Innovent Unveils Next-Generation Obesity Pipeline at ADA 2026, Featuring Oral Daily and Weekly GLP-1 Candidates, Amylin Analog, and INHBE siRNA
核心洞察
Innovent Biologics (搜索) presented preclinical and Phase 1 data on four next-generation metabolic candidates at the 2026 ADA Scientific Sessions, including oral daily (IBI3032 (搜索)) and oral weekly (IBI3042 (搜索)) small-molecule GLP-1 receptor (搜索) agonists.
IBI3032 (搜索) demonstrated 10.11% body weight reduction over 4 weeks with a gradual dose-titration regimen in a Phase 1 MAD study, with a manageable safety profile and no treatment-related serious adverse events.
IBI3042 (搜索), potentially the first once-weekly oral small-molecule GLP-1 agonist, showed superior or comparable efficacy to Orforglipron in preclinical models and is expected to enter clinical studies by end of 2026.
Innovent Biologics (搜索) presented a comprehensive suite of preclinical and early clinical data from its next-generation obesity (搜索) and metabolic pipeline at the 2026 American Diabetes Association (ADA) Scientific Sessions in New Orleans. The presentations, delivered on June 7–8, 2026, showcased four distinct programs — IBI3032 (搜索), IBI3042 (搜索), IBI3040 (搜索), and IBI3046 (搜索) — that collectively aim to address key unmet needs in weight management, including tolerability, muscle preservation, dosing convenience, durability of weight loss, and integrated comorbidity management.
Dr. Lei Qian, Chief R&D Officer (General Biomedicine) of Innovent, stated, "At this year's ADA Scientific Sessions, we are pleased to present a series of new data in obesity (搜索) and metabolic diseases, which is an important step in establishing Innovent as an emerging leader and innovator in this field."
IBI3032 (搜索): Oral Daily Small-Molecule GLP-1 Receptor (搜索) Agonist
IBI3032 (搜索) is a novel, orally bioavailable non-peptidic GLP-1 receptor (搜索) agonist discovered via structure-based design. Preclinical data (Abstract No. 1678-P) revealed potent activation of the human GLP-1R with an EC₅₀ of 0.53 nM, high selectivity, and minimal β-arrestin recruitment. In cynomolgus monkeys, IBI3032 demonstrated an oral bioavailability of 24.5% and a half-life of 6.3 hours. In a 28-day study using hGLP-1R knock-in DIO mice, oral IBI3032 produced dose-dependent body weight reductions: 1 mg/kg achieved −1.8%, 6 mg/kg achieved −8.0%, and 12 mg/kg achieved −10.8% relative to vehicle. In a 28-day cynomolgus monkey study, once-daily oral IBI3032 at 1 mg/kg produced 11.2% body weight loss versus vehicle. Notably, compared to the marketed small-molecule GLP-1R agonist Orforglipron, IBI3032 demonstrated significantly superior weight-loss efficiency, achieving markedly greater body weight loss at half the dose in preclinical models.
Phase 1 clinical results (Abstract No. 1690-P) from single-ascending dose (SAD) and multiple-ascending dose (MAD) studies further characterized the candidate. The SAD study enrolled 40 participants with or without overweight/obesity (搜索) (BMI 20–40 kg/m²) receiving single doses of 0.3 mg, 1.0 mg, 3.0 mg, and 6.0 mg. The MAD study enrolled 79 overweight/obese participants (BMI 24–40 kg/m²) receiving once-daily oral IBI3032 (搜索) for 4 weeks across dose-titration regimens ranging from 0.6 mg to 10 mg.
Pharmacokinetic analysis showed that systemic exposure increased in an approximately dose-proportional manner across the 0.3–6 mg range, with peak plasma concentration occurring 5–12 hours post-dose and a terminal elimination half-life of approximately 2 days, supporting once-daily dosing.
The safety profile was manageable: nearly all treatment-emergent adverse events were mild to moderate, with no treatment-related serious adverse events reported. No cases of acute pancreatitis, acute kidney injury, acute gallbladder disease, major adverse cardiovascular events, thyroid C-cell hyperplasia, or thyroid carcinoma were observed.
