Exelixis, Inc. (EXEL) Q1 2024 Earnings Name Transcript

Exelixis, Inc. (NASDAQ:EXEL) Q1 2024 Earnings Convention Name April 30, 2024 5:00 PM ET

Firm Contributors

Varant Shirvanian – Director of Investor Relations
Michael Morrissey – President and Chief Government Officer
Christopher Senner – Government Vice President and Chief Monetary Officer
P.J. Haley – Government Vice President, Industrial
Amy Peterson – Government Vice President, Product Improvement and Medical Affairs and Chief Medical Officer
Dana Aftab – Government Vice President, Discovery and Translational Analysis and Chief Scientific Officer

Convention Name Contributors

Joseph Catanzaro – Piper Sandler
Jason Gerberry – Financial institution of America
Michael Schmidt – Guggenheim Companions
Gregory Renza – RBC Capital Markets
Joyce Zhou – TD Cowen
Andy Hsieh – William Blair
Jay Olson – Oppenheimer
Chris Shibutani – Goldman Sachs
Derek Archila – Wells Fargo
Silvan Tuerkcan – Residents JMP
David Lebowitz – Citi
Jeffrey Hung – Morgan Stanley
Lukas Shumway – BMO Capital Markets
Peter Lawson – Barclays

Operator

Good day, women and gents, and welcome to Exelixis First Quarter 2024 Monetary Outcomes Convention Name. My identify is Towanda and I will likely be your operator right now. As a reminder, this name is being recorded for replay functions.

I’d now like to show the decision over to your host for right now Mr. Varant Shirvanian, Director of Investor Relations. Please proceed.

Varant Shirvanian

Thanks, Tawanda. Thanks all for becoming a member of us for the Exelixis First Quarter 2024 Monetary Outcomes Convention Name. Becoming a member of me on right now’s name are Mike Morrissey, our President and CEO; Chris Senner, our Chief Monetary Officer; P.J. Haley, our Government Vice President of Industrial; Amy Peterson, our Chief Medical Officer; and Dana Aftab, our Chief Scientific Officer who collectively will evaluation our progress for the primary quarter 2024 ended March thirty first, 2024.

Through the name right now, we’ll discuss with monetary measures not calculated in accordance with usually accepted accounting ideas. Please discuss with right now’s press launch which is posted on our web site for a proof of our causes for utilizing such non-GAAP measures, in addition to tables deriving these measures from our GAAP outcomes.

Through the course of this presentation, we will likely be making forward-looking statements concerning future occasions and the longer term efficiency of the corporate. This consists of statements about attainable developments concerning discovery, product growth, regulatory, business, monetary and strategic issues.

Precise occasions or outcomes might in fact differ materially. We refer you to the paperwork we file from time-to-time with the Securities and Trade Fee, which underneath the heading Danger Components establish necessary elements that would trigger precise outcomes to vary materially from these expressed by the corporate verbally and in writing right now, together with, with out limitation, dangers and uncertainties associated to product business success, market competitors, regulatory evaluation and approval processes, conducting medical trials, compliance with relevant regulatory necessities, our dependence on collaboration companions, and the extent of prices related to discovery, product growth, enterprise growth and commercialization actions.

With that, I will flip the decision over to Mike.

Michael Morrissey

All proper. Thanks, Varant, and because of everybody for becoming a member of us on the decision right now. Exelixis is off to a powerful begin in 2024 and had a productive first quarter throughout all elements of our enterprise. We’re happy to see each income and demand progress for the corporate’s Cabozantinib franchise within the US and globally.

Prime precedence is to maneuver the needle for sufferers and shareholders by advancing Cabo, Zanza and the remainder of our thrilling pipeline to enhance the standard-of-care for sufferers with most cancers. Now we have lots to cowl right now, so let’s leap proper into it with the important thing highlights for the quarter, together with, first, we noticed a powerful efficiency of the Cabozantinib enterprise within the first quarter of 2024 with continued progress in demand and income year-over-year in comparison with first quarter of 2023.

Even with typical seasonal headwinds that had been additional magnified by the implementation of the IRA, CABOMETYX maintained its standing because the main TKI for RCC in each the first-line IO TKI market and the second-line monotherapy section.

First quarter 2024 Cabo franchise internet product revenues grew 4% year-over-year in comparison with first quarter 2023. Highlighting its position as a worldwide main TKI international cabozantinib franchise internet product revenues generated by Exelixis and its companions grew roughly 9% year-over-year within the first quarter of 2024 in comparison with first quarter 2023.

As mentioned beforehand, we’re excited in regards to the potential for extra Cabo progress with the brand new indications on the horizon that P.J. and Amy will talk about shortly. Chris will evaluation our full first quarter 2024 monetary leads to his ready remarks.

Second, we proceed to advance our industry-leading pipeline throughout all levels of preclinical and medical growth. Our prime priorities for 2024 are to advance potential new Cabo indications for NET and metastatic CRPC and expedite Zanza medical growth with each present and new pivotal trials in addition to potential new mixture methods. XB002 cohort growth stays a transparent focus for us and XL309 continues to generate thrilling momentum within the artificial lethality house.

Lastly, we’re thrilled with our progress in advancing new candidates in discovery and preclinical growth, concentrating on a variety of stable tumor indications that comprise an IND pipeline of each small molecules and biotherapeutics, which we anticipate to evolve shortly over the subsequent a number of years.

Third, ultimate reply briefs for the second MSN ANDA trial had been submitted in February and we proceed to anticipate a ruling within the first half of 2024. Whereas we won’t converse to any specifics right now, this stays a vital milestone for the corporate and the Cabozantinib franchise. Exelixis will proceed to vigorously shield our mental property rights with respect to Cabo and our different differentiated molecules we pursue on behalf of sufferers with most cancers.

Lastly, fourth, we anticipate enterprise growth actions to ramp up considerably as we acquire readability on the result of the patent litigation. Importantly, we’re exploring choices to collaborate with different organizations in value and compound sharing preparations in a way just like our prior Cabozantinib checkpoint mixture endeavors.

As well as, we’re fastidiously reviewing the aggressive panorama on an enterprise-wide stage to establish extra later-stage belongings that we consider by way of our distinctive Cabozantinib lens match into our GU and GI oncology-focused drug growth and commercialization platform.

So with that please see our press launch issued an hour in the past for our first quarter 2024 monetary outcomes and an in depth record of key company milestones achieved within the quarter.

I will now flip the decision over to Chris.

Christopher Senner

Thanks, Mike. For the primary quarter of 2024, the corporate reported whole revenues of roughly $425 million. which included Cabozantinib franchise internet product revenues of $378.5 million. CABOMETYX internet product revenues had been $376.4 million and included roughly $6 million in medical trial gross sales.

