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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 Chief R&D Officer, who will provide a clinical update. 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. 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 and any future filings. 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 thanks everyone for joining today’s webcast. I’m pleased to be with you today to discuss our 2024 full year performance and share some color on what’s ahead for the company. I’ll start by quickly touching on a few key highlights about our full year performance. Starting with zerlasiran, our siRNA for high Lp(a). The ALPACAR-360 Phase 2 study of zerlasiran in ASCVD patients with high Lp(a) delivered positive results that were featured in a late-breaker at AHA and published in JAMA. The study showed Lp(a) reductions exceeded 90%, effects were durable and zerlasiran was observed to be well tolerated. These data support a competitive profile that we believe can be further defined in Phase 3. The Silence team supported by top cardiologists have done an outstanding job designing what we are confident is a highly differentiated Phase 3 program for zerlasiran. We recently met with global regulatory agencies on the design and received very positive feedback across the board. The Silence team has also been successfully executing on core readiness activities for Phase 3 development, including manufacturing readiness. Turning to divesiran, our first-in-class siRNA for polycythemia vera. The SANRECO’s Phase 1 study of divesiran delivered positive results that exceeded our expectations. Data were highlighted at ASH and showed divesiran completely eliminated the need for phlebotomy in all well-controlled patients. The safety and tolerability profile continues to look very favorable. In addition, we started dosing patients in the SANRECO Phase 2 study and the European Commission granted divesiran Orphan Drug Designation for PV. As a reminder, divesiran also has FDA Fast Track and Orphan Drug Designations for PV. In terms of other pipeline advancements, we are pleased to have our third siRNA from our GOLD platform entered the clinic in 2024 under our AstraZeneca collaboration. We value this partnership very much and are proud of the program we were able to advance together. We look forward to its further progress and the potential to earn additional milestones. We also progressed several preclinical siRNA candidates for hepatic targets. Turning to Slide 5 and what’s next for our company. This morning, we announced that in 2025, we are prioritizing investment in programs targeting rare conditions where we believe we can deliver on clear unmet needs with first-in-class and/or best-in-class siRNAs. Divesiran is a great example of that. We remain confident in our zerlasiran program for high Lp(a) and believe we have very differentiated design for our Phase 3 program. However, today, we are making clear that we will only initiate the Phase 3 outcomes study once a partner is secured. This strengthens our cash position into 2027 and gives us flexibility to invest in our innovative pipeline, while we continue partnering discussions for zerlasiran. We have listened very carefully to our shareholders and made this decision with their collective feedback in mind. I want to reiterate that we continue to believe strongly in zerlasiran’s potential. There are very few cardiovascular assets in development that aim to treat an unmet medical condition as large as the Lp(a) opportunity. We are hopeful we will secure the right partner to bring this very promising program forward. Until a partner is secured, we do not plan to provide any further updates. Turning now to divesiran. We announced this morning that we completed follow-up in the Phase 1 portion of SANRECO this month and look forward to presenting more data from that study at medical meetings this year. The outstanding data from the SANRECO Phase 1 study have generated a lot of excitement from the medical community and patients who want to be involved with the program. In fact, we also announced this morning that we anticipate full enrollment in the SANRECO Phase 2 study by the end of this year. While we are currently focused on the PV indication for divesiran, we continue to believe it has broader therapeutic potential. Given the outstanding PV results we have seen in Phase 1, we are planning an investor event later this year and look forward to discussing the program in more detail then. In addition to divesiran, we were pleased to announce today that we plan to start a Phase 1 study of SLN548, our wholly-owned siRNA targeting complement factor B in the second half of this year. Steve will go into a bit more detail on this in a few minutes. In terms of what’s next for our GOLD platform, we have multiple undisclosed programs that have generated encouraging preclinical data. This includes the three targets that we’ve retained global rights to following the conclusion of the Hansoh Pharma collaboration we announced this morning. We are evaluating these programs as part of our broader portfolio and we’ll determine which ones we want to bring forward ourselves or potentially partner. As I mentioned, we will be prioritizing targets in rare conditions where we believe we can deliver valuable competitive profiles to address patient needs. In addition, we plan to invest selectively in our extrahepatic work where we are seeing promising early data from programs targeting multiple cell types. We look forward to sharing more as we move ahead and these data mature. With that, I will now turn the call over to Rhonda to review our 2024 financial performance and guidance for 2025. Rhonda?

Thank you, Craig. First, I would like to point out that effective January 1, 2025 Silence has transitioned from a foreign private issuer to a U.S. domestic issuer, which requires us to comply with the U.S. domestic reporting requirements under the Exchange Act. We are now required to file periodic reports and registration statements on U.S. domestic issuer forms with the SEC in accordance with U.S. GAAP as opposed to IFRS and in U.S. dollars versus British pound. Now let me turn to the financials. For the year ended December 31, 2024, the company recorded $43.3 million in revenues versus $31.6 million in 2023. The increase of $11.7 million is largely due to the collaboration arrangements we have entered for development of candidates utilizing our siRNA platform. As Craig mentioned, our AstraZeneca collaboration continues to advance nicely and we are hopeful that this program will continue to move forward and allow us to receive additional milestones. Turning to the Hansoh Pharma collaboration, we announced this morning that Hansoh opted not to pursue further development under our collaboration. As a reminder, this was a collaboration to develop siRNAs using our GOLD platform for three undisclosed preclinical liver targets. Hansoh formerly had options to license China region rights on two of the targets and global rights on the third target. As a reminder, we record revenue from our collaborations based on percentage of contract completion. Therefore, in 2024, we recognized $24.6 million resulting from a cumulative catch-up following the completion of all required obligations to Hansoh under the collaboration. Finally, during 2024, we recorded the remaining royalty revenue from Alnylam of approximately $144,000. 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 they are attributable to the revenues. These expenses were $11.8 million in 2024 compared to $12.9 million in 2023. As expected, R&D costs rose in 2024 to $67.9 million versus $56.9 million in 2023. This increase was primarily due to advancing our proprietary zerlasiran and divesiran programs, which Craig previously mentioned. We also strategically invested in further development of our platform and identifying new targets to further expand our proprietary pipeline. General and administrative costs were $26.9 million in 2024 versus $26.2 million in 2023. The increase was primarily as a result of additional legal and accounting expenses required to transition to filing as a U.S. domestic issuer, including our transition to U.S. GAAP. The company’s net operating loss for the full year of 2024 was approximately $63.3 million versus $64.4 million in 2023. The decrease in our net loss is due to the increase in revenue, partially offset by the increase in R&D costs as a result of advancing our programs in clinical development. We reported other income of approximately $4.5 million, which largely represents the accretion of our U.S. treasury bill compared to $1.8 million in 2023. We also reported approximately $13.7 million from the benefit of our R&D tax credit in the UK compared to $11.9 million in 2023. The company’s net loss for the full year of 2024 was approximately $45.3 million versus $54.2 million in 2023. The company’s cash, cash equivalents and short-term investments were $147.3 million at the end of December of 2024. This includes cash and cash equivalents of $121.3 million and short-term investments of $26 million. Turning to Slide 8 and the 2025 cash guidance. As Craig mentioned, we have made the decision only to initiate the zerlasiran Phase 3 outcomes study once we have secured a partner. This allows us to extend our projected runway into 2027. I’ll echo Craig’s comments that we are prioritizing programs targeting rare conditions where we see the opportunity to deliver on clear unmet needs with innovative siRNA therapies. This includes divesiran for PD, which remains a top priority. In addition, we look forward to advancing additional programs in our pipeline, including our extrahepatic work. With that, I’ll turn the call over to Steve for a clinical update. Steve?

