Inside Startup Investing with Chris Lustrino

Re-Programming Viruses to Fight Brain Tumors—Inside Siren Biotechnology


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On this week’s Inside Startup Investing, Dr. Nicole Paulk—founder & CEO of Siren Biotechnology—details her AAV gene-therapy “FedEx truck” that can deliver anti-tumor cytokines directly to brain cancers. Early animal data show 86 % complete responses; the FDA has signaled a fast-track path for Siren’s first-in-human trial set for 2026. With analog comps like Keytruda earning $30 B a year, Siren’s upside—and impact—could be enormous.

Highlights include...

  • Why viruses? AAV viruses don’t cause disease in humans yet efficiently deliver genetic payloads; Siren re-engineers them to express anti-tumor cytokines.
  • Twin “firsts.” Siren pursues the first AAV-based cancer therapy and the first single virus platform scalable to hundreds of indications.
  • Animal data. >500 mouse models show 86 % complete responses; large-animal pig study indicates strong safety with real-world neurosurgical delivery.
  • Clinical plan. Combined Phase 1/2 trial in adults with recurrent high-grade gliomas targeted for 2026 with potential for rare-disease (orphan) fast-track.
  • Market context. Current SOC for brain tumors is largely ineffective; analogous immunotherapies like Keytruda generate ~$30 B annually.
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Inside Startup Investing with Chris LustrinoBy Kingscrowd, Sam Fiske

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