Type 2 Diabetes VK0612 is a potent, orally available, inhibitor of fructose-1,6-bisphosphatase. VK0612 has successfully completed six Phase 1 trials and a Phase 2a proof of concept study. Five of the Phase 1 trials demonstrated the safety, tolerability, and pharmacokinetic profile of VK0612 in healthy volunteers. The sixth Phase 1 trial was a Phase 1b study in patients with poorly-controlled type 2 diabetes. The Phase 1b and 2a studies demonstrated the safety and clinical proof-of-concept for inhibition of fructose-1,6-bisphosphatase as a potential therapy for type 2 diabetes.
Phase 2a Proof-of-Concept Summary The Phase 2a proof-of-concept trial was conducted in patients with moderate to severe type 2 diabetes. In this trial, patients received either placebo or VK0612 (10, 50, 100 or 200 mg capsule) once-daily for 28 days. At the highest dose, a statistically significant and clinically meaningful reduction in fasting plasma glucose (FPG) from baseline was achieved on Day 28 relative to placebo (mean placebo-adjusted change of -28.9 mg/dL). In the subgroup of patients with baseline FPG ≥ 180 mg/dL treated with 200 mg, the decrease in FPG was even more substantial (-49.7 mg/dL, placebo-adjusted). The overall incidence of treatment-emergent adverse events during the trial was low, including GI events. Moreover, mean fasting plasma lactate levels remained within normal limits in all groups, and no sustained lacticemia (lactate >4.5 mM on two consecutive visits) was observed.
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DGAT-1 Inhibitor Program DiacylGlycerol Acyl Transferase-1 (DGAT-1) is a key enzyme involved in the formation of triglycerides and is highly expressed in human fat metabolism sites such as intestine, liver, and adipose. Dietary triglycerides cannot be absorbed directly in the gastrointestinal, or GI, tract and are broken down into free fatty acids and monoglycerol in the intestine by pancreatic lipase. Once absorbed, the free fatty acids and glycerol are reassembled into triglycerides at the site of absorption, called an enterocyte, and packaged into chylomicron particles to be transported in the lymphatic system to be used throughout the body. DGAT-1 is one of two enzymes that catalyze the steps of triglyceride biosynthesis from mono- or diacylglycerol and fatty acids, and is mainly distributed in the intestine, liver and adipose tissue.
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EPOR Agonist Program Erythropoietin (EPO) acts on its receptor to stimulate the differentiation of bone marrow hematopoietic cells to form red blood cells. Various recombinant human EPO derivatives are marketed as erythropoiesis-stimulating agents (ESAs) for the treatment of anemia due to renal failure or cancer chemotherapy (e.g., Aranesp™, Epogen™, Eprex™, and Procrit™).
Activation of downstream signaling pathways results in proliferation, survival (anti-apoptosis) and differentiation of thyroid progenitor cells into red blood cells
We have developed a series of orally-available, small molecule agonists of the EPO receptor that may provide additional benefit in the treatment of anemia with improved safety, tolerability, and patient acceptance due to the convenience of oral administration and the lack of excessive erythropoietic stimulation. Anemia results from a decrease in red blood cells and is typically experienced by patients with renal complications, cancer patients and HIV/AIDS patients. These patients currently receive recombinant human EPO and other erythropoiesis-stimulating agents, or ESAs.
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