The Long Run with Luke Timmerman Ep135: John Maraganore on Developing a New Class of Medicines
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May 8, 2023 John Maraganore, founding CEO of Alnylam Pharmaceuticals who led development of RNA interference therapeutics. He recounts the long road to creating a new drug class. Topics include RNAi delivery challenges, strategic use of LNPs and GalNAc conjugates, target selection and rare-disease commercial strategy, clinical setbacks and recoveries, partnerships that validated the approach, and how computation and AI are accelerating discovery.
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Get Industry Experience Before Starting A Biotech
- Work at a mid/large biotech first to learn drug discovery, development, and commercialization.
- Maraganore recommends companies like Biogen or Genentech as training grounds before founding your own biotech.
Partnerships Scaled The Platform Build
- Alnylam raised large capital over time through equity and pharma partnerships, using alliances both for funding and validation.
- Over 19 years they raised ~$7.5B and invested ~$5B, with half the capital from partnerships and upfront payments.
Delivery Was The Defining Technical Bet
- Alnylam pursued two delivery strategies in parallel: lipid nanoparticles and ligand conjugates.
- Those complementary approaches ultimately enabled robust delivery to the liver and unlocked the platform's clinical success.