Gross to internet for the Cabozantinib franchise within the first quarter of 2024 was 32.9%, which is larger than the gross to internet we skilled within the fourth quarter of 2023, however total, according to our expectations. This improve in gross to internet deductions within the first quarter of 2024 is primarily associated to larger Medicare Half D and PHS bills.

Traditionally, we now have skilled larger Medicare Half D bills within the first quarter of the yr as a consequence of many Half D sufferers transferring by way of the donut gap initially of the calendar yr.

Our CABOMETYX commerce stock decreased by roughly 350 models when in comparison with the fourth quarter of 2023 of roughly 2.4 weeks readily available. As I discussed on our fourth quarter earnings convention name, we skilled a commerce stock construct within the fourth quarter of 2023 of roughly 1,000 models and that we had noticed a listing drawdown in January.

As mentioned beforehand, Exelixis took a 2.2% value improve on January 1, 2024. This value improve is greater than offset by the upper gross to internet deductions throughout the first quarter of 2024. Additionally, whereas we do not present quarterly income steering, we do see some seasonality in internet product income tendencies, the place first quarter internet product revenues have traditionally been decrease than the next quarters in a yr.

Should you analyze the final seven years of first quarter internet product income and examine them to the reported annual internet product revenues of the identical yr, in lots of these years, the primary quarter internet product revenues are within the vary of 21% to 23% of our annual internet product revenues. We took this seasonality affect under consideration when getting ready our annual internet product income steering of $1.65 billion to $1.75 billion, which we’re reiterating on right now’s name.

As a reminder, medical trial gross sales have traditionally been uneven between quarters and we anticipate this to proceed in future quarters. Complete revenues additionally included roughly $47 million in collaboration revenues, together with roughly $40 million of royalty earned from Ipsen and Takeda on their gross sales of Cabozantinib of their territories.

Our whole working bills, excluding restructuring expenses for the primary quarter of 2024 had been roughly $363 million in comparison with $398 million within the fourth quarter of 2023. The sequential lower in these working bills was primarily pushed by decrease drug discovery and common and administrative bills within the first quarter of 2024.

In January 2024, we introduced the restructuring of our enterprise, which included a headcount discount of 174 FTEs. The entire value of this restructuring within the first quarter of 2024 had been roughly $33 million, which embrace severance and employee-related prices, asset impairment and contract termination prices.

Provision for revenue taxes for the primary quarter of 2024 was roughly $12 million, in comparison with a provision for revenue taxes of roughly $18 million for the fourth quarter of 2023. The corporate reported GAAP internet revenue of roughly $37 million or $0.12 per share on a completely diluted foundation for the primary quarter 2024. The corporate additionally reported non-GAAP internet revenue of roughly $52 million or $0.17 per share on a completely diluted foundation.

Non-GAAP internet revenue excludes the affect of roughly $50 million of stock-based compensation expense internet of the associated revenue tax impact. Money and investments for the quarter ended March 31, 2024 was roughly $1.6 billion.

Through the first quarter of 2024, we repurchased roughly $191 million of Exelixis shares at a mean value of $22.8. We stay dedicated to totally executing on the $450 million share repurchase program we introduced in January 2024. Combining the 2023 and 2024 share repurchase program, we’ll return $1 billion to our shareholders by the top of 2024.

This stage of money and investments supported by our ongoing money movement from operations gives Exelixis with the pliability to put money into inside R&D actions to pursue exterior enterprise growth alternatives to develop our pipeline and permits us to return capital to our shareholders by way of our $450 million share repurchase program. And at last, we’re reiterating our full yr 2024 monetary steering, which is detailed on Slide 14 of our earnings presentation.

And with that I will flip the decision over to P.J.

P.J. Haley

Thanks, Chris. Within the first quarter of 2024, group continued to execute at a excessive stage, which has resulted in CABOMETYX persevering with to be the primary prescribed TKI in RCC and second-line HCC.

Moreover, CABOMETYX together with nivolumab stays the primary TKI plus IO mixture in first-line renal cell carcinoma. Almost about prescriptions, CABOMETYX TRx quantity grew 4% year-over-year in Q1 2024 relative to Q1 2023. In the identical interval, the TKI market basket was flat.

Moreover, the enterprise stays robust, each by way of demand and new affected person begins. CABOMETYX continued to carry out properly within the first quarter from each a market and aggressive perspective.

CABOMETYX once more led the TKI market basket in TRx share at 40%. As we now have mentioned beforehand, the first-line RCC market is extraordinarily aggressive. And Q1 was the sixth full quarter wherein CABOMETYX plus nivolumab, stay the primary prescribed TKI plus IO mixture in first-line RCC.

Moreover, long-term knowledge from the CheckMate -9ER research now with a minimal of 4 years follow-up was offered at ASCO GU this yr and continues to bolster the management place that CABOMETYX has within the RCC market.

Trying ahead, the business group is worked up in regards to the optimistic outcomes from the CABINET trial in neuroendocrine tumors in addition to the CONTACT-02 trial in metastatic castration-resistant prostate most cancers, which Amy will talk about in some element.

Neuroendocrine tumors comprise a big and heterogeneous affected person inhabitants. The sufferers develop into metastatic and progress remedy choices develop into restricted. The one oral remedy choices are sunitinib and everolimus and there has not been an approval within the US for an oral agent in NET since 2016.

There’s a robust unmet want for brand new choices for sufferers who’ve progressed on systemic remedy. There are roughly 8,000 incident second-line plus drug-treatable sufferers yearly within the US. Roughly 20% of those sufferers are SSTR adverse and in lung NETs, that proportion is larger with 40% to 60% being SSTR adverse.

Most NET sufferers will obtain many traces of remedy, partially because of the extra indolent nature of the illness relative to different stable tumors. Now we have performed preliminary market analysis, which reveals that oral therapies account for roughly 50% of the utilization on this market within the second-line plus setting.

The CABINET research had a various inhabitants, together with pancreatic, further pancreatic and lung NET sufferers. SSTR optimistic or adverse sufferers in addition to beforehand handled with Lutathera. Regulatory approval for CABINET would doubtlessly place Cabo to assist a broad vary of NET sufferers.

Metastatic castration-resistant prostate most cancers is a big market with vital unmet medical want, the place the first therapeutic choices stay novel hormonal remedy, chemotherapy and radioligand remedy. There’s a vital unmet want on this affected person inhabitants, notably for sufferers progressing on an NHT and who want to delay chemotherapy.

