Leede Jones Gable analyst Douglas Loe provided an update on Wednesday on drug developer ProMIS Neurosciences (ProMIS Neurosciences Stock Quote, Charts, News, Analysts, Financials TSX:PMN), saying strong clinical results from a peer company working on Alzheimer’s disease are a positive for ProMIS.
Japan-based Eisai Co announced on Wednesday that its Phase 3 Clarity AD 1,795-patient trial showed a highly statistically significant reduction of clinical decline, hitting the study’s primary endpoint and all key secondary endpoints with drug lecanemab, an investigational anti-amyloid beta protofibril antibody for the treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD).
The data showed lecanemab at a biweekly dosage of 10 mg/kg body weight generated statistically significant (27 per cent) slowing of cognitive decline at a 18 months follow-up compared to placebo, with cognitive impairment measured by the widely-used CDR-SB scale on clinical dementia.
“Additionally, the lecanemab Clarity AD study results prove the amyloid hypothesis, in which the abnormal accumulation of Aβ in the brain is one of the main causes of Alzheimer’s disease, when targeted with a protofibril-binding therapy. Eisai believes these findings will create new horizons in the diagnosis and treatment of Alzheimer’s disease as well as further activate innovation for new treatment options,” said Haruo Naito, Eisai CEO, in a press release.
Commenting on the results and on amyloid beta research on AD in general, Loe said recent studies on the role of beta-amyloid deposition in the brain as it relates to AD have been not come out too positive, citing a Phase 3 study by Janssen and Pfizer on bapineuzumab and Eli Lilly on solanezumab. Those challenges have thus called into question the future of research on beta-amyloid as it relates to AD progression.
But Loe said a lot depends on the form of amyloid beta, with ProMIS and Eisai both focusing on a specific oligomeric form of amyloid, which the companies hope to show to be more relevant.
“Our PMN investment thesis rested squarely on our diligence that revealed evidence to us that a specific oligomeric form of amyloid could be more relevant than monomers or plaques on impacting cognitive impairment and the most clinically-advanced therapies designed to directly test this hypothesis (lecanemab) has now generated strong Phase 3 evidence that oligomer/protofibril-targeted therapies can indeed be relevant in mitigating AD symptoms,” Loe wrote.
“Accordingly, we believe that Phase 3 Clarity AD data, while directly relevant to lecanemab, of course, are indirectly relevant to PMN-310’s medical prospects through the mechanistic validation they confer,” he said.
Loe pointed out that lecanemab was developed by Eisai’s Sweden-based partner BioArctic AB and that it conceptually resembles ProMIS’ own amyloid-oligomer-specific mAb PMN-310.
“PMN-310 in that it targets a unique oligomeric amyloid structure called protofibrils, and protofibrils were shown by BioArctic/Eisai to have their own unique neurotoxic cognition-impacting activity that was independent of any other amyloid forms. Accordingly, we have long seen lecanemab and its suite of clinical studies that now includes Clarity AD as being relevant to how PMN-310 could impact cognition as well, even though we were mindful that PMN-310 targeted a distinct non- protofibril oligomeric amyloid form,” Loe said.
On ProMIS’ progress, Loe said he is still expecting the company to advance preclinical activities ahead of an Investigational New Drug (IND) application with the US FDA, with that filing likely to be submitted for review before the end of the fourth quarter 2022 and with formal Phase 1 clinical testing of PMN-310 to start during the first half of 2023.
“Commencement of this trial is the key milestone we are tracking in our PMN investment thesis at present, and we are optimistic that a suitable/safe PMN-310 dose can be identified in that trial by end-of-FQ423,” Loe wrote.
“We remain positive about the role that PMN-310 could play in mitigating AD progression through its documented amyloid-oligomer-specific binding and we are thus encouraged that a related mAb that also targets an amyloid oligomer form has not solidly demonstrated clinical efficacy on mitigating cognitive impairment in a large and well- controlled Phase 3 study,” he said. “We believe that Clarity AD/lecanemeb data thus provide supporting evidence for our PMN-310-based investment thesis for PMN and for the role of oligomers/protofibrils in AD pathophysiology.”
With the update, Loe maintained a “Speculative Buy” rating on ProMIS Neurosciences and a one-year price target of $28.50 per share, which at the time of publication represented a projected one-year return of 313 per cent. PMN shares rose almost 21 per cent in trading on Wednesday, bringing the stock to a year-to-date return of negative four per cent.