From Stanford to Startup: Dr. Neal Amin on Building Sculpta Bio
After 20 years in academic research, Dr. Neal Amin left his Stanford faculty position to start Sculpta, a company pioneering a “Protein Sculpting” approach to treat neurodegenerative diseases. In their first year, the team was awarded recognition from Alnylam for their platform technology, including the first-ever human single-cell Atlas of RNA Splicing. We reached out to Neal to learn about his journey from professor to founder.
What made you decide to leave your Stanford faculty position and start Sculpta?
There was both a push and a pull. The push came from the hierarchy and departmental politics at Stanford, which I was neither good at navigating nor particularly interested in. Though I continued to publish my work in top tier journals, I was stymied when I sought basic resources to get an independent lab going. The pull emerged as I began meeting people in the Bay Area startup ecosystem. The energy and passion of the founder community made me feel at home, while I felt increasingly out of place and uninspired in academia. Before long, starting my own company was all I could think about.
You call your approach “Protein Sculpting.” Can you explain what that means and how it’s different from traditional gene therapies for neurodegenerative diseases?
Nearly all genomic medicines seek to either increase or decrease the expression of target proteins. For example, AAVs and gene therapies overexpress genes while CRISPR and siRNAs knock them down or out. I call these approaches “up/down biology.”
We saw a huge opportunity to use a type of genomic medicine called antisense oligonucleotides (ASOs) to modulate targets in a new way. By tapping into the biology of alternative RNA splicing, we found that we can intentionally change the mRNA coding sequences within cells to create new protein variants. Instead of increasing or decreasing levels of a target, we are changing the structure and function of disease-causing proteins in the brain.
For example, we can use an ASO to skip an exon that encodes for one domain of a protein that has disease-causing effects. We are incredibly excited by the therapeutic potential of these new mechanisms, especially since larger biotechs and big pharma have not been pursuing them.
You’ve had a big first year: $2.6M raised, building your team, and earning recognition from Alnylam for creating the first-ever human single-cell Atlas of RNA Splicing. What moment made you feel most confident you made the right decision to leave academia?
I can honestly say that I have never once looked back on my decision to leave academia. Even during all the rough stretches of fundraising, scientific setbacks, and business challenges, I have felt that founding a company has been a privilege. It is a chance to take a real shot at the kind of impact on human health that drew me to physician-scientist training in the first place.
What impact do you hope Sculpta will have on patients with Alzheimer’s, Parkinson’s, and ALS?
Impatience is central to our mission. The status quo for patients with devastating neurodegenerative diseases is simply not acceptable. Neurodegeneration should be treated as a societal emergency, much like COVID was, when urgency unlocked unprecedented scientific progress in mRNA vaccines.
Our goal at Sculpta is to develop treatments that can stop the progression of neurodegenerative disease and reverse many forms of brain damage that have already accumulated. I believe humanity deserves no less of an ambitious agenda, and I believe the evidence is out there that this is truly possible.
What’s the best piece of advice you’d share with other scientists considering leaving academia to start a company?
Don’t build in stealth. Talk to as many people as possible about your idea, especially outside of academia. Many scientists overestimate the risk of being scooped. As a result, they will chronically miss out on opportunities for critical feedback from diverse stakeholders.
Sculpta is based at MBC BioLabs in San Francisco.
