NEW YORK--(BUSINESS WIRE)--United Neuroscience (UNS), a clinical stage biotechnology company dedicated to developing best-in-class therapies for Alzheimer’s disease (AD) and other neurodegenerative disorders, today announced positive Phase 1 data for UB-311, its novel synthetic peptide vaccine targeting beta amyloid (Aβ) in the treatment of AD. The Phase 1 data, which was published in the Alzheimer’s & Dementia: Translational Research & Clinical Interventions journal from the Alzheimer’s Association, showed that UB-311 was safe and well-tolerated with a 100 percent response rate and high anti-Aβ antibody titers across patients.
The insidious, decades-long buildup of misfolded Aβ oligomers, fibrils and amyloid plaques is believed to play a pivotal role in brain cell injury leading to dementia and is a major focus for drug development efforts. Several late stage clinical trials are currently testing passive immunotherapy with monoclonal antibodies (mAbs) targeting Aβ with some reporting encouraging results.
Active vaccination of human individuals against Aβ has also long been pursued but has yet to be effectively achieved. Most active vaccine efforts have either reported low antibody titers and responder rates or significant safety issues such as T-cell mediated encephalitis. UB-311 is a novel UBITh™ active vaccine targeting the N-terminus of Aβ, designed to induce high B-cell specific responses while avoiding T-cell inflammation. UB-311 was previously shown to generate considerable site-specific antibodies across mice, guinea pigs, macaques and baboons and to also reduce Aβ1–42 oligomers, protofibrils, and plaque load in the transgenic hAPP751 mouse model of AD.
“We are leveraging our commercially proven UBITh vaccine platform that has sold over three billion doses and has shown that we can safely break immune tolerance to endogenous proteins,” said Chang Yi Wang, Chief Scientific Officer of UNS. “We are eager to validate our platform to target clinical brain disorders.”
In the UB-311 first-in-human trial reported today, 19 patients with mild-to-moderate AD were immunized with three doses of the vaccine at enrollment, four weeks and 12 weeks, and monitored until week 48. No major adverse events were reported in the study, including absence of ARIA-E, a treatment emergent safety issue that has plagued other anti-Aβ mAbs in development. Injection site swelling and agitation were the most common adverse events reported. Immunogenicity results showed that UB-311 vaccination had a 100 percent responder rate and induced strong anti-Aβ antibody titers that preferentially recognized the aggregated forms of Aβ. In a small subgroup of patients with mild AD over 60 years of age, stabilization or improvement in three cognitive scales from baseline to week 48 was observed.
“Our positive Phase 1 clinical trial results show that our active vaccination approach against endogenous pathogenic proteins has an acceptable safety and tolerability profile in patients, which was the primary endpoint of the study,” said Ajay Verma, Chief Medical Officer of UNS. “The ability of our platform to break self-tolerance in patients and safely elicit therapeutic autoantibodies, or ‘endobodies’ as we like to refer to them, suggests that we are on the right path and have overcome prior challenges. We believe our ‘endobody vaccine’ approach could provide therapeutic and prophylactic treatment for Alzheimer’s disease as well as many other neurodegenerative diseases.”
“In addition to the high response rate and antibody titers, our Phase 1 results may show some preliminary indications of efficacy,” said Mei Mei Hu, Chief Executive Officer of UNS. “We believe there is a potential for this therapy to be effective in a large population of patients, and have designed our Phase 2 trial to target patients in the initial stages of AD where we expect UB-311 to have the greatest effect.”
UNS’ ongoing Phase 2 active immunotherapy trial of UB-311 in early-to-mild AD patients is fully enrolled. Results from the Phase 2 trial are expected in mid-2018.
About United Neuroscience
United Neuroscience (UNS) is a clinical-stage biotech company dedicated to the development of best-in-class immunotherapeutics for the brain. UNS was founded to address the social and economic burden of Alzheimer’s and other neurodegenerative diseases and seeks to rapidly advance candidates into and through clinical trials with the goal of delivering breakthrough treatments to patients. For more information please visit www.unitedneuroscience.com