LM11A-31-BHS / PharmatrophiX - LARVOL DELTA

The Progressive Supranuclear Palsy Clinical Trial Platform - Regimen B: LM11A-31 (clinicaltrials.gov) - P2 | N=147 | Enrolling by invitation | Sponsor: Adam Boxer | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

CurePSP Announces Enrollment of First Participant in the PSP Trial Platform (Yahoo Finance) - "Led by the University of California, San Francisco (UCSF) and funded by a five-year grant of up to $75.4 million from the National Institute on Aging (NIA), the PTP is being conducted at 50 sites nationwide...The trial aims to enroll 440 participants over 2 years. Unlike traditional clinical trials, the PTP is designed so that 75% of participants receive an active drug during the first year, reducing the number of patients assigned to placebo. After that, all participants receive an active drug...Two of the drugs being tested are LM11A-31, from PharmatrophiX, and AADvac1, from Axon Neuroscience."

Enrollment open • CNS Disorders • Progressive Supranuclear Palsy

PTP: The Progressive Supranuclear Palsy Clinical Trial Platform (clinicaltrials.gov) - P2 | N=440 | Recruiting | Sponsor: Adam Boxer | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

Pharmacological modulation of p75 neurotrophin receptor in microglial cells improves resilience to rotenone cytotoxicity. (PubMed, Front Pharmacol) - "In the present study, we investigated whether pharmacological modulation of p75NTR by LM11A-31 could protect microglial cells against Rotenone (Rot)-induced toxicity, a widely used tool to mimic PD...These protective effects involve the rescue of redox balance, suppression of pro-inflammatory signaling, preservation of cytoarchitecture, also resulting in increased cell survival. Overall, targeting p75NTR may represent a promising therapeutic strategy to counteract microglial dysfunction and neuroinflammatory processes associated with Parkinson's disease."

Journal • CNS Disorders • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease • CASP3 • CD68 • NGFR • PPARA

Inadvertent p75NTR signaling might cause inconsistencies in the neuroprotection offered by mesenchymal stem cells. (PubMed, Mol Cell Neurosci) - "Addressing these inconsistencies through further studies will be critical to ensuring the safety and efficacy of BMSC applications in clinical settings. In this regard, concomitant inhibition of p75NTR using small molecules such as LM11A-31 may have potential to avoid contradictory effects of BMSC transplantations caused by unpredictable release of excess BDNF in the transplanted site."

Journal • CNS Disorders • Orthopedics • Transplantation • NGFR

Taming the "death receptor": translating the first-in-class p75NTR modulator LM11A-31 from basic biology, across broad preclinical models, to clinical proof-of-concept. (PubMed, J Transl Med) - "Together, these studies expand our understanding of p75NTR function and support p75NTR modulation as a promising therapeutic strategy across diverse pathological conditions."

Journal • Preclinical • Review • Alzheimer's Disease • CNS Disorders • Human Immunodeficiency Virus • Huntington's Disease • Infectious Disease • Inflammation • Movement Disorders • NGFR • RHOA

The Progressive Supranuclear Palsy Clinical Trial Platform - Regimen B: LM11A-31 (clinicaltrials.gov) - P2 | N=147 | Not yet recruiting | Sponsor: Adam Boxer | Trial completion date: Jul 2029 ➔ Sep 2030 | Initiation date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Jul 2029 ➔ Sep 2030

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

PTP: The Progressive Supranuclear Palsy Clinical Trial Platform (clinicaltrials.gov) - P2 | N=440 | Not yet recruiting | Sponsor: Adam Boxer | Trial completion date: Jul 2029 ➔ Sep 2030 | Initiation date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Jul 2029 ➔ Sep 2030

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

Chronic p75 Neurotrophin Receptor Modulation with LM11A-31 Attenuates Seizure Progression and Network Hyperexcitability in Pentylenetetrazol Kindling. (PubMed, Neuropharmacology) - "We investigated whether pharmacological modulation of p75NTR with the small-molecule ligand LM11A-31 attenuates seizure progression and network dysfunction, defined as increased ECoG power and RMS amplitude reflecting enhanced neuronal synchronization and hyperexcitability in a pentylenetetrazole (PTZ) kindling model. In parallel, LM11A-31 partially restored antioxidant capacity and reduced oxidant load and lipid peroxidation. Pharmacological modulation of p75NTR signaling with LM11A-31 suppresses seizure progression and mitigates electrophysiological, synaptic, inflammatory, and oxidative alterations associated with PTZ kindling."

Journal • CNS Disorders • Epilepsy • Inflammation • IL6 • NGFR • SYP • TNFA

The nerve growth factor receptor p75NTR interacts with toll like receptor 4 and the alarmins high mobility group box-1 and nucleophosmin: a novel inflammatory mechanism in psoriasis. (PubMed, Br J Dermatol) - "p75NTR up-regulation and signalling contribute to alarmin release and amplification of TLR4/NF-κB inflammatory pathway in psoriasis. p75NTR can be considered a sensor of inflammation required for full activation of TLR4-dependent inflammatory signalling. Thus, p75NTR targeting, may represent a novel therapeutic strategy to counteract psoriatic chronic inflammation."

IO biomarker • Journal • Dermatology • Immunology • Inflammation • Psoriasis • CCL20 • HMGB1 • IFNG • IL17A • IL22 • IL6 • MT-CO2 • NGF • NGFR • NPM1 • TLR4 • TNFA

SMALL-MOLECULE P75NTR MODULATOR MITIGATES COGNITIVE, MOTOR, AND STRUCTURAL DEFICITS IN A MOUSE MODEL OF SYNUCLEINOPATHY (ADPD 2026) - "By enhancing neuronal resilience and limiting α-syn–induced degeneration, LM11A-31 offers a strong neuroprotective approach and current data further supports its potential to target vulnerability pathways and bolster intrinsic cellular defenses."

