First-Ever Platform Trial for Progressive Supranuclear Palsy Enrolls Its Inaugural Participant

CurePSP announced that the PSP Trial Platform (PTP) has enrolled its first participant, marking what researchers describe as a landmark shift in a field that has historically struggled to run large-scale trials. The platform design, modeled on the HEALEY ALS Platform Trial, is intended to test multiple drugs for progressive supranuclear palsy (PSP) simultaneously and add new candidates over time rather than starting each study from scratch.¹

“We expect this trial to rapidly accelerate efforts to identify effective PSP therapies by increasing the number of promising drugs tested, while expanding access to potential treatments to more patients,” Adam Boxer, MD, PhD, Endowed Professor in Memory and Aging at UCSF and lead study principal investigator, said in a statement.¹ The trial is funded by a 5-year grant of up to $75.4 million from the National Institute on Aging (NIA).

Trial design

The PTP (NCT07173803) is structured as a perpetual platform trial governed by a single master protocol. Participants first enroll in the master protocol and undergo baseline screening; once eligible, they can be randomized into any regimen actively enrolling at the time, with new drug regimens able to be added later without restarting the trial from scratch.^1,2

Two regimens are enrolling initially: Regimen A testing AADvac1 and Regimen B testing LM11A-31, each randomizing participants 3:1 to active drug or matching placebo within that regimen.^2,3 The primary outcome across regimens is change in disease severity at 52 weeks on the 15-item modified PSP Rating Scale (mPSPRS-15), a scale ranging from 0 to 52 in which higher scores indicate more severe symptoms.⁴

Eligible participants must have a clinical diagnosis of possible or probable PSP Richardson's syndrome per 2017 Movement Disorder Society criteria, symptoms present for 5 years or less, an MMSE score of 25 or higher, and the ability to walk at least 10 steps with minimal assistance.

Unlike a conventional single-drug placebo-controlled trial, the design is intended to limit placebo exposure: CurePSP said 75% of participants will receive an active drug during the first year, after which all participants receive active treatment.¹ The trial aims to enroll 440 participants across 2 years, with the platform expected to run through at least 2030.^1,5

About the initial drug regimens

LM11A-31, from PharmatrophiX, is an orally available small molecule that modulates the p75 neurotrophin receptor, a target implicated in both neuronal survival signaling and multiple tau pathological mechanisms, including phosphorylation, acetylation, misfolding, and spreading.^5,6

In a phase 2a trial in 242 patients with mild-to-moderate Alzheimer disease, LM11A-31 met its primary safety and tolerability endpoint, with significant drug-placebo differences on prespecified secondary and exploratory imaging and CSF biomarker measures consistent with slowed disease progression, though no significant effect on cognitive outcomes was observed in that trial.⁶

"Rather than targeting a single downstream consequence of disease, LM11A-31 is designed to protect neurons and their synaptic connections while addressing multiple mechanisms that drive neurodegeneration, including toxic tau biology," Frank M. Longo, MD, PhD, co-founder of PharmatrophiX, said in a statement.¹

AADvac1, from Axon Neuroscience, is an active immunotherapy designed to generate antibodies against pathological tau protein.¹ In the 24-month, 196-patient phase 2 ADAMANT trial in mild Alzheimer disease, AADvac1 met its primary safety endpoint and induced anti-tau antibodies in more than 80% of treated participants; a post hoc analysis restricted to patients with confirmed amyloid and tau pathology showed AADvac1 significantly reduced blood NfL by 58% and slowed clinical decline on the CDR-Sum of Boxes by 27% relative to placebo.^7,8

AADvac1 has also been selected as the first tau-directed regimen in a separate NIH-funded combination-therapy platform trial in Alzheimer disease led by Boxer and Keith Johnson, MD, of Harvard Medical School.⁹ "AADvac1's inclusion is an important step forward, built on more than two decades of our dedicated research into tau protein, a key driver of the disease pathology in PSP," Michal Fresser, CEO of Axon Neuroscience, said in a statement.¹

REFERENCES
1. CurePSP Announces Enrollment of First Participant in the PSP Trial Platform. News release. CurePSP, Inc. August 7, 2026. Accessed August 12, 2026. https://www.psp.org/news/details/curepsp-announces-enrollment-of-first-participant-in-the-psp-trial-platform
2. Progressive Supranuclear Palsy Clinical Trial Platform. ClinicalTrials.gov identifier: NCT07173803. Accessed August 12, 2026. https://clinicaltrials.gov/study/NCT07173803
3. Progressive Supranuclear Palsy Clinical Trial Platform - Regimen A: AADvac1. ClinicalTrials.gov identifier: NCT07217665. Accessed August 12, 2026. https://clinicaltrials.gov/study/NCT07217665
4. Progressive Supranuclear Palsy Clinical Trial Platform - Regimen B: LM11A-31. ClinicalTrials.gov identifier: NCT07264283. Accessed August 12, 2026. https://clinicaltrials.gov/study/NCT07264283
5. PharmatrophiX Selected for Landmark UCSF-Led Platform Trial in Rare Neurodegenerative Disease, Unveils New Data at Tau Global Conference. News release. PharmatrophiX. Accessed August 12, 2026. https://pharmatrophix.com/pharmatrophix-selected-for-landmark-ucsf-led-platform-trial-in-rare-neurodegenerative-disease-unveils-new-data-at-tau-global-conference/
6. Shanks HR, Chen K, Reiman EM, et al. p75 neurotrophin receptor modulation in mild to moderate Alzheimer disease: a randomized, placebo-controlled phase 2a trial. Nat Med. 2024. doi:10.1038/s41591-024-02977-w. https://www.nature.com/articles/s41591-024-02977-w
7. Axon Announces Positive Results From Phase II ADAMANT Trial for AADvac1 in Alzheimer's Disease. News release. Axon Neuroscience SE. April 3, 2020. Accessed August 12, 2026. https://www.prnewswire.com/news-releases/axon-announces-positive-results-from-phase-ii-adamant-trial-for-aadvac1-in-alzheimers-disease-300914509.html
8. Novak P, Kovacech B, Katina S, et al. ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer's disease. Nat Aging. 2021;1(6):521-534. doi:10.1038/s43587-021-00070-2
9. Axon Neuroscience's Immunotherapy Selected for a Landmark Combination-Therapy Alzheimer's Clinical Trial in US, Supported by a USD 151 Million Grant. News release. Axon Neuroscience SE. Accessed August 12, 2026. https://www.biospace.com/press-releases/axon-neurosciences-immunotherapy-selected-for-a-landmark-combination-therapy-alzheimers-clinical-trial-in-us-supported-by-a-usd-151-million-grant