Background

UB-311 is a synthetic peptide vaccine developed by United Neuroscience, a spin-off of United Biomedical. UB-311 couples a helper T-cell epitope designed with United Biomedical's UBITh® platform to the Aβ1–14 sequence, packaged in a proprietary vaccine-delivery system. The approach aims to stimulate a T-helper type 2 regulatory immune response over a T-helper type 1 proinflammatory response, and to avoid cross-reactivity with similar endogenous antigens, i.e., autoimmune responses.

A peer-reviewed paper on preclinical studies in small animals, baboons, and macaques reported that the vaccine generated N-terminal anti-Aβ antibodies, which neutralized Aβ toxicity and promoted plaque clearance. The paper also claimed that the vaccine evoked no anti-Aβ cellular responses in a transgenic mouse model for AD, and that both acute and chronic dosing were safe and well-tolerated in cynomolgus macaques (Wang et al., 2007).

Findings

In 2010/2011, a Phase 1 safety, tolerability, and immunogenicity trial evaluated three doses of UB-311 in 19 people with mild to moderate Alzheimer's disease, 14 of whom continued into a long-term follow-up study. At two sites in Taiwan, three shots were administered intramuscularly at baseline, four weeks, and 12 weeks; the follow-up study observed participants out to 48 weeks. Results were reported to have shown that the vaccine was safe and well-tolerated, with the most common adverse events being injection site swelling and agitation. UB-311 produced a specific antibody response in all participants tested (Wang et al., 2017).  At CTAD 2017, company scientists claimed the elicited antibodies bound Aβ oligomers, fibrils, and plaques, but not monomers. They reported no amyloid-related imaging abnormalities after vaccination (Dec 2017 conference news).

In October 2015, a Phase 2 trial at four sites in Taiwan started enrolling 43 people with a diagnosis of mild Alzheimer's disease confirmed by amyloid PET, an MMSE between 20 and 26, and a CDR of 0.5 or 1. This study compared two dosing regimens—three priming shots followed by two boosters, and three priming shots followed by four boosters—to placebo, administered over 60 weeks. Besides primary outcomes of safety/tolerability and immunogenicity, this study also assessed cognitive, functional, global, and neuropsychiatric outcomes 18 weeks after the last dose. A safety extension began in August 2018, with 34 participants receiving three or five additional vaccinations over 96 weeks.

In a January 2019 press release, the company announced results of the placebo-controlled portion of the study. UB-311 was safe and generated Aβ antibodies in 96 percent of participants. Changes in secondary endpoints reportedly favored immunization but missed statistical significance. According to results presented at the 2020 CTAD conference, people who received four boosters declined only half as much on the CDR-SB, ADCS-ADL, ADADS-Cog as those who received two boosters or placebo. The same group also showed a modest reduction in brain amyloid at the end of the study. Adverse events data are posted on clinicaltrials.gov. None were judged to be caused by the drug. Results were published after peer review (Yu et al., 2023). 

In December 2019, United Neuroscience terminated the extension of this trial based on “a treatment assignment error.” No further information is available.

At CTAD 2020, a Phase 3 development plan was presented, consisting of two identical, double-blind, placebo-controlled, 73-week studies. The parallel trials are to enroll a total of 3,218 participants with MCI or mild AD, who are to receive three priming and four booster immunizations. The CDR-SB is planned as the primary outcome; secondary and exploratory outcomes include a range of cognitive, functional, and biomarker measures. No start date or study locations were announced, and the study was not listed in clinical trial registries. United Neuroscience has been renamed Vaxxinity.

In May 2022, the U.S. FDA granted UB-311 fast-track designation for Alzheimer’s disease, facilitating expedited development and review.

As of January 2023, the company is seeking a partner for Phase 3 development, and has not registered nor begun a large trial of UB-311 (investor presentation slide #10).

For all English-language clinical studies, see clinicaltrials.gov.