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Silence Therapeutics Halts Phase III Development of Zerlasiran, Seeks Partnership for Cardiovascular Drug

• Silence Therapeutics has paused the Phase III development of zerlasiran, its RNA-silencing therapy for cardiovascular diseases, until securing a strategic partnership, extending their cash runway into 2027.

• The company's lead candidate zerlasiran demonstrated promising results with approximately 90% median maximum Lp(a) reduction at 48 weeks in high-risk cardiovascular patients.

• The strategic pivot allows Silence to focus resources on rare disease programs, including divesiran for polycythemia vera, with Phase II SANRECO study enrollment expected by year-end.

Silence Therapeutics announced today it will temporarily halt the Phase III development of its cardiovascular drug candidate zerlasiran, pending the securing of a strategic partnership. The decision comes despite receiving positive regulatory feedback from the FDA regarding the planned Phase III cardiovascular outcomes study.
"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," stated Craig Tooman, CEO of Silence Therapeutics. The company's CFO, Rhonda Hellums, noted that this strategic decision extends their projected cash runway into 2027, with current financial resources standing at $147.3 million as of end-2024.

Promising Clinical Results and Mechanism of Action

Zerlasiran, an investigational short interfering RNA (siRNA) therapeutic, has shown significant promise in clinical development. The drug works by silencing the LPA gene, which produces proteins found in lipoprotein(a) (Lp(a)), a cholesterol molecule associated with cardiovascular risk. Recent data from June 2024 demonstrated the drug's impressive efficacy, achieving a median maximum Lp(a) reduction of approximately 90% at 48 weeks in high-risk patients with elevated baseline Lp(a) levels.

Strategic Shift Toward Rare Diseases

The pause in zerlasiran's late-stage development aligns with Silence's revised corporate strategy for 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," explained Tooman.

Focus on Divesiran Development

As part of this strategic realignment, Silence is advancing its mid-stage asset divesiran for polycythemia vera. The company has completed the Phase I SANRECO study, with results scheduled for presentation at upcoming medical conferences. Additionally, the Phase II SANRECO study is progressing well, with full enrollment expected by the end of the year.
The company maintains ongoing discussions with potential partners for zerlasiran, with the timing of Phase III development contingent upon securing a suitable collaboration. This strategic approach allows Silence to maintain its promising cardiovascular program while optimizing resource allocation for rare disease initiatives.
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