Sanegene Bio and Innovent Announce Phase I Clinical Results of SGB-3908 (AGT siRNA) at AHA 2025, Highlighting Potential for Biannual Dosing in Hypertension Treatment
SANEGENEBIO
Small Nucleic Acid Drug Developer
Innovent
High-end Biologics Developer
▷SGB-3908 Single Dose Demonstrates Persistent and Potent Reduction of AGT Levels with Preliminary Antihypertensive Efficacy
▷The clinical Phase I study data of SGB-3908 further supports its potential for subcutaneous administration every six months to achieve blood pressure reduction, with subsequent clinical development set to commence.
On November 10, 2025, SANEGENEBIO, a company focused on innovative RNAi drug research and development, and Innovent Bio jointly announcedSmall interfering RNA (siRNA) drugs targeting angiotensinogen (AGT)The main results of the first-in-human (FIH) Phase I clinical study of SGB-3908 (Innovent Bio's research and development code: IBI3016) were presented at the digital poster session of the 2025 American Heart Association (AHA) Scientific Session. Director Wang Fangfang from Peking University Third Hospital orally presented the study findings on-site as the speaker.
The FIH study (NCT06501586 / CTR20242500) of SGB-3908 (AGT siRNA) is a randomized, double-blind, placebo-controlled, single ascending dose trial conducted in healthy subjects and patients with mild hypertension. It aims to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) profiles following subcutaneous administration of SGB-3908.
As of July 1, 2025, a total of 40 healthy subjects and subjects with mild hypertension were randomly assigned to 5 cohorts (with a ratio of 6:2 for the SGB-3908 dose group to the placebo group in each cohort). All subjects were Chinese, with a median age (range) of 37 years (24–54 years), 30% being female, an average BMI of 25.2 kg/m², and a mean baseline 24-hour ambulatory blood pressure of 122/74 mmHg. No significant differences were observed in baseline characteristics across the groups.
SGB-3908 Achieves Long-Lasting and Potent Reduction of AGT Levels with a Single Dose, Along with Preliminary Blood Pressure Decrease
After a single dose, serum AGT levels were significantly and persistently reduced by more than 95% at maximum, with the reduction remaining stable for six months.: Cohorts 1~5 of the SGB-3908 dose groups reached their maximum reductions of 91.7%, 91.4%, 94.7%, 96.2%, and 97.5%, respectively, at approximately 4 weeks. At 3 months, the sustained reductions for each dose group were 91.2%, 90.0%, 93.8%, 96.5%, and 97.0%, respectively. At 6 months, the reductions for each dose group were maintained at 85.9%, 84.0%, 90.8%, 93.8%, and 96.4%, respectively.
At 3 months, all dose groups of SGB-3908 achieved a reduction in blood pressure.: Cohorts 1 to 5 of SGB-3908 showed changes in the 24-hour average daytime ambulatory systolic/diastolic blood pressure relative to baseline of −8.8/−9.7, −2.1/+0.8, −7.1/−5.5, −11.0/−12.5, and −16.7/−14.7 mmHg, respectively, compared to −3.2/−5.7 mmHg in the placebo group. The changes in average nighttime ambulatory systolic/diastolic blood pressure were −9.4/−3.3, −7.1/−4.9, −15.1/−10.7, −11.6/−6.7, and −16.0/−12.9 mmHg, respectively, compared to −5.0/−2.6 mmHg in the placebo group.
Good safety and tolerability, with no unexpected safety signals.
SGB-3908 demonstrated good safety and tolerability over six months, with no severe adverse events (AE) or serious adverse events (SAE) observed, and no hypotension events occurred. All adverse events were mild to moderate and reversible.
The principal investigator of the study, Director Haiyan Li from Peking University Third Hospital, stated:
Hypertension is the most prevalent non-communicable disease in China, with an estimated 245 million adults suffering from hypertension. It is also the leading risk factor for increased cardiovascular disease incidence and mortality. Millions of people die each year from cardiovascular diseases associated with hypertension, imposing a significant socioeconomic burden. Despite the availability of numerous oral medications for hypertension treatment, issues such as poor medication adherence and aldosterone escape persist, resulting in suboptimal overall blood pressure control. However, siRNA targeting AGT, with its unique molecular advantages, can effectively improve patient compliance and potentially address aldosterone escape by providing long-term blood pressure reduction and suppressing the activity of the renin-angiotensin-aldosterone system (RAAS) at its source. I am pleased to see that the Phase I research results of SGB-3908 were presented at the AHA conference, demonstrating good safety and preliminary efficacy, laying a solid foundation for subsequent clinical development.
