Silence Therapeutics Plc (SLN): Our View on Upcoming Ph.2 SANRECO Readout, +Mgmt Commentaries

Research evidence excerpt

Silence Therapeutics Plc (SLN): Our View on Upcoming Ph.2 SANRECO Readout, +Mgmt Commentaries

Goldman Sachs Silence Therapeutics Plc (SLN)

Ph. 2 SANRECO readout in PV is a key near-term catalyst

Rusfertide’s 44% placebo-adjusted response rate (capturing Hct control and

absence of PHL) will be the bar. In our discussion with SLN, mgmt sees rusfertide’s

(RUS) Ph. 3 VERIFY trial data as the benchmark for divesiran. Recall that rusfertide’s Ph.

3 VERIFY results (details in Exhibit 3 below), showed that RUS + PHL +/- CRT achieved

highly statistically significant proportion in responder rates (defined as absence of PHL

eligibility measured by Hct level) compared to the placebo arm (77% versus 33%;

p<0.0001) as well as a reduction in phlebotomies versus placebo (-32%; p<0.0001) and

improvements in Hct control and patient-reported outcomes (both significant) with an

encouraging safety profile (AEs were primarily Gr1-2 injection site reactions; no SAEs

were deemed related to the drug). While SLN is leveraging a slightly different primary

endpoint in SANRECO (primarily based on Hct<45% control between weeks 18-36 vs.

VERIFY’s 20-32 weeks without phlebotomy use), we believe a placebo-adjusted efficacy

of a similar magnitude to RUS’s 44% on its primary endpoint will be needed to validate

DIV’s profile and competitiveness towards a best-in-class profile. However, we caution

that divesiran’s 18-week period is more stringent than VERIFY’s shorter 12-week period

to show Hct control.

High placebo effect is potential. While we believe Divesiran (DIV)’s treatment effect as

shown in the Ph. 1 study is encouraging, we foresee risk for meaningful placebo effect in

the Ph. 2 trial based on RUS’ Ph. 3 VERIFY study that showed 33% pbo effect and higher