientific rationale why we're excited about it. And hope and believe there is an opportunity for cooperative or synergistic activity between cabozantinib results in immune-permissive environment and checkpoint inhibitors, and I think in RCC even though there is a lot of progress that we can look actually now that has been made in the last several years, there's still opportunity for improvement with a deepening of response and extension of time driven endpoint. Regarding time line, we hope to initiate study and patient enrollment shortly. And we're working on that. With respect to read out, it is too early at this point and won't speculate at this point.

Silvan Turkcan -- Oppenheimer -- Analyst

Great. And how will this study impact your spending? I saw you reaffirmed your guidance for this year. Going forward, will there be a significant impact from adding the study or not?

Christopher J. Senner -- Executive Vice President and Chief Financial Officer

Yeah. Silvan, this is Chris. We've included the COSMIC-313 and future studies in our guidance numbers so -- for 2019. So it's fully included.

Silvan Turkcan -- Oppenheimer -- Analyst

Great. Thank you so much.

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Thank you Silvan.

Operator

Thank you. Our next question is from Kennen MacKay from RBC Capital Markets. Your line is now open.

Justin Burns -- RBC Capital Markets -- Analyst

Hi. This is Justin on for Kennen. Thanks for taking my questions. Couple quick ones on 313 from us. Just wondering if you have an idea of the efficacy part? Do you think the FDA is expecting to see approval here? And additionally, what interim analysis are built in here, if any?

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

So as I described earlier on in the prepared remarks, I talked about the design of the study. It's being randomized study comparing the approved checkpoint inhibitor combination and enabling the triplet, primary endpoint, secondary endpoint includes overall survival.

In terms of analysis of we're conducting interim analysis over survival of around about the time of final analysis of PFS and beyond that I can't really, it's very critical.

Justin Burns -- RBC Capital Markets -- Analyst

Okay. And one quick one on the impact of the patient shift for Cabo in Q1. Is this something you expect to continue going forward throughout the quarter? Is this just sort of a one-time seasonality of that? You're not expecting to repeat for the year?

Christopher J. Senner -- Executive Vice President and Chief Financial Officer

Yeah, Justin, this is Chris. I guess, what we look at is we did provide guidance or provided projection here that gross to net would be between 19% and 20% for 2019. And the way to look at it is, what we've seen in 2018 and 2017 is that we start the year with higher growth than that, it goes down, it's part during the year and comes back up at the end of the year. So the expectation is that it will all be within the projection that I provided earlier in my prepared remarks.

Justin Burns -- RBC Capital Markets -- Analyst

Okay. Thank you very much.

Operator

Thank you. Our next question is from Ted Tenthoff from Piper Jaffray. Your line is now open.

Ted Tenthoff -- Piper Jaffray -- Analyst

Great. Thank you very much for taking my question. Congrats on solid quarter. I'm trying to get a sense for beyond RCC liver. Great progress here in terms of expanding the label. Obviously, focus on advancing Cabo combination with different I/O therapies. What are the next kind of most exciting indications we should be looking for in paying attention to? Thank you.

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

So we're actively working on design to improve the trials. And I mentioned some of the indications of interest. So, too early to speak about initiation time frame. But we certainly look forward to updating you on that. But in general, indication include bladder cancer, lung cancer as well as a promising indications that may emerge from the COSMIC-021 study that is ongoing in variances.

Ted Tenthoff -- Piper Jaffray -- Analyst

Yeah. Okay, cool. Makes a lot of sense. All right. Excellent. Thank you guys for the update and thanks.

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Thanks Ted.

Operator

Thank you. Our next question is from Peter Lawson from SunTrust Robinson Humphrey. Your line is now open.

Peter Lawson -- SunTrust Robinson Humphrey -- Analyst

Hi. Thanks for taking my question. Just if I may have missed this, the gross to net, is that higher this year versus last year Q1? And what's the larger-than-expected impact from this quarter versus last year's Q1?

Christopher J. Senner -- Executive Vice President and Chief Financial Officer

Yeah. Peter, this is Chris. So, yes, it's higher this year versus Q1 last year and it's also higher versus Q4 last year. I would say that it's not necessary -- the impact of Medicare durable is not necessary larger than we expected. It was what we expected, but it is larger than prior periods, partly because of the utilization, but also to a large degree based on the fact that discount to beneficiaries that went up from 50% to 70%.

Peter Lawson -- SunTrust Robinson Humphrey -- Analyst

Got you. Is there anyway of quantifying that in dollar terms?

