Good morning. I would like to welcome you to the Silence Therapeutics conference call to discuss results from the ongoing SANRECO Phase 1 study. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question-and-answer session where you will have the opportunity to ask questions. Thank you. I would now like to turn the call over to Gemma Hopkins, Vice President of Investor Relations and Corporate Communications. Thank you, Sonia, and thanks, everyone, for joining us. Joining me on today's call are Craig Tooman, our President and CEO, and Steven Romano, our Head of R&D. Rhonda Hellums, our Chief Financial Officer, will also be available for questions. Please note that during the Q&A, we will limit questions to the topic of our divesiran and PV program. Today's press release and presentation are available on our corporate website at silence-therapeutics.com. Before we begin, I would like to remind you that this call will contain remarks concerning Silence's future expectations, clinical development plans, and prospects, which constitute forward-looking statements for the purposes of the Safe Harbor Provision under the Private Securities Litigation Reform Act of 1995. Our actual results may differ from those contemplated by these forward-looking statements. Factors that could cause these results to differ materially are described in today's press release, as well as our filings with the SEC. Any forward-looking statements that we make on this call are based on assumptions as of today, and we undertake no obligation to update these statements as a result of new information or future events. With that, I'd like to turn the call over to Craig. Craig? Thank you, Gemma. Today is an exciting moment in the history of Silence, and we are thrilled to share some compelling data with you from the ongoing SANRECO Phase 1 study of divesiran in patients with polycythemia vera, or PV. Divesiran is the first siRNA in this phase of development in PV. PV represents a real unmet medical need. It is a rare but serious blood cancer with limited treatment options. Patients require frequent phlebotomies. Our Phase 1 program to date has demonstrated that divesiran has eliminated the need for phlebotomy in all well-controlled patients, and this has been accomplished with infrequent dosing. To date, divesiran has also been well tolerated with no serious safety issues. The emerging profile of divesiran, both in its treatment range of patient severity and durability, appears very promising. We are very encouraged by these results and what they could mean for patients, physicians, families, and everyone in the PV community. At Silence, we continue to demonstrate the broad applicability of our mRNAi GOLD™ technology platform, and the results we see in today's PV program are a credit to a very dedicated team focused on bringing this program to patients as quickly as possible. As you will hear, we are planning to start the phase 2 study by the end of this year. As a reminder, divesiran has FDA Fast Track and Orphan Drug designations for PV. Before I hand it over to Steve, I'd like to take a moment to acknowledge the people who have and continue to contribute to this important study, including the 21 PV patients who have enrolled to date, site investigators, and Silence team members. I'll now turn the call over to Steve to discuss the SANRECO program and divesiran PV data in more detail. Steve? Thanks, Craig, and good morning, everyone. I'm delighted to share these results with you. As a reminder, PV is a rare myeloproliferative neoplasm, a type of blood cancer that is associated with erythrocytosis, or an increase in the production of red blood cells. Other blood cell types, including WBCs and platelets, may also be increased. The increase in RBC mass, corresponding to a substantial elevation of hematocrit, leads to a higher incidence of thrombotic or clotting events and an increase in adverse CV outcomes. PV is associated with a range of burdensome symptoms, including fatigue, cognitive disturbance, and pruritus, and additionally, longer term can transform to myelofibrosis and even acute myeloid leukemia. PV impacts around 150,000 individuals in the US and 3.5 million worldwide. The aim of the treatment is to maintain hematocrit less than 45%, a level that is associated with a reduced incidence of thrombosis and CV-associated death. Treatment usually requires routine phlebotomy, which is venipuncture and blood removal, along with low-dose aspirin. Many patients, regardless of risk level, require the addition of cytoreductive agents to ensure achievement of treatment goals. Phlebotomy, while helpful, is time-consuming, may not maintain patients at safer hematocrit levels consistently, and can contribute to iron deficiency and overall symptom burden. So treatments that could reduce the dependency on this intervention should potentially benefit patients. As a reminder, divesiran is a 19-mer double-stranded, blunt-ended, small interfering RNA that targets TMPRSS6, expressed