UB-311 / Vaxxinity - LARVOL DELTA

Amyloid Vaccine UB-311 Demonstrates Positive Findings With No ARIA-E Cases in Published Phase 2 Study (NeurologyLive) - P2 | N=47 | NCT02551809 | "'The UB-311 Phase 2a program accomplished its goals of establishing safety and tolerability, while generating high levels of anti-amyloid antibodies. The gradual, natural titration of antibody titers through this approach may have contributed to a lack of ARIA-E in this study,' study investigator Jeffrey Cummings...Trends for decreased amyloid burden at week 78 were observed only in the Q3M treatment group."

Media quote • P2 data

Vaxxinity Announces Publication of UB-311 Safety, Tolerability, Immunogenicity, and Clinical Efficacy Data from Phase 2a Trial in Alzheimer’s Disease (GlobeNewswire) - P2a | N=43 | NCT02551809 | Sponsor: United Neuroscience Ltd. | "Vaxxinity, Inc...today announced the print publication of Phase 2a clinical trial data in The Lancet's eBioMedicine (Volume 94, 104665, August 2023), stating that UB-311 'was safe and well-tolerated,' with early clinical data demonstrating a trend for slowing cognitive decline in mild Alzheimer's disease (AD)....Jeffrey Cummings...commented, 'The UB-311 Phase 2a program accomplished its goals of establishing safety and tolerability, while generating high levels of anti-amyloid antibodies. The gradual, natural titration of antibody titers through this approach may have contributed to a lack of ARIA-E in this study. Vaccine approaches such as UB-311 represent important ways forward in advancing treatment and prevention of Alzheimer’s disease and offer the potential to transform the treatment landscape by providing participants with an accessible therapeutic option.'"

Media quote • P2a data • Alzheimer's Disease • CNS Disorders

Vaxxinity Announces Publication of UB-311 Safety, Tolerability, Immunogenicity, and Clinical Efficacy Data from Phase 2a Trial in Alzheimer’s Disease (GlobeNewswire) - P2a | N=43 | NCT02551809 | Sponsor: United Neuroscience Ltd. | "Vaxxinity, Inc...today announced the print publication of Phase 2a clinical trial data in The Lancet’s eBioMedicine (Volume 94, 104665, August 2023), stating that UB-311 'was safe and well-tolerated,' with early clinical data demonstrating a trend for slowing cognitive decline in mild Alzheimer’s disease (AD)....Trends of slowing disease progression were observed across key cognitive and functional measures for UB-311-treated versus placebo-treated participants over 78 weeks of observation, including a 48% slowing of decline on CDR-SB in the UB-311 quarterly boosting group."

P2a data • Alzheimer's Disease • CNS Disorders

Safety, tolerability, immunogenicity, and efficacy of UB-311 in participants with mild Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 2a study. (PubMed, EBioMedicine) - P2a | "These results support the continued development of UB-311."

Journal • P2a data • Alzheimer's Disease • CNS Disorders • Pain

Vaxxinity Reports Third Quarter 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - “Research and development expenses were $12.5 million and $23.4 million for the three months ended September 30, 2022 and 2021, respectively. The $10.9 million decrease consisted of decreases in program-specific costs of $14.6 million and increases in non-program costs of $3.6 million. Of the program-specific decrease, $14.9 million was related to our UB-612 COVID-19 vaccine program, $0.7 million to our UB-311 Alzheimer’s disease program and $0.3 million to our UB-312 Parkinson’s disease program, partially offset by increases in spend of $1.3 million on our VXX-401 hypercholesterolemia program.”

Commercial • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

Vaxxinity Receives FDA Fast Track Designation for UB-311 for Treatment of Alzheimer’s Disease (GlobeNewswire) - “Vaxxinity, Inc…announced that UB-311, an anti-amyloid beta immunotherapeutic vaccine, has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer’s disease.”

Fast track designation • Alzheimer's Disease • CNS Disorders

Vaxxinity Reports Third Quarter 2021 Financial Results and Provides Corporate Updates (GlobeNewswire) - "UB-311 targets toxic forms of aggregated amyloid-β in the brain to fight Alzheimer’s disease (AD)...We currently expect to initiate the Phase 2b portion of the study in the second half of 2022...As of September 30, 2021, cash and cash equivalents were $89.4 million...The $15.8 million increase consisted primarily of an increase of $12.7 million related to our UB-612 clinical trial in Taiwan (primarily consisting of materials and manufacturing costs as well as increases in CRO costs), increased personnel costs of approximately $1.8 million, and increased UB-311 costs (primarily production related) of approximately $0.9 million."

