Q3 2020 Exelixis Inc Earnings Call

[music].

Operator: Good day, ladies and gentlemen, and welcome to the Exelixis 3rd Quarter 2020 Financial Results Conference Call. My name is Holly, and I'll be your operator for today. As a reminder, this call is being recorded for replay purposes.

Good day, ladies and gentlemen, and welcome to the Exelixis third quarter 2020 financial results Conference call. My name is Holly and I'll be your operator for today as a reminder, this call is being recorded for replay purposes I would now like to turn the call over to your host for today Ms., Susan Hubbard Executive Vice President.

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 go ahead. Thank you, Holly, and thank you all for joining us for the Exelixis third quarter 2020 financial results conference call. Joining me on today's call are Mike Morrissey, our President and CEO, Chris Senner, our Chief Financial Officer, Issa Schwab, our Chief Medical Officer, Peter Lamb, our Chief Scientific Officer, and PJ Haley, our Executive Vice President of Commercials, who will together review our corporate, financial, commercial, During the call today, we will refer to financial measures not calculated according to generally accepted accounting principles.

In a public affairs and Investor Relations. Please go ahead.

Thank you Holly and thank you all for joining us for the Exelixis third quarter 2020 financial results Conference call.

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 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.

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 competition, regulatory review and approval processes, conducting clinical trials, compliance with applicable regulatory requirements, our dependence on collaboration partners, and the level of cost associated with discovery, And with that, I will turn the call over to Mike. All right, thank you, Susan, and thanks to everyone for joining us on the call today. Exelixis continued to advance all components of our business in the third quarter as we built the foundation to accelerate revenue growth for Cabo Santanib in 2021 through potential new commercial opportunities and a variety of mission-critical development and regulatory milestones.

Issued an hour ago for our third quarter 2020 financial results and an extensive list of key corporate accomplishments.

Susan T. Hubbard: Please see our press release that was issued an hour ago for our third quarter 2020 financial results and an extensive list of key corporate accomplishments. The highlight of the quarter was the ESMO presentation of the positive results from Checkmate 90R, the Phase 3 pivotal trial evaluating the Combo-Nevo combination and Firstline RCP. We're excited to highlight the compelling activity of the CABO and NEBO doublets, notably the significant improvement in overall survival, with a doubling of both progression-free survival and objective response rate and extended duration of response, the improved tolerability with low discontinuation rates, and improvements in health-related quality of life compared to. The FDA has accepted our application and granted a priority review with the PDUFA date of February 20, 2021. The Exelixis commercial organization is launch ready, and the United States should have approval come sooner.

Michael M. Morrissey: Our urgency and focus are driven by the consistent feedback from ESMO that an IER represents best-in-class IOTKI data and reinforced by recent market research, which indicates that a large number of previously untreated RCC patients could benefit from the combination of these two market-leading single agents. When the size of the first-line RCC patient population and the long duration of PFS observed with the Cabo Nevo doublet are viewed together, we project a While first-line RCC remains our top priority as the next commercial growth opportunity for CABOS Antenib, we continue to make important progress with key discovery and development activities while advancing CABOS' potential utility in additional oncology indications.

Accurate.

Well first line RCC remains our top priority is the next commercial growth opportunity for Cabozantinib, we continued to make important progress with key discovery and development activities, while advancing Carlos potential utility in additional oncology indications nodes.

Michael M. Morrissey: Notable progress has been made in Q3 and throughout 2020 in enrolling the four COSMIC trials, including O2-1, 311, 312, and 313, as well as initiating three new global phase three pivotal trials of cobizantinib in combination with etizolizumab as part of the CONTACT clinical trial program. The success of CHECKMATE 9-ER, coupled with data presented this year at various ASCO meetings for CABO-IO combinations in liver, prostate, lung, and bladder cancers, highlights the important role CABO's antenna can play as a unique and differentiated TKI backbone.

15, plus years of clinical experience with Cabo to a broad and accelerated development plan that has the potential to demonstrate a substantially improved risk profile compared to more typical early stage programs.

Michael M. Morrissey: These early signals of compelling efficacy and tolerability may provide potential encouraging read-through for current pivotal trials in new indications. Finally, Exelixis continues to make significant progress in our growing early-stage pipeline. We are excited to advance XL092 into ICI combination cohorts and share the initial details of its discovery and early clinical pharmacokinetic characterization, which validates our overall efforts to build an improved next-gen multi-targeted TKI that phenocopies CAVO's target inhibition profile with a more user-friendly clinical half-life. We aim to apply our 15 plus years of clinical experience with CABO to a broad and accelerated We anticipate Excel 09.2 will move into full development in 2021.

We anticipate XL Onein two will move into full development in 2021.

Beyond Xol nine to our early stage pipeline continues to advance nicely with internal discovery efforts in a number of important new collaborations to reinforce our growing presence in receipts we.

We expect to file up to four new ideas over the next six months as a result of our internal efforts and the work of our discovery partners I'm incredibly proud of the commitment and focus displayed by the entire Exelixis team as we continue to drive our business forward. During these challenging times, so with that I will turn the call over to Chris.

Michael M. Morrissey: Beyond XL-092, our early stage pipeline continues to advance nicely with internal discovery efforts and a number of important new collaborations to reinforce our growing presence in ADC. We expect to file up to four new INDs over the next six months as a result of our internal efforts and the work of our discovery partners. I'm incredibly proud of the commitment and focus displayed by the entire Exelixis team as we continue to 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 Q3 financial results. Thanks, Mike. For the third quarter of 2020, the company reported total revenues of $231.1 million. Total revenues for the quarter included comprehensive franchise net product revenues of $168.6 million.

Cash and investments for the quarter ended September Thirtyth 2020 was over $1.5 billion.

Now turning to our fiscal year 2020 financial guidance.

We are updating the financial guidance, we provided earlier this year to reflect the changes to our business in the second half of 2020, we.

Christopher J. Senner: Net product revenues in the third quarter of 2020 were negatively impacted by lower demand and a decline in host filler inventory. However, total revenues also included $62.5 million in collaboration revenues from Ipsen, Takeda, and Genentech. Our total operating expenses for the third quarter of 2020 were $273.7 million compared to $183.9 million in the second quarter of 2020. R&D expense was the primary driver of the increase in total operating expenses, which increased by approximately $61.8 million and was primarily related to increases in licensing and milestone fees associated with existing and new business development activities, stock-based compensation expense, and clinical trial expenses from our continuing investments in Cabo San Antonio and our emerging pipeline. Provision for or The company reported a gap net loss of $32 million or $0.10 per share basic for the third quarter of 2020. The company also reported non-gap net income of $11.2 million or $0.04 per share on a fully diluted basis.

As has preclinical development work at our network of CRM sales.

As a result, we now have the opportunity to file to full I. Indeed in the next six months. This.

This quarter, we could file by at least for the CDK seven inhibitor, well, one or two from our Aurigene collaboration which going forward, we will refer to as the XL Wellington.

And the tissue factor targeting AIDC icon to from our iconic collaboration which we will refer to as the XP 002 going forward.

Christopher J. Senner: Non-GAAP net income excludes the impact of approximately $43 million of stock-based compensation expense net of the related income tax effect. Cash and Investments for the quarter ended September 30, 2020 were over $1.5 billion. Now turning to our fiscal year 2020 financial guidance. We are updating the financial guidance we provided earlier this year to reflect changes in our business in the second half of 2020. We are maintaining our total revenue guidance, which we expect to be in the range of $900 and $950 million, to the Higher Milestone in R&D Reimbursement Revenue. Net product revenues are expected to be in the range of $700 and $725 million. The cost of goods sold is expected to be approximately 5% of net product revenue.

Christopher J. Senner: Research and development expenses are increasing due primarily to higher forecasted licensing expenses and are expected to be in the range of $550 and $575 million, which includes non-cash expenses related to stock-based compensation of approximately $40 million. Selling general administrative expenses are increasing due primarily to incremental personnel-related costs and are expected to be in the range of $290 and $300 million, which includes non-cash expenses related to stock-based compensation of approximately $70 million.

Angiogenesis.

Oh 40 caves are expressed in various immune cell types in the human microenvironment and activation promotion immune suppression.

For example, activation of actual murder on tumor associated macrophages promotes immune suppressive M. Two macrophage phenotype.

Activation of budget are to promote T rig NBRC proliferation, while met activation inhibits antigen presentation by dendritic cells.

Upregulation activation of met in a soaps suppressive subset of neutrophils also occurs in response to immune checkpoints located in preclinical model and install to drive resistance.

Cabozantinib shown promising activity in combination with PD, one or PDL, one antibody, even phase 1 billion phase III clinical trials.

Christopher J. Senner: Guidance for the effective tax rate in 2020 is decreasing and is now expected to be in the range of 14 and 16 percent. And finally, we are projecting cash investments to be in the range of $1.5 and $1.6 billion. This guidance does not include the impact of potential new business development activities.

Peter Lawson: And with that, I'll turn the call over to Peter. Thanks, Chris. I'm happy to provide an update on our preclinical development and pipeline expansion. Work at our Discovery Laboratories in Alameda is continuing, following stringent protocols to protect the health of our employees. It was exciting to see the ongoing flow of data, and we're continuing to make progress on an early stage discovery. And I'd like to take this opportunity to thank all of our Discovery Team members for making this happen. Work at our discovery partners, particularly Invenra, Origine, and Iconic, has continued to advance, as has preclinical development work at our network of CROs. As a result, we now have the opportunity to file four INDs in the next six months.

Peter Lawson: This quarter we could file INDs for the CDK7 inhibitor AUR102 from our Origin collaboration, which going forward we will refer to as XL102, and the tissue factor targeting ADC, ICON2, from our iconic collaboration, which we will refer to as XB002 going forward. Early next year, we could also file IMDs for XL265, a tankinase-focused TKI from our internal laboratory, and a second compound from our origin collaboration with a novel mechanism. We recently presented data on XL092, our next-generation MET-VEGFR-Axl-MIR inhibitor that is currently in Phase I trials at the recent EORTC-NCI-AHC Army meeting. In addition, Auradine presented data on XR102, the CDK7 inhibitor, at the same meeting, and Iconic presented data on XB002, the tissue factor targeting ADC, at the recent World ADC We plan to present data on Excel 265 and the second origin compound at major scientific meetings next week.

Over four cohorts and two formulations dose dependent increases in Cmax and you see a resident.