Thanks, Rhonda. As Craig mentioned, we made great progress advancing divesiran, a first-in-class siRNA for PV in 2024. The SANRECO Phase 1 results were impressive and have garnered enthusiasm from the program. The Phase 2 study is enrolling very nicely. And as Craig mentioned, we anticipate full enrollment by the end of this year. 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 acute myeloid leukemia. PV impacts around 150,000 individuals in the U.S. 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 along with a 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. At the bottom of this slide, we have a quote from Nona, who is living with PV. She says, the PV aspect means that you have to have phlebotomies regularly. And I think the most crippling thing about that is the fatigue. We are hopeful based on the SANRECO Phase 1 data that divesiran has the potential to greatly reduce and even eliminate the need for phlebotomy. Turning to Slide 12 and divesiran, a first-in-class siRNA for PV, I’ll quickly review how divesiran works for those less familiar. 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. Turning to the SANRECO Phase 1 study. The design was open label with 3 cohorts and enrolled 21 PV patients. We tested doses of 3, 6 and 9 milligrams per kilogram, consisting of 6, 8 and 7 patients respectively. All patients were scheduled to receive 4 doses at 6-week intervals and then were followed for 16 additional weeks for a combined total of 34 weeks of treatment and follow-up. Key inclusion criteria for the trial subjects included 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 were allowed. And given the exploratory nature of the Phase 1 study, both well-controlled patients, that is those with hematocrits 45% or less and those less well-controlled with hematocrits greater than 45% were included. As Craig mentioned, all patients completed the follow-up period this month and the Phase 1 study is now complete. The data slides I’m about to show you are from the ASH presentation in December and include 19 PV patients with a combined history of 79 phlebotomies in the 6 months prior to enrollment. You can see historic phlebotomy details are in orange shades to the left of center and capture all events up to day 1, the time of the first dose administration. To the right of center in blue shades are any phlebotomies recorded during the trial, both treatment period as well as the follow-up period. No 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. Only 5 phlebotomies occurred during the treatment period, all were in patients who entered the study with high baseline hematocrit levels, those over 45%. 2 phlebotomies occurred in the 16-week follow-up period following the last administered dose. In fact, no patient with hematocrit less than 50 at baseline required a phlebotomy during the treatment period. These data are very promising. 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, again those with hematocrit levels less than or equal to 45% as well as those with high baseline hematocrit levels. You can see here that divesiran reduced hematocrit levels in all patients regardless of baseline levels. Divesiran also demonstrated robust target engagement. You can see here, we observed early and sustained hepcidin elevation. Importantly, these elevations are within the physiologic range of hepcidin levels. Importantly, divesiran was safe, well tolerated at all doses tested. The majority of treatment-emergent adverse events were mild, none over Grade 2. There were no treatment-related serious adverse events or TEAEs leading to discontinuation. So in summary, the Phase 1 data showed that divesiran eliminated the need for phlebotomy in all well-controlled patients, lowered hematocrit levels in all patients regardless of baseline levels and the safety tolerability profile continues to look very favorable. We look forward to presenting additional Phase 1 data at medical congresses this year. Here is a high level look at the design for the ongoing Phase 2 portion of SANRECO. This is a randomized double-blind study evaluating divesiran in up to 40 PV patients. Unlike the Phase 1, where we allowed patients to enter with a range of baseline hematocrit levels, all patients entering the Phase 2 will have hematocrit level below 45%. The study is 36 weeks and we are assessing two different dose levels and regimens. The primary endpoint is the percent of patients with hematocrit at or below 45% without the need for phlebotomies. We will also be assessing the effect of divesiran in improving PV-related symptoms. As we mentioned, the study is enrolling nicely and we anticipate full enrollment by the end of this year. Turning now to SLN548, our wholly-owned siRNA targeting complement factor B. The complement system is a critical component of the innate immune system and is made up of several dozen liver-derived proteins and protein fragments. It complements the ability of antibodies and phagocytic cells to rid the body of the foreign microbes as well as help clear cellular debris, including damaged cells. It plays an important role in inflammation. There are 3 distinct biochemical pathways that can lead to activation of the complement cascade and include the classical, alternative and lectin pathways. Importantly, both deficiencies and overactivation of the complement system play a role in a broad range of conditions with immune components. Given the complexity of the complement system pathways and a large number of proteins involved, there are a plethora of potential targets for therapeutic intervention. SLN548 is an siRNA targeting complement factor B and could potentially play a therapeutic role in conditions associated with overactivation of this pathway, including complement-mediated renal diseases, among others. The long-acting profile of our GOLD platform compounds could allow for the development of an infrequently-dosed therapeutic option. We’re excited to advance this compound into a first-in-human study in healthy volunteers later this year. This slide is a brief summary of the Phase 1 study design. It is a randomized, double-blind, placebo-controlled single ascending dose study that plans to enroll up to 32 healthy volunteers across four dose cohorts. The primary objective is to evaluate the safety and tolerability of SLN548 in healthy subjects as well as the pharmacokinetic and pharmacodynamic profile. They incorporate sentinel dosing and all patients will be vaccinated and receive prophylactic antibiotics as appropriate. We look forward to sharing more details about this program, including our development strategy at a future time. As Craig mentioned, we anticipate starting the study in the second half of this year. With that, I’ll turn the call back over to Craig.

