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.

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.

Al Sandrock predicts Alzheimer's treatment will shift from managing symptoms to prevention. Like cholesterol, amyloid buildup will be monitored via routine blood tests, allowing for treatment to be administered early to prevent irreversible neuron loss before cognitive impairment begins.

The focus in Alzheimer's treatment is moving from merely slowing decline in late-stage patients to early prevention. By using anti-amyloid drugs to clear plaques before significant brain damage occurs, it may be possible to prevent the disease's onset entirely.

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.

Avenco's NKEV therapy is designed for nasal spray delivery, avoiding hospitalization. The vesicles can be freeze-dried, shipped at room temperature, and reconstituted at home. This dramatically simplifies logistics and improves user-friendliness compared to complex, cryopreserved cell therapies, representing a major leap in manufacturability and patient access.

The use of Natural Killer (NK) cells for Alzheimer's wasn't a planned discovery. A company observed remarkable cognitive improvement in an Alzheimer's patient they were treating for post-chemotherapy infection risk. This serendipitous finding redirected research towards neurodegeneration, highlighting the unexpected pathways to innovation in drug development.

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.

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.