The most important upcoming catalyst in neuroscience is Eli Lilly's TRAILBLAZER-ALZ 3 study, which aims to prevent Alzheimer's in at-risk patients. A positive result is expected to show a much larger effect size than seen in treating existing disease, potentially creating a massive new market and shifting the entire neurodegenerative paradigm.

While Natural Killer (NK) cells themselves are too large to cross the blood-brain barrier, the nanoscale extracellular vesicles (EVs) they produce can. This allows Avenco to harness the therapeutic potential of NK cells for neurodegenerative diseases by delivering their active cargo directly into the brain, solving a fundamental delivery challenge.

Isaac Stoner's company, MindImmune, posits that Alzheimer's is an immune response to amyloid plaques causing neuron damage. Their therapeutic approach targets immune cells outside the brain to treat a CNS disease, a paradigm shift from traditional methods that focus solely on the brain.

Gamma secretase inhibitors, a class of drugs initially developed for Alzheimer's disease and later failed in other solid tumors, were successfully repurposed for desmoid tumors. This was due to their specific activity on the Wnt/Notch signaling pathways that drive this rare disease.

The GSK3 inhibitor was developed for CNS diseases, requiring high specificity and the ability to cross the blood-brain barrier. These same pharmaceutical characteristics—potency and lipophilicity—proved highly advantageous for treating cancer, demonstrating an unexpected but effective therapeutic pivot from neuroscience to oncology.

Dr. Radvanyi emphasizes that foundational discoveries in immunotherapy arose from basic immunology and serendipitous observations, like his own unexpected T-cell proliferation with an anti-CTLA-4 antibody. This highlights the risk of over-prioritizing translational research at the expense of fundamental, curiosity-driven science.

The first iPSC therapies focused on CNS and eye diseases not because they were the biggest markets, but because their differentiation protocols were discovered first—sometimes by accident, like leaving cells in an incubator over Christmas break. This shows how scientific serendipity, not strategy, can shape a field's initial direction.

The next era of CNS drug development will shift from single-target therapies for late-stage disease to early intervention. This involves using biomarkers to detect disease before symptoms appear and intervening with multimodal approaches that address multiple biological pathways simultaneously, such as amyloid, tau, and metabolic deficits in Alzheimer's.

The company's lead molecule was initially invented to treat CNS diseases like Alzheimer's. A pivot occurred when a postdoc with an interest in oncology tested the compounds against refractory tumors, uncovering their true potential and leading to the company's formation around a new indication.