Q1 2025 Arvinas Inc Earnings Call
Thank you for standing by my name is scaling I won't be the operator for today's call.
At this time I would like to welcome each and every one of you to the Earth Venus first quarter. It went up to 25 earnings call.
So I've been placed on mute to prevent any background noise. After the Speakers' remarks, there will be a question and answer session. If you would like to ask a question. During this time seems a press star followed by the number one on your telephone keypad.
Speaker Change: It is now my pleasure to turn today's call over to our venous Vice President of Investor Relations, Jeff Boyle. Please go ahead.
Jeff Boyle: Thank you and good morning, everyone. Thanks for joining us earlier today, we issued.
Jeff Boyle: A press release with our first quarter of 2025 financial results, which is available on Investor section of our website at <unk> Dot com.
Speaker Change: Joining the call today are John Houston, Our Venice, as Chief Executive Officer, President and Chairperson, Noah Berkowitz, our Chief Medical Officer, and Andrew <unk>, Our Chief Financial Officer, our Chief Scientific Officer.
Speaker Change: Casey was scheduled to join US this morning, but had an unanticipated personal event and we will not be able to before.
Speaker Change: Before we begin the call I will remind you that today's discussion contains forward looking statements that involve risks uncertainties and assumptions. These risks and uncertainties are outlined in today's press release and in the company's recent filings with the Securities and Exchange Commission, which I urge you to read our actual results may differ materially from what is discussed on today's call.
And now I'll turn the call over to John.
Speaker Change: Thanks, Jeff and good morning, everyone and thank you for joining US today as you saw in our earnings release. This morning, we have reached an important moment in our Venice as progress as a company.
Speaker Change: Recently shared the first ever positive pivotal data for our protect the greater Vegas trends, which we are moving towards filing in registration. In addition, we continue making great progress with our pipeline and shared exciting first in human data for <unk> 102 are locked to the greater and excellent preclinical combination data for <unk>.
Speaker Change: Three our Bcl six degrees are in hematology.
Speaker Change: We also recently received a safe to proceed from the FDA for <unk>, <unk> six or <unk> the integrator.
Speaker Change: We will discuss each of those items on the call today, Noah will review the clinical progress for both Vegas trend or <unk> and for <unk> 102.
Speaker Change: You also then review our recent preclinical combination data for <unk>, three and provide an update on <unk>.
Speaker Change: Finally, Andrew will provide a financial overview, including our capital allocation priorities.
Speaker Change: He is an updated cash runway guidance.
Speaker Change: However, before we get into a data update I'd like to cover three important topics upfront.
Speaker Change: We remain.
Speaker Change: Excellent progress towards our filings and Registrational plans for <unk> in the second line plus ESR, one mutant breast cancer based on the strong data from the <unk> study, we have a high conviction that <unk> has the potential to be a best in class monotherapy treatment for patients in a second line ESR one mutant setting.
Speaker Change: We are all on track to submit a regulatory filing with health authorities in the coming months.
Speaker Change: We believe there is an attractive opportunity for <unk>.
Speaker Change: As a second line plus ESR, one mucin treatment in metastatic breast cancer, and we will discuss this opportunity in Greek.
Speaker Change: To detail after our <unk> presentation in June.
Speaker Change: Secondly, we have aligned with Pfizer on the removal of the two phase III combination trials from our joint development plan. There were planned for this year.
Speaker Change: The first of these trials was a combination with our CDK 646 inhibitor in the second line setting and based on recent discussions with health authorities and our observations from other trials involving biomarker selected populations. We believe EUR therapies will be restricted to patients with ESR one mutations in the second line plus.
Speaker Change: Same thing.
Speaker Change: With this in mind, we have removed we've moved the second line ITT combination trial, which was planned to initiate in 2025 from our joint development plan.
Speaker Change: The second trial was the first line combination trial with a term of cyclic Pfizer CDK <unk> inhibitor, which was also planned to initiate in 2025.
Speaker Change: After reviewing the totality of emerging information, including external data results the evolving treatment landscape in metastatic breast cancer and long term capital allocation, we are aligned with Pfizer to remove this first line combination study from our joint development plan as well.
Speaker Change: We and Pfizer will continue to evaluate our ongoing combination studies in the second line plus setting and generated valuable data in metastatic breast cancer to inform our path forward.
Speaker Change: In addition, Pfizer is adding event that combo cohort to the ongoing phase one clinical trial with our investigational <unk> six inhibitor. This trial will be operationalized and funded solely by Pfizer.
Speaker Change: As these trials complete we will make data driven decisions about whether further investment in each of these combinations is warranted I look forward to sharing additional details in the coming months as our trials continue.
Speaker Change: The third major topic is our company wide cost reduction effort. The recent challenges in the capital markets are prompting us to extend our cash runway and ensure our programs reached data milestones before additional capital as needed.
Speaker Change: An important step in this process is maximizing our efficiency and reducing our operating expenses wherever possible.
Speaker Change: We have implemented a restructuring that includes a workforce reduction of approximately one third of the company portfolio re prioritization and overall cost reductions of approximately $80 million annually on a full year run rate basis.
Speaker Change: Although difficult the workforce reduction, which will result in streamlined operations across the entire organization is a prudent decision that we believe will appropriately size the company for future success.
Speaker Change: We are also re prioritized our research portfolio to focus on assets that have the greatest potential to deliver the most value for patients physicians and shareholders.
Speaker Change: Our clinical programs <unk> hundred two in neuro degeneration, and <unk> hundred 93, and hematology remain on track to deliver important clinical data later this year.
Speaker Change: Overall these steps will result in a combination of cost savings and cost avoidance of approximately $500 million over the next three years.
Speaker Change: Net result of these actions is a change in our guidance to extend our cash runway into the second half of 2028.
Speaker Change: We believe these significant cost savings and our refined capital allocation strategy. In addition to our strong balance sheet will allow us to advance our early development portfolio in a timely and efficient manner as well as ensuring a financially disciplined approach to commercial readiness.
Speaker Change: Before I continue I do want to thank all the talented employees who are directly impacted by this decision.
Speaker Change: Im proud of the progress we have made together and want to acknowledge their contributions and commitment to discovering and developing new treatment options for patients with life altering diseases.
Speaker Change: We wish the best for these colleagues as they transition to new opportunities I also want to thank the employees, who are continuing the journey with us our Venice as each of them will be instrumental in helping us achieve the ambitious goals, we have laid out for the company.
Speaker Change: I'll now turn the call over to the team to review our current our recent data and the details from the quarter a return at the end of the call to review the milestones that we anticipate for the remainder of 2025, but for now I'll turn the call over to Noah.
Noah: Thanks, John and good morning, everyone.
Noah: Together with Pfizer, we were pleased to announced positive phase III results from the <unk> II trial earlier in the first quarter. These data the first from a pivotal trial with a protester greater represents an exciting and validating step forward for our platform.
Noah: As John mentioned, we are excited to announce that data from the <unk>. Two trial were selected for a late breaking oral prison.
Noah: <unk> at the American Society of clinical oncology or Astro meeting in late May and we will also be featured in the asphalt press program <unk>. Two abstract has been selected for inclusion in the 2025 Best Tabasco program. In July. This program is important it's run by <unk> to increase access to.
Noah: Clinically impactful research for those who are unable to attend the annual meeting.
Noah: Given our plans to present, the full data set vasco, which imposes an embargo on the presentation I will only be providing commentary on the information previously disclosed in the top line data release and patients with ESR, one mutant tumors that exceeded the pre specified hazard ratio of zero.