Peter Lawson: I will recap some of the key data from the XL092 presentation. XL092 is intended to build on the in-depth understanding that we've gained with respect to the clinical activity of cabozantinib, both as a single agent and in combination. Cabazantinib is a potent inhibitor of the RTKs MET, VEGFR2, AXL, and MYR, which are widely expressed on tumor cells and on cells in the tumor microenvironment. Both MED and AXL are overexpressed in a variety of solid tumors, and their activation drives tumor growth, survival, invasion, and metastasis. In particular, upregulation of MET and, increasingly, AXL has been linked to resistance to multiple therapeutic interventions, including chemotherapy, targeted therapy, anti-angiogenic therapy, radiation, and immune checkpoint blockade. Both MEG and VEGFR2 are also expressed in the tumor endothelium, and their activation promotes tumor angiogenesis. All four RTKs are expressed in various immune cell types in the human microenvironment, and their activation promotes immune suppression. For example, activation of Axel and Mer on tumor-associated macrophages promotes the immune-suppressive M2 macrophages.

By Dr. Camilo pasta.

Peter Lawson: Activation of VEGFR2 promotes Treg and MDSC proliferation, while MET activation inhibits antigen presentation by dendritic... Upregulation and activation of MET in a suppressive subset of neutrophils also occurs in response to immune checkpoint blockade in a preclinical model and is thought to drive resistance. Cabazazinib has shown promising activity in combination with PD-1 or PD-L1 antibodies in Phase 1b and Phase 3 clinical trials. In the clinic, Kawazantanib has a terminal heart life of about 99 hours, which results in initial drug accumulation and an extended washout period when the drug is withdrawn. Our aim in optimizing XL092 was to identify a compound with a similar target inhibition profile to cabozantinib, but with a shorter clinical half-life. The in vitro profile of Excel092 shows that it is a potent inhibitor of MEK, VEGFR2, AXL, and Mer in biochemical and cellular assays, with the relative activities against these RTKs being comparable to Kawasaki. Oral dosing of XL092 to tumor-bearing mice results in profound inhibition of MET and AXL activity in tumors and of ZFR2 activity in lung tissue, consistent with its in vitro profile.

311, 312, and 313 studies, where these have either completed or are nearing full enrollment on a global level.

And we are on track for topline results for these trials, it's previously shared.

Importantly, we have also been able to start up the three phase three trials under the contact truth faith.

Peter Lawson: XL092 is highly active at well-tolerated doses in multiple xenograft models with activity that is comparable to kerosene. XL092 has also been tested in the CT26 murine syngeneic colon carcinoma model, both as a single agent and in combination with a PD-1 antibody. This model is relatively refractory to PD-1 antibodies, and a PD-1 antibody alone did not improve the survival of mice compared to VX1. In contrast, single agent XL092 significantly improves survival. Notably, the combination of XO-092 and PD-1 antibody resulted in a further improvement in survival, suggesting synergistic activity for the combination. Additionally, all treatments were well tolerated.

Peter Lawson: Exelin 9-2 is currently in a Phase 1 trial in patients with advanced solid tumors. Over four cohorts and two formulations, those dependent increases in CMAX and AUC are evident. The terminal half-life for Exel 09-2 is between 20 and 28 hours, significantly shorter than the 99-hour terminal half-life for Kepler-9.

Valuation of the combination with T. The reason that in a parallel phase one be part of the study while completing single agent dosing.

Peter Lawson: Overall, the data show that XL092 meets the goal of maintaining the cabozantinib target inhibition profile while having a significantly shorter clinical pharmacokinetic. We've had a very busy quarter from a business development perspective and are progressing a number of discussions. We continue to assess opportunities in both the small molecule and biologic space, which we find scientifically compelling and where we see a clear path forward for us to effectively develop and commercialize our products, with an emphasis on clinical or neoclinical stage programs. We recently announced new collaborations with Redwood Catalan and NVE Therapeutics to develop novel ADCs using their respective site-specific conjugation and payload technologies.

We are also in the late stages of planning a broad and comprehensive development program for example, or nine true across various tumor indications.

Lines of therapy and settings of interest.

And intend to pursue the comprehensive evaluation of Axa aren't true in combination with various establish checkpoint inhibitors and potential new combinations, including promising new checkpoint inhibitor to platts as well as other combination partner interest.

We have a deep until Elektron division in Teekay eyes, and extensive experience with Cabozantinib.

And see many opportunities to build on and expand the therapeutic settings as we plan for potential tumor indications and lines of therapy for EXL Onein, two combinations, including first cars to market strategies for.

Issa Schwab: Through these collaborations, we intend to develop a pipeline of ADCs to address a broad spectrum of tumor types by targeting selected tumor antigens specifically matched to the most appropriate payloads for a given indication. These would follow on from what would be our first ADC to reach the clinic, XB002, which is the subject of our collaboration with ICONIC, and for which an IND filing could occur in the near future. We look forward to providing additional updates on these BD discussions as they come. I'll now turn the call over to Peter. Thank you, Peter. I'm pleased to provide an update on our Kabbalantian Regulatory and Development Program, our progress on Excel 092, and new compounds moving toward IND. I'll start with Checkmate 90R.

So high unmet need indications with potential for accelerated development.

Second moving beyond Kabul strategies and building our clinical experience in tumors recovers antennas is approved or being developed with the goal to develop new standards of care with novel and expanded combinations.

Issa Schwab: We've made a lot of progress since the positive top-line results were announced for cabozantinib and nivolumab combination in first-line RCP in late April by BMS and Exelixis. As you recall, the study demonstrated a significant benefit over the comparator sunitinib for all three efficacy endpoints, including a significant improvement in overall survival with a 40% reduction in the risk Additionally, the combination of carbazantinib at 40 milligrams daily and nivolumab was generally well tolerated and associated with a low discontinuation rate, while maintaining an improved quality of life compared to sunitinib.

Issa Schwab: Detailed results of the study were presented by Dr. Tony Tureri at the recent virtual ESMO conference, in the Presidential Symposium, and favorably discussed by Dr. Camilo Porta. On the basis of the results from the trial, we have made great regulatory progress together with BMS and our partners Ibsen and Takeda. We have completed the Supplemental NDA filing concurrently with BMS's Supplemental BLA filing in the United States in August, and FDA has recently accepted the submissions for priority review and signed a PDUFA date of the 20th of February, 2021. Concurrently with the U.S. submission, BMS and Ibsen have also completed the submission in Europe to the EMA, and the filing was validated on September 12th, 2020. Further international findings have also been made, including in Switzerland, Australia, Canada, and Brazil, with many more to follow in short order.

Greatly improved versus more typical early stage programs.

And I'll close with a brief word regarding our R&D candidates.

We are working towards R&D filing before and this year for EXL, one or two in the CDK seven inhibitor that has been discovered by our partner Aurigene.

As well as for Expedia Eurs, there were two or icon to have first biologic product candidate an 80 c. that has been discovered by iconic.

Additional R&D candidates also are making good progress and we'll reach R&D filing in the next few months.

And with that I'll hand, the call over to Peter.

Thank you Lisa.

Pleased to discuss the Cabometyx business as we head into 2021, which will be a transformative year for the brand as we anticipate our first potential combination approval in first line kidney cancer and subsequently further combination data presentations for Cabo.

The strong 90 R&D to position Cabometyx to return the franchise to significant revenue growth.

Issa Schwab: And also, just a few days ago, our partner Takeda, together with Ono Pharmaceuticals, announced the submission of concurrent SNDAs for the combination of carbamazepine and volume up for advanced RCC in Japan. Besides the progress on Checkmate 90-R, the ongoing Phase 3 program for Khabazan Chinep continues to make rapid progress. We have continued our efficient execution of the COSMIC-021, 311, 312, and 313 studies, which have either completed or are nearing full enrollment on a global level.

Momentum build with the launch could further be driven by additional data read outs in other important indications is the robust Cabo development program continues to generate data.

I will discuss the opportunities at 90, our provides exelixis looking forward as we continue to build upon the foundation in RCC, where we remain the number one prescribed single agent Teekay.

We are pleased that cabometyx market share remains stable in Q3, and our key segments in both RCC and HCC.

Issa Schwab: And we are on track for top nine results for these trials, as previously shared. Importantly, we have also been able to start up the three phase three trials under the contact tracing, Phase III program in collaboration with Roche, and all three studies are now screening and enrolling patients globally. Looking back on this quarter, I am thrilled with the progress of the Corpus Anciens.

Issa Schwab: and the level of execution by both our own teams and our clinical network teams, who together have been able to make significant progress despite the challenging times and conditions around the world due to the global pandemic. I'll now turn to the progress on our Excel 092 program and our new IND project. As Peter described in detail, Exel-092 is our next generation MET, Axel, MIR, and VEGFR tyrosine kinase inhibitor that has been designed with a similar target profile as cabozantinib, but with a shorter pharmacokinetic half-life. This is expected to allow for rapid and flexible management of tolerability while maintaining the efficacy profile associated with potent Our ongoing Phase I study has already confirmed that the goal of designing a molecule with a shorter chromocokinetic half-life has been accomplished.

Demonstrating the broad potential for Cabo medics with Nemo in the first line setting.

Additionally, ICI combinations constitute approximately 20% of the second line RCC market.

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

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

The <unk> team has significant experience and RCC with two prior successful launches and we look forward to the opportunity to educate physicians on the 90, our data post approval. So that more patients have the opportunity to benefit from Kabul medics therapy, and the first line setting.

The strength of the 90, our data speaks for itself.

The doubling of medium progression free survival in RR and superior overall survival versus Sunitinib, which provides us with strong differentiation versus the other Io combination therapies currently available.

Importantly, clinical benefits were observed in the vast majority of patients in the trial, resulting in a low rate of primary progression, regardless of Imd's C risk status or patient subtype supporting broad used in the marketplace.

Issa Schwab: And we've recently begun the evaluation of the combination with atazolizumab in a parallel phase 1B part of the study while completing a single agent dose. We are also in the late stages of planning a broad and comprehensive development program for Excel 092 across various tumor indications, lines of therapy, and settings of interest, and Intend to pursue the comprehensive evaluation of Exel-092 in combination with various established checkpoint inhibitors and potential new combinations, including promising new checkpoint inhibitor duplets, as well as other combination partners of interest. We have a deep and solid foundation in TKIs and extensive experience with carbazantinib and see many opportunities to build on and expand the therapeutic settings as we plan for potential tumor indications and lines of therapy for XL092 combinations, including first-to-market strategies for high unmet need indications with potential for accelerated, Second, moving beyond CABU strategies and building on clinical experience in tumors where cabozantinib is approved or being developed with the goal to develop new standards of care with novel and expanded combinations.

In addition, the optimized carbo combination starting dose of 40 milligrams 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 and our research.

Taken together the combination of a best in class TK highlight kaaba with a well established immune checkpoint inhibitor like <unk> and RCC, along with the strong efficacy and safety data from Checkmate 90 are present, the opportunity to share compelling and highly motivating story to our customers and enabled broad.

Positioning across clinical risk groups and first line RCC.

Feedback on the Checkmate 90, our data with both academic and community oncologist has been extremely positive and we believe we can leverage the success and prescriber familiarity of both <unk> and neveau to gain traction quickly and the combination setting when approved.

Our team is laser focused on launch preparation as we stand ready to engage our customers and both live in virtual settings as appropriate as soon as FDA approval is granted.

At the same time as we launched <unk> in combination and the first line there will continue to be patient progressing from ICI based therapy into the second line that will be eligible for carbo medics monotherapy.

We continue to capture a very high percentage of that patient population and belief capo may grow in the second line setting as well.

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

The 90, our data positions carbon evo to take significant market share and the first line setting and provides insight into the potential duration of therapy for Cabo medics in combination.

The median progression free survival per investigator was over 19 months and the median duration of response was over 20 months in the study pointing to the potential for the duration of therapy to be significantly longer than Kabul monotherapy.

Issa Schwab: Third, expanding the TKI footprint by investigating new indications in the IO white space where XL092 can potentially improve outcomes through cooperative activity with immune oncology compounds. And finally, exploring new opportunities and approaches in treatment settings that might be accessible to Excel 092 with potentially improved tolerability due to its shorter half-life. With the goal to potentially start late-stage trials as soon as 2021, we are focusing on advancing 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. Based on our 15 years of experience and clinical success with Cabo D'Angenex, we are highly confident that the RTK inhibition profile of XL092 should also have broad utility, and the shorter half-life for the chemically distinct molecule is likely to offer potential advantages and differentiation as well.

Taken together the increase in first line market share and duration, along with the potential growth and second line positions that <unk> RCC business to vector towards the run rate of $1.5 billion and U S revenue by the end of 2022.

This projection is of course contingent upon our modeling and assumptions, which include a total of five ICI combinations in the marketplace. Furthermore.

Furthermore, this does not include any potential incremental revenue from cosmic 313, the triplet of capo neveau it'd be or any other new carbo data readouts.

Beyond 90 are we are very excited by the Cabozantinib development program as it moves forward broadly across multiple indications with different combination partners. We look forward to building on this momentum and RCC HCC DTC and other potential future indications such as prostate Malone is our development program or.

Valuation cabozantinib in combination with immune checkpoint inhibitors advances.

Our team remains highly focused and motivated to compete every day to bring the benefit of problematics to all eligible patients as we continue to build the franchise and maximize it's clinical and commercial potential and with that I'll turn the call back over to Mike Alright, Thanks, PJ as the outlined at JP Morgan in January.

Issa Schwab: This experience and understanding drives our excitement and enthusiasm around Excel 092, and we ultimately view the development risk profile as potentially being greatly improved versus more typical early stage programs. And I'll close with a brief word regarding our IMD candidates. We are working towards an IMD filing before the end of the year for XL102, the CDK7 inhibitor that has been discovered by our partner Orgene, as well as for XP002 or ICON2, our first biologic product candidate, an ADC that has been discovered by ICON2. Additional IND candidates are also making good progress and will reach IND filing in the next few months. And with that, I'll hand the call over to Peter. Thank you, Gisela.

Patrick J. Haley: I'm pleased to discuss the CaboMedx business as we head into 2021, which will be a transformative year for the brand as we anticipate our first potential combination approval in first-line kidney cancer and, subsequently, further combination data presentations for Cabo. The strong 9ER data positioned Cabo Medics to return the franchise to significant revenue growth. The momentum built with the launch could further be driven by additional 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. We are pleased that Cabo Medex market share remains stable in Q3 across our key segments in both RCC and HC. According to Brand Impact Acuvia, Cabo Medic's TRX share was stable at 31% in Q3 relative to 30% in Q2, while at the same time, TRX volume of the RCC oral TKI market basket of Cabo Medix and Lida, Sutan, and Votrient declined in Q3 by 6% relative to Q2. Cabo Medix TRX volume declined by 3% in Q3 relative to Q2.

To treat tumors.

I'll close by thanking everyone of Exelixis for their efforts in the third quarter under conditions that appear to get more and more challenging each quarter.

The majority of our team has done working from home for more than seven months now and continues to meet the demands of our business with great teamwork expertise and energy I.

Im incredibly proud to say that the entire Exelixis team continues to work as one making every day counts as we discover develop and commercialize the next generation of our medicines for cancer patients in need of better and more effective therapies.

We look forward to updating you on our progress in the future. Thank you for your continued support and interest in Exelixis and we're happy to now open the call for questions.

Thank you at this time, we'd like to remind everyone. If you would like to ask a question. Please press Star then one on your telephone keypad to withdraw your question press the pound key our.

Our first question is going to come from the line of STK Gardien truest.

Hi, guys. Thanks for taking my questions and.

Nice over the next quarter again.

A few if I may add Peter.

Patrick J. Haley: As I mentioned, our focus is squarely on future growth of the Cabo Zancinib franchise, and we are excited by the recent outcome and presentation of the Checkmate 9ER study. We believe that these results, pending regulatory approval, may provide us with the opportunity to grow Cobblematics market share and increase duration of therapy in the first line. The 90-yard data in a presidential session was among the most high-profile presentations at the 2020 ESMO conference, and the data were extremely well-received by the KOLs and in market research we have conducted.

Patrick J. Haley: The ICI combination opportunity is large, with 15,000 RCC patients in the U.S. eligible in the first-line setting, with ICI combination therapy accounting for approximately 80% of that market. According to this brand impact data, ICI-TKI combinations constitute 50% of the first-line market and are widely used across clinical risk groups, demonstrating the broad potential for carbometics with NEVO in the first-line setting. Additionally, ICI combinations constitute approximately 20% of the second-line RCC market.

Sure and we showed already and that the molecule is behaving as hoped for.

Design.

And that it has shown a shorter hoffman with about 24 hours. So.

Patrick J. Haley: Papamedics 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. The Exelixis team has significant experience in RCC with two prior successful launches, and we look forward to the opportunity to educate physicians on the 90-yard data post-approval so that more patients have the opportunity to benefit from Cabo Medix therapy in the first-line setting. The strength of the 90-yard data speaks for itself.

And regarding further data will present data certainly when we have matured data and just know that we are hoping to start at late stage studies in 2021 and of course, we see a big data before we even get to a presenting.

Publishing it and so we can make decisions certainly little bit earlier on as you as we do you will see as we move forward in that direction.

Oh, yes, we need to take the question on the on the kinds of iron modalities might be good and good morning, everyone. Two with I mean, I think I'll be with that so the road opportunity that would be on the August PD, one PDL one cc linked floors as you have your common data, which.

Patrick J. Haley: A doubling of medium progression pre-survival and ORR and superior overall survival versus sunitinib, which provides us with strong differentiation versus the other IO combination therapies currently available. 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. Supporting broad use in the market. In addition, the optimized CABO combination starting dose of 40 milligrams 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.

Do we have clinical PMC essentially from a from kind of that.

Well if you will continue to look at the development of additional agency. They novel checkpoint inhibitors be they find the times.

Any move which could could end up being appropriate combination partners, even a doublet or potentially even triplets with with excellent mine to depending on the indication and sales.

Okay, great. Thank you Peter Thank you. So has got to be side as we said previously we're very focused on using our business development activities to expand our pipeline of either clinical and or preclinical compounds that were pursuing we've certainly did number of deals to two.

Announced this quarter with within D. and Catalent.

Patrick J. Haley: Taken together, the combination of a best-in-class TKI like CABA with a well-established immune checkpoint inhibitor like nivolumab in RCC, along with the strong efficacy and safety data from CheckMate 9ER, presents the opportunity to share a compelling and highly motivating story with our customers and enable broad positioning across clinical risk groups in first-line RCC. Feedback on the CheckMate 90R data with both academic and community oncologists has been extremely 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 when approved. Our team is laser focused on launch preparation, as we stand ready to engage our customers in both live and virtual settings, as appropriate, as soon as FDA approval is granted. At the same time as we launch CaboMedx in combination in the first line, there will continue to be patients progressing from ICI-based therapy into the second line who will be eligible for CaboMedx monotherapy.

On the AIDC side, we have a whole roster a lineup of potential deals kind of coming down the pipe when does it get done if those get done we'll talk about those in more detail. Obviously, we have I think a pretty good feeling for the kinds of activity we're looking for.

The obvious importance of if possible combining with with with with Onein two as we go forward as well.

So there is lots of lots of opportunity and it's a it's a full team effort here in terms of how we're focused to make sure that we make the right investments for the right assets at the right time for the right value right. So so but we're very excited about the recent additions to our to the network of collaborators that we have and looking forward to getting those.

Collaboration is going and really cranking at full speed.

Great. Thanks, a lot guys you bet. Thank you. Our next question is going to come from the line of Jason Gerberry with Bank of America.

Hi, Good day. Good afternoon. Good evening, everyone thought this is cheap on for Jason Thanks for taking our questions.

I guess, maybe first one for me is that you talk about Ipi combo in Reno I'll talk about that there's about 20% of the patients.

Patrick J. Haley: We continue to capture a very high percentage of that patient population and believe CABO may grow in the second line setting as well. There's a great deal to be excited about as we think about the totality of the Cabo Medix RCC business going forward. The 90-hour data positions Cabo Nevo to take significant market share in the first-line setting and provides insights into the potential duration of therapy for Cabo medics in combination. The median progression-presurvival time per investigator was over 19 months, and the median duration of response was over 20 months in the study, pointing to the potential for the duration of therapy to be significantly longer than CABO monotherapy.

Who use the Ipi combo curious do you have the split between I O I O versus Iowa, TK I in that 20% and where are these patients. The day, we can one of the therapy oil where they idle retreat in on where say they may have we seek an hour TK I am proud of mine and that switch to an island.

Hi, Mike.

Yeah, Hi, Sheila Thanks for the question is PJ I'll take that.

So as I mentioned, you know we think of the the 90, our opportunity is very large and broad and pre.

For your question looking at the current sort of market share of Io combinations in RCC. The 20% is in second line. So what we see and this is all for you to brand impact studio data in first line I O combinations account for about 80% of the market right and Thats from a large player.

Patrick J. Haley: Taken together, the increase in first-line market share and duration, along with the potential growth in second-line, positions the Cobblemetics RCC business to achieve a run rate of $1.5 billion in U.S. revenue by the end of 2022. This projection is, of course, contingent upon our modeling and assumptions, which include a total of five ICI combinations in the market. Furthermore, this does not include any potential incremental revenue from COSMIC-313, the triplet of CABO, NEVO, IPPE, or any other new CABO data readout. Beyond 9ER, we are very excited by the Cabozantinib development program as it moves forward across multiple indications with different combination partners. 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 problematic medicines 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.