Many sufferers obtain an NHT earlier than they develop into metastatic and castrate-resistant. Cabo plus Atezo represents a possible possibility for a lot of of those sufferers with novel mechanisms of motion and handy administration within the metastatic CRPC setting.

Moreover, the business group could be properly positioned to leverage the RCC group infrastructure to realize synergy in a brand new GU oncology indication. In abstract, regulatory approval in these extra indications with vital unmet want would offer the chance for continued progress for CABOMETYX within the coming years.

I’d additionally add that the business group is extraordinarily excited in regards to the progress within the pipeline notably Zanzalintinib as we look ahead to having one other product to assist sufferers with most cancers.

With that I’ll flip the decision over to Amy.

Amy Peterson

Thanks, P.J. At present, I will present a excessive stage replace on our medical stage pipeline. The group is constant the momentum throughout the entire applications we highlighted throughout our R&D Day final December, with laser concentrate on execution for the Cabozantinib franchise in addition to for our medical pipeline.

Our pipeline is broad, each by way of modalities and targets, representing a wide range of growth alternatives, which mixed with our strong translational and medical growth capabilities present an thrilling and excessive potential platform for progress. At present, I will share the progress we’re making in the direction of executing on our medical trials throughout the event pipeline and on our potential regulatory submissions for Cabozantinib.

So let’s begin with Cabozantinib and CABINET, which is a Section III research that evaluated Cabo versus matched placebo in sufferers with beforehand handled superior or metastatic pancreatic or extrapancreatic neuroendocrine tumors, which I will discuss with as pNET or epNET, respectively. The research was performed by the Alliance for Medical Trials in Oncology and Knowledge was offered by Dr. Jennifer Chan at ESMO 2023.

The research had two independently powered cohorts, one for pNET and the opposite for epNET. Notably, the PFS hazard ratio for every cohort strongly favored Cabo with hazard charges of 0.27 and 0.45 within the pNET and epNET populations, respectively. The security profile of monotherapy Cabo was according to its identified profile and no new security alerts had been recognized. This preliminary evaluation was primarily based on native assessments with restricted knowledge out there from the blinded impartial radiology committee or BIRC.

The compelling outcomes triggered an IDMC advice and Alliance resolution to cease enrollment, unblind the research and permit sufferers to cross over from placebo to Cabozantinib. The ultimate evaluation by BIRC will likely be shared at a convention later this yr and help our intention to file within the coming months.

As P.J. talked about in his part, we’re very excited in regards to the potential to carry Cabozantinib to sufferers with neuroendocrine tumors. The CABINET knowledge are fairly spectacular and strong and have permitted help Cabo as a possible new standard-of-care in a inhabitants that’s in dire want of efficient remedy choices.

Turning now to CONTACT-02. Our randomized open-label Section III research of Cabo plus Atezolizumab versus second novel hormonal remedy or NHT in sufferers with castration-resistant prostate most cancers and measurable extrapelvic tender tissue illness. We consider the information from this research help a good danger profit to sufferers and our intent to file.

Keep in mind, this can be a distinctive research inhabitants, given the requirement for measurable illness, which we intentionally selected to make sure a sturdy evaluation of PFS by BIRC. CONTACT had twin major endpoints of PFS by BIRC and OS. We anticipate having the ultimate OS evaluation within the coming months.

So what does a twin major finish level imply, it implies that for a research to be thought-about optimistic from a statistical standpoint, we solely must hit on one of many endpoints. Dr. Neeraj Agarwal offered the numerous and strong PFS outcomes at ASCO GU. The PFS hazard charge within the prespecified PFS inhabitants was 0.65 with a p-value equal to 0.0007. So statistically vital, therefore a optimistic research.

The PFS hazard charges, median and Kaplan-Meier curves and the ITT inhabitants by BIRC had been almost similar to that within the PFS inhabitants. This was additionally true for PFS in accordance with the PCWG3 standards, which incorporates bone imaging additionally assessed by BIRC. A PFS profit was noticed in all subgroups, notably in these with the poorest consequence that’s in sufferers with liver metastases and in sufferers who’ve already acquired each an NHT and Docetaxel. At this evaluation, OS demonstrated a pattern favoring Cabo Atezo.

CONTACT-02 enrolled a uniquely aggressive medical subset of mCRPC. One that’s usually highlighted for having the worst prognosis, which is mirrored by the restricted exercise with second NHT. The toxicities reported with Cabo plus Atezo had been larger than these with second NHT and this isn’t shocking, given NHTs are very properly tolerated.

Particularly in those that have already demonstrated good tolerance to prior NHT and keep in mind, the median length of prior NHT was one yr in CONTACT-02. The tolerability profile Cabo Atezo was according to the identified tolerability profile of every monotherapy agent and with the doublet from different research in addition to with different permitted IO TKI mixtures.

Placing this collectively and primarily based on the enter we have acquired from many within the GU oncology group from affected person advocacy teams and sufferers we firmly consider these findings characterize an appropriate danger profit profile and we’re dedicated to submitting this yr. So there’s various pleasure with Cabo in 2024, however I’ll flip now to Zanzalintinib the place our pleasure continues to develop.

Our Section I research have a number of growth cohorts in a wide range of tumors and mixtures. Knowledge generated from these cohorts has and can proceed to help our expanded growth for Zanza.

On the IKCS Convention and R&D Day final yr, Dr. Monty Pal offered promising knowledge with Zanza monotherapy, the place compelling and sturdy responses had been noticed in 32 sufferers with treatment-refractory clear cell kidney most cancers. All of whom had acquired prior IO and nearly all of whom are 81% have acquired prior VEGFR-TKIs together with 51% who beforehand acquired Cabo.

The ORRs of 38% within the ITT and of 24% in sufferers who had acquired prior Cabo are very encouraging particularly provided that Zanza shares the goal kinase profile of Cabo, however a shorter half-life, which you’ll hear about in additional element from Dana and which appears to lead to differential partitioning into tissues, together with tumor tissue, doubtlessly explaining the rising differentiated exercise and tolerability profile.

We’re not the one ones enthusiastic about Zanza’s potential. The GU group was very receptive to the information offered at IKCS and discussions round collaboration alternatives are ongoing.

Turning now to our pivotal research. We at the moment have three Section III research with Zanza and we’re evaluating extra pivotal research, together with alternatives for collaboration with different firms. Our most mature research is STELLAR-303. This research will consider the mixture of Zanza plus atezolizumab versus regorafenib in sufferers with non-MSI-high non-DMMR metastatic and refractory colorectal most cancers.

