Silence Therapeutics Plc

Good morning and good afternoon, everyone. Thank you for joining us today. My name is Jem 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 Helms, 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 investor 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, Jem, 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 Zolaceron, our SRNA for high LP little a, The ALPAC-R360 Phase II study of Zolaceron in ASCVD patients with high LP-Lil-A delivered positive results that were featured in a late-breaker at AHA and published in JAMA. The study showed LP-Lil-A reductions exceeded 90%, effects were durable, and Zolaceron was observed to be well-tolerated. These data support a competitive profile that we believe can be further defined in Phase III. The SILENCE team, supported by top cardiologists, have done an outstanding job designing what we are confident is a highly differentiated Phase III program for Zolaceron. 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 III development, including manufacturing readiness. Turning to Diverseron, our first-in-class SRNA for polycythemia vera. The San Rico Phase I study of Diveseron delivered positive results that exceeded our expectations. Data were highlighted at ASH and showed Diveseron 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 San Rico Phase II study, and the European Commission granted Diveseron orphan drug designation for PV. As a reminder, Diveseron also has FDA Fast-Track and orphan drug designations for PV. In terms of other pipeline advancements, we are pleased to have our third SRNA from our gold platform enter 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 SRNA candidates for hepatic targets. Turning to slide five 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 SRNAs. Dibeseron is a great example of that. We remain confident in our Zolaceron program for high LP little a and believe we have very differentiated design for our phase three program. However, today we are making clear that we will only initiate the phase three outcome 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 Zolaceron. 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 Zelaceron's potential. There are very few cardiovascular assets in development that aim to treat an unmet medical condition as large as the Lp 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 Deveseron. We announced this morning that we completed follow-up in the Phase 1 portion of San Rico this month and look forward to presenting more data from that study at medical meetings this year. The outstanding data from the San Rico 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 San Rico Phase 2 study by the end of this year. While we are currently focused on the PV indication for Deveseron, we continue to believe it has broader therapeutic potential. Given the outstanding PV results we have seen in Phase I, we are planning an investor event later this year and look forward to discussing the program in more detail then. In addition to Deveseron, we were pleased to announce today that we plan to start a Phase I study of SLN548, our wholly-owned SRNA 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 Hanso Pharma collaboration we announced this morning. We are evaluating these programs as part of our broader portfolio and will determine which ones we want to bring forward ourselves or potentially partners. 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 1st of 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 issue reforms with the SEC in accordance with U.S. GAAP as opposed to IFRS, and then U.S. dollars versus British pounds. Now let me turn to the financials. For the year ended December 31st, 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 HONSO Pharma collaboration, we announced this morning that HONSO 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. formally 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 recognize 24.6 million resulting from a cumulative catch-up following the completion of all required obligations to HONSO under the collaboration. Finally, during 2024, we recorded the remaining royalty revenue from an island 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 Zolasterin and Divisorin 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 US domestic issuer, including our transition to US 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 US Treasury bills 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 eight and the 2025 cash guidance. As Craig mentioned, we have made the decision only to initiate the Zolasterin Phase III outcome 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 Stivisarin for PV, 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?