Divesiran

iStock, Artur Plawgo 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 .

“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,” Silence CEO Craig Tooman said.\n When Silence Therapeutics unveiled its latest zerlasiran phase 2 data at the American Heart Association (AHA) conference in November, the British biotech sounded confident that the latest readout set them up for a phase 3 trial.But by the sound of Silence’s latest update, those phase 3 plans have been tuned out at the same time as the company adjusts to losing out on up to $1.3 billion in potential biobucks from a collaboration with Hansoh Pharma.Zerlasiran, a siRNA therapy designed to treat atherosclerotic cardiovascular disease by “silencing” the LPA gene, was shown to produce a placebo-adjusted reduction from baseline lipoprotein A (Lp(a)) concentration of 80% over 36 weeks, in phase 2 data shown to the AHA conference. At the time, execs at the London-based biotech said the findings would help determine the ideal dose for a phase 3 trial.But three months later, Silence has changed its tune.“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,” Silence CEO Craig Tooman disclosed in a fourth-quarter earnings release this morning.Discussions with potential partners are ongoing, according to Silence, with the biotech “progress[ing] core activities” to ensure the zerlasiran program is “phase 3 ready in the first half of 2025.” “We ended the year with over $147 million in cash, cash equivalents and short-term investments,” CFO Rhonda Hellums explained in the same Feb. 27 release. “The decision not to initiate the zerlasiran phase 3 outcomes study without a partner extends our projected cash runway into 2027 and gives us flexibility to invest in our innovative pipeline while we continue partnering discussions for this program.”That pipeline is led by divesiran, another gene silencing therapy that is currently being assessed in a phase 2 study of patients with a rare blood cancer called polycythemia vera (PV).“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. “We believe divesiran is a great example of this strategy and clinical commitment.”Silence’s execs will presumably be adjusting their plans to the fact that they can no longer hope for up to $1.3 billion in biobucks to come their way from a deal with Hansoh. The Chinese company handed Silence $16 million upfront in 2021 to kick off a collaboration using Silence’s mRNAi GOLD platform to identify therapies aimed at three undisclosed preclinical targets.But Silence revealed this morning that Hansoh has “opted not to pursue further development,” leaving Silence to “evaluate plans” to take the three programs forward on its own.