Noah: <unk> six and demonstrated a clinically meaningful improvement in progression free survival over or best friends. Additionally, <unk> continued to demonstrate a safety and tolerability profile.
Noah: Our previous studies.
Noah: We believe <unk> has the best in class profile and our plans to seek global regulatory approvals remain on track, while we are no longer planning new Registrational trials for best deck, we will continue to generate valuable data and our ongoing combination trials and we welcome Pfizer's addition.
Noah: The uptick in combination with their <unk> inhibitor to their ongoing phase one trial.
Noah: Now turn to our most advanced neuroscience program.
Noah: We have designed investigational oral prophylactic freighters to cross the blood brain barrier and selected lead to greater leucine rich repeat kinase two were locked too.
Noah: <unk> is the large multi domain scaffolding kinase that plays a critical role in affected in the lysosomal trafficking.
Noah: Unlike traditional small molecule inhibitors that only block <unk> kinase activity lark to degraders eliminate the pathological scaffolding function the GTA activity and the client activity of lock to <unk> 102, with our lead <unk> two integrator, we believe our <unk> greater.
Noah: Particularly well positioned to be evaluated in two diseases, Parkinson's disease, where PD and progressive Supranuclear palsy Rps.
Noah: Familial <unk> plastic Parkinson's disease have been associated with mark to on the basis of genetics and models of licensed Somal dysfunction.
Noah: PSP disease severity is associated with mark to genetic findings. Additionally, we have published data associating the tau pathology of PSP with Mark two mediated endo lysosomal dysfunction.
Noah: Previously we have shared preclinical data demonstrating ERP 100, two's superior target engagement enhanced potency and licensed Soma pathway engagement in comparison with <unk> inhibitors in nonhuman primates, <unk> 100 to cross the blood brain barrier, where it achieved largely targeted protein degradation and deep.
Noah: Brain regions and reduced block two protein as well as neuro inflammatory biomarkers in cerebrospinal fluid or CSF.
Noah: I'm now pleased to share with you that we have observed a similar pattern of activity in our first in human phase one clinical trial in healthy volunteers. These data were presented last month at ADP D. Our trial evaluated single doses of <unk> 102, ranging from 10 to 200 milligrams and multiple doses ranging from.
Noah: 10% to 80 milligrams, we met our objective of 50% Mark to reduction in CSF. After a single oral dose of at least 60 milligrams once daily repeated oral doses of at least 20 milligrams.
Noah: This indicates substantial central Mark III protein degradation in the phase one clinical trial of <unk> 102 was safe and well tolerated with no serious adverse events or discontinuation reported after single or multiple doses.
Noah: 102 demonstrated dose dependent median reduction in lark to protein levels compared to baseline in peripheral blood mononuclear cells confirming target engagement in the peripheral compartment.
Noah: Taken together Pharmacodynamic dynamic changes of lark to reduction in the CSF reduce biomarker levels in the periphery and an acceptable safety and Tolerability profile support further study of Mark to integrators in PD and PSP that part of the work is ongoing.
Noah: Of the phase one single ascending dose cohort in patients with Parkinson's has already begun and the multiple ascending dose cohort will begin in the second half of the year, we anticipate providing an update on PK PD safety and Tolerability from the phase <unk> cohort in patients with PD later in the year.
Noah: Data I've shared demonstrates that we can make orally bio available protect that a brain penetrant, while our lead program is focused on Mark II for PSP in PD. Our discovery portfolio focuses on additional targets that may be relevant for Huntington's and Alzheimer's disease, we look forward to sharing updates on.
Noah: These in the coming months and years, turning back to oncology AARP 393 is our investigational oral protect designed to degrade b cell lymphoma, <unk> protein or VC offsets.
Noah: <unk> six is a transcription factor a master regulator of multiple cellular processes during the b cell development, including proliferation survival and apoptosis altered Bcl six activity has been implicated as an oncogenic driver in several subtypes of non Hodgkin lymphoma.
Noah: Making an irrational therapeutic targets <unk>.
Noah: Protect mediated degradation has the potential to overcome the historically undruggable nature of Bcl six.
Noah: <unk> III Potently and rapid lead to great Bcl <unk> protein with iterative activity, which is critical to overcoming bcl fixes rapid re synthesis rate.
Noah: Painting and anti tumor activity in 2024, we shared preclinical data demonstrating that <unk> 303 drives tumor regression in multiple in vivo models of B cell driven non hodgkin lymphoma, including large b cell lymphoma, we are enrolling patients with non hodgkin lymphoma, and our phase <unk>.
Noah: One clinical trial and are on track to share initial data by the end of the year.
Noah: At AAC or this past, we presented new preclinical in vivo data for AARP 393 in <unk>.
Noah: Combination with standard of care by Robbins, and chemotherapy as well as oral investigational small molecule inhibitors.
Noah: These new data highlights.
Noah: Potential of <unk> hundred 93 to drive synergistic anti tumor activity across multiple aggressive large b cell lymphoma, xenograft models ARV $3 three enhanced tumor regressions when combined with current standards of care, including R chop and various biologics, notably <unk> 393 monotherapy.
Noah: Therapy up regulated CD 20 expression, providing mechanistic rationale for synergy with anti CD 20 therapies such as Rituximab.
Noah: Additionally, <unk> 390, <unk> demonstrated enhanced tumor regression when paired with targeted small molecule inhibitors of Bcl two ECH Julien PTK key oncogenic partners of Bcl six these results suggest that <unk> 393 may enable highly effective chemo.
Noah: Therapy free regimens, whether in combination with biologics or as part of an all oral therapeutic strategy.
Noah: We will present, new preclinical data in a patient derived model of NGL Immunoblastic T cell lymphoma or <unk> at the European Hematology Association Conference in June of this year. This is an orphan indication with high unmet high unmet and limited treatment options. We believe this will be the first preclinical.
Noah: To show human AI <unk> dependency on D C offsets.
Noah: We also plan to present preclinical combination data with an emerging standard of care by specific antibody and a model of aggressive large b cell lymphoma in the second half of the year and finally, we filed an IND for our <unk> <unk> due to greater <unk> and recently received the safe to proceed.
Noah: Letter from the FDA, we anticipate beginning a phase one trial in patients with solid tumors harboring <unk> mutations in the second half of this year.
Noah: <unk> as a driver oncogene and several major tumor types and is associated with poor prognosis and resistance to standards of care, our greater has demonstrated high potency and differentiation from inhibitors and other generators currently in the clinic. In addition to selectivity in the preclinical setting.
Noah: <unk> demonstrates robust anti tumor activity from dose responsive degradation of Kers, G 12, D and mutated cancers, including pancreatic and colorectal cancers.
Noah: Preclinical studies are protected greater has demonstrated the ability to bind both the active and inactive states of Kers G 12 D AARP 100.
Noah: <unk> <unk> six.
Noah: Will.
Noah: It will <unk>.
Noah: Eliminate rather than inhibit <unk> 12 D with in vitro potency and those that potency can be 30 fold greater than inhibitors integrators currently in the clinic in totality. These preclinical data give us confidence and we intend to show differential biology of RK risks.
Noah: Graders at a conference later this year I look forward to updating you on our progress in the coming months with that I'll turn the call over to Andrew to review, our quarterly financial information.
Andrew: Thanks, Noah and good morning, everyone I am pleased to share financial highlights for the first quarter ended March 31, 2025, as a reminder, detailed financial results for the first quarter are included in the press release, we issued this morning.
