XPro (pegipanermin) / Xencor, INmune Bio - LARVOL DELTA

INmune Bio Inc. and Quantum Computing Inc. Partner to Apply Quantum Optimization and AI to Advance Alzheimer's Drug Research and Explore New Applications for XPro (PRNewswire) - "The collaboration brings together INmune Bio's data from pre-clinical research through four clinical trials and understanding of disease biology with QCi's Dirac-3S quantum optimization machine. Working with clinical and publicly available biomedical datasets, the companies intend to use quantum computing alongside AI and conventional data analytics to uncover relationships that could help find diseases driven by the same biology XPro targets, and to prioritize those with the greatest potential for success."

Licensing / partnership • Alzheimer's Disease

Upcoming Events and Milestones (GlobeNewswire) - "(i) Submit the registrational Phase 2b/3 protocol for XPro in early Alzheimer’s disease to the FDA in [Q4 2026]; (ii) Submit for publication the Phase 2 MINDFuL imaging analyses, including the white matter and cortical gray matter findings presented at AAIC 2026."

FDA event • New P2/3 trial • P2 data • Alzheimer's Disease

Inhibition of Soluble TNF Mitigates Traumatic Brain Injury as a Risk Factor for the Development of Amyloidogenic Proteins and Functional Deficits in 3xTg-AD Mice. (PubMed, J Neurotrauma) - "Overall, treatment with XPro1595 following TBI prevented the development of amyloidogenic proteins and corresponding neurological dysfunction. Clinically, these data support the use of XPro1595 as a clinically relevant therapeutic for patients with TBI to mitigate the risk of increased Aβ levels and neurological decline subacutely post-injury."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Immunology • Oncology • Vascular Neurology • Aβ42 • CASP3 • TNFA • TNFRSF1A

INmune Bio, Inc…announced the publication of a new peer-reviewed preclinical study in the Journal of Neurotrauma examining how traumatic brain injury (TBI) drives the biological changes that link head injury to Alzheimer’s disease (AD). (The Manila Times) - "The Department of Defense-funded study; entitled: 'Inhibition of Soluble TNF Mitigates Traumatic Brain Injury as a Risk Factor for the Development of Amyloidogenic Proteins and Functional Deficits in 3xTg-AD Mice'; found that a single brain injury raised two proteins central to Alzheimer’s biology, the inflammatory cytokine tumor necrosis factor (TNF) and the neurotoxic form of amyloid beta (Aβ42), and that treatment with the Company’s lead neuroinflammation candidate, XPro1595, prevented the injury-induced rise in amyloid pathology."

Preclinical • Alzheimer's Disease

INmune Bio to Present Positive Phase 2 Imaging Data for XPro in Early Alzheimer’s Disease at AAIC (The Manila Times) - "The presentation, titled 'Concordant White Matter and Cortical Treatment Effects in a Phase 2 Study of XPro1595 in Early Alzheimer’s disease,' highlights the full chi-separation analysis of white matter myelin, together with cortical disarray measurement (CDM), an advanced diffusion-MRI measure of gray matter microstructure. The two techniques rely on different MRI contrast mechanisms: chi-separation uses magnetic susceptibility, while CDM uses water diffusion."

P2 data • Alzheimer's Disease

Concordant White Matter And Cortical Treatment Effects In A Phase 2 Study Of Xpro1595 In Early Alzheimer's Disease (AAIC 2026) - No abstract available

Discordant • P2 data • Alzheimer's Disease • CNS Disorders

Intestinal inflammation and LRRK2 R1441C mutation synergize with age to promote neurodegeneration in a mouse model of disease (WPC 2026) - "Additionally, we evaluated the therapeutic potential of a soluble TNFa inhibitor (xPro1595) in mitigating peripheral inflammation, with the goal of reducing neuroinflammation and neurodegeneration... These studies highlight the interplay between genetic susceptibility, aging, and peripheral inflammation in modulating PD risk. They further support the potential of targeted anti-inflammatory interventions as neuroprotective strategies in genetically or immunologically high-risk populations."

Preclinical • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Movement Disorders • Parkinson's Disease • LRRK2

Nmune Bio Inc…announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to XPro (pegipanermin), the company's first-in-class selective soluble TNF inhibitor, for the treatment of early Alzheimer's disease (AD). (INmune Bio Press Release) - "Phase 2 MINDFuL data, our End-of-Phase 2 alignment with FDA, and now Fast Track designation reflects a consistent regulatory and scientific case: the right mechanism, in the right patients, with a clean safety profile."

Fast track • Alzheimer's Disease

IMPLEMENTING PERSONALIZED ENDPOINTS TO SUPPORT REGULATORY AND REIMBURSEMENT DECISION-MAKING: A CASE OF GOAL ATTAINMENT SCALING (GAS) IN ALZHEIMER'S DISEASE (ISPOR 2026) - "The objective of this study was to describe a standardized strategy for implementing GAS in a Phase 2 AD clinical trial. GAS was implemented in a global, six-month, randomized, double-blind, placebo-controlled Phase 2 trial of pegipanermin (XPro1595) in 201 patients with early AD and biomarkers of inflammation... With rigorous standardization, GAS can enhance the evidentiary value of clinical trials by quantifying outcomes that are inherently meaningful to patients and caregivers. This case demonstrates how GAS can support drug development in Alzheimer's disease."

Clinical • Reimbursement • US reimbursement • Alzheimer's Disease • CNS Disorders • Inflammation

Upcoming Events and Milestones: (The Manila Times) - "The Marketing Authorization Application (MAA) for CORDStrom is scheduled for submission to the UK’s MHRA in mid-summer, followed directly by an EMA filing; CORDStrom Biologics License Application (BLA) submission to the FDA expected in Q4 2026; Additional imaging analyses from the MINDFuL trial with XPro in early Alzheimer's Disease is expected to be reported in the near future."

EMA filing • FDA filing • MHRA filing • P2 data • Alzheimer's Disease • Dermatology • Genetic Disorders

Treatment with XPro1595 of the ‘ARIA-at-risk’ Population of MINDFuL: Subpopulation Results of the 6-month Phase 2 Trial Targeting Neuroinflammation in Early Alzheimer’s Disease (AAN 2026) - P2 | "Statistically significant (nominal) beneficial effects were observed on the NPI overall, specifically with APOE e4 homozygotes, and on the subfactor of mood/depression. Conclusions With its favorable safety and the consistent directional benefits, we will continue to clinically develop XPro1595 as a treatment for this ARIA-at-risk early Alzheimer’s disease population."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Depression • Inflammation • APOE • GFAP • TNFA

UNDERSTANDING MECHANISMS OF ARIA - INSIGHTS FROM HUMAN AND MOUSE (ADPD 2026) - "ARIA, remains a significant concern with amyloid-targeted therapies (ATTs) such as lecanamab and donanemab...In one study, we have administered XPro1595, a soluble TNFα inhibitor, for the duration of anti-Aβ antibody treatment, to examine the potential role of TNFα in ARIA occurrence, In a second study, we have administered GM6001, an MMP inhibitor with high affinity for MMP9, for the duration of anti-Aβ antibody treatment, to determine the role of MMP9 in ARIA occurrence...These data suggest that the increases in TNFα with ATTs is likely not causative in ARIA development, but MMPs do seem to have a role in ARIA. Spatial multi-omic analysis of tissue from these studies is in process to gain further insights into ARIA development and modification."

Preclinical • Hematological Disorders • Inflammation • MMP9

INmune Bio’s MINDFuL Trial Featured at AD/PD 2026 Plenary as Successful Example of How to Approach Clinical Trials Targeting Inflammation in Early Alzheimer’s Disease (The Manila Times) - "Plenary Presentation Highlights How Aligning Inflammatory Biomarker Enrichment with Mechanism of Action Offers a Blueprint for Success in Alzheimer’s Drug Development...The MINDFuL trial enrolled patients enriched for inflammatory biomarkers, and the results reflected that precision: nearly all efficacy endpoints in the inflamed patient subgroup favored XPro1595, a broad and consistent signal that the right patients were identified and the drug performed as the science predicted....Following positive alignment with the FDA at a recent End-of-Phase 2 meeting, INmune Bio is advancing an integrated Phase 2b/3 registrational program for XPro1595 in early Alzheimer’s patients enriched for inflammatory biomarkers, building directly on the MINDFuL foundation with a larger, longer-duration study designed for registration."

New P2/3 trial • Trial status • Alzheimer's Disease

MINDFuL: A Study of XPro1595 in Patients with Early Alzheimer's Disease with Biomarkers of Inflammation (clinicaltrials.gov) - P2 | N=201 | Completed | Sponsor: Inmune Bio, Inc. | Active, not recruiting ➔ Completed

Biomarker • Trial completion • Alzheimer's Disease • CNS Disorders • Inflammation

Selective Inhibition of Tumor Necrosis Factor for Attenuating Alzheimer's Disease: Strategies Targeting Neuroinflammation. (PubMed, Inflammation) - No abstract available

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • Oncology • TNFA

An Open-Label Extension of XPro1595 in Patients With Alzheimer's Disease (clinicaltrials.gov) - P2 | N=11 | Terminated | Sponsor: Inmune Bio, Inc. | Active, not recruiting ➔ Terminated; Sponsor resource allocation

Trial termination • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Mental Retardation • Psychiatry

Xpro®1595 alleviates neuropathic pain by targeting spinal dorsal horn ADAM17-mediated inflammation. (PubMed, Neurobiol Pain) - "These findings demonstrate that ADAM17 is a critical driver of the neuroinflammatory cascade in neuropathic pain. Moreover, our data suggest that the analgesic efficacy of Xpro®1595 is mediated, at least in part, by disrupting this ADAM17-dependent inflammatory feedback loop."