Commercial • Trial status • Alzheimer's Disease • CNS Disorders

COVAXX CEO Works to Redefine the Idea of a Vaccine (BioSpace) - "...novel synthetic peptide vaccine, UB-311...The company expects to initiate a Phase III study in early Alzheimer’s, as well as a Phase II study in Parkinson’s patients at some point of 2021."

New P2 trial • New P3 trial • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

[VIRTUAL] Past and current vaccine and immunotherapy development in Alzheimer’s disease (CTAD 2020) - "Vaccine candidates such as CAD106 and UB-311 use selective epitopes and were developed to avoid the undesirable inflammatory effects that were seen with AN1792...Positive ADAS-cog effect sizes were seen for AN1792, Solanezumab EXPEDITION 3, BAN2401 and Aducanumab ENGAGE...Active vaccination achieving a predictable and high antibody response in amyloid positive, early AD participants increases the likelihood of technical success. The longer duration of immune response with active immunization combined with safety advantages make the modality well suited to AD"

IO Biomarker • Allergy • Alzheimer's Disease • CNS Disorders

[VIRTUAL] UB-311, a novel UBITh® amyloid beta peptide vaccine in development for Alzheimer’s disease (CTAD 2020) - "Biomarker outcomes include NfL, p-tau, tau, amyloid PET, CSF (subgroup) and plasma Aβ40 and Aβ42, and hippocampal and whole brain volume as measured by MRI. The relationship between the primary and biomarker outcomes will be assessed."

Alzheimer's Disease • CNS Disorders • Dementia • Immunology • Inflammation • Amyloid PET • MRI • Plasma Aβ40 • Plasma Aβ42

United Neuroscience reports positive Phase 1 results for active vaccine UB-311 in Alzheimer’s disease (Businesswire) - P1, N=19; "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....No major adverse events were reported in the study, including absence of ARIA-E...Results from the Phase 2 trial are expected in mid-2018."

P1 data • P2 data • Alzheimer's Disease • CNS Disorders

Baseline Characteristics for Patients with Mild Alzheimers Disease Enrolled in the Phase IIa Trial of Active Immunotherapeutic Vaccine UB-311 (AAIC 2018) - "To date, UB-311 has been well tolerated, as continuously assessed by clinical exam and MRI. Compared to other AD immunotherapeutic trials using amyloid PET scans, those subjects who progressed to the PET scan screen in the V203-AD study had a low PET screen failure rate of 18.5%. The lower amyloid burden may provide a more ideal population for an immunotherapy trial."

Clinical • IO Biomarker • P2a data • Alzheimer's Disease • CNS Disorders

United Neuroscience announces presentation at the 2018 Alzheimer's Association International Conference (AAIC) (PRNewswire) - P2, N=43; NCT02551809; Sponsor: United Neuroscience Ltd.; “United Neuroscience…announced today that the company will present at the upcoming Alzheimer's Association International Conference (AAIC) being held July 22-26, 2018, in Chicago….Title: Baseline Characteristics for Patients with Mild Alzheimer's Disease Enrolled in the Phase IIa Trial of Active Immunotherapeutic Vaccine UB-311.”

P2 data • Alzheimer's Disease • CNS Disorders

United Neuroscience strengthens vaccine pipeline with novel immunotherapy for Parkinson's disease (PRNewswire) - "UB-311 is currently in a Phase IIa study with top-line results expected by the end of the year."

P2a data • Alzheimer's Disease • CNS Disorders

An Extension Study of V203-AD Study to Evaluate the Safety, Tolerability, Immunogenicity, and Efficacy of UB-311 (clinicaltrials.gov) - P2a; N=34; Terminated; Sponsor: United Neuroscience Ltd.; Trial completion date: Apr 2020 ➔ Oct 2019; Active, not recruiting ➔ Terminated; United Neuroscience has decided to terminate V203-AD-EXT study based on review of baseline data, and the treatment assignment error issue.

