VAD044

Hereditary hemorrhagic telangiectasia is the second most common inherited bleeding disorder in the world and has been linked to severe disease burden, reduced life expectancy and a reduced quality of life. Vaderis Therapeutics’ goal to develop the first drug aimed specifically at a certain rare blood vessel disorder came one step closer today with the news that the therapy is safe and reduced nosebleeds.The therapy in question, a once-daily allosteric AKT inhibitor dubbed VAD044, was trialed in 75 patients with hereditary hemorrhagic telangiectasia (HHT), a genetic disorder that leads to abnormal blood vessels forming in the skin, mucous membranes and certain organs.Almost all HHT patients suffer from unpredictable and often debilitating nosebleeds. After 12 weeks, patients who received the 40-mg dose of VAD044 experienced “clinically meaningful” reductions in the frequency of their nosebleeds, a secondary endpoint of the trial, Vaderis said in an Aug. 27 release.The release was light on any actual data, but the Swiss company did say that regression of HHT-associated vascular lesions was also observed.Patients in the phase 1 trial either received the 40-mg dose, a 30-mg dose or placebo. The primary endpoint of the study was safety, and the data showed that VAD044 was similar to placebo when it came to the frequency and severity of off-target adverse events (AEs). On-target AEs associated with inhibiting the AKT pathway—which helps cells survive and grow in response to extracellular signals—were mostly mild, transient and resolved, the company said.Some of the patients have since been enrolled in a 12-month open-label extension, where they are receiving a 40-mg daily dose of VAD044. Interim six-month data from 27 of these patients “continue to show favorable safety and tolerability profiles with further improvements” in nosebleeds, Vaderis said.CEO Nicholas Benedict said the company is already “interacting with major health authorities to plan the pivotal phase of development for VAD044 in HHT.”“The excitement surrounding the results of the initial 12-week double-blind part of this trial is amplified by the continued improvements experienced by patients through six months,” Benedict added. HHT is the second most common inherited bleeding disorder in the world and has been linked to severe disease burden, reduced life expectancy and a reduced quality of life. Despite this health impact, there are no approved treatments for the condition, according to Vaderis, which described VAD044 as “the first novel therapy intended specifically for the treatment of HHT.”The company is also lining up the therapy to test in breast and prostate cancers, according to Vaderis’ website.“We … already see that after six months of continuous treatment with VAD044 patients experience further improvements in all [nose bleeding] endpoints compared to those seen at 12 weeks,” Hans-Jurgen Mager, M.D., Ph.D., head of the Netherlands Reference Centre for HHT and the study’s co-primary investigator, said in a statement.“It seems that VAD044 has not yet reached its peak effect on HHT disease activity at 12 weeks, and patients continue to improve over time without paying an unexpected price in terms of safety or tolerability,” Mager added.Academic centers in the U.S. are currently enrolling patients to test whether Novartis’ sarcoma drug Votrient can reduce the severity of nosebleeds in HHT. Votrient is a tyrosine kinase inhibitor that has been shown to inhibit the PI3K/Akt signaling pathway.Novartis has a more direct link to Vaderis, with the biotech having been set up in 2019 by two veterans of the Swiss Big Pharma, including Benedict himself.

Trial delivers positive results in first ever industry-led clinical trial in Hereditary Haemorrhagic Telangiectasia (HHT) VAD044 showed favourable safety and tolerability, together with exploratory efficacy across key manifestations of the disease Ongoing Open Label Extension (OLE) data at 6 months show consistent safety, tolerability and continued improvement in bleeding parameters BASEL, Switzerland, Aug. 27, 2024 /PRNewswire/ -- Vaderis Therapeutics AG (Vaderis), a clinical stage biotechnology company focused on developing treatments for rare diseases associated with vascular malformations, today announces positive results from its randomized, double-blind, dose-finding placebo-controlled Proof-of-Concept (POC) clinical trial in patients suffering from HHT. HHT, an Orphan Disease, is the second most common inherited bleeding disorder in the world frequently causing severe disease burden, reduced life expectancy and impaired Quality of Life. Despite this, there remains no approved treatment for HHT anywhere in the world. Vaderis is developing VAD044, an oral, once-daily allosteric AKT-inhibitor, the first novel therapy intended specifically for the treatment of HHT. In this controlled, double-blind trial, seventy-five patients across USA and Europe were randomized to receive either placebo, 30mg or 40mg of VAD044 for 12 weeks. Safety was the primary endpoint and VAD044 was similar to placebo as measured by both the frequency and severity of off-target adverse events (AEs). On-target AEs associated with AKT pathway inhibition, were mostly mild, transient and resolved on study drug. Almost all HHT patients suffer from unpredictable, often frequent and debilitating epistaxis which is considered the best measure of overall HHT disease activity and a key measure of disease burden. In this study, VAD044 showed a dose response on secondary and exploratory efficacy endpoints in HHT, including key epistaxis endpoints. At the end of the 12-week treatment period, patients receiving the 40mg dose experienced clinically meaningful improvements in epistaxis frequency, duration and epistaxis-free days. Regression of HHT-associated vascular lesions was also observed. Following the 12-week randomised double-blind period, patients from selected study centres were enrolled into a 12-month OLE to the study where they all receive up to 40mg VAD044 daily. Interim data for twenty-nine patients through the 6 month timepoint continue to show favourable safety and tolerability profiles with further improvements in epistaxis. Dr. Hanny Al-Samkari, the Peggy S. Blitz Endowed Chair in Hematology/Oncology at Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School (USA), co-primary investigator in the VAD044 POC trial, commented, "In this pioneering clinical trial we see already at 12 weeks substantial and clinically meaningful dose-dependent improvements in HHT disease activity with once-daily VAD044, particularly as measured by epistaxis parameters." Dr. Hans-Jurgen Mager, pulmonologist and head of the Netherlands Reference Centre for HHT at St. Antonius Hospital, Utrecht (NL), also co-primary investigator in the VAD044 POC trial, added, "These exciting results have supported the assessment of long-term treatment of HHT patients with VAD044. We have added an open-label extension to the POC trial and already see that after 6 months of continuous treatment with VAD044 patients experience further improvements in all epistaxis endpoints compared to those seen at 12 weeks. It seems that VAD044 has not yet reached its peak effect on HHT disease activity at 12 weeks, and patients continue to improve over time without paying an unexpected price in terms of safety or tolerability." Nicholas Benedict, CEO and co-Founder of Vaderis Therapeutics, commented, "The excitement surrounding the results of the initial 12-week double-blind part of this trial is amplified by the continued improvements experienced by patients through 6 months. Excellent collaboration with patient and physician organisations such as CureHHT has been a cornerstone of successful implementation of this ground-breaking trial which was achieved in a much shorter timeframe than planned. Vaderis is currently interacting with major health authorities to plan the pivotal phase of development for VAD044 in HHT." About Vaderis Vaderis is a clinical stage biotech company developing treatments for rare and orphan diseases associated with vascular malformations. There is a significant number of debilitating and largely untreated rare diseases, such as HHT (Hereditary Haemorrhagic Telangiectasia), in which patients have overactivation of AKT triggered by upstream genetic mutations resulting in vascular overgrowth. Vaderis is developing VAD044, a daily, oral allosteric AKT inhibitor, which has been investigated in a clinical proof of concept study in HHT patients and is currently in a 12 month Open Label Extension. There are no drugs approved to treat HHT and Vaderis aims to be the first company to develop a medicine for the treatment of HHT and other diseases associated with vascular malformations. Logo: For further information, please contact: