Other Pipeline Programs


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.

Phase 1b Results: Promise In Poorly-Controlled Type 2 Diabetes

Subsequent to the successful Phase 2a trial, a superior formulation was developed that provided significantly higher drug exposures relative to that used in the Phase 2a study. This formulation was evaluated in a Phase 1b study

Substantial Reductions in Fasting and 24-Hour Glycemia Measures

The Phase 1b study was a 14-day, randomized, double‐blind, placebo‐controlled, ascending multiple dose trial to assess the safety, tolerability, PK, and efficacy of VK0612 in 42 patients with type 2 diabetes. Doses of 50 mg, 200 mg, and 400 mg BID compared to placebo were evaluated. After 14 days of treatment, a rapid and pronounced dose‐related decrease in FPG was observed. Despite the relatively small study size, the results demonstrated a statistically significant impact on fasting plasma glucose levels. In addition, there were substantial dose‐related decreases in 24 hour weighted mean glucose levels, with all doses achieving statistical significance.

Inhibition of FBPase: A Potent Mechanism for Glucose Control

The combined Phase 1b and Phase 2a results demonstrate that inhibition of FBPase is an effective mechanism for lowering fasting and postprandial hyperglycemia in patients with poorly-controlled Type 2 diabetes. Importantly, VK0612 was safe at all doses, with the maximum tolerated dose in Phase 1b identified as 200 mg twice daily.

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.

DGAT-1 Mediates Absorption of Fats from the GI Tract

DGAT-1Inhibition of DGAT-1 in the enterocyte reduces post-prandial fat deposition; increases nutrient sensing, satiety.

Inhibition of the enzyme has shown to reduce fat storage in animal models and clinical trials, leading to reduction of body weight. However, non-selective systemic reduction of fat formation can lead to undesirable side effects demonstrated in DGAT-1 null mice. By introducing a unique chemical function group into the DGAT-1 inhibitors, Viking is developing a series of lead compounds that selectively inhibited DGAT-1 at enterocytes, the intestinal absorptive cells responsible for the absorption of dietary fat, and that demonstrated efficacy in animal models of dietary induced obesity.

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™).

Epogen Receptor Activation Stimulates Multiple Signaling Pathway


Activation of downstream signaling pathways results in proliferation, survival (anti-apoptosis) and differentiation of thyroid progenitor cells into red blood cells

We are developing 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.

Several small molecule EPOR agonists have been identified with encouraging in vitro and in vivo profiles. We plan to conduct further pre-clinical and clinical development in pursuit of a potential IND filing.