Clinical • IO Biomarker • Trial completion date • Trial termination

An Extension Study of V203-AD Study to Evaluate the Safety, Tolerability, Immunogenicity, and Efficacy of UB-311 (clinicaltrials.gov) - P2a; N=34; Active, not recruiting; Sponsor: United Neuroscience Ltd.; Enrolling by invitation ➔ Active, not recruiting; Trial completion date: Mar 2021 ➔ Apr 2020

Enrollment closed • Trial completion date

Researchers test vaccine capable of fighting Alzheimer's symptoms (News Farma) - "Scientists believe the disease is caused by two harmful proteins: beta-amyloid and tau. The vaccine, UB-311, is intended to elicit an antibody response by eliminating the proteins in question...The Alzheimer's vaccine is still in the testing phase, but United Neuroscience has already adopted the technology used to start working on creating another vaccine, this time to fight Parkinson's."

Review

ACTIVE IMMUNOTHERAPY WITH UB-311 VACCINE: RESULTS FROM A PHASE IIA, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 3-ARM PARALLEL-GROUP, MULTICENTER STUDY (ADPD 2019) - P2a; "Secondary outcomes included florbetapir PET, MRI, cognitive, imaging, functional, and global assessments. To date, UB-311 has been well tolerated, as continuously assessed by clinical exam and MRI, with over 300 vaccine doses administered from both Phase I and Phase IIa studies. Subjects from the Phase IIa study were eligible to join the 108-week extension study with UB-311 in which additional safety, immunogenicity and biomarker data is collected."

Clinical • IO Biomarker • P2a data

United Neuroscience to present data on Alzheimer's vaccine at the 2019 AD/PD Conference (PRNewswire) - "United Neuroscience...today announced an upcoming presentation on Phase IIa results of its lead clinical product, UB-311, at the 14th International Conference on Alzheimer's and Parkinson's Diseases (AD/PD) in Lisbon, Portugal, from March 26-31, 2019."

P2a data

Evaluate the Safety, Tolerability, Immunogenicity and Efficacy of UB-311 in Mild Alzheimer's Disease (AD) Patients (clinicaltrials.gov) - P2a; N=43; Completed; Sponsor: United Neuroscience Ltd.; Active, not recruiting ➔ Completed; Trial completion date: Feb 2019 ➔ Aug 2018; Trial primary completion date: Dec 2018 ➔ Aug 2018

Clinical • Trial completion • Trial completion date • Trial primary completion date

An Extension Study of V203-AD Study to Evaluate the Safety, Tolerability, Immunogenicity, and Efficacy of UB-311 (clinicaltrials.gov) - P2a; N=41; Enrolling by invitation; Sponsor: United Neuroscience Ltd.; Recruiting ➔ Enrolling by invitation; Trial completion date: Dec 2020 ➔ Mar 2021; Initiation date: May 2018 ➔ Aug 2018; Trial primary completion date: Nov 2020 ➔ Mar 2021

Clinical • Enrollment status • IO Biomarker • Trial completion date • Trial initiation date • Trial primary completion date

United Neuroscience announces positive top-line results from phase 2a clinical study of UB-311 vaccine in patients with Alzheimer's disease (PRNewswire) - P2a, N=43; NCT02551809; Sponsor: United Neuroscience Ltd; "The top-line Phase 2a data met the primary aims of safety and immunogenicity with a 96% response rate. All secondary endpoints - including Amyloid PET burden, CDR-SB, ADCS-ADL, ADAS-Cog and MMSE - pointed directionally in favor of UB-311, though not statistically significant with the study sample size...Additional results, including future analysis of secondary endpoints and other data, are expected to be presented at upcoming medical meetings, such as the 14th International Conference on Alzheimer's and Parkinson's Diseases, and published in peer reviewed medical journals."

P2a data

IMMUNOLOGICAL AGENTS FOR NEUROCOGNITIVE DISORDERS- A REVIEW OF THE CURRENT EVIDENCE (EPA 2019) - "Finished trials with published Results were investigating a tau vaccine (AADvac 1- positive Results , phase 1 trial) and several vaccines directed against beta-amyloid plaques (ACC-001- negative Results , two phase 2A trials, gantenerumab- it may be efficient, but more trials are needed, bapineuzumab failed, phase 3 trial, BAN2401- it was efficient in a single phase 2A trial, AN1792- phase 2A trial produced positive effects and a follow-up after 4.6 years detected low anti-AN1792 antibody titers, and CAD106- only a phase 1 trial). The level of evidence for current immunological therapies targeting AD is not very encouraging, but many trials are currently ongoing or will start in near future."