Journal • Immunology • Inflammation • Neuralgia • Pain • ADAM17 • IL1B • IL6 • TNFA • TRPV1

INmune Bio…announced that it received the official minutes from its End-of-Phase 2 (Type B) meeting with the U.S. Food and Drug Administration (FDA) (GlobeNewswire) - "The Phase 2b portion will enroll approximately 300 participants over a nine-month evaluation period designed to validate key efficacy and biomarker assumptions before expansion into the Phase 3 registration segment. The full program is expected to enroll approximately 1,000 participants, with the Phase 3 portion evaluating XPro1595 over 18 months....The FDA raised no objection to the use of Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) as the sole primary efficacy endpoint for the Phase 3 portion of the study....The FDA raised no objection to the Company’s inflammation-based enrichment strategy....INmune Bio is incorporating the FDA’s feedback into the final Phase 2b/3 protocol and anticipates submitting the protocol to the Agency for review."

Clinical protocol • FDA event • Alzheimer's Disease

Developing Topics. (PubMed, Alzheimers Dement) - P2 | "MINDFuL is a proof-of-concept study evaluating the efficacy and safety of XPro1595 (1.0 mg/kg/wk) in patients with early AD and biomarkers of inflammation. Detailed results of unblinded cognitive, functional, safety, and biomarker data will be presented."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Oncology • TNFA

XPro1595, a Selective Soluble TNF Neutralizer, in Early Alzheimer's Disease with Inflammation (ADi): Results from the Phase 2 MINDFuL Trial (CTAD 2025) - No abstract available

P2 data • Alzheimer's Disease • CNS Disorders • Inflammation

TNFR1 Suppression by XPro1595 Reduces Peripheral Neuropathies Associated with Perineural Invasion in Female Mice. (PubMed, Cells) - "Transcriptomic analysis revealed that XPro1595 in females with PNI upregulated mitochondrial, myelination, motor function, and immune regulation gene pathways while it downregulated inflammatory, extracellular matrix, and tumor progression pathways. Overall, we demonstrated that XPro1595 exhibited antitumor, neuroprotective, and analgesic properties in female mice, likely by promoting neuronal regeneration and mitochondrial function, while reducing inflammation and extracellular remodeling."

Journal • Preclinical • Oncology • Pain • TNFA • TNFRSF1A

INmune Bio Announces Two Presentations at the Upcoming 18th Annual CTAD Conference (The Manila Times)

Clinical data • Alzheimer's Disease

The effect of the nonselective TNF inhibitor etanercept, and of the selective TNF inhibitor XPro1595 on lesioned supraspinatus muscle. (PubMed, Biosci Rep) - "Though  both inhibitors had an effect on mitochondrial proteins, particularly etanercept tended to modulate mitochondrial function, and eternacept also influezed  NF-κB signaling. Modulation of mitochondrial proteome, and the  influence on  NF-κB signaling seen after etanercept treatment could correspond with its known effect on apoptosis."

Journal • Oncology • Myogenin

Inhibition of T cell infiltration and soluble TNF signaling is neuroprotective in the alpha-synuclein overexpressing mouse model of Parkinson's disease. (PubMed, NPJ Parkinsons Dis) - "In a chronic model induced with a low viral dose, treatment with either fingolimod (FTY720), which prevents T cell infiltration, or XPro1595, a selective inhibitor of soluble TNF signaling, led to improved motor function and resulted in partially protected dopaminergic cell bodies. Our results support the contribution of CD4+ T cells to αSyn-induced neurodegeneration and suggest that immune modulation can provide neuroprotection in chronic neurodegenerative conditions, offering a wider therapeutic window. Further studies are needed to determine the optimal timing and conditions for implementing immunomodulatory strategies in PD."

Journal • Preclinical • CNS Disorders • Immune Modulation • Immunology • Inflammation • Movement Disorders • Parkinson's Disease • CD4 • IFNG • TNFA

DN-TNF Platform Highlights (XPro) (GlobeNewswire) - "The company is on track to request an End of Phase 2 meeting with the FDA which is anticipated to occur in Q1, 2026....Upcoming Events and Milestones:...Imaging data from the phase 2 MINDFuL trial in Alzheimer’s Disease should be released in Q4 2025."

FDA event • P2 data • Alzheimer's Disease