Intranasal Anti-CD3 Antibody Foralumab Reduces Brain Inflammation at Low Dose in Progressive MS, but Higher Dose Misses

Tiziana Life Sciences’ intranasal anti-CD3 monoclonal antibody foralumab reduced microglial activation in the brain at its lower dose in the Phase 2a INFORM-MS trial in non-active secondary progressive multiple sclerosis (na-SPMS), but the higher dose did not show a significant effect.¹ The 50-µg dose met both primary endpoints, safety and change in microglial activation on positron emission tomography (PET), while the 100-µg dose missed the imaging endpoint.¹

Tanuja Chitnis, MD, principal investigator of INFORM-MS and professor of neurology at Harvard Medical School and Brigham and Women’s Hospital, said the results provide “encouraging evidence of the biological activity of nasal foralumab.”¹

How does nasal foralumab work?

Foralumab is a fully human antibody against CD3, a protein on the surface of T cells.¹ When given as a nasal spray, it is designed to stimulate regulatory T cells, which help dampen inflammation, rather than broadly suppress the immune system.¹ The target in INFORM-MS was microglial activation, which is believed to play a central role in the progressive biology of MS.¹

In a peer-reviewed study of 10 patients with na-SPMS treated through expanded access, published in Neurology: Neuroimmunology & Neuroinflammation, nasal foralumab reduced microglial activation on PET imaging at three and six months and increased regulatory T cells.²

Patients with na-SPMS continue to lose function without the relapses or new lesions that mark active disease, and no therapy is specifically approved for this population.³

What did INFORM-MS show?

The randomized, double-blind, placebo-controlled trial (NCT06292923) enrolled 48 patients at eight US sites: 18 received placebo, 19 received foralumab 50 µg, and 11 received foralumab 100 µg.¹ Patients were dosed in four consecutive three-week cycles over 12 weeks, and microglial activation was measured using translocator protein (TSPO) PET imaging, with 40 participants having analyzable scans.¹

In the 50-µg group, foralumab reduced microglial activation in white matter compared with placebo, with a treatment difference of −0.0231 in standardized uptake value ratio (95% CI, −0.0416 to −0.0046; P=.0168) in an analysis adjusted for baseline measures and other covariates.¹ The 100-µg group, which had the fewest patients, showed no statistically significant difference.¹

Fatigue scores improved from baseline in both foralumab groups, though the study was not powered for this secondary endpoint, and Tiziana did not report a direct comparison with placebo.¹ Disability scores did not change over the three-month study.¹

All 48 participants completed treatment, with no deaths, no discontinuations due to adverse events, and no serious adverse events related to the study drug.¹ The most common adverse events with foralumab were headache, falls, nasal congestion, and runny nose.¹

How did investors react?

Tiziana’s shares fell about 17% at the open on November 2, as the failure of the higher dose raised questions about the path forward.³

Delivering an antibody through the nose, rather than by infusion or injection, is one of several approaches developers are exploring to change how biologics are given. In a BioPharm International® interview, Chris Worrall, PhD, vice president of US business development at Nanoform, discussed how new formulation approaches could change antibody administration, calling the potential effect “almost a game changer.”

What happens next?

Tiziana plans to complete the full INFORM-MS analysis, present detailed results at an upcoming medical meeting, and meet with FDA to discuss a potential path forward in na-SPMS.¹ “We are extremely pleased that INFORM-MS successfully met its primary endpoints,” said Ivor Elrifi, chief executive officer of Tiziana Life Sciences.¹ Foralumab is also being studied in multiple system atrophy, Alzheimer’s disease, and amyotrophic lateral sclerosis.³

References

1. Tiziana announces positive topline results from Phase 2a INFORM-MS trial of intranasal foralumab in non-active secondary progressive multiple sclerosis. News release. Tiziana Life Sciences. November 2, 2026. Accessed November 3, 2026.
2. Chitnis T, Singhal T, Zurawski J, et al. Nasal foralumab for the treatment of progression independent of relapses in patients with nonactive secondary progressive multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2026;13(2):e200543. doi:10.1212/NXI.0000000000200543
3. Tiziana touts multiple sclerosis win at lower dose as high dose misses mark. BioSpace. November 2, 2026. Accessed November 3, 2026.