Sirnaomics Announces Demonstration of a Novel Mechanism of Action of Its siRNA Therapeutics for Focal Fat Reduction in Journal of Cosmetic Dermatology

HONG KONG,GERMANTOWN,Md.,and SUZHOU,China,Sept. 19,2024 -- Sirnaomics Ltd. (the "Company",Stock Code: 2257,together with its subsidiaries,the "Group" or "Sirnaomics"),a leading biopharmaceutical company engaging in discovery and development of advanced RNAi therapeutics,today announced that the company in collaboration with Dr. Mark Nestor's team from the Center for Clinical and Cosmetic Research in Miami Florida has jointly published a major breakthrough for its novel siRNA therapeutics revealing a novel mechanism of action of a significant reduction of adipose tissue in preclinical animal models. This groundbreaking work entitled "Novel injectable polypeptide nanoparticle encapsulated siRNA targeting TGF-β1 and COX-2 for localized fat reduction I: Preclinical in vitro and animal models",published at Journal of Cosmetic Dermatology,2024; 00:1-11,creates a solid foundation for the Company's RNAi-based therapeutic program for focal fat reduction treatment.

The study evaluates the efficacy of STP705,an injectable containing siRNA encapsulated within histidine-lysine polypeptide (HKP) nanoparticles targeting transforming growth factor β1 (TGF- β1) and cyclooxygenase-2 (COX-2),crucial mediators in adipocyte differentiation and fat retention,using in vitro experiments on mouse preadipocytes and in vivo trials using Diet Induced Obese (DIO) mice and Yucatan minipigs. The study results indicated that STP705 effectively reduced the expression of TGF-β1 and COX-2,with a notable decrease in adipocyte volume and lipid content without apparent adverse systemic effects. In DIO mice,the HKP- siRNA complex demonstrated precise localization to injected adipose tissue,maintaining significant gene silencing,and detectable levels of siRNA for up to 14 days post-administration. The data in minipigs showed a significant reduction in subcutaneous adipose tissue thickness up to 56 days post-administration. In conclusion: These studies support the use of targeted-siRNA therapy specifically targeting TGF-β1 and COX-2,for localized fat reduction,offering a potential minimally invasive alternative to current fat reduction methods.

Mark S. Nestor,M.D.,Ph.D.,a recognized world expert in clinical research in clinical Dermatology and aesthetics,who is a Voluntary Professor at the Department of Dermatology and Cutaneous Surgery and the Department of Surgery,Division of Plastic Surgery at the University of Miami,Miller School of Medicine and serves as Director of the Center for Clinical and Cosmetic Research™ and the Center for Cosmetic Enhancement®,Aventura,Florida,is the senior author of this publication; he comments: "The results of all of the pre-clinical studies clearly indicate the significant potential of STP705 to use as a safe and effective method of reducing localized fat accumulation and sets the stage for the clinical pathway for this indication."

Dr. Patrick Lu,the founder,Chairman and CEO of Sirnaomics,comments,"The latest publication indicated that Sirnaomics' leading drug candidate,STP705,has exhibited a novel mechanism of action,by specifically silencing TGF-β1 and COX-2 in the subdermal adipose tissue,resulted in localized fat reduction. The preclinical studies not only showed that It is safe and very well-tolerated,but also achieved preliminary efficacy in inducing adipocyte apoptosis and tissue remodeling,suggesting a safer alternative or adjunct to existing fat reduction therapies."

About Sirnaomics

Sirnaomics is an RNA therapeutics biopharmaceutical company that focuses on the discovery and development of Sirnaomics is an RNA therapeutics biopharmaceutical company with product candidates in preclinical and clinical stages that focuses on the discovery and development of innovative drugs for indications with medical needs and large market opportunities. Sirnaomics is the first clinical-stage RNA therapeutics company to have a strong presence in both Asia and the United States. Based on its proprietary delivery technologies: Polypeptide Nanoparticle Formulation and the 2nd generation of GalNAc conjugation,the Group has established an enriched drug candidate pipeline. Sirnaomics is currently holding a leadership position on advancing RNAi therapeutics for oncology application with multiple successes of its clinical programs for STP705 (Phase IIa,IIb) and STP707 (Phase I). The ongoing Phase I study of STP122G represents the first drug candidate of GalAhead™ technology entering clinical development with an encouraging therapeutic efficacy and safety readouts. Learn more at: www.sirnaomics.com.