Project Warp Speed

Project Warp SpeedProject Warp SpeedProject Warp Speed

Project Warp Speed

Project Warp SpeedProject Warp SpeedProject Warp Speed

TOGETHER WE CAN FIGHT TO FASTRACK DEMENTIA TREATMENT

TOGETHER WE CAN FIGHT TO FASTRACK DEMENTIA TREATMENTTOGETHER WE CAN FIGHT TO FASTRACK DEMENTIA TREATMENTTOGETHER WE CAN FIGHT TO FASTRACK DEMENTIA TREATMENTTOGETHER WE CAN FIGHT TO FASTRACK DEMENTIA TREATMENT

Enough is enough, 20 yrs of dementia research failures is a disgrace, the government needs to step up and take action. 

TAKE ACTION

TOGETHER WE CAN FIGHT TO FASTRACK DEMENTIA TREATMENT

TOGETHER WE CAN FIGHT TO FASTRACK DEMENTIA TREATMENTTOGETHER WE CAN FIGHT TO FASTRACK DEMENTIA TREATMENTTOGETHER WE CAN FIGHT TO FASTRACK DEMENTIA TREATMENTTOGETHER WE CAN FIGHT TO FASTRACK DEMENTIA TREATMENT

Enough is enough, 20 yrs of dementia research failures is a disgrace, the government needs to step up and take action. 

TAKE ACTION

Take Action to achieve Project Warp Speed!

Project Warp Speed

We are a grassroots campaign focused on advocating for therapeutic development to cure dementia.  Alzheimer's research is hindered by the disease's intricate nature, with multiple competing hypotheses attempting to explain its underlying mechanisms, making it challenging to identify the most effective therapeutic targets. The poor efficacy of current treatments largely stems from an incomplete understanding of the disease's true causes, as many clinical trials have focused on single pathways (such as amyloid-β and tau hypothesis) that have proven to not be the primary drivers of cognitive decline. Furthermore, the slow progression of Alzheimer's disease and the difficulty in accurately diagnosing it at early stages complicate the evaluation of potential treatments, often requiring lengthy and costly clinical trials to demonstrate meaningful results. 


From 1995-2023, over US$58 billion has been spent on Alzheimer's research. Unfortunately to date no high efficacy drugs have been brought to market. Despite the failures, the research focused on neuroinflammation is rapidly gaining scientific recognition and is extremely positive. This discovery not only enhances our understanding of neuroimmune interactions but also opens up new possibilities for therapeutic interventions in inflammatory conditions. The latest article in Nature magazine on neuroinflammation posits a groundbreaking body-brain circuit that regulates inflammatory responses, demonstrating how pro-inflammatory and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to inform the brain of emerging inflammation, and how the brain in turn tightly modulates the peripheral immune response 3

    

Our current focus is on the new neuroinflammation therapeutics, specifically Xpro1595 being developed by a US base biotech company InmuneBio. XPro1595 is an investigational therapeutic designed to selectively target and neutralize soluble tumor necrosis factor (sTNF), a pro-inflammatory cytokine implicated in neuroinflammation and neurodegeneration in Alzheimer's disease. Phase 1 results were incredible. Out of 9 participants, 5 showed stabilization of disease, 1 minor improvement and 2 had meaningful improvement. One of the participants improvement was so dramatic he returned to work, having been previously forced into early retirement. 


Results for the Phase 2 trial of 208 patients are due in June 2025; expectations are very high. Unfortunately, even with extraordinary results, the drug would not become available until 2029-2030. Considering the first patient was cured in 2020, we find it unconscionable that a further 120,000-140,000 Australians with suffer and die before treatment is widely available. 


Although critical for safe drug access, the current development process is broken. Government intervention is needed to fast track Xpro1595. Project Warp Speed is campaigning the government to develop a public-private partnership so that the day positive phase 2 are released, a Phase 3 trial is funded and ready to enroll patients to end this horrible disease.  



XPro1595 Potential Application

XPro1595 addresses the side-effects of currently approved TNF Inhibitors

Traditional TNF inhibitors cause immunosuppression and demyelination. XPRo1595 is a biologic therapy designed to target and neutralize the inflammatory cytokine TNFα. This drug has shown potential in treating various neuroinflammatory diseases by selectively inhibiting soluble TNFα without affecting transmembrane TNFα, thus reducing neuroinflammation while preserving innate immunity and myelination processes.  


Potential Diseases Treated by XPro1595


  • Alzheimer's Disease (AD): XPro1595 is currently in Phase 2 clinical trials for treating Alzheimer's disease and mild cognitive impairment. It aims to reduce neuroinflammation, slow disease progression, and improve cognitive function by targeting soluble TNFα, which is elevated in AD and contributes to synaptic dysfunction, neuronal cell death, and plaque formation. 1 2 3 


  • Mild Cognitive Impairment: Similar to its application in Alzheimer's disease, XPro1595 is being investigated for its potential to treat mild cognitive impairment by reducing inflammation and improving synaptic function. 4


  • Huntington's Disease: XPro1595 has also shown promise in preclinical models of Huntington's disease, improving outcomes by reducing neuroinflammation. 5 6


  • Multiple Sclerosis (MS): In a mouse model of multiple sclerosis, XPro1595 has been found to inhibit soluble TNF and promote remyelination, which is the repair of the myelin sheath damaged in MS. This suggests that XPro1595 could potentially be used to treat MS by reducing neuroinflammation and aiding in the repair of neural damage 7 8 


  •  Parkinson's Disease (PD): Preclinical studies have demonstrated that XPro1595 can reduce inflammation and protect dopaminergic neurons in models of Parkinson's disease. The drug has been shown to prevent the loss of these neurons and mitigate disease progression when administered either directly to the brain or peripherally via subcutaneous injection 9 


  • Treatment Resistant Depression:  XPro1595 appears to be a promising candidate for treating treatment-resistant depression by targeting neuroinflammation, a key factor in the pathology of TRD. INmuneBio plans to commence Phase 2 clinical trials in late 2024 and will further elucidate its efficacy and safety for this application. 10 11

 

  • Chronic Traumatic Encephalopathy (CTE):  Studies using mice have shown XPro1595 can reduce neuroinflammation and neuronal damage & promote remyelination which improves synaptic function. 12

Understand the Potential of XPro1595

Mapping disease and treatment response

 Many neurodegenerative diseases start, even before the first significant symptoms appear, by damaging the myelin surrounding the nerves (axons).   Myelin forms the brain's white matter and it works just like insulation - it makes the electrical signals going along the axons fast, which means efficient brain processing - thinking, remembering, or moving.   That's why white matter damage (initiated by inflammation in the brain) can not only impact these important brain functions but also lead to further damage to the nerves.   And when a nerve dies, it's irreversible. That's why it's critical to have the tools to diagnose and treat early neurodegenerative disorders.  

XPro1595 Patient Experience

Phase 1 XPro1595 clinical trial participant discusses a truly remarkable recovery from the devastating early effects of dementia. This is a world first and gives hope to millions of dementia sufferers world wide. Phase 2 trial aims to replicate this incredible result with statistically significant data through a randomized double blinded placebo trial. 

Mechanism of Action

 XPro1595 is a next-generation inhibitor of tumor necrosis factor (TNF) with a unique mechanism of action.  This allows the drug to target the detrimental effects of excessive sTNF signaling while preserving the beneficial functions of trans-membrane TNF. This selective approach may offer therapeutic benefits in various neurological and inflammatory conditions with potentially fewer side effects compared to non-selective TNF inhibitors. 

INmuneBio Investor Presentation

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Write to your local MP and demand action

Use our email template and write to your local MP to demand the government takes action to Fastrack a solution.   

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Our Vision

 A world where dementia no longer robs individuals of their memories, independence, and dignity. We envision a future where innovative treatments are swiftly and safely brought to market, offering hope and improved quality of life to millions affected by dementia. Through our collective voice and action, we will create a sense of urgency within the government and medical community to prioritize and expedite promising dementia therapies, ensuring that those suffering from this devastating condition have access to potentially life-changing treatments as quickly as possible.

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Publications

 

