The next wave of longevity investment favors 'subtractive' therapies over traditional 'additive' drugs. Startups like Nanotics, which use nanorobots to remove specific harmful molecules, are gaining traction because they avoid the inherent side-effect risks associated with introducing new compounds.

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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.

The company focuses on disease-specific 3D protein conformations, which exposes new binding sites (epitopes) not present on the same protein in healthy cells. This allows for highly selective drugs that avoid the toxicity common with targets defined by genetic sequence alone.

The fund backs underfunded, high-risk ideas that others pass on. The goal isn't just to find a unicorn; it's to contribute to science by definitively disproving a hypothesis. A failure is viewed as "crossing out a wrong answer" for the entire field.

The degradation mechanism is fundamentally superior to inhibition because it removes the entire protein, addressing both its enzymatic and scaffolding functions. This allows degraders to hit targets harder and more completely, suggesting they could become the dominant modality across oncology and other therapeutic areas.

The tech world is fixated on trivial AI uses while monumental breakthroughs in healthcare go underappreciated. Innovations like CRISPR and GLP-1s can solve systemic problems like chronic disease and rising healthcare costs, offering far greater societal ROI and impact on longevity than current AI chatbots.

Biotech companies create more value by focusing on de-risking molecules for clinical success, not engineering them from scratch. Specialized platforms can create molecules faster and more reliably, allowing developers to focus their core competency on advancing de-risked assets through the pipeline.

Beyond tackling fatal diseases to increase lifespan, a new wave of biotech innovation focuses on "health span"—the period of life lived in high quality. This includes developing treatments for conditions often dismissed as aging, such as frailty, vision loss, and hearing decline, aiming to improve wellbeing in later decades.

Voyager CEO Al Sandrock explains their AAV capsids are engineered to be so potent at crossing the blood-brain barrier that doses can be an order of magnitude lower than standard. Crucially, the capsids are also designed to *avoid* the liver, directly addressing the toxicity issues that have plagued the field.

DFJ Growth Partner Barry Shuler details their strategy of avoiding herd investments by focusing on 'life tech'—the intersection of life sciences and technology. This contrarian approach allows them to back brilliant but lesser-known visionaries in emerging fields like population genomics, where they see immense potential.

The traditional endpoint for a longevity trial is mortality, making studies impractically long. AI-driven proxy biomarkers, like epigenetic clocks, can demonstrate an intervention's efficacy in a much shorter timeframe (e.g., two years), dramatically accelerating research and development for aging.

Longevity VCs Bet on Removing Toxins, Not Adding More Molecules | RiffOn