John Maraganore, the founding CEO of Alnylam Pharmaceuticals, shares his inspiring journey from a Greek immigrant family to a biotech legend. He reveals how a serendipitous lab experience led him to create bivalirudin and pivot into business. John discusses challenges in advancing RNAi therapies, targeting TTR amyloidosis, and maintaining team morale during tough times. His insights offer valuable lessons for entrepreneurs and scientists alike, emphasizing resilience, optimism, and a patient-focused approach to innovation.
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question_answer ANECDOTE
From Side Project To Market Drug
John discovered bivalirudin during unsanctioned '20% time' work and turned it into a market drug.
The project nearly died over IP until a bivalent design produced a potent, free-to-develop inhibitor.
question_answer ANECDOTE
A Forced Pivot Built Business Skills
John was forced into business development at Biogen by leadership and financial necessity.
Reluctant at first, he found the role expanded his skills and led to deals including partnering bivalirudin.
question_answer ANECDOTE
Joining Alnylam From A Honeymoon
Phil Sharp introduced John to RNAi and Millennium licensed the early MIT work for functional genomics.
John joined Alnylam as founding CEO in 2002, signing his offer from his honeymoon suite in Mauritius.
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In our latest episode, we sit down with Dr. John Maraganore, the legendary founding CEO of Alnylam Pharmaceuticals and one of the most influential voices in modern therapeutics. Raised in a Greek immigrant family in Chicago, John’s journey is a rare blend of scientific obsession, business acumen, and relentless optimism. We cover his whole career journey. From his early days at Biogen, where he invented the anticoagulant bivalirudin (Angiomax), to taking a leap of faith on RNA interference when few believed it could work.
He opens up about being “thrust” from the lab into the business battlefield, the serendipitous experiments that changed his career, and the near-misses that almost stopped him in his tracks. We dive into how he built Alnylam from a small startup into a company with multiple approved drugs for devastating rare diseases like TTR amyloidosis, and the leadership philosophies that kept him and his team moving forward. Along the way, John shares candid lessons for today’s founders.
Whether you’re a scientist, entrepreneur, or just someone who loves stories of grit and discovery, this conversation will inspire you. Don’t miss out on this deep dive into innovation, failure, and the future of medicine.
Time Stamps
00:32 Dr. John Maraganore is introduced as the featured guest and a leader in biotech.
00:50 Asked to explain his job to a five-year-old, his answer captures a lifetime of purpose in three words.
01:05 Growing up in a Greek immigrant family shaped more than his values—it built the mindset that would drive biotech breakthroughs.
02:44 His parents wanted a doctor. One college experiment changed everything.
04:14 Snake venom, of all things, sparked his obsession with discovery.
06:20 John shares how his biotech career began at Upjohn and Biogen, inventing bivalirudin (Angiomax), and other highlights.
10:31 He talks about property hurdles behind bivalirudin’s development.
12:57 A forced career pivot from the lab to business turned out to be the twist that defined his leadership path.
17:21 Seeing science from the business side unlocked something—an insight that later shaped how he built companies.
19:09 The genomics boom at Millennium tested his ability to turn data into real drugs—and nearly broke the field in the process.
22:25 Betting on RNA interference when almost no one believed it could work.
27:40 Ten years of trial and error later, the science finally caught up to the vision.
30:57 Behind every biotech success are make-or-break partnership calls—he shares how timing meant survival.
36:14 Balancing independence with pharma partnerships became a strategy that redefined how small biotechs grow.
39:06 John shares the criteria and reasoning behind choosing TTR amyloidosis as Alnylam’s lead rare disease program.
54:22 John shares practical advice for founders facing tough market conditions.
57:47 Talking about sleep, pizza preferences, memorable child moments, and music.
1:00:43 He recommends the best reading material on drug pricing and the biotech business.
1:01:30 Conclusion and final advice from Dr. John Maraganore.