🧬 AI, Mechanisms, & the Next Wave of Drug Discovery | David Li Rerelease (4/4)
August 13, 2026
David Li explains how a research question about mischaracterized drug targets became the starting point for Meliora Therapeutics. He describes how CRISPR experiments and follow-up biology challenged the accepted mechanism for cancer drugs, and how the company uses AI and machine learning to connect chemistry, biology, biomarkers, and patient populations.
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“Think bigger. Don't worry about what others are thinking about. Think about exactly what you want and then work like hell to try to make it happen.”
David Li explains how a research question about mischaracterized drug targets became the starting point for Meliora Therapeutics. He describes how CRISPR experiments and follow-up biology challenged the accepted mechanism for cancer drugs, and how the company uses AI and machine learning to connect chemistry, biology, biomarkers, and patient populations.
David also talks through the move from private equity and life sciences software into company building. He shares how Meliora built a founding team around computational science and drug discovery, why the company is focused on creating clinically differentiated assets, and how internal programs and external partnerships fit together.
The conversation closes with fundraising in a more demanding biotech market, the psychological resilience required to lead through uncertainty, and Meliora's plans to move from seed toward a Series A. David also reflects on the Penn program that changed his path and offers one clear piece of advice: think bigger.
Key Topics Covered:
- The transition from private equity to founding Meliora Therapeutics
- Jason Sheltzer's research on mischaracterized drug mechanisms
- CRISPR knockout experiments and target validation
- Using AI and machine learning to identify mechanisms of action
- Connecting mechanism, chemistry, biomarkers, and patient populations
- Building a computational platform alongside drug discovery capabilities
- Meliora's transition into a full-stack therapeutics company
- Traditional drug discovery workflows and their blind spots
- Internal pipeline development and external partnerships
- Fundraising discipline in a difficult biotech environment
- Psychological resilience as a biotech leader
- Thinking bigger and pursuing an independent path
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Find our guest, David Li, at these links:
LinkedIn: https://www.linkedin.com/in/david-li-9aa210b
Website: https://www.melioratherapeutics.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/
Websitehttps://www.excedr.com
Intro & Outro Songs Created by OkKyojin, Owned by Excedr:
Website: https://flow.page/kyojin
Resources & Articles:
NCI: The Serendipitous Off-Target Explorer, Researcher Interview with Jason Sheltzer: https://www.cancer.gov/ccg/blog/2021/interview-off-target
Y Combinator Co-Founder Matching: https://www.ycombinator.com/cofounder-matching
Yale Ventures: Jason Sheltzer, PhD: https://ventures.yale.edu/node/3875
Companies, Universities, & People Mentioned:
Jason Sheltzer: https://ventures.yale.edu/node/3875
KKR: https://www.kkr.com/
Benchling: https://www.benchling.com/
Yale: https://www.yale.edu/
Y Combinator: https://www.ycombinator.com/cofounder-matching
Biogen: https://www.biogen.com/company.html
University of Pennsylvania: https://www.upenn.edu/
Timestamps:
00:00 Intro
02:10 Leaving Private Equity for Meliora
07:29 How David Met Jason Sheltzer
07:33 From Angel Investor to Founder
09:16 Building the Founding Team
11:38 Why Drug Discovery Must Be In-House
12:20 Rethinking the Drug Discovery Status Quo
13:59 The CDK11 Mechanism Discovery
15:45 Why Mechanism Matters Before the Clinic
17:47 Internal Pipelines and Partnerships
20:11 Fundraising in a Tougher Market
21:09 Psychological Resilience as a Leader
22:37 Meliora's Next Development Stage
24:17 The Penn Opportunity That Changed David's Path
25:42 Think Bigger
26:34 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.