Q1 2025 Kymera Therapeutics Inc Earnings Call

Text Immunology program I read five I'm Justine Koenigsberg chimeras head of Investor Relations. Please note that we are hosting today's event in lieu of our regularly scheduled quarterly update call. However, we have reported our results and filed our 10-Q. This morning for additional details on our Q1 results. Please reference our prep.

US release issued this morning, which is available in the IR section of our website.

During today's presentation, you'll hear from our team about our strategy our pipeline advancements and our next high value Immunology program.

Speaker Change: Joining me. This morning are an element of our founder President and CEO, Jared Gala, our Chief Medical Officer, and Veronica Campbell, our senior director of Immunology and project team leader of our newly introduced program IRA five.

Speaker Change: Here's a snapshot of today's agenda Nello will begin with an overview of our strategy and the opportunity with small molecule degraders.

Speaker Change: And Jared will provide a high level overview of our stat six program and we will conclude with our prepared remarks with a discussion of our newly introduced Iris five program before we open the call to questions if you'd like to ask a question. Please use the raise hand icon, which can be found at the bottom of your meeting window to help us move efficiently through the Q&A discussion.

Speaker Change: We ask that you were ready to mute your line in turn your camera on when called upon.

Speaker Change: Replay of today's event, including a copy of our corresponding presentation will be available soon after the call concludes in the investors section of our website.

Speaker Change: But before we begin I would like to remind you that today's presentation will include forward looking statements about our future expectations plans and prospects. These statements are subject to risks and uncertainties that may cause actual results to differ materially from those projected a description of these risks can be found in our most recent 10-Q filed with the.

Speaker Change: SEC any forward looking statements speak only as of today's date and we assume no obligation to update any forward looking statements made on today's call.

Speaker Change: With that let's begin mello.

So thank you Steve very exciting to be here today to share not only of pipeline upbeat, but also our new program <unk> five which were Anika will do in a few minutes I thought I'd take a few minutes here to just give you a.

Speaker Change: An update on <unk>.

Speaker Change: Strategy, where we're going some important decisions, we're making and upcoming milestones. So just to remind you <unk> was founded about actually just very recently nine years ago with the goal of building an industry, leading pipeline of medicines using a novel modality called targeted protein degradation.

Speaker Change: We believe with this modality, we can give rise to a series of new programs and medicines that can overcome the challenges that the industry has faced for the past 20 years in order to do so we've built some unique capabilities I would start with the fact that we have become a key leader in the space of targeted protein.

Speaker Change: Degradation.

Speaker Change: In doing so we've built some really unique capabilities, so he's finding and optimization of oral degraders.

Speaker Change: We have.

We've always had and continue to refine a unique target selection strategy based on pursuing traditionally on drug targets in highly qualified and validated pathways.

Speaker Change: And then as it allows us to be the portfolio. There is poised to really disrupt treatment paradigms. We have made a conscious choice a few years ago to focus in immunology and the main reason has been as I'll explain in a few slides.

Speaker Change: That particular space in these plays in time, we've been able to combine really the right target with the disruptive potential of targeted protein degradation delivering for the first time in industry oral drugs with biologic like efficacy and this is really.

Speaker Change: We are unique opportunities for chimera and for patients.

Speaker Change: So primarily founded and continues to thrive on three key pillars. One is a clear vision. So we have always believed that with the new technology not only you have an opportunity, but you have a responsibility to building a fully integrated company. So we are now building deep developed.

Speaker Change: <unk> capabilities to advance our programs into phase two and phase III studies with an eye of becoming a commercial stage company.

Speaker Change: We've been fortunate to always be well capitalized we now have as at the end of Q1 $775 million with now an extended runway into the first half of 2008.

Speaker Change: We have brought the five new molecules in the clinic since 2020, and we are on path to being able to go. These are 10 molecules in the clinic by 2026, we have dosed at this point weigh more than 300 between healthy volunteers and patients across our pipeline and one thing that we're very proud.

Speaker Change: <unk> is our ability to continue to demonstrate impeccable translation from our preclinical studies into the clinic with achieving in all of our programs more than 90% degradation with the desired efficacy and safety profile.

Speaker Change: So just a quick summary about targeted protein degradation. So the the main feature of the technologies the ability to use small molecules to remove protein. So you have almost a genetic lie knockdown or knockout effect with the flexibility.

Speaker Change: And the convenience of oral small molecules. So we were able to go after proteins that have not been drug a drug fully for the past decades with a simple oral drugs.

Speaker Change: That we're able to design synthesize and develop here at Chimera.

Speaker Change: So why immunology why is this such a unique opportunity for us and I would say for patients. So we the team did a.

Speaker Change: Work in the past year or so looking at the most common the 10, most common immune inflammatory diseases and those are a D. Asthma COPD as you can see from the slide a chess multiple sclerosis, and if you look at the seven major markets, that's about 160 million.

Speaker Change: Patients that.

Speaker Change: They are impacted by these diseases and if you look at the number of patients that aren't right now are accessing advanced that systemic therapies.

Speaker Change: Really around 5 million, so we're basically over 3%.

Speaker Change: Penetration of advanced systemic therapy into a wide variety of immune inflammatory diseases again in the seven major markets. So I don't think we have a problem of innovation in immunology, where there is plenty of great drugs.

Speaker Change: In many in many disease areas, we have a problem of allowing patients to accessing these highly effective drugs. In fact of these 5 million patients two thirds of these patients axis biologics are only one third access oral drugs in these oral drugs often are not able to.

Speaker Change: Liver the type of efficacy that biologics, Ken So we had an opportunity to expand access and expand the reach of highly innovative drugs with oral b graders that have the efficacy of these advanced systemic therapies and so when you try to put a number on their market.

Speaker Change: It's really hard to do if you look at five 3% to $5 million, it's $100 billion market or more than $100 billion market. So we're talking about 90% plus of patients that we believe are.

Speaker Change: Could be poised to receive our novel oral systemic therapies and that's a that's a very large number that obviously, it's even hard for us to quantify but our job here at <unk> to develop again as I said oral drugs that cannot only displace biologics.

Speaker Change: Because they ideally and hopefully we'll have a similar efficacy safety profile and the convenience of oral drugs Memorial Potently. We can now offer a convenient highly effective advanced therapy to the 90% of patients right now are not treated whether it's for access whether it's pricing whether it's for it.

Speaker Change: Convenience.

Speaker Change: And so in the here in this slide is really highlighting what are the challenges and the opportunities. So biologics, though as we all know transform treatment paradigms, they've transformed many diseases and how doctors treat diseases.

Speaker Change: But the challenge that comes with them is obviously there can be very expensive there can be complex and expensive to manufacture.

Speaker Change: And as well as to prescribing reimburse.

Speaker Change: I have often not always immunogenicity issue they have called storage issues. So if you're taking a biologics with you on a vacation you have to think about cold storage and obviously they bring the inconvenience.

Speaker Change: Route of administration often painful.

Speaker Change: And then again inconvenient in an industry survey that was done I think as recently as I believe a year and a half.

Speaker Change: A few hundred patients, whereas if you had an option to switch from a biologics to Anoro drive with the same profile.

Speaker Change: Would you would you make the switch and 75% of patients said, yes, so there's really not only.

Speaker Change: Fortuity, but there is a clear unmet need for patients to access for all therapies that will have a biologic like profile. So the question would be why wouldn't traditional small molecule oral drug captured that need and the answer that we tried to depict the depict here is in the bottom of the slide traditional oral.

Speaker Change: Small molecules for traditional PK PD profile. So the efficacy is driven by the ability of the drug to block their pathway 24, seven and because the PK and PD of a small molecule drug is really connected you see a sigmoidal curve.

Speaker Change: Mostly that depicts that correlation so youre not able to block the pathway constantly 24, seven but you have a peak to trough PD effect.

Speaker Change: This is very evident when you look at targets for example, I took to wear.

Speaker Change: While you're blocking the IL 23 pathway in principle, well youre not able to deliver the type of activity seen with an injectable IL 23 antibody and that's really because of small molecules in our ability to block the pathway fully with a degree there that we've shown extensively both pre clinically.

Speaker Change: <unk> and clinically we can block the pathway fully a steady state maintaining that degradation consistent and that as we've shown can mimic biologic flag pathway blockade.

Speaker Change: So there is in the next couple of slides I just wanted to share with you. Two key features of came era that I believe has made us a leader in developing unique programs, especially now in immunology.

Speaker Change: One is really around the capabilities that we've built I believe we're the best company today at finding small molecule ligands to undrawn or difficult to drive protein where some of the best.

Speaker Change: Structural biology capabilities and we've published on this extensively in peer reviewed journals on understanding coronary complex interactions of our drugs with the proteins and the three languages and we've shown consistently our ability to translate.

Speaker Change: In the clinic, our deep understanding of PK PD in different tissues in the in preclinical species and then in humans, which really de risks the translation into patients and hopefully into disease outcome and all of these capabilities have resulted in some really important okay.

Cushman: Cushman <unk> in the past few years, we delivered at this point I believe more than 90 development candidates for against Anthrax transcription factors. We've shown now extensively there are degraders are very potent very specific orally by available with a great and even distribution across these shoes.

Cushman: And we've shown over and over again as I mentioned, our ability to translate these profiles effectively into the clinic.

Cushman: Yeah.

Cushman: So another key Fisher, so we've talked about capabilities and other key Fisher of camera strategies, how we think about target selection and.

Cushman: And we have this key four pillars that had been the same since day. One we go after targets that have not been drug the drug well before where there is strong human genetics for the target.

Cushman: And importantly, where the pathway has been validated with other agents usually upstream of our targets.

