Viking Therapeutics, Inc., a clinical-stage biopharmaceutical company, focuses on the development of novel, first-in-class or best-in-class therapies for metabolic and endocrine disorders.
In January 2022, the company announced the initiation of a Phase 1 single ascending dose, or SAD, and multiple ascending doses, or MAD, clinical trial of VK2735, a novel dual agonist of the glucagon-like peptide 1, or GLP-1, and glucose-dependent insulinotropic polypeptide, or GIP, receptors. VK2735 is being...
Viking Therapeutics, Inc., a clinical-stage biopharmaceutical company, focuses on the development of novel, first-in-class or best-in-class therapies for metabolic and endocrine disorders.
In January 2022, the company announced the initiation of a Phase 1 single ascending dose, or SAD, and multiple ascending doses, or MAD, clinical trial of VK2735, a novel dual agonist of the glucagon-like peptide 1, or GLP-1, and glucose-dependent insulinotropic polypeptide, or GIP, receptors. VK2735 is being developed in both oral and subcutaneous formulations for the potential treatment of various metabolic disorders, such as obesity.
On March 28, 2023, the company announced the completion of the Phase 1 trial. The study was a randomized, double-blind, placebo-controlled, SAD and MAD study in healthy adults. The primary objectives of the study included the evaluation of the safety and tolerability of single and multiple doses of VK2735 delivered subcutaneously, and the identification of VK2735 doses suitable for further clinical development. Study investigators also evaluated the pharmacokinetics of single and multiple doses of VK2735. Based upon the results from this Phase 1 study, in September 2023, the company initiated the VENTURE study, a Phase 2 clinical trial of VK2735 in patients with obesity.
The Phase 2 VENTURE study was a randomized, double-blind placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and weight loss efficacy of VK2735, administered subcutaneously, once weekly. The 13-week study enrolled adults who were obese (BMI >= 30 kg/m2), or adults who were overweight (BMI >= 27 kg/m2) with at least one weight-related co-morbidity condition. The primary endpoint of the study was the percent change in body weight from baseline to week 13, with secondary and exploratory endpoints evaluating a range of additional safety and efficacy measures. In October 2023, the company announced the completion of patient enrollment in the Phase 2 VENTURE study, and on February 27, 2024, the company announced that patients receiving weekly doses of VK2735 demonstrated statistically significant reductions in mean body weight after 13 weeks, ranging up to 14.7% from baseline. Patients receiving VK2735 also demonstrated statistically significant reductions in mean body weight relative to placebo, ranging up to 13.1%. Based on written feedback received from the U.S. Food and Drug Administration, or the FDA, the company expects to initiate Phase 3 clinical studies of the subcutaneous formulation of VK2735 in the first half of 2025.
On March 28, 2023, the company announced the initiation of a Phase 1 clinical study to evaluate a novel oral formulation of VK2735. The study, which was an extension of the company’s recently completed Phase 1 evaluation of subcutaneously administered VK2735, evaluated daily oral doses for 28 days. On March 26, 2024, the company announced that the 28-day MAD study results highlighted positive signs of clinical activity following treatment with oral VK2735. Cohorts receiving VK2735 demonstrated dose-dependent reductions in mean body weight from baseline, ranging up to approximately 5.3%.
On January 8, 2025, the company announced the initiation of a Phase 2 clinical trial of the oral tablet formulation of VK2735. The company expects to complete this study and report initial results in the second half of 2025. VK2735 is being developed in both oral and subcutaneous formulations for the potential treatment of various metabolic disorders, such as obesity.
The company is also developing VK2809, which is an orally available, tissue and receptor-subtype selective agonist of the thyroid hormone receptor beta, or TRß. In November 2019, the company initiated the VOYAGE study, a Phase 2b clinical trial of VK2809 in patients with biopsy-confirmed non-alcoholic steatohepatitis, or NASH, or metabolic dysfunction-associated steatohepatitis, or MASH.