So thats, the a or larger population and thats the setting in which the nine year study is done. So we would anticipate you know.

Really uptake in that first line sales of the 80% about 50% of total of the market is is.

His io teekay outside.

The 20% I was referring to is.

Second line uptake of Io combinations, and that's kind of a mix of Io T.K.I., Ohio and this is again according to brand impact and you really see those coming after just a variety.

The first line agents, there's no real strong pattern, there, but I think what excites us about certainly the 90, our data in the market research we've done with.

Quite a large number of physicians at this point is that the.

The feedback on the data is very positive.

I mentioned with regards to the safety and Tolerability the efficacy data.

The quality of life data and we think we'll have a significant opportunity.

Particularly in that first line setting there and think we can.

Really drive a lot of market share and as I mentioned also.

The duration of therapy aspect will be really significant for the business when.

When we look at 19 months of PFS by investigator 20 months duration of response in the 90 or study. So we believe that that some duration of therapy will be long certainly much longer than what we see in cabometyx monotherapy.

Awesome, I guess going back to the front line down it seems to be like I always TK I kept pushing up bit by bit every other auto or so do you see there is opportunity for Iot TK I to expand further with the potential to approve of night, how and where we are right now it is at four.

Michael M. Morrissey: All right. Thanks, PJ. As we outlined at J.P. Morgan in January, 2020 is a transitional year for Exelixis as we navigate important readouts from ongoing pivotal trials like 9ER and advance our pipeline with Cabo lifecycle management activities and new indications and combinations, while at the same time building a diversified portfolio of assets. To date, 2020 has been a year of significant achievement and progress across all components of our business in the face of the COVID Fortunately, we continue to acknowledge the potential risk to our business should the pandemic continue to grow in severity, as we've all sadly seen over the last several weeks. We will close by reiterating the three key themes from today's call. First, we expect 2021 to be a transformational year for Exelixis and the Cabo franchise, as we project a 90-hour approval to accelerate revenue growth for Cabo's antique

50% I'm waiting to see if that potentially can reach waiting see that potential ceiling Brio Teekay segment, and there was like flattish yes.

Yes, great question, she and you know as I mentioned, we kind of see that potential abroad. So the 50% Io TK I, we certainly view is.

Our profile being best in class and that's the feedback we're getting.

Being very competitive there. So we think we can.

Take share in that segment, we certainly believe we can take share in the other segments, what broadly the iOS segment as well as the 20% that are teekay monotherapy because certainly this is as compelling data and as we have the opportunity to to educate physicians on it we think expand the market and really steels.

There from all all those segments to.

To benefit patients.

Awesome I guess, maybe a last one from me is that if you guys can grow by any color on your progress on your second lung and prostate cohorts in caustic or Q1, and when can we potentially expect next data update for the two particular locations. Thank you.

Michael M. Morrissey: Based on the size of the first line RCC markets and the long duration of PFS and 90R, we expect to exit 2022 with a $1.5 billion annualized run rate for RCC in the U.S. if our modeling is correct. Second, we're encouraged by XL092 as a next-gen, multi-targeted VEGF-R met-exomer inhibitor with a more user-friendly clinical half-life Expand into new and existing solid tumor indications with a variety of IO backbones and combination strategies.

Thank you probably want to take that one.

Absolutely. Thank you. Thanks for the question and I'm happy to address that.

Poor CRP C and for non small cell lung Andy.

Upland inhibited pretreated population, we have presented data early in the year and ask could you.

Michael M. Morrissey: Third, we are aggressively advancing and investigating a diverse portfolio of next-generation Exelixis cancer medicines, including both small molecule and biological modalities to increase our potential success in helping even more cancer patients with difficult to treat. I'll close by thanking everyone at Exelixis for their efforts in the third quarter under conditions that appear to get more and more challenging each quarter. The majority of our team has been working from home for more than seven months now and continues to meet the demands of our business with great teamwork, expertise, and energy. I'm incredibly proud to say that the entire Exelixis team continues to work as one to make 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.

Michael M. Morrissey: We look forward to updating you on our progress in the future. Thank you for your continued support and interest in Exelixis. And we're happy to now open the call for questions. Thank you. At this time, we'd like to remind everyone that if you would like to ask a question, please press star, then one on your telephone keypad. To withdraw a question, press the pound key.

Operator: Our first question is going to come from the line of Asthika Goonewardene with Truist. Hi guys, thanks for taking my questions, and I shoveled a nice quarter again. A few, if I may. Peter, could you maybe tell us a little bit about what mechanisms of action besides PD-1 and CTLA-4 make sense to you? I'm just wondering if you're thinking about immune agonists, vaccines, and those kinds of mechanisms as well.

Just to complete and the non small cell lung cancer cohort and the checkpoint into the habit of pretreated patient population.

Also completing enrollment with uhm 80 patients and they have a single agent cord in this study as well so.

Peter Lawson: Keisler, I totally understand that you have a lot of opportunity to accelerate the development of O9-2, and we're quite excited to see what you guys do there. But maybe I was wondering, for those of us on the outside, when would we get maybe a first glimpse of that single agent and PD-1 combo data for the dose expansion? And then, Mike, I have to ask... I mentioned $1.5 billion in cash.

They said advanced very 19, and we look forward to more mature Jacob.

And maybe just one quick follow up for me. When you said you had your industry interaction with the F D. A on the.

Lost a cohort six they'd when does that interruption happen.

We have discuss that on various conference call. So that didn't happen to awhile back when we discussed uhm. The initial encouraging observations uhm in the cohort six.

Issa Schwab: That's a nice chunk that you have there. How do you think about business development activity for 2021? Maybe some color on whether there's still going to be more licensing deals or whether acquisitions could be on the plate would be helpful. Thanks a lot, guys. All right. Thanks, Vestika. There's a lot there. Why don't we start with Gisela and Peter at 09.2. Gisela, do you want to start there?

Based upon the first 30 patients. So so we're <unk> very encouraging results in terms of subjective response, Rachel that's a while back and there'll be received that initial encouraging feedback.

Got it thank you.

Okay.

And our next question is gonna come from the line of Peter Lawson with Barclays.

Issa Schwab: Sure, absolutely. Thank you for the question. And your question was around when we get the first look at the phase one data. Peter referred to a little bit of the pharmacokinetic data that was included in the recent presentation and showed already that the molecule is behaving as hoped for when it was designed, in that it has shown a shorter half-life of about 24 hours or so.

Hey, Thanks for taking my question just hold on the revenues just if you could break out or anything around buttload amount or was it came from.

Academia or community setting and.

Infantry was this quarter.

Yeah. This is P J.

With regards to.

Quarter and demand what we saw there.

What kind of reproduce group is.

The entire market basket of.

<unk> down approximately 6%.

Issa Schwab: And regarding further data, we'll present data certainly when we have mature data. And just know that we are hoping to start late-stage studies in 2021. And, of course, we see the data before we even get to presenting or publishing it.

Really I think that's sort of a broad dynamic there in the market.

We didn't really see any differences with regards to academic or community there.

Certainly some some impacts so from Covid with regards to what we're seeing in the health care system.

Peter Lawson: And so we can make decisions certainly a little bit earlier. And as we do, you'll see us move forward in that. Yeah, and just to take your question on what kinds of IO modalities might be good to combine XL092 with, I mean, I think our view is that there's a broad opportunity there, beyond the obvious, PD-1, PD-L1, CTLA-4, as you commented, and which, you know, we already have clinical POC, essentially, from carosantinib. Obviously, we'll continue to look at the development of additional IO agents, be they novel checkpoint inhibitors or cytokines, any and all of which could end up being appropriate combination partners, either in a doublet or potentially even triplets with XL092, depending on the inhibitor. Okay, great. Thank you, Peter. Thanks, Kiswala.

Patient visits being down.

Various follow ups et cetera. So I think that's something we saw broadly with regards to the market certainly also song in the.

Those products reported earnings as well.

Yes, Peter this is Chris so from Ah.

From a reported perspective.

We reported revenue down quarter over quarter about sequential quarter about 10 million about half of that was related to demand, which kind of correlates with what PJ was talking about.

This is for covers it to enfranchise and then the remaining $5 million.

Probably about three or so is related to inventory and the rest is related to slightly higher gross to that.

Great. Thank you and then just as we think about queue for what helps drive et cetera racial those revenues and any.

Any.

Around kind of what could be happening in October.

Michael M. Morrissey: Asthika on the BD side, as we said previously, we're very focused on using business development activities to expand our pipeline of either clinical and or preclinical compounds that we're pursuing. We've certainly done a number of deals, two announced this quarter with NBE and Catalan on the ADC side. We have a whole roster, a lineup of potential deals kind of coming down the pipe.

Yes, Peter it's Mike probably.

Probably not appropriate to talk about the quarter. This early obviously the biggest driver for revenue growth as the 90 hour approval and launch as we talked about and the and the script. So.

We're ready to roll once we get the letter and we're certainly excited about the data and the potential and the team is.

Certainly very skilled and prepared to.

Get out there and educate physicians and prescribers on the date itself, but.

But that's that's the big driver and that's the big message for the call today.

Great and then just find anything around Hec any since around growth or if that was declining as well.

Michael M. Morrissey: You know, when those get done, if those get done, we'll talk about those in more detail. Obviously, we have a pretty good feeling for the kind of activity we're looking for and, you know, the obvious importance of, if possible, combining with O9-2 as we go forward as well.

Yes, Hi, Peter it's PDA again.

One thing I can say is basically HCC businesses.

Stable and cute three more.

More broadly as we look forward.

In HCC, we're obviously looking forward to the.

312 study reading out.

In combination the first line setting with the <unk> and HCC and what we've seen is.

Michael M. Morrissey: So, there's lots of opportunity, and it's a full team effort here in terms of how we're focused on making the right investments for the right assets at the right time for the right value, right? So, but we're very excited about the recent additions to the network of collaborators that we have and looking forward to getting those collaborations going and really cranking them full speed. Great, thanks a lot, guys.

Bev It says approval and Q2 is really driven significant quick uptake for that regiment and personal HCC and that that bodes well potentially for.

Other combination such.

Such as tabla <unk> should the date of the positive and also it's moving Io therapy into the first line and HCC. So as we kind of look longer term, we would anticipate a similar dynamic to what we've seen in RCC, whereas I almost forward and then the sort of.

50% or so of the market they occupied in second one kind of opens up for more TKS utilization and we think the combo medics data in our current label.

