At a Glance
- Alignment secured for integrated Phase 2b/3 trial of XPro1595 in early Alzheimer’s (MCI/mild dementia).
- Dominant-negative TNF inhibitor targets soluble TNF to reduce neuroinflammation without affecting membrane-bound TNF.
- Adaptive study enrolls ~500 patients; Phase 2b dose-finding leads seamlessly to Phase 3 efficacy readouts.
- First patient dosing Q3 2026; topline Phase 2b data expected 2028
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
INmune Bio, Inc. a clinical-stage immunology company, has achieved a major milestone in Alzheimer’s disease (AD) treatment development. On February 12, 2026, the company announced successful alignment with the U.S. Food and Drug Administration (FDA) on an integrated Phase 2b/3 registration pathway for its lead candidate, XPro1595 (pegipanermin), targeting early Alzheimer’s disease. This agreement paves the way for a streamlined trial design that could accelerate approval of this novel therapy.
XPro1595 is a dominant-negative TNF inhibitor designed to neutralize soluble tumor necrosis factor (TNF), a key driver of neuroinflammation in early AD without disrupting membrane-bound TNF. By focusing on microglial activation and synaptic dysfunction hallmarks of early-stage disease XPro1595 aims to slow cognitive decline in patients with mild cognitive impairment (MCI) due to AD or mild AD dementia. Preclinical and Phase 1 data have shown promising reductions in neuroinflammation markers, positioning it as a potential disease-modifying agent.
Key Details of the FDA-Aligned Pathway
The FDA’s endorsement confirms the viability of INmune Bio’s adaptive trial design:
- Phase 2b Dose-Finding Component: Will enroll approximately 500 patients across multiple U.S. and international sites to identify optimal dosing based on biomarkers like CSF sTREM2 and neuroimaging endpoints.
- Seamless Phase 3 Pivot: Top dose(s) from Phase 2b will roll into a pivotal Phase 3 cohort, powering the study for statistical significance on co-primary endpoints: slowing cognitive decline (via CDR-SB scale) and reducing brain atrophy (via MRI).
- Patient Population: Biomarker-confirmed early AD (MCI/mild dementia) using amyloid PET or plasma p-tau217 positivity, aligning with FDA’s emphasis on precision medicine.
- Timeline: First patient dosing targeted for Q3 2026, with topline Phase 2b data expected in 2028.
This integrated approach minimizes delays and costs compared to traditional sequential trials, a strategy increasingly favored by regulators for neurodegenerative diseases.
Strategic Implications for Alzheimer’s Treatment Landscape
Alzheimer’s affects over 6 million Americans, with few disease-modifying options beyond anti-amyloid therapies like lecanemab. XPro1595’s unique mechanism targeting innate immunity rather than amyloid or tau could complement existing treatments and address unmet needs in neuroinflammation-driven progression. Analysts view this FDA alignment as a strong de-risking event, potentially boosting INMB stock and attracting partnerships.
INmune Bio’s CEO, RJ Tesi, MD, stated: “This FDA feedback validates our Precision Medicine platform and positions XPro1595 as a frontrunner in early AD. We’re excited to advance this therapy for patients who need options beyond amyloid clearance.”
Reference
INmune Bio Announces FDA Alignment on Integrated Phase 2b/3 Registration Pathway for XPro1595 in Early Alzheimer’s Disease, 12 February 2026, https://www.inmunebio.com/index.php/newsroom/2026-news/muneionnounceslignmentonntegratedhase2b320260212040512