A sample due diligence case from the perspective of PlexoA’s scientific advisory team.
Background
A venture capital firm was evaluating a CNS-focused biotech startup preparing for its Series A raise. The company claimed to have developed a novel nanoparticle platform that could cross the blood-brain barrier (BBB) and deliver small molecules directly to neural tissues. The tech sounded promising—but the investor needed to know: Is it real, scalable, and differentiated—or just an over-polished pitch?
The Questions We Asked
Crossing the BBB is one of the biggest challenges in neuroscience drug delivery. We approached this claim with healthy skepticism and asked:
- Are their preclinical models relevant to human BBB physiology?
- Is the mechanism of transport biologically validated or just theoretical?
- Is the patent estate strong, or are there similar platforms already protected?
- What’s the development feasibility from CMC to regulatory pathways?
In the realm of biopharma, where science meets human health, the art of risk assessment is not just about mitigating dangers—it’s about illuminating the path to groundbreaking discoveries.
What We Evaluated
✅ Scientific Feasibility
- The startup used peptide-tagged nanoparticles that exploit transcytosis mechanisms to pass through endothelial cells in the BBB.
- In vitro data on cell monolayer penetration was promising, but in vivo validation was limited to one mouse model with unclear human relevance.
- No clear demonstration of targeted therapeutic effect post-BBB crossing.
✅ Model Relevance & Data Quality
- The core data came from rodent models with artificially compromised BBB (e.g., through induced inflammation).
- Lacked validation in non-human primates or models with intact BBB—raising doubts about real-world applicability.
- Imaging and PK data were presented, but raw data was not shared and statistical analyses were not peer-reviewed.
✅ IP and Competitive Landscape
- Patent filed in US and EU, covering delivery peptides and core nanoparticle design.
- However, similar approaches using receptor-mediated transcytosis already existed in literature and active patents.
- Freedom to operate was questionable.
✅ Translational Readiness
- Lack of strategic partnerships or external validations.
- CMC plans in early discussion phase—platform reproducibility and toxicity not yet assessed.
- No engagement with regulators yet (e.g., pre-IND meetings or guidance on CNS delivery expectations).
Key Findings
Early Innovation, But High Uncertainty
The platform showed creative thinking, but lacked validation in realistic models. The investor was impressed by the concept but needed more proof before writing a Series A check.
Risks Identified
- BBB model limitations
- Competitive IP with overlapping claims
- Premature claims of translational readiness
- No safety or scale-up data
What Happened Next
Following PlexoA’s report, the investor decided to pause participation in the round. They encouraged the startup to run two additional preclinical studies with appropriate animal models and strengthen their IP position.
Rather than a failed pitch, this became an opportunity: the startup revised its milestones, refined its narrative, and focused its next steps more strategically. The investor left the door open for future investment.
Why This Matters
CNS startups often face the temptation to oversell BBB penetration—because it’s hard to prove, and harder to do well. Without objective scientific review, even the most polished pitch can mask deep biological risks.
At PlexoA, we help investors and innovators ground decisions in clear, science-backed feasibility assessments—so great ideas don’t get lost in translation.
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