Our Pipeline

We believe that VX-01 has the potential to bring the first oral treatment for non-proliferative diabetic retinopathy to patients.

Oruvestat

Our orally available small molecule inhibitor has a dual mechanism of action, targeting leukocyte trafficking and pro-inflammatory products of local amine oxidation.

Oruvestat is suitable for daily oral chronic dosing to ensure that intraocular concentrations of the drug achieve profound, persistent inhibition of AOC-3 in the neurovascular unit. Previous clinical studies using AOC-3 inhibitors to treat diabetic eye diseases (1,2) were confounded using drug doses that, although effective against soluble AOC-3 circulating in plasma, were insufficient to cross the blood-retina barrier and block AOC-3 in the eye.

Diabetic Retinopathy

Oruvestat is suitable for daily oral chronic dosing to  ensure that intraocular concentrations of the drug achieve profound,  persistent inhibition of AOC-3 in the neurovascular unit. Previous  clinical studies using AOC-3 inhibitors to treat diabetic eye diseases (1,2)  were confounded using drug doses that, although effective against soluble AOC-3 circulating in plasma, were insufficient to cross the  blood-retina barrier and block AOC-3 in the eye.

MASH

Oruvestat is suitable for oral chronic dosing and is a first in class inhibitor of AOC-3 that targets multiple drivers of MASH. Oruvestat significantly reduces liver fibrosis markers and blunts disease  drivers that lead to MASH, including inflammation, fibrosis, glucose and lipid uptake.

Primary Sclerosing Cholangitis (PSC)

Oruvestat has a differentiated mechanism designed to target the key drivers of PSC. Via inhibition of both soluble and membrane bound AOC-3, Oruvestat is designed to suppress chronic cholangiopathic inflammation via reduction of leukocyte recruitment into the liver and bile ducts, reduce endothelial oxidative stress and inflammatory signalling by inhibiting AOC-3 mediated oxidative deamination and attenuate progressive biliary fibrosis through downstream reduction of inflammatory cell recruitment.

Global Rights are owned by Vantage

Global Rights are owned by Vantage

Non Proliferative Diabetic Retinopathy (NPDR)

Disease background
  • Diabetic retinopathy (DR) is a complication of diabetes and is the leading cause of visual impairment in people aged 20–65 years. It can go undetected until vision is irreversibly lost
  • More than 37 million people in the United States have diabetes, and 1 in 3 of them will develop DR
  • The risk of progressing from NPDR to early proliferative DR after 1 year is 26.3% and 50.2% in patients with DRSS levels of 47 and 53, respectively1
There is a need for a safe, orally available therapeutic to prevent the progression of NPDR to PDR
  • The current therapies for DR and DME are limited to pan-retinal photocoagulation and intravitreal (IVT) injections of anti-VEGF or steroid drug formulations
  • 15–40% of eyes fail to respond or only partially respond to VEGF inhibitors1
  • Anti-VEGF  injections are expensive, invasive and can be inconvenient to administer and are not generally used in NPDR
  • VEGF inhibitors do not improve ischemia, inflammation, do not provide neuroprotection2, and require regular continued treatment to sustain any benefit
  • Josh O. Wallsh and Ron P. Gallemore (2021). Anti-VEGF-Resistant Retinal Diseases: A Review of the Latest Treatment Options. Cells.
  • Boyer DS, Rippmann JF, Ehrlich MS, Bakker RA, Chong V, Nguyen QD. Amine oxidase copper-containing 3 (AOC3) inhibition: a potential novel target for the management of diabetic retinopathy. Int J Retina Vitreous. 2021. 12;7(1):30.

Primary sclerosing cholangitis (PSC)

Disease background
  • PSC is a progressive inflammatory liver disease, which causes the bile ducts to become scarred, slowly narrowing until bile backs up into the liver causing fibrosis
  • PSC leads to liver failure in about 10-15 years, at least a third of patients will experience liver-related death without hepatic transplantation1
  • In the UK, PSC is now the leading autoimmune liver disease indication for transplant, despite being the rarest of the autoimmune liver diseases. However, the disease reoccurs in 16.7% of patients post transplantation2
  • There is no approved therapy for PSC to date, current treatment is aimed at treating symptoms or managing complications associated with the disease
  • Estimates are that in 2019, there were 241,800 prevalent cases of primary sclerosing cholangitis worldwide among adults aged 30 years and over, and forecasts that number to increase to 277,300 prevalent cases by 20283
  • In the UK, PSC is now the leading autoimmune liver disease indication for transplant, despite being the rarest of the autoimmune liver diseases. However, the disease reoccurs in 16.7% of patients post transplantation2
  • Sirpal S, Chandok N. Primary sclerosing cholangitis: diagnostic and management challenges. Clin Exp Gastroenterol. 2017 Nov 6;10:265-273
  • Visseren T et al; European Liver and Intestine Transplantation Association (ELITA). Recurrence of primary sclerosing cholangitis after liver transplantation - analysing the European Liver Transplant Registry and beyond. Transpl Int. 2021
  • 2019 Market Spotlight - Primary Sclerosing Cholangitis - ResearchAndMarkets.com