Cushman: We usually if not always a clear path to show clinical differentiation. It early in our development strategy as.

Cushman: As well as now we're very very keen on programs that have access to large clinical and commercial opportunities. So if you look at our targets today that we're actively pursuing stat seeks an IRA at five two undrawn transcription factors, where came era has delivered the first development candidate or first that's the excess.

Cushman: Actually the first clinical entry.

Cushman: And soon the first clinical data.

Cushman: <unk> bin.

Cushman: Target had been pursued for decades.

Cushman: And really the technology has been missing and here we have first in class drug.

Cushman: With targets with strong genetic validation now Eric for the target there is been drugs, but not well with traditional small molecules.

Cushman: The beauty about our strategy is also that we're going after these.

Cushman: With that have been there.

Cushman: <unk> complementarity, so not only these are standalone important programs you know after IL 413 type one interferon cytokines B says auto antibodies I want Tialata pathways, but also you can imagine that eventually these pathways can be synergistic in how we think about further.

Cushman: Development in combination et cetera, and this is probably even more I appreciate it though if you look at the slide 13 here, where we're looking at where we're developing these assets in which not only disease area, but also in which indications. So you'll see for example for stat six we have a big F routine.

Cushman: Topic diseases, which are more often in dermatology respiratory and here you see seven or eight different diseases for a refi, which I would say its more traditional immunology rheumatology you see more in Gi and rheumatology, our RA lupus et cetera, while Iraq for S places in each of these diseases.

Cushman: So not only we can actually capture all of this is the totality of potential immune inflammatory indications, but then you can imagine when there is overlap a potential strategy down the road could be combination of these assets.

Cushman: Yeah.

Cushman: This is a slide that captures the concept there was made before about the unmet need in the space and these actually put a number to the concept. We can news start six in their concept can be applied to the other programs again, if you look at the seven major market, we have more than 100 million patients that are die.

Cushman: Nosed with th two diseases and you can see the most prevalent there it'd be asthma COPD chronic Renaissance this et cetera.

Cushman: The number of patients that have access to advanced systemic therapy right now dominated baidu pillow might be it's really around a million patients.

So we have <unk>.

Cushman: Almost 100 million patients if not more.

Cushman: That I believe we strongly believe would benefit from an oral drug that has the efficacy and safety all the injectable biologics. So an oral drug that can change how doctors prescribe medicines for patients with these diseases.

Cushman: So that's really what we're trying to do not only for <unk> six but also for Iris five in diseases that are as we've said complimentary to the stat Sig diseases. This is really around Axa Lee array crohn's disease.

Speaker Change: You see et cetera, and they're both Veronica and George will share more and then Eric four with again the more traditional one P. L are driven diseases. So.

Speaker Change: Hopefully this slide gives you a sense of the opportunities we have in front of us with oral drugs. There are really best in pathway to combine the convenience of oral drug in the accuracy of a biologic.

Speaker Change: So in this light I, just we will actually go through the upcoming milestones soon.

Speaker Change: And so I don't want to spend too much time going through the details of the slide I just want to say we have the next 18 months with the rich of milestones. We have start six upcoming data in June which we're very excited to finally get there we have phase one data at the end of the year, we have to face could be started to start there.

Speaker Change: I will tell you about IRS five so maybe I'll start I'll give you.

Speaker Change: Update on a couple of programs that will not be the subject of the later presentation. So.

Speaker Change: So first on Iraq for as you know Santa Fe is progressing Katy for seven four in two parallel phase III studies in both HSN a D. We continue to expect these studies to be completed in 2026 in first off mid 'twenty to 'twenty six with data. Shortly thereafter as you know Iraq for it was our first immunology target.

Speaker Change: The early success in that program has allowed us and has actually given us the impetus to invest even more in immunology and allowed us to build what we believe it to be.

Speaker Change: One of the best if not the best ore or immunology pipeline in this industry.

Speaker Change: And so why sell off has been advancing 474 without additional ongoing effort. There came are under the collaboration we've said that in the past as a result of these efforts. We're pleased to announce today that we have recently achieved their preclinical milestones, resulting in $20 million payment that we expect to receive in the.

Speaker Change: Second quarter, so a validation of both the strategy and the work that both teams have been doing in the past few years.

Speaker Change: Secondly, I'd like to touch on the disclosure that we released this morning and the press release around our decision around two so first I'll say that it's I think widely accepted that we're in a very volatile market.

Speaker Change: Period, not only biotechnology, but I would say the broader market and with that we believe that came era is exceptionally well positioned to navigate this uncertain environment. We have what we believe is that just said probably the best oral immunology pipeline in the industry.

Speaker Change: We have multiple upcoming catalysts that will go through later in the presentation. We have an incredible research team that continues to deliver novel programs, you've seen IRS five you'll see more.

Speaker Change: In the near in the near future.

Speaker Change: And we have a strong balance sheet of $775 million as of the end of Q1.

Speaker Change: But obviously, we can't just sit and be complacent, we continue to look for opportunities to ensure that our human as well as our capital resources are always prioritize towards the highest return activities and.

Speaker Change: And in fact with these with this philosophy that we've continued to optimize our resource allocation strategy, you've seen changes that we made in the past around our oncology investments and so it's really with the spirit of prioritizing and funding the highest return activities that we're announcing today, our strategic decision not to advance.

Speaker Change: Arctic two degree there Casey 295 into clinical development.

Speaker Change: I just wanted to take a moment to explain that well first I would like to say that we have completed our IND, enabling studies with this drug.

Speaker Change: And we have seen no adverse events in any of our studies in any of our doses. So this was as a successful IND, enabling campaign as you wish.

Speaker Change: And we continue I'm a continue to be a strong believer in the differentiator case, where it would be greater in these highly validated pathway at.

Speaker Change: At the same time.

Speaker Change: In this current environment reserve so location.

Speaker Change: It's very important and we believe resource a location and particularly our people.

Speaker Change: Two programs with the highest probability of success is paramount. So at this point, we've decided to hit pause on.

Speaker Change: Arctic two efforts and redirect those resources. So this is this decision will allow us to address two important 0.1.

Speaker Change: We're able now to dedicate more human capital as well as.

Speaker Change: Our finances to what I believe it to be one of the largest potentially one of the largest programs in the industry, our statutes programs and six to one I would say the statutes franchise and seeks to one that is.

Speaker Change: Really at the cusp of key inflection points, where also can use some of these both human and financial capital to fund.

Speaker Change: Fun Iris five in other efforts that we have in other areas and then secondly, what this decision has allowed us to do is to extend our cash runway from mid 2027 to the first half of 2028. So this is very important because now our cash runway is well beyond.

Speaker Change: Important inflection points, especially I would say well beyond the phase II readout for six to one.

Speaker Change: So I mean, you all know it's never easy.

Speaker Change: When we make this resource allocation decision, but.

Speaker Change: But I hope I was able to convey our strategic thinking around this decision and then happy for myself and the team to take questions in the Q&A at the end.

Speaker Change: So I thought I'll pause here now and pass it onto Jared for him to go through our aesthetics program.

Jared Gala: Thanks Paolo.

Speaker Change: This is a very exciting time for chimera from a development perspective.

Speaker Change: We are well positioned to achieve multiple clinical data readouts that we believe will further validate our approach and strategy.

Speaker Change: Before we formally introduced our IRA by program I'd like to give you a brief update on our ongoing and planned clinical trials for Kt six to one.

Speaker Change: Our first in class oral stat fixed to greater program and the first stat six targeted medicine to enter clinical development.

Speaker Change: The IL four IL 13 pathway drive th two inflammation and at highly validated by diplomat, an injectable biologic targeting IL four receptor alpha that inhibits IL four and IL 13 signaling and is approved for the treatment of multiple different th two allergic diseases, including atopic.

Speaker Change: Imitative and asthma.

Speaker Change: <unk> six is the obligated and specific transcription factor in the IL 413 pathway and is therefore, the critical signaling node controlling ph to inflammation.

Speaker Change: For this reason blocking the function of the Essex is expected at Phenocopy IL four IL 13 targeting.

Speaker Change: There is also a compelling genetic validation for the criticality of that sex and driving th two allergic diseases and the safety of reducing its expression.

Speaker Change: The following.

Speaker Change: First the.

Speaker Change: The pathogenic robust ethics is supported by human genetics, showing that gain of function mutations are static.

Speaker Change: Severe early onset allergic disease in humans.

Speaker Change: Second a recent publication found that human heterozygous that fixed loss of function mutations protected against severe case to asthma showing for the first time, how decrease that six protein levels can be protected against Phd of diseases.

Speaker Change: Additionally, statics knockout in mice is protected and multiple other disease models and stat six knockout mice develop normally are viable and our hurdle.

Speaker Change: So the human and mouse genetics tell us that that's ex the compelling target for treating IL four IL 13, driven allergic diseases and suggest it can be safely locked down.

Speaker Change: Only the unique pharmacology of stat six degradation has the potential to fully block IL 413 signaling with an oral daily drug and thereby phenocopy the activity and safety of an upstream biologic like diplomat.

Speaker Change: Historically the development challenge has been to design oral small molecules that can fully blocks that fixed round, the clock and thereby inhibit the IL 413 pathway to the same extent as biologics.

Speaker Change: We believe the only modality that can do this or integrators.

Speaker Change: Furthermore, if an oral stat six the greater controlling block the IL 413 pathway to the same extent as a capella mab. This has the potential to transform the treatment paradigm for all of the different th two allergic indications that have already been derisked by diplomat.

Speaker Change: Depending on <unk> has transformed the lives of patients with dermatologic respiratory and gastro intestinal tissue diseases.

