Q4 2020 Exelixis Inc Earnings Call

Good day, ladies and gentlemen, and welcome to the ex <unk> fourth quarter and full year 'twenty and 'twenty financial results Conference call. My name is Latif and I will be your operator for today as a reminder of this call is being recorded for replay purposes.

Operator: Today, ladies and gentlemen, and welcome to the Exelixis fourth quarter and full year 2020 financial results conference call. My name is Lateef, and I will 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 T. Hubbard: 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. Thank you, Latif, and thank you all for joining us for the Exelixis fourth quarter and full year 2020 financial results conference call. Joining me on today's call are Mike Morrissey, our President and CEO, Chris Senner, our Chief Financial Officer, Gisela Schwab, our Chief Medical Officer, and P.J.

Thank you Latif and thank you all for joining us for the <unk> fourth quarter and full year 2020 financial results conference call joining.

Joining me on today's call are Mike Morrissey, our president and CEO, Chris Senner, Our Chief Financial Officer, Keith for swap of our Chief Medical Officer and P. J Haley our executive Vice President of commercial who will together review of our corporate financial development and commercial progress for the fourth quarter 2020 ended December 31 2020.

Susan T. Hubbard: Haley, our Executive Vice President of Commercial, who will together review our corporate, financial, development, and commercial progress for the fourth quarter of 2020 and December 31, 2020. Peter Lamb, our Chief Scientific Officer, is also here and will join us for the question and answer session following our prepared remarks. During the call, we will refer to financial measures not calculated according to generally accepted accounting principles.

Peter Lamb, our Chief Scientific Officer is also here and will join US for the question and answer session. Following our prepared remarks.

During the call 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 the tables deriving these measures from our GAAP results.

Susan T. Hubbard: 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 discovery, product development, regulatory, commercial, financial, and strategic matters. However, actual events or results could, of course, differ materially.

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 discovery product development regulatory and commercial financial and strategic matters and actual events or results could of course differ materially we refer you to the documents we file from time.

Susan T. Hubbard: We refer you to the documents we file from time to time with the SEC, which, under the heading Risk Factors, identify important factors that could cause actual results to differ materially from those expressed by the company verbally and in writing today, including, without limitation, risks and uncertainties related to product commercial success, market completion, regulatory review and approval processes, conducting clinical trials, compliance with applicable regulatory requirements, our dependence on collaboration partners, and the level of costs associated with discovery, Now, with that, I will turn the call over to Mike.

And the time with the SEC, which under the heading risk factors and 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 completion regulatory review and approval processes conducting clinical.

While the compliance with applicable regulatory requirements, our dependence on collaboration partners and the level of costs associated with discovery product development and business development and commercialization activities and with that I will turn the call over to Mike Alright. Thank you Susan and thanks to everyone for joining us on the call today ex the Lexus ended 2021.

Susan T. Hubbard: All right. Thank you, Susan, and thanks to everyone for joining us on the call today. Exelixis ended 2020 with a strong fourth quarter and hit the ground running in January as we strive to accelerate revenue growth in 2021 and beyond with the Cabo Nevo launch and first-line RCC and a variety of mission-critical development and regulatory milestones. Please see our press release that was issued an hour ago for our fourth quarter and full year 2020 financial results and an extensive list of key corporate accomplishments.

The strong fourth quarter hit the ground running in January as we strive to accelerate revenue growth and 2021 and beyond with the combo of needle launch and first line RCC and a variety of mission critical development and regulatory milestones.

Please see our press release that was issued an hour ago for our fourth quarter and full year 2020 financial results and an extensive list of key corporate accomplishments well.

And we'll keep our prepared remarks short today as we head of full update recently at the Jpmorgan Health care conference, including providing 2021 financial guidance.

Susan T. Hubbard: We'll keep our prepared remarks short today, as we gave a full update recently at the J.P. Morgan Health Care Conference, including providing 2021 financial guidance. Obviously, we're thrilled with the recent approval for the Cabo Nevo combination and Firstline RCC based on the positive results from the Checkmate 9 ER pivotal trial. We believe we have significant momentum heading into the launch and anticipate a near doubling of Cabo RCC revenues by the end of 2022, when we expect to exit with a $1.5 billion annualized run rate in the U.S., if our assumptions and modeling are correct.

Honestly, we're thrilled with the recent approval for the Cabo and ego combination and first line RCC based on the positive results from the Checkmate <unk> pivotal trial.

We believe we have significant momentum heading into the launch and anticipate a near doubling of Cabo RCC revenues by the end of 2022, when we expect to exit with the one $5 billion annualized run rate and the U S. If our assumptions and modeling are correct.

This week will be busy for us as we share a number of important clinical updates for the Cabozantinib and <unk>, both as a single agent and ICI combination partner and.

In addition over the course of 2021, we foresee a broad slate of important discovery clinical and regulatory milestones, including the first three potential SMB of submissions seconds of the two additional ind's third advancing the cabozantinib cosmic and contract clinical trials for.

Michael M. Morrissey: This week will be busy for us as we share a number of important clinical updates for Cabozantinib at ASCOGU, both as a single agent and as an ICI combination partner. In addition, over the course of 2021, we foresee a broad slate of important discovery, clinical, and regulatory milestones, including, first, three potential SNDA submissions, second, up to two additional INDs, third, advancing the Kabo Zantenib cosmic and contact clinical trials, and fourth, building the XL092 full development program.

Force building the XL <unk> and two full development program fifth the early evaluation of our new clinical stage molecules XL, why don't you and XP and <unk> and finally, six advancing a deep bench of exciting discovery programs toward development candidate status.

It goes without saying that 2021 will be an action packed year for the ex what's his team and we're working as one to maximize the chance of success across the range of milestones ahead of us I'm incredibly proud of the commitment and focus displayed by the entire team and 2020 and excited for the future as we drive our business forward during these challenging times.

And so with that I'll turn the call over to Chris who will provide an update on our fourth quarter and full year 2020 financial results. Thanks, Mike for the fourth quarter 2020 of the company reported total revenues of $270 $1 million total revenues for the quarter included Cabozantinib franchise net product revenues of $204 million.

Michael M. Morrissey: Fifth, the early evaluation of our new clinical stage molecules, XL102 and XB002. And finally, sixth, advancing a deep bench of exciting discovery programs toward development candidate status. It goes without saying that 2021 will be an action-packed year for the Exelixis team, and we're working as one to maximize our chance of success across the range of milestones ahead of us.

Net product revenues and the fourth quarter of 2020 were positively impacted by higher demand and by an increase and wholesaler inventory cosmetics wholesaler inventory increase from approximately $2 eight weeks on hand to approximately $3 one weeks on hand.

Total revenues also included $69 $7 million and collaboration revenues from Ipsen, and Takeda and Genentech.

Our operating expenses for the fourth quarter of 2020 for $245 8 million.

Compared to $273 7 million and the third quarter 2020, R&D expense was the primary driver of the decline and operating expenses, which declined by approximately $27 $9 million and was primarily related to declines and stock based compensation expense.

Christopher J. Senner: I'm incredibly proud of the commitment and focus displayed by the entire team in 2020 and excited for the future as we drive our business forward during these challenging times. So with that, I'll turn the call over to Chris, who will provide an update on our fourth quarter and full year 2020 financial results. Thanks, Mike. For the fourth quarter of 2020, the company reported total revenues of $270.1 million. Total revenues for the quarter included composited and franchised net product revenues of $200.4 million.

Clinical trial related expenses, and licensing and milestone fees associated with the existing and new business development activities.

Benefit from income taxes for the fourth quarter, 2020 was $300000 compared to $6 million for the third quarter of 2020 of the company reported GAAP net income.

The $28 4 million or <unk> <unk> per share on a fully diluted basis for the fourth quarter 2020 of the company also reported non-GAAP net income of $43 2 million or <unk> 14 per share on a fully diluted basis.

Non-GAAP net income excludes the impact of approximately $15 million of stock based compensation expense net of the related income tax effect cash and investments for the quarter ended December 31, and 2020 was over $1 $5 billion.

Christopher J. Senner: Net product revenues in the fourth quarter of 2020 were positively impacted by higher demand and by an increase in wholesaler inventory. However, wholesaler inventory increased from approximately 2.8 weeks on hand to approximately 3.1 weeks on hand. Total revenues also included $69.7 million in collaboration revenues from Ipsen, Takeda, and Genente. Our operating expenses for the fourth quarter of 2020 were $245.8 million, compared to $273.7 million in the third quarter of 2020. R&D expense was the primary driver of the decline in operating expenses, which declined by approximately $27.9 million and was primarily related to declines in stock-based compensation expense.

Now turning to our financial guidance for the full year of 2021, which we previewed at the Jpmorgan conference in January.

Total revenues are projected to be and the range of $1. One five of $1 $25 billion net product revenues are projected to be and the range of the $950 million.

And one point of <unk> 5 billion cost of goods sold is projected to be between 5% and 6% of net product revenues for you.

Search and development expenses projected and the range of 600 and $650 million includes non cash expenses related stock based compensation of approximately $45 million.

Selling general and administrative expense is projected to be and the range of 375% and $425 million and includes noncash expenses related to stock based compensation of approximately $60 million.

Guidance for the effective tax rate in 2021 is between 20 and 22% and finally, we are projecting cash and investments to be and the range of $1 six and $1 7 billion.

The R&D expense and cash and investment guidance does not include the impact of any potential new business development activities and with that I'll turn the call over to Gisela.

Thank you, Chris and we've made great progress during the last few months of crunchy trenching and are off to a great start and 'twenty 'twenty, one and Pete to provide a brief update and now of Cabozantinib regulatory and development program highlights of progress for XL on a true and new compounds moving of tour.

Christopher J. Senner: Clinical Trial Related Expenses and Licensing and Milestone Fees Associated with the Existing and New Business Development Act, Benefit from income taxes for the fourth quarter of 2020 was $300,000 compared to $6 million for the third quarter. The company reported a gap net income of $28.4 million or $0.09 per share on a fully diluted basis for the fourth quarter of 2020. The company also reported non-gap net income of $43.2 million, or $0.14 per share on a fully diluted basis.

Its clinical evaluation.

And I'll focus on a preview of <unk> 'twenty 'twenty one and.

And the main topics today.

Starting with Checkmate <unk> and 90, our interest recently on January 22nd we announced the approval by FDA for the Cabozantinib and the volume up a combination of for the first line treatment of patients with advanced RCC.

The FDA review of the parallel Psi and filings of ex Alexis and BMS under the Artur or real time oncology of review program that enables F. D. A to expedite its review of regulatory submissions for the life threatening conditions and we are delighted that the approval right.

Christopher J. Senner: Non-GAAP net income excludes the impact of approximately $15 million of stock-based compensation expense net of the related income taxes. Cash and Investments for the quarter ended December 31, 2020 was over $1.5 billion. Now turning to our financial guidance for the full year 2021, which we previewed at the JP Morgan conference in January. Total revenues are projected to be in the range of $1.15 and $1.25 billion. Net product revenues are projected to be in the range of $950 million and $1.05 billion.

Wanted well ahead of <unk>.

Could do for the date of February 20th 'twenty 'twenty one.

F D a to approval, but based on demonstration of superiority for Cabozantinib obsessed and your volume up.

Paired with Sunitinib for all three efficacy endpoints progression free survival overall survival and objective response rate.

Additionally, the combination of Cabozantinib ex 14 milligrams QD and the volume up was generally well tolerated and associated with a low discontinuation rate.

Christopher J. Senner: Cost of goods sold is projected to be between 5% and 6% of net product revenues. Research and development expenses project to be in the range of $600 and $650 million and include non-cash expenses related to stock-based compensation of approximately $4,500. Selling General Administrative Expenses is projected to be in the range of $375 and $425 million and includes non-cash expenses related to stock-based compensation of approximately $60 million.