The first endpoint is OS within the inhabitants of sufferers with out liver mets or NLM, adopted by an analysis of OS within the ITT inhabitants ought to OS within the NLM inhabitants be statistically vital. So this isn’t a twin major endpoint. The pattern measurement for each NLM and LM sufferers is capped to make sure satisfactory variety of occasions in every of those analyses.

PI pleasure in regards to the potential of this mixture, particularly in sufferers with out liver mets has resulted in speedy uptick in enrollment and enrollment to the liver met cohort is mainly full. Enrollment to the NLM cohort needs to be full within the coming months.

STELLAR-304 is our Section III trial, which compares the mixture of Zanza plus nivolumab to sunitinib in sufferers with beforehand untreated metastatic non-clear cell kidney most cancers. This has twin major finish factors of progression-free survival and total response charge. OS is a secondary endpoint.

The likelihood of success of a research is a key strategic lever once we take into account methods to prioritize our portfolio. Provided that VEGFR-TKIs work in non-clear cell kidney most cancers that TKI IO combos work in non-clear cell kidney most cancers that Cabo monotherapy beats sutent in kidney most cancers and that Zanza has a best-in-class potential for a VEGFR-TKI. We consider this research has a fairly excessive PTS. Investigators are additionally enthusiastic about this mixture and enrollment is ongoing in a number of international locations.

STELLAR-305 is our Section II/III trial, which is able to consider Zanzalintinib together with pembrolizumab versus pembrolizumab alone in sufferers with untreated PD-L1 expressing superior or metastatic squamous cell carcinoma of the top and neck.

This research was activated late final yr, and we’re full steam forward into website activation mode. Given the rising favorable exercise and tolerability profile of Zanza and its mechanism of motion that leads to an immune permissive setting, we consider this mixture of Zanza plus Pembro might lead to improved outcomes versus single-agent Pembro and has the potential to supply sufferers a chemo-free possibility.

In fact, we’re intrigued by the LEAP-010 knowledge. And simply as we did with STELLAR-310 will make obligatory or applicable modifications to STELLAR-305 to extend the likelihood of success.

We’re all the time evaluating knowledge from Zanza and Cabo research rising knowledge from our rivals and the evolving remedy panorama to tell the design and initiation of the subsequent pivotal research for Zanza. An asset that we consider has potential for best-in-class as of VEGFR-TKI with commensurate improved exercise in sufferers that in the end switch into worth for our shareholders.

I will now briefly contact on our early medical pipeline belongings, XB002 and XL309 earlier than passing the decision over to Dana. XB002 is our tissue issue directed antibody drug conjugate incorporating a modified or a statin as a payload. Enrollment into the cohort expansions within the JEWEL-101 research is powerful and because the knowledge matures will enable us to grasp the preliminary profit danger profile. We’ll present updates when we now have knowledge maturity.

Lastly, final and positively not least, is XL309, which we’re very enthusiastic about. Dana will discuss extra on why we stay optimistic about this specific USP1 inhibitor. So within the curiosity of time, I will simply state that dose escalation cohorts are enrolling, and we hope to open mixture cohorts with PARP inhibition a bit of later this yr.

In abstract, we’re advancing a sturdy pipeline of medical stage molecules, whereas maximizing the potential profit to sufferers from our flagship asset, Cabozantinib, in excessive unmet medical want indications. We stay very optimistic about what we are able to do for sufferers who regardless of vital advances nonetheless want higher remedy choices.

And with that I will flip the decision over to Dana.

Dana Aftab

Thanks, Amy, and good afternoon, everybody. At present, I am giving a short replace on our progress within the first quarter of 2024 towards our targets for getting ready for IND filings and for advancing new compounds to growth candidate standing. After which I will wrap up with some preclinical updates on our USP1 inhibitor, XL309, and our next-generation VEGF receptor tyrosine kinase inhibitor, Zanzalintinib.

On the IND entrance, we’re making good progress on all of our pre-IND applications and are on monitor to file as much as three this yr. The primary one we anticipate to file this yr is for XB010, our 5T4 focused antibody-drug conjugate that carries the cytotoxic anti-tubulin payload MMAE. IND preparation is wrapping up quickly, so we anticipate that one to file round midyear.

The second IND we anticipate to file this yr is for XL495, which is a small molecule inhibitor of PKMYT1 that reveals artificial lethality within the context of elevated cyclin E ranges, which happens throughout a variety of tumors. IND preparation is progressing and we’re on monitor to additionally file this one round mid-2024.

The third IND we anticipate to file this yr will likely be for XB628, our bispecific antibody that targets PD-L1 together with NKG2A and shows NK cell engager exercise in preclinical fashions. The GLP Tox research for XP628 is now full and manufacturing and different actions have us on monitor for IND submitting within the fourth quarter of 2024.

Every considered one of these applications has a stable rationale for producing differentiating knowledge within the clinic. So we’re excited to get these INDs filed and to get the trials up and enrolling shortly.

By way of new growth candidates this yr, we’re at the moment on monitor to realize our targets of a minimum of two this yr with some thrilling new applications, together with a small molecule inhibitor concentrating on PLK4, which is synthetically deadly and cells of amplified TRIM37 and a novel antibody drug conjugate program.

Each of those applications characterize first or best-in-class approaches with potential to generate differentiating leads to the clinic. So we’re actually happy that we stay on monitor for placing these extra belongings into the preclinical pipeline this yr.

So now I might wish to shift gears a bit and describe some thrilling preclinical knowledge we generated for 2 of our small molecules within the medical pipeline. I will begin first with a short replace on XL309 after which describe some preclinical knowledge we have generated evaluating Zanzalintinib and Cabozantinib.

We not too long ago examined the mixture of XL309 with the selective PARP-1 inhibitor, saruparib within the preclinical breast most cancers xenograft mannequin, MDA-MB-436 wherein the BRCA1 gene is mutated. The information we generated with the mixture confirmed that at doses of each compounds that alone confirmed minimal tumor progress delay when given together resulted in very robust tumor regression that continued for a minimum of a month after dosing has ceased.

The opposite knowledge I am sharing with you right now, I feel, will assist to shed extra mild on the underlying foundation for an rising profit danger profile for Zanzalintinib that seems to be improved in comparison with Cabozantinib.

You might recall that Zanzalintinib retains the goal kinase profile of Cabozantinib, however with a PK profile that is extra optimum for dose adjusting to handle tolerability. And as you simply heard from Amy, we’re seeing what seems to be an total improved profit danger profile with Zanza with responses in some sufferers who progressed on Cabo and decrease charges of sure AEs with Zanza equivalent to hand-foot syndrome, diarrhea and fatigue.

