XPro1595

Summary

XPro1595 (pegipanermin) is an investigational dominant-negative TNF biologic engineered to selectively neutralize soluble TNF without impairing transmembrane TNF activity. It is being studied primarily for neuroinflammatory and neurodegenerative conditions including Alzheimer's disease, mild cognitive impairment, treatment-resistant depression, and other CNS disorders. Its selectivity for sTNF is intended to preserve beneficial immune functions lost with non-selective TNF inhibitors.

Mechanism of Action

XPro1595 is a second-generation dominant-negative TNF inhibitor that selectively neutralizes soluble TNF (sTNF) while sparing transmembrane TNF (tmTNF) signaling. It forms inactive heterotrimers with endogenous sTNF, blocking TNFR1-mediated pro-inflammatory signaling without suppressing tmTNF-dependent immune surveillance and neuroprotective functions mediated via TNFR2.

Routes of Administration

Goals & Uses

• Treatment-resistant depressionPsychiatryLow
• Mild cognitive impairment (MCI) treatmentCognitive DeclineLow
• Neuroprotection in CNS diseaseNeuroprotectionLow
• ALS (amyotrophic lateral sclerosis)NeurodegenerationLow
• Alzheimer's disease neuroinflammation reductionNeurodegenerationModerate

Contraindications

• Demyelinating disease (e.g., multiple sclerosis)NeurologicalModerate
• Active serious infectionsInfectiousHigh
• Active tuberculosisInfectiousHigh
• Known hypersensitivity to XPro1595 or excipientsAllergy/HypersensitivityHigh

Adverse Effects

• Injection site reactionsLocalCommon
• HeadacheNeurologicUncommonPain in the head or upper neck
• FatigueGeneralUncommonLow energy or tiredness
• Anti-drug antibodiesImmunologicUnknownAntibodies formed against the therapeutic agent
• Infection susceptibilityImmunologicUncommon

Drug Interactions

• Immunosuppressants (e.g., methotrexate, azathioprine)Moderate
• Other TNF inhibitors (e.g., etanercept, adalimumab)High
• Live vaccinesHigh

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric patientsAgeRelative
• Patients with History of MalignancyOncologyRelative
• Elderly patients with multiple comorbiditiesAge / ComorbidityRelative

Regulatory Status

• European UnionInvestigationalNo EMA marketing authorization. European clinical sites participating in some trials.
• United StatesInvestigationalFDA Fast Track Designation granted for Alzheimer's disease. Multiple Phase 1/2 trials ongoing. Not approved for any indication.
• United KingdomInvestigationalNo MHRA approval. Investigational status only.

XPro1595 (pegipanermin) has received FDA Fast Track Designation for Alzheimer's disease. It is not approved by the FDA, EMA, or any major regulatory authority. Clinical development is ongoing across multiple Phase 1 and Phase 2 trials. Developed by INmune Bio.

Evidence & Sources

No sources recorded yet.