Detailed results of the study were presented for the first time by Dr. Tony Crary.

Virtual ESMO conference and the presidential Symposium.

The presentation also included a high level analysis of health related quality of life or H R. Q O L.

And despite the fact of the study enrolled the patient population with a higher proportion of intermediate and poor risk for I M. D C as well as a lower proportion of patients with nephrectomy compared to other first time trials in RCC and the high level of quality of life results included and the primary of.

Analysis showed improved quality of life by functional assessment of cancer therapy, kidney symptom index and 19 are fixed and 19 for.

Christopher J. Senner: Guidance for the effective tax rate in 2021 is between 20 and 22%. And finally, we're projecting cash investments to be in the range of $1.6 and $1.7 billion. The R&D Expense and Cash Investment guidance does not include the impact of any potential new business development activities.

The combination of Cabozantinib and the volume up as compared to Sunitinib.

We look for but the more detailed presentation of the HR QL results and ask could you the Dr. David Chiller and do we think these results may provide important additional differentiation for the cargo neighborhood duplet compared to other first line of Teekay I O options.

Gisela Schwab: And with that, I'll turn the call over to Gita. Thank you, Chris. We've made great progress during the last few months of 2020 and are off to a great start in 2021. And I'm pleased to provide a brief update on our Carboxyntinib Regulatory and Development Program, highlighting our progress for XL092, and new compounds moving towards clinical evaluation. And I'll focus on a preview of ASCO G.U. 2021 as the main topic today.

Turning to the ongoing phase III program for Cabozantinib.

And we have continued our efficient execution of cosmic the euro to one of 311 312 and 313 studies.

And I'd have either completed or are nearing the full enrollment on a global level.

And we have either completed or are on track for top line results for these trials and as previously shared and I'll provide a brief summary on key highlights for the program.

For the cosmic 311.

And radioiodine refractory DTC patients who have received prior virtue of for our targeted therapy, we announced in December 'twenty and 'twenty that the trial met its primary endpoint of progression free survival with cabozantinib highly significantly improving PFS versus <unk>.

Gisela Schwab: Starting with CHECKMATE 9ER, a test recently released on January 22nd, we announced the approval by FDA for the carbazantinib and nivolumab combination for the first-line treatment of patients with advanced RCC. The FDA reviewed the parallel filings of Exelixis and BMS under the RTOR, or Real-Time Oncology Review Program, that enables FDA to expedite its review of regulatory submissions for Life-Threatening Conditions, and we are delighted that the approval was granted well ahead of the set PDUFA date of February 20, 2021.

With people with a 78% reduction and the risk of disease progression or death.

Belting and a hazard ratio of <unk>.

For a point to true that was highly statistically significant with a P value of less than zero point here is he or she or one.

We are working towards a supplemental NDA submission based on the strong results and the patient population with unmet medical need.

Gisela Schwab: FDA's approval was based on demonstration of superiority for carbazantinib plus nivolumab compared with solitinib for all three efficacy endpoints, progression-free survival, overall survival, and objective response rate. Additionally, the combination of carboxyantin at 40 milligrams QD and nivolumab was generally well tolerated and associated with a low discontinuation rate. Detailed results of the study were presented for the first time by Dr. Tony Tueri at the recent virtual ESMO conference and the Presidential Symposium. The presentation also included a high-level analysis of health-related quality of life, or HRQOL.

Cosmic 312 of our phase III trial of Cabozantinib, plus the cheese the lease them up versus Sorafenib for the first line treatment of advanced HCC completed a cool and the global study and mid 'twenty 'twenty and we anticipate top line results of the event driven analysis of PFS.

And the concurrent interim analysis of overall survival and the first half of 'twenty 'twenty one.

And of Cosmic 313, comparing the triplet of Cabozantinib net volume up and keeping them up versus new volume up and picking them up and first line RCC patients with intermediate or poor risk for I M. D. C is expected to reach its expanded accrual goal of eight turns out and the 40.

Gisela Schwab: And despite the fact that the study enrolled a patient population with a higher proportion of intermediate and poor risk per IMDC, as well as a lower proportion of patients with nephrectomy compared to other first-line trials in RCC, the high-level quality of life results included in the primary analysis showed improved quality of life by functional assessment of cancer therapy kidney symptom index 19, or 6019, for the combination of cabozant We look forward to the more detailed presentation of the HRQL results at ASCO-GU by Dr. David Scheller, as we think these results may provide important additional differentiation for the carbon nebo-duplet compared to other first-line TKIIO options.

And shortly.

As a reminder of we had expanded enrollment and cosmic from 15 following presentation of updated long term follow up results from the Checkmate 214.

Showing a longer median overall survival of <unk>.

48 months for the new volume up and you can name them up combination than originally assumed when would you find the cosmic 315 trial.

We look forward to the event driven analyses for the study and 2022.

For the cosmic your true born and we look forward to final analysis of the objective response rate by independent Radiology Committee of cohort six and the metastatic of TRP searching and meet the <unk> trend.

Gisela Schwab: Turning to the ongoing Phase 3 program for Cabo San Ginebra, we have continued our efficient execution of COSMIC 021, 311, 312, and 313 studies that have either completed or are nearing full enrollment on a global level.

And two you want and.

And we are planning for regulatory submissions of the results data providing.

And importantly, we're happy to report that all three phase III trials and all of collaboration program with Roche and the contact Phase III program of Act.

Gisela Schwab: And we've either completed or are on track for top-line results for these trials, as previously shared. And I'll provide a brief summary on key highlights for the program for Cosmic 311, and Radioiodine Refractory DTC patients who have received a prior VEGF-R targeted therapy. We announced in December 2020 that the trial met its primary endpoint of progression-free survival, with cabozantinib highly significantly improving PFS versus placebo with a 78% reduction in the risk of disease progression or death, resulting in a hazard ratio of 0.22 that was highly statistically significant with a P-value of less than 0.0001.

Actively enrolling patients globally.

So looking back on this quarter I am thrilled with the regulatory and clinical development progress for the Cabozantinib program and the high level of execution, but both of our own teams and our clinical partners.

I'll now turn to the progress on all the Excel on line two program and are Nick and.

New R&D projects.

First the extra on a true Oh and next generation met Axel Merck and virtue of far tyrosine kinase inhibitor with a shortage of pharmacokinetic half life is advanced and quickly and we are in the midst of evaluating the combination with the change the lease them up and a parallel phase one be part of.

The study while completing the single agent dose range study.

Gisela Schwab: We are working towards a supplemental NDA submission based on these strong results in a patient population with unmet medical needs. COSMIC 312, our phase 3 trial of carbazantinoplastatozolizumab versus serafinib, where the first-line treatment of advanced HCC completed a cool in a global study in mid-2020.

As discussed on the third quarter call or excel or non two development plan includes a broad and comprehensive program.

Cross various tumor indications.

The RP and settings of broad therapeutic interest.

We intend to pursue the comprehensive evaluation of XL and I to income.

Combination with various established of checkpoint inhibitors and.

Gisela Schwab: And we anticipate top-line results of the event-driven analysis of PFS and the concurrent interim analysis of overall survival in the first half of 2021. COSMIC-313, comparing the triplet of cabozantinib, nivolumab, and ipilimumab versus nivolumab and ipilimumab in first-line RCC patients with intermediate or poor risk As a reminder, we expanded enrollment in COSMIC-313 following presentation of updated long-term follow-up results from the TechMate-214 study showing a longer median overall survival of 48 months for the Nevolumab and Ipilimumab combination than originally assumed when we designed the COSMIC-313 trial.

And potential new combinations, including promising new checkpoint inhibitor duplex and spot.

Well it is other combination partners.

With the goal to potentially start and late stage trials as soon as 'twenty 'twenty. One we are focusing on advancing the phase <unk> dose ranging and combination with checkpoint inhibitors rapidly to move into expansion cohorts that may support data to prevent late stage development options.

Across a variety of tumor types.

And secondly, we are excited to initiate studies with our latest IMD candidates and 'twenty 'twenty one.

And with recently announced initiation of the XL one O two phase one trial and we plan to file and I N D for XP, Oh, Oh true and antibody drug conjugate or ADC targeting tissue factor shortly following completion of product release assay.

Gisela Schwab: We look forward to the event-driven analyses of Weber's study in 2020. For COSMIC-021, we look forward to a final analysis of the objective response rate by the Independent Radiology Committee of COVID-6 in the metastatic CRPC setting in mid-2021.

For both the new I N D compounds in phase one trials are designed and efficient dose escalation trials.

And with a disease specific expansion cohorts true.

Now for early assessment of initial antitumor activity and.

Gisela Schwab: And importantly, we're happy to report that all three phase three trials in our collaboration program with Roche, the contact phase three program, are actively enrolling patients globally. So looking back on this quarter, I am thrilled with the regulatory and clinical development progress for the Carbozantinib program and the high level of execution by both our own teams and our clinical partners. I'll now turn to the progress on our Excel 092 program and our next new IND project. First, Exel-092, our next generation MET, AXL, MIR, and VEGFR tyrosine kinase inhibitor with a shorter pharmacokinetic half-life, is advancing quickly.

And I look forward to updating you on progress on our clinical pipeline and the future.

And lastly is the virtual <unk> conference is starting this week I'd like to provide a brief overview of some key presentations for Cabozantinib at the conference.

We look forward to the presentation by Dr. Motzer of updated results with a longer follow up of toward the checkmate non New York trials.

And as you've seen in the abstract but are now online and also and our own press release. The efficacy of results are consistent with the early of presentation and demonstrate sustained efficacy across all key endpoints of overall survival progression free survival and the objective response rate and <unk>.

And increased and the CR rate was for the follow up.

Additionally, patients with sarcoma, histology and traditionally difficult to treat patient population derives significant and consistent benefits from the combination of cabozantinib and the volume up.

Gisela Schwab: And we are in the midst of evaluating the combination with atezolizumab in a parallel phase 1B part of the study while completing the single agent dose range. As discussed on the third quarter call, our Excel 092 development plan includes a broad and comprehensive program across various tumor indications, lines of therapy, and settings of broad therapeutic interest. We intend to pursue the comprehensive evaluation of XL092 in combination with various established checkpoint inhibitors and potential new combinations, including promising new checkpoint inhibitor duplets, as well as other combination partners.

And as I mentioned earlier, we will also see a detailed presentation by Dr. David Keller of the patient reported outcomes on health reported quality of life from Checkmate 90 yard.

And the high level, the combination of Cabozantinib and the volume up resulted in improved quality of life as compared to Sunitinib.

Reduction and disease related symptoms and a significantly extended the time to confirmed deterioration of quality of life.

Gisela Schwab: With the goal to potentially start late-stage trials as soon as 2021, we are focusing on advancing the Phase 1b dose ranging in combination with checkpoint inhibitors rapidly to move into expansion cohorts that may support data-driven late-stage development options across a variety of tumor types. And secondly, we are excited to initiate studies with our latest IND candidates in 2021. We have recently announced the initiation of the Excel 102 Phase 1 trial, and we plan to file an IND for XB002, an antibody drug conjugate or ADC targeting tissue factor, shortly following completion of product release. For both new IND compounds, phase one trials are designed as efficient dose escalation trials with a disease-specific expansion cohort to allow for early assessment of initial anti-tumor activity, and I look forward to updating you on progress The conference is starting this week; I'd like to provide a brief overview of some key presentations for Carbozantrinib at the conference.

For the final results of the phase one b trial of Cabozantinib lessened the volume up alone.

And the volume up and appealing them up and patients with advanced Genitourinary malignancies will be presented and a rapid oral presentation by Dr Paulo.

This phase one B study laid the foundation for the dose selection of Cabozantinib of 40 milligrams daily for the combination with new volume up and for the triplet combination, including also Italy and move up.

And I response rates were seen in RCC and in Europe, the oil cancer, and also and Reg U malignancies.

