Silence Therapeutics (SLN) Morgan Stanley 22nd Annual Global Healthcare Conference summary

Platform overview and strategy

• The GOLD Platform uses GalNAc oligonucleotide delivery for siRNA, targeting gene diseases primarily in the liver, with high specificity and durability demonstrated in studies.

• Two main proprietary programs focus on cardiovascular disease (Lp(a)) and an orphan disease (polycythemia vera), covering broad treatment opportunities.

• Partnerships with AstraZeneca and Hansoh provide non-dilutive funding and expand the platform's reach, with potential income up to $5 billion.

• Additional pipeline assets, including complement inhibitors, are being prioritized for advancement or partnering.

• Cash position of $189 million at end of Q2 supports operations into 2026, enabling continued investment in proprietary and partnered programs.

Lp(a) cardiovascular program (zerlasiran)

• Lp(a) is a genetically determined, independent cardiovascular risk factor affecting 20% of the global population, with no current specific treatments.

• Zerlasiran has shown robust, durable Lp(a) reductions of up to 98-99% in Phase 1 and over 90% in ongoing Phase 2 trials, with effects persisting up to 60 weeks.

• The optimal dose is likely 300 mg, enabling single injections and potentially quarterly or longer dosing intervals.

• Phase 3 trial design is set to launch in the first half of next year, with a single, event-driven CVOT expected to last 4-5 years.

• Competitive differentiation centers on higher potency and less frequent dosing compared to antisense competitors, with trial design tailored to high-risk patients.

Polycythemia vera (PV) program (divisiran/SLN124)

• PV is a myeloproliferative neoplasm with excess red blood cell production, leading to high phlebotomy needs and risk of blood clots.

• Phase 1 data showed 100% efficacy in maintaining hematocrit below 45% without phlebotomy in well-controlled patients, with significant reductions in phlebotomy for others.

• The program aims to initiate Phase 2 by year-end, focusing on well-controlled, phlebotomy-dependent patients and leveraging orphan and fast track designations.

• Dosing intervals of six weeks have been tested, with potential for less frequent dosing in future studies.

• Differentiation from competitors includes siRNA technology and less frequent dosing compared to weekly peptide-based treatments.