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

INmune Bio Inc. to Announce Top Line Results from MINDFuL Phase 2 Trial in Early Alzheimer’s on Monday, June 30th (GlobeNewswire) - "INmune Bio...will host a conference call on Monday, June 30 beginning at 8:00am EDT to present top line data from the Phase 2 MINDFuL trial in early Alzheimer’s Disease....The MINDFuL trial is an international, blinded, randomized Phase 2 trial in patients with Early AD with biomarkers of elevated neuroinflammation. Early AD includes patients with MCI (mild cognitive impairment) and mild AD. Patients must have at least one of four biomarkers of inflammation – elevated CRP, HgbA1c, ESR or ApoE4 allele. Patients receive either XPro or placebo (2:1 ratio) for 6 months."

P2 data • Alzheimer's Disease

INmune Bio Inc. Announces First Quarter 2025 Results and Provides Business Update (GlobeNewswire) - "Upcoming Events and Milestones: (i) Top-line data from the Phase 2 Alzheimer’s trial is expected in the second half of June...; (ii) Initiation of Phase 2 trial of XPro in patients with treatment-resistant depression once NIH funding is made available."

New P2 trial • P2 data • Alzheimer's Disease • Depression

Unraveling the Immune Puzzle: Role of Immunomodulation in Alzheimer's Disease. (PubMed, J Neuroimmune Pharmacol) - "Preclinical studies of immunomodulatory agents, including salidroside, festidinol, astragalin, sulforaphane, BM-MSC, simvastatin, Ab-T1, hTREM2, and XENP345, demonstrate promising effects. Additionally, clinical investigations of drugs such as simufilam, AL002, TB006, VGL101, DNL919, XPro1595, astragalus, and IBC-Ab002 underscore the therapeutic potential of targeting immune pathways in AD. This review emphasizes how neuroinflammation, microglial activation, and peripheral immune responses contribute to disease progression. By exploring immunomodulatory mechanisms, the article sheds light on potential therapeutic targets that could help mitigate AD pathology which may pave the way for novel interventions preventing neurodegeneration in AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Immunology • Oncology • CTNNB1 • TNFA

INHIBITION OF TNFA SHOWS PATHOLOGY SPECIFIC ALTERATIONS OF INFLAMMATION IN VCID MODELS (ADPD 2025) - "XPro1595, a novel soluble TNF α inhibitor, was administered subcutaneously twice weekly at 2mg/ml throughout this timeframe... Inhibition of soluble TNF α differentially impacts gene expression in models of cSVD and CAA compared to vehicle controls. Interestingly, this inhibition affects each disease model differently and suggests distinct mechanistic roles of T NFα-driven inflammation in cSVD and CAA."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Hematological Disorders • Inflammation • Metabolic Disorders • ITGA7 • TNFA • TNFRSF1B

ALZHEIMER'S DISEASE (AD) AND INFLAMMATION: BASELINE DEMOGRAPHICS AND DISEASE CHARACTERISTICS IN A PHASE -2 STUDY OF XPRO1595 IN EARLY AD (ADPD 2025) - P2 | "Innovative study designs are required for determination of treatment effects in early -stage AD. These include patient enrichment st rategies and the use of treatment -sensitive endpoints. The MINDful trial is enriched for patients with biomarker confirmed neuropathological AD and systemic inflammation deemed likely to benefit from treatment with XProTM."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Oncology • TNFA

INmune Bio Inc. Announces Year End 2024 Results and Provides a Business Update (GlobeNewswire) - "Upcoming Events and Milestones: Top line cognitive results and secondary endpoints from the AD02 trial in Alzheimer’s Disease will be available in June 2025....Data from the ongoing INKmune trial in mCRPC will be released as they become available. The next data set should be released in Q2 or Q3, 2025. A Phase II trial of XPro in patients with Treatment-Resistant Depression will begin enrollment soon once the NIH releases funds for the trial."

Enrollment status • P1/2 data • P2 data • Alzheimer's Disease • Castration-Resistant Prostate Cancer • Depression

Lack of neuroprotection after systemic administration of the soluble TNF inhibitor XPro1595 in an rAAV6-α-Syn + PFFs-induced rat model for Parkinson's disease. (PubMed, Neurobiol Dis) - "An increase in IL-6 and IL-1β levels in CSF was observed in rats treated with XPro1595, possibly explaining a lack of protective effects following treatment. Our results highlight the need to determine the importance of timing of treatment initiation, which is crucial for future applications of sTNF therapies in PD patients."

Journal • Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • HLA-DRB1 • IL1B • IL6

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

Biomarker • Enrollment closed • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Inflammation • Mental Retardation • Psychiatry

Peripherally administered TNF inhibitor is not protective against α-synuclein-induced dopaminergic neuronal death in rats. (PubMed, Neurobiol Dis) - "To do so, we administered the DN-TNF agent XPro1595 subcutaneously for a period of 12 weeks...Therefore, despite an apparently immunomodulatory effect, this did not suffice to protect against viral vector-derived α-synuclein-induced neurotoxicity. Further studies are warranted to better elucidate the therapeutic potential of soluble TNF inhibitors in PD."