Operator: You bet. Thank you, Aska. Our next question is going to come from the line of Jason Gerberry with Bank of America. Oh, hi. Good afternoon. Good evening, everyone. This is Chi on behalf of Jason.

From the celestial study and HCC second line is well positioned to to then take more of that sure and second line as patients progress beyond Io therapy and HCC.

Patrick J. Haley: Thanks for taking our question. I guess maybe the first one for me is that you talk about the ICI combo in Reno, you talk about that there are about 20% of the patients who use the ICI combo, but curious, do you have a split between IO-IO versus IO-TKI in that 20%, and were these patients, did they receive TKI monotherapy, or were they IO re-treatment where, say, they may have received an IO-TKI Yeah, hi Chi.

Great. Thanks, Thanks, so much for the details.

That theater. Thank you.

And our next question will come from the line of Andy Shame with William Blair.

Okay. Thanks for taking my questions and I hope everybody is doing well at X lexis So quick.

Question.

Regarding basically data presented at the Triple meeting so I think the takeover versus areas that there are more similarities or differences.

With the exception about.

Like a temporary 10 10 fold higher potency against actual so the first question I guess for for Peter with useless is kind of a clinical relevance.

Patrick J. Haley: Thanks for the question. This is PJ. I'll take that. So, as I mentioned, you know, we think of the 9ER opportunity as very large and broad. And, you know, as per your question, looking at the current sort of market share of I.O. combinations in RCC, the 20% is in second line.

Weiss typically you chose to optimize that specific target.

And also kind of thinking about bigger picture in 64.

Laying out the development path four O nine two.

Patrick J. Haley: So what we see, and this is all according to brand impact, excuse me, the data in first line, I.O. combinations account for about 80% of the market, right? And that's a large place and that's the large population and that's the setting in which the 9ER study is done. So we would anticipate, really uptake in that first line setting. Of the 80% about 50% total of the market is is IOTKI. The 20% I was referring to is the second line uptake of IO combinations and that's kind of a mix of IOTKI, IOIO and this is again according to brand impact and you really see those coming after just a variety of first-line agents. There's no real strong pattern there but I think what what excites us about certainly the 90-hour data and the market research we've done with you know quite a large number of physicians at this point is if the, The feedback on the data is very positive, as I mentioned, with regards to the safety and tolerability, the efficacy data, the quality of life data, and we think we'll have a significant opportunity, particularly in that first-line setting there, I think we can really drive a lot of market share, and as I mentioned, also, the duration of therapy aspect will be really significant for the business.

Just given dissimilarity how much can you kind of tikkun to what you have in house for cause they go 021.

And accelerate the development of 92.

And.

Question really derived from the fact that you're thinking about advancing that asset into late stage development.

Next year.

Yes.

I'll start Andy Thanks for the question is Eva.

Yeah. So so I think if you got the message from the presentation of the Triple meeting with will be a with only two to retain the.

Improve our recover who opened again Smith excellent.

And moving into the digital too.

Slight <unk>.

We have kind of a budget.

As opposed to give the mix.

That feature we really want to retain and a sales are annoying too.

Quite nicely in the in the in vivo setting as well.

Specifically optimised on actual potency, we wanted to be sure. It was close enough and as you correctly.

Being a business owner is definitely an emerging target of interest and maybe some issues in the middle of indications. We may go through but doesn't notice primary drawing reveal television it was really retaining echoing improvable.

Giving us something.

Significantly showed up pharmacokinetic artwork.

Okay and can easily might take the second part of this question.

Thank you. Thanks for the question answered the question like around the development, passing but can they learn happy learn uhm klezmer go to one and but we can we apply for online too and how can you try of things for me.

Patrick J. Haley: When we look at, you know, 19 months of PFS by investigator, 20 months of duration of response in the 9-ER study, so we believe that that duration of therapy will be long, certainly much longer than what we see in common medical practice. Awesome. I guess going back to the front line, it seems to be like ILTKI keeps pushing up a bit by bit every other quarter or so.

I think it is it P question of course, except 182 is Peter described thank you differentiated product Amanda Coca suggest that he has a shorter half life and <unk>.

Retaining uhm the target inhibition profile uhm that weights and 90 love with carpet <unk> very encouraging activity with until.

That is certainly I have lots of experience with Cabozantinib single aging in combination.

Patrick J. Haley: Do you see there's opportunity for ILTKI to expand further with the potential approval of 9ER and, you know, where right now it is at, you know, 40, 50%? Where do you see that potentially could reach? Where do you see the potential ceiling for the ILTKI segment in the front line setting? Yeah, yeah, great question, Chi. And, you know, as I mentioned, we kind of see that potential broad. So the 50% IOTKI, we certainly view as our profile being, you know, best in class, and that's the feedback we're getting, and being very competitive there. So we think we can take a share in that segment.

And so everything there was to learn anything really in Oh, two law enforcement got you'll find that out trying other clinical experience with cabozantinib.

It's coming to bearing in some way that we can build on let me think about the development cost for eight or nine two while we're not looking to replace Cabozantinib. They arrive at uhm viewing this is the development costs.

With the opportunity to build upon that experiencing property expand the opportunity and to indications outside the correct and near term specific indications uhm that comprise need 15 cover that into footprint.

Patrick J. Haley: We certainly believe we can take share in the other segments, you know, broadly the IOIO segment, as well as the 20% that are TKI monotherapies because, certainly, this is compelling data. And as we have the opportunity to educate physicians on it, we think we can expand the market and really steal share from all of those segments to benefit. I guess maybe the last one for me is that if you guys can provide any color on your progress with your second lung and your prostate cohorts in COSMIC-021 and when we can potentially expect the next data update for these two particular indications. Thank you. Do you want to take try that one?

All set including combination partners nine O therapy into my indication.

And so I think and we certainly see a lot of opportunities add four extra on I choose M and prior to develop and plan.

With various M N combination partners and in different at nine to therapy, but also a cross emerize different indications and that May include some of it comes down some indications, but again, we're not looking to replace comprehension everything I have an opinion to hit your head study.

Great. Thank you.

Maybe one more four P J.

Issa Schwab: Absolutely not. Thank you. Thanks for the question, and I'll be happy to address that. So for CRPC and for non-small cell lung cancer in the checkpoint-inhibited pre-treated population, we have presented data earlier in the year at ASCO-GU and also at ASCO for the non-small cell lung cancer indication, and both have shown encouraging activity for the cabozontinib and atazolizumab combination, showing response rates for CRPC of 32% with a long duration and disease control rate of Likewise, for the lung cohort, we saw a 27% response rate and a good disease control rate there as well. These cohorts, cohorts 6 and 7, have now fully enrolled in COSMIC-021, and we're following up patients to fully understand the mature data in both of these populations. Additionally, of course, we are planning towards a potential accelerated approval path, in particular for the CRPC indication where we had initial interactions with FDA, and that will be dependent upon cohort 6 data and when it's mature, but also additional cohorts in CRPC and the 021 study. So, certainly, following up these cohorts, and we look forward to providing updates as they become available for both indications, and just to complete the non-small cell lung cancer cohort and the checkpoint inhibitor pre-treated patient population, we are also completing enrollment with 80 patients, and we have a single agent cohort in this study as well.

Going back to the.

Today, the dynamic COVID-19 impact with the PKI market.

I'm just wondering if you're seeing any any inflection point.

<unk>.

And.

Abby your thoughts on when that is going to stabilize would it be like in a.

Vaccine be necessary to does it to the Senate see the hours are you anticipate some sort of stabilization going in the near term.

Yeah. Thanks for the question Andy.

I wouldn't I wouldn't want to speculate too much specifically on the RCC PKI market visa b.

Covid I think anecdotally customer feedback you do hear that things are starting to get back to normal depending on the geography the location.

Telehealth et cetera, but I think when you do look at the data that's been put out their publish from folks like the.

The.

The community Oncology Association you see that these things have impacts of screening of.

Just follow up things that may influence the patients.

Journey.

So those I think just take a little bit of time. This is broadly for oncology to kind of work through the system.

Honestly can't really there's no crystal ball for for anyone with regards to the pandemic and I think the system just working working through that but I wouldn't want to speculate uhm.

Too much looking forward, but I think what's important for us.

It was kind of Mike mentioned, we mentioned in the calls that we're very excited about 90 are with regards to.

Getting that approval.

Then being ready to go with the launch and really driving growth and the business forward for combo medics.

Without approval.

Right, Yeah, absolutely, let's look forward to that approval. Thanks for all the insights in answering all my questions.

You bet any.

And our next question will come from the line of <unk> with counting.

Hi, everyone busy for a meal or.

Issa Schwab: So, this has advanced very nicely, and we look forward to more mature data. And maybe just one quick follow-up from me: when you said you had the initial interaction with the FDA on the prostate cohort 6 data, when did that interaction happen? We have discussed that on various conference calls. So that happened a while back when we discussed the initial encouraging observations in cohort six based on the first 30 patients or so, where we've seen very encouraging results in terms of objective response rates. So that was a while back when we received that initial encouraging feedback. Got it.

November thanks for for taking out of the questions I have a couple of questions.

The carpet.

You guys mentioned about the the market trying to put your K I I'm just wondering if you see any specific train our.

A difference in terms of different market segments such.

Such as maybe the second line RTC versus the first line RPC and Weird things Brooklyn, RTC are you seeing any like.

Trent in the different risk.

Category.

In terms of.

<unk> versus.

I'm just wondering how the potential approval 90 are in fourth quarter next year or the potential data from cosmic kingwood.

Patrick J. Haley: Thank you. Thank you. And our next question is going to come from Peter Lawson with Barclays. Hey, thanks for taking my question. Just on revenues, just if you could break out anything around that low demand, whether it came from Academia, the community setting, and what inventory was this called? Uh, yeah, this is PJ.

<unk> it would kind of be worst accents.

And have a follow up question for online too. Thanks.

Yes, Hi, Leo P. J I will take that first question. So as I mentioned know broadly we've kind of presented to GTI trends.

And what they were but what I would say is when you look at the market.

For Rfc's CEC significant utilization of combinations in the frontline setting.

Christopher J. Senner: We'll just, with regard to, um... The Quarter and Demand, you know, what we saw there, kind of referred to in the script, is the entire market basket of CKADS and RCC was down approximately 6%. And, you know, really, I think that's a sort of a broad dynamic in the market. And, you know, we didn't really see any differences with regard to academic or community there.

Approximately.

80% on frontline setting is combination therapy.

In terms of Io and something else and 50% of that is Iowa, PKI. So I think a significant opportunity. There for 90 are looking forward pending approval and as I kind of mentioned, we see 90 are competing across clinical risk groups, which is what we see the.

