Favorable tolerability, strong central nervous system exposure, and dose-dependent target engagement support advancement into Phase 2 in Q2 2027
COPENHAGEN, Denmark and BOSTON, U.S., October 21 2026 – Muna Therapeutics (Muna), a clinical-stage biotechnology company developing innovative treatments for neurodegenerative diseases, today announced positive results from its Phase 1 study of MNA-001, a potent, selective, orally administered small-molecule modulator of triggering receptor expressed on myeloid cells 2 (TREM2) that support the treatment’s potential in early Alzheimer’s disease. The study demonstrated favorable safety and tolerability, strong cerebrospinal fluid (CSF) exposure, and dose-dependent target engagement in younger and elderly volunteers.
Exploratory analyses of CFS fluid showed that, after repeated dosing of MNA-001, age-related markers of microglial and innate immune activity and neuronal stress in elderly volunteers shifted toward the levels seen in younger healthy participants. These findings provide evidence of downstream biological activity in humans and support evaluation MNA-001 in early Alzheimer’s.
“We are one step closer to our ambition of restoring the brain’s protective microglial functions in Alzheimer’s,” said Michel Detheux, Ph.D., Chief Executive Officer and Board Director for Muna.“Seeing a shift in selected age-associated biology in elderly participants, alongside a favorable tolerability profile, strengthens our confidence in MNA-001’s differentiated approach and best-in-class potential as a once-daily oral therapy. Our next milestone is to determine whether this biological activity translates into meaningful benefit for patients.”
Human evidence beyond target engagement
MNA-001 was designed to activate TREM 2, a critical regulator of microglia, to enhance protective microglial responses to pathology. Microglia maintain brain health by responding to damage, clearing cellular debris and misfolded proteins, and regulating inflammation. Genetic variants that impair TREM2’s activity increase the risk of Alzheimer’s.
“The connection between TREM2 modulation and the downstream response observed in our Phase 1 study is an encouraging indicator of MNA-001’s potential for biological activity,” said Niels Plath, Ph.D., Chief Scientific Officer of Muna. “We know microglia respond to many signals, and their function changes as disease progresses, so our goal is to both activate them and restore an appropriate response to pathology. These exploratory findings provide a translational foundation for studying sustained TREM2 activation in early Alzheimer’s.”
Results clear path for Phase 2 initiation in early 2027
The randomized, double-blind, placebo-controlled Phase 1 study evaluated single- and multiple-ascending doses of MNA-001 in younger volunteers, with an additional elderly cohort. No deaths, serious adverse events (AEs), or discontinuations due to AEs were reported, and most AEs were mild.
MNA-001 achieved a CSF-to-plasma exposure ratio of approximately 1.7, demonstrating substantial exposure in the central nervous system compartment. Plasma exposure was dose-proportional, with similar pharmacokinetics in younger and elderly participants, supporting continued development as a once-daily oral therapy. Reductions in CSF and plasma-soluble TREM2 were dose-dependent and reached an apparent response plateau at well-tolerated exposures.
Muna expects to initiate a Phase 2 study in the second quarter of 2027, evaluating two doses of MNA-001 against placebo over 48 weeks, with change in plasma pTau217 as the primary endpoint. Cognitive assessments and additional fluid, imaging, and functional biomarkers will characterize treatment effects and explore potential predictors of response.
About MNA-001
MNA-001 is an investigational oral small-molecule modulator of triggering receptor expressed on myeloid cells 2 (TREM2), a critical regulator of microglia. Impairment of TREM2 activity can increase the risk of Alzheimer’s. MNA-001’s differentiated pharmacology promotes stabilization of signaling-competent TREM2 at the cell surface, supporting sustained pathway activation. It is being developed to enhance protective microglial responses, with potential for use alone or in combination with other Alzheimer’s therapies.
About Muna Therapeutics
Muna Therapeutics develops novel medicines designed to preserve brain cognition and other key functions by strengthening resilience to neurodegeneration implicated in diseases like Alzheimer’s. The company’s all-in-human discovery approach identifies mechanisms that protect the brain from disease pathology. Muna’s pipeline of disease-modifying small-molecule investigational therapies spans neurodegenerative disorders. For more information, visit www.munatherapeutics.com. Follow Muna on LinkedIn.
Media Contact:
Lia Dangelico
Deerfield Group
lia.dangelico@deerfieldgroup.com
