Vaderis forms to tackle vascular malformations with Novartis vet at the helm

Published: Aug 22, 2022

By Alex Keown

With financial backing from Medicxi, Vaderis Therapeutics AG emerged from stealth mode Monday with a focus on allosteric AKT inhibitors and a clinic-ready drug candidate.

The young biotech plans to launch a proof-of-concept clinical trial assessing its lead asset VAD044 in patients suffering from Hereditary Hemorrhagic Telangiectasia (HHT).

Also known as Osler-Weber-Rendu Syndrome, HHT is a genetic disorder that causes abnormal connections, known as arteriovenous malformations, to develop between arteries and veins. The most common areas of the body affected by these malformations are the nose, lungs, brain and liver. Over time, the malformations can cause spontaneous bleeding.

The disease can lead to shortness of breath, seizures, iron deficiency and anemia, which contribute to poor quality of life. Currently, there are no FDA-approved drugs specifically for the treatment of HHT. Vaderis aims to be the first company to drive a candidate through the clinic for this disease. It also plans to attack other diseases associated with vascular malformations.

Vaderis, based in Basel, Switzerland, the home of Roche and Novartis, was established in 2019. The company was founded with the goal of developing new therapeutics for rare and orphan diseases associated with vascular malformations.

Its mission was bolstered by the 2020 acquisition of a portfolio of allosteric AKT inhibitors from Belfast-based Almac Discovery Ltd. The acquisition was financed through a 2020 investment from Medicxi valued at 18 million Swiss francs, which in today’s dollars is about $18.8 million.

AKT is a serine kinase that plays a crucial role in vascular growth and overgrowth. There are a significant number of rare diseases like HHT in which upstream genetic mutations trigger over-activation of the serine kinase AKT, resulting in vascular overgrowth, the company noted in its announcement.

VAD044 is a once-daily, orally administered, allosteric AKT inhibitor. Vaderis believes it has the potential to treat the underlying causes of HHT and other untreated diseases associated with vascular malformations. The Phase Ia INSIGHT study will include 80 patients who will be randomized in a double-blind, controlled trial comparing two doses of VAD044 to placebo.

Novartis veteran Nicholas Benedict, CEO of Vaderis, said the company has been working with the HHT community in the lead-up to the study.

“Vaderis hopes to be the catalyst which transforms patient care in HHT. Success in the INSIGHT trial would be a major step towards developing the first ever registered treatment for HHT anywhere in the world,” Benedict said in a statement.

The Phase Ia study will be conducted in the United States, Canada and Europe. Vaderis said the INSIGHT trial is “unique in its robust design” that aims to assess a complete understanding of the safety of VAD044. J.J. Mager, M.D., Ph.D., a pulmonologist and chairman of the Global Research and Medical Advisory Board of Cure HHT, said the recruitment of the patients for INSIGHT marks a milestone in HHT clinical research. Mager is heading the investigation of VAD044.

“If successful, this trial may demonstrate the potential of this new drug to be effective beyond the symptomatic treatments we currently offer HHT patients, by addressing the course of this rare, progressive, and debilitating disease,” he said in a statement.

Source: BioSpace