Less than a month since we reported Vaxxinity’s “promising” results in a trial of UB-312, the company has released further encouraging news; new data demonstrates that UB-312 has established “clear target engagement” by slowing seeding of alpha-synuclein (αSyn) in cerebrospinal fluid (CSF) of patients with Parkinson’s disease (PD). This is described as “further validation” of Vaxxinity’s platform technology in neurodegenerative disease.
A major milestone
CEO Mei Mei Hu, who kindly spoke to us at the World Vaccine Congress in April, views the recent update as a “major milestone” for Vaxxinity.
“Our candidate has shown target engagement of the toxic species of alpha-synuclein in patients, demonstrating not only proof of our technology platform, but also proof of the mechanism of our vaccine-derived antibodies specifically engaging with the toxic target in vivo.”
This target engagement has “always been a key challenge” for neurodegeneration, says Hu, who believes this milestone is “worth celebrating”.
“It is beyond our expectation to see this in our Phase I trial.”
She thanked the participating patients and The Michael J. Fox Foundation and collaborators for work on the “cutting-edge assays” that facilitated the breakthrough.
Why target αSyn?
We were lucky to reach Dr Jean-Cosme Dodart, SVP of Research at Vaxxinity, for a few comments on this exciting news, and so we asked for some insight into the approach they are taking. Dr Dodart explains that “although mutations in the alpha-synuclein gene are rare”, aggregates in the form of Lewy bodies and Lewy neurites are “common neuropathological hallmarks” of PD. This suggests a “key role” of αSyn in PD neuropathogenesis.
Furthermore, “preformed fibrils of αSyn can induce the formation of Lewy Body-like inclusions and cellular dysfunction in cell-based assays” and preclinical animal models. These data “strongly suggest” the therapeutic potential of targeting pathological forms of αSyn.
“It is not known, however, at what stage of the disease immunotherapy against αSyn will be required. We anticipate that the earlier we intervene, even before symptoms onset, the better the outcome of therapy.”
A promising candidate
As we know from last month, UB-312 was well tolerated in trial. Furthermore, it induced anti-αSyn antibody responses, of which antibodies were detectable in the CSF. Additional analyses, other target engagement assays, and further antibody characterisation studies will continue. Dr Mark Frasier, Chief Scientific Officer at Michael J. Fox Foundation stated that “integration of critical biomarker insight into therapeutic development programmes is essential” for encouraging confidence in the approach and “designing informative trials”.
“We’re pleased to support efforts of this kind that can have major impacts for people with Parkinson’s disease.”
Dr Dodart kindly outlined some of the advantages that this vaccine will have to therapeutic endeavours, and why it perhaps more encouraging than previous efforts.
“Vaccines offer a variety of advantages over monoclonal antibodies; they are easier to manufacture, easier for patients to take, and dramatically less costly.”
Consequently, they can be scaled for “millions, or even tens of millions of people”. They can also be used for prevention. However, for neurodegenerative diseases such as Parkinson’s, showing target engagement has “always been a key challenge to overcome”. Dr Dodart describes Vaxxinity’s demonstration of target engagement a “noteworthy success”.
Next steps and other applications
The demonstration of target engagement is “promising” for Dr Dodart, not just because the antibodies are “getting where they need to and doing what we want them to do”.
“This also represents a proof of technology for Vaxxinity’s platform that we expect to translate across our pipeline in other chronic diseases, such as Alzheimer’s.”
Looking forward, Dr Dodart anticipates further clinical development for UB-312.