Andrew: Let me start with the financial implications of the corporate restructuring and the removal of the two phase III combination trials from the vet the development plan.
Andrew: The corporate restructuring and associated workforce reduction were difficult decisions to make and are impacting many talented employees.
Andrew: They were however necessary to meet our goals of reducing our cost structure and extending our cash runway to support our promising pipeline.
Andrew: The reductions were focused on reducing reducing internal costs without having an impact on clinical stage programs that will drive value over the next several years we.
Andrew: We estimate the restructuring will result in a reduction of our ongoing infrastructure costs of approximately $80 million annually with savings expected to begin to be fully realized in the fourth quarter of 2025.
Andrew: Yes.
Andrew: And in addition, we anticipate cost avoidance of approximately $350 million to $400 million.
Andrew: Over the next three to five years as a result of the removal of the two phase III combination trials from the website development plan.
Andrew: These actions will allow us to continue progressing our promising pipeline without the need for a near term cash infusion and maintain a strong financial position with a cash runway now into the second half of 2028.
Andrew: I'll now briefly touch on some key financial highlights for the first quarter of 2025.
Andrew: At the end of the first quarter, we had approximately $954 million in cash cash equivalents in marketable securities on the balance sheet compared with $1 4 billion for the year end 2024.
Andrew: Revenue for the three months ended March 31, 2025 totaled $188 8 million compared to $25 3 million for the three months ended March 31 2024.
The increase in revenue was primarily due to the accounting impact of the reduction in the <unk> collaboration agreements program budget due to the removal of the first and second line phase III trials from the development plan.
Andrew: The revenue recognition accounting for this agreement uses the percentage of completion method as the budgeted cost served as the denominator and the percent complete calculation a reduction in that budget compared the same actual incurred costs resulted in a higher percent completion, and therefore higher revenue recognized in the first quarter.
Andrew: General and administrative expenses were $26 6 million for the first quarter compared to $24 3 million for the same period of 2020.
Andrew: Research and development expenses were $90 8 million in the first quarter compared to $84 3 million for the same period of 2024, the increase of $6 5 million, which was primarily driven by a onetime inventory charge of $10 million should update partially offset by lower than expected uptake development.
Andrew: Costs and an increase in the alert two program of $5 2 million.
Andrew: Offset by a reduction in non specific research in personnel expenses of $3 6 million.
Andrew: As I mentioned earlier, taking into account the anticipated impact of the restructuring the re prioritization of the research portfolio and updated development plans and the anticipated launch of <unk>. Our updated cash runway guidance is now into the second half of 2028.
Andrew: We believe our efforts.
Efforts are focused on areas that will maximize shareholder value as we move forward as we move towards important catalysts in the coming months with that I'll turn the call back over to John for closing remarks. Thanks, Andrew These actions should offer significant clarity around our focus over the next few years and I will allow us to hit a number of.
Andrew: Key data inflection points from our early development programs as well as the potential commercial launch of <unk> with our partner Pfizer as we progressed through 2025, there will also be many opportunities to showcase why our belief and our portfolio is strong. These include data from the <unk> II trial in a late breaking oral presentation.
Andrew: At <unk> in June the first phase one data for our locked to the greater <unk> 102 in patients with Parkinson's disease and first in human phase one data for our Bcl six degree to <unk> 393, we believe our progress will continue to demonstrate the potential of our protein integrators to add meaningful value for <unk>.
Jeff Boyle: <unk> that caregivers and our shareholders as we embarked on this new chapter and I want to thank you for your continued support and with that I'll turn the call over to Jeff to begin the Q&A portion of the call.
Jeff Boyle: Thanks, John before I turn the call over to the operator I do want to remind you that in order to comply with the <unk> embargo policy, we aren't able to answer questions about the vertex to data beyond the top line results reported in our press release on March 11th.
Speaker Change: So with that operator, we please open up the queue.
Speaker Change: Okay.
Speaker Change: At this time I would like to remind everyone that in order to ask a question you May Press Star then the number one on your telephone keypad.
Speaker Change: We will pause for just a moment to compile the Q&A roster.
Speaker Change: Okay.
Speaker Change: Okay. So your first question comes from the line of Mike Michael Smith with.
Speaker Change: Guggenheim. Please go ahead.
Speaker Change: Hey, guys. Good morning, Thanks for taking our questions.
Speaker Change: I just had a few follow up questions on web tag.
Speaker Change: Help us understand a bit more on how much of a decision to not advance the TDK.
Speaker Change: CDK four six inhibitor combinations work driven by emerging data on the class overall versus specific.
Speaker Change: They're very tech to resolve.
Speaker Change: And in the second line setting how do you think the uptake will be positioned relative to other oral <unk> and <unk>.
Speaker Change: Understand how much.
Speaker Change: How much do you need to invest in our commercial infrastructure as you potentially maybe co commercializing the product in the U S. Next year. Thanks, so much.
Speaker Change: Thanks, Great question so.
Speaker Change: The first question in relation to <unk>.
Speaker Change: Is this <unk>.
Speaker Change: And based on specific information related to <unk> or the class I think we've had a general discussion with Pfizer RSV.
Speaker Change: As you see.
Speaker Change: During the market is in an ESR what music only drug you saw some of the data coming from <unk>, which also had a very strong ESR one Houston only profile.
Speaker Change: And clearly.
Speaker Change: The data we had for <unk>.
Speaker Change: Which we can discuss in detail, but we already told you has strong ESR one mutant.
Speaker Change: Data, but we didn't hear IGT.
Speaker Change: So the general discussion, we had with Pfizer was around whether or not in that second line setting.
Speaker Change: With the drugs really just be ESR, one mutant only and we came to the conclusion, that's likely to be the case and therefore the design of the study that we had was for.
Speaker Change: ITT combination with CDK four six so we decided we would drop that in.
Speaker Change: So I think that's all.
Speaker Change: I think a logical rationale for dropping that particular study based on the emerging data on <unk> in the second line setting of whether or not youre going to have just the ESR one Houston only profile overall.
Speaker Change: And in terms of positioning <unk> I think as Noah said I think.
Speaker Change: And again, you'll see the data at <unk>, but we believe we've got the opportunity to be the best in class.
Speaker Change: Of the integrators in that second line plus setting.
Speaker Change: And with that our positioning would be I think very strong in terms of our <unk>.
Speaker Change: Overall.
Speaker Change: Data set in terms of Tolerability and overall activity.
Speaker Change: So we have very great great confidence of actually be if we get approval and get to the point of launch.
Speaker Change: Once we get through the regulatory hurdles I think we'd be in a very strong position for our positioning in that marketplace.
Speaker Change: And I think with the third question was.
Speaker Change: Yes, the commercial investments that clearly.
Speaker Change: <unk> 50, 50, Coco with Pfizer, we are the leads for that what we've done is done a very kind of prudent approach to commercial builds it has been very small.
Speaker Change: All going to be data driven and the point of approval. So yes.
Speaker Change: There will be a kind of significant backend.
Speaker Change: Recruitment to get our sales force in place, but right now our commercial footprint is really really very small and we also have the <unk>.
Speaker Change: To have ongoing discussions with Pfizer about the the best way to take the molecule forward in a commercial setting both in the U S and commercially and we will be able to update all of you on that as we complete those discussions.
Speaker Change: Your next question comes from the line of Andrew Bargain Schmidt Leerink partners. Please go ahead.
Andrew Bargain: Hi, Thanks, I'm sure you guys are kind of the mix.
Andrew Bargain: Concerns over the last few weeks. So my question was about the future neuro efforts in large too.
