deniskatz

  By Denis Katz, MD, MHA Founder, Salience Clinical For decades, psychiatry has framed major depressive disorder (MDD) as a disorder of neurochemistry—an imbalance of serotonin, norepinephrine, or dopamine. This paradigm has delivered meaningful therapeutic advances. Yet it has not consistently achieved durable remission for a substantial proportion of patients. Approximately one-third remain treatment-resistant, and relapse among responders is common. Incremental modulation of synaptic signaling appears to be approaching a ceiling in its capacity to transform long-term outcomes at scale. The next shift in neuropsychiatry will not be chemical. It will be architectural. By “architectural,” we refer to the topology, coupling, and dynamic switching behavior of large-scale brain networks that govern how information is processed and regulated. From Neurotransmitters to Networks Advances in high-resolution functional MRI, multimodal imaging, and computational modeling have fundamentall...

  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...

  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...