OADs with significant Cardio-protective benefit, improving whole body insulin sensitivity with anti-obesity and systemic anti-inflammatory benefits.
AMP-activated protein kinase is a systemic regulator of cellular energy(AMPK) homeostasis, coordinating anabolic and catabolic processes in glucose and lipid metabolism. AMPK exists as a trimer with specific combinations of the subunits and their isoforms in different tissues. Connexios program comprises specific and potent compounds which activate two sub-units of this trimeric complex, thus allowing the activation of the kinase across multiple metabolically relevant tissues.
- Robust glycemic control (fasting, fed, glucose excursion, HbA1c) and improved insulin sensitivity.
- Excellent lipid control (total Cholesterol, TG and LDL-C).
- Significant reduction in body weight without change in food intake.
- Significant improvement in liver steatosis.
- Protection against myocardial ischemic/reperfusion injury.
Connexios AMPK candidates are highly differentiated from other reported activators in their ability to directly activate AMPK across multiple tissues, including the Muscle, Liver and Adipose, which is the basis of its broad efficacy potential beyond Glycemic control.
The program is currently in late lead optimization phase, with several lead-like candidates that fulfill the product profile and PoC criteria.
CNX-012, a novel orally available direct activator of AMPK shows excellent glycemic control and steeply reduces the HbA1c level and also imparts ~10% loss in body weight in a rodent model (db/db) of T2D
CNX-012 provides unique cardiovascular benefit by protecting from myocardial ischemic/reperfusion injury in left anterior descending coronary artery (LAD) ligated mice as observed using TTC stained sections of Heart