Andrew Bargain: Give us some color in the prepared comments about the role of large share of neuro diseases.
Andrew Bargain: I'm wondering how much large III degradation, you think is going to be clinically relevant and whether these would have been.
Andrew Bargain: Actually the combination approaches.
Norm: Yeah, I'll hand over to norm.
Speaker Change: Specific answer to that but we're very excited by the data we see so far was locked to our first new generation asset.
Speaker Change: First protecting the space and the first to show brain penetrant as well so that profile. We're seeing initially is very exciting.
Speaker Change: Joining us some more color to that sure.
Andrew Bargain: So Andrew Thanks for the interest in what is a very exciting first neuro degeneration directed prototype for our company.
Andrew Bargain: So indeed, we think that there are few opportunities for us to develop this year and as I outlined earlier in the call. That's because there is both the genetics that supported and then also underlying biology in these two diseases that were highlighted PSP Parkinson's disease. Your question around how much degradation.
Andrew Bargain: We wanted to achieve.
Andrew Bargain: The goal right now what had been and remains to achieve more than 50% degradation, we don't want to completely eliminate it because there is obviously functional.
Andrew Bargain: This to this to.
Andrew Bargain: This protein in terms of endo lysosomal trafficking, but when theres over expression of this increased activity you get miss trafficking and tightly tied to the pathology of these diseases. We know that on average Parkinson's disease patients have twice the level of Mark two in there.
Andrew Bargain: CSS compared to.
Andrew Bargain: Age matched controls and so we think it's prudent therefore to target something in the 50% range and so far we've seen in healthy volunteers that we can achieve that.
Andrew Bargain: And as.
As well as achieve appropriate downstream signaling. So we know that it's on target. We think on mechanism and the next thing is to really look at the data from the PD patients in the studies that are ongoing.
Andrew Bargain: Okay, and do you think it'll be a combination.
Andrew Bargain: Sure.
Andrew Bargain: Well when you say combination.
Andrew Bargain: Right now there really arent disease altering drugs in the.
Andrew Bargain: But our standard of care.
Andrew Bargain: So it's just a this may be on top of <unk>.
Andrew Bargain: Aldo.
Speaker Change: What type of treatment for patients.
Speaker Change: But this is this disease altering so I'm not sure what you mean by Combi.
Combinations.
Speaker Change: Right.
Speaker Change: And whether you think it would be on top of standard of care currently yes, yet.
Speaker Change: On top of standard of care.
Speaker Change: Okay.
Speaker Change: Thank you.
Speaker Change: Yes.
Speaker Change: Your next question comes from the line of Albemarle with UBS. Please go ahead.
Joseph: Hi, This is Joseph.
Asking for Ali Thanks for taking our question.
What is your view on the market size of <unk> in the second line plus monotherapy setting alone and I have a follow up.
Joseph: And you have a follow up joining us <unk>.
Joseph: Sure. So how do you think about the cadence of cost reductions from a modeling perspective and in terms of <unk> monotherapy.
Joseph: Monotherapy after the <unk> data can you help us think about what milestones you might be entitled to from Pfizer on approval in this setting.
Joseph: Sure.
Joseph: So the first question was.
Joseph: Relative to the market size, yes. So we've been thinking there is a really significant opportunity in that in that second line plus same thing.
Joseph: This 40000, new patients in the second line setting every year.
Joseph: Of that 40%, our ESR, one mutants only and that's our estimate some others estimate around 50%. So that's 25000 new patients in the second line.
Joseph: Space each year.
Joseph: And drugs as you know like ourselves who are out in that space Theyre, probably capturing about a third of that so there is a really significant opportunity. Therefore.
Joseph: Our goods profile of a greater like Vegas Trent.
Joseph: Hopefully capture quite a significant part of that market. So we're very excited about the opportunity in that space.
Joseph: The second question, Andrew I think it was more or less kind of a financial question, yes sure.
Speaker Change: So with regard to the restructuring.
Speaker Change: Notifications to employees have gone out this week so the restructuring has begun.
Speaker Change: As with all restructuring since there is a combination of employee reduction and cost control.
Speaker Change: I stated in my prepared remarks that we would have the full impact of the reductions by Q4, we will obviously start seeing benefit prior to that right. So we're offering.
Speaker Change: Our colleagues.
Speaker Change: Severance packages that will be paid out in Q2, So you won't see a charge in our Q1 financial statements that the notifications went out in Q2, so as a subsequent event for the purposes of our financial statements in the first quarter.
Speaker Change: But for modeling purposes, you can assume that youll start seeing savings relatively quickly Q3 will have a significant amount of savings in full impact in the fourth quarter.
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: And any color.
Speaker Change: Your next question comes from the line of Diavik Art, Sheila with Wells Fargo. Please go ahead.
Speaker Change: Good morning. This is simone on for Derek Thank you for taking our question.
Speaker Change: Or do you have to so.
Speaker Change: I know you said that after the loss to be greater.
Speaker Change: Christy 50% degradation.
Speaker Change: Zachary Derisk the target and what can we expect from this cohort in PD patients. Thank you.
Speaker Change: That's a great sign.
Speaker Change: No if you want to take that sure.
Speaker Change: I'm not sure I caught the second part but for the first the answer is it out right.
Speaker Change: These risks.
Speaker Change: So in general when you.
Speaker Change: Safety risks I.
Speaker Change: I guess that could.
Speaker Change: That could focus us on what are some of the liabilities associated with that target right. So we do know that there are.
Speaker Change: They're our findings with type two newmar.
Speaker Change: Numerous site enlargement or proliferation.
Speaker Change: That could be associated with.
Speaker Change: Collagen deposition in the lung.
Speaker Change: Also note that theres some of that utilization.
Speaker Change: Seen with and these are all the competitors right.
Speaker Change: So that utilization.
Speaker Change: Proximal tubule.
Speaker Change: In the kidney is some tightening going on in the background. So whoever's doing that a few of us. Please.
Speaker Change: Please.
Speaker Change: So.
Speaker Change: So that's known and Thats been a challenge for inhibitors for reasons that we have our own hypotheses and it's probably too much to go into on the call right now we have seen minimal ever.
Speaker Change: Evidence for the type two numerous sites enlargement.
Speaker Change: Have associated the much reduced.
Speaker Change: Pneumocyte proliferation that we observe with harder greater rather than what's observed with inhibitors.
We associate that with <unk>.
Speaker Change: Different protein depth.
Speaker Change: Different profile of protein deposition in the alveoli. So we think that we have a differentiated profile compared to inhibitors and we're tracking patients in the meantime in our study we looked at diffusion capacity in the month and we're measuring renal function on an ongoing basis and so far things have.
Speaker Change: Been safe to proceed.
Speaker Change: In terms of your second question has to do with the <unk>.
Speaker Change: <unk> cohort expectation, but I'm not sure what you meant by the expectation there in terms of timing or results.
Speaker Change: The results are going to have good results come out.
Speaker Change: Sure.
Speaker Change: Or what could we see.
Speaker Change: Well so healthy.
Speaker Change: I mentioned earlier PV patients have twice the level of.
Speaker Change: <unk> two protein.
Speaker Change: <unk> in the CSF and presumably in deep brain regions compared to healthy volunteers. So.
Speaker Change: We would expect in our sat in our <unk> studies, we can recapitulate, what we saw in healthy volunteers, we could see now in higher baseline.
Speaker Change: Our two levels degradation that is achieving greater than 50% reduction, which is our target and then on top of that because they also have.
Speaker Change: Neuro inflammation and other signs of neuro.