I O T K I.

To get therapy doing now, it's getting share and favorable.

Intermediate and poor risk and we see 90 are potentially competing across all of those well as well as across all competitors.

Christopher J. Senner: You know, certainly some impact still from COVID with regard to what we're seeing in the healthcare system. Patient visits being down, you know, various follow-ups, etc. So I think that's something we saw broadly with regard to the market and certainly also saw in the reporting earnings of those products. Yeah, Peter, this is Chris.

With regards to the second line, we see problematics, retaining our market share kind of across segments, certainly and the second one currently are key segment, there and have the potential for growth and we really get the the vast majority of patients were progressing from an Io based therapy and the second line. So.

And could see potential growth there.

Christopher J. Senner: So from a reporting perspective, we reported revenue down quarter over quarter about sequential quarter about $10 million. About half of that was related to demand, which kind of correlates with what PJ was talking about. This is for Cabo Zenit and Franchise. And then of the remaining $5 million, probably about three or so is related to inventory, and the rest is related to slightly higher gross.

As we look forward. So I think we're looking at.

Just the potential to grow broadly pending.

The approval of 90 or which were extremely excited about.

Okay. Thanks, So in terms of the first night <unk>.

<unk> are you seeing a more of like.

Sequencing trained up the use of iwai over since I O T. K R or are you maintain as a fan.

Yeah, we've got.

If you look at one of the slides, we've got that broken out.

A bar chart for you so we see about 50% of the first line.

I O T Kat currently and I would say.

Michael M. Morrissey: Great, thank you. And then, just as we think about Q4, what helps drive acceleration on those revenues and any color around kind of what could be happening in October? Yeah, Peter, it's Mike.

That's that's either maintaining or slightly been increasing as what we've seen over the last.

Couple of quarters, So I think that that shows that <unk> is really.

Is kind of resonating broadly in the market place. So I think there is the opportunity to really built on that momentum.

Patrick J. Haley: Yeah, probably not appropriate to talk about the quarter this early. Obviously, the biggest driver for revenue growth is 90 hour approval and launch, as we talked about in the script. So, you know, we're ready to roll once we get the letter. And we're certainly excited about the data and the potential, and the team is certainly very skilled and prepared to, you know, get out there and educate physicians and prescribers on the data. So, but that that's the big driver. And that's the big message.

With problematics potential 90 or approval.

I see so regarding the 092 I'm just wondering.

If you I can if I any potential indication that will allow you to go through with the the X ray ready to redecorate path.

Yeah. This is <unk>. Thanks for the question I think this will be entirely day check attendance declined it's a little bit early to speculate at this point.

And the page one steady we have incorporated expansion cohort and specific indications and asked me and learn more about the compound secondly examined the daytime.

Patrick J. Haley: Great. And then just finally, anything around HCC, any sense around growth or if that was declining as well? Yeah, hi Peter. It's PJ again.

Make a data driven decision.

Patrick J. Haley: You know, one thing we'll say is that basically, the HCC business is stable in Q3. And, more broadly, as we look forward in HCC, we're obviously looking forward to the 312 Study Reading Out in combination in the first line setting with the Tezo in HTC. And what we've seen is Bev Atezo approval in Q2 really drove significant quick uptake for that regimen in first-line HCC and that bodes well potentially for another combination, such as Cabo Atezo, should the data be positive. And also, it's moving IO therapy into the first line in HCC. So as we kind of look longer term, we would anticipate a similar dynamic to what we've seen in RCC, whereas IO moves forward.

Got it okay. Thank you so much you're very helpful.

Okay. So yeah.

Our next question will come from the lineup Michael Schmidt with Guggenheim.

Hey, guys. Good afternoon, and thanks for taking my questions. Maybe just a couple of follow up to prior questions Uhm. It's it's been a little while now since as malware or the check the 90, our data was presented.

Just wondering what feedback has been now from from K well since it's been awhile in one right what your level of engagement.

Physicians has.

I'll have to let you with Feedbag in that regard and also wondering.

Hi, we should think about potential inclusion an empty hand guidelines prior to approval of the combination of February.

Yeah, Hey, Michael This is P. J, so I'll just with regard to the second part of an NCC.

I won't I won't.

Speculate on what they are when they might do it.

You have to kind of wait and see how that goes with regards to feedback.

We've.

Patrick J. Haley: And then that sort of, you know, that 50 percent or so of the market that they occupied in second line kind of opens up for more TKI utilization. And we think the Cabo Medix data in our current label from the Celestial Study in HCC in second line is well positioned to take more of that share in second line as patients progress beyond IO therapy in HCC. Great. Thanks. Thanks so much.

We've talked to a lot of Kols conducted many add boards and we've also done.

Market research.

With a significant amount of community and academic positions. So we're talking well over 100 physicians at this point. So I think we've got a really nice sampling and flavor of feedback and it's all been extremely positive and we believe this will be a best in class combination in terms of I O T K I.

Really looking at the totality of the data it's impressive.

When you look at the the efficacy in terms of its the only combination.

Susan T. Hubbard: You bet, Peter. Thank you. And our next question will come from the line of Andy Shea with William Blair.

Doubles progression free survival survival objected response rate by increasing improving overall survival and doing that while it maintains.

Peter Lawson: Okay, thanks for taking my questions, and I hope everybody is doing well at Exelixis. So, I have a question regarding data presented at the TRIPLE meeting. So, I think the take-home message there is that there are more similarities and differences, you know, with the exception of about a tenfold higher potency against Axel.

Quality of life relative to submit in it which is really novel in the setting and I think you're kind of wrap all that up in the fact that this is a new optimize dose of 40 milligrams daily.

In terms of with combination in Evo here and physicians are viewing is very favorable and looking at.

That they're getting.

Peter Lawson: So, the first question, I guess, for Peter or Gisela is kind of the clinical relevance, you know, why specifically you chose to optimize that specific target. And also, kind of thinking about the bigger picture and things like Gisela for kind of laying out the development path for O9-2, but just given the similarities, how much can you kind of peek into what you have in-house for COSMIC-021 and accelerate the development of O And, you know, that question really derives from the fact that, you know, you're thinking about advancing that asset into late-stage development next year. Maybe I'll start, Andy.

[noise] efficacy that they really.

Want to use for their patience with.

A tolerability sort of safety profile and quality of life.

Really like.

And can kind of build on their experience really both these agents separately so.

It's been very favorable I think we're excited we're ready to go and launch it.

Sort of across the board both virtually an in person and I think that to the entire team just just looking forward to having the opportunity to.

To get out there and educate on the data.

Okay, and then on on cosmic three one to the frontline liver cancer study I guess, how do you think about potential differentiation from the the approved to Sandra give asking combination and if it should purely and efficacy question are there other factors at play that might sway.

Peter Lawson: Thanks for the question. Yeah, so I think that you got the message from the presentation of the triple meeting that the aim of O92 was to retain the target profile of CABO, so potent against MEX, EXEL, and potent against VEGFR2. There was one slight wrinkle there where with CABO, the VEGFR2 potency is more potent against that than MEX, and that feature was very much retained in EXEL092. I think that plays out quite nicely in the in vivo setting as well. Yeah, we didn't specifically optimize for actual potency.

Wait for sessions to prescribe one versus the other combinations potentially pending success help with me.

Yeah, Michael P jail.

Address that as well I think obviously.

You will have to get a positive study and the answer to that will be.

Data dependent I think a couple of things I think about that setting those we're seeing and multiple data sources. The turtledove combination do well in terms of rapid uptake in the first line.

First one share of already 30% to 50%. So that said I think we'll there'll be a great opportunity to differentiate depending on the data with.

Instead of an Io Bev option and Iot K I option. So novel mechanism of action and this is.

A tumor type very much like renal where TKS have been backbone of therapy for over a decade. So I think that that will will be well, we'll do well from an experienced standpoint, there and then I think there's certain nuances.

Peter Lawson: We wanted to be sure it was potent enough, and as you correctly say, it turned out to be a bit more potent. I mean, it is definitely an emerging target of interest in many solid humans and a lot of indications we may go to, but that was not a primary driver of the optimization. It was really retaining that target profile while giving us something that has a significantly shorter pharmacokinetic after-effects. Do you want to take the second part of his question?

With regards to Bevacizumab in terms of the inclusion criteria potential.

Potential places, where physicians will want to think about what are appropriate patients given that that safety profile where.

Perhaps.

We will have a slight advantage there, obviously raptor really waiting to see the data, but certainly represents a large potential growth opportunity and the first one is setting and the <unk>.

Interim potentially some opportunity for those patients progressing on Io.

Based therapy and the second one HCC.

Issa Schwab: Thank you. Thanks for the question. So the question was around the development path and what can we learn or have we learned from COSMIC-021 and what can we apply to O9-2 and how can we drive things forward. I think this is a key question. Of course, Exel O9-2, as Peter described, is a differentiated product, and the profile suggests that it has a shorter half-life while retaining the target inhibition profile that we've learned to love with carbazantinib, and we've seen very encouraging activity with it.

Okay, and then one maybe for Peter Gisela, just an excellent online too so given the similar.

Finding characteristics of that Monica electrical cabinet Uhm telematics.

And.

I guess the shorter half life.

How would one expect that to translate into a different yet it clinical profile is it is it mainly a safety advantage uhm or might that enable.

Any other potentially higher dosing pushing efficacy maybe further and.

The result of that.

Are there certain potential indications echelon 19 might be.

Issa Schwab: So with that, certainly, we have lots of experience with carbazantinib as a single agent and in combination. So everything that we've learned and anything really in COSMIC-021 but also in other clinical experience with carbazantinib is coming to bear in some way that we can build on when we think about the development path for Exel O9-2. While we're not looking to replace carbazantinib, we're rather viewing this as a development path with the opportunity to build upon that experience and broadly expand the opportunity into indications outside the current and near-term specific indications that comprise the existing carbazantinib footprint, also including combination partners, line of therapy, and tumor indications.

Patiently pulsation go lots of two Calmat aches for example.

Yeah the city is that.

And thank you for the Christian I think the I think.

<unk>. The question is a Honda C extra wuyda hotline transferring it into differentiated profile I think at the key here is that is very Suzanne management, and my management of tele ability could be improved and.

Could sit side and will quickly is T. J explained earlier comprehension, depending on the house side and Goodbye shop time.

It's longer so that's like the expect it to be shorter than and at first and then could uhm subsides. It looks like you.

Uhm and so like would be potentially resulting in if your bill while you're just twinkling T K I in that fashion.

