Good morning, everyone, and thanks for joining us at the Morgan Stanley Global Healthcare Conference. I'm Mike Ulz, one of the biotech analysts here. It's my pleasure to introduce Steve Romano, Head of R&D from Silence Therapeutics. Just as a quick reminder, the format for today is a fireside chat, but if anyone in the audience has a question, please raise your hand and we'll make sure we address it in our discussion. But before we get started, I just need to read a quick disclosure. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. With that, Steve, thanks for joining us today and maybe to kick things off, I'll just hand it over to you to make some introductory comments, and then we can go into the Q&A. Thank you, Mike. It's nice to be here. Just maybe just a few words on Silence. We are a global biopharmaceutical company, clinical stage, that focuses on the development of small interfering RNA compounds. We've been fortunate. We have what we refer to as our GOLD platform, which means GalNAc oligonucleotide delivery platform, and we target the liver using GalNAc as the ligand. But we have a range of technologies that we apply to our compounds and provides us with the IP. We have a very robust IP library, and that includes the sequences, the manner in which we choose our sequences, the chemistry modifications that we apply to our sequences to ensure that they're durable, potent and safe, as well as IP around the linkers that we use to attach our sequences to the GalNAc and direct it to the hepatocytes. The bottom line is, we've been successful over the last few years. We've really transferred to being from a research company into a clinical stage company, and we've had three products in the market. Our lead compound now that we're really focused on, obviously, is divesiran. Yep. Great. Thanks for that introduction, Steve. Maybe we can focus on the lead program, divesiran, in development for polycythemia vera. You recently shared some very promising phase II data, but before we dig into some of that, maybe you can just give us a brief background on the disease, kind of what patients experience and what the unmet need is. Yeah, sure. Polycythemia vera is a rare myeloproliferative neoplasm. It is associated in almost all patients with a JAK2 mutation. It is a driver mutation, and it leads to an overproduction of red blood cells. You can also have an overproduction of other blood cell lines. The issue is that when you have an overproduction of RBCs, red blood cells, your hematocrit, which is the portion of your blood, the volume of your blood that is associated with the RBCs, it grows, and it causes viscosity of the blood, and that can induce thromboembolic events and other severe cardiovascular outcomes. In these patients, what you try to do is reduce the hematocrit and retain hematocrit below 45%, which is considered a more safe range for these patients. There was a very nice study that was done back and published in The New England Journal of Medicine back in 2012 or so, 2013, that demonstrated that even if you maintain patients in the range of 46%- 50% versus under 45%, the former have four times elevation of cardiovascular death and cardiovascular events such as thromboembolism and bleeding. That is the target of treatment, maintaining these patients below 45%. Most of these patients are older patients, although we see patients as young as their 30s. About 85% of the patients are over 40, and a good portion of the patients present older than 60. We typically divide the population into high risk or low risk. The high-risk population is based on being over 60, because that places you at a higher risk just based on age, or any age patient that also has had a history of a thromboembolism. We really aim our treatment at reducing the likelihood of having thromboembolisms or other cardiovascular events, and we do that by giving them phlebotomies, which is really the first-line treatment, which is simply removing blood from the patient with some regularity. That can work, but actually can complicate their symptomatic presentation and the burden of the symptoms, because these patients tend to be iron deficient, even at baseline, because their bone marrow is chewing up iron to create and make the RBCs, overproduce RBCs. You add to that by removing blood in order to help them, so you are complicating their iron deficient status and contributing to the symptom burden. If we can do anything to reduce the need for phlebotomy, that would be tremendous. I just want to add one more point about that is only about 75%, 80%. No more than 25% or 30% of patients maintain their hematocrit below 45% on a regular basis. There is a huge issue here and a gap in treatment that we think divesiran may be able to serve. Yeah. Makes sense. I guess, how should we think about the market opportunity there and where you might fit into the current market? I know there's Yeah other agents out there as well. Yeah, it's a good question. Bottom line is there are a number of other different therapies out there besides phlebotomy. We often use cytoreductive agents such as hydroxyurea. There are newer compounds like the pegylated interferons like BESREMi, or for instance, the JAK compounds, which are used second or third line, but they are available for patients as well. And then very recently, the first hepcidin-directed therapy, which is a mimetic, was approved, and I think that's very exciting. The opportunity for us is probably in the range of $1 billion - $2 billion for our compound. The space, I think, is going to be growing with the entry of a new class of medicines that is largely well tolerated, safe, but