Thanks, Steve. In summary, our decision to only initiate the Phase 3 outcomes study of zerlasiran once we’ve secured a partner extends our projected cash runway into 2027. This gives us flexibility to invest in our innovative pipeline, while we continue partnering discussions. We remain confident in zerlasiran and we’ll provide an update when there is one. On this slide, you can see our anticipated clinical milestones for 2025. For divesiran, we completed follow-up in the Phase 1 SANRECO study this month and we will present additional data at the medical meeting this year. We anticipate full enrollment in the Phase 2 SANRECO PV study by year-end. We are also planning to host a divesiran-focused event later this year. So stay tuned for more information on that. For SLN548, we are planning to start the Phase 1 study in healthy volunteers in the second half of this year. We are also looking forward to progressing our extrahepatic work and sharing these data at the appropriate time. The Silence team remains very, very focused on executing to deliver life-changing siRNA therapies to patients in need. With that, I’ll pass back over to the operator for your questions.

Thank you. [Operator Instructions] Our first question comes from the line of Mike Ulz of Morgan Stanley. Your line is now open.

Good morning and thanks for taking the question. Maybe just one focused on zerlasiran, I guess, to the extent you can, if you could provide some color on partnership discussions? And then just how important is the HORIZON data to those discussions, which we’re expecting, I guess, first half of next year now? And then maybe secondly, just talk about some of the types of partnership structures you are considering? Thanks.

Thanks, Mike. We are not going to comment specifically on the ongoing partnership discussions today, but it is interesting to note that since the recent shift in the timing of the HORIZON readout, companies, including Novartis have pledged more funding for Lp(a) studies. So interesting phenomenon, look, we’re not a one product company. We’ve got a portfolio of assets with great potential. And as you know, divesiran is a great example of that. And it is a fine balance to kind of manage the resources amongst the products and we want to make sure we get the best returns. So that’s our announcements today. Silence has really done an excellent job. I’d give us all, the team all full credit for getting zerlasiran to this point, which is designing this highly differentiated Phase 3 program. We continue to believe in its high value potential, very competitive profile, substantial market potential that we’ve talked about on multiple occasions. And we are actively engaged. So I will say that we remain actively engaged in partnering discussions and hopeful we’ll be able to secure the right partner to bring this very promising program forward, both in development and commercially. So I won’t say more on that, but we will update you if there is something to update you on regarding the partner.

Great. Thank you.

Thank you. [Operator Instructions] Our next question comes from the line of Kostas Biliouris of BMO Capital Markets. Your line is now open.

Hello, everyone. Good morning. Thanks for taking our questions. Maybe one question on zerlasiran and one on divesiran from us, how ready are you for the Phase 3 trial? And specifically, from the time we secure a partner, how fast do you think you can start the Phase 3 and will the partner be able to potentially make changes to the Phase 3 design or do you think the Phase 3 design is set and the partner is to kind of agree to that? And the second question on divesiran is, would you consider evaluating divesiran in hereditary hemochromatosis given the relevance of the target there? Thank you.

So, we are in a logistical phase. We are wrapping up Phase 3 readiness activities, which are on track to complete by mid-year. So, we are in a little bit of a period where we can make some fine-tuning if we needed to do that with a partner. But we have advanced very, very nicely across the team in order to be prepared, including as I mentioned, manufacturing preparedness, which is very important. So, there is some time, a bit of time before the track that we had outlined before really gets more fixed, if you will. In terms of HH, Steve, do you want to comment on HH?

Yes, sure, Kostas. So, yes, we are certainly obviously focused on the PV program and executing that. But we do know because of our mechanism that it applies actually across a fairly broad range of conditions where hepcidin may play a role or manipulating the hepcidin pathway may play a role therapeutically. So, we are looking at that. And HH is one of those, of course. So, we haven’t declared any additional work specifically with regards to trial work, but we are examining the opportunity to expand our program.

Thanks very much.

Thank you. One moment for our next question. Our next question comes from the line of Richard Law of Goldman Sachs. Your line is now open.

Thanks. Good morning everyone. So, a couple of questions for me. What is the goal for divesiran regarding differentiation? Can you differentiate clinically for rusfertide besides dosing frequency? And also, what are the biggest hurdles that you see for partnering zerlasiran? Thanks.

Steve, do you want to take differentiation, divesiran?

Yes. So, first of all, we want to be the first sRNA to the market for PV. So, we are very excited about that opportunity. And clearly, and I wouldn’t minimize it that, one of the major differentiations, of course is going to be the infrequency of dosing. And in fact, as I mentioned, as we move forward into completion of the Phase 2, we may have an idea of even less frequently dose regimen versus what we evaluated in Phase 1. The other things we will look for, obviously, are symptomatic improvement, etcetera. So, we will look across the range of important dimensions to measure outcome in this disease. But until those – that work is done, it’s hard to say what point of differentiation or points of differentiation will be available. But the bottom line is the convenience factor is going to be a very important one. And we hope that that long-term effect could have an impact on the likelihood that patients maintain hematocrit at levels that are safe and below 45 consistently. So, more to come on that as the profile of the drug is known.

In terms of partnering and hurdles, really no single item for the parties is different for every one that we have had dialogue with. The dialogues do tend to be a little bit around the notion of business strategy and recognition and intrigue in the very large market opportunity. So, we are – we remain very confident in the program as we discussed. The dialogues continue and we will pursue that. As you know, partnerships often don’t really happen on a clock. It involves coincidence and needs and timing amongst the parties, but we are very active. I can tell you that. And thank you for the question.

Yes. Thank you.

Thank you. [Operator Instructions] Our next question comes from the line of Keay Nakae of Chardan. Your line is now open.

Yes. Thanks. A question about the candidates being developed for Hansoh, is there anything there worth continuing to pursue on your own or how do we view the status of that?

Yes. Thank you. We are very interested in the programs that we have been developing in that productive partnership. We have seen and continue to see encouraging preclinical data in each of the programs. Now, we will actually retrieve those programs and have the opportunity either to develop them ourselves or potentially partner or license. So, it actually gives us the control to determine what we want to do with those, but obviously, in the context of having good data. I don’t know, Rhonda, if you want to reiterate a little bit of the financials on that because it’s not abundantly clear perhaps.

Yes, sure. So, as I mentioned, the revenue did show the cumulative catch-up. So, because we have no further obligations in our collaboration, all the original upfront milestones are basically recognized at the end of the year. So, we don’t anticipate further from Hansoh. However, we will continue to have revenue from AstraZeneca as that program continues. And then all the other additional new targets from the AstraZeneca collaboration could potentially add some revenue to that as well.

Okay. Thank you.

[Operator Instructions] Our next question comes from the line of Myles Minter of William Blair. Your line is now open.

Hi everyone. Thanks for taking the questions. First one on zerlasiran, just in your regulatory discussions, did you actually propose a dose to take forward into that Phase 3? I know you said 300 milligrams previously, but you have not associated a frequency with that. That’s the first one. Second is, I take a lot of questions about how a 5 to 10 sort of nanomole per liter increase in hepcidin that you get with divesiran actually confers the efficacy you are seeing when rusfertide theoretically gets much higher than that. So, maybe you can talk about the difference between the endogenous trigger that you are getting with TMPRSS6 inhibition and maybe the safety ramifications between that and giving a hepcidin mimetic in PV, that would be helpful? Thanks very much.

Steve, both of those for you.

Yes. Well, yes, so yes, the question is with regards to the differences in a way of intervening on the pathway, the hepcidin pathway. So, yes, obviously rusfertide is an exogenously administered hormone. So, naturally it’s not a surprise that you typically get larger exposures based on that. Ours is manipulating the pathophysiology, the underlying physiology and increasing the internal production of hepcidin. It’s less important the level, as we have already learned in Phase 1 than the correlation with that increase on clinical benefit. And what we see very clearly, as we have shown you, is with that increase in hepcidin within the physiological range, which by the way, is 20-fold to 40-fold higher than the baseline of these patients who come in, in our Phase 1 study with very low levels of hepcidin is corresponding, it appears correlating with robust outcome, which is a reduction in the need for phlebotomy and the maintenance of hematocrit. So, that is very, very clear that we are getting the intended effect clinically, which is in fact, the registrable endpoints for this program and other programs. And we are doing that by increasing hepcidin within levels of the physiological range, but much above the baseline. So, I think that’s very important.

In terms of the dose frequency in the agency deliberations?

Yes. But I should also add that the safety – because you asked about safety, and it’s – we cannot really comment comparatively on safety until you actually conduct your program. And even then it’s going to be cross program comparisons. We want to be very careful about that. But clearly, our compound is very safe, what we are seeing in Phase 1 and what we are beginning to see in Phase 2 is a very safe profile, okay. And with regards to the interactions with the agency around, if I think the question was around zerlasiran. But we have talked to the agency naturally about what we believe is the reasonable dose, I should say, the optimal dose and frequency. This is a very competitive space. So, we are not sharing that information at this point. But obviously, when you talk to regulators about a Phase 3 program, you need to be pretty confident about the decisions you are making. I will leave it at that.

And as also further advised obviously, our Phase 3 planning and design. Thank you.

That makes sense. Thanks for the questions.

Thank you.

Thank you. I am showing no further questions at this time. I would now like to turn it back to Craig Tooman for closing remarks.

Just want to thank you all for joining us on today’s call. We really look forward to keeping you updated on our progress. Very excited about the opportunities in front of us and have a great day.

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 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)(a). As I mentioned, today we reported positive top line 36 week data from the ongoing Phase 2 study in patients with high Lp(a)(a). Steve will discuss this in more detail, but in summary, Lp(a)(a) reductions were consistent with Phase 1 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)(a). Phase 3 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 1 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 are very pleased to enter the clinic with the first product candidate under our AstraZeneca collaboration in February, triggering a $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 in 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 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 of our platform and identifying new targets to further expand our proprietary pipeline. General and administrative costs were GBP20.6 million in 2023 versus GBP19.6 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 GBP43.3 million versus a net loss of GBP40.5 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 in clinical development. The company's cash and cash equivalents were GBP54 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 31, 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 and 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 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) 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 milligram and 450 milligram doses. We don't need the 600 milligram dose we explored in the single dose study. Turning to the ongoing ALPACAR-360 Phase 2 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 over125 nanomoles per liter at high risk of ASCVD events. Zerlasiran was administered at 300 milligrams subcutaneously every 16 or 24 weeks and 450 milligrams every 24 weeks to patients with a median baseline Lp(a) of approximately 215 nanomoles per liter. 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 are 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 3. Bottom line, we're very excited about the emerging Phase 2 data, which are consistent with Phase 1 results and continue to support 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% and 50% are 4 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 4 fold 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 1/2 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 1 open label study and that will be followed by a Phase 2 study. In the Phase 1 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 1 study, so the goal here is to learn as much as possible about dosing and therapeutic effect. All patients entered the study are phlebotomy dependent. The nice thing about this program is, even in Phase 1, we're looking at well-defined clinical outcomes, including the maintenance of hematocrit and the number of phlebotomies. So 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 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.