Christopher J. Senner -- Executive Vice President and Chief Financial Officer

No, I wouldn't want to give that level of detail at this point of time.

Peter Lawson -- SunTrust Robinson Humphrey -- Analyst

Okay. And then, just on the level (ph) launch. Just kind of the ability to target medical oncologist versus interventional radiologists, has there been any traction there or any change in the way you're thinking?

P.J. Haley -- Senior Vice President, Commercial

Yeah. Hi, Peter. This is P.J. Thanks for the question. So, we've really been preparing the strategy that target not only medical oncologist, but the key multi-disciplinary teams, certainly the top institutions, which includes the interventional radiologists as well as the hepatologist. Typically, we're seeing good momentum and feedback from those whole teams.

We know some hepatologists are also writing for CABOMETYX, which is encouraging. And I think that's all leading to what we're seeing in terms of having a really nice awareness this early in the launch and as well as sort of those new prescription, and the market share uptake we're seeing and taking shares so quickly from regorafenib.

So, I think the teams got a good strategy in targeting that multi-disciplinary team and really balancing the RCC business where we're getting some -- really some synergy and having incremental account access and RCC discussions as well, which is just sort of creating synergy for the business.

Peter Lawson -- SunTrust Robinson Humphrey -- Analyst

Great. Thanks so much. Thanks for taking the questions.

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Thank you.

Operator

Thank you. Our next question is from George Farmer from BMO Capital Markets. Your line is now open.

George Farmer -- BMO Capital Markets -- Analyst

Hi. Thanks for taking my question. Have the opportunity to dig up some early data that you have with nivo/ipi in Cabo. I guess that was from ASCO-GU last year. I don't know, if this data that we have is stale, but it doesn't look like PFS has been hit and that's study has it's been hit. Is that thing was a Phase 1 study?

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

So, the Phase I study that you're referring to is the Andrea Apolo trial and patients, mixed population of patients with advanced GU tumors. And this has been reported various times. And just to focus on, for instance, the RCC population and previously treated RCC patients. She had observed with the combination to 50% response rate, and this durable responses to P16 wasn't reported at that time. But the patient for treatment for extended periods of time. I think for the urothelial cancer experience good report P16 than it was in previously experienced patients in the order of 13 months or so.

George Farmer -- BMO Capital Markets -- Analyst

Right. So there hasn't been any other updates since, right?

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Not at this time. No.

George Farmer -- BMO Capital Markets -- Analyst

Okay. And to confirm, I don't know you said this, your new Phase 3 the COSMIC-313, is that going to be with low dose Ipi?

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Yeah. The dose was established in the Phase Ib in ipilimumab dose is 1 milligram per kilogram every given schedule.

George Farmer -- BMO Capital Markets -- Analyst

Great. And then with the key note results and the excitement generated by the combining the checkpoint with TKI. We've been hearing from some physicians that there maybe reason why one would want to swap-out in life time replace with CABOMETYX. Do you have any feel for that? Have you done any of your own polling with physicians to see if they may just combine pembro with cabo instead of or maybe sooner after within light ups in the event of some adverse -- more serious adverse events with that combinations?

Michael Morrissey -- President and Chief Executive Officer

Yeah. Hey, George, it's Mike. Fair question. Obviously, that's something we don't want to engage in relative to an unapproved use for Cabo. So, we've heard that shattered too. We'll just stay out of it, because we're not labeled for that, so.

George Farmer -- BMO Capital Markets -- Analyst

Okay. Great. Thanks very much.

Operator

Thank you. Our next question is from Stephen Willey from Stifel. Your line is now open.

Stephen Willey -- Stifel -- Analyst

Yeah. Thanks for taking the question and thanks for all the color, HCC it's helpful. Maybe just a question for P.J. regarding HCC. Should we talk a little bit, maybe just about what the physician feedback is with respect your ability to take market share from like drafted into the second line? Is that a perception around safety, efficacy? Are these patients who, for whatever reasons, just haven't seen prior sorafenib, just curious as to as the kind of what's driving the uptake there?

P.J. Haley -- Senior Vice President, Commercial

Yeah. Thanks for the question, Stephen, and happy to talk about that a bit. As I mentioned, sort of the research we're pleased with the awareness already and the feedback generally, we're pleased with the awareness already and the feedback generally we're getting on the CABOMETYX profile and the CELESTIAL data is very favorable. And kind of -- in terms of looking at efficacy feedback, it's tracking very well relative to the other TKIs. I think the differentiation point has really always been the broad dataset from CELESTIAL, all the different subgroups that patients did not need be tolerant to prior sorafenib. So I think physicians are really looking at it as a drug they can use very flexibly. And that feedback is very strong. And we're seeing that translate into new prescriptions as I mentioned significantly sort of -- or I should say the majority of which are coming from right or at this point.

