Suzhou Siran Biotechnology Co.,Ltd.

Pipeline

Disease Area	Indication	Platform	Targets
Liver Disease	Hepatitis B	Dual-Target	PD-L1+HBV Potential FIC and BIC
Liver Disease	Hepatitis B	Single-target	PD-L1 FIC
Metabolic Disease	Obesity	Adipose tissue delivery	ALK7 Potential BIC
Metabolic Disease	Obesity	Dual-target	To be disclosed Potential BIC
Cardiovascular Disease	Hypertension	Single-target	AGT Potential BIC

Introduction to Chronic Hepatitis B Treatment

Chronic hepatitis B virus (HBV) infection is a significant global public health concern. In 2019, approximately 296 million people worldwide were living with chronic HBV infection, with 1.5 million new cases annually. China accounts for about 86 million chronic HBV carriers, with 1 million new infections each year. HBV-related cirrhosis causes an estimated 331,000 (279,000 - 392,000) deaths globally per year, while HBV-related hepatocellular carcinoma (HCC) leads to 192,000 (162,000 - 224,000) deaths annually. The Chinese HBV drug market is projected to reach 64.8 billion RMB in 2024 and 85.8 billion RMB by 2030, maintaining a growth rate of approximately 14%.

Regarding chronic hepatitis B (CHB) treatment, conventional therapies include nucleos(t)ide analogs (NAs) and pegylated interferon-alpha (PegIFN-α), both of which exhibit low overall hepatitis B surface antigen (HBsAg) clearance rates.

Functional cure for CHB requires a triple mechanism: suppression of HBV replication, reduction of HBsAg levels, and restoration of exhausted HBV-specific immune function. However, monotherapy cannot address all three mechanisms. NAs effectively suppress HBV replication, siRNA-based therapies demonstrate strong HBsAg suppression, while PegIFN-α and PD-L1 inhibitors show potential for restoring innate immunity and achieving functional cure in select populations. The development of novel CHB therapies faces challenges such as low functional cure rates and HBsAg rebound post-clearance. Improving sustained functional cure rates remains an urgent unmet need.

Introduction to Obesity Treatment

In recent decades, overweight/obesity has emerged as a significant global health threat, predisposing individuals to various metabolic disorders such as diabetes, hypertension, ischemic heart disease, and cancer. According to the latest research report published in *The Lancet*, over 1 billion people worldwide were living with obesity in 2022, with 43% of adults classified as overweight.

The rising prevalence of obesity and increasing demand for weight loss interventions have driven substantial growth in the global anti-obesity drug market, expanding from 1.8 billion in 2016 to 2.6 billion in 2020. Projections estimate the market will reach 4.4 billion by 2023, reflecting a compound annual growth rate (CAGR) of 13.62% from 2016 to 2023.

GLP-1 receptor agonists have demonstrated significant efficacy in weight reduction. However, challenges such as weight regain after discontinuation, concurrent loss of lean muscle mass, and intolerable adverse effects have highlighted the need for novel therapeutic strategies that achieve healthier weight loss outcomes.

Introduction to Hypertension Treatment

Hypertension represents a significant public health concern. The global prevalence of hypertension (defined as blood pressure ≥140/90 mmHg or current use of antihypertensive medication) doubled from 650 million to 1.3 billion between 1990 and 2019, affecting one-third of adults worldwide. The China Hypertension Survey (2012–2015) estimated that 245 million Chinese adults have hypertension. In China alone, the hypertension treatment market has surpassed the hundred-billion-yuan threshold.

Although awareness, treatment, and control rates of hypertension in China have improved significantly, the treatment rate remains at only 45.8%, with a control rate of merely 16.8%. Notably, the corresponding rates in the United States during the same period were 70% (treatment) and 48% (control). To achieve a 50% control rate in China, an additional 87 million hypertensive patients would require effective treatment.

The development of novel antihypertensive drugs with improved efficacy, safety, and convenience—aimed at enhancing control rates, reducing dosing frequency, improving patient adherence, and addressing unmet clinical needs in both general and treatment-resistant hypertension—remains a critical priority.

SA1211

SA1211 is a GalNAc-conjugated siRNA therapeutic candidate independently developed by Suzhou SiranBio based on its dual-target platform technology. It simultaneously targets HBV X gene and PD-L1 mRNA, combining the functions of SA011 and SA012 to address the triple mechanism of CHB treatment: HBV replication suppression, HBsAg reduction, and restoration of HBV-specific immune function.

Nonclinical pharmacodynamic studies demonstrate that SA1211 Dimer rapidly reduces HBsAg and HBV DNA levels, with 80% of animals achieving undetectable HBsAg and HBV DNA, along with a high rate of seroconversion. (Relevant findings were presented at the 2024 AASLD poster session.)

SA1211 is currently in the IND-enabling stage.

SA012

SA012 is a GalNAc-conjugated siRNA therapeutic candidate independently developed by Suzhou SiranBio, targeting hepatocyte PD-L1 mRNA to restore HBV-specific adaptive immunity. Compared to traditional anti-PD-L1 monoclonal antibodies for CHB treatment, SA012 offers unique advantages: 1) Precise targeting: SA012 acts specifically on hepatocyte PD-L1 to restore exhausted HBV-specific CD8+ T cell function, exerting antiviral effects. 2) Enhanced efficacy: Due to its favorable safety profile, SA012 enables higher dosing in clinical settings, ensuring sufficient and durable therapeutic effects. 3) Improved safety: The liver-specific targeting of SA012 minimizes systemic immune-related adverse events, enhancing patient compliance.

Study results show that a single dose of SA012 effectively and persistently clears HBsAg and HBV DNA in humanized PD-1/PD-L1 mice. When combined with other anti-HBV agents (e.g., VIR-2218 or Bepirovirsen), SA012 demonstrates significant synergistic effects without viral rebound throughout the study period. (Relevant findings were presented at the 2024 EASL poster session.)

SiranBio has completed the development of the SA012 PCC molecule.

SA030

ALK7 (ACVR1C), a type I receptor of the TGF-β superfamily, is structurally characterized as a single-pass transmembrane protein with predominant expression in white and brown adipose tissues. Upon ligand binding, ALK7 activates the Smad 2/3/4 signaling cascade, downregulating lipase expression to suppress lipolysis. Pharmacological inhibition of ALK7 promotes fat breakdown while preserving lean mass.

SiranBio ALK7-siRNA project can achieve selective fat reduction without compromising muscle mass.

SA016

SA016 is a GalNAc-siRNA therapeutic candidate for hypertension, independently developed by Suzhou SiranBio. It targets angiotensinogen (AGT) mRNA within the RAAS signaling pathway and is designed for administration once every six months. SA016 is intended for monotherapy in mild-to-moderate hypertension and as an adjunct to first-line antihypertensive drugs in treatment-resistant hypertension.

Nonclinical studies demonstrate that SA016 exhibits comparable in vitro and in vivo activity to Alnylam’s hypertension candidate, Zilebesiran, with significantly lower off-target activity in vitro. Rat toxicology studies revealed no hepatic pathological changes. Based on these findings, SA016 is anticipated to achieve a sustained 6-month pharmacodynamic effect in clinical settings, mirroring Zilebesiran, with a favorable safety profile.

SiranBio has secured the SA016 PCC (preclinical candidate) molecule and is seeking collaborative development partners.