Preclinical • CNS Disorders • NGFR

MODULATION OF THE P75 NEUROTROPHIN RECEPTOR ATTENUATES TAU PHOSPHORYLATION AND PROMOTES SYNAPTIC RESILIENCE IN ALZHEIMER'S DISEASE (ADPD 2026) - "Across tauopathy mice and humans with AD, targeting of p75NTR is associated with a decrease in accumulation of multiple pathological forms of tau and a decrease in biomarkers linked to synaptic degeneration. This supports the proposition that LM11A-31 has broad, robust effects on fundamental p75-related neurodegenerative mechanisms."

Alzheimer's Disease • CNS Disorders • CSF T-tau • NGFR • p-tau181

Small molecule modulation of the p75 neurotrophin receptor promotes dendritic spine resilience to pathogenic tau species and reduces their accumulation. (PubMed, Acta Neuropathol Commun) - No abstract available

Journal

BDNF Val66Met protects oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer. (PubMed, Sci Transl Med) - "On the basis of these findings, we evaluated two therapeutic strategies: the p75NTR modulator LM11A-31 and a compound we have developed, CN016. The BDNF Met66 variant shows about 49% prevalence in East Asian populations and 1 to 20% in other ethnic groups, suggesting population-specific susceptibility to CIPN. These findings establish BDNF genetic variation as a crucial determinant of CIPN risk and validate two promising therapeutic approaches, providing a foundation for personalized neuroprotective strategies in cancer treatment."

Journal • Colorectal Cancer • Oncology • Pain • Solid Tumor • BDNF • NGFR

Drug Development. (PubMed, Alzheimers Dement) - "Our findings highlight the disruption of neuronal-glial communication in tauopathy and suggest that C31 treatment ameliorates aspects of this crosstalk, potentially by directly engaging microglia in addition to its known protective role in synaptic integrity and plasticity. These results provide further insight into C31's mechanism of action and its therapeutic potential for neurodegenerative diseases."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • ABCA1 • APOE • LRP1 • NGFR • NTRK2 • SORL1

Drug Development. (PubMed, Alzheimers Dement) - "These findings support the hypothesis that modulation of p75NTR signaling, a key mechanism and hub upstream from a broad network of AD/ADRD degenerative signaling networks, leads to a reduction of synaptic and glial pathology. The transcriptomic findings indicate some degree of overlap between the mouse findings and human AD degenerative mechanisms. This overlap and these preclinical findings are consistent with biomarker and proteomic findings observed in a recent phase 2a clinical trial of LM11A-31 with mild-moderate AD participants."

Journal • NGFR

The Progressive Supranuclear Palsy Clinical Trial Platform - Regimen B: LM11A-31 (clinicaltrials.gov) - P2 | N=147 | Not yet recruiting | Sponsor: Adam Boxer

New P2 trial • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

New Considerations for Accelerating Combination Therapy Trials to be Showcased at 2024 Clinical Trials on Alzheimer’s Disease Conference (PRNewswire) - "The Alzheimer's Drug Discovery Foundation (ADDF) will be leading a roundtable, 'Advancing Combination Therapy: Discussion on Key Considerations, Perspectives, and Promising Avenues for the Future of Alzheimer's Treatments,' at the 2024 Clinical Trials on Alzheimer's Disease (CTAD) conference, which will be held October 29th through November 1st in Madrid, Spain...CTAD will feature several key sessions from ADDF-funded investigators, whose work in drug development and biomarkers is shaping and leading the field towards the holy grail of Alzheimer's treatments—combination therapy and precision medicine, similar to cancer care."

P1/2 data • P2 data • P2a data • Alzheimer's Disease • CNS Disorders

Study of LM11A-31-BHS in Mild-moderate AD Patients (clinicaltrials.gov) - P1/2; N=242; Completed; Sponsor: PharmatrophiX Inc.; Active, not recruiting ➔ Completed; Trial completion date: Sep 2020 ➔ Jun 2020

Clinical • Trial completion • Trial completion date • Alzheimer's Disease • CNS Disorders

[VIRTUAL] ALZHEIMER’S DRUG DEVELOPMENT PIPELINE: NOVEL TARGETS AND INNOVATIVE APPROACHES (AAT-ADPD 2020) - "Selected (non-exhaustive) examples of agents addressing these alternate pathways include: posiphen for presenilin processing; ALZ-801 and AAVrh.10hAPOE2 addressing ApoE-related biology; DHP1401, CT1812, LM11A-31-BHS, and AR1001 focus on synaptic function; levetiracetam, deferiprone, GV1001, and NDX-1017 for neuroprotection; COR388, niflamapimod (VX-745), and GV-971 for immunity and inflammation; AMX0035, AUS-131 and MP-101 for mitochondrial energetics; candesartan, telmisartan, and dabigatran for vascular factors; liraglutide, dapagliflozin, for metabolic dysfunction; MAPTRx/BIIB080 is an RNA-based intervention and vafidemstat and apabetalone are epigenetic interventions; and lupron, a hormonal intervention (gonadotropin-releasing hormone receptor agonist). One novel combination approach consists of losartan, amlodipine, atorvastatin and exercise and rasagiline is an example of molecule with pleiotropic effects on dopamine and disease-biology pathways...Novel designs..."

Alzheimer's Disease • CNS Disorders • APOE

Study of LM11A-31-BHS in Mild-moderate AD Patients (clinicaltrials.gov) - P1/2; N=242; Active, not recruiting; Sponsor: PharmatrophiX Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Oct 2019 ➔ Sep 2020; Trial primary completion date: Oct 2019 ➔ Jun 2020

Clinical • Enrollment closed • Trial completion date • Trial primary completion date