Financial Data and Key Metrics Changes - For the year ended December 31, 2024, the company recorded revenues of $43.3 million, an increase from $31.6 million in 2023, representing a growth of $11.7 million largely due to collaboration arrangements for siRNA platform development [20][21] - The company's net operating loss for 2024 was approximately $63.3 million, a slight decrease from $64.4 million in 2023, attributed to increased revenue offset by rising R&D costs [26] - The net loss for 2024 was approximately $45.3 million compared to $54.2 million in 2023, with cash, cash equivalents, and short-term investments totaling $147.3 million at the end of December 2024 [27] Business Line Data and Key Metrics Changes - The Phase 2 study of zerlasiran showed positive results with Lp(a) reductions exceeding 90%, supporting a competitive profile for further development in Phase 3 [5][6] - Divesiran's Phase 1 study results indicated it completely eliminated the need for phlebotomy in well-controlled patients, with a favorable safety profile [8][14] - The company plans to prioritize investment in programs targeting rare conditions, with divesiran for polycythemia vera (PV) remaining a top priority [10][29] Market Data and Key Metrics Changes - The company has received Orphan Drug Designation for divesiran from the European Commission, and it also holds FDA Fast Track and Orphan Drug Designations for PV [8] - The market opportunity for treating high Lp(a) is significant, with few cardiovascular assets targeting this unmet medical condition [12] Company Strategy and Development Direction - The company will only initiate the Phase 3 outcomes study for zerlasiran once a partner is secured, extending its cash runway into 2027 [28][53] - The focus will be on advancing innovative siRNA therapies for rare conditions, with a commitment to delivering life-changing treatments [29][56] - The company is evaluating multiple undisclosed programs from its GOLD platform for potential development or partnership [17] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of zerlasiran and divesiran, highlighting the positive feedback received from global regulatory agencies regarding the Phase 3 program design for zerlasiran [6][12] - The company is actively engaged in partnership discussions for zerlasiran, with a focus on securing the right partner for development and commercialization [61] Other Important Information - Silence has transitioned to a U.S. domestic issuer effective January 1, 2025, requiring compliance with U.S. GAAP and SEC reporting [19] - The company plans to start a Phase 1 study of SLN548, targeting complement factor B, in the second half of the year [50] Q&A Session Summary Question: Can you provide some color on partnership discussions for zerlasiran? - Management did not comment specifically on ongoing partnership discussions but noted increased funding for Lp(a) studies from companies like Novartis [59][61] Question: How ready is the company for the Phase 3 trial of zerlasiran? - The company is wrapping up Phase 3 readiness activities and is on track to complete them by mid-year, allowing for some adjustments with a partner [67] Question: What is the goal for divesiran regarding differentiation? - The goal is to be the first siRNA to market for PV, with a focus on infrequent dosing and symptomatic improvement as key differentiators [75][78] Question: What are the biggest hurdles for partnering zerlasiran? - Hurdles vary by party, but discussions often revolve around business strategy and the recognition of the large market opportunity [79][80] Question: What is the status of the candidates developed for Hansoh? - The company is interested in the programs developed under the partnership and will evaluate the opportunity to develop them independently or through partnerships [84]