Alzinova's vaccine candidate ALZ-101 is designed to selectively target toxic amyloid-beta oligomers that play a central role in the development of Alzheimer's disease.
The company's Phase Ib study, which was completed in January 2025, demonstrated that ALZ-101 has an excellent safety profile with minimal side effects and induces a robust, long-lasting immune response in patients with early Alzheimer's disease. Functional and cognitive data, along with a positive effect on the biomarker neurofilament light chain (NFL), indicate that the vaccine can slow the progression of the disease. Active vaccination, such as ALZ-101, also has several advantages over monoclonal antibody therapy because it provides a long-lasting immune response, requires fewer administrations, is more cost-effective and can ultimately be used preventively in early Alzheimer's disease.
With this promising data behind it, Alzinova is now approaching Phase II, confident that ALZ-101 will offer better efficacy and fewer side effects compared to existing treatments.
Rights issue finances phase II preparations
To finance the next step in development, Alzinova is conducting a rights issue that could raise SEK 35,7 million for the company. The issue, which runs from April 17 to May 6, will be used to complete preparations for the phase II study. This includes production of the final drug product, preclinical studies according to regulatory requirements and government applications. The capital also strengthens the company's financial position during ongoing partner dialogues with global pharmaceutical companies, which could facilitate future financing and commercialization.
Drug substance ready for the next step
As recently as last week, Alzinova announced that the drug substance for ALZ-101 is ready, enabling production of the vaccine and the start of the phase II study this year. The substance, produced by Polypeptide Laboratories in France, meets strict GMP standards. The collaboration between the companies will continue to optimize the manufacturing process, focusing on efficiency, scalability and regulatory requirements for later clinical phases and potential commercialization.
Alzinova's CSO comments
To gain deeper insight into ALZ-101 – and in particular its mechanism of action – but also what observed biomarker data indicate for further development, we reached out to Alzinova’s co-founder and Chief Scientific Officer Anders Sandberg.
Can you describe in a little more detail ALZ-101's mechanism of action and what makes it unique compared to existing treatments?
– ALZ-101 is an active vaccine that contains a unique antigen: a specific, stabilized form of Abeta oligomer. When we first studied how this antigen affected the immune system in experimental animals, we found that the response was surprisingly specific – the antibodies were directed almost exclusively against this oligomer form, and not against other forms of Abeta. This is remarkable because vaccines usually give rise to a polyclonal response with many different antibody types.
– Other vaccines targeting Abeta tend to elicit antibodies against a different part of the molecule – the so-called N-terminus. This is a less effective strategy, as this region is not specific for the toxic forms of Abeta. The result is that the antibodies largely bind to harmless, physiological forms and thus lose their therapeutic potential. In ALZ-101, the immunodominant epitope is instead located in the middle of the peptide – an area with unique structure in the oligomeric form – which means that the antibodies only bind to this particular harmful form in the brain.
Why does it matter that a laboratory animal develops an immune response to a synthetic oligomer?
– There are countless synthetic variants – such as ADDLs, globulomers, amylospheroids, beta-amyballs, protofibrils and several others – whose physiological relevance is highly questionable. The point of ALZ-101 is that its antigen should mimic the pathological forms of Abeta that actually occur in human brains, in order to train the immune system to identify and neutralize these. Although knowledge of the truly relevant oligomers is still limited, we know that only a small fraction of the oligomers found in patients' brains are directly harmful. Therefore, it is not enough for a treatment to be “oligomer-specific” – it must also be selective, or preferably completely specific, for the toxic oligomeric forms of Abeta.
– To investigate this further, we collaborated with researchers at the University of Gothenburg and the University of Amsterdam. Together, we analyzed whether antibodies directed against the antigen in ALZ-101 could neutralize toxic Abeta in brain extracts from patients. In this proof-of-concept study, we used the antibody ALZ-201, which was developed from mice immunized with ALZ-101 and which exhibits specificity for the antigen in ALZ-101. The results were very promising: ALZ-201 reacted with only a very small proportion of all Abeta in the extracts, but still had a strong ability to neutralize the toxicity.
– It is precisely these properties – an immunodominant epitope that gives rise to a specific immune response against physiologically relevant, toxic Abeta – that make ALZ-101 unique among the therapies currently being developed for Alzheimer's disease.
How does ALZ-101's selectivity help avoid unwanted immune reactions?
– The ALZ-101 vaccine is specifically designed to target the toxic Abeta oligomers linked to Alzheimer's disease. This high selectivity means that the vaccine only focuses on these harmful structures, improving the immune response and reducing the risk of side effects.
– By modifying the central part of the peptide in ALZ-101 that normally stimulates a B-cell-driven immune response against the N-terminus of Abeta – which is present in all forms of Abeta – the vaccine instead causes the immune system to produce antibodies against the central parts of the Abeta oligomers. These structures are unique to the toxic forms of Abeta. In this way, ALZ-101 avoids the N-terminal part and reduces the theoretical risk of inducing autoimmunity against the body's own Abeta. However, it should be added that there is no evidence that immunization with synthetic Abeta antigens would actually risk causing an autoimmune reaction against endogenous Abeta.
– An even more important advantage of ALZ-101 is that it avoids activating an inflammatory and harmful T-cell response. T-cells are immune cells that, if activated incorrectly, can lead to inflammation and tissue damage. An example of this is seen in a previous clinical trial with the AN-1792 vaccine, which also targeted Abeta, where an unwanted T-cell response caused severe brain inflammation in some patients and forced the study to be discontinued. In ALZ-101, the part of the peptide that can trigger this harmful T-cell response has been modified, which essentially eliminates the risk of similar side effects.
Can you tell us more about the findings regarding biomarker data from the phase Ib study?
– In our study, we included established biomarkers in cerebrospinal fluid, with a particular focus on those relevant to Alzheimer's disease. We analyzed specific disease markers such as phosphorylated Tau (P-Tau181), total Tau (T-Tau), neurogranin and amyloid-beta (Abeta). In addition to these, we studied markers linked to neuroinflammation, such as YKL40 and sTREM2, as well as a more general marker of nerve damage – neurofilament light chain (NFL).
– These biomarkers are well-established and are used both for diagnostics and to predict how the disease will develop in individual patients. They change slowly over several years as amyloid plaques build up in the brain. However, once symptoms appear, the changes in most of these markers are relatively small – with the exception of NFL.
– Our results showed a dose-dependent, but overall limited, effect on P-Tau181, T-Tau and neurogranin early during treatment. This effect appears to be linked to exposure to the antibodies generated by the vaccine. However, the effect decreased over time and was no longer measurable after longer treatment. We could also not see any clear impact on Abeta levels.
– Although this may be perceived as negative, it is in fact in line with the specificity of the vaccine for oligomers – ALZ-101 does not affect plaque, even in a mouse model where treatment was initiated preventively. However, we observed an effect on NFL in the patients who received active treatment from the start of the study, which is a very interesting observation.
– It should be noted that since there are currently no drugs that clearly slow the progression of the disease – not even the approved antibodies against Abeta – we still do not know how these biomarkers change in response to a treatment that really makes a difference. When plaque reduction with antibody therapy is used, some markers such as P-Tau181 and neurogranin can decrease, while others, such as NFL, often remain unchanged, despite the expectation of improvement. This raises questions about many therapies that claim to be disease-modifying, but are at the same time in line with the weak therapeutic effect that has actually been observed for them.
– We suspect that many of the established biomarkers primarily reflect plaque-related pathology, while a parallel disease process continues in the background – a process that current antibody therapies do not seem to affect. Our hope is that our treatment instead targets this alternative, plaque-independent pathology. Overall, the results suggest that we act through a unique mechanism of action that is clearly different from both approved drugs and those in clinical development.
What bearing do biomarker data such as NFL have on the design of the phase II study?
– NFL was raised as a secondary endpoint, but none of the other biomarkers. We will also include other markers, such as p-Tau217, not least for differentiation against approved therapies to show that we are truly “first-in-class”.
Let's end with a more personal question: As co-founder and former CEO, you have been part of Alzinova's journey from the beginning. How does it feel to now be approaching a milestone like Phase II studies?
– The short answer is incredibly fun… The journey has undeniably been long – from an idea that grew out of pure curiosity to an imminent proof-of-concept study. Drug development is one of the most complex areas there is, where everything from financing and production to preclinical and clinical safety and efficacy must work together, and under strict regulations. Despite that, we are now ready to take the next step.
– It is an achievement we at Alzinova are proud of – especially considering that we are a small company. In many ways it is reminiscent of the children's book The Little Engine That Could. We may be small, but we have the tenacity and drive to keep climbing the hill year after year. Thanks to the team's expertise and positive attitude, we are convinced that, just like the little blue locomotive, we will make it over the mountain – and reach our goal: to deliver a medicine to patients that really makes a difference. The concept is simply too good not to be pursued.
See also: Alzinova's CEO Tord Labuda visited BioStock's studio to tell us more about the ongoing rights issue: “The potential and need is enormous”
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This material has been prepared for marketing purposes and is not, and shall not be deemed to constitute, a prospectus under applicable laws and regulations. The full terms and conditions of the rights issue and further information about the company have been set out in a prospectus which has been published and published on the website of the above-mentioned company.