Journal • Preclinical • CNS Disorders • Movement Disorders • Oncology • Parkinson's Disease • CD68

Developing Topics. (PubMed, Alzheimers Dement) - P1b | "Synaptic dysfunction is associated with both the clinical symptoms and core pathologies of AD. These findings provide further evidence of disease-specific and dose-related target engagement for XProTM in AD."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Oncology • TNFA

Ablation of CCL17-positive hippocampal neurons induces inflammation-dependent epilepsy. (PubMed, Epilepsia) - "In conclusion, our data demonstrate that sterile pyramidal neuronal death is sufficient to cause epilepsy in the absence of other pathological processes. The CCL17-DTR mouse line may thus be a valuable model for further mechanistic studies on epilepsy and assessment of antiseizure medication."

Journal • Absence Seizure Disorder • CNS Disorders • Epilepsy • Infectious Disease • Inflammation • Oncology • CA3 • TNFA • TNFRSF1A

INmune Bio Inc. Announces Third Quarter 2024 Results and Provides Business Update (GlobeNewswire) - "Top-line data from the Phase 2 Alzheimer’s trial is expected in the second quarter of 2025."

P2 data • Alzheimer's Disease • CNS Disorders

INmune Bio Inc. Announces Publication in Cell Reports Demonstrating XPro Promotes Remyelination (GlobeNewswire) - "INmune Bio, Inc...announces the publication of a seminal paper in the journal Cell Reports that demonstrates XPro1595 promotes remyelination in an animal model of demyelinating disease...'Our data identify solTNF as a critical cytokine checkpoint that converts microglia from a reparative, remyelinating cell to a damaging, demyelinating cell. These data suggest that blocking soluble TNF is a promising strategy for treating demyelinating diseases.'...'These new data further support the potential for XPro1595 in neurodegenerative diseases by restoring glia function to improve key components of neurodegeneration at multiple levels, including restoration of synaptic function, remyelination, and ceasing cell loss.' INmune anticipates reporting top-line cognitive results of an ongoing blinded randomized Phase II in Early AD patients in the first half of 2025."

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

INmune Bio Inc. Completes Enrollment for Phase 2 Trial in Early Alzheimer's Disease (GlobeNewswire) - "INmune Bio Inc...announced today that it closed enrollment for its Phase 2 trial on Friday, 27 September. This global, blinded, randomized Phase 2 trial (the 'AD02 trial') is focused on patients with Early AD and biomarkers of elevated neuroinflammation. Enrollment of new patients into the trial was concluded after the Company determined that there are sufficient patients currently in screening to meet the trial’s target of 201 patients."

Enrollment closed • Alzheimer's Disease • CNS Disorders

INmune Bio Announces Results of Additional Blinded Interim Analysis of Phase 2 Alzheimer's Disease Trial Demonstrating Correlation between EMACC and CDR-SB Endpoints (GlobeNewswire) - P2 | N=201 | MINDFuL (NCT05318976) | Sponsor: Inmune Bio, Inc. | "An independent review confirmed a highly significant correlation (p<0.001) between baseline scores on EMACC and CDR-SB, the secondary endpoint in the AD02 trial. CDR-SB is the clinical rating scale most used in AD registration studies...The difference in EMACC performance between patients with CDR global ratings of 0.5 (prodromal AD) and those rated 1.0 (mild dementia) was very large, with an effect size (Cohen’s d) of 0.87 (p<.0001). This demonstrates EMACC's ability to accurately differentiate between disease stages, highlighting its sensitivity and precision...'We look forward to completing enrollment near the end of this quarter and to announcing topline data approximately six months from the last patient enrolled.'"

Biomarker • Enrollment status • P2 data • Alzheimer's Disease • CNS Disorders

Unveiling the role of astrogliosis in Alzheimer's disease Pathology: Insights into mechanisms and therapeutic approaches. (PubMed, Int Immunopharmacol) - "D-ALA2GIP, TRAM-34, Genistein, L-serine, MW150 and XPro1595 are examples of few drugs targeting astrogliosis. Therefore, this study may aid in the development of a potent therapeutic agent for ameliorating astrogliosis mediated AD progression."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • NTRK2 • PPARA • TFEB

An Open-Label Extension of XPro1595 in Patients With Alzheimer's Disease (clinicaltrials.gov) - P2 | N=11 | Active, not recruiting | Sponsor: Inmune Bio, Inc. | Trial completion date: Sep 2024 ➔ Dec 2024

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

MINDFuL: A Study of XPro1595 in Patients With Early Alzheimer's Disease With Biomarkers of Inflammation (clinicaltrials.gov) - P2 | N=201 | Recruiting | Sponsor: Inmune Bio, Inc. | Trial completion date: Dec 2024 ➔ Apr 2025 | Trial primary completion date: Dec 2024 ➔ Mar 2025

Biomarker • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Inflammation • Mental Retardation • Psychiatry

INmune Bio Inc. Announces Second Quarter 2024 Results and Provides Business Update (GlobeNewswire) - "Upcoming Events and Milestones: (i) Full enrollment in the Phase II XPro trial for treatment of neuroinflammation as a cause of Alzheimer’s Disease is expected before the end of Q3 followed by top-line data approximately six months from the last patient enrolled; (ii) Initiate a Phase II trial of XPro in patients with Treatment-Resistant Depression 2H 2024."