Durable responses and and encouraging median overall survival of $15 nine months, we're seeing and this phase one trial, including heavily pretreated patients with various G U malignancies.

And Fortunately, we will also see the first presentation of the NCIC check of sponsored tap merge or swap. The 1500 trial results and papillary RCC by Justice and bunch of Paul as part of the oral presentation session on February 13.

He will present the results of a for arm randomized trial, comparing each of three experimental arms of <unk>.

Gisela Schwab: We look forward to the presentation by Dr. Mozart of updated results with a longer follow-up for the CHECKMATE-9ER trial. As you have seen in the abstracts that are now online and also in our own press release, the efficacy results are consistent with the earlier presentation and demonstrate sustained efficacy across all key endpoints of overall survival, progression-free survival, and objective response rate, including an increase in the CR rate with further follow- Additionally, patients with sarcomatoid histology, a traditionally difficult-to-treat patient population, derived significant and consistent benefit from the combination of carbazantinib and nivolumab.

Cabozantinib tablet unit and Chrisette unit versus Sunitinib.

The guideline recommended therapy for papillary RCC.

While both established Tennessee, and Kentucky Nib arms for discontinued as a result of planned futility analyses.

Zanten of demonstrated superior PFS over to niche and it and this randomized phase two trial.

And lastly, there will be and intriguing retrospective analysis of Cabozantinib and.

And the RCC patients with brain metastases presented by Dr. Laura Perish and Dr. Tony true Aerie, showing and encouraging high interest cranial and systemic response rate and this patient population with difficult to treat disease.

Gisela Schwab: As mentioned earlier, we will also see a detailed presentation by Dr. David Keller of the patient-reported outcomes on health reported quality of life from Checkmate 9 ER. At a high level, the combination of carbazantinib and nivolumab resulted in improved quality of life as compared to fenutinib, with a reduction in disease-related symptoms and a significantly extended time to confirmed deterioration of quality of life.

Yeah, very much looking forward to these presentations and to all of the new results of asks do you and 21.

And hope that you will be able to join us for our investor briefing on February 13 at 530 P. M. Eastern two here renowned RCC experts Dr. Tony true Aerie joked of Daniel George After some bunch of Paul and Dr Green of them Okay.

Gisela Schwab: Further, final results of the Phase 1b trial of carbazan kinep plus nivolumab alone or nivolumab and ipilimumab in patients with advanced genitourinary malignancies will be presented in a rapid oral presentation by Dr. Apollo. This Phase 1b study laid the foundation for the dose selection of carbazantinib of 40mg daily for the combination with High response rates were seen in RCC and in urothelial cancer and also in rare G.E.U. molecules.

Discuss the most recent important trial results and RCC that will be presented at the conference and provide their expert opinion and further context on the implications for the clinical management of patients with advanced RCC.

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

Thank you Gisela I am pleased to discuss the <unk> business with regards to queue for 2020, and importantly to discuss the first combination of approval for <unk> <unk>.

Gisela Schwab: Durable responses and an encouraging median overall survival of 15.9 months were seen in this Phase 1 trial, including heavily pretreated patients with various GU malignancies. Importantly, we will also see the first presentation of the NCIC-TIP-sponsored PAPMED or SWOG 1500 trial results in papillary RCC by Dr. Sumanta Pal as part of the oral presentation session on February 3rd. He will present the results of a four-arm randomized trial comparing each of the three experimental arms of cabozantinib, sabolitinib, and crizotinib versus zunitinib. The guideline recommended therapy for papillary RCC.

<unk> received approval for use in first line RCC and combination with Napoleon up on January 20, <unk> and the team immediately began promotion of the.

The strong 90 of our data and recent approval position and the Cabozantinib franchise to return to significant revenue growth.

<unk> ended the year with the strong Q4, and we expect the launch of 90 or to build on that momentum. Additionally.

Additionally, potential growth could be further driven by data readouts and other important indications as the robust combo development program continues to generate data.

I will discuss the opportunity that 90 or provides excellent and looking forward as we continue to build upon the foundation and RCC, where we remain the number one prescribed single agent <unk>.

Before turning to 90 or I will highlight a few of the key metrics for Q4.

And our ex volume for <unk> increased by 8% and Q4 relative to Q3.

And while the overall and our ex market volume was stable.

Patrick J. Haley: While both the sabolitinib and crizotinib arms were discontinued as a result of planned futility analyses, cobizantinib demonstrated superior PFS over sunitinib in this randomized phase 2 trial. And lastly, there will be an intriguing retrospective analysis of Kabozantinib's effect in RCC patients with brain metastases, presented by Dr. Laura Hirsch and Dr. Tony Tueri, showing an encouraging high intracranial and systemic response rate in this patient population with difficult-to-treat disease. We are very much looking forward to these presentations and to all the new results of ASCQ-GU21 and hope that you will be able to join us for our investor briefing on February 13 at 5.30 p.m. Eastern to hear renowned RCC experts Dr. Tony Tureri, Dr. Daniel George, Dr. Sumanta Pal, and Dr. Raina McKay discuss the most recent important trial results in RCC that will be presented at And with that, I will hand the call over to PJ. Thank you, Gisela.

This translated to an increase of intermec share from 30% to 32% for <unk>.

The increase of prescriptions in Q4 was primarily driven by growth and second line RCC, new patient market share is more of ICI experienced patients have progressed to the second line setting.

Turning to the first line.

The ICI combination opportunity is large and with 15000 RCC patients and the U S eligible for treatment.

With ICI combination therapy, consisting of approximately 80% of that market.

According to this brand impact data ICI combinations constitute about 50% of the first line share and are widely used across clinical risk groups, demonstrating the broad potential for <unk> with Nemo and the first line setting.

<unk> was approved in RCC over 40 years ago.

During this time it has developed very strong brand equity and is viewed as the best in class PKI in RCC.

The excellence of the team has significant experience and RCC with two prior successful launches and we look forward to this opportunity to educate physicians on the 90 of our data. So the more patients can benefit from Kabul medical therapy, and the first line.

The strength of the 90 of our data speaks for itself the doubling of medium progression free survival and <unk> and.

Superior overall survival for cylinder.

Importantly, clinical benefits were observed and the vast majority of patients from the trial, resulting in a low rate of primary progression, regardless of <unk> risk status for patient subtype supporting broad use in the marketplace.

Patrick J. Haley: I'm pleased to discuss the Cabo Medics business with regard to Q4 2020, and importantly, to discuss the first combination approval for Cabo Medics. Cabo Medics received approval for use in First Line RCC in combination with Novolumab on January 22nd, and the team immediately began promotion. The strong 90-hour data and recent approval position the Cabo Zanthine franchise to return to significant revenue growth. Cabo Medics ended the year with a strong Q4, and we expect the launch of 9ER to build on that momentum.

In addition, the.

Optimized carbo combination starting dose of 40 milligrams daily yielded a compelling safety and tolerability profile, along with the low treatment discontinued discontinuation rate and favorable and quality of life all of which has been notable with physicians and our research and discussions.

<unk>.

The 90 or data for particularly impressive when considered in the context of the challenging patient population enrolled and the study which had more IMD see poor risk patients and fewer patients with nephrectomy use than any other than other phase III studies and first line RCC.

Patrick J. Haley: Additionally, potential growth could be further driven by data readouts and other important indications as the robust Cabo development program continues to generate. I will discuss the opportunity that 9ER provides Exelixis looking forward as we continue to build upon the foundation in RCC, where we remain the number one prescribed single agent TKF. Before turning to 9ER, I will highlight a few of the key metrics from Q4. NRX volume for Coppomedics increased by 8% in Q4 relative to Q3, while the overall NRX market volume was stable.

Taken together the combination of of best in class <unk> combo with a well established immune checkpoint inhibitor like nimble enough and RCC supported by a strong efficacy and safety data from Checkmate <unk> presents excellent exist with the opportunity to share of compelling and highly motivating story to our customers.

And to enable broad positioning across all clinical risk groups and first line RCC.

Feedback on the Checkmate <unk> 90 of our data with both academic and community oncologists as the positive and we believe we can leverage the success of the prescriber familiarity of both Cabo and the Nemo to gain traction quickly and the combination setting.

Patrick J. Haley: This translated to an increase in NRX share from 30% to 32% for Cabo Meta. The increase in prescriptions in Q4 was primarily driven by growth in second-line RCC new patient market share as more ICI-experienced patients have progressed to the second-line setting. Turning to the first line,

There's a great deal to be excited about as we think about the totality of the combo medics RCC business looking forward.

With regards to the launch of 90 or we are extremely pleased with the rapid execution of our experienced team, which was well prepared and is deeply experienced and the RCC market.

Patrick J. Haley: The ICI combination opportunity is large, with 15,000 RCC patients in the U.S. eligible for treatment, with ICI combination therapy accounting for approximately 80% of that market. According to this brand impact data, ICI TKI combinations constitute about 50% of the first line share and are widely used across clinical risk groups, demonstrating the broad potential for COBLOMEDICS with NEVO in the first line setting. Cabo Medics was approved in RCC over four years ago, and during that time, it has developed very strong brand equity and is viewed as the best in class TKI in RCC.

<unk>, reaching out to customers immediately the afternoon of approval.

We have received positive feedback on the label and data and prescribers of generally expressed enthusiasm for the combination.

Many of our digital promotional tactics went live the day of approval and the team is fully enabled to detailed customers virtually all of where appropriate and person.

Additionally, we have already executed numerous speaker programs, including the national broadcast.

While it is early to discuss any metrics from the launch I can say that we are very pleased with the energy and execution of the launch thus far and continue to be optimistic on 90 are based on our initial customer feedback.

Beyond <unk>, we are very excited about by the Cabozantinib development program as it moves forward broadly across multiple indications and with different combination partners.

Patrick J. Haley: The Exelixis team has significant experience in RCC with two prior successful launches, and we look forward to this opportunity to educate physicians on the 90-hour data so that more patients can benefit from KaboMedix therapy in the first line. The strength of the 90-hour data speaks for itself, a doubling of medium-progression pre-survival and ORR and superior overall survival versus. Importantly, clinical benefits were observed in the vast majority of patients in the trial, resulting in a low rate of primary progression, regardless of IMDC risk status or patient subtype.

We look forward to building on this momentum in RCC, and HCC DTC and other potential future indications such as prostate and lung as our development program evaluating cabozantinib in combination with immune checkpoint inhibitors advances.

Our team remains highly focused and motivated to compete every day to bring the benefit of <unk> to all eligible patients as we continue to build the franchise and maximize its clinical and commercial potential and with.

With that I'll turn the call back over to Mike Alright. Thanks P. J as we outlined at Jpmorgan a few weeks ago 2021 has the potential to be a transformational year for <unk> as the launch the combo and Evo combination of first line RCC and set the stage to pursue numerous additional indications with new data readouts.

Patrick J. Haley: Supporting broad use in the market. In addition, the optimized CABO combination starting dose of 40 mg daily yielded a compelling safety and tolerability profile along with a low treatment discontinuation rate and favorable quality of life, all of which has been notable with physicians in our research and discussions.

And potential NDA filings all of my Bill all while building a diversified portfolio of assets that provide significant growth opportunities I'm excited for ESCO to you of this weekend and hope everyone can join us for our virtual Investor meeting on Saturday afternoon at 230 PM Pacific time, 530 pm Eastern.

Patrick J. Haley: The 90-hour data are particularly impressive when considered in the context of the challenging patient population enrolled in the study, which had more IMDC, poorer patients, and fewer patients with nephrectomies than other Phase III studies in first-line RCC. Taken Together The combination of a best-in-class TKI like CABO with a well-established immune checkpoint inhibitor like nivolumab in RCC, supported by strong efficacy and safety data from CheckMate 9ER, presents Exelixis with the opportunity to share a compelling and highly motivating story with our customers and to enable broad positioning across all clinical risk groups in first-line RCC.

