Mesoporous silica particles (MSPs) are thermally and chemically stable porous materials composed exclusively of silicon dioxide. Here we report the results of a First-in-Man clinical trial evaluating engineered MSPs with controlled surface area, pore volume, pore size, particle size and morphology, named SiPore, in obese but otherwise healthy male volunteers (n=20). SiPore is orally ingested and passes through the body without being absorbed and is safely eliminated via the feces. The clinical effects of SiPore were significant reduction in several metabolic and cardiovascular risk factors. HbA1c was reduced by 5% and LDL-C by 15% on average from baseline, both clinically meaningful reductions. Adverse events observed were mild and transient. These promising effects led to further investigations into SiPore’s mode of action.
We hypothesized that SiPore acts as a molecular sieve by sequestration of biomolecules in the gastrointestinal tract, which could explain the observed clinical results. This merited a more detailed analysis of the interaction between SiPore and digestive enzymes. SiPore significantly sequestered amylase and lipase in vitro while MSPs with smaller pore size had no effect. Lipase and amylase were depleted by SiPore from more complex biological matrices, such as porcine pancreatin and mouse intestinal fluid. Moreover, SiPore inhibited the activity of human salivary amylase in human saliva. Further studies of amylase depletion in vitro indicated that the availability of pores of a certain pore size is a critical parameter for enzyme sequestration.
This innovative mode of action, combined with SiPore’s promising safety profile, makes SiPore an exciting candidate for treatment or prevention of metabolic diseases, particularly prediabetes and type 2 diabetes (T2D). SiPore is currently being investigated in an ongoing clinical trial in 40 prediabetic or newly diagnosed T2D subjects (NCT03823027).
M.E. Lindgren: Employee; Self; Sigrid Therapeutics AB. E. Rollman Waara: Employee; Self; Sigrid Therapeutics AB. B. Benziane: Employee; Self; Sigrid Therapeutics. H. Vallhov: Employee; Self; Sigrid Therapeutics. N. Iqbal: None. E.V. Johnston: None. T. Bengtsson: Other Relationship; Self; Atrogi, Sigrid Therapeutics.