We now have some preclinical knowledge, which we expect assist to elucidate these variations between the 2 molecules. First, we have continued to discover potential variations within the organic goal profiles of the compounds and each had been not too long ago run aspect by aspect in the identical experiment in a PRISM display on the Broad Institute.

It is a large-scale various most cancers cell line display that determines the results of compounds on cell viability throughout roughly 900 distinct cell traces representing over 45 most cancers subtypes. The outcomes we received again from the display confirmed the compounds had been remarkably related by way of their skill to affect cell viability, which largely confirms the speculation that the important thing organic goal profiles of Cabo and Zanza are basically the identical.

Given the same goal profile, we hypothesized {that a} potential rationale for the improved profile we’re seeing within the clinic with Zanza may be associated to variations in tissue drug concentrations between tumors and regular wholesome tissue when in comparison with Cabo.

Due to this fact, we performed tissue distribution research in each rats and mice and noticed that in comparison with Cabozantinib, Zanzalintinib confirmed larger free drug concentrations in tumors and decrease free drug concentrations in regular tissues. This translated to stronger on-target exercise for inhibition of MET in tumors by Zanza.

These outcomes had been a bit shocking as we had not anticipated such differentials in tissue partitioning between these two molecules, however the outcomes actually are according to and I feel assist clarify the apparently improved profit danger profile as rising with Zanza within the clinic.

So with that I will flip the decision again over to Mike.

Michael Morrissey

All proper. Thanks, Dana. I’ll shut by highlighting the 2 long-standing Exelixis executives are retiring after serving our firm for almost 20 years. First, Peter Lamb, EVP of Scientific Technique was with Exelixis for almost 25 years. And as you all know, made an outsized affect on our drug discovery efforts throughout his tenure on the group.

Moreover, Laura Dillard, our EVP of Human Sources, spent almost 20 years main our HR efforts to make sure we’re holding tempo with the evolution and progress of the corporate. On behalf of your entire Exelixis group, I might wish to thank each Peter and Laura for his or her friendship, dedication to Exelixis and most significantly, dedication to most cancers sufferers on a world stage. We want all of them the most effective as they begin their retirement.

So with that, I need to thank your entire EXEL group for his or her efforts to help our discovery growth and business actions. We’re off to an ideal begin in 2024 and anticipate this yr to be vital for our science and the sufferers we hope to serve sooner or later.

We constructed and are continually fortifying Exelixis as an enormous small firm with all that we do each hour of every single day. The Exelixis group is extremely motivated to exceed expectations and our mission to assist most cancers sufferers recuperate stronger and dwell longer.

We look ahead to updating you on our progress sooner or later and thanks to your continued help and curiosity in Exelixis and we’re joyful to now open the decision for questions.

Query-and-Reply Session

Operator

Thanks. [Operator Instructions] Our first query comes from the road of Joe Catanzaro with Pipa Sandler. Your line is open.

Joseph Catanzaro

Yeah, hello, thanks for taking my query, and recognize you taking the time right here. So I am questioning in the event you might elaborate a bit in your earlier feedback within the occasions of a optimistic consequence with reference to MSN patent litigation and type of curiosity in searching for later-stage belongings in GU, GI, oncology. I assume, how would you outline later stage? Is that this type of modality agnostic? And what measurement deal do you assume you can execute with the stability sheet and readability across the Cabo income tail? Thanks.

Michael Morrissey

Sure, Joe, it is Mike. Thanks for the query. Sure, this is not actually a brand new strategy. We talked about this earlier within the yr as we had been implementing the restructuring focusing our BD efforts on later-stage belongings by way of new modalities which are both in or coming into pivotal trials in addition to their concentrate on serving to us discover collaborations with Zanza and different molecules in our pipeline to collaborate on by way of value and/or compound sharing preparations. So, look, we’re very all for constructing a pipeline. We have got an ideal discovery, growth and business group and late-stage belongings match properly into that total strategy, whether or not they be already in pivotal trials are about to enter. We predict we are able to add a number of worth as we go ahead. So would not need to touch upon measurement, would not need to remark and positively on particular person targets. We’re modality agnostic by way of small molecules and biologics. Now we have, I feel, an excellent eye for good knowledge and good compounds. Once more, the Cabo lens, if you’ll, actually informs that. We talked about that at R&D Day again in December. So we’re all in, by way of discovering potential belongings to have the ability to carry into our pipeline and that can proceed as we go ahead.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of Jason Gerberry with Financial institution of America. Your line is open.

Jason Gerberry

Hey, guys. Thanks for taking my query. So mine I simply wished to comply with up on the any key business alternative slide. I am simply curious the way you guys assume a sign like that would ramp. The second line incidence, it is a decent-sized quantity. I simply surprise in regards to the availability of a longtime oral TKI, which wasn’t studied head-to-head in opposition to, if that creates a barrier in any respect or would possibly sluggish the launch versus the launches we’re accustomed to seeing like CheckMate -9ER simply given the necessity to doubtlessly retrain physicians or educate them about your knowledge? Thanks.

P.J. Haley

Sure. Hello, Jason. That is P.J. Thanks for the query. I might say we’re actually excited in regards to the knowledge that Amy went into a bit of extra element on. As I discussed, we have type of performed some preliminary market analysis. We have actually had some advisory boards. I assume what I might say at a excessive stage is there’s a number of enthusiasm for the information. I do not assume there will be something considerably completely different than prior launches. You talked about 9ER by way of type of trajectory or uptake or type of retraining physicians per se. I feel they’re very snug, clearly, with TKIs and even on this setting. So we expect this can be a very nice alternative doubtlessly ought to we obtain approval. For Cabo, as I spoke to, I feel the broad inhabitants that was studied with reference to pancreatic, further pancreatic, website of origin, tumors, together with lung, which is a bit of bit completely different from among the different brokers, which weren’t studied as broadly in addition to the truth that had been studied in SSTR optimistic adverse in addition to type of having a contemporary knowledge set, which included a number of sufferers handled with Lutathera earlier than the research actually offers us the potential to be broad and I feel, in a way, very user-friendly for oncologists who’re actually searching for one thing new on this setting.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of Michael Schmidt of Guggenheim. Your line is open.

Michael Schmidt

Hey, guys. Thanks for taking my questions. I had one for Amy on STELLAR-305. And so simply questioning how the enrollment standards within the research in comparison with that from KEYNOTE-048 or LEAP-010. And to what diploma you’re feeling like it’s possible you’ll want to regulate the trial primarily based on the LEAP-010 knowledge that was offered not too long ago? And what your confidence stage is in demonstrating a optimistic total survival pattern, which was clearly not the case in LEAP-010. Thanks a lot.

Amy Peterson

Sure. Thanks for the query, Michael. It was very attention-grabbing to truly get an opportunity to see the ultimate — the outcomes from the presentation earlier this yr by way of LEAP-010. Notably an ORR and a PFS that favored LEN/PEM, however an OS that did not. And an attention-grabbing length of response with monotherapy PEM favored over the doublet. So this can be a completely different inhabitants, frontline head and neck a bit of bit extra frail, than different affected person populations. And we’re all for making an attempt to uncover as a lot as we are able to. Across the dose of LEN, the dose reductions and the way a lot that will have aggregated a affected person’s skill to obtain full Pembro dose. So we’re busy deeply making an attempt to grasp that and if want be make a change to the 305 research with regard to dose within the context of very a frailer affected person inhabitants, if you’ll. I feel that there is a differentiation between Zanza and LEN in that Zanza does inhibit the TAM kinase household, which is implicated, if you’ll, in favoring an immune permissive setting. So the mechanism of motion of Zanza is completely different from LEN. And due to that would very possible have a differential consequence and we consider it’ll. So we’ll see how — what in the end must be modified and we’ll hold you posted on these modifications as they’re made. Proper now the eligibility standards for essentially the most half are posted on clinicaltrials.gov. And the place we have to make an replace, we’ll.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of Gregory Renza with RBC Capital Markets. Your line is open.

Gregory Renza

Nice. Good afternoon, Mike and group. Thanks for the updates and thanks for taking the query. Mike perhaps simply to ask a bit of bit constructing on the neuroendocrine tumor alternative actually properly in context with respect to Cabo. However as you do take into consideration Zanza and the combo optionality there and the white house that you’ve. I am questioning in the event you might simply remark a bit about Zanza on this indication. I imply is there alternative? And what are the potential growth move as you concentrate on combos would doubtlessly Zanza and Luta remedy be one thing to discover? Thanks once more.

Michael Morrissey

Sure, Greg, thanks for the query. It is an ideal one. I can punt over to Amy and P.J. to opine upon, Amy?

Amy Peterson

Sure, positive. As I discussed throughout the name, we’re all the time assessing what’s the subsequent neatest thing to consider for Zanzalintinib. We have a look at all issues which are strategic in our evaluation. So I talked in regards to the likelihood of technical success. That is an enormous one for us to think about in addition to the time it takes to conduct the research and the aggressive and evolving panorama and the worth proposition. And I’d say that neuroendocrine tumor is excessive on the record for Zanza and we’re very all for it. I will let P.J. remark a bit of bit on the business.

P.J. Haley

Sure. I imply I feel simply at a excessive stage, if I’m going again to type of the chance right here, actually, a big unmet medical want, as I discussed, with not many new therapies, actually any oral remedy is being permitted since 2016. So I feel there’s a number of room to maneuver on this tumor sort, particularly. The orals, as I discussed, in my remarks and on the slide account for roughly 50% of the second line plus inhabitants. So if you concentrate on Lutathera, for instance, which is doing over $400 million in income yearly. Principally a second line-plus inhabitants, they’ve the NETTER-2 knowledge at ASCO GI this yr, however these income type of predate that. In order that’s a fairly vital alternative in lower than 50% of that market. So I feel this can be a huge house that is actually there is a excessive urge for food for brand new therapies, for brand new trials and actually a chance for this market to develop over time. So I see it as very thrilling.

Michael Morrissey

Sure, that is nice, P.J. I’d simply add. I feel the best way we talked about NET right here, and we’re actually enthusiastic about actually the CABINET knowledge and the alternatives to go ahead with Zanza, we expect NET is just like what we noticed with RCC again within the 2014, 2015, 2016 time. And there is a lot of similarities between the 2, despite the fact that they’re clearly completely different — very completely different indications. So we’re enthusiastic about this. We hope to speculate extra as we go ahead. Plenty of alternatives with Zanza and different potential mixtures. So keep tuned. As that evolves, we’ll hold you within the loop.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of Yaron Werber with TD Cowen. Your line is open.

Joyce Zhou

Hey, guys. That is Joyce on for Yaron. Thanks for taking the query. Perhaps simply one other follow-up on the NET market alternative. I feel you guys have beforehand stated that the prevalent inhabitants is about 5 instances the scale of the second-line plus incident inhabitants or about 40,000 sufferers. Simply questioning how a lot of that market you assume you possibly can seize or pull into this chance with Cabo and/or Zanza? Thanks.

P.J. Haley

Sure. Hello, Joyce. That is P.J. Thanks for the query. I feel as I discussed, the 8,000 sufferers, these are type of new incident sufferers in a given yr. And as you talked about, the prevalent inhabitants is far bigger. I feel I would not need to speculate earlier than we get to a label on the potential upside or the place it’d play out within the market, however I feel once we take into consideration the 8-Ok sufferers, et cetera, that is type of the baseline, and there actually may very well be many extra sufferers provided that that is an indolent illness the place sufferers obtain many traces of remedy that may be type of on the market. However once more, I feel we have to wait till we get out there to essentially get an excellent sense of that. However we’re very assured and cozy within the 8,000 sufferers as it’s being a extremely vital potential alternative for Cabo.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of Andy Hsieh with William Blair. Your line is open.

Andy Hsieh

Nice. Thanks for taking our questions. Two fast one, in the event you do not thoughts. One monetary one, scientific. By way of Medicare D publicity, Chris, do you thoughts reminding us your publicity there for the Cabo franchise? A number of firms like Gilead type of known as out the potential affect subsequent yr stemming from the Medicare Half D redesign, in order that’s half one. Half two, very provocative differential partitioning knowledge, Cabo versus Zanza. I’m curious, one, how was that determines? Would it not be primarily based on type of radio labeling experiments? After which maybe from a speculation perspective, do you might have any type of preliminary working by way of why that’s? Is that type of a distinction in passive diffusion or perhaps transporters are concerned? So these are the 2 questions. Thanks.

Michael Morrissey

Sure. Thanks, Andy. It is Mike. Dana, why do not you’re taking that second query first, after which we’ll punt it over to P.J. for the Medicare Half D query.

Dana Aftab

Certain. Okay. Thanks for the query, Andy. Sure, so by way of the partitioning, we generated knowledge in rats, and that is actually knowledge for getting ready for the mass stability research in people. That was the primary type of view into differential partitioning into regular tissues that we received. In order that was utilizing radio-label drug. So in fact, that measures every part metabolites and anything that is hooked up to the radioactive tracer. By way of the tumors and really the information that I confirmed on the slide got here from type of a side-by-side experiment in mice the place we had been figuring out the compound concentrations by mass spectrometry. And at doses that generated related free drug concentrations within the plasma, which once more had been decided by doing protein binding experiments, et cetera, we noticed these free drug concentrations in regular tissues and tumors, and that was simply considered one of a number of consultant regular tissues. So we’re nonetheless producing a number of knowledge. There’s clearly a number of completely different elements that go into how medicine distribute inside a dwelling animal or individual, together with issues like protein binding, tissue binding, which includes different elements aside from protein, membranes, lipids and whatnot, transporter results, pH-dependent results. There are such a lot of completely different items of the puzzle that go into understanding how this occurs. So we’re nonetheless gathering knowledge to attempt to perceive the total mannequin that’s driving these variations. And what I’d simply say is keep tuned as we generate extra knowledge and publish these knowledge that can hopefully lay out the total mechanism of how this occurs. However I need to say that it was a shock to us to see this occur. We had not anticipated or predicted that this might occur with these medicine a precedence.

Michael Morrissey

Nice. Thanks, Dana. P.J.?

P.J. Haley

Sure. So, hello, Andy, our Half D — Medicare Half D accounts are roughly 40% of the enterprise. And as you realize, with reference to the IRA, that can proceed to evolve in 2025. So the out-of-pocket cap for sufferers will likely be even decrease subsequent yr, round $2,000 and in addition will probably be unfold out over a month-to-month foundation. So the considering is that would doubtlessly cut back the burden on sufferers even additional.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of Jay Olson with Oppenheimer. Your line is open.

Jay Olson

Hey, thanks for offering this complete replace and for taking our query. For Zanza, are you able to speak about once we ought to anticipate to see some mixture knowledge. And Bristol not too long ago talked about preliminary medical proof-of-concept for Opdualag in non-small cell lung most cancers. What’s your considering and curiosity stage within the mixture of Zanza with Opdualag and STELLAR-002? Thanks.

Amy Peterson

Certain. Thanks for the query. I will take that. That is Amy. So that you noticed within the slides, we do have a wide range of cohorts that we’re increasing in each STELLAR-001 and STELLAR-002 and together with PD-1 along with different IO brokers, together with CTLA-4 and LAG-3. We’ll current the information when it’s mature. A few of these are early line cohorts. It simply takes some time since you need to get ORR, you need to get DOR, you need to get PFS. A few of them truly even have OS, they’re event-driven. And we simply have to attend for these occasions earlier than we are able to report on that. In terms of curiosity with mixture companions, I additionally offered the assorted mixtures that we’re doing, not solely IO, IO, IO, but additionally we now have the collaboration with HIF-2 alpha, and we’re trying one other mixtures. So I’d say that we’re data-driven. And we’ll go the place the mixtures inform us we should always go, however we’re and we stay open. I feel that what we’re persevering with to establish and uncover is that the flexibility for Zanza to mix with all of those different brokers is definitely relatively simple that is fairly properly tolerated at full doses. And so we do not assume that there is a difficulty by way of Zanza’s skill to mix with any of those brokers. It simply must be — the choice to maneuver ahead into extra research simply must be made upon the information that we see because it matures within the 001 and 002 cohorts.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of Akash Tewari with Jefferies. Your line is open.

Unidentified Analyst

Hello. That is Cathy on for Akash. I simply wished to comply with up on the Medicare Half D query that was requested earlier. And particularly on how will the restructure of the catastrophic protection part affect Cabo within the coming years? And likewise how does Exelixis particularly plan to mitigate these pricing impacts? Thanks.

Michael Morrissey

Thanks for the query. That is Mike. Sure, I actually would not need to touch upon what is going on to occur within the years forward. Now we have a fairly good thought about what to anticipate relative to ’25 and past. So once more, I would not need to opine past what’s occurring in 2024. And we now have a excessive diploma of confidence that we have that actually good sense of the place that is going and methods to navigate these completely different modifications. So transferring full steam forward and once we get to ’25 and past, we’ll speak about these modifications then, okay? Thanks.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of Chris Shibutani with Goldman Sachs. Your line is open.

Chris Shibutani

Nice. Thanks very a lot. Maybe in the event you might assist us perceive your prioritization of capital allocation between the share repurchases and the enterprise growth exercise, I feel Joe had tried to ask earlier and recognizing that you just aren’t essentially considering of sharing specifics. But it surely sounded as if it was contingent upon the result of the MSN IP resolution so that you can maybe lean in additional deliberately on the BD entrance. I simply wished to verify I understood since you additionally included in your launch that you just plan on finishing the share repurchase allocation that the Board permitted for the total yr 2024. Thanks.

Michael Morrissey

Sure. Thanks for the query, Chris. Sure, I’d not actually assume these two actions are mutually unique. Now we have loads of money. We’re producing free money each quarter. We have been worthwhile for years. I feel we now have the urge for food to do each. As Chris and others — we have all talked about beforehand, the share buyback between final yr and this yr will likely be $1 billion. The concept that we need to add extra late-stage belongings to our portfolio, actually is smart within the context of rising the enterprise by way of each prime line and backside line progress by having a diversified providing of merchandise that we are able to use within the context of our growth and commercialization platform to maneuver the needle for sufferers and shareholders. So we’re actually very excited in regards to the choices we now have forward of us. Getting past getting certainty with the ANDA is the primary precedence. As soon as we now have that in place then I feel the subsequent steps are comparatively simple with how we need to maneuver the enterprise. So thanks for the query and joyful to comply with up at a later time if you’d like.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of Derek Archila with Wells Fargo. Your line is open.

Derek Archila

Hey, guys. Thanks for taking the query. So simply, I assume one from us, how do you envision the Cabo approvals in each prostate and neuroendocrine tumors, how does that change the quantity progress profile of Cabo relative right now? How a lot acceleration might we doubtlessly see sooner or later? Thanks.

P.J. Haley

Sure. Derek, that is P.J. So actually, we do not need to give steering past this yr, particularly on income or quantity. I assume, I might type of reiterate a few of my earlier feedback with reference to NET clearly and CRPC, for that matter, each vital areas of unmet medical want. As I discussed, NET is 8,000 sufferers within the second line plus setting and extra broadly, we now have the potential to be actually have a broad alternative in that market. CRPC is clearly a extremely massive market, once more, in the end with restricted remedy choices with reference to major remedy choices being chemo, NHT, radioligand remedy, however you are speaking about tens of 1000’s of sufferers. So we’re very excited in regards to the alternatives. And will we now have the chance to carry them to market and assist sufferers, we expect there will be actually vital alternative for progress.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of Silvan Tuerkcan with Residents JMP. Your line is open.