And time.

I'll close by thanking everyone and ex selections for their efforts in 2020 under what we're obviously extremely challenging conditions, while we may be starting to see the light at the end of the Covid tunnel, we continue to acknowledge the potential risks to all of US and of course to our business should the vaccine rollout stalled and incur.

We are proud to say that the entire ex Lexus team continues to work as one with great teamwork expertise and energy and making every day count as we discover develop and commercialize the next generation of our medicines for cancer patients in need of better and more effective therapies and we look forward to updating you on our progress and the future. Thank you for your <unk>.

Continued support and interest and ex Lexus and we're happy to now open the call for questions.

Okay.

Thank you to ask a question you will need to press star one on your Touchtone telephone to withdraw your question press the pound key please standby, while we compile the Q&A roster.

Patrick J. Haley: Feedback on the Checkmate 90 arc data with both academic and community oncologists has been positive, and we believe we can leverage the success and prescriber familiarity of both CABO and NEVO to gain traction quickly in the combination setting. There's a great deal to be excited about as we think about the totality of the Cabo Medics RCC business. With regard to the launch of 9ER, we are extremely pleased with the rapid execution of our experienced team, which was well prepared and deeply experienced in the RCC market, started reaching out to customers immediately the afternoon of approval.

Our first question comes from the line of <unk> <unk>.

Our team of true Securities. Your line is open.

Hi, guys. Thanks for taking my questions and.

Congratulations on the.

We'll execute in 2020.

I thought of a quick question for the P. J.

Curious on the rebound on scripts that we're seeing and for Q could you give us a sense of what proportion of the 200 basis points of growth and share.

Patrick J. Haley: We have received positive feedback on the label and data, and prescribers have generally expressed enthusiasm for the combination. Many of our digital promotional tactics went live the day of approval, and the team is fully enabled to engage customers virtually or, where appropriate, in person.

Was from second line.

A bit of a quick financial question for Chris.

What's the expectation for SG&A for the next good for the net.

Few quarters, all of the expected to sort of stay in line with the with for you. Thanks.

Yes.

This is P. J thanks for the question.

With regards to Q4 and the scripts and we certainly had a.

Strong quarter closing the year as we've discussed and the.

Patrick J. Haley: Additionally, we've already executed numerous speaker programs, including a national broad, While it is early to discuss any metrics from the launch, I can say that we are very pleased with the energy and execution of the launch thus far and continue to be optimistic on 9ER based on our initial customer feedback. Beyond 9ER, we are very excited by the CABA's Antidote Development Program as it moves forward broadly across multiple indications and with different combination partners.

And the remarks, and really well I'm not going to go into sort of specific details of the proportion of that driven by various market segments.

Clearly the second line market share growth that we experienced and RCC was with strong and.

Driving a lot of that so I won't go into detail beyond that but.

And I will say is we did see strength across all of the segments.

Patrick J. Haley: We look forward to building on this momentum in RCC, HCC, DTC and other potential future indications, such as prostate and lung, as our development program evaluating cabozantinib in combination with immune checkpoint inhibitors advances. Our team remains highly focused and motivated to compete every day to bring the benefit of Cobblemetics to all eligible patients as we continue to build the franchise and maximize its clinical and commercial potential. And with that, I'll turn the call back over to Mike.

A bit of momentum also in the second line HCC.

As that market evolves as well so we're pleased with that.

And look forward to building on that momentum as we go forward here and.

And 2021, particularly with the 90 yard of lunch.

And stick as Chris So I guess a question on SG&A was going to be relatively the same as Q4 Q3 and Q4, we did give guidance of.

$375 million to $425 million.

Michael M. Morrissey: All right, thanks, PJ. As we outlined at JP Morgan a few weeks ago, 2021 has the potential to be a transformational year for Exelixis as we launch the Combo and Evo combination and first-line RCC and set the stage to pursue numerous additional indications with new data readouts and potential SNDA filings. All while building a diversified portfolio of assets that provide significant growth opportunities. I'm excited about ASCO G.U.

And that which would if you look at that on the just an average basis. If you look to the midpoint that's $400 million. So the run rate there is and that.

And we'd be in the $100 million range. So.

That's what I'm not going to give you quarterly guidance, but that's kind of where we're looking at.

And our SG&A growth going too.

Great. Thanks, guys for the questions Alright, Thank you Africa.

Yes.

Thank you. Our next question comes from the line of Jason <unk> of Bank of America. Your question. Please.

Hey, guys. Thanks for taking my questions.

Michael M. Morrissey: this weekend and hope everyone can join us for our virtual investor meeting on Saturday afternoon at 2.30 p.m. Pacific time, 5.30 p.m. Eastern. I'll close by thanking everyone at Exelixis for their efforts in 2020 under what were obviously extremely challenging conditions. While we may be starting to see the light at the end of the COVID tunnel, we continue to acknowledge the potential risks to all of us and, of course, to our business should the vaccine rollout stall.

And you just on the early stage pipeline just for on X L. O. Nine two can you talk a little bit about it and.

And the key internal hurdles on the efficacy side as you think about when you ultimately evaluate the expansion cohorts and make your decision to move Exelon and two into pivotal trials. Later this year and then you know.

And with numerous shots on goal emerging with the new the clinic pipeline has the imperative to do Biz Dev lessened and any way or does it ultimately remain unchanged in terms of thinking about perhaps some more more advanced asset later, along and development that could occur.

Michael M. Morrissey: I'm incredibly proud to say that the entire Exelixis team continues to work as one with great teamwork, expertise, and energy in making every day count as we discover, develop, and commercialize the next generation of our medicines for cancer patients in need of better and more effective therapy. We look forward to updating you on our progress in the future. Thank you for your continued support and interest in Exelixis.

The company Cabo and the portfolio yes.

Yes, Jason Thanks for the question Gisela do you want to take the first one and then I'll loop back and get the second one.

Sure happy to do until the thank you for the question. So ex <unk> is making good progress as I mentioned and.

Operator: And we're happy to now open the call for questions. Thank you. To ask a question, you will need to press star one on your touchtone telephone.

And its phase one study and also and the phase one for your evaluation with occasionally some of them.

Operator: To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from the line of Asthika Goonewardene of Trust Securities. Your line is open.

And we look forward to for the combination approaches and as we're making decisions based upon expansion cohorts and the early observations.

Asthika Sarith Goonewardene: Hi guys, thanks for taking my questions and congratulations on a well executed 2020. I've got a quick question for PJ. I'm just curious about the rebound on scripts that we're seeing in 4Q. Could you give us a sense of what proportion of that 200 basis points growth in share was from second line? And then a quick financial question for Chris. What's the expectation for SG&A for the next few quarters?

And certainly we'll be looking at the continuum of safety and Tolerability as well as.

It gets the signals and those will be very much dependent on the indication that we will take forward of course, and and the competitive environment and so it's a a variety of factors that we will consider and certainly chicken to account the data that will be emerging from the expansion cohorts.

Patrick J. Haley: Are we expecting to sort of stay in line with 4Q? Thanks. Yeah, hi, Asthika. This is PJ.

Patrick J. Haley: Thanks for the question. With regard to Q4 and the scripts, I mean, we certainly had a strong quarter ending the year, as we've discussed in the remarks, and really, I'm not going to go into sort of specific details of the proportion of that, you know, driven by various market segments. Clearly, the second-line market share growth that we experienced in RCC was strong and driving a lot of that, so I won't go into detail beyond that, but what I will say is we did see strength across all the segments, a bit of momentum in second-line HCC as that market evolves as well, so we're pleased with that. And, you know, look forward to building on that momentum as we go forward here in 2021, I think it's Chris.

Fantastic. Thank you on the.

On the BD side look obviously, we're looking at a range of opportunities across the continuum of.

The stages of assets, we've done a number of early stage backend loaded small upfront deals and there is certainly more of those to be done in the.

And the short to midterm, we of a queue of those lined up and we think that the very important part of building our early stage portfolio. The complements our our internal discovery efforts around small molecules and I think that makes a lot of sense relative to building.

Pipeline for the future. We're looking at a variety of I would say mid and late stage assets as well obviously.

The different questions there in terms of the value proposition and as Im sure Youre aware of things are pretty frothy right now out there as well as the as the data that goes with those opportunities. So we're looking closely and if we find the right the right assets the right opportunity at the right cost and then we will be inclined to move those forward, but again.

Christopher J. Senner: So I guess your question on SG&A was going to be relatively the same as Q4 Q3 and Q4. You know, we did give guidance of 375 to $425 million. You know, that which would, if you look at that on just an average basis, you know, if you look to the midpoint, that $400 million. So the run rate there is in that, Yeah, we'd be in the $100 million range.

We're not looking at the at the at the reality of Overpaying for assets just because.

Of the frothy market dynamics and people looking for a lot so within the mainly.

And maintain a high level of discipline, as we have and the past and and Gulf of good science and good value at the same time.

Alright, thanks, Thank you.

Thank you. Our next question comes from the line of Andy Yeah.

William Blair Your line is open.

Okay. Thanks for taking my question so.

The first one.

Maybe dis less so.

I'm just wondering if you can frame expectations for us for the kind of mid year update for cohort six and as the company policy you want to have the pitch of follow up.

Operator: So, you know, that's what I'm not going to give you quarterly guidance on, but that's kind of where we're looking at our SG&A growth going forward. Great. Thanks, guys, for the questions. All right, thank you, Asthika. Thank you. Our next question comes from the line of Jason Gerberry of Bank of America. Your question, please. Hey, guys.

And basically the mature dataset so.

And we expect kind of the full 130 patients from that cohort around mid year.

Sure so of what we're aiming for is the independent radiology review of four cohorts six and we had presented as you know.

Jason Matthew Gerberry: Thanks for taking my questions. Two, just on the early stage pipeline, just on XL092, can you talk a little bit about any key internal hurdles on the efficacy side as you think about when you ultimately evaluate the expansion cohorts and make your decisions to move XL092 into typical trials later this year? And then, you know, with numerous shots on goal emerging from the new-to-clinic pipeline, has the imperative to do BizDev been lessened in any way, or does it ultimately remain unchanged in terms of thinking about perhaps a more advanced asset later along in development that could accompany Cabo in the portfolio thing? Yeah, Jason, thanks for the questions. Gisela, you want to take the first one, and then I'll loop back and get the second one.

Last year and at school and ask could you the initial cohort and.

Also of about 40 patients for cohort six and we're very pleased with the outcome. There was a response rate.

And 32%.

And durable responses observed and niche.

The metastatic CRP C population, but the combination and that paired with a good tolerability profile.

<unk> has completed enrollment of the 130 patients and we're looking to see.

And the independently assessed.

Objective response rate and.

And so that's really what we're aiming for and later in 2021.

Got it that's very helpful.

And maybe for P J.

Look at slide number 31.

Gisela Schwab: Excel 092 is making good progress as I mentioned in its Phase 1 study and also in the Phase 1b evaluation with atazolizumab and we look forward to further combination approaches and as we're making decisions based upon expansion cohorts and early observations certainly we'll be looking at the continuum of safety tolerability as well as efficacy signals and those will be very much dependent on the indication that we will take forward of course and the competitive environment so it's a variety of factors that we will consider and certainly take into account the data that will be emerging from the expansion cohort. Fantastic.

Has the true of frontline patient new patient share of breakdown and.

And I think that.

Basically the same graph the you've shown.

And <unk>.

Q3, just curious if there is any sort of material change as we exited Q4 or maybe a little bit into Q1.

About any sort of material change to that picture.

Yeah.

P J thanks for the question.

What I'd say as we look at certainly a lot of different data sources with regards to.

Market share and various data elements for the market. So I think regardless of what we looked at and over time and these are.

Yes, I'd say relatively in the ballpark.

Io combo share of being 75% to 80%.

