Good day, and thank you for standing by. Welcome to the Silence Therapeutics 2023 full-year results webcast and conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there'll be a question-and-answer session. To ask a question during the session, you will need to press star one and one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one and one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to our first speaker today, Gem Hopkins. Please go ahead. Good morning and good afternoon, everyone. Thank you for joining us today. My name is Gem Hopkins, Vice President of Investor Relations and Corporate Communications at Silence. Joining me on today's call are Craig Tooman, our President and CEO, who will provide an update on the business, Rhonda Hellums, our Chief Financial Officer, who will review our financial performance, and Steven Romano, our Head of R&D, who will provide an update on our clinical programs. For those of you participating via conference call, the accompanying slides can be accessed by going to the Investors section of our corporate website at www.silence-therapeutics.com. Turning to slide two, I'd like to remind you that during today's call, management will make projections or other forward-looking statements regarding anticipated future events or the future financial performance of the company, including clinical development, timing, and objectives of therapeutic potential of our product candidates, our operational plans and strategies, anticipated milestone payments, anticipated operating and capital expenditures, business prospects, and projected cash runway. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent annual report on file with the SEC. In addition, any forward-looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as any subsequent date. We specifically disclaim any obligation to update such statements. With that, I'd like to turn the call over to Craig. Craig? Thank you, Gem, and welcome, everyone. Thank you for joining us today. 2023 was a year of strong execution across Silence and setting ourselves up for what we anticipate being a very data-rich year in 2024. In fact, we were very pleased to announce just this morning positive top-line phase II data for zerlasiran in patients with high Lp(a) levels, which we will discuss more in a moment. But first, I want to remind everyone what we accomplished in 2023. While this was clearly a challenging year in the broader market, I'm very proud of our team's relentless focus and commitment to deliver on our promises to both our shareholders and our patients. We remained very focused on the fundamentals of the company, and that is clearly bearing fruit today. Looking back over the year, we completed enrollment in our zerlasiran phase II program for high Lp(a) in just four months, highlighting the unmet need and growing excitement from the medical community for zerlasiran. We also reported positive multiple-dose data from the APOLLO study in patients with ASCVD and high Lp(a). You'll recall we saw significant Lp(a) reductions of up to 99%, which was durable out to 201 days. In addition to zerlasiran, we made great progress advancing SLN124, or divesiran, in the clinic for polycythemia vera, or PV. This is an area that we think siRNA and divesiran are particularly well-suited to address. The ongoing phase I study is open-label, and the emerging data continue to look promising. During the year, we also continued to execute across our partner portfolio, achieving $14 million in milestones between our AstraZeneca and Hansoh collaborations. We are particularly pleased that we now have a clinical program with AstraZeneca. While 2023 was primarily focused on advancing our clinical programs, we did not lose sight of the fact that we are increasingly being understood as a platform company. While we have been focusing our efforts on our clinical successes, we also made very strategic investments in early-stage projects where we see clear opportunity to either be first-in-class or best-in-class in areas of high unmet need. The buyback of our complement assets from Mallinckrodt is a great example of that. Our GOLD platform is advancing results across multiple programs, and that's driving strong new partnership interest. Partnering has always been a key facet of our business and an area we expect will continue to evolve considerably. Turning to our 2024 key strategic priorities, we've already made great strides against each pillar so far this year, starting with our lead proprietary clinical programs and zerlasiran for high Lp(a). As I mentioned, today we reported positive top-line 36-week data from the ongoing phase II study in patients with high Lp(a). Steve will discuss this in more detail, but in summary, Lp(a) reductions were consistent with phase I results and support a competitive profile for zerlasiran to potentially address the needs of up to 1.4 billion people worldwide living with Lp(a). Phase III planning activities are well underway to ensure we fully maximize the potential of this high-value asset and are well-positioned to bring it to patients as soon as possible. We are equally excited about the ongoing divesiran PV study. As I mentioned, the phase I study is open-label, and the emerging data look promising. Our team has done