  1.  MUC4 is a biomarker of metastasis in TNBC and its downregulation by blocking soluble TNF prevents metastasis in combination with immunotherapy
  2.  INB03: a new immune checkpoint inhibitor that reprograms macrophage polarization, boosts ADCP, and reverts T-cell exhaustion markers
  3.  Dominant negative biologics normalise the tumour necrosis factor (TNF-α) induced angiogenesis which exploits the Mycobacterium tuberculosis dissemination 
  4. Cranial venous-outflow obstruction promotes neuroinflammation via ADAM17/solTNF-α/NF-κB pathway following experimental TBI. 
  5. Selective Inhibition of Soluble Tumor Necrosis Factor Alters the Neuroinflammatory Response following Moderate Spinal Cord Injury in Mice.
  6. Soluble TNF mediates amyloid-independent, diet-induced alterations to immune and neuronal functions in an Alzheimer’s disease mouse model.
  7. Blocking soluble TNFα sensitizes HER2-positive breast cancer to trastuzumab through MUC4 downregulation and subverts immunosuppression.
  8. L- and T-type Ca2+ channels dichotomously contribute to retinal ganglion cell injury in experimental glaucoma. 
  9. Selective inhibition of soluble tumor necrosis factor signaling reduces abdominal aortic aneurysm progression.  
  10. Sustained TNF signaling is required for the synaptic and anxiety-like behavioral response to acute stress.  
  11. Co-expression of TNF receptors 1 and 2 on melanomas facilitates soluble TNF-induced resistance to MAPK pathway inhibitors.  
  12. Selective inhibition of soluble TNF using XPro1595 improves hippocampal pathology to promote improved neurological recovery following traumatic brain injury in mice. 
  13. Selective targeting of Tumor Necrosis Factor Receptor 1 induces stable protection from Crohn's-like ileitis in TNF ΔARE mice.  
  14. TNFα increases tyrosine hydroxylase expression in human monocytes.
  15. Selective inhibition of soluble TNF using XPro1595 relieves pain and attenuates cerulein-induced pathology in mice.
  16. Pharmacological inhibition of soluble tumor necrosis factor-alpha (sTNFα) 2 weeks after high thoracic spinal cord injury does not affect sympathetic hyperreflexia.
  17. Microglia, inflammation and gut microbiota responses in a progressive monkey model of Parkinson's disease: A case series.
  18. Attenuating Neurogenic Sympathetic Hyperreflexia Robustly Improves Antibacterial Immunity After Chronic Spinal Cord Injury.
  19. Targeting soluble tumor necrosis factor as a potential intervention to lower risk for late-onset Alzheimer's disease associated with obesity, metabolic syndrome, and type 2 diabetes.  
  20. TNF deficiency causes alterations in the spatial organization of neurogenic zones and alters the number of microglia and neurons in the cerebral cortex
  21. Topical Administration of a Soluble TNF Inhibitor Reduces Infarct Volume After Focal Cerebral Ischemia in Mice.
  22. Chronic psychological stress during adolescence induces sex-dependent adulthood inflammation, increased adiposity, and abnormal behaviors that are ameliorated by selective inhibition of soluble tumor necrosis factor with XPro1595.
  23. Systemic inhibition of soluble TNF with XPro1595 exacerbates a post-spinal cord injury depressive phenotype in female rats.
  24. XPro1595 ameliorates bone cancer pain in rats via inhibiting p38-mediated glial cell activation and neuroinflammation in the spinal dorsal horn.
  25. Inhibition of soluble TNFα prevents adverse atrial remodeling and atrial arrhythmia susceptibility induced in mice by endurance exercise.
  26. Group A Streptococcus Subcutaneous Infection-Induced Central Nervous System Inflammation Is Attenuated by Blocking Peripheral TNF.
  27. Effects of early life stress on cocaine conditioning and AMPA receptor composition are sex-specific and driven by TNF.  
  28. TNFR1 inhibition is therapeutic for neuropathic pain in males but not females.
  29. Translational control of depression-like behavior via phosphorylation of eukaryotic translation initiation factor 4E.
  30. Soluble TNFα signaling within the spinal cord contributes to the development of autonomic dysreflexia and ensuing vascular and immune dysfunction after spinal cord injury.
  31. Involvement of mGluR I in EphB/ephrinB reverse signaling activation induced retinal ganglion cell apoptosis in a rat chronic hypertension model.  
  32. Deprivation-Induced Homeostatic Spine Scaling In Vivo Is Localized to Dendritic Branches that Have Undergone Recent Spine Loss.
  33. Inhibition of TNF reduces mechanical orofacial hyperalgesia induced by Complete Freund's Adjuvant by a TRPV1-dependent mechanism in mice.
  34. Trypanosoma brucei growth control by TNF in mammalian host is independent of the soluble form of the cytokine.
  35. Systemic TNF-α produces acute cognitive dysfunction and exaggerated sickness behavior when superimposed upon progressive neurodegeneration.
  36. Hippocampal TNFα Signaling Contributes to Seizure Generation in an Infection-Induced Mouse Model of Limbic Epilepsy.
  37. Therapeutic inhibition of soluble brain TNF promotes remyelination by increasing myelin phagocytosis by microglia.
  38. Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice.
  39. Toll-like Receptor 4 Mediates Morphine-Induced Neuroinflammation and Tolerance via Soluble Tumor Necrosis Factor Signaling.  
  40. Inhibiting tumor necrosis factor-α before amyloidosis prevents synaptic deficits in an Alzheimer's disease model.
