Dr. Nicholas Hertz is the co-founder and former CSO of Mitokinin, a biotech company developing therapies targeting damaged mitochondria in neurodegenerative disease. Mitokinin was recently acquired by pharmaceutical giant AbbVie. In this episode, Nick recounts the journey from academic research on PINK1 biology to founding a startup and advancing a clinical candidate. He provides insights into the drug discovery process, optimizing lead compounds, translating basic findings into therapies, and partnering with big pharma. Nick also shares lessons learned along the way about focusing on robust science, being adaptable, and maintaining ambition to help patients.

Key topics covered:

• Background on Mitokinin’s approach of activating PINK1 to clear damaged mitochondria
• Founding a company based on academic research and discoveries
• Navigating from tool compounds to optimizing in vivo activity and drug properties
• Using mitochondrial biomarkers like phospho-ubiquitin to track target engagement
• Partnering with AbbVie: alignment on science, IP transfer after acquisition
• Importance of reproducibility, following the science to clinic-ready agents
• Planning the next neurodegeneration startup based on past experience
• Advice for startups: pick projects wisely, focus on robust science over hype

Notable Quotes: (edited slightly for clarity and length)

"What PINK1 does is signal when mitochondria have gone bad and need to be cleared away."

"Seeing PINK1 mutations lead to early Parkinson's cemented the link between mitochondrial health and neurodegeneration."

"The biggest challenge was getting enough brain exposure and potency for in vivo efficacy."

"We developed assays to measure phospho-ubiquitin levels in patient samples and use it as a pharmacodynamic marker."

"With AbbVie, we were aligned on making a safe drug you'd feel comfortable giving to your own family."

"I enjoyed the journey more than the destination. Now I want to get back in the lab and do more science."

"Focus on projects you believe in and doing the most robust, reproducible science."

"I consider failing to help patients in Phase 3 trials a failure, even if you already exited successfully."

Links:

Mitokinin website (this link may become obsolete as Mitokinin becomes part of AbbVie)

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