Preclinical data show HT-4253 reduces neuroinflammation and tau pathology; a second details a Phase 2a biomarker trial in pre-symptomatic APOE4 carriers via UAE genomics

LONDON, July 13, 2026 /PRNewswire/ — Halia Therapeutics today announced two posters at the Alzheimer’s Association International Conference (AAIC) 2026, July 12–15, linking preclinical data on its LRRK2 inhibitor HT-4253 to a biomarker trial to prevent or delay Alzheimer’s disease (AD).

Halia’s approach is grounded in genetic resilience: some APOE4 carriers, protected by a RAB10 variant, never develop Alzheimer’s. HT-4253 reproduces that protection by inhibiting LRRK2, an upstream regulator of the RAB10 pathway.

“Our preclinical data show HT-4253 engages LRRK2, lowering neuroinflammation and tau phosphorylation and restoring microglial function,” said David Bearss, Ph.D., CEO of Halia Therapeutics.

AAIC Presentations:

HT-4253, A Brain-Penetrant LRRK2 Inhibitor, Targets Neuroinflammation and Tau Pathology for AD Prevention in APOE4 Carriers

Wednesday, July 15, 2026, 7:30 a.m.–4:15 p.m.  •  Session: [In-Person Posters Wed] Drug Development: Human  •  Location: Exhibit Hall  •  Poster: Wednesday-0025 (Abstract #3245)

In human cell-based models, HT-4253 inhibited LRRK2 autophosphorylation and Rab10 phosphorylation, confirming target engagement. In iPSC-derived microglia (2D and 3D organoids), it reduced pro-inflammatory cytokine secretion; in iPSC-derived neurons, it decreased tau phosphorylation; and it restored phagocytic function in interferon-γ–exhausted BV2 microglia.

Design of a Phase 2a Trial of LRRK2 Inhibitor HT-4253 in Pre-symptomatic APOE4 Carriers Identified via Population-scale Genomics in the UAE

Monday, July 13, 2026, 7:30 a.m.–4:15 p.m.  •  Session: [In-Person Posters Mon] Drug Development: Human  •  Location: Exhibit Hall  •  Poster: Monday-0081 (Abstract #5843)

After a Phase 1 trial with a favorable safety profile, Halia designed an early-intervention study using population-scale UAE genomics to identify cognitively normal APOE4 carriers. Candidates are screened with C2N Diagnostics’ PrecivityAD2™ blood test for elevated AD biomarkers signaling emerging amyloid pathology. Eligible participants enroll in a 48-week study of once-daily HT-4253, tracking blood-based biomarkers to assess whether it can alter disease onset and progression.

ABOUT HT-4253 AND THE LRRK2–RAB10 PATHWAY

HT-4253 is a brain-penetrant, small molecule inhibitor of leucine-rich repeat kinase 2 (LRRK2), a stress-recruited endolysosomal kinase that regulates membrane trafficking by phosphorylating Rab GTPases, including Rab10. Halia’s hypothesis: persistent LRRK2 signaling, particularly in microglia, links major Alzheimer’s pathologies: impaired lysosomal clearance, tau pathology, and chronic neuroinflammation.

ABOUT HALIA THERAPEUTICS

Halia Therapeutics, headquartered in Lehi, Utah and founded in 2017, is the genetic resilience company. Its secondary program, HT-4253, is in clinical development to prevent or delay Alzheimer’s disease in APOE4 carriers. Halia’s pipeline targets the RAB10 pathway through LRRK2 (upstream) and NEK7 (downstream) to regulate NLRP3 inflammasome activation, a driver of inflammation implicated in Alzheimer’s, cancer, cardiovascular disease, and other chronic conditions.

Investor Contact
Leigh Salvo
New Street Investor Relations
leigh@newstreetir.com

Media Contact
Taylor Avei, Head of Business Development
Halia Therapeutics
tavei@haliatx.com • haliatx.com

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SOURCE Halia Therapeutics