deniskatz

  Executive Summary For decades, neurology has operated within a syndromic framework grouping patients by observable symptoms rather than underlying biology. That model is reaching its limits. CNS disorders are now being redefined through molecular signatures, circuit-level dysfunction, and digital phenotypes . This is not a technological evolution it is a structural reset of how drugs are developed, evaluated, and approved. Sponsors who continue to build programs around broad diagnostic categories and legacy endpoints will increasingly fail not because their science lacks merit, but because their development strategy is misaligned with biological reality. Salience Clinical operates at the intersection of neuroscience, regulatory strategy, and precision development helping sponsors translate biological complexity into approvable labels, differentiated value , and durable market position . Target Audience: Chief Medical Officers, Heads of R&D, and Clinical Development Leaders a...

  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 most capital-intensive and failure-prone domain in biopharma. The so-called “Alzheimer’s graveyard” reflects decades of scientific promise undermined by regulatory, operational, and strategic misalignment. Yet the landscape is shifting. The emergence of amyloid- and tau-targeting therapies has demonstrated that regulatory approval is achievable but only when supported by disciplined development architecture. Success in 2026 is defined by translational clarity : the ability to demonstrate that biological modification leads to measurable and meaningful functional benefit in patients. The Success Gap 99.6% historical failure rate (2002–2012) 18-year gap between novel disease-modifying approvals (2003–2021) $300M+ average s...

  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...