Speaker Change: And has become one of the largest drugs in this industry.

We think we can change the treatment paradigm and reaching even broader patient population with an oral drug targeting stat six across all the indications derisked by detailing map.

Speaker Change: And perhaps open up new opportunities and additional allergic indications beyond these.

Speaker Change: We had a robust preclinical data set to support this program and I'll walk you through this at a high level.

Speaker Change: Pre clinically <unk> 61 was shown to be exquisitely selective aesthetics and shows no functional inhibition of other stats.

Speaker Change: It's a great stat fix it low picomolar concentrations across all disease relevant human primary cell types evaluated, including lymphocytes myeloid cells epithelium cells and smooth muscle cells among others.

Speaker Change: We've shown pre clinically that kt sector, one is more potent than diplomat that blocking IL four and IL 13 pathway functions relevant the th two disease manifestations and cell system, and an equal or superior to diplomat at blocking th two inflammation in preclinical disease models.

Speaker Change: This is demonstrated in the mouse house dust mite asthma model at doses, achieving 90% or greater so that six degradation.

Speaker Change: Overall, the preclinical data generated highlight the best pathway potential of Kt 61, given that the pillar mab like activity and the convenience of an oral pill.

Speaker Change: And higher species, including dogs and monkeys, we have shown with oral daily dosing that we can fully integrated static at steady state and all relevant tissue types and we did not observe any adverse safety findings and four week GOP Tox studies in nonhuman primates in rodents.

Speaker Change: In light of the enormous potential for Kt 61 to transform the treatment paradigm for patients with th two allergic diseases. We have adopted an accelerated development strategy that begins with phase one studies in healthy volunteers and 80 patients to quickly enable demonstration of clinical proof of concept and inform dose selection for phase.

Speaker Change: As to the dose range finding studies.

Speaker Change: Our plan is around two Sentinel phase III trials, and a D and asthma starting in Q4 2025 in Q1 2026, respectively that will enable dose selection and the subsequent phase III Registrational studies, not just in a D and asthma, but also across multiple other dermatologic respiratory and gastro intestinal.

Speaker Change: Indications derisked by Capella Mad.

Speaker Change: The phase one healthy volunteer Sad Mad study has been completed and we're on track to report data next month.

Speaker Change: The primary objective is to show, we can robustly degrades the ethics in blood and skin, which we define as a reduction of 90% or more at doses that are safe and well tolerated.

Speaker Change: Given the extensive clinical pathway validation by diplomats all the human stat sexed genetics data and the preclinical data we generated showing the pillow mab like activity with 90% of ethics degradation in disease models of asthma and <unk>.

Speaker Change: We believe that if we can achieve this study objective it will largely derisked the program and meaningfully increase the probability of success.

Speaker Change: As we move into patient studies.

Speaker Change: We're also looking at how Kt six to one impacts several circulating teams two biomarkers, including target IGD.

Speaker Change: Our expectation entering the trial was that the effect would likely be comparable to what has been reported in healthy volunteers for diplomat.

Speaker Change: As we have said, we believe the best opportunity to show a significant effect on th two biomarkers will come in patient studies for baseline levels are greatly elevated due to IL 413 pathway activation.

Speaker Change: Importantly, while completing the phase one healthy volunteer study, we were able to initiate the first Katy 61 trial in <unk> patients well ahead of what we had initially planned.

Speaker Change: The ongoing phase one b trial named broaden it a single arm open label trial that will enroll about 20 moderate to severe atopic dermatitis patients.

Speaker Change: Patients will be administered Katie 61, once daily for four weeks.

Speaker Change: The key study aim is to show that robust ethics degradation in blood and skin lesions by Katie 61 has a few pillar malbec effect on multiple biomarkers in the blood and on the transcriptome of active 80 skin lesions.

Speaker Change: The study will also assess Katie $60 effect on clinical endpoints, such as easy and pruritus and R. F.

Speaker Change: We expect to report the phase one data in the fourth quarter.

Speaker Change: So in summary, we believe that targeting stat Sig for degradation with Katie 621 is the only oral small molecule approach with the potential to achieve a diplomat like profile with once daily dosing.

Speaker Change: We're approaching Katie 61 development with a strong sense of urgency and focus on execution.

Speaker Change: This program has enormous potential to dramatically change the way, we can treat patients with inflammatory diseases and expand their access the transformative drugs.

Speaker Change: We're excited by the progress we've made and completing our phase one healthy volunteer trial and initiating our phase one b trial in <unk> patients and look forward to sharing data next month for healthy volunteers and later this year for 80 patients and gearing up for the start up phase II B trials in <unk> and asthma.

Speaker Change: I'd like to pause here and introduce Brian Campbell the research lead on the IRR by program.

Speaker Change: With her team she's done a terrific job advancing this exciting program into development candidate and into IND, enabling studies and we are excited to share the details with you now.

Speaker Change: Thanks, Sharon I'm, Brian Campbell senior director of Immunology at Chimera.

Speaker Change: Worked okay meera for eight years and I'm proud to be part of his pioneering team working to develop transformative treatments for chronic any illogical diseases.

Speaker Change: The project team read I'm very excited to share with you. The story of a first in class Iris five degree there.

579, and why we believe it has the potential to be the first iris five targeted oral therapy to deliver transformative activity in several dramatic in autoimmune diseases.

Speaker Change: Were you just standard of care drugs, including several biologics.

Speaker Change: Today I will cover first how K mirrors TPG approach has a unique opportunity to provide a novel therapy against what has been historically and drive transcription factor.

Speaker Change: There I will describe the well established biological function of Iris five in the genetic and clinical pathway validation.

Speaker Change: Next the clinical development and commercial opportunities Iron five presents then I'll describe the exciting preclinical data package for a development candidate T. T 579, and finally, the expected timelines and next steps for the program.

Speaker Change: I'd like to start by introducing our latest first in class oral development candidate <unk> 579 to 80 579 is a highly potent and selective oral degrader of Iris five which is an essential signaling node and genetically a clinically validated immune pathways driving inflammation in multiple autoimmune diseases.

Speaker Change: The significant unmet patient need.

Speaker Change: Sure details in the coming slides on the robust activity of T. G 579, and primary cell systems, including patient throwing herself and preclinical efficacy models of our eight lupus. In addition, chant 579 has a highly encouraging safety profile in preclinical Tox studies that was well tolerated at up to two.

Speaker Change: Wonderful above the predicted human efficacious dose.

Speaker Change: Telling preclinical characterization of <unk> 579 is consistent with the innovative science, you've shared across our immunology pipeline.

Speaker Change: This program well on the path of development.

Speaker Change: The program is currently in IND, enabling studies are on track to initiate phase one testing in early 2020.

Speaker Change: Okay.

Speaker Change: Now I'll encourage discussion of a rigorous approach to target selection IRA meets all our criteria of what we think makes a compelling target from Boral P. P. D approach Iris five is it on drug target with strong human genetic validation and supporting biological functional data within pathways that have been clinically valid.

Speaker Change: David.

David: As seen in the pathway image on the right eye or five as a central node activating downstream of pattern recognition receptors that are recognized for it our self antigens and is critical for mounting a pro inflammatory response are there.

David: Gampel downstream the Amazon launch Telos, seven G L R H and killer nine activation.

There are five regulates type one interferon responses.

David: Inflammatory cytokines, such as IL, 12, TNF and IL six antibody production at <unk>.

David: Depression itself and activation specific making iron five attractive target potential to block immune dysregulation, while sparing normal cell function.

David: Iris five is a highly validated target human genetics and clinically pathway.

David: Validation.

David: Pyrophyte functional risk variants that had been identified associate with increased susceptibility to loopnet showrooms are a IBD in systemic sclerosis.

David: Clinical validation, yeah, you're a five regulated pathways have been validated by multiple cytokines biologics and b cell targeting agents highlighting the importance of pro inflammatory mediators like type one interferon TNF Alpha IL 12, and IL 23, and auto immune disease pathogenesis I'll expand on these.

David: Two points in subsequent slides.

David: Irobot has been challenging to try to be likely due to its multiple complex activation steps splicing isoforms and high degree of ire, aside I or a family member homology.

As previously reported TBD is well suited to the pre underwrite transcription factor targets like IRA side, where a single specific binding event drives molecule activity and can disrupt all iris five signal.

David: Let's discuss iris five more in disease contacts and is a master regulator of innate and adaptive response I.

David: Five is selectively expressed in Madrid himself monocytes macrophages and B cells.

David: Halfway specific IRA five just regulation is Sal excuse me like dependent and auto immunity is activated by pattern recognition receptors that can recognize nuclear self antigens in the body to initiate and amplify both innate and adaptive immune responses.

David: By increasing pro inflammatory cytokines like TNF Alpha IL six IL 12, IL 23 type one interferons and pathogenic auto antibodies. This can lead to immune complex formation and propagate subsequent inflammation and autoimmune diseases, such as lupus <unk> systemic sclerosis and dermatomyositis.

David: Among others, therefore targeting Iris five offers the opportunity for a transformative and multi pronged approach to treat these complex and heterogeneous diseases.

David: Now, let's look further into the genetics associated with IRA side.

David: Literature shows the pathogenic role of IRA five is supported by human genetics for multiple genome wide Association studies identify iris five as an autoimmune susceptibility genes.

David: Specifically, if you look at the bottom left chart.

David: [noise] analysis G boss studies have shown iricize to be strong risk blokeish lupus with risk appetites and functional variance identified in patients that are associated with high serum interferon alpha levels anti double stranded DNA auto antibodies or anti RNA, one binding protein antibodies.