an excellent job enrolling and overseeing this trial, and we are on track to report data by June of this year. On the partnering side, as I mentioned, we were very pleased to enter the clinic with the first product candidate under our AstraZeneca collaboration in February, triggering the $10 million milestone payment to us. This is another great example of the productivity of our GOLD platform and how synergies with great partners can create unique development opportunities. Beyond our current clinical programs, we are committed to advancing and expanding our proprietary pipeline. Here's a look at our proprietary pipeline. In addition to the zerlasiran and divesiran programs, we have the two complement assets, two undisclosed targets that we're working on with Hansoh that are wholly owned to us outside the China region, and several other undisclosed programs. Silence has always been a platform company. We've been in the siRNA arena for over two decades and have developed extensive know-how and IP. We are starting to see the fruits of that labor and the potential for our platform to produce a pipeline of differentiated programs with zerlasiran and divesiran clinical profiles now emerging. We believe we are at the early stages of what we can do with this technology platform. We have generated encouraging preclinical data across other portfolio programs that we look forward to talking more about as they get closer to the clinic. Importantly, underpinning all of this is a strong balance sheet following the $120 million PIPE financing we completed in February. With that, I'll turn the call to Rhonda for a review of our financials. Thank you, Craig. For the year ended December 31st, 2023, the company recorded GBP 25.4 million in revenue versus GBP 17.5 million in 2022. The increase of GBP 7.9 million was primarily driven by the advancement of targets in our partner programs. As a reminder, we record revenue from our collaborations based on the percentage of contract completion. As Craig mentioned, our AstraZeneca collaboration continues to advance nicely. In 2023, AstraZeneca nominated the first product candidate, and we received a $10 million option fee. In February of this year, that candidate entered the clinic, and we will receive another $10 million milestone. We also advanced our three Hansoh targets and achieved $4 million in development milestones from two of those programs in 2023. Under our Mallinckrodt collaboration, you will recall we reacquired two of the preclinical complement assets last March. As a result, we recognized a GBP 8 million cumulative catch-up adjustment to revenue when the contract modification was complete for the unrecognized revenue for those two assets. This month, Mallinckrodt notified us that they will not pursue further development of SLN501 following the completion of the phase I study. This will conclude all activities and commitments under the Mallinckrodt collaboration. Any remaining unrecognized revenue under this collaboration will be recorded in the first quarter of 2024. Finally, during 2023, we recorded approximately GBP 569,000 in royalty revenue from Alnylam. The expenses related to our partner programs, including the portion of our employees' time dedicated to these programs, are recorded as cost of sale as these are attributable to the revenues. These expenses were GBP 10.3 million in 2023. As expected, R&D costs rose in 2023 to GBP 44 million versus GBP 35.6 million in 2022. This increase was primarily due to advancing our proprietary zerlasiran and divesiran programs. We also strategically invest in further development of our platform and identify new targets to further expand our proprietary pipeline. General and administrative costs were GBP 20.6 million in 2023 versus GBP 19.6 million in 2022. The increase was primarily a result of non-cash share-based expenses related to the granting of employee share options. We continue to be prudent in our spending. The company's net loss for the full year of 2023 was GBP 43.3 million versus a net loss of GBP 40.5 million in 2022. The small increase in our net loss is due to the increase in R&D as a result of advancing our programs and clinical development. The company's cash and cash equivalents were GBP 54 million or approximately $68.8 million at the end of December 2023. As Craig mentioned, we were pleased to announce in February an oversubscribed private placement of approximately 5.7 million ADSs at $21 per ADS, resulting in gross proceeds of $120 million. We are delighted to have expanded our shareholder base with this group of top-tier biotech investors. We also raised an additional $20 million in proceeds in January of 2024 from sales of our ADSs under our ATM. Together with our cash at December 31st, we have significantly increased our cash balance in early 2024 to over $200 million. Further, as our collaborations continue to advance, we anticipate that we will achieve additional milestones. As mentioned earlier, we have already achieved $10 million in early 2024. We estimate that our cash will now extend our runway into 2026. We continue to be committed to responsibly investing in initiatives that will advance our pipeline and expand our platform in new targets. We also continue to evaluate additional partnering