Innovent Biologics and Sanegene Bio Announce Phase 1 Clinical Results of IBI3016 (SGB-3908), a Novel siRNA Therapeutic Targeting AGT for Hypertension

November 10,Innovent Bio and SANEGENEBIO jointly announced,Targeting Angiotensinogen (AGT) small interfering RNA (siRNA) drug IBI3016The main results of the first-in-human (FIH) Phase 1 clinical study of SANEGENEBIO's research and development code: SGB-3908 were presented at the digital poster session of the 2025 American Heart Association (AHA) Scientific Sessions.

This FIH study (NCT06501586 / CTR20242500) is a randomized, double-blind, placebo-controlled, single ascending dose trial conducted in healthy subjects and patients with mild hypertension, aiming to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) profiles following subcutaneous administration of IBI3016.

As of July 1, 2025, a total of 40 healthy subjects and subjects with mild hypertension were randomly assigned to five cohorts (with a ratio of 6:2 for the IBI3016 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 baseline mean 24-hour ambulatory blood pressure of 122/74 mmHg. There were no significant differences in baseline characteristics among the groups.

Single-dose administration of IBI3016 achieves sustained and potent reduction in AGT levels along with preliminary blood pressure decrease.

• After a single dose, serum AGT levels were significantly and persistently reduced, with a maximum reduction of over 95%, which remained stable for 6 months.Cohorts 1 to 5 of the IBI3016 dose groups reached their maximum reductions at approximately 4 weeks, which were 91.7%, 91.4%, 94.7%, 96.2%, and 97.5%, respectively. 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 IBI3016 achieved a reduction in blood pressure:The changes in 24-hour average daytime ambulatory systolic/diastolic blood pressure relative to baseline for IBI3016 dose groups 1 to 5 were −8.8/−9.7, −2.1/+0.8, −7.1/−5.5, −11.0/−12.5, and −16.7/−14.7 mmHg, respectively, while the placebo group showed −3.2/−5.7 mmHg. The changes in nighttime average ambulatory systolic/diastolic blood pressure for each dose group were −9.4/−3.3, −7.1/−4.9, −15.1/−10.7, −11.6/−6.7, and −16.0/−12.9 mmHg, respectively, while the placebo group showed −5.0/−2.6 mmHg.

Good safety and tolerability, with no unexpected safety signals

• IBI3016 demonstrated good safety and tolerability within 6 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.

IBI3016 (SANEGENEBIO R&D Code: SGB-3908) isInnovent Bio and SANEGENEBIO jointly develop an AGT-targeted siRNA drug for the treatment of hypertensionIBI3016, developed based on SANEGENEBIO's proprietary small nucleic acid drug development platform using GalNAc liver-targeting delivery technology, inhibits the synthesis of AGT through the RNAi mechanism. Preclinical trial data shows that IBI3016 can inhibit the synthesis of AGT in the liver, potentially leading to a sustained reduction in AGT protein, further resulting in decreased Ang II, and ultimately achieving vasodilation and blood pressure reduction.

References:
[1] Innovent Bio and SANEGENEBIO jointly announce the Phase I clinical study results of IBI3016 (AGT siRNA) presented at the 2025 AHA conference. From https://www.prnasia.com/story/511019-1.shtml

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