very effective. What's really interesting, and I'll just reflect on this for a moment, is the label for rusfertide, which is the mimetic, actually has an indication that's quite broad. It is for erythrocytosis, even though we all are studying patients that are phlebotomy dependent and meet certain criteria to get involved in the trials. The indication that was given to them is actually very encouraging because we think this is a great pathway to exploit for helping patients to manage their condition much better. I think that is a good indication of potential size of the market even expanding. Yeah. Makes a lot of sense. Maybe you can talk about your mechanism of action. Yeah. Kind of how it relates to rusfertide. Yeah. Rusfertide, what we are all targeting with these new class of medicines are targeting hepcidin pathway. Hepcidin is the major modulator of iron in the body. These patients often have low levels of hepcidin. What our compound does is target TMPRSS6. TMPRSS6 is a negative regulator of the hepcidin pathway. If you block TMPRSS6, you elevate hepcidin. Hepcidin will reduce the amount of iron that is available for the bone marrow, so it essentially restricts iron to the bone marrow and therefore will starve the bone marrow and the erythrocytes of iron that is necessary. Therefore, you see a nice drop in hematocrit. The mimetic that was just approved is actually an exogenously administered hormone, and that is a peptide, a synthetic peptide, and that is given on a weekly basis by injection. The way our compound works is to increase the endogenous production of hepcidin. It is targeting the same pathway, but in a different manner. Yeah. What are the advantages of getting endogenous hepcidin versus exogenous? Well, I think it is a couple items. First of all, with the technology we have, siRNAs are very durable. Yeah. You can give them very infrequently. But the reason why that is important is it means that they are elevating hepcidin, so the biomarker that we are targeting, they are elevating hepcidin in a durable fashion. Right. You have a consistent elevation of hepcidin, a smooth increase and maintenance of hepcidin levels that clearly is associated with the benefit of the drug versus giving an exogenously administered hormone, which does work obviously. Yeah It has to be given on a regular basis. Yeah. Understood. With that background, maybe we shift into some of the data you shared. Yeah. Phase II results from your SANRECO study. We thought they were best in class, but maybe you can highlight your thoughts on the data and high level some of the key takeaways there. Yeah. I think the results really were terrific. We were very satisfied with that. We got a response rate of close to 90%, about 88%, and that compared with a placebo response of about 19%. The placebo-adjusted response was just under 70%. That's a very robust effect. That is actually looking at patients. The response criteria was patients who were able to maintain hematocrit below 45 throughout the period from week 18 - 36. It was a 36-week study. Everybody adjusts to their assigned treatment in the first 18 weeks, drug or placebo, and then from 18 - 36 weeks, you evaluate the response. That 90% response refers to, or nearly 90% response refers to the percent of patients that were able to maintain their hematocrit below 45 without the need for phlebotomy. Very, very robust. The interesting thing about this trial is that we looked at two different dose strategies on the active drug. Besides placebo, which a third of the patients received, two-thirds received the drug, but they received the drug at either Q6 week intervals, which was essentially replicating or confirming one of the dose arms that we had in our phase I, or they received it at a Q12 week interval. A ll patients received 6 mgs per kg, which was the dose we decided was most reasonable to bring forward into phase III. What we did show was that either Q6 weeks or Q12 weeks was actually very effective, similarly so, in achieving that very high level of response. Very excited about that, and we'll move forward with that every 12-week arm into our phase III program. Can you just put that dosing interval into perspective? Q12 weeks. Yeah You mentioned durability versus what maybe is the competitors out there. Yeah. The hepcidin mimetic, of course, is given on a weekly basis, and that's injected subcutaneously. The ASO, which is being developed, sapablursen, is given on a monthly basis. That's very typical of the requirements for an antisense oligonucleotide. They tend to be a bit less potent and durable. But sapablursen has already shared their phase II data in a once-a-month injection, a Q4-week injection. Ours, of course, is a Q12-week injection, again, sub-Q. There are compounds behind us. For instance, Disc Medicine has a monoclonal antibody that's targeting the same pathway, targeting TMPRSS6. They are looking at, I believe, at both Q2 and Q4 week, and we just heard something about their Q2 week data, and perhaps we'll hear about their Q4 week data at ASH. We are really sitting in a very enviable position where we have a durable compound that confidently suppresses hematocrit to below 45% and can be given on a quarterly basis, which by the way, fits nicely into the way these patients are managed because these patients are seen on a regular basis. Because in order to maintain hematocrit below 45%, you have to keep a close eye on these patients. A quarterly dosing strategy would really fit into the routine manner in which these patients are treated. Yep. Makes sense. Maybe just back to the phase II data you shared and maybe talk a little bit about the placebo response what you saw there and sort of how it compares to your expectation. Yeah. When we powered the study, when we were starting the phase II study, we assumed about a 20% placebo response rate, but we didn't really have a lot to hang our hats on, and we didn't have the rusfertide phase III data yet. We also suggested that we would have a very robust effect above that, somewhere in the 40%-50% range. So I think we were very good at our expectations as placebo came in around 19%. The effect was higher than we had initially anticipated, but you always plan a comfortable margin Yeah to be sure that the trial is powered appropriately for a good positive outcome. So that was really what we did. Now, rusfertide showed about a 77% response rate and about a 33% placebo response rate. But naturally, that was in a larger population. So when you move from smaller populations, we had 48 patients in our phase II, to a 250-patient study, for instance, and I think they enrolled closer to 300, it's not surprising that you get more variability. But they still showed a robust effect. That 44% placebo-redacted rate obviously was robust, and the drug is now approved. Again, we have a close to 70% placebo-adjusted effect, 69%. So we hope that carries through into the phase III. Yeah. Makes sense. I know this was a sort of top-line release, but maybe you could just talk about some of the secondary endpoints, kind of hematocrit control, iron markers, PROs, things like that. Yeah Just kind of what you're seeing there. Yeah. Well, we've submitted an abstract to ASH, so hopefully we'll get that accepted, perhaps an oral, which would be great. We'll be able to go into the details of all the indices of the iron indices as well as all the blood indices, also show the curves for hemoglobin Yeah and hematocrit. We didn't share that in the top-line results. But as anticipated, very similar to what we saw in phase I, you see a relatively rapid reduction in hematocrit in the first two to three weeks even, and then that persists in a durable fashion. You see the same thing with hemoglobin, as you would expect. With hepcidin, which is the biomarker of import, you see an elevation of that hepcidin with a general maintenance of that as well. So all that laboratory effect that we saw in the phase I that sort of parallels the effectiveness on the clinical side, we're seeing that mirrored in the phase II. So you'll see more of that. Other secondary outcome measures, as you mentioned, are evaluating symptoms, and we did include a symptom score that's typically used in this disease state and other similar myeloproliferative conditions. We also have the PROMIS, which is targeting or specifically evaluating fatigue. We will have that data. We will share that data. Another secondary outcome measure was the rate, because in the U.S., the FDA has agreed to a response criteria, as I mentioned, but in the EMA in Europe, they really want to look at a reduction in the rate of phlebotomy. We showed a very effective and statistically significant effect on that as well. We will share all that information in full at the meeting Yeah including the symptom management data. Yep. Great. Maybe you can comment just on what you saw for the safety profile. Yep. Maybe provide a little color on anemia, thrombocytopenia, Yeah and reaction site reactions. Yeah. I think the profile of the drug was very similar to what we saw in phase I. We had an independent safety review committee that reviewed the data on a regular basis from the phase I study as well as in the phase II. By the way, the protocol was a combined phase I/phase II, so we have that view of the safety throughout both of those programs. Yes, you do see an elevation of platelets. This is very typical of restriction of iron to the bone marrow. You get a sort of a bias towards the production or a higher production of the megakaryocyte line, which is a platelet line. So you do see an elevation of platelets. It happens relatively quickly over the first few weeks, but then it plateaus. We saw an increase in the 30% range, not different from the phase I, very similar to the profile that you saw with rusfertide. That same mechanism, very predictably inducing a reactive thrombocytosis. We are not seeing patients' platelet counts go to dangerously high levels. Keep in mind that many of these patients, based on their disease state, will have elevated platelets when they come in. I think it was simply demonstrating that the drug's mechanism is very similar to what we have seen and produces a similar effect. Naturally, many of these patients have indices in the anemic range when they enter the study. They are heavily phlebotomized, some patients come in with relatively hematocrits that are generally obviously all below 45, but some of them are quite much below that. You have to be cautious about that. We only had two adverse events reported as anemias. These are well-honed investigators. They are hematologists. They understand the condition. They only reported two that they considered to be clinically significant. We will review all the data and the laboratory data in time as well. Generally speaking, the tolerability was very good. ISRs, concerns around injection that you have with any compound that you inject subcutaneously or intramuscularly, in this case sub-Q, we saw actually very few injection site reactions. Actually, much fewer than we saw in phase I. I think we feel very confident about the tolerability Yeah of the drug. Generally, safe and tolerated as it was in phase I with no new safety issues. Yeah or signals. Yep. I know this was a top-line sort of release, but any feedback or have you shared the data with some physicians, and what kind of feedback are you- Well, naturally, we spoke with some of our experts that are advising us, and these are folks that are very familiar with the entire portfolio of products available in development. Yes, we got very encouraging feedback. Yeah, no, we're very excited. I think people do believe it's potentially a best-in-class compound based on the efficacy we're seeing. I'm always cautious as a drug developer. You've got to wait till you confirm those results in a phase III. This is phase II. I think everything's pointing in the direction of having a very, I think, valuable profile for patients and for physicians who manage these patients. Understood. I guess maybe just back to rusfertide and when you think about comparing your data to theirs. I know it's sort of phase II to a phase III. Yeah. You've got to be cautious there, but just key points of differentiation that you think have come out so far. Yeah. Again, I want to be very careful. They have an effective product that's been approved, so that's great. It's the first hepcidin-directed therapy that's approved that makes it a little easier for us, for instance, because we know that a drug targeting this mechanism with this mechanism, targeting this pathway, is likely to move in the same direction. We're very confident also because the types of patients that they enrolled are very, very similar to the patients we enrolled in phase I and phase II. So we feel very confident about that. I think obviously that one of the distinctions is convenience, and now convenience is not going to carry the day. Efficacy Yeah is going to carry the day, but convenience is important because convenience actually can translate into greater compliance in the marketplace. When you need to have an injection on a weekly basis or any more frequently than we have, there's an opportunity, unfortunately, to miss doses and obviously the control of your symptoms and your condition is going to be affected by that. With a durable compound, with a mechanism like ours, if confirmed in phase III, that's a real advantage. I think the value proposition is not around the infrequent dosing, but the fact that you can confidently, with infrequent dosing, maintain hematocrit below 45. As I mentioned earlier, that's the goal of these patients, keep their hematocrit below 45 to reduce the likelihood of cardiovascular symptom outcomes. Yep. Got it. I also just wanted to ask about your response definition versus theirs. Yep. They used a little bit more of a stringent approach. Well, Or less stringent. Sorry, I mixed it up. Yeah. But have you kind of run that analysis, or what do you think would happen if you did? Well, we really don't have to because we have such a high response criteria. Yeah. I don't think we even have folks on the margin that might have been moved into the response criteria arm, I mean, the positive response arm. No. I think we did a very clean thing. We just said, "Look, under 45. If you hit 45 or above, you're a non-responder. If you drop out of the study for any reason, you're a non-responder." We had very strict criteria. We're looking at that now, Mike, to decide whether we continue to do that in phase III or whether we consider something more akin to what rusfertide did, which gives you a little bit of more flexibility around the margins, if you will. Yeah. But I think we're so confident in the effect that we're seeing, I'm not sure that's going to make a difference in the end either way. Do you think it's easier to sort of run the study and run the analysis with your sort of response definition? Well, if you can remove any burden from the investigator. Yeah. Okay. Do they have to calculate? I know it seems like a very simple thing, to be honest with you, but having been on that side of things as well in the past, if you've got two or three or four or half a dozen studies running and you have to think of different criteria for each of your studies, anything you can do to make it easier and more convenient both for the patient and the physician, I think helps. It may seem like a minor thing, as long as it doesn't have a meaningful impact— Yep in your outcome measure that you're evaluating. Makes sense. I wanted to come back to rusfertide a little bit. I know you do not want to make too many comments there, but any thoughts on just labeling or pricing and what that means for how you think about that? Well, I think their price that they have obviously negotiated is very much akin to what we had assumed. If you look at some of the premium price products in this market, the pegylated interferon like BESREMi or the Jakafi compound, they have waxed over 200,000 annual. We had assumed that they would come out perhaps even at a premium to that, and I think they did come out with a slight premium. I think that underscores at least the economic sort of proposition, that in an area where you have an orphan condition where the need is great to have newer therapies, you are going to have a relatively low bar for access and reimbursement, because this is an orphan condition. I think we feel confident about that. I think one of the best things about the label, again, is the indication, because we are studying really the same population of patients. Although for purposes of clinical trial and operationalizing your population for clinical trial inclusion, you go after a phlebotomy-dependent patient, you define it in a particular way, just to make sure that you can make generalizations from that population into a label. I think it is great that, in fact, the label