1. Clear MOA
(1) sGC is an enzyme in the cardiopulmonary system that relaxes vascular smooth muscles, resulting in pulmonary vasodilation, reduced PAH, and improved cardiac output.
(2) Soluble guanylate cyclase (sGC) stimulators are medications used to treat PAH, CTEPH, HFrEF and CKD.
2. High efficacy in vitro.
(1) The asset is better than 2nd generation of sGC stimulator Vericiguat.
(2) Asset has a desirable selectivity. The IC50 values were 7.74 μM for human PPARγ, 3.05 μM for human 5-HT2B and 5.79 μM for rat Sodium Channel, Site 2, corresponding to 1187-times, 467-times, and 888-times.
3. Better efficacy in vivo.
(1) Improved MCT-induced increase in RVSP.
(2) Prevented the increases in LVSP and LVEDP on abdominal aortic constriction-induced cardiac pressure overload in rats.
(3) Improved the survival rate and GSI (glomerulosclerosis index) in the diabetic nephropathy model.
4. The asset is not an inhibitor of CYPIA2, 2B6, 2C8, 2C19, 2D6 or 3A4 and is not an inducer of CYP1A2, 2B6, or 3A4. It is a substrate of P-gp but is not a substrate of BCRP.
5. Good safety.
(1) No effects were noted on the central nervous systems (30 mpk in rats) and respiratory function (10 mpk in dogs).
(2) No mutagenic and chromosome aberration risk.
(3) Well-tolerated in single-dose toxicity after PO to rats (≤ 400 mpk) or dogs (≤ 2000 mpk).
6. Great Phase 1 data: well tolerated, the half-life indicated suitability for once-daily dosing.
1. Asset type: sGC stimulator
2. Indication: Pulmonary arterial hypertension (PAH), Chronic thromboembolic pulmonary hypertension (CTEPH), Heart failure with reduced ejection fraction (HFrEF), Chronic kidney disease (CKD)
3. Modality: Small molecular
4. Research phase: Phase 1, IP has been granted in US, AU, CN
5. Cooperation demands: License-out or co-development
6. Research progress：
(1) Phase 1 trial is ongoing.
(2) The GSI after asset administration is lower than that of Losartan.
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