Speaker Change: <unk> for agility or.
Speaker Change: Sure.
Speaker Change: Neuronal death that we can capture some signals of this with 28 days of treatment in the Mad study. So we are looking at Biomarkers and.
Speaker Change: Sure.
Speaker Change: Hope that we can see that signal and the Mac.
Speaker Change: Thank you.
Speaker Change: Okay.
Speaker Change: Your next question comes from the line of <unk>.
Speaker Change: <unk> with Jefferies. Please go ahead.
Manoj: Okay. This is manoj and for Argos disciplined question will you need any overall survival data trends.
Speaker Change: Regulatory submission.
Speaker Change: The expected timeline for market entry there.
Speaker Change: Just one more on <unk>.
Speaker Change: Are you considering any partnerships will make neuro programs there. Thanks.
Speaker Change: Going back to the I'm, sorry, just going back to that first question could you repeat that.
Speaker Change: In terms of regulatory filings.
Speaker Change: Any overall survival trend for regulatory submission.
Speaker Change: Oral.
Speaker Change: Hello, one overall cutaway.
Speaker Change: Trend.
Speaker Change: Overall survival versus I'm, sorry, yes.
Speaker Change: So.
Speaker Change: So overall, we can't really talk about our data beyond what has been shared in our topline results and we recommend that you.
Speaker Change: Joining us.
Speaker Change: <unk> to hear the presentation.
Speaker Change: Certainly in an answer to your question about how that impacts.
Speaker Change: Submissions ultimately.
Speaker Change: Regulators generally want to see that there are no adverse overall survival findings.
Speaker Change: When winter months, PFS, which is a surrogate.
Speaker Change: For us, but it is something that is.
Speaker Change: There just isn't any companies don't power <unk> when they submit.
Speaker Change: And then the second question you asked about neuroscience and partnering.
Speaker Change: Clearly as we move forward and this Facebook and PSP Parkinson's disease, we've always said that.
Speaker Change: This would be an area that could lend itself to having a strategic partner would end up being settling the hawkinson area quite significant sized trials.
Speaker Change: But right now we're in a good position to be able to move our program forward to significant data inflection points.
Speaker Change: <unk> will review potential partners at that point.
Speaker Change: Thanks.
Speaker Change: Okay.
Speaker Change: Your next question comes from the line of Jonathan Miller with Evercore ISI. Please go ahead.
Jonathan Miller: Hi, guys. Thanks for taking my question.
Jonathan Miller: I'll do one more on that Doug maybe since we haven't spoken about the first line potential there.
Jonathan Miller: You're a little more vague about the rationale for not proceeding with the <unk> phase three.
Speaker Change: Is your expectation that nextgen estrogen receptor directed therapies.
Speaker Change: We're not going to be relevant in first line in general or is this more to do with that digs profile or more to do with the <unk> profile of the data that you've seen in the combination so far maybe I guess I'll start with that.
Speaker Change: Then secondly.
In Bcl.
Speaker Change: Six program.
Speaker Change: How much data in NHL patients can we expect to see.
Speaker Change: In the next handful of releases and would you expect to be able to show.
Speaker Change: Or is there or at least meaningful efficacy data that will allow us to comp to other recent NHL data sets.
Speaker Change: Yes, great questions.
Speaker Change: I'll take the first one I know it can take the second one secondly.
Speaker Change: Big decisions like this around.
Speaker Change: Going forward and over the first line study they don't happen overnight. So it's been lots of discussion with our colleagues at Pfizer.
Speaker Change: As it was a genesis of that final decision.
Speaker Change: Was <unk>.
Speaker Change: Pfizer looking at.
Speaker Change: Basically our press release from our <unk>, two data, where we say that we have <unk> mutant only but we havent IGT.
And without going into the data if you just take that as the opening gambit.
Speaker Change: It probably started a conversation around do ER degraders work against Wild type either in the second line setting which is a reasonable question.
Speaker Change: But then I think from Pfizer and took it to the next level, which is do they work in the first line setting.
Speaker Change: So I will give you their Venice view, we believe they do we believe that <unk> will work very effectively in the frontline setting.
Speaker Change: For several years, we've talked about the difference between first line and second line disease in the second line disease.
Speaker Change: Probably around 40% of the patients of ESR one mutate.
Speaker Change: Mutations.
Speaker Change: Basically give them an endocrine sensitivity.
Speaker Change: And their own 60% of the patients have tumors that have wild type and other driver mutations that are largely in the crane insensitive.
Speaker Change: With the second line trial was that we'd be able to capture wherever endocrine sensitive group of tumors that are in that broader ITT net.
Speaker Change: But in reality, what you saw that we missed the ITT wishes, telling you that there's not as many.
Speaker Change: Integrate insensitive tumors in that space. However, in the first line setting. We believe is a very different story, we believe that maybe ESL.
Speaker Change: <unk> mutations represent maybe only 5% of what you see in the first line setting the vast majority of the tumors, we'd be wild type, but most significantly we believe those will be in the crane sensitive and therefore available to be tackled.
Speaker Change: Tackled by a drug like <unk>. So that's our belief is still is.
Speaker Change: But we're in a partnership with Pfizer and I think they want to have more mature data not just from our internal programs and data center, but also the external world they want to see what's going to happen with <unk> the Roche.
Speaker Change: The greater which is in the first line.
Speaker Change: So if that comes out and it's positive in the first line setting and that's going to be a great signal for all the year therapies <unk> as well.
Speaker Change: <unk>.
Speaker Change: Interesting data coming out from Serena six more mature data there could also influencer and of course as our data matures overall I think Pfizer also want to see our current term aside glib.
Speaker Change: Combo mature in terms of that data set also.
Speaker Change: So yes, there's a number of different things that Pfizer, we'd like to see in terms of maturity of data, both our internal data and the external data.
Speaker Change: And as to say we are in a partnership.
Speaker Change: Good partners can look at two different data sets in two different scenarios and maybe come out with different options.
Speaker Change: But where we are.
Speaker Change: We're going along with this decision from.
Speaker Change: The team to opt out of the first line study.
Speaker Change: And we move on and basically where we have taken the money that was targeted for that study. That's the budget allows us to plan to fund the rest of our portfolio, which is a very exciting portfolio in a more aggressive way.
Speaker Change: And as data matures at Pfizer come back to us and say they actually do want to do a first line study we could assess that at a later date, but right now.
Speaker Change: That is not in our plan and we move on.
Speaker Change: <unk>.
Speaker Change: Regarding <unk>, we're early in the dose escalation, but we shared that we expect to share results later in the year I don't think we can order offering more guidance on that right now think of it as several cohorts.
Speaker Change: Do you expect to be.
Speaker Change: Okay.
Speaker Change: Sorry for the year.
Speaker Change: Yes.
Speaker Change: Or do we expect we would share.
Speaker Change: Where we are in terms of.
Speaker Change: Sure.
Speaker Change: 50 and efficacy.
Speaker Change: Yeah.
Speaker Change: Do you expect to be in the dosing range would you expect to be reaching dose levels that are where you want them to be from the perspective of the level of degradation youre expecting.
Speaker Change: To drive efficacy.
Speaker Change: We may be yes.
Speaker Change: Okay.
Speaker Change: Alright, thanks, so much.
Speaker Change: Sure.
Speaker Change: Your next question comes from the line of <unk> Ahmad with Bank of America. Please go ahead.
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: Okay I have a few questions as well.
Speaker Change: Thank you.
Speaker Change: You had talked about the market opportunity for <unk>.
