HT-4253 / Halia Therap - LARVOL DELTA

Study to Evaluate the Effect of HT-4253 for the Prevention of Alzheimer's Disease in APOE4 Carriers (clinicaltrials.gov) - P2 | N=112 | Recruiting | Sponsor: Halia Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Aug 2027 ➔ Jul 2028 | Trial primary completion date: May 2027 ➔ Feb 2028

Enrollment open • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders

Design of a Phase 2a Trial of LRRK2 Inhibitor HT-4253 in Pre-symptomatic APOE4 Carriers Identified via Population-Scale Genomics and Blood-Based Biomarkers (CTAD 2026) - No abstract available

Biomarker • Clinical • P2a data • LRRK2

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

Preclinical • Alzheimer's Disease

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

Trial status • Alzheimer's Disease

UAE launches first genomics-driven clinical trial to prevent Alzheimer’s disease (PharmaTimes) - "The trial will evaluate HT-4253, Halia Therapeutics’ investigational therapy, in asymptomatic individuals who carry the APOE4 gene variant...Eligible participants will be invited for screening through targeted outreach led by the Department of Health, based on approved genomic eligibility protocols. All activity is conducted under regulatory oversight to ensure responsible and ethical use of genomic data....The trial will be conducted in Abu Dhabi, led by IROS, with clinical data linkage enabled by Malaffi, the emirate’s longitudinal health information exchange."

Trial status • Alzheimer's Disease

Design Of A Phase 2a Trial Of LRRK2 Inhibitor HT-4253 In Pre-symptomatic APOE4 Carriers Identified Via Population-scale Genomics In The UAE (AAIC 2026) - No abstract available

Clinical • P2a data • LRRK2

HT-4253, A Brain-Penetrant LRRK2 Inhibitor, Targets Neuroinflammation And Tau Pathology For AD Prevention In APOE4 Carriers (AAIC 2026) - No abstract available

Inflammation • LRRK2

Study to Evaluate the Effect of HT-4253 for the Prevention of Alzheimer's Disease in APOE4 Carriers (clinicaltrials.gov) - P2 | N=112 | Not yet recruiting | Sponsor: Halia Therapeutics, Inc.

New P2 trial • Alzheimer's Disease • CNS Disorders • APOE

Halia Therapeutics Completes First-in-Human Phase 1 Study of HT-4253, a Novel LRRK2 Inhibitor Targeting Neuroinflammation (PRNewswire) - "Halia Therapeutics, Inc., a clinical-stage biopharmaceutical company redefining treatment paradigms through inflammation-targeted and resilience-driven therapies, today announced the successful completion of its first-in-human Phase 1 clinical trial evaluating HT-4253 in healthy adult volunteers...The randomized, double-blind, placebo-controlled single- and multiple-ascending-dose (SAD/MAD) trial (ClinicalTrials.gov Identifier: NCT06537817) was conducted at CMAX Clinical Research in Adelaide, Australia...The primary objectives of the trial were safety and tolerability, with secondary endpoints assessing pharmacokinetics (PK) and pharmacodynamics (PD. HT-4253 was generally well tolerated across all dose levels, with no serious adverse events reported. A comprehensive Clinical Study Report (CSR) is anticipated in Q4 2025."

Trial completion • Trial status • CNS Disorders

Study to Evaluate HT-4253 in Healthy Subjects (clinicaltrials.gov) - P1 | N=80 | Completed | Sponsor: Halia Therapeutics, Inc. | Recruiting ➔ Completed

Trial completion

Halia Therapeutics to Attend Global Health Exhibition 2024 (PRNewswire) - "Halia Therapeutics will host an exhibition booth to showcase its efforts in targeting two indications, Alzheimer's disease and obesity. Halia's candidate HT-4253 is a LRRK2 inhibitor administered orally with excellent brain penetration. LRRK2 is a key modulator of neuroinflammation, which plays a critical role in neurodegenerative diseases. HT-6184 is a first-in-class, selective and orally bioavailable inhibitor of the NEK7/NLRP3 inflammasome. HT-6184 is being tested in combination with semaglutide to target inflammation, which has been linked to obesity-related metabolic dysfunction."

Clinical • Alzheimer's Disease • CNS Disorders • Inflammation • Obesity

Halia Therapeutics Announces First Healthy Volunteer Dosed with HT-4253, a Novel Oral LRRK2 Inhibitor Targeting Neuroinflammation in Alzheimer's Disease (PRNewswire) - "Halia Therapeutics...announced that the first healthy volunteer was dosed in its Phase 1 clinical trial evaluating its LRRK2 inhibitor, HT-4253, for a potential treatment for Alzheimer's Disease....The Phase 1 clinical trial (ClinicalTrials.gov ID: NCT06537817) is a first-in-human, randomized, placebo-controlled, double-blind study evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of HT-4253. This study will employ a single ascending dose (SAD) and multiple ascending dose (MAD) format, designed to explore the potential of HT-4253 to inhibit LRRK2—a critical enzyme designed to explore the potential of HT-4253 to inhibit LRRK2."

Trial status • Alzheimer's Disease

Study to Evaluate HT-4253 in Healthy Subjects (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Halia Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

Halia Therapeutics Joins Forces with Southern Star Research Pty Ltd to Advance Clinical Development of Novel LRRK2 Inhibitor, HT-4253 for Neurodegenerative Diseases (PRNewswire) - "Halia Therapeutics, Inc...today announced a pivotal strategic collaboration with Southern Star Research Pty Ltd...This partnership marks the initiation of a Phase 1 clinical trial for Halia's pioneering LRRK2 inhibitor, HT-4253, signaling a significant leap in the fight against debilitating neurodegenerative conditions such as Alzheimer's Disease...The trial is set to commence in Q4 2024, with preliminary results expected in 2025."

P1 data • Trial status • Alzheimer's Disease • CNS Disorders

Study to Evaluate HT-4253 in Healthy Subjects (clinicaltrials.gov) - P1 | N=80 | Not yet recruiting | Sponsor: Halia Therapeutics, Inc.

New P1 trial