Stephen Willey -- Stifel -- Analyst

Okay. That's helpful. And then just looking now at COSMIC-021 study, I guess, you got 20 expansion cohorts. I think some of which have been totally enrolled for a while now. Can you maybe just give us a little bit color around just how you are thinking about the communication strategy? And should we be expecting to see presentations related to all these at some point? Should we be expecting to see presentations related to just those indications that you're planning to move forward with? I guess any characterization that would be helpful? Thank you.

Michael Morrissey -- President and Chief Executive Officer

Yeah. Steve, it's Mike. As we've said previously, we're going to speak to and present data from 021 as we have fully enrolled cohorts with long enough follow-up time be able to present stable data. As Gisela has alluded to so many times, we also have the ability to expand cohorts based upon signs of activity that we think are encouraging. So it's a study that is enrolling rapidly and is one that we're certainly very excited in from the standpoint of existing cohorts, but also adding additional cohorts.

As we've said previously, we're in a situation today where we're really focused on presenting mature, stable data. We're trying to avoid a situation where we're kind of leaking out data every meeting three or four times a year, having response rate change, et cetera. We think that's something that we can -- at our current state we should just avoid based upon kind of our -- the overall maturity of our organization.

That being said, you're liable to see us start additional late-stage trials based on the data from 021, probably before you actually see the data supporting that, the good example is liver, where we started 312 recently. Just because we're seeing data on a regular basis, we understand how to make it all fit with the competition and with the value it can bring in the temporal aspects of that. And then as that data matures, we'll get that out.

So lots of moving pieces here. We're excited about the combination. Certainly, the validation and first-line nivo look really encouraging. And we're going full speed ahead.

Stephen Willey -- Stifel -- Analyst

All right. Very helpful. Thank you.

Susan Hubbard -- Executive Vice President of Public Affairs and Investor Relations

Thanks, Steve.

Operator

Thank you. Our next question is from Paul Choi from Goldman Sachs. Your line is now open.

Paul Choi -- Goldman Sachs -- Analyst

Hi. Good afternoon and thank you for taking our questions. Mike, I wanted to ask you now that you have $1 billion plus cash and investments building up here. Just your latest thoughts with regard to business development and either finding strategic assets or entering into partnerships, any additional clinical collaborations here? And just thoughts on un-diversifying the revenue base with respect to other assets, potentially besides cabozantinib?

Michael Morrissey -- President and Chief Executive Officer

Yeah. I mean, the answers are yes, yes, yes and yes. I mean, we're very interested in doing all those things. We talked about that pretty extensively in the past. We have -- as I mentioned in my prepared remarks, we got a pretty broad efforts between research, development, BD, commercial, finance, strategic thoughts as well as about how we go about doing this. We have a pretty high bar for what we're looking for in terms of data, in terms of franchise opportunity, whether it be early stage asset or late-stage asset. But we have a lot of momentum there. And I think the right balance of urgency and energy and focus along with being very pragmatic and very thoughtful.

And you're right. We generated $1 billion in cash and we've earned that, right? And we want to make sure that we maximize its potential going forward in terms of, again, building up a broad early stage pipeline, diversifying across morality, diversifying across pathways in different approaches, as well as looking at late stage, mid-stage, early stage asset.

So we've got a lot going on. And again, I don't feel any pressure to do a deal, just to do a deal to spend that money. It's the contrary. We want to make sure that we maximize the value of those -- that hard earned cash that we've got and then we can then catalyze that to grow the business going forward.

So a lot going on as we finish some of these transactions and there's meeting in the queue, we will make sure to update you on a why them and what we like about them as well as how we think that will fit into our portfolio.

Paul Choi -- Goldman Sachs -- Analyst

Okay. Thanks for that. And then I had, I guess, a clinical question, with regard to COSMIC-313, you're focusing on the poor and intermediate risk population similar to what was studies as a priority in the CheckMate 214 study. But just with regard to testing this -- triple combination in a favorable risk population, I was wondering if you could give your thoughts there?

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Yeah, we focused on the poor and intermediate risk population for exactly the reason that you're stating, the approval for those 214 versus that was achieved by the 214 study, when we were ipi in this patient population. So we wanted to build on this outcome. And also, I think, it's fair to say the poor and the intermediate risk population obviously is -- in greater need if you will for additional effective therapy. So that's really the dimensional.