Speaker Change: Barrick Teck to patients that that were positive in the study mentioned that there too.
Speaker Change: One third of the 25000 patients on that drug does your market data would give you any feedback at that profile of 130 patients are and is there anything different about the other two third.
Speaker Change: That could make that potentially more attractive.
Speaker Change: Patients and then can you just provide any color on the remaining Pfizer milestones do you expect to realize from here on out.
Speaker Change: And if there are any specifically related to the collaboration and then the last one I'm sorry, if I missed this but are you still planning on exploring that Doug and first line metastatic breast.
Speaker Change: Certainly.
Speaker Change: So firstly so.
Speaker Change: So first of all yes in terms of the patient population.
Speaker Change: <unk> in the second line, yes, so we think based on our assessments and some of the other external data 40000, new patients in that second line setting, which we believe as I said before 40% of our ESR what mutant.
Speaker Change: <unk> in that second line plus overall setting.
Speaker Change: So one reason only that's probably.
Speaker Change: 16.
Speaker Change: 2016 to 25000 patients that are then available I think Australia has done remarkably well to capture a significant number of those patients I think there is a growing opportunity in that market too to have more effective drugs in there.
Speaker Change: And it's a growing I think it's a growing space. So yes, we think it was as I said before are really significant.
Speaker Change: Opportunity and we also believe is a very good opportunity to have a very targeted launch into that space. There is a probably around 6000 oncologists that drive 70% to 80% of the prescriptions in this space. So we can also target.
Speaker Change: S. Prescribing population I think very effectively so I think yes, a really significant exciting opportunity.
Speaker Change: As it relates to cat.
Speaker Change: <unk> miles of general milestones and Pfizer.
Speaker Change: So with regard to the <unk>.
Speaker Change: The Pfizer agreement, we are entitled to a milestone on first approval and do not believe we've disclosed the exact amount of that.
Speaker Change: So disclose them now, but we are entitled to something and then I think you asked a question specifically regarding cat six there's certainly nothing in the contract specifically regarding cat six.
Speaker Change: So no it would be related to the first approval, which would be obviously the uptick.
Speaker Change: And then the final thing you asked was I think do you see any opportunity.
Speaker Change: <unk> in the first line, while my answer I mean, clearly the decision was made by now with Pfizer is not to go forward.
Speaker Change: In the first line setting and we've also said that from a business perspective, we think.
Speaker Change: <unk> would do well in that first line setting so let's see how data matures over the web repeated the time the data is needed to mature.
Speaker Change: But as I said earlier bright note.
Speaker Change: We move on the money that we had sequester for that first line study, there's not going to get moved to other parts of our portfolio and we are very excited about those opportunities as well.
Speaker Change: Your next question comes from the line of Peter Lawson with Barclays. Please go ahead.
Peter Lawson: Great. Thank you thanks for taking the questions.
Speaker Change: Couple of questions on that.
Peter Lawson: Commercialization so <unk>.
Speaker Change: You kind of walk through the size of the sales force you need.
Peter Lawson: And then your comments just around <unk>.
Peter Lawson: <unk> in first line does this the Pfizer partnership preclude you from going off from finding a different partner to run that first line study.
Peter Lawson: And if you could walk through kind of that processes potentially we can link for a first line study.
Peter Lawson: Yes, so start off with the size of the sales force as I mentioned.
Peter Lawson: It's going to be a fairly targeted.
Peter Lawson: I think financially prudent approach that will be taking obviously in a 50 50 setting whatever we do feasible.
Peter Lawson: Matching in the U S.
Peter Lawson: <unk> 6000 in coal just.
Peter Lawson: Where we can target, we should drive that 70% of prescriptions. So.
Peter Lawson: I think we're going to have an effective but.
Peter Lawson: Appropriately sized sales force.
Peter Lawson: To hit there.
Peter Lawson: In terms of other partners.
Peter Lawson: Absolutely not no we were not.
Peter Lawson: Our partnership with Pfizer.
Peter Lawson: We are.
Peter Lawson: Very pleased with the partnership with have the size over the last years have been very supportive and good partners can also have different views and Thats right now we've got a different view about the first line setting, but we agree overall with the decision.
Peter Lawson: And we will see what happens as the data matures for Pfizer, but as I said right now we take the money that we had sequester for that and we move it into other things in our portfolio and I think thats going to be a big value driver for our Venice.
Speaker Change: Got you. Thank you and then just on the Cat fits combination is that under the same kind of profit share terms of agreement with Pfizer or is that separate.
Peter Lawson: Separately.
Peter Lawson: Well.
Peter Lawson: Well <unk>, yes, because <unk> is everything to do with bad <unk> everything we do with <unk> is in that partnership.
Peter Lawson: <unk> is wholly owned by Pfizer So.
Peter Lawson: In that scenario as we've talked about before we wanted to profile against the whole series of different.
Peter Lawson: Potential combinations. So we're actually excited to see Pfizer, putting vamp into that cat six study they are paying for it.
Peter Lawson: And if it <unk> well, we will get the benefit through the <unk> side of that.
Peter Lawson: Great. Thanks for taking the questions.
Speaker Change: Your next question comes from the line of Paul Choi with Goldman Sachs. Please go ahead.
Paul Choi: Hi, Thank you good morning, everyone and thanks for taking our question.
Paul Choi: I just wanted to ask if you have any sort of gating items are any remaining thing to do.
Paul Choi: Prior to schedule in your pre NDA meeting.
Paul Choi: And will that comm, presumably post post Vasco here are just some clarity on the color of when you plan to meet with FDA would be helpful. As part of your second half of this year our filing timeline.
Paul Choi: And my second question is just on the look to program.
Paul Choi: Parkinson's is just sort of when the next sort of.
Paul Choi: Data update could potentially be expected from that program I think the early data that you presented looked looks interesting and promising just curious sort of what timelines for next week to the next dataset might be thanks for taking our questions.
Paul Choi: Thank you.
Paul Choi: No.
Paul Choi: <unk>.
Paul Choi: Sure.
Paul Choi: We've met with the FDA for pre NDA meeting.
Paul Choi: So we feel that we are cleared to move forward and.
Paul Choi: And that's why we've conveyed in this in the prepared remarks that were.
Paul Choi: Moving ahead with our submission enthusiastically.
Paul Choi: Regarding <unk> two next datasets, we've said that we'll share information later this year.
Paul Choi: Even though we said that we'll start to Matt in the second half I'm not sure. If we can squeeze the most data at any meaningful conference by the end of the year. So we expect that we'll be sharing data from the sad portion.
Martin: Thanks Martin.
Speaker Change: No no naming prince yet.
Martin: Okay. Thank you very much.
Speaker Change: Your next question comes from the line of Tyler Van Buren with TD Securities. Please go ahead.
Speaker Change: Hi, This is <unk> on for Tyler so.
Speaker Change: First question are you still confident in pfizer's commitment to the partnership to commercialize <unk> in the second line <unk> mutant setting are you in any discussions to reevaluate the details of the partnership that is selling the asset to Pfizer for royalties.
Speaker Change: And then my next question is where do you envision the cat six combo in the treatment paradigm could eventually serve as a backbone treatment.
Speaker Change: Yes, thanks for the question and Noah can take the second one.
Speaker Change: <unk>.
Speaker Change: Although all of the interactions we have with Pfizer on <unk> and the planning for regulatory filing the NDA getting ready for hopefully an approval and potential launch are all all full blast.
Speaker Change: The team that joined teams are laying out a significant plans.
Speaker Change: As you would expect for a launch that could be at some point next year.