The VOYAGE study was a randomized, double-blind, placebo-controlled, multicenter trial designed to assess the efficacy, safety, and tolerability of VK2809 in patients with biopsy-confirmed NASH/MASH and fibrosis ranging from stages F1 to F3. The primary endpoint of the study evaluated the relative change in liver fat content, as assessed by magnetic resonance imaging, proton density fat fraction, or MRI-PDFF, from baseline to week 12 in subjects treated with VK2809 as compared to placebo. Secondary objectives included the evaluation of histologic changes assessed by hepatic biopsy after 52 weeks of dosing.
In January 2023, the company announced the completion of patient enrollment in the VOYAGE study, and in May 2023, the company reported that the VOYAGE study successfully achieved its primary endpoint, with patients receiving VK2809 experiencing statistically significant reductions in liver fat content from baseline to Week 12 as compared to placebo.
In June 2024, the company announced positive 52-week histologic data from the VOYAGE study, with up to 75% of patients treated with VK2809 achieving NASH/MASH resolution with no worsening of fibrosis as compared to 29% for placebo (p=0.0001), up to 57% of VK2809-treated patients achieving =1-stage improvement in fibrosis with no worsening of NASH/MASH as compared to 34% for placebo (p<0.05), and up to 48% of VK2809-treated patients achieving both resolution of NASH/MASH and a =1-stage improvement in fibrosis as compared to 20% for placebo (p=0.01). Adverse events, including GI-related adverse events, were similar among VK2809-treated patients vs. placebo at week 52 and consistent with prior data reported at week 12. VK2809 has been evaluated in eight completed clinical studies, which enrolled more than 400 subjects.
The company is also developing VK0214, which is also an orally available, tissue and receptor-subtype selective agonist of TRß for X-linked adrenoleukodystrophy, or X-ALD, a rare X-linked, inherited neurological disorder characterized by a breakdown in the protective barriers surrounding brain and nerve cells. The disease, for which there is no approved treatment, is caused by mutations in a peroxisomal transporter of very long chain fatty acids, or VLCFA, known as ABCD1. As a result, transporter function is impaired, and patients are unable to efficiently metabolize VLCFA. The TRß receptor is known to regulate the expression of an alternative VLCFA transporter, known as ABCD2. Various preclinical models have demonstrated that increased expression of ABCD2 can lead to normalization of VLCFA metabolism. Preliminary data suggest that VK0214 stimulates ABCD2 expression in an in vitro model and reduces VLCFA levels in an in vivo model of X-ALD.
In June 2021, the company initiated a Phase 1b clinical trial of VK0214 in patients with X-ALD. This trial was a multi-center, randomized, double-blind, placebo-controlled study in adult male patients with the adrenomyeloneuropathy, or AMN, form of X-ALD. The study enrolled patients across three cohorts: placebo, VK0214 20 mg daily, and VK0214 40 mg daily.
In October 2024, the company announced results from the Phase 1b clinical trial, which showed VK0214 to be safe and well-tolerated following once-daily dosing over the 28-day study period. In addition, significant reductions were observed in plasma levels of VLCFAs and other lipids, as compared to placebo.
Other clinical programs include VK5211, an orally available, non-steroidal selective androgen receptor modulator, or SARM. In November 2017, the company announced positive top-line results from a Phase 2 proof-of-concept clinical trial in 108 patients recovering from non-elective hip fracture surgery. Top-line data showed that the trial achieved its primary endpoint, demonstrating statistically significant, dose-dependent increases in lean body mass, as well as reductions in fat following treatment with VK5211 as compared to placebo. The study also achieved certain secondary endpoints, demonstrating statistically significant increases in appendicular lean body mass and total lean body mass for all doses of VK5211 compared to placebo.
Development Pipeline
The company has a preclinical program focused on developing dual amylin and calcitonin receptor agonists, or DACRA, for the potential treatment of obesity.