almost exclusively in the liver. It was designed and developed utilizing our proprietary mRNAi GOLD™ siRNA platform technology, which consists of several key components, including proprietary RNA sequences and linkers conjugated to GalNAc ligands. We utilize a toolbox of chemical modifications, which allows for the design of stable, potent, durable, yet reversible compounds directed at silencing expression of a specific liver gene target. TMPRSS6 is a negative regulator of hepcidin, the body's master regulator of iron metabolism, including its absorption, distribution, and storage. The therapeutic hypothesis for the use of divesiran in PV patients is the following: by silencing TMPRSS6, hepcidin production and release by liver hepatocytes will increase, leading to the restriction of iron to the bone marrow and thus reducing the excessive production of red blood cells, a process dependent on availability of iron. The Phase 1 trial design was informed in part by the data generated in the completed Phase 1 Healthy Volunteer study, as well as the overall safety and tolerability profile observed in both the Healthy Volunteer study and a completed Phase 1 study in patients with iron-loading conditions such as beta thalassemia. The trial is open label, allowing for up to 4 cohorts, and each cohort consists of up to 8 patients. As a fourth cohort has not been deemed necessary, the final data set will include patients from three cohorts with doses of 3, 6, and 9 mg/kg, respectively. All patients will receive 4 scheduled doses at 6-week intervals, corresponding to weeks 0, 6, 12, and 18. All patients are then followed for 16 additional weeks for a combined total of 34 weeks of treatment and follow-up. Key inclusion criteria for the trial subjects include a diagnosis of PV based on WHO criteria and a history of requiring a minimum of 3 phlebotomies in the previous 6 months or 5 phlebotomies in the previous 12 months. Patients on stable doses of cytoreductive agents are allowed, and given the exploratory nature of this phase 1 study, both well-controlled patients, i.e., those with hematocrits 45% or less, and those less well-controlled with hematocrits greater than 45%, were included. As of today, 21 patients have been enrolled across the three ascending dose cohorts of 3 mg per kg, 6 mg per kg, and 9 mg per kg, consisting of 6, 8, and 7 patients, respectively. We intend to close enrollment in the phase 1 trial this month. The data presentations I will share with you today are based on a data cut-off date of March 29th and will therefore include all available data at all data points for 16 of the 21 patients enrolled. We intend to present a detailed presentation of all enrolled patients at a research meeting later this year. To date, divesiran has been well tolerated with no major safety issue identified. This experience is consistent with the safety and tolerability profile observed in previous completed trials. This table provides a summary of baseline characteristics of the 16 PV patients included in today's data presentations. The majority of patients are age 60 and older. Based on study site geography, there is a mix of Caucasian and Asian patients. All but one patient was on aspirin, and a majority were also on cytoreductive agents, specifically hydroxyurea. Eight patients were enrolled at hematocrit levels associated with good control, 45% or below. The remaining eight patients had elevated hematocrits, including three greater than 50% at baseline. None reported a history of previous thrombosis. This slide displays all recorded phlebotomies, both pre and post-dose. Historic phlebotomy details are in orange shades to the left of center and capture all events up to day one, the time of the first dose administration. To the right in the diagram, in blue shades, are any phlebotomies recorded during the trial through March 29th, as previously noted. None of the eight patients entering the trial with well-controlled hematocrit levels required a phlebotomy. In other words, 100% of this group maintained adequate control of hematocrit as per treatment guidelines. Of the eight patients entering the trial with hematocrit levels above 45%, two patients each required one phlebotomy. The baseline hematocrits of these two patients were 56% and 53%. None of the other six patients with hematocrits above 45% has required a phlebotomy to date. To reiterate the key takeaway points from this slide, all patients who were well controlled at baseline maintained hematocrit control during divesiran treatment. None required a phlebotomy, 100% response rate in this group. Although we'll want to evaluate change in phlebotomy rate pre and post-entry when the study is complete, what we can say at this point is that there were 59 phlebotomies recorded for all patients in the six months prior to study entry, and to date, only two phlebotomies have occurred during the treatment period. Lastly, the 2 phlebotomies observed during treatment occurred in 2 patients