Silence Therapeutics Adjusts Strategy Amid Partner Loss and Phase 3 Delay

Silence Therapeutics, a British biotech company specializing in gene silencing therapies, has announced significant changes to its strategic plans following the loss of a major collaboration and a delay in its Phase 3 trial for a cardiovascular drug candidate.

Zerlasiran Phase 3 Plans on Hold

Silence Therapeutics has put the brakes on its plans to initiate a Phase 3 cardiovascular outcomes study for zerlasiran, its siRNA therapy targeting atherosclerotic cardiovascular disease. Despite reporting promising Phase 2 data at the American Heart Association conference in November, which showed an 80% placebo-adjusted reduction in lipoprotein A (Lp(a)) concentration over 36 weeks, the company has decided to delay the next phase of development.

Craig Tooman, CEO of Silence Therapeutics, stated, "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." The company is currently in discussions with potential partners and aims to be "phase 3 ready in the first half of 2025."

Financial Implications and Pipeline Prioritization

The decision to postpone the zerlasiran Phase 3 study has significant financial implications for Silence Therapeutics. CFO Rhonda Hellums revealed that the company ended the year with over $147 million in cash, cash equivalents, and short-term investments. She explained that the delay "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."

In light of these developments, Silence is shifting its focus to rare diseases. Tooman emphasized, "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." The company's lead candidate in this area is divesiran, currently in a Phase 2 study for polycythemia vera (PV), a rare blood cancer.

Hansoh Collaboration Terminated

Adding to the strategic shifts, Silence Therapeutics announced the termination of its collaboration with Hansoh Pharma. The partnership, initiated in 2021 with a $16 million upfront payment from Hansoh, held the potential for up to $1.3 billion in biobucks. The collaboration aimed to use Silence's mRNAi GOLD platform to identify therapies for three undisclosed preclinical targets.

Silence revealed that Hansoh has "opted not to pursue further development," leaving the British biotech to "evaluate plans" for advancing the three programs independently. This unexpected development removes a significant potential revenue stream and adds pressure to Silence's pipeline strategy.