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 speakers' presentation, there will be a question-and-answer session. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to turn the conference over to your 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 2, 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, the 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 of 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's 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 2 data for zerlasiran in patients with high Lp(a)(a), 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 remain 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 2 program for high Lp(a)(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)(a). You'll recall we saw significant Lp(a)(a) reductions of up to 99%, which was durable up 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 1 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…

Thank you, Craig. For the year ended December 31, 2023, the company recorded GBP25.4 million in revenue versus GBP17.5 million in 2022. The increase of GBP7.9 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 to 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 an GBP8 million cumulative catch up adjustments to revenue when the contract modification was complete with 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 1 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 GBP569,000 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 sales as these are attributable to the revenues. These expenses were GBP10.3 million in 2023. As expected, R&D costs rose in 2023 to GBP44 million versus GBP35.6 million in 2022. This increase was primarily due to advancing our proprietary zerlasiran and divesiran programs. We also strategically invest in further development…

Thanks, Rhonda. As Craig mentioned, we were pleased to announce this morning positive top line 36 week data from the ALPACAR-360 Phase 2 study of zerlasiran in patients with high Lp(a)(a). Zerlasiran has demonstrated a consistent clinical profile that we believe is ideal for advancing into Phase 3 and eventually for treating patients living with high levels of Lp(a)(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 nanomoles per liter. Here we saw Lp(a) reductions up to 98% following a single dose with effects persisting over a five month period, very effective, durable and well tolerated. In the multiple dose study, we evaluated ASCVD patients with high Lp(a)…

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 2 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 mRNA 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. [Operator Instructions] And 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?

Yes. So 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. So 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. So we're going to preserve that for a upcoming research meeting later in this year. What we did share was the median change from baseline at week 36. But remember at week 36, we're between intervals. So remember, we're testing a dose ranges here. We're testing 300 and 450, but we're testing them at 16 weeks and 24 weeks. So that 36 week time point, which is the primary point for evaluating the time average change is in between intervals. And 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 2 data to update our PK and PD modeling in order to make sure we make the best choice going forward to the Phase 3. So 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 research meeting and we'll get greater confirmation of our dose and range later this year. We are confident that 300 milligrams is a well-supported dose and it's unlikely we will require a dose above that.

Got it. That's very helpful. Thank you and congratulations again.

Thanks, Ulz.

Thank you. We will now go to the next question. And 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 3 design? And then on the PV side, a twofold question. In the press release, you mentioned that the PV data continued 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 [indiscernible] 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 1 multiple dose and single dose and now the Phase 2. So, while we are gleaning new insights from the intervals, and also the doses, it has been very, very consistent. And Steve, I'll let you expound 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 and our categorization of our data looking very good is with that in mind. Steve, I'll hand over to you.

Yes, sure, Craig. And thank you, Kostas for the questions. So maybe I'll start with PV since it's top of mind. Yes, 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 1, 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 2, which is looking at 16 weeks 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 to 16 and to 24, 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 3.

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 in 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. And 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 3 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 3? And separately, do you need to wait for the 48 week data or the longer term data, or can you -- or a potential partner go ahead with end of Phase 2 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. And 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 like 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 compliment. Maybe you have a comment on that portfolio view.

Yes. 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 -- those two assets back in-house. The [C3] (ph) areas, I'll speak for ourselves at Silence. The C3 areas are 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 nonclinical development space, considerations for clinical targets with those, which we'll disclose over time.

In terms of the Phase 3 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.

Yes.

Yes, sure. Thanks, Craig. Yes, so we, 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.

Yes, 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 3 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, etcetera. 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 advance into Phase 3. 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 3 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, but we will move into a phase -- into a discussion with the agency and we'll wait -- 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. So 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.

Thank you.

Thank you. We'll now go to the next question. And your next question comes from the line of Myles Minter from William Blair & Company. Please go ahead.

Hi. You've got Sarah on for Myles. Congrats on the data. And thanks for taking the question. So, from us, can you guys comment on how many patients in each dose group achieved Lp(a) levels below kind of that 120 nanomole per liter and 72 nanomole per liter threshold 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 data, not sure quite what we can say without query, but up to you.

Yes. No, unfortunately, we can't share that information yet. We'll certainly -- we 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.

Excellent. Thank you.

Thanks, Sarah.

Thank you. [Operator Instructions] And 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 EFC?

Yes, that would be a reasonable expectation. So we'll confirm that in the near 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 3?

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 3.

Okay. Alright. 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. And 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.