with very high baseline hematocrit levels of 56% and 53%. In fact, none of the 13 patients entering the trial with hematocrit levels of 50% or below, 8 well controlled, and 5 with hematocrit levels of 46%-50%, have required a phlebotomy to date. These data are very promising. As we observed in the previously reported healthy volunteer study, divesiran demonstrated robust target engagement. In cohorts 1 and 2, the 3 mg/kg and 6 mg/kg group, for which hepcidin data are available across a relevant time frame, we observed early and sustained hepcidin elevation. Importantly, these elevations are within the physiologic range of hepcidin levels. In both cohort one and cohort two, which include all patients in each, regardless of baseline hematocrit level, i.e., well controlled or not, patients treated with divesiran reach target hematocrit levels based on group means. Another way of viewing divesiran's effect on hematocrit is mean change from baseline, and again, these data are for all patients in each cohort, regardless of baseline hematocrit. A clinically meaningful and consistent reduction is seen in both groups, with evidence suggesting a dose response. Given the fact that we included a range of patients in this trial, regardless of baseline hematocrit, it's important to evaluate the effect of divesiran on both well-controlled patients, those with hematocrit levels less than or equal to 45%, as well as those with high baseline hematocrit levels. On this slide, patients from either cohort are included based on individual baseline hematocrit. As you can see, on average, well-controlled patients, of which there were 8, maintained hematocrit levels in that range. As I showed earlier, none required a phlebotomy during the period of observation being reported on today. Additionally, meaningful reductions were seen in the group of 8 patients entering the trial at hematocrit levels as high as 56. These data include the 2 high hematocrit patients who each required a single phlebotomy during the treatment period, as reported in this data set today. As was mentioned, divesiran works by increasing hepcidin and thus restricting iron to the bone marrow, leading to a reduction in RBC production and subsequent hematocrit levels. But what we see here is that ferritin levels during divesiran treatment are increasing and sustained at higher than baseline levels, reflecting an increase in systemic iron stores from redistribution of iron and an improvement in iron deficient status of most of these phlebotomy-dependent patients. Iron restriction to the bone marrow can lead to elevations in platelet levels. Divesiran, in general, has been associated with limited increases in platelet counts. In addition, looking at change from baseline in platelet levels, there's no suggestion of a dose effect. In fact, the higher dose appears to show similar and limited elevations across the time points. We will continue to follow this important blood parameter as the trial progresses. In summary, regarding efficacy in the data set shared today, all divesiran-treated patients who were well controlled at baseline remain so without the need for phlebotomy. All patient groups, regardless of baseline hematocrit, demonstrated reduction in control of hematocrit. Divesiran was associated with elevation of hepcidin irrespective of iron status, demonstrating robust target engagement. Divesiran was associated with elevation of ferritin, a key indicator of systemic iron content, representing improvement in iron deficient status. Though the study is ongoing and rates cannot be calculated, only 2 phlebotomies were recorded during divesiran treatment, in contrast to a total of 59 phlebotomies reported during the 6 months prior to study entry. Regarding safety and tolerability to date, there have been no drug-related serious adverse events observed. There have been no withdrawals due to divesiran-related adverse events. Mild injection site reactions have occurred in a number of patients, though all events were categorized as Grade 1 and were fully resolved. We look forward to presenting a fuller data set later this year at a research meeting. I'll now turn the call back to Craig. Thank you, Steve. We hope you share our enthusiasm for these impressive data today and the potential that divesiran represents. What we see today is a very clear picture. We are excited about the potential for divesiran to be the first siRNA therapy for PV. As many of you know, Silence has been an innovative siRNA company for many years and is beginning to be recognized as a true platform company. While today we're focusing on the divesiran PV program, we also continue to see very impressive results in our Lp(a) program and some of our partner programs, and we look forward to updating you with our continued progress. We're now happy to take your questions. To ask a question during the session, you will need to press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. We will now take our first question. Please