Zerlasiran

“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.

Plus, news about Alopexx, Medigene, EpimAb and Belite Bio: Hansoh backs out of siRNA pact with Silence Therapeutics: The London-based biotech said Hansoh has decided not to pursue further development of three siRNAs. The companies have been collaborating on the programs since 2021 as part of a deal that includes $1.3 billion in potential milestones. Silence also said it will not advance its treatment candidate for high Lp(a), dubbed zerlasiran, into a Phase 3 cardiovascular outcomes study until it secures a partner. The zerlasiran pause should extend its cash runway into 2027. — Ayisha Sharma Vir Biotechnology seeks ex-China partner for hepatitis B combo: The San Francisco-based biotech said further development of its monoclonal antibody tobevibart and siRNA elebsiran will depend on securing a development and commercialization partner. The company anticipates functional cure data from a Phase 2 study of the combination in the second quarter. — Ayisha Sharma A biotech IPO three years in the making: Alopexx, a Cambridge, MA-based biotech that has been trying to go public since winter 2022, updated its NYSE listing plans this week to say it aims for $9.9 million in net proceeds from a potential Wall Street debut as “ALPX.” The clinical-stage startup is working on antibodies and vaccines for bacterial, fungal and parasitic infections. — Kyle LaHucik Medigene, EpimAb join forces to develop T cell engagers: The multi-target deal combines Medigene’s T cell receptor know-how with EpimAb’s CD3 antibody and T-FIT technology. Both companies will share ownership over the resulting bispecific treatments for immune-mediated diseases, including solid tumors. The financial terms of the deal were not disclosed. — Ayisha Sharma Safety board clears Belite Bio’s Stargardt disease trial: The independent data safety monitoring board said Belite’s Phase 3 study of tinlarebant in teenage patients can proceed without any changes based on an interim analysis. This means the biotech doesn’t need to enroll any more patients to boost the trial’s statistical power. The study is set to end in the fourth quarter. — Ayisha Sharma