  41. Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in Mice.
  42. Oligodendroglial TNFR2 Mediates Membrane TNF-Dependent Repair in Experimental Autoimmune Encephalomyelitis by Promoting Oligodendrocyte Differentiation and Remyelination.
  43. Inhibition of Soluble Tumor Necrosis Factor Prevents Chemically Induced Carcinogenesis in Mice.
  44. Transmembrane TNF-α is sufficient for articular inflammation and hypernociception in a mouse model of gout.  
  45. TNF compromises lysosome acidification and reduces α-synuclein degradation via autophagy in dopaminergic cells.
  46. Soluble Tumor Necrosis Factor Alpha Promotes Retinal Ganglion Cell Death in Glaucoma via Calcium-Permeable AMPA Receptor Activation.
  47. Transmembrane TNF-TNFR2 Impairs Th17 Differentiation by Promoting Il2 Expression.  
  48. Putative role of protein kinase C in neurotoxic inflammation mediated by extracellular heat shock protein 70 after ischemia-reperfusion.
  49. An adaptive role of TNFα in the regulation of striatal synapses.
  50. AAV-dominant negative tumor necrosis factor (DN-TNF) gene transfer to the striatum does not rescue medium spiny neurons in the YAC128 mouse model of Huntington's disease.
  51. Dendritic-cell exosomes cross-present Toll-like receptor-ligands and activate bystander dendritic cells.
  52. Altered expression of oligodendrocyte and neuronal marker genes predicts the clinical onset of autoimmune encephalomyelitis and indicates the effectiveness of multiple sclerosis-directed therapeutics.
  53. Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling.
  54. Systemically administered anti-TNF therapy ameliorates functional outcomes after focal cerebral ischemia.
  55. Central but not systemic administration of XPro1595 is therapeutic following moderate spinal cord injury in mice.
  56. Peripheral administration of the selective inhibitor of soluble tumor necrosis factor (TNF) XPro®1595 attenuates nigral cell loss and glial activation in 6-OHDA hemiparkinsonian rats.
  57. Selective effects of a therapeutic protein targeting tumor necrosis factor-alpha on cytochrome P450 regulation during infectious colitis: Implications for disease-dependent drug-drug interactions.
  58. Inhibition of soluble tumor necrosis factor is therapeutic in Huntington's disease.
  59. Tumor necrosis factor suppresses NR5A2 activity and intestinal glucocorticoid synthesis to sustain chronic colitis.  
  60. Tumor necrosis factor-neuropeptide Y cross talk regulates inflammation, epithelial barrier functions, and colonic motility.
  61. Chronic dim light at night provokes reversible depression-like phenotype: possible role for TNF.
  62. Neutralization of membrane TNF, but not soluble TNF, is crucial for the treatment of experimental colitis.
  63. Peripheral elevation of TNF-α leads to early synaptic abnormalities in the mouse somatosensory cortex in experimental autoimmune encephalomyelitis.
  64. Differential expression and tumor necrosis factor-mediated regulation of TNFRSF11b/osteoprotegerin production by human melanomas.  
  65. Inhibition of soluble tumor necrosis factor ameliorates synaptic alterations and Ca2+ dysregulation in aged rats.
  66. Tumour necrosis factor-mediated macrophage activation in the target organ is critical for clinical manifestation of uveitis.
  67. Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands.
  68. Inhibition of soluble tumour necrosis factor is therapeutic in experimental autoimmune encephalomyelitis and promotes axon preservation and remyelination.
  69. Allergic lung inflammation is mediated by soluble tumor necrosis factor (TNF) and attenuated by dominant-negative TNF biologics.
  70. Transmembrane tumour necrosis factor is neuroprotective and regulates experimental autoimmune encephalomyelitis via neuronal nuclear factor-kappaB.
  71. Delayed dominant-negative TNF gene therapy halts progressive loss of nigral dopaminergic neurons in a rat model of Parkinson's disease.
  72. zVAD-induced necroptosis in L929 cells depends on autocrine production of TNFα mediated by the PKC-MAPKs-AP-1 pathway.  
  73. Soluble TNF, but not membrane TNF, is critical in LPS-induced hepatitis.
  74. Virally infected and matured human dendritic cells activate natural killer cells via cooperative activity of plasma membrane-bound TNF and IL-15.
  75. Novel mutants of human tumor necrosis factor with dominant-negative properties.  
  76. Dominant-negative tumor necrosis factor protects from Mycobacterium bovis Bacillus Calmette Guérin (BCG) and endotoxin-induced liver injury without compromising host immunity to BCG and Mycobacterium tuberculosis.
  77. Inhibition of soluble TNF signaling in a mouse model of Alzheimer's disease prevents pre-plaque amyloid-associated neuropathology.
  78. Intranigral lentiviral delivery of dominant-negative TNF attenuates neurodegeneration and behavioral deficits in hemiparkinsonian rats.  
  79. Dominant-negative inhibitors of soluble TNF attenuate experimental arthritis without suppressing innate immunity to infection. 
  80. Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson's disease.
  81.  JNK and tumor necrosis factor-alpha mediate free fatty acid-induced insulin resistance in 3T3-L1 adipocytes. 
  82.  Inactivation of TNF signaling by rationally designed dominant-negative TNF variants. 

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