David: There's genetic associations and functional variance have also been identified are a IBD systemic sclerosis and multiple sclerosis.

David: Looking at mouse knockout studies, IRA fact knockout mice are viable and fertile what's normal b cell development in the bottom chart, showing a mouse model of who this iris five plays an essential role in lupus development in pathogenesis that is interestingly independent of type one interferon pathway as shown in the server.

David: Rival curves below where returns at all knocked out Iris five thank you.

David: So it increased protection versus or knocked out of interferon a receptor that results in modest protection against lupus.

David: Additionally, knockout studies demonstrated attenuated disease and other mouse models of lupus array in IBD, showing biological functionality and supporting the therapeutic potential of Iris five degradation.

David: As previously mentioned Iris five is only expressed in a limited number of cell types and only activated by specific stimuli.

David: Indicates the IR five degradation has the potential to selectively block inflammation to restore immune regulation.

David: Dendritic cells monocytes and macrophages when activated by members of the Taylor family or other pattern recognition of receptors like ducting.

David: Mediate a pathogenic immune response to the many pro inflammatory cytokines, including TNF Alpha IL, six and type one interferon.

David: In addition, IRA five is activated by and just one little toll like receptors and T cells, resulting in pathogenic autoantibody production. There are many agents, which are approved and targeting some of these trial finally toward mediators like anti TNF Alpha anti IL 12 23.

David: Hi, interferon alpha and so much target T cells directly further validating the target.

David: The multifaceted functions of Iris five which are current specific cell context upon specific stimuli point to superior efficacy and tolerability profiles compared to current agents for autoimmune disease.

David: Potential to be best in class to treat complex diseases, like lupus Shoguns, NRA IBD and ovens.

David: The development opportunity for targeting IRA five as Vas and there are numerous potential indications across multiple immunological therapeutic areas.

David: Total potential patient impact of more than 10 million patients.

David: 579, our oral iron five Degrader is designed to block the source of multiple pro inflammatory mechanisms and improve on effectiveness.

David: Ability and Tolerability over currently approved agents and diseases, such as Ari lupus sjogren systemic sclerosis, IBD among others listed on this slide.

David: Well, our Iris five degree there has the potential to be a transformative oral therapy is superior to oral and biologics standard of care across all indications on the fly as a result of its broad but cell specific mechanism.

David: Now, let's look at the exciting profile of <unk> 579, and its impact across the biological mechanisms and pathways as Jeff discussed we have an incredible opportunity with T. T 579.

David: And its potential to have an enormous impact on the treatment of autoimmune diplomatic diseases.

David: As we walk through the preclinical characterization, we hope you will share our enthusiasm for what we believe is another high value target to emerge in our pipeline.

David: I will show you is a potent selective activity of T. T 579 in normal human primary shots donor cells from lupus patients and indeed, those disease models of lupus NRI.

David: I'll start with tainted by southern Nine's effect in human primary cells from healthy donors.

David: Thank you 579 is an exquisitely selective to breeder as you have seen from our programs over and over we look at concentrations well above that achieving maximal degradation of our intended target.

David: There are five is the only protein debris that out of the 10000 or so proteins that were detected by Nasdaq.

David: No other IRS family proteins for degraded to any extent looking.

David: Looking at specific cell based assay degradation of Iris, three and IRA seven which our IRS five closest family members again, we see no degradation, even at concentrations as high as 10, Mike Rimmel.

David: Additionally, as seen on the right change 579 is a very potent degrader of Iris five <unk> 579 demonstrated picomolar to an animal or potencies across function functionally relevant human cell types evaluated.

David: <unk> b cells dendritic cells macrophages and monocytes all key players in the pathogenesis of inflammation associated with iron are fine.

David: As seen with our other integrated programs. It is critical for us to understand degradation across all relevant cell types in preclinical settings.

David: To build the right translational package to predict our human efficacious doses.

David: Next we wanted to demonstrate cell activity not only from proteomics, but also to downstream pathway activated biology, and Iris five cellular globalization <unk>.

David: 579 selectively depletes Iris five over other key transcription factors within the same pathway axes and downstream appeal, our seven NTL or eight activation. This is an important aspect of K T 579, given the high sequence homology between Iris five Iris three and IRA seven actually.

David: Understanding on the Si depleting IRA five with loan animal the concentration of <unk> 579 leaves. These other critical transcription factors completely intact.

David: These data provide additional evidence that the functional inhibition was observed in subsequent slides is driven through iris five depletion only and highlight how selected the compound is.

David: In addition, we show we can degrade IRR side, both in the cytoplasm nucleus as shown in the bottom panel.

David: Here, we see that <unk> 579 demonstrated potent inhibition of key pro inflammatory cytokines and type one interferon production downstream of TR for CLR, seven until Ari and nine activation and primary selling older assets shown in the table in grass for example.

David: We showcased at 579 can block IL 12, interferon beta production and monocytes and block the production of TNF Alpha and IL 23, and P. D M C.

David: These data highlight <unk> 5090 broad has potent activity that is both sell and stimuli dependent.

David: Additionally, transcriptome makes analysis demonstrates the T. T 579, dampened type one interferon response and select interferon stimulated genes that are reported to be elevated and systemic autoimmune diseases, such as lupus and childrens.

David: Type one interferon responses can be induced by Edison will kill our seven until our age activation via single stranded RNA nuclear yourself the antigens.

David: And the last differential gene analysis demonstrates that J T 579 can block the type one interferon at least as effectively as an anti <unk> seven inhibitor S. A matter in that concentration is predicted to be clinically active.

David: On the right. We see that takes you five 719, chief comparable inhibition to ask them that are in our select ISG that've been associated with increased disease activity in lupus.

David: Turning now to <unk> five seven nine's activity in patient derived donor cells.

David: We examine 80 579 impact of lupus patient dry P. D M D.

David: And just one little to Golar seven eight activation can be IRA five dependent and J T 579, effectively blocked CLR seven any induced pro inflammatory cytokines and interferon beta production.

David: These data include some patients with Iris five common functional variance, while we observed similar activity on both iron five degradation and downstream functional effects.

David: By inhibiting pro inflammatory cytokines in type one interferon, we hope to reduce inflammation suppressant development of auto antibodies and ultimately mitigate the progression of autoimmune diseases like lupus independent of virus genotype, we plan to share more of these data and subsequent presentation.

David: Continuing with the lupus patient samples on this slide you can see how kt by 79 significantly inhibits IGT production and diesel <unk>.

David: Third with TPG, b with or without <unk> 579 for seven days.

David: Dan Loeb is double stranded DNA nuclear self antigens or anti double stranded DNA complex. It can activate Anderson will kill our nine in B cells.

David: Leading to B cell activation differentiation and pathogenic autoantibody production.

David: This data really shows the promise of an IRA five directed treatment to reduce the b cell mediated inflammatory cascade in these patients.

David: And finally, let's turn to the in vivo preclinical data.

David: And the first model shown here reevaluate and <unk> five seven nine's activity and mouse acute killer models that elicit a potent inflammatory cytokine response.

David: In these studies <unk> 579 dose orally once a day for four days and she deep degradation of identified here measured in the spleen importantly, as we discussed with other programs in our pipeline the greeters require higher doses in mouse models compared to other species due to higher plasma protein binding and lower.

David: Kennedy Wilson higher species like N H P, which is more translatable to humans, we can achieve full degradation at much lower doses.

David: Then on the fourth day killer, serving a killer ninth stimulates administered systemically and T. T 579 activity was compared to <unk> seven eight inhibitor and 5049 as shown on the chart to the right as expected only J T 579, like a dose dependent inhibition of cytokines in both models.

David: Blocking both DLR seven until our nine induced cytokines, including TNF Alpha and also IL six IL 12, and interferon beta which are not shown here.

David: Demonstrate G T five seven ninth advantage in blocking both CLR seven ETR nine activities, which should translate to greater efficacy in several autoimmune diseases. This potential advantages further supported by mouth CLR knockout studies, <unk>, seven and chiller nine double knockout like a greater impact on disease answer.

David: Set in severity in mouse models of Lupus for example.

David: In addition, these acute studies allowed us to select active doses for use in chronic mouse models of lupus NRA.

David: And the next few slides, we will go over our preclinical efficacy studies and show you our Iris five degreed or G. T 579 compares to existing agents and lupus and are a models Pinot copying Iris five knockout studies.

David: To start MRO L. P. R mice heavy susceptible genetic background and single gene mutation and fast quickly developing lupus like symptoms and manifestations.

David: These biomarkers can be detected as early as eight weeks of each treatment began at week 10 and ended at week 19, when mice are expected to present with extensive kidney pathology.

David: 579 daily oral dosing was well tolerated at both doses of 50 Megs per Kid and 200 mix per kg for the duration of treatment.

David: T 579 demonstrated sustained and near complete reduction of proteinuria and 100% survival at both doses achieving at least 85% degradation with activity superior to approved or clinically active drugs, such as Apple matter in two flavors fitness cyclophosphamide and an anti interferon.

David: Preceptor mouse surrogate antibody administered at the top dose reported in literature additional endpoint Readouts are currently ongoing.

David: Next we evaluated the impact of Biographize degradation in the long term MTB W. One spontaneous this model using an earlier potent and selective IRA five tool degrading.

David: Mr. Greater was used for proof of concept in this model while characterization was ongoing for our development candidate G. T 579.

David: MTB W. One my heavy polygenic background and spontaneously develop lupus that present with high levels of circulating anti double stranded DNA anti Amy's proteinuria and immune complex mediated primary alone nephritis similar to human lupus.

David: Treatment was initiated at week 21 during early onset of disease.

David: Daily oral doses than IRA five degrader for four months, well tolerated and doses that achieved greater than 80% IRA five degradation.

Speaker Change: <unk> reduction of proteinuria near complete reduction of circulating serum anti double stranded DNA auto antibodies generally better than standard of care Cyclophosphamide approved anti interferon a receptor one surrogate and clinical stage testing agents as another and Andrew purpose Sidney.

Speaker Change: These are really exciting results that demonstrate the ability of an oral iron five degree to to achieve similar activity on iris five to genetic depletion, we will be testing <unk> 579 in this model and we expect it to look very similar to just given the similar potency of the drugs and we plan to share the results at a subsequent presentation.

Speaker Change: Next in the antigen induced arthritis mass model of our a daily oral dosing with T. G 579, and achieved approximately 90% degradation led to significant reduction in joint smiling comparable to Tofacitinib.

Speaker Change: IRA five degradation feeder copies IRA if I knock out it leads to reduction in ankle swelling circulating pro inflammatory cytokines as shown here with IL 12.

And infiltrating inflammatory pathogenic T H, one T cells evaluate by slow which is also shown here on the right.

Speaker Change: These data exemplify the potential for an oral iron five to greater to impact multiple inflammatory biology and autoimmune diseases.

Speaker Change: As part of JT five seven ninth preclinical characterization, we looked at degradation of eye or five across several preclinical species.

Speaker Change: Shown on the chart to the right with daily dosing for seven days the observed J T 579 can robustly deplete Iris five at steady state with low oral doses in nonhuman primates.

Speaker Change: Fortunately the degradation was measured 24 hours after the last dose.

Speaker Change: K T 579 was also very well tolerated with no adverse effects or relevant findings up to 200 for the predicted human efficacious exposure and our non GOP toxicology studies in both nonhuman primate and finally in rodents derisk.

Speaker Change: Derisking, our path to human translation and proof of concept.

Speaker Change: In summary, I've shown you that first IRA five has the potential to be the first broad anti inflammatory that.

Speaker Change: Effectively addresses immune dysregulation, while sparing normal cell function.

Speaker Change: And both human and mouse genetics, along with preclinical validation, indicating best in class profile for Iris five in treating lupus sjogren, alright, and other diseases next J T 579 stands out as a highly selective potent oral iron therapy breeder.

Also our in vivo studies show that Iris five degradation leads to robust cytokine inhibition and demonstrate superior or comparable efficacy in lupus and remodels compared to approved drugs in the space.

Speaker Change: In addition, 80 579 achieved complete degradation across multiple preclinical safety species and relevant tissues, maintaining a favorable safety profile, but last we're very happy that this program is progressing in IND, enabling studies and we expect it to be on T. T 579 into the clinic in early 2002.

Speaker Change: 26, as we believe the first oral iron five degree there.

Speaker Change: With that I'd like to now turn the call back to <unk> for his closing remarks.

Speaker Change: Okay.

Speaker Change: Thank you Veronika, it's always exciting to hear these stories, even if I've heard that multiple times internally I think when we do these public disclosure or is it just an exciting time to put all of our data out there and show how productive the team can be and more importantly, the level of sophistication that the team goes when we build these preclinical.

Speaker Change: Packages, so very excited to take this program into the clinic. So why don't I, maybe complete this presentation today by going through our pipeline and spending a bit more time on the upcoming milestones and then we look forward to take questions from the audience in the analyst So.

Speaker Change: So first as we've repeated now multiple times, obviously Casey 61 is moving very rapidly and as we've said.

Speaker Change: Likely much more rapidly than we anticipated, which is great which is a great problem to have.

Speaker Change: We've been able to complete our healthy volunteer study in really dosing in March.

Speaker Change: We are.

Speaker Change: Collecting the last small data points and then well.

Speaker Change: We're really excited to being able to share our phase one healthy volunteer data in June. So that's an important date on your calendar.

Speaker Change: As you also know we have started a phase one b E D study.

In April.

Speaker Change: And again kudos to the team the 61 team for being able to do that as I said very rapidly. We're now recruiting patients and we expect to be able to share data from this study in the fourth quarter of the year. The team is already gearing up to initiate these two large phase two studies so.

Speaker Change: We'll start the study in the fourth quarter of 'twenty five and the asthma study in the first part of 'twenty six.

So a very busy with all this activity is so important to data readouts healthy volunteer in June and then the patient data in the fourth quarter of the year and then we'll embark in this large studies that.

Speaker Change: We'll obviously take longer than the phase one B study and we'll share more details about expectations around timing and data readouts as we get as we get closer to them.

<unk> five <unk>.

Speaker Change: K T 579 is Veronica said, the preclinical package, both in safety and efficacy looks extremely impressive and so we're expecting to file an IND towards year end, starting a phase one early next year with data with phase one data already next year.

Speaker Change: Then as we mentioned with direct for we expect to have data in 26 for both HSN E D.

Speaker Change: Thank you everybody for taking the time I know it was during the morning on a Friday.

Speaker Change: But hopefully you will appreciate the level of details that we shared today and we're happy to reconvene in take questions. Once we get together in a couple of minutes.

Speaker Change: Okay.

Speaker Change: Thank you.

Speaker Change: At this time, if you would like to ask a question. Please click on the raise hand button, which can be found on the black bar at the bottom of your screen.

Speaker Change: If you joined by phone please dial <unk> nine on your key pads to raise your hand.

Speaker Change: When it is your turn you will receive a message on your screen inviting you to join as panelist.

Speaker Change: Please accept and wait until you were promoted to panelist. Please on mute your audio.

Then on your camera and ask you a question.

Speaker Change: As a reminder, we are allowing analysts to one question and one related follow up today.

Speaker Change: We will now pause a moment to assemble the queue.

Speaker Change: Yeah.

Speaker Change: Right.

Speaker Change: Your first question will come from Derek ocular with Wells Fargo. Please.

Please on mute and ask your question.

Speaker Change: Okay.

Speaker Change: Derek we can't hear you can you are.

Speaker Change: Ah mute if Kevin.

Kevin: Hi can you hear me.

Dan: Oh, yes, yes. This is does this have on for Dan.

Speaker Change: Thanks for taking our questions just a quick one from US can you talk a bit about your confidence I'm targeting stat Sig City D and are showing an effect in the four week study like should we expecting a relatively noisy dataset given it's such a short study. Thanks.

Speaker Change: Yes. Thanks for the question. So obviously the underpinning of this program is dead.

Speaker Change: IL four enter routine Mount signal through statistics to propagate signal and to impart downstream th two cytokines.

Speaker Change: So the Derisking and the expectations that were set on this program are purely driven by the data that's been shown in a theater already by the best IL, four and 13 agent, which is <unk>, which is actually the only drug that box.

Speaker Change: So we know with that drug even even four weeks you can actually generate quite compelling differentiated data set. The first one is that even in four weeks you can impact both circulating in skin biomarkers of th two information very robustly and actually if you look at the peak.

Speaker Change: Data for weeks.

Speaker Change: In terms of easy scores.

Speaker Change: And others clinical endpoints why is it that would not reached maximal effect they are quite robust.

Speaker Change: And so.

Speaker Change: We given all the preclinical data that we've generated on this on our program with kids six to one and the fact that all the models and assays that we ran this coupon through we've shown it to be like in fact in some cases even.

Speaker Change: Better effect.

Speaker Change: We expect that we'll be able to see really robust data first in biomarkers, because that's really what the study will be powered on.

Speaker Change: But also clinical end points.

Speaker Change: Got it thanks.

Speaker Change: The next question comes from the line of Jeet Mukherjee with B T. I G. Please on mute and ask your question.

Speaker Change: Mhm.

Jeet Mukherjee: Hey, Good morning can you hear me.

Speaker Change: Yes, we can see here isn't it great.

Speaker Change: Good question.

Speaker Change: Maybe just one question around the decision not to advance the TIK. Two program you, obviously talked about that the children in the context of bank capital conscious in the macro backdrop, but it appears you've swaps TIK two for perhaps IRS five so was there anything there in terms of the molecules profile or just the evolving competitive.

Speaker Change: Landscape that influenced your decision thanks.

Speaker Change: Yeah, Great question. So I think it's important to maybe spend even a bit more time as you are suggesting so.

Speaker Change: We remain and I can say even personally I remain confident in CSD.

Speaker Change: I think to the opportunity with any greater.

Speaker Change: I think that the decision is really around.

Speaker Change: Today, where we are with both resources, both human and capital we feel like.

Speaker Change: Being able to power up even more so on the six to one program given that it's really accelerated in terms of pace.

Speaker Change: And obviously I can't speak to the data, but obviously, we have a lot of confidence going into these larger studies.

Speaker Change: Given the risk reward in that program, we feel like that's the place where we want to go.

Speaker Change: And put a lot of resources in.

Speaker Change: I think the Iris five program is actually quite different from peak to peak.

Speaker Change: It is true to reflect that at its peak to space.

Speaker Change: Obviously, there is a lot of competitive intensity, we will look at not just Q2, but I always look at all the other 23 drugs out there including.

Speaker Change: Quite impressive J&J peptide obviously the bar in this space has been raised.

Speaker Change: We think Iris five is a totally different program I think that's going to be a best in class product for a wide variety of diseases and Thats a program. We want to go all in would be first the competitive intensity is at right now in that program and those pathways as close to zero and we have an opportunity to have a highly differentiated profile. So that's again.

Speaker Change: There is obviously competitive intensity.

Speaker Change: The risk reward the conversations that have happened within the company on how programs have been prioritized that we're alluding to is fair.

Speaker Change: But at the same time I would say the main driver is we have the largest program in the industry.