is for erythrocytosis. It is not saying for phlebotomy-dependent PV patients. It is for erythrocytosis. That allows an intervention with that drug and hopefully drugs to follow like ours, at really any point in the treatment sort of algorithm, which is great. If you have an elevated hematocrit that you need to control, then hepcidin-directed therapies should be top of line based on safety and efficacy. Yep. Makes sense. You mentioned some of the competitors recently too. I guess one, maybe we can start with Disc Medicine and they just shared some data. Yep. Kind of your thoughts there and maybe how it compares. Yeah. There are different ways and different mechanisms you can utilize to address this issue. The monoclonal antibodies are targeting TMPRSS6 as well. That is a very reasonable mechanism to apply to that specific target. I think the issues with monoclonal antibodies are can you get to a reasonable timeframe? They demonstrated Q2 weeks and they have Q4 week in their trial, so we will see. It is not likely, even with sort of the ways that you can engineer antibodies and introduce certain mutations to extend their half-life, that you are not likely to get much further than that. That is a reasonable approach. I think the important thing here is, yes, this is getting to be a very interesting area. People are interested in it, but I think the most important thing for us is really to look forward. We are a first-in-class siRNA. The only thing between us and the hepcidin mimetic that was approved is the sapablursen, and that is an ASO. Yep. I do believe that the siRNA is a more potent mechanism. Based on their phase II data, I am always very careful about cross-study comparisons. Based on their phase II data, they didn't have placebo, so it's hard to sort of adjust the effect they'll see in a placebo controlled phase III study. The efficacy doesn't look to be as good as rusfertide or as potent as rusfertide, and clearly our data is very good as well. I think we need to focus on getting to the market as quickly as possible and shortening the timeframe essentially behind the completion of a phase III, behind sapablursen. I wanted to get your thoughts on next steps from here. Yeah. I think you're planning a phase III study and maybe have an end of phase II also planned. That's right. Maybe just talk about that meeting and what the focus is. Is there any specific question you need feedback on to figure out what the design will be or just maybe help us understand that? Yeah. Fortunately, we have had some nice interactions with the agency in preparation for finalizing the phase II study design, and that was all with the anticipating that that would be a supportive trial for the complete submission. Assuming a single phase III, which we believe is obviously the path forward, we have resolved a lot of issues around the definition of the population. Yeah The response criteria, et cetera. Obviously, we will have to tinker with that and confirm it all. Going in, I think we feel pretty confident, and we just have to secure that agreement. I think one of the bigger issues is if you look at the effect size of our drug from both phase I and phase II, you do not need a very large study to confirm that effect. There is no question. If you are just looking at the primary outcome measure of response and ability to maintain hematocrit below 45 without the need for phlebotomy, we could do that with a relatively small study. So the question is, how large should our study be? If we want to target some of the subjective responses, which are always a little trickier, they have greater variance in the scoring and responses, you have to build that into your power assumption. One of the other things we have to consider, so that we will manage because we have got the phase II data. We will extrapolate from that phase II data and consider the power assumptions for those important secondary outcome measures in the phase III study. What we do not know yet is what is the minimum requirement for safety exposure. Because if we can do a study less than 250, and I say 250 because that is what rusfertide set out to do. They over-enrolled to closer to 300. That is what sapablursen is doing. Our assumption is perhaps that is because you need to reach a minimum requirement even for an orphan condition of exposure. I think that is going to be an important question because that affects the cost of the phase III program, the timing to get it complete, et cetera. If we can reduce that phase III study requirement and still meet the objectives both from a regulatory standpoint, but from a labeling and commercial standpoint, that would be very, very helpful. That, I think, is one of the bigger issues. The other thing is, with any drug in a relatively new class of medicine, you have to just agree on the safety parameters and how you are going to capture that. There is learnings I am sure the FDA will apply to us from having just reviewed rusfertide data in detail. We will get that feedback, but we feel pretty confident. The other thing, and I should have mentioned this earlier, is we are moving from a weight-based dosing to a flat dosing. We do have preliminary agreement on how to get there with the agency, and we generated some bioavailability data. We are moving to a higher concentration product that will reduce the need for multiple injections to down to two for phase III and beyond, which is great given that they are injected infrequently. But we also have to prepare for launch. At launch, we want to have a PFS, a prefilled syringe. Having that flat dosing allows us to obviously develop the prefilled syringe and