The search for a partner for zerlasiran is ongoing, according to Silence. In the meantime, the biotech will focus its resources on divesiran, which it is testing for polycythemia vera and other hematologic indications.
Silence Therapeutics is pressing pause on the late-stage development of its RNA silencer zerlasiran for cardiovascular diseases—at least until it finds a collaborator with whom it can take the therapy forward.
“While we remain confident in our zerlasiran program for high Lp(a), we will only initiate the Phase 3 cardiovascular outcomes study once a partner is secured,” CEO Craig Tooman said in a statement on Thursday. “The decision not to initiate the zerlasiran Phase 3 outcomes study without a partner extends our projected cash runway into 2027,” Silence CFO Rhonda Hellums added.
By the end of 2024, Silence had $147.3 million in cash, cash equivalents and short-term investments.
In its press announcement on Thursday, Silence additionally revealed that the FDA had given it “positive regulatory feedback” regarding a planned Phase III cardiovascular outcomes study for zerlasiran. Talks with potential partners are “ongoing,” the biotech disclosed, noting that the timing of its late-stage development for zerlasiran will depend on finding a collaborator.
Zerlasiran is an investigational short interfering RNA (siRNA) molecule that works by silencing the LPA gene, which encodes for a certain protein found in lipoprotein(a), also known as Lp(a), a type of cholesterol molecule. Through this mechanism, zerlasiran lowers the level of Lp(a) in the body, in turn potentially reducing the risk of cardiovascular complications, such as heart attacks and strokes.
Silence has seen notable success with zerlasiran’s gene-silencing approach. In June 2024, the biotech reported that the siRNA therapeutic at 48 weeks elicited a median maximum Lp(a) reduction of around 90% in patients with high Lp(a) at baseline and who were deemed to be at high risk of atherosclerotic cardiovascular disease events.
The decision to pause zerlasiran’s Phase III development is in line with Silence’s growth strategy for this year. “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 siRNAs,” Tooman said.
At the forefront of this pivot is the mid-stage asset divesiran, which the biotech is developing for polycythemia vera. Silence will present data from the Phase I SANRECO study, which has concluded, at medical congresses this year. As per Tooman, the company also expects to fully enroll the Phase II SANRECO study of divesiran by year-end.
Diversiran is also being tested for several other hematologic indications, as per Silence’s pipeline page.
