Earlier today, Alzinova announced encouraging outcomes from the phase Ib extension study (part B) of ALZ-101, its vaccine candidate targeting Alzheimer’s disease. The study, which involved patients receiving treatment for a period exceeding 84 weeks, reaffirmed the vaccine’s strong safety and tolerability profile. Impressively, more than 95% of participants displayed a robust and durable immune response, even when dosing intervals were extended. This reinforces the potential of ALZ-101 as a long-lasting treatment option for Alzheimer’s patients, suggesting substantially less health care administration required for long-term treatment compared to current antibody alternatives.

Exploratory analyses of cognitive and functional parameters revealed a positive, dose-dependent trend correlated with treatment. While we want to emphasize that that this is not an efficacy study and should not be interpreted as such, we are excited by this and argue that it, coupled with the strong immune response, provides an early indication of ALZ-101’s potential efficacy in slowing disease progression. There was previously a slight worry given that the initial analysis of part A1 in the phase Ib study suggested no clear change on biomarkers and cognition. However, these exploratory endpoints change slowly in Alzheimer’s disease and the likelihood of being able to detect something in a shorter early phase clinical trial is therefore low. For example, this was the case in the first clinical phase I study of lecanemab (BAN2401), where no measurable effects of the treatment on CSF biomarkers were detected. Yet, the candidate would later go on to exhibit a clear treatment effect in subsequent efficacy studies and, eventually, reach market approval.

Being able to observe such signs of efficacy at this early stage of development is therefore truly encouraging and shows promise for the upcoming efficacy studies with ALZ-101. Furthermore, we believe that being able to point at initial clinical data that indicate efficacy could be of high significance for ongoing partner discussions and the preparations for the upcoming phase II study. The company itself has stated that it intends to accelerate partnering efforts following the results from the phase Ib study and mentioned in today’s webcast that it has ongoing discussions with potential partner but that the majority of them have awaited study results.

Asymptomatic Amyloid Related Imaging Abnormalities (ARIA) were observed in both treatment and placebo groups. Localized brain swelling (ARIA-E) was detected in one patient, while microhemorrhages (ARIA-H) were detected in nine patients. However, these occurrences were non-symptomatic and align with known risks associated with anti-Aβ therapies. These can also occur spontaneously in individuals with mild cognitive impairment (MCI) or Alzheimer's disease.

Although the sample size limits definitive conclusions, we argue that these preliminary results support continued development. As such, we expect the company to continue to prepare for the upcoming phase II trial, with the aim of validating the vaccine's efficacy. Alzinova mentioned in its webcast that Alzheimer's Disease Composite Score (ADCOMS) and Clinical Dementia Rating – Sum of Boxes (CDR-SB) are likely to be the primary efficacy endpoints in upcoming trials, as is standard in clinical trials in Alzheimer's disease. ADCOMS is a clinical tool designed to assess disease progression and cognitive decline in individuals with prodromal Alzheimer's disease or MCI due to Alzheimer's disease. Similarly, CDR-SB refers to a method used to quantify the severity of dementia based on a detailed assessment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care.