Speaker Change: But probably you may be if you remove the GSD one drugs.

Speaker Change: And we got our resources at the maximum that we can do at this point in time.

Speaker Change: Thanks for taking the question.

Speaker Change: Our next question will come from Mark from with TD Cowen. Please on mute your line and ask your question.

Speaker Change: Thanks for taking my questions would be on the IRS five Bernie disclosed today.

Speaker Change: Because you know as you get into the clinic, what does the minimum target profile in terms of degradation and look like and.

Speaker Change: As we get the clinical data.

Speaker Change: As you highlighted in <unk>.

Nello: With your intro Nello.

Nello: The bar and some of these other diseases, where you started going after oral <unk>.

Nello: Things like psoriasis like is extremely high there really isn't much room, even there or to some extent to push efficacy higher.

Nello: But some of these disease, you're talking about for Iris five there is certainly much more room for clinical improve for efficacy improvement how important is that as to ultimately show versus just kind of matching available therapies, but offering.

Speaker Change: Yes, the world convenience.

Nello: Yeah.

Speaker Change: Yeah, I think it's a great question, maybe I can start and others controller.

Nello: So firstly I think that's very insightful question I will start with.

Just looking at our preclinical data as you can appreciate I know, we only have just gone through a bit and you didn't have a lot of time to digest or at least so far it looks like once we at least 80% degradation in our board.

Nello: Able to deliver some really best in class profile. So we're actually doing more work to understand is even less than 80% degradation sufficient to drive.

Nello: Activity that we've seen so I guess to answer your question. There is more work that we're doing.

Speaker Change: I think if you look at and just being both Lucas and IRA, but I will start maybe with the lupus model.

Speaker Change: Nearly targeting IRS and despite translational models of logos.

Seems to have by far the best effect.

Speaker Change: Which I think if you look at approved therapies and logos.

Speaker Change: Right now they don't really work very well, so there's clearly unmet need on the efficacy so being able to deliver boats.

Speaker Change: Efficacy and convenience that is superior to existing or even clinically active drug I think is really what we're trying to deliver there so maybe even.

Speaker Change: Once that over some of the conversations we've been having in the past few months and then the team with Veronica leadership has come up with a an extremely well behaved molecule that we believe will be highly differentiated in their clinic, but generally there aren't good for you guys.

Speaker Change: I think I'd only add that as well.

Speaker Change: Certainly.

Speaker Change: No that number one we can achieve greater than 90% knockdown of iris five across multiple different species, including higher species like nonhuman primates in that.

Speaker Change: You know unfortunately studies that can be achieved with very favorable safety. So I think that's very important.

Speaker Change: Also very interesting to note that Joseph your question around the world how much do we really need it and it's 90% or greater is safe, it's very interesting that these sort of heterozygous.

Speaker Change: Mice are actually fairly well protected from diseases like lupus. So it's possible, we might not need that much knockdown or efficacy, but we know we can achieve the degree of knockdown high degree of knockdown that that would be safe to us could be very important for us.

Speaker Change: Yeah, No I think our expectation is again that we would see superior efficacy and that's because of the multiple biology that we can hit with Iris client, Brian as we talked about during the presentation.

Speaker Change: Being able to impact auto antibody producing cells type one interferon and then also proof one parameter cytokines there could be very important when you go after complex and heterogeneous diseases.

Speaker Change: Like those like like lupus, so I think even compare it to let's say in the full amount we would expect to have a lot more efficacy.

Speaker Change: Great. Thanks, Brian.

Speaker Change: Thank you.

Speaker Change: Our next question will come from the line of Ellie Merle with UBS Securities. Please on mute and ask your question.

Ellie Merle: Hey, guys.

Ellie Merle: Just on I R. S. Five just a quick search there's obviously a lot of literature showing that <unk> plays a critical role in a lot of diseases, but curious how you're thinking about balancing the safety here it looks like Theres. Some data showing that IRS five can act as a femur are tumor suppressor I mean, obviously, we're new to this target. It seems like gets involved in a lot of diseases.

Ellie Merle: But just can you explain why you're comfortable with the safety here and I know on the last question you mentioned.

Ellie Merle: So you can even got disease protection or modification, perhaps with the 50% degradation just from a clinical development perspective, even if early on 90% degradation of safe would you also explore moving forward with say, 50% degradation, 90% with multiple dose levels and.

Ellie Merle: Multiple times.

Ellie Merle: Specific it's really only expressed in a subset of sales.

Ellie Merle: And it's also really only activated in the presence of diseases. There are multiple either IRS. There are contributing to let's say immune surveillance from a safety perspective from an infection perspective. So it is really one of those only grade targets and Thats why its been pursued.

Speaker Change: Without much knowledge, because with a lot of failures by the whole industry in the past 10 years at least that we know of.

Speaker Change: Because he actually combines these broad anti inflammatory effect at 12, 23, IL six TNF IGT.

Speaker Change: <unk> type one interferon, but in a context specific manner and Thats really why even in these preclinical studies we can remove.

Speaker Change: Remove the target completely we've gone to one report the Bob that dose and have not seen any activity there or.

Speaker Change: Do you want to take that I know you had the answer to that question.

Speaker Change: Question better than I do yeah no no. Thank you for the question you know that was part of our intelligence in the beginning we evaluated the target setting.

Speaker Change: You mentioned and we want to cross and Kathy Ta aggregate studies, there's actually very little evidence that loss of INR five associated with cancer and in fact, when you left it seems like gain of function is associated.

Speaker Change: With cancer and.

Speaker Change: The one report that Pops up from from one lab there has been.

Speaker Change: No follow up work.

Speaker Change: With a target that's more highly expressing himself.

Speaker Change: Sort of hard.

Speaker Change: Hard to believe that Lawson of breast cancer.

Speaker Change: Now at the helium sell will be.

Speaker Change: Cancer. So there has been really no follow up there and again with our broader analysis, we don't really see a risk in that area.

Roger: Thank you thanks Roger.

Roger: Great. Thanks.

Speaker Change: Your next question comes from the line of Sudan, Nogales them with Stephens. Please on mute and ask your question.

Speaker Change: Hi, Good morning, and thank you. This morning for the detailed presentation and for taking my questions. My first one is on the IRS by program in your preclinical work or any of the literature out there did the degradation of IRA <unk> trigger any feedback mechanisms that may have activated Iraq for <unk> 88 <unk>.

Speaker Change: Other IRS that could be a means of causing like a non targeted bolt relapsed in a disease state whenever.

Speaker Change: Treated in humans going forward.

Speaker Change: Yes, no. That's a great question. So this is something we pay a lot of attention to across our programs rate do we see a either a receipt and evolving potential resistance mechanisms or other pathways coming into play.

Speaker Change: We haven't seen any of that in our studies is Veronica showed some of these are probably some of the longest studies that we've run pre clinically you would see the Lucas model, except for months study I think Myles, where those 106 days in a row.

Speaker Change: Correctly.

Speaker Change: And with that we Havent seen during this study.

Speaker Change: And obviously.

Speaker Change: The MISO have taken that at the end, but but even when we when it's happened yet.

Speaker Change: Other studies with those and then stopped dosing we have not seen any.

Speaker Change: Kind of players will rebound off.

Speaker Change: Of these inflammatory pathways.

Speaker Change: The beauty about this inflammatory pathways is that these are not.

Speaker Change: Over expressed or activated and inflammatory processes or sorry, not over expressed.

Speaker Change: Just signal through there is just a signal that then moves into a particular pathway in this case, let's say <unk> five.

Speaker Change: So the reason to kind of increase of protein expression.

Speaker Change: Going down or removing which will make the sale kind of react we are producing some other protein. So anyway. The short answer is we haven't seen and we don't expect to see it we haven't seen them for any program so far.

Speaker Change: Great I appreciate that and just if I can squeeze in a follow up just in regards to the statutes that fix program and the degradation I think you've mentioned before obviously, you're also achieving a pretty high level of static degradation hopefully in that.

Speaker Change: In human population as well in your trial.

Speaker Change: Between the different indications and going after with stats ex degradation does the level of that degradation need to be exceeding 90% for all of the indications or the different between each wants to get clinical benefit specific to each type for instance, with AE.

Speaker Change: Skin and blood.

Speaker Change: Are there kind of targets between the two different.

Speaker Change: Tissue types there.

Speaker Change: And it comes to that looking at the stats the degradation to a form of clinical benefit.

Speaker Change: It's a great question.

Speaker Change: Think that there is kind of two answers one.

Speaker Change: Our goal of our phase one study was to hopefully being able to achieve 90% plus in blood and skin. The reason for that is there to break one pre clinically we have shown in mice that if we get to 90% plus we have to be like effect. The second reason is why do we want to have also the same targeting scheme is because we don't want.

Speaker Change: To be left with the question.

Speaker Change: Well, what if we had more than 90% degradation in skin.

Speaker Change: With the activity look like so that's why we went out we would like to target a profile that has similar degradation in both blood and schemes. So that we maximize the probability of success second part of your question, which actually was Ali's questions that I don't think I answered is what is the level of big renovation needed for a particular disease.

Speaker Change: As for boats that takes them withdrawing that are at five as well I think that's why we're so keen on running at least for sub six for now immediately these phase II dose ranging studies give us the ability to correlate.

Speaker Change: A degradation profile with a clinical outcome that will allow us to select the right dose for phase III. So right now we are.

Speaker Change: Of course that takes at least we're going.

Speaker Change: Based on our preclinical data, we are going into the clinic with the expectation of that 90% plus is the desired profile.

Speaker Change: But once we ran a phase II study, where we will be able to ask your questions a multiple dose multiyear degradation profile, we might other than that.