VK2735
Activation of the GLP-1 receptor has been shown to decrease glucose, reduce appetite, lower body weight, and improve insulin sensitivity in patients with type 2 diabetes, obesity, or both. More recently, research efforts have explored the potential co-activation of the GIP receptor as a means of enhancing the therapeutic benefits of GLP-1 receptor activation. VK2735 is a dual agonist of the GLP-1 and GIP receptors that the company is developing for the potential treatment of various metabolic disorders. VK2735 is being developed in both subcutaneous and oral formulations for the potential treatment of various metabolic disorders, such as obesity.
VK2735 Subcutaneous
Based upon the results of the Phase 2 VENTURE study and the previous Phase 1 subcutaneous study, the company is currently preparing for the initiation of Phase 3 clinical studies for VK2735 subcutaneous in the first half of 2025.
Phase 2 Clinical Data for VK2735 Subcutaneous
In September 2023, the company initiated the VENTURE study, a Phase 2 clinical trial of VK2735 in patients with obesity. The Phase 2 VENTURE study was a randomized, double-blind placebo-controlled study that evaluated the safety, tolerability, pharmacokinetics, and weight loss efficacy of VK2735, administered subcutaneously, once weekly. The 13-week study enrolled adults who were obese (BMI >= 30 kg/m2), or adults who were overweight (BMI >= 27 kg/m2) with at least one weight-related co-morbidity condition. The primary endpoint of the study was the percent change in body weight from baseline to week 13, with secondary and exploratory endpoints evaluating a range of additional safety and efficacy measures. In October 2023, the company announced the completion of patient enrollment, and in February 2024, the company reported that the Phase 2 VENTURE study successfully achieved its primary endpoint and all secondary endpoints, with patients receiving VK2735 demonstrating statistically significant reductions in body weight compared with placebo. Additionally, the study showed VK2735 treatment to be safe and well-tolerated, with the majority of treatment emergent adverse events, or TEAEs, being categorized as mild or moderate.
Body Weight Reductions
Patients receiving weekly doses of VK2735 demonstrated statistically significant reductions in mean body weight after 13 weeks, ranging up to 14.7% from baseline. Patients receiving VK2735 also demonstrated statistically significant reductions in mean body weight relative to placebo, ranging up to 13.1%. Statistically significant differences compared to both baseline and placebo were observed for all doses starting at week one and continuing throughout the 13-week treatment period. Reductions in body weight were progressive through the course of the study, with no plateau observed for weight loss at 13 weeks. All doses of VK2735 also demonstrated statistically significant differences relative to placebo on the key secondary endpoint assessing the proportion of patients demonstrating at least 10% weight loss. Up to 88% of patients in VK2735 treatment groups achieved =10% weight loss, compared with 4% for placebo.
Safety and Tolerability
VK2735 demonstrated encouraging safety and tolerability following 13 weeks of once-weekly dosing. Discontinuation rates in the VENTURE study were low and well-balanced among patients treated with VK2735 compared with placebo. A total of 23 patients (13%) discontinued treatment in the study, 5 (14%) in the placebo cohort and 18 (13%) among VK2735-treated cohorts.
Among patients receiving VK2735, the majority (92%) reported drug-related TEAEs as mild or moderate in severity. The majority of TEAEs that were gastrointestinal, or GI, in nature (95%) were also reported as mild or moderate. Nausea was reported among patients receiving both VK2735 (43%) and placebo (20%). Among subjects receiving VK2735, the majority of reported nausea (68%) was characterized as mild (32% moderate, none severe). Vomiting was reported in 25/140 (18%) VK2735-treated patients compared with none reported among patients receiving placebo. GI-related adverse events were generally observed early in treatment, with decreasing frequency upon repeat dosing. Across the combined VENTURE study arms, the weekly rate of nausea did not exceed 5% at any point after the first week of treatment. One patient receiving VK2735 experienced an SAE of dehydration that was characterized as related to the study drug.
