recently presented new data that reinforce how the binding profile of its monoclonal antibody (mAb) drug PMN310 differs from other biopharmas' amyloid-targeting mAbs, reported Leede Jones Gable analyst Dr. Douglas Loe in an August 5, 2022 research note.
"Our investment thesis predicts that this uniqueness could be relevant to [PMN310's] prospects as an Alzheimer's disease-reversing therapy," Loe added.
Specifically, Loe relayed, the data showed PMN310 selectively binds to neurotoxic beta amyloid oligomers and not to monomers or higher-order plaques. This was determined through a series of comparative tests ProMIS conducted on PMN310 and other mAbs. The biotech presented the findings via a poster session at the recent Alzheimer's Association International Conference (AAIC).
"We believe that if toxic amyloid oligomers are shown in forthcoming years to be as relevant to Alzheimer's disease cognitive impairment as we currently predict, [then] PMN310's oligomer-selective binding can be important to its clinical success," Loe wrote.
According to the analyst, the AAIC data achieve two ends. First, they "nicely show that PMN310 does indeed exhibit all of the oligomer-selective binding characteristics that it was designed to exhibit," he wrote.
Second, the data give "us confidence that ProMIS is advancing well on its investigational new drug-enabling testing and that PMN310 can indeed advance into formal Phase 1 testing in fiscal year 2023."
Loe reviewed the results of ProMIS' experiments, in which it quantified, via surface plasmon resonance, and compared the degree of binding by PMN310 and other mAbs (Eli Lilly's solanezumab and donanemab, Roche's crenezumab, Eisai's lecanemab and Biogen's aducanumab) to various aggregated forms of beta amyloid.
The first set of tests assessed the binding of these mAbs to amyloid monomers. PMN310 bound minimally, but the presence of monomers only mildly affected the mAb's ability to bind to its true target, larger oligomers. Donanemab also showed minimal binding, but where it falls short, Lowe wrote, is in its measurable degree of binding to amyloid plaques. Unlike PMN310 and donanemab, solanezumab and crenezumab showed a high degree of monomer binding.
ProMIS also evaluated the binding of the mAbs to low molecular weight amyloid oligomers, ranging from two to 12 amyloid monomers in aggregate, after they were preincubated with monomeric protein. All of the tested mAbs bound to these oligomers, Loe noted, but the preincubation had a greater effect on the mAbs exhibiting tighter binding to monomers, solanezumab and crenezumab.
Only PMN310 showed a high level of oligomer-selective binding, differentiating it from its peers.
In another battery of tests, ProMIS evaluated the binding of the mAbs to beta amyloid oligomers isolated from soluble brain extracts. All of the mAbs bound to those oligomers, lecanemab more so than the others.
Finally, ProMIS tested the binding of mAbs to amyloid plaques of the type found in Alzheimer's disease patients' brain tissue. PMN310 did not bind at all while all of the others, even lecanemab, did to some degree.
"Absence of detectable PMN310 binding to amyloid plaques could be as relevant to the mAb's safety profile as to its efficacy in reversing oligomer-impacted cognitive impairment," Loe commented.
Leed Jones Gable rates ProMIS Neurosciences Inc. a Speculative Buy with a $28.50 target price.
ProMIS Neurosciences Inc. last closed at $6.04 on August 9, 2022. The company has around 7.2 million shares outstanding and a market cap of $44.81 million. It is currently trading at $7.74.
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