Speaker Change: The Midwest and 19 sufficient I don't know if we expect that more than 90 as needed, but that's why we run the dose ranging study is really to establish those relationships.

Speaker Change: Great I appreciate the details here and thanks again for the detailed presentation today.

Speaker Change: And the next thank you.

Speaker Change: It was not.

Speaker Change: Your next question comes from the line of Vikram <unk> with Morgan Stanley. Please on mute and ask your question.

Speaker Change: Great. Good morning can you hear me.

Speaker Change: Jeff.

Speaker Change: Sure.

Speaker Change: Thanks for taking the questions and for the presentation.

Speaker Change: We had a follow up question on Iraq.

Speaker Change: I know you've alluded to how.

Speaker Change: Calendar and this target has been through your prepared remarks, and also to be responsive to the last few questions.

Speaker Change: But we were wondering if you could thinking a bit more detail about <unk>.

Speaker Change: Prior competitive approaches that may have been attempted for RFID, then where specifically these approaches may have faltered in all 579 had been engineered specifically to address some of the missteps that.

Speaker Change: Other other other than the space may have faced in the past and I have a follow up but I'll save that for proposed to your response.

Speaker Change: Okay.

Speaker Change: I think thats a great question so.

Speaker Change: The main challenge with IRS side actually I would say from a chemistry perspective, you just probably being the hardest program in the company.

Speaker Change: And the reason is identifying.

Speaker Change: The highly specific IRS, five binder or for others. It has been an inhibitor is extremely difficult. There is a high sequence homology Veronica assure you I read one seven versus five three and 730 <unk>.

Speaker Change: <unk> five.

Speaker Change: And we were I would say also lucky to find it.

Speaker Change: Thanks to the great team that we have a molecule that is basically 100% specific to either re fi does not bind to NTIA rates.

Speaker Change: The other point is IRS brings.

Speaker Change: These kinds of complex.

Speaker Change: Activation.

Speaker Change: And I think you have to really inhibit or.

Speaker Change: Type of via <unk> web the typewriter by office REIT type of biology, and with our drug we bind to.

Speaker Change: Basic and degrees all types of <unk> and.

Speaker Change: And so.

Speaker Change: <unk> has been a really difficult target to drug I think is probably under appreciated how difficult that is being then and this is a highly.

Speaker Change: I think this program.

Speaker Change: There's a lot of a lot of focus on by I think the external immunology community because these would be the first time that we finally hit this target selectively in well.

Speaker Change: Great and then.

Speaker Change: As a follow up.

Speaker Change: On the development program, how broad of an initial development plan do you think you'll end up per se for 579 is it reasonable to expect something like 61, where you started with the two set of Centennial indication excuse me and then go from there.

And related to me.

Speaker Change: You mentioned the mid 2020 runway.

Speaker Change: How how far in development do you think you could get with 579 through that time point.

Speaker Change: Thanks.

Speaker Change: Alright, so I'll answer high level so.

Speaker Change: First.

Speaker Change: I think it's a bit early for us to get into the actual development plan, but what I would say is that there is a plethora of opportunities where I think there was an earlier comment from many of our colleagues, but there was quite asked which is this drug can actually really really makes a difference.

Speaker Change: For many patients with this let's call it three months a lot of people.

Speaker Change: Inflammatory diseases.

Speaker Change: So.

Speaker Change: We believe that this is going to be.

Speaker Change: Also a relatively broad development program with more than one indications that would be prioritized.

Speaker Change: I think the run rate.

Speaker Change: Just to be clear I think we said first half of 2008, you gave us mid 28 I'll take it if you also give us the money.

Speaker Change: Alright.

Speaker Change: I think what we said.

Speaker Change: What we've said is that we plan to start phase one early next year, we plan to complete phase one within that year.

Speaker Change: So you can expect that we will have some meaningful clinical data within this runway.

Speaker Change: Very helpful. Thank you appreciate IC Eric ratios.

Speaker Change: Your next question.

Speaker Change: Your next question will come from the line of Eric Joseph with Jpmorgan. Please.

Speaker Change: Ask your question.

Eric Joseph: Thanks for taking my questions.

Speaker Change: So the IRS five can you talk a little bit about the relative infection risk given the broader or more pan product laboratory cytokine suppression profile here.

Speaker Change: To what extent are you able to bottle that pre clinically perhaps and then.

Speaker Change: It sounds like.

Speaker Change: Lupus or ethylene being one of the lead.

Speaker Change: But one of the focal indications with this approach have you pre clinically.

Speaker Change: Looked at the comparative efficacy of 579 versus some of the B cell depleting or modulating approaches.

Speaker Change: The extent of this is also a feasible to do it at nice levels.

Speaker Change: Yeah.

Speaker Change: Alright, great question.

Speaker Change: I'm going to let you guys answer on the.

Speaker Change: Infection risk we have tons of answers I don't want to give all the answers.

Speaker Change: Do you want to go first and then.

Speaker Change: You can speak to that.

Speaker Change: Some other aspects of it.

Speaker Change: No. Thanks for the question.

Speaker Change: We don't think that Iris five will work like a broad immuno suppressant right and the reason for that is because it's really selectively expressed in dairy.

Speaker Change: Themselves.

For that I am asking is really where it's highly expressed.

Speaker Change: Not only that but it's also specifically activities.

Speaker Change: Certain stimuli. So I think that combination when we will continue certain autoimmune diseases will be an advantage.

Speaker Change: Because we won't have this broad immunosuppression against against all.

Speaker Change: Austin I really only the ones that are elevated and those autoimmune diseases that we're going after them.

Speaker Change: And then the immune surveillance you can tell by the other <unk> right exactly so legal meeting showed Irish three instead of an impact and those are really important for viral infections rank those are actually the.

Speaker Change: Transcription factors that drive high type one interferon response, so by leading those intact and iron walking a fine. We don't think we'll have anything else to be let's say.

Speaker Change: Hello, Matt.

Speaker Change: We probably expected.

Speaker Change: Glass can vary Unblocking all type one interferon response.

Speaker Change: So that's just two things are important and then Eric I think your second question was around comparison to diesel the theaters I mean, the data that Brian showed so far the comparison not been to the B cell depleters per se, but we have look the comparisons Lucas models to <unk> inhibition.

Speaker Change: All our 708 inhibition with.

Speaker Change: At the motor and outdated Huron receptor antibodies. So we've been at these comparable pumping better actually in our activity in those models compared to all of those standard of care even cyclophosphamide.

Speaker Change: And I think probably looking at B cell depleters will be something that we can do in the future I think it's important to recognize that.

Speaker Change: IRA find impacts multiple different components of inflammation diesel is one part of that inflammation, but there's also been the British cell component, but also the T cell component that is stimulated by macrophages and dendritic cells. So we would anticipate that we would have a broader effect and potentially could be even more active than the more sort of selective DSO completed unsafe.

Speaker Change: I think yes, I think.

Speaker Change: So a better tolerated and it's actually not that anti CD 20 years as an example performed very well in these business models.

Speaker Change: Okay, they need anything else.

Speaker Change: No no.

Speaker Change: Thanks appreciate you taking the questions.

Speaker Change: Thank you. Your next question will come from favorable cash it with Leerink. Please on mute and ask your question.

Speaker Change: Hey, guys. Good to see you thanks for taking the question.

Speaker Change: So we're still early in a few days of work I think you said now.

Speaker Change: And the target.

Speaker Change: There is one other kind of disclosed development program for IRS five nothing allosteric modulator could you talk a little bit about like how you kind of see the potential benefits of a greater approach over an allosteric modulator.

Speaker Change: Yes, I mean as I mentioned earlier there are disclosed programs, we haven't seen any data. So we don't comment on those because they are just a word on this slide.

Speaker Change: But I think the main the main really challenge has been can you do is sell actively.

Speaker Change: And then Ken New block all of the functions of <unk>, Inc.

Speaker Change: Including all despising variance right Veronica and I think it's really hard to do.

Speaker Change: I'm going to say, it's impossible to do.

Speaker Change: We believe in our hands, it's extremely hard to do with an inhibitor. Then you put on top of it. The fact that we didn't need to be there. If the need is to block <unk> five at high level continuously obviously, we made the case that degree Theres Elisa once a day oral drug with a low dose with inhibitor to stay on top of that target.

Speaker Change: 2017 is going to be really difficult, but I think for this one is really be selective.

Context independent inhibition is going to be hard, but we'll see.

Speaker Change: Got it great. Thanks for taking the question.

Speaker Change: Your next question.

Speaker Change: Geoff Meacham with city. Please on mute your audio and ask your question.

Speaker Change: Hey, guys. This is michelle on for Jeff.

Speaker Change: Thanks for all the questions I really have presentation.

Speaker Change: First of all out of five so there has been like genetic link between certain IRS five isoforms and lupus susceptibility. So are there any concerns that seven nine could exacerbate disease in some subset of patients and whether you have designed this.

Speaker Change: Kind of the greater target specific isoform selective effect.

Speaker Change: Yes.

Speaker Change: Brian.

Speaker Change: I think the second one was if we get all the I suppose and we selectively target certain Isa form Center express can in theory patients yes.

Speaker Change: That's really difficult to do because the ice performance to really some specific expression right. So.

Speaker Change: That would be really hard to do what we do know is that.

Speaker Change: Seven 910 degree all the different lines to firms that are expressed whether it's.

Speaker Change: Those that are caused by the variance or not which might actually be important in these autoimmune diseases. Because there are also other mechanisms. Besides the variance that can turn either in Taiwan. So we believe that really the best is to try and block all of the different <unk>.