A key finding emerged from the dose-titration analysis. In the cohort starting at 0.6 mg with a seven-step escalation to 9 mg (n=12), 4-week treatment led to an average 10.11% body weight reduction, while vomiting incidence remained at 8.3%. Compared with cohorts using aggressive escalation with high starting doses and large dose increments, this slow-titration regimen with lower initial doses, smaller incremental jumps, and prolonged escalation cycles lowered gastrointestinal adverse event risk while retaining weight-lowering efficacy. Additional Phase 1 studies are ongoing to further refine optimal dose-titration schemes.
IBI3042 (搜索): Once-Weekly Oral Small-Molecule GLP-1 Receptor (搜索) Agonist
IBI3042 (搜索) is positioned as potentially the world's first once-weekly oral small-molecule GLP-1 receptor (搜索) agonist candidate, with clinical studies expected to begin by the end of 2026. Preclinical results (Abstract No. 2543-P) demonstrated GLP-1R activation in cAMP assays without β-arrestin recruitment in NanoBiT assays.
In human GLP-1 receptor (搜索) knock-in mice, IBI3042 (搜索) at 0.4 mg/kg orally maintained significant glucose-lowering effects for at least 7 days, outperforming Orforglipron at the same dose. In DIO humanized GLP-1R knock-in mice, IBI3042 at 1 mg/kg twice weekly showed comparable efficacy to Orforglipron 1.5 mg/kg once daily, while the 3 mg/kg twice-weekly dose demonstrated superior efficacy. In contrast, Orforglipron at 3 mg/kg twice weekly showed no notable efficacy.
In obese cynomolgus monkeys, IBI3042 (搜索) produced robust, dose-dependent body weight reduction with twice-weekly oral dosing (1.5–4.5 mg/kg). The 1.5 mg/kg twice-weekly regimen achieved efficacy comparable to Orforglipron 1 mg/kg once daily, while the 4.5 mg/kg twice-weekly regimen demonstrated superior body weight reduction. The 7 mg/kg once-weekly regimen also matched the efficacy of Orforglipron 1 mg/kg once daily.
IBI3040 (搜索): Novel Amylin Analog
IBI3040 (搜索) is a highly potent agonist of the amylin and calcitonin receptors. Preclinical data (Abstract No. 3077-LB) showed that in a 2-week study in DIO rats, IBI3040 at 2 and 10 nmol/kg administered every three days resulted in dose-dependent body weight reductions of 8.82% and 11.11%, respectively, compared to vehicle. In a combination study, IBI3040 plus semaglutide produced a weight reduction of −14.7%, compared to −10.12% for IBI3040 monotherapy and −3.01% for semaglutide monotherapy, indicating an additive effect. Compared to cagrilintide, IBI3040 displayed a favorable pharmacokinetic profile, high solubility, and stability without fibril formation at physiological pH (7–8).
IBI3046 (搜索): INHBE-Targeting siRNA
IBI3046 (搜索) is an INHBE-silencing RNAi therapeutic designed to enhance adipose lipolysis with sustained effects. Preclinical results (Abstract No. 2662-P) demonstrated potent and durable mRNA knockdown in an hINHBE knock-in mouse model. In efficacy studies, IBI3046 monotherapy resulted in a 13% reduction in body weight and a 50% decrease in fat mass relative to control. In combination with a low dose of a GLP-1 receptor (搜索) agonist, IBI3046 achieved 20% body weight loss and an 80% reduction in fat mass. Additionally, IBI3046 extended the duration of suppressed weight regain following drug withdrawal. The candidate is designed for dosing every three to six months, potentially offering improved adherence and quality of life for patients with diabetes and obesity (搜索).
Dr. Qian emphasized that these programs "represent key progresses of our next-generation obesity (搜索) pipeline with global potential, which are designed to address unmet needs around tolerability, muscle preservation, dosing convenience, durability of weight loss and management of obesity-related comorbidities."