Matthew Leoni, CMO of Merida Biosciences, on Navigating the Challenges and Opportunities in Neuroscience Drug Development

🧠 Navigating the Complex World of Neuro Drug Development

Challenges, Innovations & the Future of Neuroscience | Power to the Patients Podcast

🎙️ Guest: Matthew Leoni, CMO, Merida Biosciences

“You have to respect the drug gods — they can be cruel. You need humility and an awareness of what you don’t know when designing trials.”

👋 Episode Overview

In this episode, Matt Leoni, former SVP of Global Clinical Development at Cerevel and current CMO at Merida Biosciences, shares insights from his 17+ years in the industry. Drawing from leadership roles at Cerevel, Otsuka, Novartis, and others, Matt reflects on the challenges unique to neuro drug development, the tension between innovation and risk-aversion, and why he’s optimistic about disease-modifying therapies.

🧭 Top Takeaways

✅ Neuro trials face unique headwinds: subjective endpoints, placebo effects, and operational variance.

✅ Incremental improvements matter, but real transformation needs better measures and willingness to take risks.

✅ Disease-modifying therapies — aided by AI, genetic targeting, and multimodal approaches — could change the landscape.

🔑 Key Topics Covered

1. Guest Background

• MD/MBA from University of Pennsylvania; trained in pathology before moving directly into industry.
• Career path through dermatology, immunology, MS, psychiatry, and neurology drug development.
• Leadership roles in both large pharma and biotech, including recent work in Parkinson’s, epilepsy, and schizophrenia.

2. The Problem They’re Solving

• Neuro has some of the highest trial failure rates due to subjective endpoints and placebo effects.
• Patient populations are saturated; repeated trial participation increases placebo response.
• Lack of sensitive, objective measures makes it hard to detect true drug effects.

3. Their Innovation or Contribution

• Advocating for alignment on new, more sensitive endpoints that still address patient relevance.
• Pushing for multi-modal approaches combining symptom relief, neuroinflammation targeting, and genetic insights.
• Encouraging earlier physician exposure to clinical trials to build pathways into industry.

4. Challenges & Barriers

• Regulatory and financial structures incentivize incremental improvements over radical innovation.
• Difficulty in retrofitting novel mechanisms into existing, accepted scoring systems (e.g., PANSS).
• Resistance to abandoning entrenched endpoints even when they have limitations.

5. Vision for the Future

• Disease-modifying therapies as the “holy grail” for neurodegenerative and psychiatric conditions.
• AI, CRISPR, and precision medicine to unlock deeper understanding of neural networks.
• Breakthroughs likely to start in oncology and rare diseases, then migrate to psychiatry.

💬 Speaker Spotlights

On the difficulty of neuro drug development:

“It’s one of the hardest things to do — you’re measuring how people feel, and that’s inherently variable.”

On trial design humility:

“You have to respect the drug gods… have humility and know what you don’t know.”

On innovation vs. incentives:

“We’re incentivized to chase what works rather than break the mold — it’s not what breeds the most innovation.”

On disease modification:

“We’re on the cusp of a new generation of drugs that could change the trajectory of disease.”

On psychoplastogens:

“If they can deliver the psychedelic horsepower without the trip, they could be our first real disease-modifying therapy in psychiatry.”

🎧 Listen to the Full Episode:

• Spotify
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💡 Keep Exploring

• Subscribe to Power to the Patients
• Follow: Matthew Leoni on LinkedIn
• Related episodes:
  • *Gerard Sanacora on Glutamate, GABA, and the Future of Interventional Psychiatry*
  • *Dina Burkitbayeva on Building Mental Health Biotech Companies*

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