opportunities that could provide additional non-dilutive funding and further extend our cash runway. With that, I will turn the call over to Steve for a clinical update. Steve? Thanks, Rhonda. As Craig mentioned, we were pleased to announce this morning positive top-line 36-week data from the ALPACAR-360 phase II study of zerlasiran in patients with high Lp(a). Zerlasiran has demonstrated a consistent clinical profile that we believe is ideal for advancing into phase III and eventually for treating patients living with high levels of Lp(a). Just a quick reminder for those of you less familiar with Lp(a), this is a key cardiovascular risk factor that is almost entirely genetically determined. This means that unlike other cardiac risk factors, Lp(a) can't be modified by diet or exercise. Your level of Lp(a) is the same at age five as it is at age 45. High Lp(a) is considered to affect around 20% of the world's population. It's associated with a high risk of heart attack, stroke, and aortic stenosis. You need pharmacological intervention to manage high Lp(a). There are currently no approved therapies that selectively lower Lp(a). Clearly, this is a major unmet need in cardiovascular disease and why we're so excited about the potential for zerlasiran. Fortunately, the recognition of Lp(a) as a key cardiovascular risk factor is growing rapidly. Major societies are now including Lp(a) in their testing guidelines. We expect awareness to grow even more in the coming years, particularly as new therapies become available. Now turning to our zerlasiran clinical program. First, I want to remind you what we saw in APOLLO phase I program. In the single-dose study, we evaluated healthy volunteers with high Lp(a) greater than or equal to 150 nmol/L. Here, we saw Lp(a) reductions up to 98% following a single dose with effects persisting over a 5-month period. Very effective, durable, and well-tolerated. In the multiple-dose study, we evaluated ASCVD patients with high Lp(a) and saw Lp(a) reductions up to 99% following repeated doses with effects persisting at 201 days. Again, very effective, durable, and well-tolerated. The multiple-dose study also showed we can achieve substantial Lp(a) reduction at the 300 mg and 450 mg doses. We don't need the 600 mg dose we explored in the single-dose study. Turning to the ongoing ALPACAR-360 phase II study and the positive 36-week top-line data we reported this morning. As a reminder, the study enrolled 178 subjects with baseline Lp(a) levels at or over 125 nmol/L at high risk of ASCVD events. Zerlasiran was administered at 300 mg subcutaneously every 16 or 24 weeks and 450 mg every 24 weeks to patients with a median baseline Lp(a) of approximately 215 nmol/L. I want to emphasize that today we are only looking at 36-week data for the primary endpoint. As designed, this is a 60-week study that's still ongoing. Secondary endpoints, including change in Lp(a) from baseline to week 48, week 60, and potential effects on other lipids and lipoproteins, are still being evaluated. Today, we're pleased to report the study met its primary endpoint and demonstrated a highly significant reduction from baseline in Lp(a) compared to placebo at week 36. Median percentage reduction in Lp(a) of 90% or greater were observed for both doses at week 36. No new safety concerns were identified during this treatment period. Zerlasiran continues to be very well-tolerated. These preliminary data support at least quarterly dosing and potentially longer. We need to review the 48-week data and updated modeling before we confirm dosing regimen for phase III. Bottom line, we're very excited about the emerging phase II data, which are consistent with phase I results, and continue to support a competitive profile for treating patients with high Lp(a). We look forward to reviewing the 48-week data expected in the second quarter of this year. Turning to divesiran, our second wholly owned siRNA for hematological disorders. What we really like about this program is we're targeting a pathway that's central to the production of hepcidin, the master regulator of iron in the body. Divesiran works by silencing TMPRSS6, a negative regulator of hepcidin, to modulate endogenous hepcidin. This has a range of potential therapeutic benefits. We've demonstrated proof of mechanism in healthy volunteers and are currently focused on polycythemia vera. Polycythemia vera is a rare blood disorder with significant unmet needs. PV affects around 150,000 people in the U.S. and around 3.5 million people worldwide. Elevated hematocrit is a hallmark of the disease. The treatment goal is to maintain hematocrit levels at less than 45% to reduce cardiovascular and major thrombotic events. Patients with hematocrits between 45%-50% are four times more likely to die from cardiovascular causes or major thrombotic events. Phlebotomy is the current standard of care. This is burdensome, and most patients are iron-deficient at diagnosis. Repeated phlebotomy exacerbates this. Cytoreductive therapies are also used but may not be effective at reaching control and can be associated with significant adverse events. In PV, divesiran is designed to inhibit TMPRSS6 expression to raise hepcidin and reduce iron delivery to the bone marrow. Iron restriction reduces