VAD044

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:

Focused on developing treatments for rare diseases associated with vascular malformations Recruited first patients in Proof-of-Concept study for lead drug candidate VAD044 Financed by Medicxi in 2020 BASEL, Switzerland, Aug. 22, 2022 /PRNewswire/ -- Vaderis Therapeutics AG (Vaderis), a clinical stage biotechnology company focused on developing treatments for rare diseases associated with vascular malformations, today announced its emergence from stealth and initiation of its INSIGHT proof-of-concept clinical trial in patients suffering from Hereditary Haemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu Syndrome. Vaderis was established in 2019 and in 2020 raised over CHF18 million from Medicxi, enabling progression of its lead asset into the clinic and successful completion of Phase 1a. Emergence from Stealth Vaderis was founded with the unique aim to develop therapeutics for rare and orphan diseases associated with vascular malformations. In April 2020 Vaderis acquired a portfolio of allosteric AKT inhibitors from Almac Discovery Ltd of Belfast, UK. AKT is a serine kinase which plays a crucial role in vascular growth and in vascular overgrowth. There is a significant number of rare diseases such as HHT in which upstream genetic mutations trigger over-activation of the serine kinase AKT, resulting in vascular overgrowth. Such diseases frequently manifest in ways that are debilitating, disfiguring, painful and sometimes life-threatening. The vast majority of these diseases are currently left untreated except for symptomatic interventions which tend to offer patients limited temporary relief of individual symptoms. VAD044 is a once daily, orally administered, allosteric AKT inhibitor which has the potential to treat the underlying cause of these diseases. If successful, Vaderis would be the first company in the world to develop a medicine for the treatment of HHT and other diseases associated with vascular malformations. Initiation of Clinical PoC in HHT In pursuit of the company's core objective, Vaderis announces the initiation of the first study of VAD044 in HHT patients. Known as the INSIGHT proof-of-concept trial (INternational Study InvestiGating HHT), the study is unique in its robust design aimed at achieving a thorough understanding of the safety of VAD044 in HHT patients. A total of 80 HHT patients across the USA, Canada and Europe will be randomised in a double-blind, controlled trial comparing two doses of VAD044 to placebo. Initiation of the INSIGHT trial follows Health Authority approvals including FDA, Health Canada and key European agencies. J.J. Mager, MD, PhD, pulmonologist at St. Antonius Hospital Utrecht, Chairman of the Global Research and Medical Advisory Board of Cure HHT and lead investigator of the INSIGHT trial commented, "The first patients recruited into the INSIGHT trial mark an exciting milestone in HHT clinical research. 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." Nicholas Benedict, CEO of Vaderis added, "Working together with the HHT community, both caregivers and patient associations, 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." Giovanni Mariggi, Partner at Medicxi and Chairman of Vaderis said, "Our vision is to create a unique company dedicated to delivering breakthrough therapies for rare diseases caused by vascular malformations. Initiation of the INSIGHT trial is an important milestone on the way to realising this vision. It is testament to the significant progress made by the company over the last two years". About Vaderis Vaderis is a clinical stage biotech company with the aim to develop medicinal treatments for rare and orphan diseases associated with vascular malformations. Since its founding in 2019, Vaderis raised a Series A financing from Medicxi and acquired a portfolio of allosteric AKT inhibitors from Almac Discovery Ltd of Belfast, UK. There is a significant number of debilitating and largely untreated rare diseases, such as HHT (Hereditary Haemorrhagic Telangiectasia), in which patients suffer from over-activation of AKT triggered by upstream genetic mutations resulting in vascular overgrowth. There are no drugs approved anywhere in the world which specifically treat HHT. Vaderis aims to be the first company to develop a medicine for the treatment of HHT and aims to treat other diseases associated with vascular malformations. About Medicxi Medicxi is a healthcare-focused investment firm with the mission to create and invest in companies across the full drug development continuum. Leveraging deep expertise in drug development and company creation spanning over two decades, Medicxi invests in early and late-stage therapeutics with a product vision that can fulfill a clear unmet medical need. For more information, please visit: Logo - SOURCE Vaderis Therapeutics AG