A Small Molecule Drug Candidate for Alzheimer’s Treatment

During the 2025 AD/PD International Conference on Alzheimer‘s and Parkinson‘s Diseases and Related Neurological Disorders in Vienna, Galimedix Therapeutics presented pre-clinical data on an oral drug, GAL-201. The data highlight the small molecule’s ability to modulate amyloid beta (Aβ) aggregation, demonstrating beneficial effects on synaptic plasticity and neuroinflammation.

GAL-201 is designed to bind misfolded Aβ monomers and prevent their aggregation into toxic oligomers and protofibrils – early drivers of Alzheimer’s disease. The results suggest that early intervention with GAL-201 may slow or halt Alzheimer’s disease progression. We spoke with Alexander Gebauer, Co-founder and Executive Chairman of Galimedix to learn more.

What makes GAL-201 unique among the current wave of amyloid-targeting Alzheimer’s drug candidates, especially considering the challenges faced by previous approaches?
 

Looking at the currently approved amyloid-targeting antibodies, Galimedix’s small molecules offer potential advantages based on preclinical results to date, including: no antibody-specific immunological side effects; oral delivery, which is much more convenient for patients; prevention of the formation of all toxic Aβ species instead of merely extracting some of those already formed; and easy to manufacture with formulation stability.

Other advantages, including over other small molecules in development, are higher potency in detoxifying Aβ, leading potentially to lower or fewer doses; high selectivity for misfolded monomers, leaving physiological (non-misfolded) monomers, which are important for normal neuronal function, intact – ultimately leading to a better cognitive outcome with reduced risk of unwanted side effects. Our candidates are expected to work regardless of genotype (APOE4-independent), and we have data supporting a long-lasting, self-propagating effect even when dosing is interrupted (so, even if, for example, a patient skips doses by accident, which can easily happen in a mild cognitive impairment or Alzheimer’s disease population).

Can you walk us through the mechanism by which GAL-201 interacts with misfolded Aβ monomers, and how this prevents toxic aggregate formation?
 

The underlying trigger for neuroinflammation seems to be the Aß-induced neuronal cell death. Neuroinflammation itself then enhances the disease process. If Aß-toxicity can be stopped or at least significantly reduced, neuroinflammation will also be stopped or reduced.

GAL-201 targets a specific binding motif that is only exposed on misfolded Aβ monomers, leaving normal Aβ monomers intact. The misfolded monomers and GAL-201 (or GAL-101) then form so-called “clusters,” which are clearly distinct from the beta-sheet structure Aß aggregates seen in AD patients. These clusters are then digested and removed from the system, resulting in detoxification of pathological Aβ. 

GAL-101, a closely related compound, is in clinical trials. What have you learned from GAL-101 that informs your development strategy for GAL-201?
 

GAL-201 is a chemically closely related follow-up compound to GAL-101 but has separate patent protection. According to our current data, GAL-201 has the same mechanism of action as GAL-101. Their pharmacological characteristics are similar, but not identical. From the ongoing phase I study with GAL-101, we are seeing an excellent safety profile in humans and therefore expect the same for GAL-201. As a result, the dosage of GAL-201 in patients should not be limited by tolerability and we can aim for maximum clinical efficacy.

We also expect GAL-201 to have a better safety profile than currently available anti-Aβ antibodies. No regular brain imaging will be required to monitor patient safety, which should improve patient’s treatment compliance and result in significantly reduced costs for payors.

Beyond Alzheimer’s, Galimedix is exploring indications such as dry age-related macular degeneration (AMD) and glaucoma…
 

That’s right. There are now many independent studies implicating toxic Aβ oligomers as an underlying cause of neurodegenerative diseases of the retina in the eye, such as glaucoma and dry AMD, thus supporting our approach to study these indications, as well as Alzheimer’s, with our product candidates.

We also have independent affirmation of our approach through our strategic collaboration with a leading ophthalmology player, Théa Open Innovation.

Galimedix has roots in both the US and Germany — how has this transatlantic setup shaped your development strategy or collaboration opportunities?
 

At this time, we are run virtually, with our team mainly in Europe and Israel. However, establishing ourselves as a US (Delaware) corporation is helpful for US investors and enables us, if we so choose, to grow in the US. Our foothold in Germany – and in Israel – is of course helpful in applying for funding, as well as establishing feet on the ground in Europe. Germany is also where I and others in our team are based. Personally, I am spending a significant amount of my time in the US, attending scientific meetings and speaking to potential investors.

What are the next steps for GAL-201? Are there plans for a clinical trial in the near future?
 

At this point in time, we are focused on advancing GAL-101 through a phase II study with GAL-101 eyedrops in dry AMD (funded by Théa but run by Galimedix) and continuing a phase I study with GAL-101 capsules. This is the first step before we can move forward in Alzheimer’s disease. So far, we are not seeing any safety signals and have excellent plasma pharmacokinetic results. In the future, assuming we can secure the necessary funding, we are planning to progress GAL-201 into clinical development.