And you know the majority of that being Iot Kai So I'd say that's.

Gisela Schwab: Thank you. On the BD side, look, obviously, we're looking at a range of opportunities across the continuum of We've done a number of early-stage, you know, back-end-loaded, small upfront deals, and there's certainly more of those to be done in the short- to mid-term. We have a queue of those lined up, and we think that's a very important part of building our early-stage portfolios that complements our internal discovery efforts around small molecules, and I think that makes a lot of sense relative to building a pipeline for the future.

Roughly what we're looking at now and we're very excited to really.

Move <unk> forward with vivo into that Iot CAD market.

And so it kind of mentioned and the team is really excited.

And working hard and the launch we're getting a lot of great feedback and.

The heck of a lot of activity with that so I think it'll be exciting to kind of moving forward in combination in first line.

Okay.

Thanks, that's helpful. So last question.

And for Peter.

And so as we think about.

The company kind of moving away from 265.

Gisela Schwab: We're looking at a variety of, I would say, mid- and late-stage assets as well. Obviously, different questions there in terms of the value proposition, and as I'm sure you're aware, things are pretty frothy right now out there, as well as the data that goes with those opportunities. So, you know, we're looking closely, and if we find the right asset, the right opportunity at the right cost, then we'll be inclined to move those forward. But again, we're not looking at the reality of overpaying for assets just because of the frothy market dynamics and people looking for a lot.

Average really was asking about relevant political question regarding the rules of the Cape and kinase and.

So I was just wondering if you're bringing forward any other lead candidates that could potentially fill that void.

Or youre, just basically kind of focusing on other.

Early stage asset.

Yes, I think I think.

What we learned from the.

And from 265 experience with what's kind of helpful and I think February obviously scientifically interesting on the basis of that we're going to be focusing on earlier stage programs for the internal discovery going forward rosin and rosin and.

Michael M. Morrissey: So, we're going to maintain a high level of discipline, as we have in the past, and go for good science and good value at the same time. All right. Thanks.

And the attempt to do what kind of deliver version of it takes ex.

And so on.

Alright, great. Thanks for answering my questions.

Operator: Thank you. Thank you. Our next question comes from the line of Andy Sia on behalf of William Blair. Your line is open. Okay, thanks for taking my question. So, first one, maybe Diesla.

Okay. Thank you.

Thank you. Our next question comes from yarn Werber of Cowen your.

Your line is open.

Great. Thanks for taking my question and congrats on the launch and the nice quarter.

Maybe just a couple of question one just any inventory changes can you just remind us kind of where did you finish inventories in Q4, and then I have a question when we look at the data the phase one data for Cub and Evo Cub and Evo.

Andy Sia: So, I'm just wondering if you can frame expectations for us for the kind of mid-year update for Cohort 6. I know the company policy, you know; you want to have sufficient follow-up and basically mature data sets. So, you know, can we expect kind of the full 130 patients from that cohort around mid-year? Sure, so what we're aiming for is the independent radiology review for cohort six. We presented, as you know, last year at ASCO and ASCO-GU the initial cohort of about 40 patients for cohort six, and we're very pleased with the outcome there, with a response rate of 32% and durable responses observed in this metastatic CRPC population, but the combination, and that paired with a good tolerability profile. We have completed enrollment of the 130 patients, and we're looking to see the objective response rate. I got it.

And the this is patients remind us who they need to of failed one prior therapy of the obviously couldnt of failed the PD one and so is the sort of second line therapy the.

Data is obviously better obviously very small simple, but better than carbo alone and the maybe your but when we're trying to compare it to a cabo knievel and first line.

The response rate is higher the median OS is slightly lower but again is this the data looks pretty good but is this sort of of second line population just give us a little bit of sense. How you think about it. Thank you.

And your own great. Great question is why don't we start Gisela why don't you answer the last question first and then Chris can cover the inventory question.

Sure.

Happy to and regarding the NTIC tip studied the finish line B study that will be presented by Dr. Paul This.

Gisela Schwab: That's very helpful. And maybe for TJ, if you look at slide number 31, you have basically a front-line new patient care breakdown. And I think that's basically the same graph that you showed in Q3. Just curious if there's any sort of material change as we exited Q4 or maybe a little bit into Q1. Any sort of material change to that picture?

This is a trial that was conducted and patients with advanced <unk> malignancies and patients must have received at least one prior therapy could have received multiple prior therapies. So lets see rather heavily pretreated patient population and across the board.

And so it's I would say and answer the question the second and later line.

Patrick J. Haley: Yeah, PJ, thanks for the question. You know, what I say is we look at certainly a lot of different data sources with regard to market share and various data elements in the market. So I think, regardless of what we look at, and over time, these are, relatively in that ballpark, IO combo share being 75-80%, and the majority of that being IOTKI. Roughly what we're looking at now, and we're very excited to really move Cabo Metics forward with Nevo into that IOTKI market.

And that we're looking at and the results and deck you will see in more detail explained and as could you.

Okay.

And as Chris and so on your inventory question.

And as I mentioned in my prepared remarks, the complement of inventory weeks on hand increased from about $2 eight weeks on hand, and Q3 to about $3 one weeks on hand, and Q4 and.

And this is equal to approximately $7 $5 million the <unk>.

Patrick J. Haley: As I kind of mentioned, the team is really excited and working hard on the launch. We're getting a lot of great feedback and a heck of a lot of activity with that. So I think it'll be exciting, and it will move us forward in combination and first. Okay, thanks, that's helpful.

Net revenue line.

Great. Thank you.

Welcome and thank you.

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

Hey, guys congrats on the quarter and thanks for taking my questions.

Well I thought of this brand impact data that you highlight on slide 30 was interesting.

Peter Lawson: So, last question, this is for Peter. So, as we think about, you know, the company kind of moving away from 265 and so on, that passage really was asking about, you know, relevant clinical questions regarding the roles of the TAM kinases. So, I'm just wondering if you are bringing forward any other lead candidates that could potentially fill that void, or you're just basically kind of focusing on other, you know, early stage aspects.

Yes.

Mid 90 or with the combination now of proof.

What market share of you ultimately think you might be able to achieve and the first line RCC setting and.

And what areas do you expect to gain market share is at the.

Of a therapy the <unk>.

For the Io Io combos.

Secondly, I thought the CNS data from ask of June is quite interesting and I was wondering to what degree and snowing.

And whether any of the other key items.

Peter Lawson: Yeah, I think, you know, what we learned from the Excel 265 experience was kind of helpful and, I think, fairly relatively scientifically interesting. On the basis of that, we're going to be focusing on earlier stage programs for our internal discovery going forward, rather than an attempt to do a kind of do-over version of 265.

The cross the blood brain barrier or whether that.

Aspect of differentiation and.

And then lastly on ex one or two.

CDK seven inhibitor.

Wondering if you could just help us understand how all of that.

Right.

And in the breast cancer space.

Okay.

Thanks, so much.

Thanks, Michael why don't we why don't we start there Peter do you want to take the 102 question first and then.

Keith look into the brain Mets and P. J can do the the question about the brand impact.

Sure. So the question I think it was specifically around the opportunity for <unk>.

CDK for them and what it is in excess of one or two and.

And breast cancer.

And.

Andy Sia: Alright, great. Thanks for answering my questions. Okay, Andy.

There were a number of.

Fairly compelling pieces of the preclinical data that support coming and with the CDK <unk> inhibitor and <unk>.

Operator: Thank you. Thank you. Our next question comes from Yaron Werber of Cohen. Your line is open.

The multiple settings.

Triple negative breast cancer.

The state of showing that.

One of the thin cell lines of dependent upon the CDK seven for <unk>.

Yaron Werber: Great, thanks for taking my question and congrats on the launch and a nice quarter. Maybe just a couple of questions. One, just any inventory changes?

And so I'm pretty compelling zincograph thinking of that as well.

And the positive breast cancer is a direct connection between the CDK seven of an estrogen receptor whereby you.

See the case that when actually post release yesterday and was that the increases as transcriptional activation potential.

Operator: Can you just remind us kind of where you finished inventories in Q4? And then I have a question. When we look at the data, the phase one B data for CARBONIVO, CARBONIVO, IPI, these patients tell us that they need to have failed one prior therapy. They obviously couldn't have failed PD-1.

Okay and combinations.

You all antagonist for various types of Mike makes a lot of sense.

And then finally and I think you alluded to this seem to keep 70 of the upstream of CDK four and six so it may well be.

And place to go in terms of resistance. The current CDK, four and six inhibitor and so at least those three kind of different flavors of you Blake of things it could be explored and the breast cancer setting.

Gisela Schwab: So is this sort of a second line therapy? The data's obviously better, obviously a very small sample, but better than CARBO alone in the mid-year. But when we're trying to compare it to a CARBONIVO in the first line, the response rate is higher, and the median OS is slightly lower. But again, is this, the data looks pretty good, but is this sort of a second line population? Just give us a little bit of a sense of what you think about it.

Yeah.

Thanks, Peter Thats, great deals for you one do the <unk> question.

Absolutely, yeah, very and happy to see the presentation and asks.

Could you on this retrospective analysis of patients with brain metastases from.

The RCC and and importantly, this study.

Both patients with uncontrolled brain metastases at baseline and also pay for.

Operator: Thank you. Yeah, you've got great, great questions. Why don't we start, Kiesla? Why don't you answer the last question first, and then Chris can cover the inventory question.

<unk> with control of the disease at baseline and then bulk and.

Groups and impressive of responses intracranial of responses and also the systemic and responses were observed.

Gisela Schwab: Sure, happy to. Regarding the NCI CTEP study, the Phase 1b study that will be presented by Dr. Paul, this is a trial that was conducted in patients with advanced GU malignancies, and patients must have received at least one prior therapy and could have received multiple prior therapies. So it's a rather heavily pre-treated patient population across the board. And so I would say and answer the question and later line that we're looking at in the results that you will see in more detail explained, could you? Okay. Yaron, this is Chris.

And I'm highlighting that because of patients with uncontrolled brain disease are usually excluded from clinical trials and uncertainty from large phase III trials for Christmas.

Potential complications that may occur and those patients and you.

Usually they have to have control of disease to be included if at all and largest studies and that vein and I, just and very important observation and certainty and under studied of group of patients.

Christopher J. Senner: So on your inventory question, you know, as I mentioned in my prepared remark, the KyberMedx inventory weeks on hand increased from about 2.8 weeks on hand in Q3 to about 3.1 weeks on hand in Q4. And this is equal to approximately, you know, seven and a half million dollars in net revenue. Great, thank you. Thank you.

That said in terms of the penetration of blood brain barrier of we know that.

And that Cabozantinib as the.

The ability to penetrate the blood brain barrier of us and seen that and very early at.

Evaluations and our preclinical studies.

And in the context of the brain metastases of upgrading involvement even.

Michael Schmidt: Thank you. Our next question comes from Michael Schmidt of Guggenheim. Your line is open.

Operator: Hey guys, congrats on the quarter, and thanks for taking my questions. Well, I thought this brand impact data that you highlighted on slide 30 was interesting. Checkmate 9ER With the combination now approved, what market share do you ultimately think you might be able to achieve in the first line RCC setting and in what area? Data from. And then lastly, on Act One of... Hey, thanks, Michael. Why don't we start there?

Without the histology and sometimes the blood brain barrier and they'd be compromised and.

And so that instead of a feature and that adds to but it's not perhaps are completely dependent on the penetration of the blood brain barrier.

And looking at the results and the.

And at a high level of that are being reported at ash could you share.