Silvan Tuerkcan

Yeah, thanks. Congrats on the quarter and thanks for taking my query. I simply need to ask in regards to the overlap in gross sales drive and name factors between RCC and a possible gross sales drive for prostate most cancers. And mainly, what I am making an attempt to get to, is, are you able to inform us what’s type of the incremental value for doubtlessly launching NET in prostate most cancers?

Michael Morrissey

Sure. Silvan, thanks for the query, P.J., why do not you tackle each by way of prostate RCC after which on the GI aspect, NET and HCC.

P.J. Haley

Sure, joyful to, Mike. Thanks for the query, Silvan. So I will begin with RCC. We see actually vital overlap by way of GU oncologists, proper? So whether or not it is locally setting and even an academia particularly, GU-onc focus are actually treating nearly all of these GU indications. So once more, vital overlap there, which is doubtlessly nice for a variety of causes. One, we actually, as I discussed in my ready remarks, we are able to leverage our present RCC infrastructure. So with out having to speculate considerably to construct that for a possible prostate most cancers launch. And two, these are physicians who’re very accustomed to Cabozantinib in RCC managing negative effects, et cetera. In order that may very well be actually one thing that will be in our favor as properly. Almost about NET, a number of these is 50% plus actually 60% plus are GI associated. Now we have one other type of sleeve of our group, if you’ll, is GI-focused, and there is a heavy overlap there as properly with our name factors, each locally in addition to, once more, in academia, who’re — physicians who’re treating NET in addition to these GI tumors. So once more, it is a very nice potential for us to leverage our present infrastructure in addition to launch right into a market the place a number of the prescribers have present consolation and familiarity and admittedly, optimistic experiences in accordance with all our market [Technical Difficulty] tumors whether or not it is HCC, thyroid most cancers, DTC or in many various settings in renal cell carcinoma. In order that’s actually one thing we look ahead to.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of David Lebowitz with Citi. Your line is open.

David Lebowitz

Thanks very a lot for taking my query. Once you mentioned the technique Zanza versus Cabo going ahead, it appears it is clearly an effort to concentrate on completely different total indications. Does that technique evolve within the occasion of an unfavorable MSN2 ruling?

Michael Morrissey

Sure, David, thanks for the query. Sure, I would not need to — we would not need to speculate on that proper now. So I feel we have made the dedication to evolve the general strategy by way of how we’re creating TKIs, VEGFR are concentrating on TKIs over to Zanza, and that is nonetheless the plan going ahead. We predict we now have what appears wish to be an rising enchancment in total exercise and security, the totality of knowledge. It is nonetheless early. We’d counsel that. So we’re all in on Zanza and there is a number of pleasure there locally. And we’re having, I feel, a number of very attention-grabbing productive discussions about how we’d mix with Zanza. So a lot of alternative, lots to do there. So keep tuned.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of Jeff Hung with Morgan Stanley. Your line is open.

Jeffrey Hung

Thanks for taking my query. Following up on the neuroendocrine tumor prevalent inhabitants. Given heterogeneity of tumors, are you planning to stratify the prevalent inhabitants to concentrate on particular subgroups initially? I recognize any particulars you possibly can present. Thanks.

P.J. Haley

Sure, Jeff, that is P.J. Thanks for the query. Typically, what I’d say is as we focus popping out of the gate, provided that, as I discussed, we type of actually have broad inclusion standards in our research of whether or not that is website of origin, SSTR receptor standing, what sufferers have been beforehand handled with, we actually consider we now have the chance to go proper out of the gate. Ought to we be permitted and launched this very broadly. And I feel that will likely be in what we’re listening to in advert boards, et cetera, very a lot appreciated and adopted properly from a doctor group perspective as a result of they want new choices, for actually all of those sufferers. And in some circumstances like proper now for sufferers who’ve been on a wide range of therapies. So I feel it could be a broad alternative and we’d actually place it to as such.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of Etzer Darout with BMO Capital Markets. Your line is open.

Lukas Shumway

Hello. That is Lukas Shumway on for Etzer. Thanks for taking my query. For the prostate and NET filings, what are the important thing elements which are going to affect just like the timing of these filings, what are you ready on for these? And are these solely going to be US filings? Are we additionally searching for ex-US? And are there another gating elements for submitting these?

Amy Peterson

Thanks, Lukas. That is Amy. I will take that query. So I am unable to touch upon what our companions are going to be doing with regard to ex-US. submitting. Cabo is in collaboration underneath a — collaboration settlement with Ipsen for non-US, non-Japan and with Takeda for Japan. What we’re centered on and what I discussed within the name is that we wanted the information by BIRC so as to full the file for a submitting. And we now have the information, and we’re in discussions, and we actually are hoping to have the ability to submit within the coming months for the CABINET research. For CONTACT, I additionally talked about we now have ultimate OS, which we’re anticipating within the coming months. The research was a optimistic research. Statistically vital OS is just not required to ensure that the research to be optimistic. We confirmed a very nice pattern favoring Cabo/Atezo, which I’ll level out, given the — what else is happening in prostate most cancers by way of radioligand to PSME4 belongings the place initially hazard ratios for OS had been above one. Novartis simply introduced there is a lower than one, most likely very shut to 1, the truth that we had a pleasant pattern, I feel, can also be supportive of a risk-benefit profile that’s — that favors the sufferers. And so keep tuned. We’ll let you understand how conversations and filings progress with the company.

Operator

Thanks. Please standby for our subsequent query. Our subsequent query comes from the road of Peter Lawson with Barclays. Your line is open.

Peter Lawson

Thanks for taking the questions. Chris, only a query on the share buyback and ideas on increasing that particularly if there is a adverse consequence round IP, would that be one thing you’ll develop or speed up?

Christopher Senner

Hey, Peter, thanks for the questions. It is Chris. Sure, I am not going to invest on what we will do relying on the completely different variables round outcomes on the MSN trial. We’re — as I discussed in our ready remarks, we’re dedicated to executing on the $450 million, we did $191 million within the first quarter, and we’re dedicated to getting the remaining performed this yr.

Operator

Thanks. At the moment, there aren’t any additional questions. And so I’d now like to show the decision again over to your host Varant for closing remarks.

Varant Shirvanian

Thanks, Towanda, and thanks all for becoming a member of us right now. We welcome your follow-up calls with any extra questions you might have that we had been unable to deal with throughout right now’s name. Thanks.

Operator

Women and gents, this concludes right now’s convention name. Thanks to your participation. You might now disconnect.