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 infec↑tion, with 1.5 million new cases annually. China ac≠counts 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, maintaβining a growth rate of approximately 14%.

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

Functional cure for CHB requires a triple mechanism: s♦uppression of HBV replication, reduction of HBsAg levels, and restoration of exhausted HBV-specifi←c immune function. However, monotherapy cannot address all three §mechanisms. NAs effectively suppress HBV replication, ≤siRNA-based therapies demonstrate strong HBsAg suppression, while PegIFN-αε and PD-L1 inhibitors show potential for restoring innate im♦munity and achieving functional cure in select popu✘lations. The development of novel CHB therapies faces challenges su§ch as low functional cure rates and HBsAg rebound post-clearance. Improving sustained functio<nal cure rates remains an urgent unmet need.

Introduction to Obesity Treatment

In recent decades, overweight/obesity has emerged as a significant global health th→reat, predisposing individuals to various metabolic di$sorders such as diabetes, hypertension, ischemic heart disease, and cancer. Acc∑ording to the latest research report published in *The Lancet*, over 1 billion p↔eople worldwide were living with obesity in 2022, with 43% of adults claφssified 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 t o 2.6 billion in 2020. Projections estimate the market will reach 4.4 billion by 2↔023, reflecting a compound annual growth rate (CAGR) of 13.62% from 201•6 to 2023.

GLP-1 receptor agonists have demonstrated significant efficac‍y in weight reduction. However, challenges such as weight regain after discontinua<tion, concurrent loss of lean muscle mass, and intolerable adverse effects have hig∞hlighted the need for novel therapeutic strategies that achie✘ve 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 o"r current use of antihypertensive medication) doubled from 650 ≠million to 1.3 billion between 1990 and 2019, affecting one-third of adults worldwide. The Chi↓na Hypertension Survey (2012–2015) estimated that δ245 million Chinese adults have hypertension. In China alone, the hypertensio₽n treatment market has surpassed the hundred-billion-↓yuan threshold.

Although awareness, treatment, and control rates of hypertension" in China have improved significantly, the treatment ra↔te remains at only 45.8%, with a control rate of merely 16.8%. Notably, the correspon÷ding rates in the United States during the same period were 70% (treatmeΩnt) and 48% (control). To achieve a 50% control rate in China, an ad₩ditional 87 million hypertensive patients would require effective tre♣atment.

The development of novel antihypertensive drugs with improved efficacy, safety, an>d convenience—aimed at enhancing control rates, reducing dosing frβequency, improving patient adherence, and addressing unmet clinic♠al needs in both general and treatment-resistant hypertension—remains a critical priority÷.

SA1211

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

Nonclinical pharmacodynamic studies demonstrate that SA1211 Dimer rap≠idly reduces HBsAg and HBV DNA levels, with 80% of anima ls achieving undetectable HBsAg and HBV DNA, along with a high rate of seroconversi>on. (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 b✔y Suzhou SiranBio, targeting hepatocyte PD-L1 mRNA to restore HBV-specific aσdaptive immunity. Compared to traditional anti-PD-♥L1 monoclonal antibodies for CHB treatment, SA012 offers unique advantφages: 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 safe ty profile, SA012 enables higher dosing in clinical settings, ensuring s♣ufficient and durable therapeutic effects. 3) Improved safety: The liver-specific targeting of S÷A012 minimizes systemic immune-related adverse eve±nts, enhancing patient compliance.

Study results show that a single dose of SA012 effectively and persistently clea•rs 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 sy∞nergistic 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 aγ single-pass transmembrane protein with predominant expressiλon in white and brown adipose tissues. Upon ligand binding,♠ ALK7 activates the Smad 2/3/4 signaling cascade, downregulating lipase expression to suppress lipo×lysis. 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, i↕ndependently developed by Suzhou SiranBio. It targets angiotenβsinogen (AGT) mRNA within the RAAS signaling pathway and is designed for admini∏stration once every six months. SA016 is intended for mon≈otherapy in mild-to-moderate hypertension and as an ↕adjunct to first-line antihypertensive drugs in treatment-resistant hypertensio★n.

Nonclinical studies demonstrate that SA016 exhibits comparable in vitr o and in vivo activity to Alnylam’s hypertension candidate, Zilebe÷siran, with significantly lower off-target activity in vitro.↔ Rat toxicology studies revealed no hepatic pathological changes. Based on t₹hese findings, SA016 is anticipated to achieve a sustained 6-month pharmacodynamic effect in clini↓cal settings, mirroring Zilebesiran, with a favorable safety profile.

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