Phase 1 Clinical Data for VK2735 Subcutaneous
In January 2022, the company announced the initiation of a Phase 1 SAD and MAD clinical trial of VK2735. The Phase 1 trial was a randomized, double-blind, placebo-controlled SAD and MAD study in healthy adults. The SAD portion of the study evaluated VK2735 in healthy adults, while the MAD portion of the study enrolled healthy adults with a minimum body mass index of 30 kilograms per meter squared. The primary objectives of the study were to evaluate the safety and tolerability of single and multiple doses of VK2735 administered subcutaneously, and to identify suitable doses for further clinical development. The secondary objective was to evaluate the pharmacokinetics of VK2735 in healthy subjects. The SAD portion of the study evaluated escalating single doses of VK2735. In the MAD portion of the study, subjects received VK2735 once weekly for 28 days.
In March 2023, the company announced the completion of the Phase 1 trial and the related results from this Phase 1 study.
In the SAD portion of the study, VK2735 demonstrated promising safety and tolerability, as well as a predictable pharmacokinetic profile. Following single subcutaneous doses, VK2735 demonstrated a half-life of approximately 170 to 250 hours, a Tmax (time to reach maximum plasma concentration) ranging from approximately 75 to 90 hours, and excellent therapeutic exposures.
In the 28-day MAD portion of the study, VK2735 demonstrated encouraging tolerability and positive signs of clinical activity. All cohorts receiving VK2735 demonstrated reductions in mean body weight from baseline, ranging up to 7.8%. Cohorts receiving VK2735 also demonstrated reductions in mean body weight relative to placebo, ranging up to 6.0%. Statistically significant differences compared to placebo were maintained or improved at the day 43 follow-up time point, 21 days after the last dose of VK2735 was administered.
VK2735 demonstrated encouraging safety and tolerability following repeated dosing. The majority of observed adverse events (98%) were reported as mild or moderate. The majority of GI-related adverse events (99%) were also reported as mild or moderate. One SAE was reported in a subject receiving VK2735. A subject with a history of cholelithiasis (gallstones) experienced an SAE of acute choledocholithiasis (gallstone obstruction). Nausea was reported among subjects receiving both VK2735 (58%) and placebo (50%). Among subjects receiving VK2735, the majority of reported nausea (89%) was characterized as mild (11% moderate). Vomiting was reported in 6/31 (19%) VK2735-treated subjects and 1/10 (10%) subjects receiving placebo.
VK2735 Oral
Based upon the positive Phase 1 oral results from the 28-day MAD study, in January 2025, the company announced the initiation of a Phase 2 VENTURE-Oral Dosing Trial of VK2735 tablet formulation in patients with obesity. The Phase 2 VENTURE-Oral Dosing Trial is a randomized, double-blind, placebo-controlled multicenter study designed to evaluate the safety, tolerability, pharmacokinetics, and weight loss efficacy of VK2735 dosed as an oral tablet once daily for 13 weeks. The trial will enroll approximately 280 adults who are obese (BMI =30 kg/m2), or adults who are overweight (BMI =27 kg/m2) with at least one weight-related co-morbid condition. Patients will be evenly randomized to one of six dosing arms or placebo. The primary endpoint of the study is the percent change in body weight from baseline after 13 weeks of treatment. Secondary and exploratory endpoints will evaluate a range of additional safety and efficacy measures. The company expects to complete this study and report initial results in the second half of 2025.
The company previously reported positive results from the 28-day Phase 1 MAD clinical trial of the tablet formulation of VK2735 in healthy volunteers with a BMI =30. Cohorts receiving VK2735 demonstrated dose-dependent reductions in mean body weight from baseline, ranging up to 8.2%. Cohorts receiving VK2735 also demonstrated reductions in mean body weight relative to placebo, ranging up to 6.8%. Persistent weight loss effects were observed at follow-up visits through day 57, ranging up to 8.3% from baseline, four weeks after the last dose of VK2735 was administered. An exploratory assessment of the proportion of subjects achieving at least 5% weight loss after 28 days demonstrated that up to 100% of VK2735-treated subjects achieved =5% weight loss, compared with 0% for placebo.
