Silence Therapeutics (NASDAQ: SLN) drew attention at the H.C. Wainwright 28th Annual Global Investment Conference on Sept. 15, 2026, as investors focused on its lead siRNA program, divesiran, for polycythemia vera (PV), and the company's broader pipeline trajectory.
Divesiran targets TMPRSS6, a gene regulating hepcidin, the master controller of iron metabolism. In the Phase II SANRECO trial, top-line results reported in August 2024 showed that 88% of divesiran-treated patients maintained hematocrit below 45% without phlebotomy, compared with 19% on placebo. Weight-based dosing was evaluated at 3 mg/kg, 6 mg/kg and 9 mg/kg, with the 6 mg/kg level advanced into schedule studies of every six weeks (Q6) and every 12 weeks (quarterly, Q12). Both extended schedules kept hematocrit below the 45% threshold in more than 90% of patients.
Hepcidin levels rose within two to three weeks of dosing and remained elevated beyond the last administration. Reactive thrombocytosis was observed but stayed below clinically concerning levels — under 1.2 million to 1.5 million platelets per microliter. A 2013 New England Journal of Medicine study cited by the company found a fourfold increase in cardiovascular death and thromboembolic events in PV patients maintained at hematocrit levels of 46%–50% versus below 45%.
Steve Romano, executive vice president of research and development at Silence, described the mechanism as "very elegant and rather simple" and well aligned with the underlying pathophysiology of PV.
The company said it has raised more than $200 million since the Phase II data release to fund Phase III development of divesiran and selectively prioritize other programs. An End of Phase II meeting with the FDA is targeted for the end of 2024, with Investigational New Drug filings for both SLN365 and SLN098 planned for the second half of 2025. A fuller divesiran dataset is scheduled for presentation at the American Society of Hematology meeting in December 2024.
Competitive sizing is also a consideration: other PV programs, including Protagonist's combination with Takeda and Ono's sapablursen, are targeting patient populations of around 250 in pivotal studies.
Beyond divesiran, Silence outlined progress across several siRNA programs. SLN365 targets GPR146, a non-LDL receptor pathway, for homozygous familial hypercholesterolemia. SLN098 targets inhibin beta E to improve body composition and preserve lean muscle mass, though the company stressed it is not intended as a standalone obesity therapy. SLN312, an AngPTL3 inhibitor, had its global rights returned from AstraZeneca following Phase I work. Zerlasiran, a Phase III-ready program targeting lipoprotein(a) for cardiovascular disease, is currently on hold while Silence awaits a partner and reviews Novartis' Lp(a)HORIZON results.
Silence shares surged 176% over the prior year and were trading at a market capitalization of approximately $764 million at the time of the conference. Analyst price targets ranged from $10 to $75. The stock closed at $13.02, down 2.18% on the day of referenced live data.
Patrick Trucchio, senior health analyst at H.C. Wainwright, characterized the company as a clinical-stage biotech advancing an siRNA platform across rare and cardiometabolic indications, with divesiran anchoring the pipeline.