Speaker Change: Both from a global setting and from a U S setting so OLED, thus going forward well and as I said before we think is a significant opportunity in terms of the <unk>.
Speaker Change: There is no ambiguity there is a change there overall in terms of the broader scope of what we initially had is a collaboration with Pfizer. When we started off we were hoping for monotherapy first line adjuvant, which is quite a significant opportunity right. Now we are going to be very focused on making.
Speaker Change: The best ESR, one mutant degree.
Speaker Change: The greater in that second line plus setting.
Speaker Change: And I think as I said earlier, we wait to see how data matures for for Pfizer over whatever period of time, but we move on we move on in terms of making sure that we can get the best loan as possible.
Speaker Change: Once we hopefully get an approval and we are <unk>.
Speaker Change: Developer <unk> mutant only profile in that second line.
Speaker Change: Your line.
Speaker Change: Opportunity is clear that.
Speaker Change: Actions are looking for additional options in that space.
Speaker Change: And we believe that will provide that.
Speaker Change: We look forward to moving it forward. So yes. There is no. There is no no change in that game plan, but with Pfizer.
Speaker Change: Regarding the cat six.
Speaker Change: Yes.
Speaker Change: So in the prepared remarks, you heard us.
Speaker Change: As mentioned that while.
Speaker Change: There are no registration trials planned for Fab Tech, we continue to produce data from ongoing studies and in fact, there is a.
Speaker Change: New study is of where the starts were getting that debt to cap and.
Speaker Change: I think it's well.
Speaker Change: Well premature to project.
Speaker Change: And we had to because it's simply a phase one study, but I think it just demonstrates that we're looking to.
Speaker Change: Combined uptake.
Speaker Change: As we March into the second line space with other drugs to explore combinations that can bring more value to patients. So afterwards to see those results.
Speaker Change: Okay.
Speaker Change: Thank you so much.
Speaker Change: Your next question comes from the line of Clipper did better kornberg through risk Securities. Please go ahead.
Speaker Change: Hey, guys. Thank you so much for taking my question I have a couple of things first of all <unk> 90, I know you're currently enrolling patients in phase one trial I was just wondering how easy it has been too Andrew locations. You just seem to have a lot of centers open and also based on the recent preclinical combo data that you presented at ACR.
Speaker Change: Are you getting a better sense of where you think the drug and the combinations might stick in the landscape.
Speaker Change: And then just just.
Speaker Change: Question on your FDA communications with with some of the changes happening at the FDA is there any concern in terms of delayed timelines for meetings or review processes. Thank you.
Speaker Change: Yes, I'll take the second one first thing nor can I talk about the <unk> III and clearly there's a lot of.
Speaker Change: External.
Speaker Change: Changes that were monitoring in this space and suddenly.
Speaker Change: With the FDA from a from a node Venice perspective, we have no we have noticed no delay and no impact with their interactions with the FDA, which.
Speaker Change: Which is great.
Speaker Change: But obviously, we're going to continue to monitor that and as we've seen in the press. Some other companies have said, maybe a different experience so far so good with us.
Speaker Change: But I can say, we'll monitor that going forward.
Speaker Change: No.
Speaker Change: Yes, So 393, I think we can say that while the study began last year enrollment was slow at the beginning this is a phase one study. So by nature is slow. So it was I think a bit slow last year, there's a lot of enthusiasm and we see that we.
Speaker Change: And generate a backlog of patients now and it's enrolling steadily.
Speaker Change: In terms of where a 193 fit into the landscape.
Speaker Change: Well certainly depending on.
Speaker Change: The data that we generate there is the possibility of it being monotherapy will have to see.
Speaker Change: What the overall benefit risk as monotherapy, but we're quite enthusiastic about from the preclinical models that we've shared recently is its ability to combine with many other drugs for particularly with with.
Speaker Change: With bi specifics and particularly because it also seems to increase CD 20 expression, which could create a real synergistic opportunity.
Speaker Change: Thank you.
Speaker Change: Sure.
Speaker Change: Your next question comes from the line of Mr. Hymowitz with Citigroup. Please go ahead.
Hymowitz: Alright, great. Thank you very much for taking the questions I have three questions. So the first one is given the combo with the cat six and the <unk> have you are Pfizer produced any preclinical work that would support that combo or could you discuss the rationale for that combo Lana.
Hymowitz: On a scientific medical basis second question is we haven't talked much about supply chain could you just review the structure and geographic location for the manufacturing supply chain for <unk> as well as for the <unk>.
Hymowitz: It is domiciled and then the last question John You gave a very comprehensive answer with respect to the <unk>.
Hymowitz: <unk> for for Pfizer stopping the frontline study I'm just wondering if the if the factors related to the novel novel combo with the turbo as well as the potential to do.
Hymowitz: Our need to do a four arm study, perhaps could tease out contribution of components.
Hymowitz: Was irrelevant factor in that decision or not thank you.
Hugo: Thanks Hugo.
Hymowitz: <unk>.
Hymowitz: So yes, the first one.
Hymowitz: Did you do any clinical work with cat six and bad debt I think thats if that is no.
Hymowitz: I think the rationale.
Hymowitz: Really related to the fact that Pfizer very.
Speaker Change: We're excited by the profile of Cat six.
Speaker Change: I do think we see the potential of the combination with <unk> and.
Speaker Change: <unk> potentially will receive its cat six and positioning <unk> as being a.
Speaker Change: Really strong.
Speaker Change: A combination.
Speaker Change: No way anything you'd add to that yes, just some experience with four best Finfet looks attractive so.
Speaker Change: Yes.
Speaker Change: In terms of supply chain.
Speaker Change: So pfizer are accountable for the supply of event thus based in.
Speaker Change: During a skinny in Ireland.
Speaker Change: So we haven't had any supply chain issues.
Speaker Change: And you asked the question where does the IP resides.
Speaker Change: Here with us.
Speaker Change: With our Venice.
Speaker Change: And then a really interesting question Yigal the novel novel with a terminal.
Speaker Change: Opposition of components I'm sure that has factored into some of the thinking the broader view I gave is maturation of data the external environment.
Speaker Change: I'm sure.
Speaker Change: As part of the rationale but.
Speaker Change: Finally, I want to see.
Speaker Change: Our current of turbo.
Speaker Change: <unk> data mature that's in the second line setting, but they want to see what that looks like overall.
Speaker Change: So I'm sure that has factored into the broader decision, making around datasets and changing landscape, but yes, great question. Thank you.
Speaker Change: Okay. Thank you very much.
Speaker Change: Your next question comes from the line of Steven Schneiderman with BMO capital.
Speaker Change: Please go ahead.
Speaker Change: Hi, This is Michael Hoffman on for Ed Thanks for taking our question.
Speaker Change: Thinking about the LR RK to greater again, I know Biogen just announced today that enrollment in their phase II study is now complete with the results from 2026 I just wanted to ask how you are starting to think of the competitive positioning for your integrator versus others.
Speaker Change: Your confidence is yours can be differentiated versus slightly more advanced programs.
Speaker Change: Nor do you want to take that sure. Yes. So thanks, we certainly look at it.
Speaker Change: Biogen Denali partnership enthusiastically, we think it's validating to some degree.
Speaker Change: But validating for an inhibitor that doesn't get brain penetration and does not.
Speaker Change: And deliver significant inhibition in the brain.
Speaker Change: And so therefore with the two greater that guests.
Speaker Change: Significant brain penetration and can lead to.
Speaker Change: More than 50% degradation, eliminating all functions of mark to not just the kinase activity, we think that puts us in a very competitive spot. So we're looking forward to those results that stay.