Issa Schwab: So I think we certainly see a lot of opportunities for Exel 092's broad development plan with various combination partners and in different lines of therapy, but also across an array of different indications. And that may include some of the carbamazantin indications, but again, we're not looking to replace carbamazantin if we're not looking to do head-to-head studies. Great, thank you. And maybe one more question for

And that could translate into it improves safety profile and transfer and I bet advantages and that could N. B a notable uhm and the shorter half life of course, it's also important so I'm thinking about pairing surgery uhm indications.

[laughter] administration, where bowling Keeling H balance, please and things like that will always have to be kept in mind when guilting a longer have nice at T. K I DS targets, making it far.

Patrick J. Haley: Going back to the kind of the dynamic COVID-19 impact with the TKI market. I'm just wondering if you're seeing any any inflection point. And, you know, maybe your thoughts on when that is going to stabilize? Would it be, would like a vaccine be necessary to see that or, or you anticipate some sort of stabilization going in the near term? Yeah, thanks for the question, Andy. You know, I wouldn't, I wouldn't want to speculate too much specifically on the RCC TKI market vis-a-vis COVID. You know, I think anecdotally, customer feedback, you do hear that things are, you know, starting to get back to normal, depending on the geography, the location, you know, telehealth, etc. But I think, you know, when you do look at data that's been put out there published from folks like the community COAH, the Community Oncology Association, you see that, you know, these things have impacts of screening, of, you know, just follow up, things that may influence the patients. Journey.

And so that could be uhm, setting, where a shorter how can I fix ourselves fantasy.

Yeah, but this would be a very specific indication here Uhm General V C extra on a two H one it's a compound that can potentially have a broad and diversified development that including such indication.

Thank you.

Okay. Thank you so much.

Thank you Michael.

Our next question will come from the line of Kennon Mackay with RBC capital market.

Hi, Thanks for taking the question.

I was hoping the the 10th would come up a little bit about specifically <unk> color move on to check in 90, our profile would be differentiated in the eyes with physicians versus some of the other.

Checkpoint.

Combo that are already approved essentially.

What's what's gonna be the edge that dries physicians to choose how 'bout Nemo over any of the other combinations. Thank you.

Yes. They came in this as a pjs of take that.

As I was kind of referring to earlier I think the the data really compelling and we've heard this from.

Broadway in market research Kols like first of all is the only not only the only Iot cat that the only combination this dominantly PFS and objected response rate, while improving survival. So I think when you look at the totality of the efficacy data that's very compelling.

Patrick J. Haley: So those, I think, just take a little bit of time. This is broadly for oncology to kind of work through the system. Obviously, you can't really, you know; there's no crystal ball for anyone with regard to the pandemic.

Furthermore, the safety and Tolerability profile.

I think look really good disposition.

Discontinuation rate.

Right.

Really good with the 40 milligram dose and then if you look at the.

The quality of life data right.

It's maintaining quality of life, despite adding a second drug.

Patrick J. Haley: And I think the system is just working through that, but I wouldn't want to speculate. [inaudible] Right. Yeah, absolutely. Look forward to that approval. Thanks for all the insights and answering all my questions. You bet it. And our next question will come from the line of Yaron Werber with Cowan. Hi everyone, this is Leo.

And providing all that clinical benefit that we've talked to which is unique.

Relative to other Iot Kia's. So I think that's really compelling for physicians and we've heard really good feedback on it so I think that gives us.

A lot of opportunity to position as broadly successfully cross risk groups.

Favorable intermediate and poor and with regards to any potential competitors.

Yeah, Hey, Kevin It's Mike.

That's a really good question and we've done a lot of market research in terms of Edwards and blinded market research and it has been very consistent.

Issa Schwab: Hi, I'm Yaron Werber. Thanks for taking our questions. I have a couple of questions.

Sort of feedback I would also refer you back to the analyst.

Issa Schwab: First, regarding carbon. You guys mentioned the market trend for GKI. I'm just wondering if you see any specific trend or difference in terms of different market segments, such as maybe the second line RCC versus the first line RCC? And within the first line RCC, are you seeing any different trends in the different risk categories in terms of favorable risk versus, I'm just wondering how the potential approval of 9-ER in the first quarter next year or the potential data from COSMIC 3.13 would kind of reverse that trend? And I have a follow-up question for 092. Thanks. Yeah, hi, Leo, PJ, I'll take that first question.

Discussion that we had.

The asthma presentation back.

Back in September.

Live for very.

Kind of top tier kols.

Presentation is still on on our website online and I would definitely recommend people take a listen to that there was a lot of great discussion there a lot of great perspective, there on why they think this is not only very a very competitive combination, but really veteran towards best in class as well so.

Thanks Bye pizza.

Okay.

And our next question is going to come from the line of Chad Master with Needham and company.

Hello, everyone. Thanks for scraping Amanda says go on for Chad just the one question from from Us.

Uhm.

Are there indications that are gonna be revisited with X L zero nine to work or Cabo faced certain challenges and development.

Patrick J. Haley: So as I mentioned, you know, broadly, we've kind of presented the TKI trends and what they were. But what I would say is when you look at the market, for RCC, you see significant utilization of combinations in the frontline setting. Approximately 80% of the frontline setting is combination therapy, in terms of IO and something else, and 50% of that is IO TKI.

This is getting a kick dead could go back to the development plan for it so on that too and they certainly an area where a couple of Don King at M. S N <unk> commercialized and with me.

I'm looking now at different kinds of therapy different combinations.

Patrick J. Haley: I think there is significant opportunity for 9ER, you know, looking forward, pending an approval. And as I kind of mentioned, we see 9ER competing across clinical risk groups, which is what we see the current IO TKI therapy doing now. It's getting share and favorable intermediate and poor risk, and we see 9ER potentially competing across all of those well, as well as across all competitors.

Within.

<unk> to my type and then it took me uhm and the Uhm product development plan, but we also see opportunity and and very different combinations that haven't been explored with kind of a time.

Let me see opportunity.

Different ninth of therapy earlier, nine to therapy across indications, including abdomen and you answering indications given the target D profile of the compound.

Patrick J. Haley: You know, with regard to the second line, we see Cabo Medics retaining our market share kind of across segments, certainly in the second line, currently our key segment there, and we have the potential for growth, and we really get the vast majority of patients who are progressing from an IO-based therapy in the second line. As we look forward, I think we're looking at, you know, just the potential to grow broadly pending the approval of 90 hours, which were extremely. Okay, thanks. So in terms of the first line, RCC dynamics, are you seeing more of a decreasing trend in the use of IOIO versus IOTKR, or is it still maintained the same? Yeah, I mean, if you look at one of the slides, we've got that broken out in a bar chart for you. So currently, we see about 50% of the first line as IOTKI.

And.

We really are being this.

Opportunity to build and comprehension of development and and from the kind of comprehension development plan more broadly.

That's M y.

Like the Rams opportunity.

Alright. Thank you for taking the question on congratulations on all the progress.

Thank you count.

And our next question will come from the line of Stephen Wiley with Stifel.

Yeah. Thanks for squeezing it. So just a quick question I know on on the kind of year and twenty-two run right got into that you're providing I think it might be you had mentioned or P. J I mentioned that you expect there to be ethics five ICI.

TKL cabos to be approved at at that point.

I know you spoke a little bit to the inputs regarding just treatment duration that you guys were maybe assuming that number but.

Issa Schwab: And I would say, you know, that's either maintaining or slightly increasing what we've seen over the last couple quarters. So I think that that shows that IOTKI is really, is kind of responding broadly in them. So I think there's the opportunity to really build on that momentum with Cabo Medics in a potential nine ER. Thanks. So regarding the 092, I'm just wondering if you identify any potential indication that will allow you to go through the X-ray ready, the rectal path. Yeah, this is Gisela.

Could you, maybe just say I guess, yes, or no whether or not you guys are assuming that you guys have a majority market share relative to those other.

Those combo competitors and and maybe to watch them.

Yes, Cvs might yeah, we don't want to give that level of data from a competitive point of view I would say if it's a it's a very conservative market share estimate.

Arguably comparable but certainly we're not we're not going off on on market share ledge. If you will in terms of as soon as we get a very large majority market share either so.

We're taking I think a very conservative view here, obviously Ah Delaware of.

Of duration of treatment approximately based upon the PFS data is.

Issa Schwab: Thanks for the question. I think this will be entirely data-dependent, and at this point, it's a little bit early to speculate.

A strong driver.

Those of that run rate, but we're being conservative in terms of the expectation for market share, leaving top side for growth as well, even beyond 313 and other other cargo activities in that in that indication.

Issa Schwab: So in the phase one study, we have incorporated expansion cohorts in specific indications, and as we learn more about them, we will certainly examine the data and make a data-driven decision. Got it.

Okay, and then just real quickly on.

311, I know that there's.

I guess, an interim read coming this quarter.

Issa Schwab: Okay, thank you so much. It's very helpful. Thanks. And our next question will come from the line of Michael Schmidt with Guggenheim. Hey, guys. Good afternoon, and thanks for taking my questions.

Should we expect to see any kind of data I guess within a press release or was that something where you guys are just gonna be are just going to state. Yes, we hit the threshold for filing no. We didn't we're going forward.

Patrick J. Haley: Maybe just a couple follow-up questions to prior questions. It's been a little while now since, as you know, when the Check the 90-Hour Data was presented. Just wondering what feedback there has been now from KOLs, since it's been a while, and wondering what your level of engagement with physicians has provided feedback in that regard, and also wondering how we should think about potential inclusion in NCCN guidelines prior to approval of the combination in February. Yeah, hey, Michael, this is PJ.

Yeah. It's R. K guitar study so we have more more.

More more flexibility with what we say and when we say it. So we normally put some level of kind of Uber top line data in a press release to give people some sense of the of the results and I'm, assuming we'll do that here, but.

That remains to be seen so stated.

Alright, that's helpful. Thank you yep, thank Dave.

And our next question will come from the lineup Paul Choi with Goldman Sachs.

Alright, well this is charged for empty on for Paul. Thanks, So much for taking our questions. I just had a quick question on the X 192 Phase one study I noticed that previously there was a cohort designated for non small cell lung cancer that cohort appears to have been edited to drop that indication of this.

Patrick J. Haley: So, with regard to the second part, I mean, NCC and I, you know, I won't, I won't speculate on what they are, when they might do it; we just have to kind of wait and see how that goes. With regard to feedback, you know, we've talked to a lot of KOLs, conducted many ad boards, and we've also done market research with a significant amount of community and academic positions. So, you know, we're talking about well over 100 physicians at this point. So I think we've gotten a really nice sampling and flavor of feedback. And It's all been extremely positive.

