Silence Therapeutics (SLN) investor relations material

Pipeline overview and technology

• Focus on small interfering RNA (siRNA) technology with durable, reversible gene silencing effects.

• Lead program is a TMPRSS6-targeting compound for polycythemia vera, currently in phase II.

• Lp(a) compound, zerlasiran, is phase III-ready and partnership discussions are ongoing, pending external trial data.

• ANGPTL3 compound, developed with AstraZeneca, is returning to the company after phase I completion.

• Preclinical programs include GPR146 for lipid disorders and an activin E-targeting compound for obesity and cardiovascular risk.

Polycythemia vera (PV) market and clinical need

• PV is a chronic myeloproliferative neoplasm with high risk of thromboembolic events and cardiovascular death.

• Disease management focuses on maintaining hematocrit below 45 to reduce risk, with phlebotomy and cytoreductive agents as standard treatments.

• Orphan condition with 150,000–170,000 patients in the US and similar numbers in Europe; majority are treated after diagnosis.

• Premium-priced market with existing drugs like BESREMi and Jakafi exceeding $200,000 WAC price.

• Payers and HTA feedback incorporated into phase III design to ensure access and reimbursement.

Clinical trial progress and expectations

• Phase II PV trial is fully enrolled, with top-line results expected by mid-August.

• Phase I showed all dose cohorts maintained hematocrit below 45 without phlebotomy; 6 mg/kg dose selected for phase II.

• Phase II is placebo-controlled, testing two dosing intervals, aiming for robust effect over placebo (targeting >44% placebo-adjusted response).

• Differentiation from competitors includes less frequent dosing (Q6 or Q12 weeks) and durable siRNA mechanism.

• Safety profile to date is favorable, with no grade 3 adverse events and low injection site reactions.