stand by. The first question comes from the line of Kostas Biliouris from BMO Capital Markets. Please go ahead. Your line is now open. Good morning, everyone. Thanks for taking our question and congrats on the strong data. A few questions from us, Steve. The first one is on the dosing regimen. You dosed every 6 weeks. Do you think based on that data, 6 weeks is the final regimen you will be taking forward, or do you think you can go even less frequently? A second question is on the dose response effect you see with the third cohort so far and whether you think you will be going to the third cohort, 9 mg per kg is what you may be using, or you don't really need the 9 mg per kg? Because if I remember correctly, in healthy volunteers, you saw a kind of ceiling effect below 9 mg per kg. The third question is, based on this data, how are you thinking about the commercial positioning of this drug, given that Protagonist is focusing on frequently phlebotomy patients? Would you consider something like that, or you can even target patients with infrequent phlebotomy requirement? Thank you so much. Congrats again on the data. Yes, thank you. Thank you so much. I think I got all those questions. The first was the frequency of dosing. As you know, we had a regimen here of Q6 weeks. Based on the data we're collecting and continue to collect, we do see an opportunity potentially for a less frequent dosing strategy, but that will not be determined until we complete phase 1 and move into phase 2. That, I hope, answers that question. As you can see from the phlebotomy slide I showed you, the persistence of control goes well beyond the time for some of these patients for whom a next dose might have been scheduled had they continued to a fifth dose, for instance. We're seeing good durability. Around the dose response for the third cohort, it's a little too early to tell. Again, as you can see, we still are ongoing and need to follow that cohort out a bit further. But so we'll hold off on that answer till we complete the trial. But we're seeing a very robust and persistent effect in both of the lower dose regimens. So I'll leave that for you. And with regards to commercial, the bottom line is we're still planning the details of our phase 2 and 3 program. We're confident that the data suggests a robust effect across a number of patient types, but that has not yet been determined. I hope I got all of your questions answered. Thanks so much. Very helpful. Thanks for taking my 17 questions. Thank you. We will now take our next question. Please stand by. The next question comes from the line of Mike Ulz from Morgan Stanley. Please go ahead. Your line is now open. Dear Mike Ulz, your line is now open. Please go ahead. Sorry about that. Thanks for taking the question and congratulations on the data as well. Maybe a couple of follow-ups. So the 2 patients that needed a phlebotomy that had high hematocrit at baseline, I guess, do you think that could be potentially dose-related? So in other words, if they were at the 9 mg dose, maybe those patients wouldn't have had a phlebotomy. And then maybe just secondly, if you can share how you're thinking about dosing in the phase 2 study. Thanks. Yes, Mike. With regards to those two patients, keep in mind that in practice, when physicians have patients who maintain elevated hematocrits, they want to intervene. In our trial, we did not dictate the timing of intervention. We were exploring those higher hematocrit patients at baseline, but we're not dictating treatment. The bottom line also is, as you can see, even in those two patients, you're seeing a reduction in frequency based on their history. Again, moving forward, we're very likely, as other programs have done, to restrict the entry criteria for patients in phase two and three to control hematocrits for purposes of looking at maintenance of a response or control of hematocrit. The bottom line is this is exploratory, and we wanted to see the effect across a broad group, and we have seen a very compelling effect across that group. With regards to dosing in the phase 2, again, until we complete phase 1, we will not confirm the dosing going forward. But again, as you can see, we chose a reasonable time frame, infrequent dosing at Q6 weeks, and the data suggests that it is an opportunity to consider a longer interval between dosing as we move forward. Got it. Thanks and congrats again. Thank you, Mike. Thank you. We will now take our next question. Please stand by. The next question comes from the line of Keay Nakae from Chardan. Please go ahead. Your line is now open. Yes, thanks. Also, congrats on the data. Question on slide 9 in terms of the number of patients that completed the study in each of the cohorts. What are the reasons for patients perhaps not completing the study? Yeah, that's a very easy question because the study is ongoing. We've had no dropouts from the study as of yet. We're hoping, obviously, as we continue and complete the trial, we'll have more and complete data for future presentations. Okay. And the second question I had was with respect to the background meds, the cytoreductive agents that patients may have been on. Are you seeing any greater synergies with different background drugs in terms of the benefit of your drug? Yeah. So what we've done is we have allowed patients on stable doses of their cytoreductive agents to enter the trial, and then we're obviously moving them through the treatment regimen as we described, with the hopes that their background therapy would be maintained. We have not yet completed the trial. We will look back at any type of additional effect or benefit, but I think it's too early to tell. Keep in mind, this is still a phase 1 trial, so the numbers are limited. We will continue to evaluate the background therapies and any impact it may have on effect. As you can see, though, the effect is very consistent across all of the patients in the data set that I've shared today. Right. So I guess where we're really going with that is as we move forward into phase 2, and you touched on this earlier in terms of the enrollment criteria, how are you perhaps thinking of maybe narrowing that, obviously, in the phase 2? Yeah. We are currently considering the details of the phase 2, and we'll share those once we get to that point where we have a confirmed protocol. Okay. Well, very good. Thanks. Thank you. Thank you. We will now take our next question. The next question comes from the line of Patrick Trucchio from H.C. Wainwright. Please go ahead. Your line is now open. Good morning, everyone. This is Luis Santos for Patrick. Congratulations on the promising data. Our questions are more on the data that you gathered or plan to gather on the symptom improvements, quality of life improvements. If you can share any color on that or the plans to gather that kind of data. The second question would be more, would the six-week dosing regimen fit the Medicare Part B coverage plan, or would that be under a different kind of coverage? Thank you so much. Yeah. So I'll answer the first question. So the first question was around the evaluation of impact on symptoms, and we are capturing that. So it's too early yet. We'll have a look at that data once the study is complete, and we'll certainly want to continue to evaluate that in the phase 2 and 3 portion of the development program. Necessarily, it's important to evaluate a benefit or an impact, at least, on the symptom burden of these patients. So we'll be measuring that. And on the issue around how the drug is going to be used, right now in our clinical program, it's a vial and syringe. So it's too early to determine the commercial presentation and the consequences of that around payment right now. Great. Thank you. Thank you. We will now take our next question. And the next question comes from the line of Sarah Schram from William Blair. Please go ahead. Your line is now open. Hi. You've got Sarah on from Myles. Thanks for taking the question. So yeah, just any comments that you can give us on the degree and the kinetics of the TMPRSS6 knockdown between the doses and how this compares to what you guys have seen in the prior phase 1 studies? And then I have a quick follow-up as well. Yeah. We're not measuring that here. As you know, in a preclinical, we showed a very robust suppression of TMPRSS6. I think the important thing is we're seeing the association of the pharmacology on the clinical outcomes, both hematocrit maintenance or reduction in hematocrit, depending on the level that you start with, as well as the impact on phlebotomy rate. Got it. Makes sense. And then have you guys seen any potential signals of iron overload with the increased ferritin, or is this something that you could envision as a concern with continued dosing if that ferritin continues to increase? Thanks. Yeah. No, we certainly have not. Keep in mind, most of these patients are iron deficient when they enter the study. That's compounded by the need for frequent phlebotomies. So what we're seeing is an improvement in their iron status, but I don't think we're concerned about iron overload. Got it. Thank you. Congrats on the data. Thank you very much. Thank you. As there are no further questions, I would now like to hand over to Craig Tooman for any closing remarks. Thank you. I'd just like to thank one more time the Silence Therapeutics team that has and will continue to contribute to the ongoing effort to advance what appears to be a very promising development candidate. Also to all the patients and clinical sites that are participating in this study. We can't advance innovations without the participation of patients and healthcare providers, so we appreciate that greatly. Thank you all, and we're happy to take individual questions later. You can reach out to Gem, and we look forward to presenting the full data set at a research meeting later this year. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect. Speakers, please stand by.