Point. So I'm just wondering has your thinking of evolved somehow on this indication in terms of how you wanted maybe approach it usually go not too because I see that on slide I think 30 of the presentation. SCLC is still listed as a potential target. So I'm. Just wondering how are you thinking about long at this point. Thank you very much.

Absolutely, none can certainly skill S interest and as a potential indication in various different settings and as we go forward and that should be about a variety of combination approaches containing X O O 928.

Patrick J. Haley: And, you know, we believe this will be a best in class combination in terms of IOTKI. You know, really looking at the totality of the data, it's impressive. When you look at the efficacy in terms of it's the only combination that doubles progression-free survival, survival, and objective response rate while increasing, improving overall survival and doing that while it maintains quality of life relative to synitinib, which is really novel in this setting. And I think you kind of wrap all that up in the fact that this is a new, optimized dose of 40 milligrams daily. [inaudible] efficacy that they really want to use for their patients with, you know, a tolerability sort of safety profile and quality of life that they really like, and can kind of build on their experience with both these agents separately.

Backbone at B R. A ceremony, including lung cancer, an hour talk processed and then okay.

Hey, Charlie any thank you very much.

Thank you for Tonight. Thank you.

Thank you I'll now turn the conference over two season Hubbard for closing comments.

<unk>. Thank you Holly and thank you all for joining US today, we certainly welcome your follow up calls with any additional questions. You may have that we are not able to address on today's calm.

Thank you and thank you all for joining US today, we walked in your follow up calls and we appreciate your participation you may now disconnect.

Michael M. Morrissey: So it's been very favorable. I think, you know, we're excited; we're ready to go and launch it sort of across the board, both virtually and in person. And I think that the entire team is just looking forward to having the opportunity to get out there and educate people on the data. Okay, and then on COSNIC 312, the frontline liver cancer study, I guess, what do you think about potential differentiation from the approved Tysandric-Avastin combination? And is it purely an efficacy question? Are there other factors at play that might sway physicians to prescribe one versus the other combination, potentially a pending success, obviously?

[music].

Patrick J. Haley: Yeah, Michael, PJ, I'll address that as well. You know, I think, obviously, you will have to get a positive study, and the answer to that will be, you know, data dependent. I think, you know, a couple of things as I think about that setting, though, are we're seeing in multiple data sources that the TezOBEV combination does well in terms of rapid uptake in the first line, you know, seeing first line share of already 30 to 50%. So that said, I think it'll be a great opportunity to differentiate, depending on the data, with a, you know, instead of an IOBEV option, an So I think, you know, that they will do well from an experience standpoint there.

Issa Schwab: And then I think there are certain nuances with regard to Bevacizumab in terms of the inclusion criteria and potential places where physicians will want to think about what are appropriate patients given that safety profile where, perhaps, we'll have a slight advantage there, but obviously, we'll have to really wait and see the data, but certainly represents a large potential growth opportunity in the first line setting. And, you know, in the interim, potentially some opportunity for those patients progressing on an IO-based therapy into the second one. Okay, and then one maybe for Peter or Gisela.

[music].

Issa Schwab: So it's on XL-092. So given the similar, you know, binding characteristics of that molecule to carbamates and, I guess, the shorter half-lives, how would one expect that to translate into a differentiated clinical profile? Is it mainly a safety advantage or might that, you know, enable potentially higher dosing or pushing efficacy maybe further?

Issa Schwab: As a result of that, you know, are there certain potential indications where SRE-092 might be more advantageously positioned relative to cavimatics, for example? This is Gisela. Thank you for the question. I think the key question is how does the shorter half-life translate into a differentiated profile.

Issa Schwab: I think the key here is that adverse event management and management of tolerability could be improved, and adverse events could subside more quickly. As Peter explained earlier, carbamazepine has a long half-life in the rush hour. It's longer, so that would be expected to be shorter, and adverse events could subside more quickly. And so it could potentially result in a, if you will, more user-friendly TKI in that fashion. And that could translate into an improved safety profile in terms of other advantages that could be notable. The shorter half-life, of course, is also important when thinking about peri-surgery indications or administration where wound healing as well as bleeds and things like that will always have to be kept in mind when dosing a longer half-life TKI that targets VEGFR.

Issa Schwab: And so that could be a setting where a shorter half-life is also of benefit. But this would be a very specific indication. In general, we see Exel-092 is a compound that can potentially have a broad and diversified development plan, including such indications as just mentioned. Okay, thank you so much. Our next question will come from the line of Kenan Mackay with RBC Capital Markets. Hi. Thanks for taking the question. I was hoping that the team could comment a little bit about specifically how Cabo Nevo and the Checkmate 90-hour profile would be differentiated in the eyes of physicians versus some of the other checkpoint TKI combos that are already approved. Essentially, what's going to be the edge that drives physicians to choose Cabo Nevo over any of the other combinations?

Patrick J. Haley: Thank you. Yeah, this is PJ, so I'll take that. You know, as I was kind of referring to earlier, I think the data are really compelling. And we've heard this from, you know, broadly in market research and from KOLs. Like, first of all, it's the only, not only the only IOT-KI, but the only combination that's doubling PFS and objective response rate while improving survival. So I think when you look at the totality of the efficacy data, that it's very compelling. You know, furthermore, the safety and tolerability profile, I think, looks really good to physicians. Low discontinuation rate, the AU rate, you know, really good with the 40 milligram dose. And then if you look at the quality of life data, right, it's maintaining quality of life despite adding a second drug and providing all that clinical benefit that we've talked about, which is unique. Relative to other IOT-KIs

Patrick J. Haley: So I think that's really compelling for physicians, and we've heard really good feedback on it. So I think that gives us, you know, a lot of opportunity to position it broadly successfully across risk groups, you know, favorable, intermediate, and poor, and with regard to any potential competitors. Yeah, hey Ken, it's Mike. You know, that's a really good question.

Michael M. Morrissey: And we've done, you know, a lot of market research in terms of ad boards and blinded market research, and it's been a very consistent set of feedback. I'd also refer you back to the analyst discussion that we had following the ESMO presentation back in September, with four very, you know, kind of top tier KOLs.

Patrick J. Haley: That presentation is still on our website, and it's still online. And I would definitely recommend people take a listen to that. There was a lot of great discussion there, a lot of great perspective on why they think this is not only a very competitive combination but, you know, really vectoring towards best in class as well.

Patrick J. Haley: Thanks, bye. Thanks, PJ. And our next question is going to come from the line of Chad Messer with Needham & Company. Hello, everyone. Thanks for squeezing me in. This is Guillaume for Chad. Just one question from us.

Issa Schwab: Um, Are there indications that are going to be revisited with XL092 where Cabo faced certain sets of challenges in development? Well, this is Gisela. Just to go back to the development plan for Excel-092, there are certainly areas where carbamazepine has been developed, is commercialized, and where we can now look at different lines of therapy, different combinations within a tumor type. And that is certainly in the broader development plan. But we also see opportunity in very different combinations that haven't been explored with carbamazepine. We see opportunity in different lines of therapy, earlier lines of therapy, across indications, including adjuvant and neoadjuvant indications, given the target and profile of the compound.

[music].

Issa Schwab: And so we really are viewing this as an opportunity to build on the carbamazepine development plan and from the carbamazepine development plan more broadly with a wide array of opportunities. All right. Thank you for taking the question and congratulations on all the progress. Thank you, Gail. And our next question will come from the line of Stephen Wiley with Stiefel. Yeah, thanks for squeezing me in. So just a quick question.

Issa Schwab: I know on the kind of year-end 22 run rate guidance that you're providing, I think Mike, you had mentioned or PJ had mentioned that you expect there to be, I think, five ICI TKI combos to be approved at that. And I know you spoke a little bit about the inputs regarding just treatment duration that you guys were maybe assuming in that number. Can you maybe just say, I guess, yes or no, whether or not you guys are assuming that you guys have a majority market share relative to those other guys... Yeah, Steve, it's Mike. Yeah, we don't want to give that level of data from a competitive point of view.

Michael M. Morrissey: I would say it's a very conservative market share estimate that's arguably comparable. But certainly, we're not, you know, we're not going off on a market share ledge, if you will, in terms of assuming we get a very large majority market share either. So, you know, we're taking, I think, a very conservative view here, obviously, a doubling of duration of treatment, a doubling of the run rate approximately, based upon the PFS data is, you know, a strong driver of that run rate. But we're being conservative in terms of the expectation for market share, leaving some upside for growth as well, even beyond 313 and other other, Okay, and and and then just I know that there's an, I guess, an interim read coming this quarter. Should we expect to see any kind of data within a press release?

Michael M. Morrissey: Or is that something where you guys are just... are just going to state, "Yes, we hit the threshold for filing. No, we didn't." We're going forward. Yeah, you know, it's our study. So we have more, more, more flexibility with what we say and when we say it. So we normally put some level of kind of uber-top line data in a press release to, you know, give people some sense of the results.

Michael M. Morrissey: And I'm assuming we'll do that here. But, you know, that remains to be seen. So stay tuned. That's all. Thank you. And our next question will come from the line of Paul Choi with Goldman Sachs.

Issa Schwab: Hi, everyone. This is Charlie Ferranti on behalf of Paul. Thanks so much for taking our questions. I just had a quick question on the XL092 Phase 1 study. I noticed that previously there was a cohort designated for non-small cell lung cancer, and that cohort appears to have been edited to drop that indication at this point.

Issa Schwab: So I'm just wondering, has your thinking evolved somehow on this indication in terms of how you want to maybe approach it using 092? Because I see that on slide 30, I think, 30 of the presentation, NSCLC is still listed as a potential target. So just wondering how you're thinking about lung cancer at this point. Thank you very much. Absolutely, lung cancer is certainly still of interest as a potential indication in various different settings.

[music].

Issa Schwab: And as we go forward, and as we develop a variety of combination approaches, containing XL092 as a backbone, we are certainly including lung cancer in our thought process and in our plan. Good, Charlie. Any follow-up? Thank you very much. That's all for tonight. Thank you. Thank you. I'll now turn the conference over to Susan Hubbard for closing comments. Great. Thank you, Holly, and thank you all for joining us today. We certainly welcome your follow-up calls with any additional questions you may have that we were not able to address on today's call.

Susan T. Hubbard: Thank you. And thank you all for joining us today. We welcome your follow-up calls, and we appreciate your participation. You may now disconnect.

Operator: [inaudible] Oh! Oh! Oh! Oh! Oh! Oh! Oh! Oh! , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , You're watching the Daily Show with The Daily Show.

Unknown Executive: I'm your host of The Daily Show. I'm here to talk to you about the latest news. I'm here to talk to you about the latest news. I'm here to talk to you about the latest news.

[inaudible] It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. It's Me. ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? , , , , , , , , , , ,