Paul Choi -- Goldman Sachs -- Analyst

And any thought to test the triplet in the favorable risk population?

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Not immediately, but that may come in the future.

Paul Choi -- Goldman Sachs -- Analyst

Okay, Thank for that. I'll let others jump in to queue here.

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Thanks, Paul

Operator

Thank you. Our next question is from Asthika Goonewardene from Bloomberg Intelligence. Your line is now open

Asthika Goonewardene -- Bloomberg Intelligence -- Analyst

Hi, guys and thanks for taking my question. So looking at 426 in JAVELIN, we saw some slight differences in the PFS into OS on the line marking analysis is particularly upfront under analysis there between the two studies. And I asked this question last quarter and like you said you will need to see the data to really comment. And now that we've seen the data, I wanted to get your view on in which of these two trials suite in time behave more like what you would expect in the real-life setting? And I have a follow up after.

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Yes. You're asking first trial comparison and those are obviously difficult in fact was errors and issues. I think importantly one were to look at composition of the patient population. And, in particular, the risk categories and they were not identical. You look at these two studies in terms of what one would expect, of course, to mention as I think there is range of expectation, of course, and I think we look forward to the outcome of CheckMate 9ER study and on -- that makes sense so we won't comment on the specifics of outcome here.

Asthika Goonewardene -- Bloomberg Intelligence -- Analyst

Okay. And then, of course, the synergy between PD-1 and TKIs what makes the combo with -- the CABO particularly attractive, but when we had CABO nivo, CABO Nivo ipi. You know, obviously would expect more toxicity. I'm curious to know what are the -- what kind of dose reductions are allowed -- were allowed in 9ER and you plan on allowing on 313? And then also maybe what gives you the confidence that if you do a lot of these dose reductions in CABO, what gives you confidence that this low-dose of CABO has enough exposure to generate these hypothetical synergistic effects with PD-1?

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Yes. Certainly, to answer detail question, and the study quarter close as one really expect. There are provisions for dose reductions and in order to safeguard patients and they are very much in line with one would expect. So in response to internal cabozantinib internal are dose reduction or dose we're seeing and the same growth also in terms of dose for the checkpoint inhibitor. So I won't go into all this detail as the protocol. So I think that the general approach. Regarding cabozantinib exposure with presented and published exposure response analysis with single agent cabozantinib and know that even though cabozantinib maintain, so I think appropriate dose management for adverse events is expected to maintain actually

Michael Morrissey -- President and Chief Executive Officer

Yes, and I would just add that -- based on the Phase Ib experience where we see high response rates long, durable response with the doublet, the triplets, et cetera -- we feel pretty comfortable starting at 40 and then being able to see a response and then maintain that response as patients move -- forward in their treatments, if dose reduction a hold is needed, the data would support they can still maintain that response. So got good data they. We feel good about and very excited to get the 313 going and also see the results from 9ER.

Asthika Goonewardene -- Bloomberg Intelligence -- Analyst

Excellent. Thanks guys. Looking forward to see you.

Susan Hubbard -- Executive Vice President of Public Affairs and Investor Relations

Yes. Thank you.

Operator

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

Susan Hubbard -- Executive Vice President of Public Affairs and Investor Relations

Thank you, Gigi, and thank you all for joining us today. We certainly welcome your follow-up calls and any questions that we weren't unable to address in today's call.

Operator

Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program. You may now disconnect.

Duration: 73 minutes

Call participants:

Susan Hubbard -- Executive Vice President of Public Affairs and Investor Relations

Michael Morrissey -- President and Chief Executive Officer

Christopher J. Senner -- Executive Vice President and Chief Financial Officer

P.J. Haley -- Senior Vice President, Commercial

Gisela M. Schwab -- President, Product Development and Medical Affairs and Chief Medical Officer

Andy Hsieh -- William Blair -- Analyst

Yaron Werber -- Cowen -- Analyst

Michael Schmidt -- Guggenheim -- Analyst

Silvan Turkcan -- Oppenheimer -- Analyst

Justin Burns -- RBC Capital Markets -- Analyst

Ted Tenthoff -- Piper Jaffray -- Analyst

Peter Lawson -- SunTrust Robinson Humphrey -- Analyst

George Farmer -- BMO Capital Markets -- Analyst

Stephen Willey -- Stifel -- Analyst

Paul Choi -- Goldman Sachs -- Analyst

Asthika Goonewardene -- Bloomberg Intelligence -- Analyst

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