Daniel O'Connell, CEO of Acumen Pharmaceuticals, on Oligomers, Innovation, and Hope in Alzheimer’s

🧠 Redefining Alzheimer’s: Targeting the Real Culprit

CEO of Acumen | Power to the Patients Podcast

🎙️ Guest: Daniel O’Connell, CEO of Acumen

“We think we’ve identified the true toxic target in Alzheimer’s — and that gives us real hope for safer, more effective treatments.”

👋 Episode Overview

Daniel O’Connell, CEO of Acumen, brings over 25 years of neuroscience investment and company-building experience to one of medicine’s hardest challenges: Alzheimer’s disease. In this conversation, he shares the journey from Acumen’s early seed-stage science to today’s pivotal phase 2 trial, and explains why targeting amyloid beta oligomers — not plaques — could change the trajectory of treatment.

🧭 Top Takeaways

• ✅ Alzheimer’s research is shifting beyond plaques to target oligomers, the true toxic species.
• ✅ Early Acumen trial results suggest improved safety and promising biomarker engagement.
• ✅ Advances in blood-based biomarkers could accelerate diagnosis and trial efficiency.
• ✅ Patients should feel a renewed sense of optimism as treatments evolve.

🔑 Key Topics Covered

1. Guest Background

• 25 years in CNS company building and investing.
• Early seed investor in Acumen; later became CEO.
• Has worked with ~25 neuroscience companies over his career.

2. The Problem They’re Solving

• Alzheimer’s is notoriously difficult: failures, skepticism, and a history of inconclusive trials.
• Traditional focus on amyloid plaques often didn’t correlate with symptoms.
• Patients and families need safer, more effective, and more accessible treatment options.

3. Their Innovation or Contribution

• Acumen is pioneering therapies that directly target amyloid beta oligomers — believed to be the real toxic species in Alzheimer’s.
• Early results show encouraging safety and biomarker engagement.
• Current Altitude AD phase 2 study could become registration-ready.

4. Challenges & Barriers

• Clinical trials in Alzheimer’s require large, long, and expensive studies (540 patients in phase 2).
• Recruitment challenges, especially ensuring diversity.
• The need for validated biomarkers to speed go/no-go decisions.

5. Vision for the Future

• More precise identification of patients through blood-based biomarkers.
• Safer, subcutaneous treatment options to improve access and convenience.
• A future where Alzheimer’s care is more hopeful, with combination therapies and earlier interventions.

💬 Speaker Spotlights

On why oligomers matter:
“Plaques are the pathological hallmark, but oligomers are the potent toxins — binding directly at the synapse and driving memory loss.”

On early trial results:
“Even with just three doses, we saw a 20–25% reduction in amyloid PET signal — along with strong safety data.”

On what patients should know:
“We are in a moment of progress. There are reasons for patients and caregivers to have hope.”

On the biggest bottleneck:
“If I could wave a magic wand, we’d have validated biomarkers that allow for smaller, faster studies — instead of 500 patients over 18 months.”

🎧 Listen to the Full Episode

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💡 Keep Exploring

• Subscribe to Power to the Patients for more conversations on neuroscience innovation.
• Learn more about Acumen’s Alzheimer’s research
• Connect with Daniel on LinkedIn

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