Innovent Biologics and SanegeneBio have announced encouraging Phase 1 clinical results for IBI3016, an experimental small interfering RNA (siRNA) therapy targeting angiotensinogen mRNA for hypertension treatment. The preliminary data, presented at the 2025 American Heart Association scientific sessions, demonstrated sustained and potent AGT mRNA suppression with preliminary evidence of antihypertensive efficacy after single-dose subcutaneous administration.
Sustained AGT Suppression and Blood Pressure Reduction
The first-in-human Phase 1 study (NCT06501586/CTR20242500) enrolled 40 healthy subjects and patients with mild hypertension across five dose-escalating cohorts. Following single-dose administration, serum AGT levels were significantly and durably reduced, with maximum reductions exceeding 95% and sustained inhibition lasting up to six months.
Cohorts 1-5 reached maximum AGT suppression at approximately four weeks, achieving reductions of 91.7%, 91.4%, 94.7%, 96.2%, and 97.5%, respectively. At six months, AGT reductions remained substantial at 85.9%, 84.0%, 90.8%, 93.8%, and 96.4% for the respective cohorts.
Three months after administration, all treated cohorts demonstrated meaningful blood pressure reductions. The 24-hour mean ambulatory daytime systolic/diastolic blood pressure changes from baseline were -8.8/-9.7, -2.1/0.8, -7.1/-5.5, -11.0/-12.5, and -16.7/-14.7 mmHg for Cohorts 1-5, respectively, compared to -3.2/-5.7 mmHg for placebo. Nighttime blood pressure changes showed similar patterns, with reductions of -9.4/-3.3, -7.1/-4.9, -15.1/-10.7, -11.6/-6.7, and -16.0/-12.9 mmHg for the treatment cohorts versus -5.0/-2.6 mmHg with placebo.
Favorable Safety Profile
IBI3016 demonstrated favorable safety and tolerability over the six-month observation period. No severe adverse events or serious adverse events were observed, and importantly, no hypotension events occurred. All reported adverse events were mild to moderate in severity and reversible.
The study population consisted entirely of Chinese subjects with a median age of 37 years (range 24-54 years), 30% female representation, mean BMI of 25.2 kg/m², and baseline 24-hour ambulatory blood pressure mean of 122/74 mmHg. No significant differences in baseline characteristics were observed across treatment groups.
Addressing Unmet Medical Need
Dr. Haiyan Li, Principal Investigator and Director of Peking University Third Hospital, emphasized the clinical significance of these findings. "Hypertension is the most prevalent non-infectious disease in China, and the estimated number of adults with hypertension in China is about 245 million," Li stated. "Although there are many oral drugs for the treatment of hypertension in clinical practice, there are still problems such as poor medication adherence and aldosterone escape, resulting in a low overall blood pressure control rate."
The global burden of hypertension affects 1.4 billion people worldwide, with only about 20% of patients effectively controlled through medication or lifestyle interventions. Poor medication adherence has become a major challenge in hypertension treatment, as current antihypertensive drugs require daily administration.
Mechanism and Development Strategy
IBI3016 is a GalNAc-conjugated experimental RNAi-based medicine designed to inhibit AGT synthesis through RNA interference. Preclinical data show that IBI3016 can inhibit AGT synthesis in the liver, leading to lasting decreases in AGT protein and subsequent reductions in angiotensin II, ultimately resulting in blood vessel dilation and blood pressure reduction.
Dr. Lei Qian, Chief R&D Officer of General Biomedicine from Innovent, highlighted the therapeutic potential: "With their long-acting effects and stable efficacy, siRNA drugs have shown great application potential in chronic conditions such as cardiometabolic diseases that require sustained, long-term management."
The Phase 1 data support the potential for biannual subcutaneous dosing, which could significantly improve patient adherence compared to daily oral medications. Dr. Yuyan Jin, Senior Vice President of Clinical and Non-Clinical Development at SanegeneBio, noted that "IBI3016 as a transformative RNAi innovative therapeutic promises to address existing issues such as poor adherence to traditional drugs and aldosterone escape."
Next Steps in Development
Based on these encouraging preliminary results, the companies plan to initiate next-step development soon. The sustained AGT inhibition and preliminary antihypertensive effects observed in both healthy subjects and patients with mild hypertension provide strong support for subsequent clinical development phases.
The collaboration leverages SanegeneBio's expertise in siRNA drug discovery and Innovent's extensive clinical experience in cardiovascular and metabolic diseases. SanegeneBio, founded in 2021, utilizes its proprietary LEAD™ tissue-selective RNAi delivery technology and has R&D operations in Boston, Shanghai, and Suzhou.