Patrick J. Haley: Peter, do you want to take the one or two questions first, and then Gisela can do the brain maps, and PJ can do the question about brain impact? Sure, so if I caught the question, I think it was specifically around, you know, opportunity for CDK7 inhibitors and Excel 102 in breast cancer, and there were a number of very compelling pieces of preclinical data that support coming in with a CDK7 inhibitor. In multiple settings, certainly in triple negative breast cancer, there's data showing that a lot of those cell lines are dependent upon CDK7 for growth, and some pretty compelling xenograft data there as well. In ER-positive breast cancer, there's a direct connection between CDK7 and the estrogen receptor, whereby CDK7 actually phosphorylates the estrogen receptor and increases its transcriptional activation potential, to get in combination there with

Very happy to see and high response rate and this very underserved patient population.

Great. Thanks, Michael This is P J with.

As regards to the first line of uptake I think I won't.

Discuss specific numbers with regards to market share, but I think we have really the opportunity to.

Gained share broadly and the market and I mean that in a few different ways, whether we look at the competitive landscape with regards to ICI, PKI, ICI ICI or even expanding.

Combinations into Teekay and mono therapy.

We certainly see that we see broad potential across.

Clinical risk groups favorable intermediate and poor risk groups with the strength of our data overall.

Certainly excited about the large body of.

Data that will be presented at <unk> for you this weekend to help kind of prescribed.

Prescribers learn more about.

About combo and I think as we think about that.

Particularly with reverse of the combination we're really going to be helped by the experience of the prescribers have with the <unk>.

<unk> and RCC at this point.

It is viewed as the best in class Teekay.

According to our market research and I think what we're going to see is the optimized dose of 40 milligrams and kind of the.

Peter Lawson: Your antagonists of various types make a lot of sense. And then finally, and I think you alluded to this, 7 is upstream of CDK 4 and 6. So it may well be an interesting place to go into resistance to currents. So there's at least those three kinds of different flavors, if you like, of things that could be explored in breast cancer.

The tolerability profile of low discontinuation rate with regards to of the combination and really how that translated to improved quality of life and 90 of our I think is really going to help us.

Drive utilization across all of these different categories.

Gisela Schwab: Thanks, Peter. That's great. Isla, do you want to do the brain mech question?

Super Thank you.

You're welcome Michael Thank you.

Thank you. Our next question comes from Peter Lawson from Barclays. Please go ahead.

Gisela Schwab: We are happy to see the presentation at ASCO-GU on this retrospective analysis of patients with brain metastases from RCC, and importantly, this study assessed both patients with uncontrolled brain metastases at baseline and also patients with controlled disease at baseline, and in both groups, impressive responses, intracranial responses, and also systemic responses were observed. So, and I'm highlighting this because patients with uncontrolled brain disease are usually excluded from clinical trials and, certainly, from large phase three trials because of potential complications that may occur in those patients.

The quarter and thanks for taking my questions, just Don and first line RCC and <unk>.

The potential broad use of Cabo plus PD one.

Nishu is do you think of easier to penetrate is it things like patients with brain Mets.

Yes, Peter this is P. J I'll talk about that I mean, again I think we do really see the broad potential here.

And when we look at the current utilization of ICI and Teekay.

On the market, we see it utilized broadly.

And particularly in the community setting so I think.

And we will have the opportunity to.

And of prescribers and really want to utilize it for a variety of their patients, particularly looking at the risk benefit profile.

And the strong efficacy across subgroups and.

Thinking about the.

Gisela Schwab: Usually, they have to have controlled disease to be included, if at all, in larger studies. So in that vein, it is a very important observation and certainly an understudied group of patients. That said, in terms of penetration of the blood-brain barrier, we know that carbazantinib has the ability to penetrate the blood-brain barrier.

The tolerability profile, and particularly of the quality of life, which is just something.

And not often seen in.

Adding therapy, adding and the second or third therapy or whatever it is and a.

The combination and seeing improved quality of life and oncology. So we think that will give us really a broad opportunity.

And then just on the first line single agent Teekay ice segment kind of your analysis of that.

Patrick J. Haley: We've seen that in very early evaluations in preclinical studies. In the context of brain metastases or brain involvement, with other histologies, sometimes the blood-brain barrier may be compromised, and so that is a feature that adds to, but it's not perhaps completely dependent on the penetration of the blood-brain barrier, but looking at the results at a high level that are being reported at ASCO-GU, we are very happy to see a high response rate in this very underserved patient This is PJ.

Kind of share do you think you have for US is limited.

And the likes of it.

Honestly and the TK.

Monotherapy categories, where we do see.

And the last few quarters historically as more of the legacy Teekay items.

And if you look at the the market share data that you know, that's where you see some significant of usage.

Which is Gisela mentioned has kind of been the.

The guideline recommended therapy for non nuclear so.

And so you see sutent and <unk>, there and I think with the.

Patrick J. Haley: With regard to first line uptake, you know, I won't, you know, discuss specific numbers with regard to market share, but I think we really have the opportunity to gain share broadly in the market. And I mean that in a few different ways, whether we look at the competitive landscape with regard to ICI TKI, ICI ICI, or even, you know, expanding combinations into TKI. Monotherapy, you know, we certainly see that.

The data, we havent <unk> as well as the other.

Data sets the Gisela described whether that's the <unk> looking at.

Papillary RCC, that's why you see some of the mono therapy. So I think the breadth of the data being presented will help us be more competitive there and historically that's really been more.

Yes.

More of Motrin and student use outside of certainly the.

Top of use that we have there.

Do you think that's the kind of and easier area to penetrate that single agent for first line Teekay Mani.

I really think the.

I think the combo, who as you know.

Going to be just such a big opportunity and our data is so strong that that should be.

Patrick J. Haley: We see broad potential across clinical risk groups, favorable, intermediate, and poor risk groups with the strength of our data overall. Certainly excited about the large body of data that will be presented at ASCO-GU this weekend to help kind of, you know, prescribers learn more about CABO. And I think, you know, as we think about that, particularly with regard to the combination, we're really going to be helped by the experience that prescribers have had with CABO medics and RCC at this point. It is viewed as the best in class TKI according to our market research.

Really probably where we see rapid uptake.

And there'll be more of a dynamic.

Certainly, possibly a more dynamic market as we launch into that because thats certainly what were going to be focused on.

Okay. Thanks, so much thinks of the coke.

And that theater.

Yeah.

Thank you. Our next question comes from Jay Olson of Oppenheimer. Your line is open.

Hey, Jay you with force.

Yes can you hear me.

We sure can now.

Great. Congrats on all of the progress and thank you so much for taking the questions. Since you rapidly grown the top line $2 billion and just a few short years would you consider the key steps and timeline for growing to $2 billion and revenue and then I had a question about your attitude and collaboration where you recently.

Patrick J. Haley: And, you know, I think what we're going to see is the optimized dose of 40 milligrams and kind of the Tolerability Profile, Low Discontinuation Rate, with regard to the combination and really how that translates to improved quality of life in 9ER, I think is really going to help us drive utilization across all these different categories. Thank you. You're welcome, Michael. Thank you. Thank you. Our next question comes from Peter Lawson of Barclays. Please go ahead.

We added another ADC to your portfolio.

What are the key points of differentiation and Youre looking for and your adcs versus competitors and is there a rationale to combine and ADC with Cabo or <unk>.

Yes, Jay its Mike Great quick questions. Peter why don't you start there and then I'll finish up.

Yeah. So.

As you've seen we've done a number of ADC and related.

Appeals and partnerships over the last six months or so.

And they all intended to.

We work well together and.

Essentially the way we are setting up building a pipeline of.

The ADC is too.

Hi, folks, particularly on the Venlo collaboration who are the ones, who can go out and find for kind of the antibodies and binders.

Peter Lawson: Thanks for taking questions. Just in first line RCC, beyond that potential broad use of CARBO plus PD-1, what niches do you think are easier to penetrate? Are they things like patients with brain and bone mesh? Yeah, Peter, this is PJ.

Ladies and live and the raw material and we feel like for us from making the ADC and the deal.

As we did late last year with catalysts and with the N B E.

And then give us access to contemporary and site specific conjugation technology.

Believed to be increasingly important in terms of advancing high quality agencies into the clinic.

And it also gave us access to Orion and the range of pretty interesting interesting payloads.

Patrick J. Haley: I'll talk about that. I mean, again, I think, you know, we do really see the broad potential here. And when we look at, you know, the current utilization of ICI TKI in the market, we see it utilized broadly. Prescribers really want to utilize it for a variety of their patients, particularly looking at that risk-benefit profile and the strong efficacy across subgroups and you know thinking about the tolerability profile and particularly the quality of life, which is just something not often seen in adding therapy, adding a second or third therapy, whatever We think that will really give us peace.

And obviously, you can pick which payload for kind of do based on which tumor types. We ultimately we ultimately want to target.

So with respect to one of other gene fits into the if they have a very interesting antibody masking technology.

Essentially.

As the small peptide it'd be like let's say from the binding domain of the antibody and.

And.

Really with use of its ability to bind to the to the target of antigen, but it's relief and the tumor specific fashion.

It depends on.

And quickly increase protease activity of the tune of surface within clip. This peptide off so it's really intended to increase the therapeutic index of the like for any off target side effects that may encourage you to finding to target the normal tissue.

And this is the target and.

And the tumor and yes, if we think from us.

The profile of point of view that's the.

Very attractive technology to have and other than the side also pointed out it actually broadens out and potentially the target's face from the ADC field as well.

Patrick J. Haley: Thank you. And then just on that first line, single agent TKI segment, kind of your analysis of that, what what kind of share do you think you have versus Lempitnebo in life? You know, honestly, in the TKI monotherapy category is where we do see, you know, In the last few quarters, historically, it's more the legacy TKIs. If you look at the market share data, that's where you see some significant usage, which as Gisela mentioned, has kind of been the... Guideline Recommended Therapy for Non-Clear Cell.

And with the miles technology, you can start looking at targets, which you maybe you wouldn't want to pursue.

And didn't have some kind of the tumor specific T cell activation and going on.

So you know.

And I think if you put those things together.

Hopefully you can start to see where we think hopefully the differentiation is going to come here.

It's from using.

And having access to.

And some of the most modern conjugation technologies the.

And it really enables you to get a homogeneous product.

Some of the issues with the.

People have seen with the agencies over the years really stem from the big mixed use of things and.

And I can create and manufacturing issues as well ultimately.

Moving to the toxicity.

Patrick J. Haley: So you see Sutin and Botrien there, and I think with the data we have in 9ER, as well as the other data sets that Gisla described, whether that's PapMet looking at papillary RCC, that's where you see some of the monotherapies. So I think the breadth of the data being presented will help us be more competitive there. And historically, that's really been more of a votarian and student use outside of, you know, certainly the cabo use that we have.

So that's the plan, that's definitely plentiful and the 86 basis moving more to do there and.

And obviously, we have all the first ADC.

Ex vivo to which are both related.

The way to the clinic and.

And the not too distant future.

Fantastic Peter Thanks for that deep dive into the the the overall ADC approach and certainly we're excited about having aging collaboration in place now to be able to move that forward too.

Jay in terms of your first question look we're all about growing top line revenue, obviously that is incumbent upon yes, good clinical trial data successful regulatory outcomes and then.

Obviously very very strong commercial execution.

Jay Olson: Do you think that's kind of an easier area to penetrate than the single agent first first line TKI mono? Well, I really think the I think the combo is, you know, going to be just such a big opportunity. And our data is so strong that that should be really probably where we see rapid uptake, and it'll be more of a dynamic, certainly possibly a more dynamic market as we launch into that because that's certainly what we're going to be. Okay, thanks so much. Thank you. Our next question comes from Jay Olson of Oppenheimer. Your line is open. Hey Jay, are you with us? Yep, can you hear me?

<unk> seen that over the last few years in terms of our renal and liver programs and obviously, there's a lot going on right now in terms of the.

The commercial launch based on <unk> for first line renal with Cabo needle. So that's the big driver for us and the new and the.

The immediate short term.

