Alzheimer's can be understood as a vascular disease rooted in nitric oxide deficiency. This decline impairs blood flow, glucose uptake, and inflammation regulation in the brain. Therefore, strategies to restore nitric oxide address the physiological root causes of the disease, not just the symptoms like plaque buildup.

As AI enables early disease prediction (like Grail's cancer test), the number of sick patients will decrease. This erodes the traditional drug sales model, forcing pharma companies to create new revenue streams by monetizing predictive data and insights.

Similar to how Gilead was viewed before its stock surge, Biogen is seen as a sleepy big-cap with a declining core business. However, it has several underappreciated near-term catalysts in Alzheimer's (tau program), SLE, and lupus that could re-rate the stock.

Novo Nordisk's large semaglutide Alzheimer's trial failure highlights a critical design flaw: launching a massive study without first using smaller trials to validate mechanistic biomarkers and confirm central nervous system penetration. This serves as a cautionary tale for all CNS drug developers.

Despite AI's power, 90% of drugs fail in clinical trials. John Jumper argues the bottleneck isn't finding molecules that target proteins, but our fundamental lack of understanding of disease causality, like with Alzheimer's, which is a biology problem, not a technology one.

Voyager CEO Al Sandrock suggests the 30% average efficacy of new Alzheimer's drugs isn't uniform. Instead, some patients may see a complete halt in progression while others see no benefit. He argues the next critical step is predicting these responders, which will determine whether future therapies like anti-tau agents should be added on or used as a replacement.

Eli Lilly ran the fastest-accrued Alzheimer's study in history by going direct-to-patient. This model, using televisits and centralized diagnostics, is highly effective for preventative medicines where motivated patients can be recruited online.

After several tau-targeting antibodies failed, including J&J's pazdenimab, confidence in blocking extracellular tau is waning. The field's new hope is Biogen’s Biv80, an antisense drug that prevents tau protein production at the mRNA level, a mechanism that has shown potential to reverse pathology in early data.

The long-term vision for Alt-Pep's diagnostic extends beyond symptomatic patients or those with family histories. The goal is for it to become a routine screening assay, administered annually to the general population to catch the disease at its earliest molecular stages, changing the paradigm from treatment to prevention.