Oral VK2735 continued to demonstrate encouraging safety and tolerability following 28 days of once-daily dosing at doses up to and including 100 mg. The majority (99%) of TEAEs reported to date have been mild or moderate, with the majority (90%) reported as mild. Similarly, all observed GI adverse events have been reported as mild or moderate, with the majority (84%) reported as mild. Mild nausea was reported in 23 (32%) VK2735-treated subjects compared with 11% among placebo subjects. No moderate or severe nausea was reported. Vomiting was reported in three (4%) VK2735-treated subjects. Diarrhea was reported in five subjects (7%) receiving VK2735 compared with four subjects (21%) receiving placebo.
Despite reduction in VK2735 exposure, significant reductions in body weight were observed, with subjects reporting mean body weight change of -4.0% from baseline at Day 28 (p<0.0001).
Novel Selective TRß Agonists for Metabolic Disorders and Adrenoleukodystrophy
VK2809 and VK0214 are novel, orally available, selective TRß agonists in development for metabolic disorders and X-ALD. Thyroid hormone receptors are found in various tissues throughout the body. TRß is the major receptor isoform expressed in the liver, and thyroid hormone receptor alpha, or TRa, is the major isoform expressed in the heart. The unique properties of the company’s TRß agonists are designed to reduce or eliminate the deleterious effects of extra-hepatic thyroid receptor activation.
VK2809 in NASH/MASH
In November 2019, the company initiated the VOYAGE study, a Phase 2b clinical trial of VK2809 in patients with biopsy-confirmed NASH/MASH.
The VOYAGE study was a randomized, double-blind, placebo-controlled, multicenter trial designed to assess the efficacy, safety, and tolerability of VK2809 in patients with biopsy-confirmed NASH/MASH and fibrosis ranging from stages F1 to F3. The study targeted enrollment of approximately 340 patients across five treatment arms. The primary endpoint of the study evaluated the relative change in liver fat content, as assessed by MRI-PDFF, from baseline to week 12 in subjects treated with VK2809 as compared to placebo. Secondary objectives included the evaluation of histologic changes assessed by hepatic biopsy after 52 weeks of dosing.
In January 2023, the company announced the completion of patient enrollment in the VOYAGE study, and in May 2023, the company reported that patients receiving VK2809 demonstrated statistically significant reductions in liver fat at week 12, which was the primary endpoint in VOYAGE. Importantly, patients receiving VK2809 continued to demonstrate statistically significant reductions in liver fat content at week 52, with the mean relative change from baseline ranging from 37% to 55%. The response rate in this study, defined as the proportion of patients experiencing reduction in liver fat =30%, ranged from 64% to 88%, with all treatment arms demonstrating statistically significant improvement compared to placebo.
In June 2024, the company announced positive 52-week histologic data from the VOYAGE study. On the secondary endpoint of NASH/MASH resolution with no worsening of fibrosis, VK2809-treated patients demonstrated NASH/MASH resolution ranging from 63% to 75%, compared with 29% for placebo (p<0.05 for each VK2809 treatment group). Across the combined VK2809 treatment groups, 69% achieved NASH/MASH resolution (p<0.0001 vs. placebo). Resolution of NASH/MASH was defined as a non-alcoholic fatty liver disease activity score, or NAS, of 0 or 1 for inflammation and 0 for ballooning.
On the secondary endpoint evaluating improvement in fibrosis with no worsening of NASH/MASH, VK2809-treated patients demonstrated improvement in fibrosis ranging from 44% to 57%, compared with 34% for placebo (p<0.05 for the 5 mg and 10 mg QOD cohorts). Across the combined VK2809 treatment groups, 51% achieved improvement in fibrosis with no worsening of NASH/MASH (p=0.03 vs. placebo). Improvement in fibrosis without worsening of NASH/MASH was defined as a =1-stage improvement in fibrosis and no increase in NAS for ballooning, inflammation, or steatosis.
On the secondary endpoint evaluating the proportion of patients experiencing both resolution of NASH/MASH and improvement in fibrosis, VK2809-treated patients demonstrated improvement ranging from 40% to 50%, compared with 20% for placebo (p<0.05 for the 5 mg and 10 mg QOD cohorts). Across the combined VK2809 treatment groups, 44% achieved this endpoint (p=0.003 vs. placebo).
VK2809 in NAFLD
In September 2018, the company announced top-line results from its 12-week, Phase 2 clinical trial of its lead clinical program’s drug candidate, VK2809, in patients with NAFLD and elevated LDL-C. The study successfully achieved its primary endpoint, with patients receiving VK2809 demonstrating statistically significant reductions in LDL-C compared with placebo. In addition, the trial’s secondary endpoint was achieved, with VK2809-treated patients experiencing statistically significant reductions in liver fat content compared with placebo.
Reduction in LDL-C
Patients receiving VK2809 demonstrated statistically significant reductions in LDL-C of 20% or more, compared with placebo-treated patients. In addition, VK2809-treated patients demonstrated statistically significant improvements in other lipids, including atherogenic proteins apolipoprotein B and lipoprotein (a).
Reduction in Liver Fat Content
Patients receiving VK2809 experienced statistically significant reductions in liver fat content, as assessed by MRI-PDFF, relative to placebo after 12 weeks of treatment.
Safety and Tolerability
No SAEs were reported among patients receiving VK2809 or placebo. Mean alanine aminotransferase, or ALT, levels among patients receiving VK2809 were reduced relative to those of patients receiving placebo. Among patients with elevated baseline ALT levels, those receiving VK2809 also demonstrated reduction relative to placebo. There were no clinically or numerically meaningful differences in direct bilirubin, indirect bilirubin, alkaline phosphatase, or international normalized ratio between patients treated with VK2809 or placebo. In addition, no meaningful changes to the thyroid hormone axis were observed among VK2809-treated patients compared with placebo-treated patients.
Phase 1 Clinical Data for VK2809
VK2809 has also been evaluated in seven Phase 1 clinical trials. The initial Phase 1 safety, tolerability, and pharmacokinetic study of VK2809 was conducted in 2006. This was followed by a 14-day Phase 1b clinical trial in 56 patients with mild hypercholesterolemia, defined as baseline plasma LDL-C of at least 100 mg/dL. This study was initiated in 2007 and completed in 2008. VK2809 was shown to be safe and well-tolerated across doses ranging from 0.25 mg to 40 mg per day. There were no serious adverse events, and the frequency of adverse events in VK2809-treated patients was similar to placebo-treated patients. The clinical trial results also showed dose-related reductions in fasting LDL-C and fasting triglyceride levels at day 14. Significant placebo-adjusted LDL-C reductions from baseline were observed at doses of 5 mg and above, and ranged from approximately 15%-41%, while placebo-adjusted triglyceride levels were reduced by more than 30% at doses of 2.5 mg and above. In addition, statistically significant reductions of lipoprotein a, or Lp(a), and apolipoprotein, or Apo(B), which are positively associated with a patient’s risk of developing cardiovascular disease, were observed in certain cohorts. In addition, VK2809 was evaluated in five additional Phase 1 trials, evaluating the pharmacokinetics, pharmacodynamics, potential drug-drug interaction of VK2809 when co-administered with a statin, alternative dosing regimens, and hepatic impairment, respectively.
VK0214 in X-linked Adrenoleukodystrophy (X-ALD)
The company is developing VK0214 for X-ALD, a rare X-linked, inherited neurological disorder characterized by a breakdown in the protective barriers surrounding brain and nerve cells. X-ALD is caused by mutations in a peroxisomal transporter of VLCFA known as ABCD1. As a result, transporter function is impaired, and patients are unable to efficiently metabolize VLCFA. TRß is known to regulate the expression of an alternative VLCFA transporter, known as ABCD2. Various preclinical models have demonstrated that increased expression of ABCD2 can lead to normalization of VLCFA metabolism. Preliminary data suggest that VK0214 stimulates ABCD2 expression in an in vitro model and reduces VLCFA levels in an in vivo model of X-ALD.
