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Navigating Regulatory Hurdles in Alzheimer’s Drug Development

March 18, 2026

Protecting Sponsor Capital, Managing Risk, and Maximizing Probability of Success Denis Katz, MD, MHA Clinical Scientist & Development Strategist Founder, Salience Clinical, LLC Executive Summary Alzheimer’s disease (AD) drug development remains the highest-stakes arena in biopharma. While the "Alzheimer’s Graveyard" is littered with multi-billion dollar failures, a new era of amyloid and tau-targeting therapies has proven that the regulatory path is navigable—but only for those with a disciplined risk architecture. Success in 2026 is driven by Translational Clarity : the ability to prove that biological changes translate into human functional benefit. The Success Gap ● 99.6%: Historical failure rate (2002–2012). ● 18 Years: The approval drought between novel disease-modifying therapies (2003–2021). ● $300M+: The average sunk R&D cost of...

The Architectural Turn in Depression Why Network Topology Will Redefine CNS Strategy

March 14, 2026

By Denis Katz, MD, MHA Founder, Salience Clinical For decades, psychiatry has framed major depressive disorder (MDD) as a disorder of chemistry, an imbalance of serotonin, norepinephrine, or dopamine. That model produced meaningful therapeutic advances, yet it has not consistently delivered durable remission for a substantial proportion of patients. Roughly one-third remain treatment resistant, and among responders, relapse is common. Incremental modulation of synaptic signaling alone appears to have reached a ceiling in its ability to transform long-term outcomes at scale. The next shift in neuropsychiatry will not be chemical. It will be architectural. By “architectural,” we mean the topology, coupling, and switching behavior of large-scale brain networks that shape how information is processed. From neurotransmitters to networks Advances in high-resolution functional MRI, multimodal imaging, and computational modeling over the past decade have transformed our unde...

The Architectural Turn in Depression Why Network Topology Will Redefine CNS Strategy

March 01, 2026

The Architectural Turn in Depression Why Network Topology Will Redefine CNS Strategy By Denis Katz, MD, MHA Founder, Salience Clinical, LLC For decades, psychiatry has framed major depressive disorder (MDD) as a disorder of chemistry , an imbalance of serotonin, norepinephrine, or dopamine. That model produced meaningful therapeutic advances, yet it has not consistently delivered durable remission for a substantial proportion of patients. Roughly one-third remain treatment resistant, and among responders, relapse is common. Incremental modulation of synaptic signaling alone appears to have reached a ceiling in its ability to transform long-term outcomes at scale. The next shift in neuropsychiatry will not be chemical. It will be architectural. By “architectural,” we mean the topology, coupling, and switching behavior of large-scale brain networks that shape how information is processed. From neurotransmitters to networks Advances in high-resolution functional MRI, multimodal imagi...