erythropoiesis, resulting in lower red blood cell production. As I mentioned, we showed proof of mechanism in healthy volunteers. In this study, divesiran increased hepcidin up to fourfold and reduced serum iron by about 50% after a single dose. The effects persisted for at least two months, which was the study period, and divesiran was well-tolerated. As Craig mentioned, we were pleased to kick off the SANRECO phase I/II PV study last January and have made great progress with enrollment throughout the year. This is a two-part study. We're currently in the phase I open-label study, and that will be followed by a phase II study. In the phase I study, we are testing divesiran in a wide range of PV patients, including those with high baseline hematocrit as well as those who are well-controlled. Remember, this is a phase I study, so the goal here is to learn as much as possible about dosing and therapeutic effect. All patients entered in the study are phlebotomy dependent. The nice thing about this program is even in phase I, we're looking at well-defined clinical outcomes, including the maintenance of hematocrit and the number of phlebotomies. Since this is an open-label study, we can see the data, and as Craig mentioned, the emerging data are encouraging. We look forward to presenting these data publicly sometime before the end of June. As a reminder, divesiran has FDA fast track and orphan drug designations for PV. With that, I'll turn the call back over to Craig. Craig? Thanks, Steve. 2023 was all about execution, and the Silence team delivered on all fronts. 2024 is poised to be an exciting year for our proprietary clinical programs. This morning, we announced positive top-line 36-week data from the phase II study of zerlasiran in patients with high Lp(a), and we expect 48-week data in Q2 followed by 60-week data in Q4. We remain on track to report PV data with divesiran by June. We see substantial potential for our mRNAi GOLD platform across a range of genetic diseases and look forward to communicating more as we move ahead. I'd like to thank everyone for listening today, and I'll pass back over to the operator for your questions. Thank you. To ask a question, 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. Once again, if you'd like to ask a question, please press star one and one on your telephone. We will now go to your first question. One moment, please. Your first question comes from the line of Mike Ulz from Morgan Stanley. Please go ahead. Hey, guys. Thanks for taking the question, and congratulations on the data. Maybe just a question related to the data. If you could provide maybe additional color on the curves, potentially, between the two doses. Just curious if one stands out relative to the other. And then maybe, Steve, you also mentioned waiting for the 48-week results to sort of decide which dose to go forward with. What kind of criteria will you be looking for there in those data? Thanks. Steve? Yeah. Thank you for the question, Mike. First of all, let's just remember what we're presenting here is the primary outcome measure, which was a time average change from baseline. That's the reference to a very significant change. We're not sharing the details of that because this is a rather novel endpoint, and I don't believe any other companies in this space have yet revealed data with regards to this endpoint. We're going to preserve that for an upcoming research meeting later this year. What we did share was the median change from baseline at week 36. But remember, at week 36, we're between intervals. Remember, we're testing two dose ranges here. We're testing 300 mg and 450 mg, but we're testing them at 16 weeks and 24 weeks. That 36-week time point, which is the primary point for evaluating the time average change, is in between intervals. This is why we need to wait to see 48-week data as well. Now, what I can say very clearly, and remember, I've talked to many of you about this before, we are going to look at all of the data from our single ascending, our multiple dose data, and the ongoing phase II data to update our PK and PD modeling in order to make sure we make the best choice going forward to the phase III. I can't really tell you too much more about the differences between the lines, as you were suggesting. We'll preserve that information for a research meeting, and we'll get greater confirmation of our dose and range later this year. We are confident that 300 mg is a well-supported dose, and it's unlikely we'll require a dose above that. Got it. That's very helpful. Thank you and congratulations again. Thanks, Mike. Thank you. We will now go to the next question. Your next question comes from the line of Kostas Biliouris from BMO Capital Markets. Please go ahead. Good morning, everyone. Thanks for taking our question, and congrats on the very strong data. A couple of questions from us. One on the Lp(a) and one on the PV program. On the Lp(a) program, maybe any new information that these data provide compared to the previous one that can help you better inform the phase three design. And then on the PV side, a two-fold question. In the press release, you mentioned that the PV data continue to look promising. Any additional color around the parameters that you may be referring to here? And