As I mentioned and as Gisela mentioned, we have a number of potential NDA filings. This year top line data results for first line liver prostate thyroid kind of lung trials going so all in all probably nine or 10 pivotal trials ongoing right now with with kind of and various various io functionalities and.

Certainly with the opportunity to do more going forward, the next wave or even two coming beyond that with the 92. So so our focus is really on top line growth and our focus is making sure that we are executing extremely well the cross that.

Operator: Yes, you sure can now. Oh, great. Congratulations on all the progress, and thank you so much for taking the questions. Since you've rapidly grown the top line to a billion dollars in just a few short years, what do you consider the key steps and timeline for growing to $2 billion in revenue?

Clinical regulatory commercial framework, so that we can that we can meet our aspirations for success.

The Super helpful. Thanks for sharing the vision with us.

Got it. Thank you yeah. Thanks Jay.

Thank you. Our next question comes from the line of Kennan Mackay of RBC capital markets. Please go ahead.

Michael M. Morrissey: And then I had a question about your Adygean collaboration, where you recently added another ADC to your portfolio. What are the key points of differentiation you're looking for in your ADCs versus competitors? And is there a rationale to combine an ADC with Cabo or O92? Yeah, Jay, it's Mike.

Hi, Thanks for taking the question and congrats on the progress and what a year.

And just for Christmas for P. J can you talk a little bit more with the metrics behind the Cabo Q4 results the.

The pruning out of sprint was and often surprised but I'm kind of having a hard time justifying demand versus gross to net versus the.

The inventory changes.

Peter Lawson: Great, great questions. Peter, why don't you start there and then I'll, I'll finish up. Yeah, so as you've seen, we've done a number of ADC-related deals and partnerships over the last few years, and they are intended to work well together, essentially the way we're setting up, building a pipeline. All the ADCs are too.

<unk> mentioned, so if there is anything you can comment.

Comment around demand after you back out of inventory and gross to net that out and hugely.

Hugely helpful.

And lastly, this was discussed a little bit, but doing love to hear of the team's perspective once more on sort of the small bit of detail we've heard from the competitive and then.

The matter of Keytruda combo, and the clear trial, obviously impressive median PFS and hazard ratio of there, but that can obviously be defined by.

Peter Lawson: We have folks, particularly our Embedded Collaboration, who are the ones who can go out and find those antibodies and binders. They're the raw materials, if you like, for actually making the ADCs. The deals we did late last year with Catalan and with the NBE then give us access to, you know, contemporary site-specific conjugation technologies, believed to be increasingly important in terms of advancing high-quality aid. And it also gave us access to a range of pretty interesting payloads, and obviously, we can pick which payloads we're going to do based on what we, ultimately, want to tie.

Baseline demographics. Thanks, so much.

It's Mike Thanks for those questions and certainly they are both really important questions why don't we start with P. J, Let me give you a quick.

Update on that Conundrum, if you will and then we'll move over to Gisela to chat about the car.

Cabo and the other competitive programs.

Yes, hi, keen and it's the P. J. Thanks for the question so with regards to the.

And the prescription data and kind of demand in Q4, and our revenue and I don't know that I'm going to be able to solve the conundrum so to speak but.

Certainly.

What we would say is we see I don't want to comment on any methodologies or the way.

And your capture rates et cetera of the third party prescription data providers.

Peter Lawson: So with respect to where AllerGene fits into this, they have a very interesting antibody masking technology. It's a small peptide, if you like, that sits in the binding domain of the antibody. But it's released in a tumor-specific fashion, so it actually depends on... greatly increased protease activity at the tumor surface, which then clips this peptide off.

But we do see variation and that.

Quarter to quarter with with our products with other products and the market basket. So I think thats just kind of.

And for better force part and parcel of that over time.

And one thing I could even point out with regards to Q4.

If you look at the TR ex data for.

For <unk> for example, I think they were up about 6%, whereas the Q over Q U S revenue.

Peter Lawson: So, it's really intended to increase the therapeutic index, if you like, for any on-target side effects that may occur due to binding to non-target normals versus the target in the tumor. And we think from an overall profile point of view, that's a very attractive technology to have. And as an aside, I'll also point out, it actually broadens out potentially the target space in the ADC field as well. With mouse technology, you can start looking at targets.

It was up 23%. So you just see some discrepancies there of some variability.

I think as we look at it.

Certainly the <unk>.

<unk> of the strong momentum, we had closing the year and.

And really just setting us up well.

For Q1, and and the launch that's ongoing.

Awesome.

Because you want to say a few words about the competitive the competitive situation.

Absolutely, yes, so with respect to the land him data.

C N and she is everyone on the call is she and the abstract for.

And I ask it to you for the clear study and certainly of C and D efficacy data and see a positive study here, which is good news for patients all of mines.

Peter Lawson: He maybe wouldn't want to pursue this if he didn't have some kind of tumor-specific activation. So, you know, I think if you put those things together. Hopefully, you can start to see where our point of differentiation is going to come from here. It's from using, I think, some of the most modern conjugation technologies there that really enable you to get a homogeneous product, and some of the issues really stem from there being mixtures of things that can create manufacturing issues as well.

I think the abstract and is the little sparse on the.

A description of the patient population and I think that is the key there we'll be looking ashwin and more detail are available later and the week Monday.

And then the full of data are being presented in terms of the data that we can glean from the abstract with and thanks for putting the on the comparator arm with Sunitinib that it has been used in other studies as well and.

Jay Olson: So that's the plan, that's definitely the plan from the ADC space, there's probably more to do there, and obviously, we have our first ADC. XB-002, Fantastic, Peter. Thanks for that deep dive into the overall ADC approach. I'm certainly excited about having Adagene collaboration in place now to be able to move that forward, too. Jay, in terms of your first question, look, we're all about growing top-line revenue. Obviously, that is incumbent upon good clinical trial data, successful regulatory outcomes, and then, you know, obviously, very, very strong commercial execution.

On Checkmate 90 of our study and again the keynote four to six trial and when looking at the results here for.

The Sunitinib arm and the clear study, we see and <unk> performance, that's a little bit more akin to the keynote four to six trial with the high response rates for Sunday and Nip of 36 per cent and then overall survival that has not been reached and.

Jay Olson: We've seen that over the last few years in terms of our renal and liver programs, and obviously, there's a lot going on right now in terms of, you know, the commercial launch based on 9ER for first-line renal in Cabo Nevo. So, that's a big driver for us in the immediate to short term.

And after 27 months median follow up and.

And that of course indicates and that the population and.

May be.

The population of AR and less.

Oh, hi favorable risk.

Michael M. Morrissey: As I mentioned and as Gisela mentioned, we have a number of potential SNDA filings this year, top-line data results for first-line liver, prostate, thyroid, and lung trials going. So, our focus is really on top-line growth, and our focus is making sure that we are executing extremely well across that clinical regulatory commercial framework so that we can meet our aspirations for success. Super helpful. Thanks for sharing that vision with us.

Population of patients.

When we look at the Checkmate 90 of our data of where the median OS had been reached after 'twenty for them.

And a follow up with Sunitinib.

The niche and at the showing of 29 months median O S.

So we'll be curious and and looking for a more detailed description of.

Operator: You bet. Thank you. Yeah, thanks, Jay.

Ken Shields: Thank you. Our next question comes from the line of Kenneth McKay of RBC Capital Markets. Please go ahead. Hi, thanks for taking the question and congratulations on the progress. And what a year.

And the patient population and in particular, we will be looking at the distribution of.

Of the patient population by the risk category of favorable versus intermediate or poor risk and.

Operator: Thank you Chris or PJ. Can you help a little bit more with the metrics behind the Cabo Q4 results? The pre-announced print was an awesome surprise, but I'm sort of having a hard time justifying demand versus gross to net versus the inventory changes you mentioned. So if there is anything you can comment on around demand after you back out inventory and gross to net, that would be hugely helpful. And lastly, this was discussed a little bit, but I'd really love to hear the team's perspective once more on sort of a small bit of detail. We heard from the competitive Lendima Keytruda combo in the clear trial. Obviously, an impressive median PFS and hazard ratio there, but that can obviously be defined by baseline demographics. Thanks so much. It's Mike.

The number of patients with the nephrectomy versus notch of which May of course effect of objective response and CR rates and then also other.

Variables, such as patients and metastatic spread tick two of them more oregon's.

With metastatic disease and patients with bone of brain metastases, and liver metastases and I'll make a chance for prognostic factors and their own right and.

Perhaps as a measure of tumor burden the.

Some of target lesion diameters.

And if that is being presented the there's a lot to learn and for sure and this dataset and and outside of the variables for will be looking at and the and the patient population.

Christopher J. Senner: Thanks for those questions, and certainly they're both really important questions. Why don't we start with PJ, give you a quick update on that conundrum, if you will, and then we'll move over to Gisela to chat about Cabo and other competitive programs? Yeah, hi, Keenan. It's PJ.

And just to finish off the air in terms of safety.

And quality of life, you'll be looking for it and those datasets as well that was not going into depth of certainty on the safety side and there was no mention of quality of life and the abstract.

Gisela Schwab: Thanks for the question. So, you know, with regard to the prescription data and the kind of demand in Q4 and our revenue, I don't know that I'm going to be able to solve the conundrum, so to speak. But, you know, certainly, what we would say is we see it. I don't want to comment on any methodologies or the way, you know, capture rates, etc., of the third-party prescription data providers. But we do see variation in that. You know, quarter to quarter with our products and other products in the market basket. So I think that's just kind of, for better or for worse, part and parcel of that over time.

And so we look forward to all of the detailed presentation and also of course, we are holding the investor event on Saturday.

With the number of key experts in RCC, the picture of it George Pal and Mackay.

Mkay, who will discuss the.

New information coming out of the ask could you you want to go up and you'll be able to China just for that event.

Absolutely. Thanks, so much.

Great Ken and thank you.

Thank you. Our next question comes from the line of Stephen Willey of Stifel. Your question. Please.

Yes, good afternoon, and thanks for taking the question.

Maybe just the follow up on the <unk> dynamic question. So I know that there was a I think there was a large phase III trial using cash.

Christopher J. Senner: You know, one thing I could even point out with regard to Q4: If you look at the TRX data for ExitNet, for example, I think they were up about 6%, whereas their Q over Q US revenue was up 23%. So you just see some discrepancies there, some variability. You know, I think as we look at it, it's indicative of the strong momentum we had closing the year and really just setting us up well, you know, for Q1 and the launch that's ongoing.

<unk> as a comparator arm that initiated in the fourth quarter of last year. So I guess can you just speak to what extent the trial surprise trials supply for that study may have impacted product revenue and the fourth quarter. If at all and I guess, if not how does that get accounted for.

So Steve Thanks, It's Chris.

I'm not going to comment about the other trials and what's going on out there and that's it.

If there was revenue and the future you would account for that as normal revenue.

Okay.

Gisela Schwab: Gisela, would you like to say a few words about the competitive situation? Absolutely, yes. So with respect to the LENPM data, we've seen, as everyone on the call has seen, the abstract for ASCODE GU for the clear study and certainly seen the efficacy data, and we see a positive study here, which is always good news for patients. I think the abstract is a little sparse on the description of the patient population, and I think that is the key that we'll be looking at when more detail is available later in the week when the full data are being presented.

And then maybe just the follow up on diesel and his comments regarding the potential incidence rate of favorable risk patients and.

And the clear trial.

I guess I understand the notion that a higher seen the response rate would imply a greater proportion of them.

The favorable risk of patients, perhaps and clear.

But I know that these favorable risk patients are also a headwind on the event driven data with respect to PFS and OS because those patients inherently do better.

<unk>.

So was just wondering if you can somehow.

