Voyager CEO Al Sandrock outlines a focused strategy: remain specialists in neurology, but broaden the therapeutic modalities (gene therapy, proteins, oligonucleotides). This allows them to pursue well-validated CNS targets that are considered "undruggable" by traditional small molecules, which have historically been the only option for crossing the blood-brain barrier.

To normalize the ethically fraught practice of embryo gene editing, startups like Preventive are shifting the narrative from just curing disease to radical cost reduction. They claim editing embryos could cost $5,000, a fraction of the $2 million price tag for current adult gene therapies.

Founder Sean Ainsworth intentionally started his pioneering AAV gene therapy in an ocular setting before any Western approvals existed. Because an intravitreal injection uses a very small vector amount, it provided a significant safety advantage and a manageable way to prove the technology before attempting systemic delivery.

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.

The commercial advantage of one-time CRISPR/Cas9 therapies is shrinking. Advancements in RNA modalities like siRNA now offer durable, long-lasting effects with a potentially safer profile. This creates a challenging risk-reward calculation for permanent gene edits in diseases where both technologies are applicable, especially as investor sentiment sours on CRISPR's long-term safety.

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.

Renowned gene therapy pioneer Jim Wilson was forced to spin out ultra-rare disease programs into a new company after his initial venture failed to attract VC funding. This demonstrates that even elite scientific leadership cannot overcome investor disinterest in this segment without powerful, predictable government incentives like transferable priority review vouchers.

The success of Praxis's small molecule for a genetic epilepsy presents a strategic alternative to cell and gene therapies. In an era where complex modalities face funding, safety, and commercial hurdles, advanced small molecules offer a viable and potentially more practical path for treating genetic disorders.

Venture capital for US seed and Series A cell and gene therapy companies has collapsed from a historical high of 17-21% of deals to only 7% this year. The sharp decline is driven by a confluence of factors including patient deaths, persistent manufacturing challenges, and growing regulatory uncertainty.