Based upon the positive results from the VK0214 Phase 1 SAD and MAD study, in June 2021, the company initiated a Phase 1b clinical trial of VK0214 in patients with X-ALD. The Phase 1b trial was a multi-center, randomized, double-blind, placebo-controlled study in adult male patients with the AMN form of X-ALD. The study enrolled patients across three cohorts: placebo, VK0214 20 mg daily, and VK0214 40 mg daily. The primary objectives were to evaluate the safety and tolerability of VK0214 in subjects with AMN, when administered once-daily over a 28-day dosing period. Secondary objectives included an evaluation of the pharmacokinetics of VK0214 following 28 days of dosing in this population. An exploratory objective was to evaluate the effects of VK0214 on plasma levels of VLCFAs in subjects with AMN.
In October 2024, the company announced the results from this study, noting that VK0214 was shown to be safe and well-tolerated following once-daily dosing over the 28-day study period. In addition, significant reductions were observed in plasma levels of VLCFAs and other lipids, as compared to placebo.
Highlights from the study results include:
Reductions in VLCFAs
In addition to safety and tolerability, the study included an exploratory assessment of changes in plasma levels of VLCFAs after 28 days of dosing. VLCFAs are considered biomarkers of disease in patients with X-ALD. Treatment with VK0214 resulted in significant reductions in mean VLCFA levels at both doses evaluated, 20 mg/day and 40 mg/day, compared to placebo. Importantly, cohorts receiving VK0214 demonstrated reductions in mean plasma levels of the 26 carbon lysophosphatidyl choline (C26:0-LPC) derivative, a key diagnostic marker.
Reductions in Plasma Lipids
In addition to VLCFA changes, subjects who received VK0214 demonstrated reductions in other plasma lipids. Mean reductions relative to baseline and placebo were observed for LDL-C, apolipoprotein B, or ApoB, and lipoprotein (a), or Lp(a), following 28 days of treatment.
Safety and Tolerability
VK0214 demonstrated encouraging safety and tolerability following 28 days of once-daily dosing. Treatment emergent adverse events were reported as mild to moderate; one subject in the placebo cohort experienced a wrist fracture that was characterized as a severe adverse event. GI adverse events were slightly higher among placebo subjects (33%) compared with VK0214-treated subjects (11%). The company’s intent is to pursue partnering or licensing opportunities for VK0214 prior to conducting additional clinical studies.
Phase 1 SAD and MAD clinical trial of VK0214
In September 2020, the company initiated a randomized, double-blind, placebo-controlled Phase 1 SAD and MAD clinical trial of VK0214 in healthy patients. The primary objective of the study was to evaluate the safety and tolerability of VK0214 administered orally for up to 14 days. The secondary objective was to evaluate the pharmacokinetics of VK0214 following single and multiple oral doses. The first portion of the study evaluated single doses of VK0214; in the second portion of the study, subjects received VK0214 once daily for 14 days. Subsequent cohorts in both portions of the study received successively higher VK0214 doses.
In June 2021, the company announced the results of the study. VK0214 was shown to be safe and well-tolerated at all doses evaluated in this study. VK0214 demonstrated dose-dependent exposures, no evidence of accumulation following multiple doses, and a half-life consistent with anticipated once-daily dosing regimens. While the study’s primary objective was to evaluate safety and tolerability, laboratory assessments included a lipid panel to determine potential pharmacodynamic effects following exposure to VK0214.
VK5211: A SARM for Hip Fracture
VK5211 is an orally available, non-steroidal SARM in development for the treatment of patients recovering from non-elective hip fracture surgery. VK5211 is designed to selectively produce the therapeutic benefits of testosterone in muscle and bone tissue with improved safety and tolerability. Tissue selectivity is critical in treating patients recovering from hip fracture. These patients experience elevated rates of metabolic breakdown of muscle tissue and loss of bone mineral density. This results in a loss of muscle strength, an increased risk of additional fractures, and increased mortality.