Dr. Jin Yuyan, Senior Vice President of Clinical and Non-clinical at SANEGENEBIO, stated:
Hypertension Still Faces Significant Unmet Clinical Needs Worldwide. SGB-3908, a transformative RNAi innovative therapeutic drug, has the potential to address existing issues such as poor compliance with traditional drugs and aldosterone escape. With the dedicated collaboration and professional commitment of Peking University Third Hospital Research Center, Innovent Bio, and SANEGENEBIO, the Phase I trial of SGB-3908 achieved promising interim results and was presented at an international conference. The findings demonstrated that SGB-3908 exhibited good safety, sustained AGT inhibition, and preliminary blood pressure-lowering effects in healthy subjects and patients with mild hypertension, providing strong support for subsequent clinical development. Moving forward, we will continue our close cooperation with Innovent Bio to efficiently execute the clinical development plan, fully advance the R&D progress of SGB-3908, and strive to achieve positive outcomes as soon as possible to unlock its therapeutic value. This will bring a more effective, safer, and better-compliance innovative treatment option to patients with hypertension.
Dr. Lei Qian, Chief Development Officer of Innovent Bio's Integrated Pipeline, stated:
Innovent Bio is committed to becoming a leading innovative pharmaceutical company in the field of chronic diseases, benefiting a wide range of patients with innovative therapies. siRNA drugs, with their long-lasting effects and stable efficacy, have demonstrated significant application potential in chronic disease areas that require long-term management, such as cardiometabolic disorders. Leveraging SANEGENEBIO’s technological advantages in siRNA drug development and Innovent Bio’s extensive experience in clinical development for cardiometabolic diseases, we have successfully obtained the interim results of the Phase I clinical trial for SGB-3908, which has bolstered our confidence for subsequent clinical development. We will adhere to scientific rigor and high-quality, efficient clinical development while closely collaborating with SANEGENEBIO to bring this innovative therapy to a broad population of hypertension patients as soon as possible.
About Hypertension
Hypertension, as a common chronic disease, has seen the global number of patients rise to 1.4 billion, yet only about 20% of them have achieved effective control through medication or lifestyle interventions.[1]Hypertension not only increases the risk of cardiovascular and cerebrovascular diseases but also may lead to complications such as kidney damage and vision loss. With the aging population and the prevalence of risk factors like obesity, lack of physical activity, and unhealthy diet, the global prevalence of hypertension continues to rise. Although there are currently effective antihypertensive treatments available in clinical practice, these medications need to be taken daily. Since hypertension is often asymptomatic or has mild symptoms, patients may forget to take their medication, leading to poor adherence—a major challenge in the current treatment of hypertension. With the groundbreaking advancements in RNA interference (RNAi) technology and targeted delivery systems, siRNA therapies utilizing GalNAc conjugation technology have shown great potential in the field of hypertension treatment. These innovative therapies, through long-acting and precise regulation of pathogenic gene expression, have the potential to completely transform the traditional treatment model where hypertensive patients need to "take medication daily."
About SGB-3908
SGB-3908 (Innovent Bio R&D code: IBI3016) is a siRNA drug targeting Angiotensinogen (AGT) co-developed by SANEGENEBIO and Innovent Bio for the treatment of hypertension. SGB-3908, developed based on SANEGENEBIO's proprietary GalNAc liver-targeting delivery technology, inhibits AGT synthesis through the RNAi mechanism. Preclinical trial data show that SGB-3908 can inhibit AGT synthesis in the liver, potentially leading to a sustained reduction in AGT protein, further resulting in decreased Ang II levels, ultimately causing vasodilation and blood pressure reduction.
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References:
[1] WHO. Global report on hypertension 2025.