then given the activity that we see in the PV space with the recent Takeda Protagonist partnership, any thoughts around the potential partnership for the PV program? Thank you very much and congrats again. Thank you, Kostas. Let me just say that the amazing thing about this technology is how consistent it is, and it's been very consistent, as Steve mentioned, across the phase I, multiple dose and single dose, and now the phase II. So while we are gleaning new insights from the intervals and also the doses, it has been very, very consistent, and Steve already expounded on that. In terms of PV, we are aware of the endpoints that others have studied in this arena, and we've looked at it very closely. Our categorization of our data looking very good is with that in mind. Steve, I'll hand over to you. Yeah, sure, Craig. And thank you, Kostas, for the questions. So maybe I'll start with PV since it's top of mind. Yeah. So when we say it's looking promising, it's because in this study, we are actually evaluating relevant clinical outcomes. Now, it's observational, so we're not doing inferential stats because it's phase one. But what we can look at is the number of phlebotomies as well as the maintenance of hematocrit. So we're looking at both of those. So when we say it continues to look good, it's because we're looking at those two indicators of efficacy. So we really look forward to sharing that data more fully over the next few months. Again, with regards to the dosing of the Lp(a), remember, you see, we didn't test directly in this trial 12-week intervals. And that's important because, as I've said before, and I'll repeat it because I think it's really important, we're going to look across the single, multiple dose, and the data we're getting from the phase II, which is looking at 16 and 24 weeks, which brackets the range across a broad array of dosing intervals and choose the best one. So we really need to update our PK/PD modeling, which we'll do with the 36-week data, and we'll continue to do that with the 48-week data. But we want to see, since we've given this dose relatively infrequent, Q16 and Q24, that 48-week data will be important as we progress to a confirmation of a specific dose and, more importantly, an interval that we'll choose going into phase III. Maybe just a quick comment on partnering for PV. We are a company that likes partnering very much. Our proprietary programs are obviously exhibiting just excellent data, but we continue to look at partnerships, new and current partnerships, and are very happy with the way those are also playing out. PV is an area that Silence ourselves could pursue, we believe, in the chassis that we have and that we can build. But to be honest, there are also companies and parties that are very interested in partnering with us as well. So as part of the portfolio, we'll continue to look at that mix. Thank you. Very helpful. Thank you. We'll now go to the next question. Your next question comes from the line of Patrick Trucchio from H.C. Wainwright. Please go ahead. Thanks. Good morning and congrats on the data today. Just a couple of follow-up questions from me. The first is, as we look ahead to a potential phase three program for zerlasiran, can you tell us how you would intend to move this program forward? Would you look to do this on your own or maybe find a collaboration partner ahead of phase three? And separately, do you need to wait for the 48-week data or the longer-term data, or can a potential partner go ahead with an end-of-phase II meeting with the FDA before then? And then separately, just on SLN501, I'm wondering why Mallinckrodt decided not to move ahead with the program. Something about the data, or was this a strategic decision? And more broadly, can you discuss your strategy with moving a complement program forward? So let me start in reverse order of SLN501. As you know, and we announced today, yes, Mallinckrodt did let us know that they'll not be pursuing that. You'll recall that we actually bought back the two preclinical assets last year that we believe were the best fit for Silence. We saw the preclinical data and liked that very much. It's always been a kind of a portfolio view for us. Steve, you've been at Mallinckrodt and are now with us. You've been on both sides and kind of spearheaded that complement. Maybe you have a comment on that portfolio view. Yeah. Well, only that. We, as you know, brought back two preclinical assets, the data of which are very, very good. So the bottom line is we've always looked at this as a portfolio opportunity, even as we brought those two new assets back in-house. The C3 areas, I'll speak for ourselves as Silence. The C3 area is a complex area. It's very competitive. We feel like the additional targets, which we've not disclosed, may actually give us a more competitive opportunity to be competitive in that space. And we are actually evaluating, as we move forward in the preclinical and non-clinical development space, considerations for clinical targets with those, which we'll disclose over time. In terms of the phase III for zerlasiran, I want to tell you and be clear that we're full steam ahead. We've been planning this protocol for over a year. This is something that we've tested with KOLs, with our great