Speaker Change: <unk> five <unk>.

Speaker Change: Not seen any yes, we wanted to get his arms, because we want to get into a broader population and also.

Speaker Change: We in our hands already we know that there is biology studies this is relevant.

Speaker Change: There's nothing to do with the with the.

Speaker Change: Despite being ISO forms activation right right.

Speaker Change: Alright.

Speaker Change: Our activation.

Speaker Change: That's one trend.

Speaker Change: Trying to catch up.

Speaker Change: Our next question will come from Michael Schmidt with Guggenheim. Please on mute and ask your question.

Michael Schmidt: Hey, guys good morning.

Speaker Change: I just want to come back to <unk>.

Speaker Change: The 86 to one and stat Sig set, especially if we're heading into the June update coming up here very soon how important will be interpretation of some of the PD marker analysis in this phase one healthy volunteer study, especially given that as you mentioned earlier.

Speaker Change: Biomarkers and how fees are really very now at baseline and asking because there was a lot of variability, especially with <unk> and some of the <unk> study as to how meaningful is interpretation of these biomarkers in that June data and perhaps then following up on your upcoming phase <unk> study in patients.

Speaker Change: <unk> yeah. So what are some of the things that you're trying to address in this study ahead of starting a randomized phase two trial.

Speaker Change: And later this year are there any particular outcome or questions. We're trying to answer in patients before starting a phase III.

Speaker Change: Yes.

Speaker Change: I was thinking about a rapid way to give you an answer on all the questions, which is we made the case for the beginning for this program that <unk> performed I can feel them up and so I would say the expectation across the studies is to perform like the pillow might be in the healthy volunteer study, obviously, the Viva Zimmer Lucas that seeks to gradation, but.

Speaker Change: Whatever they saw in Biomarkers, you should expect that from us in the <unk> study.

These are nice 28 day study of both Biomarkers and clinical endpoint I would say, we expect to see it look like.

Speaker Change: That's probably that's quite because the quickest way to answer these questions. In addition to do pillar mob.

Speaker Change: The beauty about working and protein degradation that if you're good you can actually understand what's going on you just don't look at some biomarkers. After your dose of drug but you can see okay. What is the level of pathway blockade it where they can you can.

Speaker Change: <unk> in blood and skin and so we're going to be able to look at degradations that takes in blood screening, obviously safety is going to be Paramount for this for this drug in this in this environment in this in this landscape.

Speaker Change: But in terms of Biomarkers I would just say that we expect to have to be light because that's what we've seen.

Speaker Change: All along in our preclinical study and we've been saying for for a while.

Speaker Change: And maybe just a quick follow up.

Speaker Change: Can I ask a follow up.

Speaker Change: On dosing in particular.

Speaker Change: Depicts than is typically given at a high initial loading dose.

Speaker Change: Then there is a lot lower maintenance does how do you think about that in context of the K T. Six foot 61.

Speaker Change: Dynamics.

Speaker Change: Is that something that you're aligning to for a phase II grass.

Speaker Change: Well, obviously I can't speak to the data I just would go through preclinical data with <unk> six to one we're able to achieve in preclinical models.

Speaker Change: The full extent of the desired legalization in ours.

Speaker Change: And so.

Speaker Change: Based on the data we've never built a loading dose module pre clinically and we hope that will be the case in the clinic.

Speaker Change: Thank you.

Speaker Change: Your next question will come from the line of <unk> <unk> with Jefferies. Please on mute and ask your question.

Speaker Change: Please proceed jaffray's forecaddie. Thank you for taking my question maybe.

Speaker Change: Maybe another question on the <unk> program.

Speaker Change: Could you. Please provide some additional color on the dose level you will see in <unk>.

Speaker Change: Alright, Thanks lumpy trial, because this is a single arm trial.

Speaker Change: How does it compare to the highest dose tested in the house volunteer studies, and hallmark iterate towards a potential dose that youre going to use in the upcoming phase III trial. Thank you.

Speaker Change: Yeah. Thank you. It's a great question, we can really comment on the dose. What we've said is we have a target in terms of degradation.

Speaker Change: And we believe that is an important target, which as we've said, 90% plus in blood and skin.

Speaker Change: And that is the target that we like to explore in patients.

Speaker Change: But I am not going to speak to the dos and the profile once we once we share.

Speaker Change: The volunteer data, we can talk a bit about the <unk>.

Speaker Change: But.

Speaker Change: And then as we as we shared the data from <unk>, we're talking about the doses we're likely.

Speaker Change: Okay. Thank you.

Andy Chien: Your next question will come from Andy Chien with Wolfe Research. Please on mute and ask your question.

Andy Chien: Hey, Thank you for taking the question an IRR of five do.

Andy Chien: Do you see this concept as a conceptual equivalent to a combo therapy, including.

Andy Chien: Linda mob in Africa, and are probably mob and perhaps also humira is this like a dual biologic or maybe triple biologic.

So in terms of the studies that you're.

Andy Chien: You have done in vivo.

Andy Chien: We have reasons to believe that your.

Speaker Change: Act like a dual drug or even even a triple drug so I noticed in the mouse model you've tested you tested do crab is sitting there and if not are separately, but can you combine them in mice and then would you see it by the efficacy that way. Thank you.

Speaker Change: So I'll take a quick and then maybe Jared and Brian I know you guys can cannot so.

Speaker Change: <unk>.

Speaker Change: So I think that as we've said that the beauty of the IRS five is that you cannot actually yes, you can imagine having a mall tie offsets combo in a single drug.

Speaker Change: Any context specific manner right.

Speaker Change: Like if you think about anti TNF or <unk> 23, or anti interferon. These are antibodies that block those cytokines independently of what's going on in your body. This is why they work well, but they also have in many cases in some cases, they have some side effects because you've probably got.

Speaker Change: Want to remove all of your type one interferon consistently over time.

Speaker Change: So the beauty about IRS by why each of broadband bundles reagent, but also well tolerated, it's because we only do it in the SaaS docs in those Dcs context, maybe Joe do you want to comment on that from a medical clinical perspective, what would that mean.

Speaker Change: Yes, no I mean, I think the fact that we can have this sort of broad effect, that's context specific and hopefully therefore have a safety profile that would be very favorable.

Speaker Change: Should allow us even though the single agent to potentially have activity that are equivalent to combining multiple different drugs I think with that being said I think nello earlier in his presentation talked about how these various pathways that are in our pipeline are complementary right, whether it's take to Iris five now <unk> five.

Speaker Change: Iraq for and Stat six months think about combining these right across certain diseases. If there are potential synergies that could be obtained especially if a drug like <unk> five ends up being safe and well tolerated.

Speaker Change: It really opens up the optionality, especially as an oral drug for combining several different oral drugs from within our pipeline or combining our drug with other standard of care agents that are out there, but again I think we our expectation based on the data that Bronco shorted. The preclinical models is that we should have substantial activity, even as a single agent and so it's not as big.

Speaker Change: We are obligated to combine it but we certainly have that optionality.

Speaker Change: I think we were operating in.

Speaker Change: Especially over time, maybe one last question then we'll wrap up.

Speaker Change: Thanks, Andy.

Speaker Change: Your last question will come from Cal Patel with B Riley. Please on mute and ask your question.

Cal Patel: Yeah, Hey, good morning, and thanks for squeezing me in here.

Speaker Change: No I just had one question on the.

Speaker Change: <unk> kinetics that you mention are here with the staff 60 greater.

Speaker Change: In patients.

Speaker Change: Year end.

Speaker Change: For the iron ore program previously.

Speaker Change: And that in the paper that was published there was a rebound.

Speaker Change: The protein between <unk> 14 to <unk> 28.

Speaker Change: Would you attribute it to the variability in the method used the testing method used in the.

Speaker Change: The storage conditions, so I guess going forward what steps are you taking to ensure that the kinetics.

Speaker Change: More accurately reflect the true target knockdown, rather than having a measurement or sampling with Nokia and managers.

Speaker Change: Yes, maybe just to thanks for the question just to kind of make sure. We're all on the same page so with Eric for what we've shown is in <unk>.

Speaker Change: In the healthy volunteer studies, we were able to show robust degradation, we using mass spec.

Speaker Change: Technology that would follow from obviously they want to date 14. When you go into this is browser starting the patient study.

Speaker Change: It's really hard to use mass back because the isolation procedure, it's difficult to using multiple sides that you are using so we ended up using.

Speaker Change: Flow and flow of what happens is unfortunately that the in some cases the sample.

Speaker Change: Ken can deteriorate and so it makes it more difficult to measure.

Speaker Change: The effect.

Speaker Change: On the of the degree there with time.

Speaker Change: And so what we have.

Speaker Change: What we have planned for obviously the FCC, starting six to one and the and the phase <unk> studies that we will have several opportunities to ensure that we can measure protein levels as well and I think I can.

Speaker Change: Can't speak because I will speak about the data as well, but I think once we ship basketball until data it might be easier for me to comment more on your question.

Speaker Change: Okay. Thanks, very much virtually no question.

Speaker Change: There are no more questions at this time I would now like to turn the call over to Natalie remind all fee for clothing manner.

Natalie: Thank you first I wanted to thank everybody for attending our call I want to thank the team at <unk> for putting together a great story today.

Natalie: Obviously, we have a lot of more opportunities ahead of us to engage further on some exciting milestones that were reaching soon in the Meanwhile, ECS further questions you know where to find us.

Natalie: We want to make sure that the richness of the data we shared today can be appreciated with foolish. So again. Thank you for everybody everybody for attending the slides on our website.

Natalie: So you can review in your own time.

Natalie: We will see you actually soon.