Clinical Data for VK5211
In November 2017, the company announced positive top-line results from its 12-week, Phase 2 clinical trial of VK5211 in patients who recently suffered a hip fracture. Top-line data showed that the trial achieved its primary endpoint, demonstrating statistically significant, dose-dependent increases in lean body mass, as well as reductions in fat following treatment with VK5211 as compared to placebo. The study also achieved certain secondary endpoints, demonstrating statistically significant increases in appendicular lean body mass and total lean body mass for all doses of VK5211 compared to placebo. VK5211 demonstrated encouraging safety and tolerability in this study, with no drug-related SAEs reported.
The Phase 2 clinical trial was a randomized, double-blind, placebo-controlled, parallel group, international study designed to evaluate the efficacy, safety, and tolerability of VK5211 in patients recovering from hip fracture surgery. A total of 108 patients were randomized to receive once-daily VK5211 doses of 0.5 mg, 1.0 mg, 2.0 mg, or placebo for 12 weeks.
Pipeline Program Targeting Metabolic Disease with Large Unmet Medical Need
The company has a preclinical program focused on developing dual amylin and calcitonin receptor agonists, or DACRA, for the potential treatment of obesity. Amylin has important effects on glucose management, glucagon production, gastric emptying time, and satiety. Amylin analogs have been shown to significantly reduce body weight and dosage of insulin. Dual amylin and calcitonin receptor agonists are the most potent amylin receptor agonists. Cagrilintide is a dual amylin/calcitonin receptor agonist that is currently in clinical development. Preclinical studies to date have demonstrated potent activity of a series of novel, internally developed, amylin and calcitonin dual agonists.
Master License Agreement with Ligand
On May 21, 2014, the company entered into a Master License Agreement, as amended on each of September 6, 2014, April 8, 2015, and March 21, 2016, or the Master License Agreement, with Ligand pursuant to which, among other things, Ligand granted to the company and its affiliates an exclusive, perpetual, irrevocable, worldwide, royalty-bearing right and license under (1) patents related to (a) its VK2809 and VK0214 programs and any other compounds consisted by specified TRß patents and any derivatives of such compounds, or TRß Compounds, (b) the company’s VK5211 program and any other compounds consisted by specified SARM patents and derivatives of such compounds, or SARM Compounds, (c) its VK0612 program and any other compounds consisted by specified FBPase patents and derivatives of such compounds, or FBPase Compounds, (d) its DGAT-1 program and any other compounds consisted by specified DGAT-1 patents and derivatives of such compounds, or DGAT-1 Compounds, and (e) its EPOR program and any other compounds consisted by specified EPOR patents and derivatives of such compounds, or EPOR Compounds, and (2) related know-how controlled by Ligand; and (3) physical quantities of TRß Compounds, SARM Compounds, FBPase Compounds, DGAT-1 Compounds, and EPOR Compounds, or, collectively, the Licensed Technology, to research, develop, manufacture, have manufactured, use, and commercialize the Licensed Technology in and for all therapeutic and diagnostic uses in humans or animals.
Government Regulation
The company’s drugs must be approved by the FDA through the new drug application, or NDA, process before they may be legally marketed in the U.S.
The company relies, and expects to continue to rely, on third parties for the production of clinical and commercial quantities of its products in accordance with cGMP regulations.
In the U.S., the company is subject to complex laws and regulations pertaining to healthcare ‘fraud and abuse,’ including, but not limited to, the federal Anti-Kickback Statute, the federal False Claims Act, and other state and federal laws and regulations.
Research and Development
During the year ended December 31, 2024, the company incurred $101.6 million in research and development expenses primarily related to its efforts in conducting the VK2735 Phase 2 VENTURE clinical trial, the VK2735 Phase 1 subcutaneous clinical trial, the VK2735 Phase 1 oral clinical trial, VK2809 Phase 2b VOYAGE clinical trial, and the VK0214 Phase 1b clinical trial.
History
Viking Therapeutics, Inc. was founded in 2012. The company was incorporated under the laws of the state of Delaware in 2012.