Speaker Change: Successful then I think we're.
Speaker Change: There'll be a lot of enthusiasm for this program if their study is.
Speaker Change: The phase III program failed, but it has some directional data that supported Theres also going to be quite significant enthusiasm, but overall.
Speaker Change: We just do not believe that inhibitors get you there and.
Speaker Change: And the fact, you will see the continuing our continuous updates from our studies to see the benefits from the integrator.
Speaker Change: I appreciate it guys. Thank you.
Speaker Change: Your next question comes from the line of Neil <unk> with Cantor Fitzgerald. Please go ahead.
Speaker Change: Hey, guys. Thanks for taking the questions maybe a BD strategy question.
Speaker Change: Are you open to bringing in external assets just given your balance sheet.
Speaker Change: And then you got earlier.
Speaker Change: Earlier.
Speaker Change: That's in the pipeline, maybe talk a little bit that your conviction and departmental strategy there it.
Speaker Change: Okay.
Speaker Change: And our data.
Speaker Change: When you're looking at making some decision Dan.
Speaker Change: And then second maybe just for the Cat six.
Speaker Change: When should we anticipate.
Speaker Change: The data.
Speaker Change: And then what would be the bar that you have to have given the Italian early phase one trial.
Speaker Change: And now I can clarify.
Juan: Yes Juan.
Speaker Change: Alright.
Speaker Change: All commentary thank you.
Speaker Change: Yes.
Speaker Change: Okay tackle the cat six in that part of it in terms of the BD strategy I think.
Speaker Change: Overall, we have always been out there looking at opportunities to supplement suddenly our technology.
Speaker Change: And as we go forward.
Speaker Change: If there was an asset there that complemented our lead programs I think we'd be open to that obviously, we've been our Genesis as a company has been a platform based company and we're very proud of that and our portfolio is replete with really exciting the greatest but yes. There was.
Speaker Change: A significant opportunity to to get an asset that complemented I don't think we have any issue with that.
Speaker Change: It was another sub saying that I can remember with a subset of your question regarding capex.
Speaker Change: <unk> just to frame. This study this is a.
Speaker Change: This is a phase one studies just very exploratory so there no timelines associated with this we are going we can dose. The first patient yet is really shared in the spirit of.
Speaker Change: That will continue to look for nice combinations that could be practice informing and.
Speaker Change: Continued to expand the attractiveness of our already potentially best in class uptake in the second line setting and so that would be the case with the <unk> combination also is pfizer's wholly owned drug.
Speaker Change: We don't call the shots there in any way and we're just looking to see what we can generate that combo and right now the thought is for e-commerce.
Speaker Change: Okay. Thank you.
Speaker Change: Sure.
Speaker Change: Okay.
Speaker Change: Your next question comes from the line of James <unk> with <unk>. Please go ahead.
Speaker Change: Great. Thank you for taking the question.
Speaker Change: Was wondering if you've thought about potential end CCN guideline inclusion for some of your.
Speaker Change: <unk> CDK four six data to support combination use just given some of the notable PFS data you've shown at San Antonio 2023, and thereby allow doctors to use a CDK four six off label in combination with <unk> in the second line setting and my second question was just around your G. <unk> greater can you maybe talk about how that compares to <unk>.
Speaker Change: Telus is the greater than.
Speaker Change: Some of them, perhaps subpar efficacy and safety data have shown that.
Speaker Change: Last year it is now thanks.
Speaker Change: Northwest Teva sure.
Speaker Change: The first question. The second one was about useful to you the first one.
Speaker Change: <unk>.
Speaker Change: Yes, so look we continue to generate.
Speaker Change: But we're going to be sharing the maturation of our combination.
Speaker Change: We will.
Speaker Change: This will be discussed with.
Speaker Change: Commercial and medical affairs team about how to best share this information and be as practice informing as possible.
Speaker Change: I don't want to get ahead of myself and speak about in CCM guidelines.
Speaker Change: But but overall, we would share whenever physicians needs to make the best decisions, though obviously, we're seeking a monotherapy label and that's the only way we will be marketing the drug for monotherapy use.
Speaker Change: Regarding the <unk> integrator.
Speaker Change: I think I mentioned in the prepared remarks that we've seen that we have 30 times.
Speaker Change: <unk> see some other inhibitors integrators in this space one of the challenges for our leading to greater in this space is the.
Speaker Change: Our pilot toxicity or I guess as evidenced by trends <unk> been seeing that may be limiting in the dose.
Speaker Change: The dosing of that drug.
Speaker Change: In our case, we don't believe that this will be a limitation for our drug.
Speaker Change: Six and but of course, we're just starting our dosing of patients in the second half of this year.
Speaker Change: Thank you.
Speaker Change: Thanks.
Speaker Change: Your next question comes from the line of Susan Logan Askmen with Stephens Inc. Please go ahead.
Speaker Change: Hi, Good morning, and thank you for taking my questions. This morning, I wanted to kind of dig deeper into the details for the ESR. One mutant patients again that are naive to treatment I believe you mentioned earlier in the call about approximately 5%.
Speaker Change: ESR mutant.
Speaker Change: In the first line setting.
Speaker Change: Is that with the monotherapy design actually going to be well positioned to be more of a standard of care EBIT also in the first line that kind of.
Speaker Change: Demonstrate the DSO immune as well or would there be some additional trials or anything else that needs to be done there.
Speaker Change: And then with the total of about 40% I guess, the second my patient that ESR mutant.
Speaker Change: Is that more specific to first line patients that were treated with CDK. Four six inhibitors are also other treatments as well thanks.
Speaker Change: Yes, so just for.
For clarity.
Speaker Change: In the second line setting we believe around 40% of the patients have tumors that have ESR one Newton.
Speaker Change: Profiles.
Speaker Change: And that offers a potential 40000 patients that could be.
Speaker Change: Amenable to a drug like <unk>.
Speaker Change: So that's exciting as a great opportunity in the first line setting.
Speaker Change: Yes.
Speaker Change: Thanks, Brian and maybe a little bit 5% of the patients have tumors that have used our mutation the rest have.
Speaker Change: <unk>.
And the biggest difference we believe is.
Speaker Change: Wild type.
Speaker Change: In the second line setting is probably in decline insensitive, but well site in the first line setting is endocrine sensitive so there's a significant opportunity. There. So our belief is that that was in that setting I would do well, but we have made this joint decision with Pfizer not to go there and we move on to other things and in the second line.
Speaker Change: Setting, where we still see a significant opportunity and it will be.
Speaker Change: Seeking approval for our drug in that setting and ideally then launching into that second line setting along is upon us Pfizer.
Speaker Change: <unk> significant opportunity there and and.
Speaker Change: And as I said before we wait to see what the maturing information is in the first line setting both from our point of view of our data, but also the data coming from other companies.
I appreciate it thanks for the clarity there.
Speaker Change: Thank you.
Speaker Change: Okay.
Speaker Change: And that concludes our Q&A session for today I will now turn the call back over to John <unk>.
Speaker Change: Please go ahead.
Speaker Change: Well, thanks, operator, and thank you everyone. We gave you a lot of information today to digest.
Speaker Change: It remains for me just to say that we are incredibly confident about the future direction of the company and.
Speaker Change: It will be you'll be hearing more from us with additional updates through the year. So thank you very much for your time this morning.
Speaker Change: Thank you everyone that concludes today's call you may now all disconnect have a nice day.
Speaker Change: Okay.
Speaker Change: Yes.