Gisela Schwab: With a high response rate for sunitinib of 36% and an overall survival that has not been reached after 27 months median follow-up, and that, of course, indicates that the population may be a population of less favorable risk population patients. When we look at the CheckMate 90R data where the median OS had been reached after a 24-month follow-up with sunitinib showing a 29-month median OS. So, we'll be curious and looking for more detailed descriptions of the patient population and in particular, we'll be looking at the distribution of the patient population by risk category, favorable versus intermediate or poor risk, number of patients with nephrectomy versus not, which may, of course, affect objective response and CR rates, and then also other variables such as patients' metastatic spread to two or more organs with metastatic disease, patients with bone or brain metastases or liver metastases, all negative prognostic factors in their own right, and perhaps as a measure of tumor burden, the sum of target lesion diameters, if that is being presented.

Somehow extrapolate those two things for me.

Or do you think the difference this year will be more driven by some of the other baseline variables that you've talked about like nephrectomy status and.

Visceral Mets et cetera.

And Steve It's Mike, Yes, there is a lot of open.

Open questions about the the data because it hasnt been presented yet so.

Our our recommendation is before we get too much into the weeds, let's see the data and let's talk about it on Saturday.

Alright, and then just lastly on the XO and nine two phase one.

And I noticed that.

You specified hormone receptor positive breast cancer as a target indication both for <unk>.

Mono therapy and for combination with it and.

Was just curious if you could maybe provide some of the rationale there just kind of given some of the.

And are welcoming PD, one out of one data that we've seen there thus far thank you.

Sure.

Hello, Peter and want to comment on the.

Yeah.

Sure and I'm happy to comment on the and phase one expansion cohort. So we have the.

The dose expansion cohorts based upon the observations.

Of course, the and learnings from the Cabozantinib program single agent experience as well as.

Gisela Schwab: So, there's a lot to learn for sure in this data set, and those are the variables we'll be looking at in this. And just to finish off, in terms of safety and quality of life, we'll be looking for those data sets as well. They were not going into depth, certainly on the safety side. And there was no mention of quality of life in the abstract.

And I S T and Ctrip studies and and that stage.

The single agent Cabozantinib combinations and <unk>. This is an indication we have seen where we've seen some activities for cabozantinib is the single agent mm.

And aren't curious about and the combination.

Ken Shields: So we look forward to all the detailed presentations. And also, of course, we are holding the investor event on Saturday with a number of key experts in RCC, Dr. Tewari, George, Pal, and McKay, who will discuss the new information coming out of ASCO-GU. And we hope that you'll be able to join us for that event. Absolutely. Thanks so much.

And with a checkpoint inhibitor and <unk>.

Given the.

The cooperative activity that we are assuming here between the two of pathway and.

And if you wanted to comment for Destiny.

No I was kind of just add the mechanistically.

The the rationale for combining.

So nothing too with checkpoint inhibitors is very broad.

And is applicable to multiple multiple different tumor types.

Operator: Great, Ken, thank you. Thank you. Our next question comes from the line of Stephen Willey of Stiefel. Your question, please. Yeah, good afternoon.

Some of the individual targets of of I'm trying to like met for example of suddenly up regulated and liver expressed and.

And and breast cancer as well for those.

Stephen Douglas Willey: Thanks for taking the question. Maybe just to follow up on the 4Q dynamic question. So I know that there was, I think there was a large phase three trial. Cabo has a comparator arm that started in the fourth quarter of last year. So I guess, can you just speak to what extent that trial supply, trial supply to that study may have impacted product revenue in the fourth quarter, if at all? And I guess, if not, how does that get accounted for? So Steve, thanks. It's Chris.

And the potential for kind of direct right Cumulus idle effects from the from the drug itself, but it's really around the breadth of the changes.

We've seen the Clinton and Cabo and then they'll seen pre clinically with we live in line two on different components of the of the immune system.

Okay. Thank you for taking the questions.

Thank you. Our next question comes from Paul Choi of Goldman Sachs. Your question. Please.

Yeah.

Thank you and good afternoon, and thank you for taking our questions.

Christopher J. Senner: Yeah, I'm not going to comment about the other trials and what's going on out there. But if there was revenue in the future, you would account for that as normal revenue. Okay. Maybe just to follow up on Gisela's comments regarding the potential incidence rate of favorable risk patients in the CLEAR trial. I guess I understand the notion that a higher C-Native response rate would imply a greater proportion of favorable risk patients. Perhaps I'm not clear.

I had one commercial question for either Chris or P. J and that's with respect to the to the gross to net trends can you maybe just comment on how that how that progressed over the course of <unk> versus <unk> and as youre promoting the all of the frontline combination here of how we should think about gross the gross to net for.

<unk> over the course of 2021 relative to 2020.

Thanks, Paul So yeah, I mean gross to net was slightly down in Q Q4 versus Q3.

Operator: But I know that these favorable risk patients are also. I headwind on the event-driven data with respect to PFS and OS because those patients inherently do better on SUNY. So, I was just wondering if you could.

And we did have the.

The higher proportion of commercial patients in the quarter, so that did impact our gross to net.

And and.

Michael M. Morrissey: Transcribed by https://otter.ai. Or do you think the differences here will be more driven by some of the other baseline variables that you talked about, like nephrectomy status and Visceral Mads, et cetera? Hey Esteem, it's Mike.

From a 2021 perspective, we're looking at gross to net.

And as we based on our guidance that we've put forward you know the 950 million to the.

The ability of the bill.

And $50 million.

Revenue guidance number growth and gross to net and that 25 to 26 per cent range.

Gisela Schwab: Yeah, there's a lot of open, open questions about the data because it hasn't been presented yet. So our recommendation is before we get too much into the weeds, let's see the data, and let's talk about it on Saturday.

For 2021, Okay. That's very helpful. Thanks, I appreciate the detail and then Mike.

And my follow up question on the clinical side as well.

Stephen Douglas Willey: All right. And then, just lastly, on the Excel 09-2 Phase 1. I think I noticed that you've specified hormone receptor positive breast cancer as a target indication both for monotherapy and for combination with itezo and was just curious if you could maybe provide some of the rationale there, just kind of given some of the underwhelming PD-1 L1 data that we've seen there thus far. Thank you. Sure. Gisela, Peter, would you like to comment on that?

With respect to the ex all of 92 program can you maybe for Gisela can you maybe just comment on your level of visibility with respect to the efficacy and safety profile for the monotherapy and and the combinations.

And I ask this with regard to your comment and the PR and earlier comments just that that you plan to.

Proceeding to pivotal is by by year end here. So I was just you know the.

The level of confidence and visibility that gives you.

For being able to move into the pivotal trials by by year end here.

Stephen Douglas Willey: Sure, and I'm happy to comment on the phase one expansion cohort. So we have built those expansion cohorts based upon observations, of course, and learnings from the Cabo San Chinub program, single agent experience, as well as IST and CTEP studies in that space, either single agent Cabo San Chinub or combinations.

Yeah and happy to.

The address that question and the.

Excellent and I'm truly single agent phase.

Stage, one study and its been ongoing for a little bit and.

The dose escalation study and as we escalate to higher dosage and and get towards the identification of the M. T D.

And we obviously have followed up patients for quite some time and we'll be looking forward to presenting data at the scientific meeting to present, the safety and efficacy across the study and of course of the dose ranging but.

Gisela Schwab: And this is an indication where we've seen some activity for Cabo San Chinub as a single agent and are curious about the combination with a checkpoint inhibitor, given the cooperative activity that we are assuming here between Peter, if you wanted to comment further. No, I would just add that, mechanistically, we think the rationale for combining... O9-2 with checkpoint inhibitors is very broad and is, you know, applicable to Some of the individual targets of O92, like MET, for example, are certainly upregulated and overexpressed in breast cancer as well as in Direct Tumor Cytolith. The rug itself.

The data that we're seeing that's far edge and consistent with the help me sit out and.

And in terms of constructing the molecule.

And the pharmacokinetic profile and that's borne out and.

And as hoped for as was mentioned earlier.

Early on and the call and so we.

We see the program and to a large degree derisked given and.

Paul Choi: It's really around the breath, Susan. Changes that, you know, we've seen certainly with Cabone and now seen pre-clinically with O9-2 on different components of the immune system. Okay, thank you for taking the questions. Thank you. Our next question comes from Paul Choi of Goldman Sachs. Your question, please. Thank you. Good afternoon. And thank you for taking our questions. I have one commercial question for either Chris or PJ, and that's with respect to the growth to net trends.

And that except one and two it's very similar and this target profile, it's cabozantinib and we certainly have many many years of experience with.

And with Cabozantinib is the single agent and in combination so that is the.

And the backdrop.

From which we are making the comment of hoping to initiate pivotal studies and 2021.

Christopher J. Senner: Can you maybe just comment on how that progressed over the course of 4Q versus 3Q? And, as you're promoting the frontline combination here, how should we think about the gross net progression over the course of 2021 relative to 2020? Thanks, Paul. So yeah, I mean, gross net was slightly down in Q4 versus Q3.

So maybe just a quick follow up so the.

Is the correct and frontier of that Youll be just advancing the monotherapy into each of pivotal trials or do you could you also be able to advance the combination.

Yeah.

I think that it says something would be addressing them as they move forward and accumulate data and then the.

Ultimately initiate the pivotal trials.

Okay. Thank you very much.

Yes.

Yeah.

Thank you at this time I'd like to turn the call back over to today's host Susan Hubbard and Susan Hubbard for closing remarks.

Paul Choi: And, you know, we did have a, Higher proportion of commercial patients in the quarter, so that did impact our gross event. And from a 2021 perspective, you know, we're looking at gross net as we as we, you know, based on our guidance that we put forward, you know, 950 million to, The 50 million revenue guidance number, we're looking at gross to net in that 25 to 26 percent, question on the clinical side is, with respect to the XL092 program, can you maybe for Gisela, can you maybe just comment on your level of visibility with respect to the efficacy and safety profiles for the monotherapy and the combinations?

Thank you and thank you all for joining US today, we are running quite a bit over on time, So we'll need to wrap up the call but on the thank you for joining us and certainly welcome your calls with any follow up questions.

Okay.

Ladies and gentlemen that does conclude today's call. Thank you for your participation you may disconnect. Your lines at this time of a great day.

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Paul Choi: I ask this with regard to, you know, your comment in the PR and earlier comments just that you plan to, you know, proceed into pivotals by year-end here. So I was just wondering the level of confidence and visibility that gives you a sense of being able to move into the pivotal trials by year-end. I'm happy to address that question. The Excel 192 single-agent Phase 1 study has been ongoing for a little bit.

Yes.

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Paul Choi: Dose Escalation Study, and as we escalate to higher doses and get towards identification of the MTD, we obviously have followed up patients for quite some time, and we'll be looking forward to presenting data at a scientific meeting to present both safety and efficacy across the study and across the dose ranging. The data that we're seeing thus far is consistent with how we set out in terms of constructing the molecule and the pharmacokinetic profile has borne out as hoped for, as was mentioned earlier on in the call, and so we see the program, to a large degree, de-risked given that Exel-092 is very similar in its target profile as carbazantinib, and we certainly have many, many years of experience with carbazantinib as a single agent and in combination, so that is the backdrop from which we are making the comment of hoping to initiate pivotal studies in 2022.

Okay.

Non-GAAP.

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Gisela Schwab: So maybe just a quick follow-up. So, is the correct inference here that you'll be just advancing the monotherapy into pivotal trials, or do you think you'll also be able to advance the combination? I think that it's something we'd be addressing as we move forward and accumulate data and then ultimately initiate.

All of it.

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Paul Choi: Okay, thank you very much. Thank you. At this time, I'd like to turn the call back over to today's host, Susan Hubbard, for her closing remarks. Thank you. I want to thank you all for joining us today. We are running quite a bit over on time, so we'll need to wrap up the call, but I want to thank you for joining us and certainly welcome your calls with any follow-up questions. Ladies and gentlemen, that does conclude today's call.

Paul Choi: Thank you for your participation. You may disconnect your lines at this time. Have a great day. Thanks for watching! ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ???