🧬 Let the Science Lead: Building Successful Biotechnology | Nicole Paulk (Part 3/4)
April 6, 2026
In this episode of The Biotech Startups Podcast, Nicole Paulk recounts her unlikely evolution from frustrated academic to biotech founder — driven by years of watching gene therapy companies wastefully rebuild the same tech stack from scratch, a pandemic lockout that barred her from her own UCSF lab, and a sneaky incorporation scheme that was less grand vision, more workaround to get back to the bench. She shares how a frantic three-day cancer grant, a fever-dreamed logo, and a Best Startup win at UCSF's entrepreneurship course led to a $6,000,000 Founders Fund seed with no board attached, and how Siren's unconventional early bet on unglamorous CMC manufacturing optimization — paired with years of deliberate stealth — became the company's most powerful and defensible competitive advantage.
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"Just that ability to have pure, unfettered, unbothered, and undistracted time to just really go hard and let the science take you where it will. I think that could be transformative."
In this episode of The Biotech Startups Podcast, Nicole Paulk recounts her unlikely evolution from frustrated academic to biotech founder — driven by years of watching gene therapy companies wastefully rebuild the same tech stack from scratch, a pandemic lockout that barred her from her own UCSF lab, and a sneaky incorporation scheme that was less grand vision, more workaround to get back to the bench. She shares how a frantic three-day cancer grant, a fever-dreamed logo, and a Best Startup win at UCSF's entrepreneurship course led to a $6,000,000 Founders Fund seed with no board attached, and how Siren's unconventional early bet on unglamorous CMC manufacturing optimization — paired with years of deliberate stealth — became the company's most powerful and defensible competitive advantage.
Key Topics Covered:
- The Gene Therapy Tech Stack Problem: Every AAV company rebuilding the same wheel — and the bold idea that sparked Siren
- Founding Siren: How a pandemic lockout, a brain tumor grant, and a sneaky incorporation gave birth to a biotech company
- Founders Fund & the Boardless Seed: $6M, no board, no permission needed — and why Nicole thinks more startups should start this way
- The Unglamorous CMC Bet: Going all-in on manufacturing optimization from day one — boring on purpose, defensible forever
- Stealth, IP, and Operating in an Accelerating World: Why the old rules on patents and publishing are dead — and what founders should do instead
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Find our guest, Nicole Paulk at these links:
LinkedIn: https://www.linkedin.com/in/nicolepaulk/
Website: https://sirenbiotechnology.com/
Find our host, Jon Chee, at these links:
LinkedIn: https://www.linkedin.com/in/jonchee
Learn more about Excedr:
LinkedIn: https://www.linkedin.com/company/excedr/
Website: https://www.excedr.com
Intro & Outro Songs Created by OkKyojin, Owned by Excedr:
Website: https://flow.page/kyojin
Resources & Articles:
AAV Gene Therapy Overview:
AAV as a Clinical Gene Therapy Vector:
What Is AAV Gene Therapy?: https://www.creative-diagnostics.com/what-is-aav-gene-therapy.htm
Viral Vectors in Gene & Cell Therapy (AAV included): https://patienteducation.asgct.org/understanding-cell-gene-therapy/viral-vectors
The Age of AAV in Gene Therapy:
CMC Requirements for Gene and Cell Therapy INDs: https://pacificbiolabs.com/gene-therapy-cmc-requirements/
Companies, Universities, & People mentioned:
Founders Fund: https://foundersfund.com
Bayer (Collaborator incubator context): https://www.bayer.com
NIH (National Institutes of Health): https://www.nih.gov/
Jennifer Doudna: https://www.linkedin.com/in/jennifer-doudna-79b63527/
Scott Nolan: https://www.linkedin.com/in/scottpnolan/
Timestamps:
00:00 Intro
02:19 Frustrations with Gene Therapy's "Reinvent the Wheel" Problem
03:41 The Vision for a Universal AAV Gene Therapy
07:00 Ballooning Costs and the Perverse Incentives of the Gene Therapy Market
09:31 The UCSF Brain Tumor Gift and a Frantic Three-Day Two-Pager
11:55 COVID Shuts Down the Lab: Industry vs. Academia as Essential Workers
12:27 Incorporating Siren as a Sneaky Way to Get Back to Work
14:16 UCSF Entrepreneurship Course, Winning Best Startup, and Landing Founders Fund
16:02 The Freedom of $6M with No Board: Moving Fast and Doing Better Science
24:15 Going All-In on CMC: The Unglamorous but Smart Early Move
28:41 Staying Stealth: When to Come Out and When to Stay Hidden
34:49 The Future of Biotech: Small, Nimble, and Focused Teams
37:33 Outro
The Biotech Startups Podcast gives you a front-row seat to the business and science of building a biotech. Hosted by Jon Chee, CEO of Excedr, the show features honest conversations with founders, execs, and investors about their work, their companies, and how they got there. From scientific breakthroughs to startup lessons, each episode explores what it really takes to grow a life science company—from pre-seed to IPO.