development team, and also some external advisors. So we feel like we're in very, very good shape in terms of the planning for that. In terms of the funding for that, Rhonda, maybe you just want to touch on that. And then Steve, maybe you want to touch on your conviction of the protocol as well. Yep. Yeah, sure. Thanks, Craig. Yes. So of course, with the raise that we did in the beginning of this year, we are anticipating that we have the ability to continue to move that forward. As Craig mentioned earlier, we are actively looking at different partnerships. So we have been very open about looking at partnerships for this program specifically, but also other programs as well. So we feel like we have the resources we need to continue to advance this program so that we can keep this momentum moving. Yeah. And I'll just add, as Craig suggested, just a couple of comments. We are well advanced with regards to the design of the phase III protocol. And as I've talked to many of you about, we've got great input by leading experts, renowned experts in the field of lipidology as well as clinical trialists, etc. So we feel very confident. In fact, that's where we really feel the opportunity could be to distinguish our compound from others that are currently advanced into phase III. The types of patients we include, some of the specific criteria for inclusion and exclusion, the ability for that data potentially to read through to the label. So we're thinking very, very robustly about how best to position our phase III program. But that's advancing very nicely. And we will move. I think someone had asked this as well, and I didn't reference it. We will move into a phase into a discussion with the agency. We'll have that 48-week data at that time point because I think that is an important piece of information to help confirm our dosing strategy going forward as well as the final design of the trial. We feel very good about the progression we've made and the opportunity to differentiate in that way. Terrific. That's so helpful. Thank you very much and congrats again. You're welcome. Thank you. Thank you. We will now go to the next question. Your next question comes from the line of Miles Minter from William Blair. Please go ahead. Hi. You've got Sarah on from Miles. Congrats on the data, and thanks for taking some questions. So from us, can you guys comment on how many patients in each dose group achieved Lp(a) levels below kind of that 120 nmol/L and 72 nmol/L thresholds associated with cardiovascular disease risk? And then just a quick clarification on SLN501. Would you guys look to reacquire those rights back from Mallinckrodt like you guys have done with some of those other assets, or do you guys kind of feel like you're good on the complement targeting assets at the moment with what you've currently got? Thanks. So let me again go in reverse order and just say for 501, again, from that portfolio review that we took upon ourselves before we brought the two assets in, we really like those for the size of Silence and the competitive arena that it is in and made that determination when we brought those two in-house. So no further expectation on that. And Steve, in terms of the segregation of data, not sure quite what we can say without query, but up to you. Yeah. No, unfortunately, we can't share that information yet. We'll certainly need to preserve some of those details, obviously, for a presentation at a research meeting, which we'll do later on this year, hopefully by the end of summer. So we'll share that information in much more detail over the coming months. Makes sense. Thank you. Thanks, Sarah. Thank you. Once again, as a reminder, if you would like to ask a question, please press star 1 and 1 on your telephone keypad. We will now go to the next question. Your next question comes from the line of Keay Nakae from Chardan. Please go ahead. Yes. Thanks. So in terms of the scientific meeting to present the data, should we guess that could be ESC? Yeah. That would be a reasonable expectation. So we'll confirm that in the nearer future. Okay. Great. And then when we think about the guidance on the runway into 2026, what does that include in terms of commencing a phase three? Rhonda? Yes. Hi. So that does assume that we would kick that off, and we would continue to prep for that. Again, that does include some of our current collaboration programs. We do anticipate some additional milestones from that, so that is included in our runway as well. And again, we continue to look for any partnering opportunities that will, of course, extend that runway further with the non-dilutive funding first. But that does assume that we would kick off a phase III. Okay. All right. Very good. Thank you. Thank you. Thank you. There are currently no further questions. I will hand the call back to Craig for closing remarks. Well, thank you all for joining us on this call. I'm extremely proud of our 2023 performance and overall results. As I mentioned at the beginning of this call, 2023 set us up for what we expect to be a very data-rich year. With that, building recognition of Silence as a true platform company, we look forward to keeping you updated on our progress. Thank you and have a great day. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.