Enrollment status • New P2 trial • P2 data • Alzheimer's Disease • Depression

INmune Bio Inc. Announces New Phase 1 Study Data Demonstrating Dose-Dependent Effect of XPro on Proteins that Regulation Synapses in Alzheimer’s Patients (GlobeNewswire) - P1 | N=20 | NCT03943264 | Sponsor: Inmune Bio, Inc. | "INmune Bio Inc...is pleased to be presenting results of a new and advanced proteomic analysis at this year’s annual Alzheimer’s Association International Conference (AAIC) in Philadelphia, PA. The poster summarizes dose-related changes in the cerebrospinal fluid (CSF) proteome in patients with Alzheimer’s disease (AD) treated with XProTM in the company’s phase 1b study....The new analysis revealed that a 12-week treatment with XPro™ resulted in a significant change in synaptic proteins, which are essential for communication between neurons."

P1 data • Alzheimer's Disease • CNS Disorders

INmune Bio, Inc. Completes Blinded Interim Analysis of Phase II Alzheimer’s Disease Trial (GlobeNewswire) - "INmune Bio Inc...today confirmed the Phase II Alzheimer’s Disease clinical trial, AD02, is appropriately powered following a blinded sample size re-estimation using the trial’s primary endpoint, the Early Mild Alzheimer’s Cognitive Composite (EMACC). The third-party evaluation concluded that the trial design, operational execution, data collection, and management are of the highest quality. INmune Bio commissioned a third-party group of statisticians and neuropsychologists to evaluate the interim data of patients who completed the 6-month trial. The main goal of the blinded analysis was to evaluate the power and performance characteristics of the primary endpoint, the EMACC."

Trial status • Alzheimer's Disease • CNS Disorders

Dose-related modulation of the synaptic proteome after short-term treatment with XPro1595 for Alzheimer's disease (AAIC 2024) - P1b | "Synaptic dysfunction is associated with both the clinical symptoms and core pathologies of AD. These findings provide further evidence of disease-specific and dose-related target engagement for XPro TM in AD."

Alzheimer's Disease • CNS Disorders • Oncology • TNFA

An Open-Label Extension of XPro1595 in Patients With Alzheimer's Disease (clinicaltrials.gov) - P2 | N=11 | Active, not recruiting | Sponsor: Inmune Bio, Inc. | Recruiting ➔ Active, not recruiting | N=261 ➔ 11 | Trial completion date: May 2026 ➔ Sep 2024 | Trial primary completion date: May 2026 ➔ May 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Mental Retardation • Psychiatry

Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer's disease. (PubMed, Neurobiol Dis) - "Interestingly, inhibiting the inflammatory cytokine, soluble tumor necrosis factor (TNF) with the brain-permeant soluble TNF inhibitor XPro1595 was able to restore aspects of HFHC-induced metabolic inflammation, but only in male mice...Collectively, these results suggest that HFHC diet impairs metabolic and inflammatory pathways in an AD-relevant genotype and that soluble TNF has sex-dependent roles in modulating these pathways across anatomical compartments. Modulation of energy homeostasis and inflammation may provide new therapeutic avenues for AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Gastrointestinal Disorder • Inflammation • Obesity • Oncology

INmune Bio Inc. Announces $9.7 Million Registered Direct Offering Priced At-the-Market Under Nasdaq Rules (GlobeNewswire) - "INmune Bio, Inc...today announced today that it has entered into definitive agreements for the sale and purchase of 986,000 shares of its common stock and warrants to purchase up to an aggregate of 986,000 shares of its common stock at an offering price of $9.84 per share of common stock and accompanying warrant. The warrants include an acceleration clause upon positive top-line data in the Company’s Phase 2 Alzheimer’s Disease program...The warrants terminate on the earlier of (1) the two (2) year anniversary of the initial exercise date of the warrant or (2) thirty (30) trading days following the reporting of positive top-line data (EMACC) in the Phase 2 Alzheimer's program of XPro1595...The net proceeds is expected to fund the Company through the readout of the ongoing Phase 2 trial (AD02) in patients with Early Alzheimer’s Disease (AD) using XPro and through the metastatic castration-resistant prostate cancer (mCRPC) Phase 1 trial using the INKmune technology."

Financing • Alzheimer's Disease • Castration-Resistant Prostate Cancer • CNS Disorders • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor