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…

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…

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…

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.