Major Milestone Achieved: SiPore® Data Strengthens Path to World's First Oral Medical Device for Blood Sugar Control in Prediabetics

• Sigrid Therapeutics announces publication of key scientific study showing activity and stability of amylase remain unaffected when confined in SiPore® mesoporous silica pores
• Results provide further support for medical device claim that MSPs act exclusively as “molecular sieves”
• Sigrid’s patented MSPs technology SiPore® to physically prevent digestive enzymes from interacting with food already being used in prediabetes, diabetes, weight control and oral health applications

Stockholm, August 16^th, 2023: Sigrid Therapeutics today announced the publication of a scientific study in the peer-reviewed journal ACS MATERIAL Au demonstrating that alpha-amylase retains its enzymatic activity when confined in SiPore® mesoporous silica pores (MSPs).

Professor Tore Bengtsson (Stockholm University), Sigrid Co-founder and CSO comments: “The results from this important study strongly indicate that the impact of Sigrid’s SiPore® technology on glucose homeostasis shown in our previous studies in animals and man is not due to altered enzyme activity. In contrast, the findings are compatible with a mode of action by which orally ingested MSPs exclusively act as “molecular sieves”, physically preventing digestive enzymes from interacting with food and consequently reducing the breakdown of carbohydrates and fats. Therefore, the study provides further support for our case to classify Sigrid’s SiPore® formulations as medical devices, not pharmaceuticals”.

In this in-vitro study, the MSPs were prepared with sufficiently large pores (11.2 nm) to allow a significant amount of α-amylase adsorption. The MSPs were studied with respect to the α-amylase adsorption and enzymatic activity using a large (potato starch) and a small (CNP-G3) probe (substrate). Pancreatic α-amylase adsorbed in the pores of MSPs displayed high activity and retained its conformation. The adsorption capacity was about 21% (w/w). When the small probe molecule was tested (CNP-G3), the activity was high. No activity was observed with the large probe molecule (potato starch). The latter had a hydrodynamic diameter much larger than the pore size of the silica.

"This data bolsters the understanding of SiPore21®'s mechanical mode of action and reinforces its medical device classification”, says Sana Alajmovic, Co-founder & CEO, Sigrid Therapeutics. “We are excited about the prospect of obtaining approval for SiPore21® as the world's first oral medical device dedicated to blood sugar control in prediabetics”, concludes Sana Alajmovic.

SiPore21® is Sigrid’s lead product, developed as an orally ingested gel for the reduction of long-term blood sugar, HbA1c, in prediabetics and early stage type 2 diabetics. The product's potential lies in its ability to address the critical need for non-invasive, user-friendly solutions for blood sugar management in populations at risk. SiPore21® is currently undergoing its third clinical testing phase within the largest commercial prediabetes trial ongoing called SHINE.By targeting prediabetics and early stage type 2 diabetics, SiPore21® showcases Sigrid Therapeutics' dedication to proactively tackling the global diabetes epidemic.

Title and link to the scientific publication:

Activity and Stability of Nanoconfined Alpha-Amylase in Mesoporous Silica ACS MATERIAL Au, 2023, https://doi.org/10.1021/acsmaterialsau.3c00028. Publication date: August 4, 2023

For more information, please contact:

Tore Bengtsson, Professor at the Department of Molecular Biosciences, Stockholm University

Phone: +46 70 5473994

Email: Tore.Bengtsson@su.se

Sana Alajmovic, Co-founder & CEO, Sigrid Therapeutics
Phone: +46 72 3893396
Email: sana@sigridthx.com

About Mesoporous silica particles (MSPs)

Mesoporous silica particles (MSPs) are a type of ingestible synthetic amorphous silica particles that can be produced with a large surface area and a range of pore sizes. Studies in mice, published in Nanomedicine^1,2 have shown that food efficiency was reduced by 33% leading to a positive effect on metabolic profile with significant lower levels of adipose tissue formation and leptin, together with lower levels of circulating insulin. Weight gain was thus sufficiently attenuated. Additional pre-clinical results published in Advanced Healthcare Materials³ showed that these findings are compatible with a mode of action whereby a portion of the enzymes are trapped inside the MSPs resulting in an enzyme-blocking effect reducing the break down of food and thus reducing the energy uptake into the body.This mode of action was further confirmed in vivo when MSPs added to milk led to reduced lipid absorption compared to control⁴.

About Sigrid Therapeutics

Sigrid Therapeutics (Sigrid) is a clinical-stage consumer focused healthtech company pioneering a new class of engineered materials to prevent and treat metabolic disease and disorders, including type 2 diabetes. The Company’s lead product, SiPore21®, is an orally-administered medical device based on the Company’s proprietary platform technology, SiPore®. Designed to act locally in the gut, SiPore21® consists of precisely engineered micron-sized mesoporous silica particles (MSPs) with tailored porosity. Clinical data confirms the beneficial effects of SiPore® technology on a range of metabolic parameters and its excellent safety profile^3-7. SiPore21® benefis from a unique mode of action, employing a mechanical entrapment of amylase within its porous structure. This physically hinders the interaction of digestive enzymes with food, effectively reducing the breakdown of carbohydrates and fats⁸. SiPore21® is being developed as the first oral medical device for blood sugar control in people at risk of developing type 2 diabetes. https://www.sigridthx.com/.

References

1. Large pore mesoporous silica induced weight loss in obese mice, Nanomedicine, 2014,https://www.futuremedicine.com/doi/10.2217/nnm.13.138.
2. Mesoporous Silica with Precisely Controlled Pores Reduces Food Efficiency and Suppresses Weight Gain in Mice, Nanomedicine, 2020, https://www.futuremedicine.com/doi/10.2217/nnm-2019-0262.
3. Entrapping Digestive Enzymes with Engineered Mesoporous Silica Particles Reduces Metabolic Risk Factors in Humans, Advanced Healthcare Materials, 2020, https://doi.org/10.1002/adhm.202000057.

4. Towards mesoporous silica as a pharmaceutical treatment for obesity - impact on lipid digestion and absorption, European Journal of Pharmaceutics and Biopharmaceutics, 2022, https://doi.org/10.1016/j.ejpb.2022.02.001.
5. Oral intake of mesoporous silica is safe and well tolerated in male humans, PLoS ONE, 2020, DOI: 10.1002/adhm.202000057. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240030
6. Engineered mesoporous silica reduces long-term blood glucose, HbA1c, and improves metabolic parameters in prediabetics, Nanomedicine, 2021, https://doi.org/10.2217/nnm-2021-0235.
7. Mesoporous Silica Particles Retain their Structure and Function While Passing Through the Gastrointestinal Tracts of Mice and Humans, ACS Applied Materials & Interfaces, 2023, https://doi.org/10.1021/acsami.2c16710.
8. Activity and Stability of Nanoconfined Alpha-Amylase in Mesoporous Silica ACS MATERIAL Au, 2023, https://doi.org/10.1021/acsmaterialsau.3c00028. Publication date: August 4, 2023.