have that in preparation for the time that we launch the product. Yeah. We have to get agreement on those points. Yep. Got you. I know focus is more on getting the phase III design locked in and started, but I guess longer term, commercially, is this something you might decide to launch on your own, partner, what's the thought there? Yeah. Well, we have a lot of thinking to do with regards to that. Right now, we certainly can go ahead with the development ourselves. We've got the funding, of course, that we brought in, over $201 million following the results of the phase II, so we can fund the study through to top-line results. But we're not a commercial company right now. Yeah. And obviously, we'd consider a range of potential opportunities based on the economics. Yep. Understood. Maybe you want to touch on some of your pipeline assets. I know the focus is more divesiran. Yeah but there's quite a number there, so if you want to just give a quick preview. Yeah. No, thank you. We are a pipeline company, and we have several products in the pipeline. We are having returned to us from AZ, SLN312. SLN312 is an ANGPTL3 compound, so it's targeting a non-LDL receptor-dependent means of reducing LDL and other atherogenic lipid components. That has completed phase I with AZ. The decision to return it was not the data. The data looked great, and in fact, AZ has been presenting that data at lipid and cardiovascular meetings since midsummer. Strategically, they decided not to move that into phase II, so that will come back to us. That's an interesting compound. We also have a GPR146, which is a novel compound, first in class, that is also targeting a non-LDL receptor-dependent means of reducing the production of very low-density lipid proteins. There is an opportunity potentially even to consider those in combination. There is some preclinical data that's been completed by an academic site in Europe that demonstrated sort of the synergy between the two, and that could be a very interesting area for us, moving away from. Because our focus really is in rare and orphan conditions, that's given the size of our company, it would be very reasonable to consider either of those for a condition such as homozygous familial hypercholesterolemia. The other compound we have is an inhibin E compound. This is a very interesting class of medicines. The genetic data support a reduction in cardiovascular risk factors in these patients. It's currently in the clinic. Wave Life Sciences has a compound in the clinic, Arrowhead Pharmaceuticals has a compound in the clinic. I think the issue here is determining in what population is it best suited. I don't think it's going to be utilized purely in the management of obesity because the drugs that we have for weight loss per se are very potent, but they do have issues. There's Achilles' heels, like for instance, with the incretins, you lose a lot of weight, but a good portion of that weight loss is actually lean muscle mass. Inhibin E actually can redistribute, or I should say, change the body composition so you reduce fat in the places that are most dangerous. So visceral fat, hepatic fat, and you retain skeletal muscle, so you retain lean muscle. Whether it's going to be used in a combination with incretins, whether it's to use to minimize weight regain in patients that go off the GLP-1 class, whether it's used in a group of obese patients at metabolic risk. That is a complicated space that needs to be figured out. We are not likely to bring that product into full development. Yeah. Those are large studies. Yeah. We did just generate preclinical data in a proof of concept murine model, mouse model, that showed a very competitive profile to the same data sets that are produced by Arrowhead and Wave Life Sciences. Both of those compounds, GPR146 and inhibin E, can actually reach IND by end of next year if we prioritize those for investment going forward. Yeah. Complement factor B program. Yeah, complement factor. Yeah. We have a compound that has a very competitive profile. It is phase I ready, but again, it is going to be part of the portfolio we now have to reprioritize. Got you. Or I should say prioritize. Now that we have got funding to get us through to the top line results of phase III, we will look at the cost of that study. We will determine where we want to really spend our money with regards to prioritizing some of these compounds. It could be through collaborations, it could be on our own. Yep. The other thing I want to say is we are also focused on extrahepatic. Yep. We have a substantial effort targeting other cell and tissue types besides hepatocytes, and we've had some very good preclinical sort of work ongoing. We haven't shared all that data, but we're also entering certain collaborations that could expand that effort as well. In time, probably in the new year, we'll be able to talk more about that. Got you. Maybe we got one minute left. Yeah. Maybe I'll squeeze one more question in here. Sure. Just CEO search, just updates there, thinking on that. Yeah. Absolutely, we have been looking for a CEO. I think we got a little bit too close to the phase II data and the funding requirements. I think now we are in a much better position. We have got the funding for the phase III program, our lead compound, and obviously we have got great results. I think that will attract a number of candidates that will really help us and hopefully have a CEO in place by end of year. Yep. That is our Chairman and our organization's intent. Yep. Okay, great. We are out of time. Why do not we end it there? Steve, thanks so much. Appreciate it. Thanks, Mike. Thank you.