Halverson Therapeutics

Halverson Therapeutics operates at the intersection of two long-standing failures of pharmaceutical industry economics: the failure to develop treatments for diseases that affect very small numbers of patients, and the failure to develop oral, brain-penetrant small molecules for the central nervous system at all. The first failure has begun to be addressed by the regulatory environment that emerged from the Orphan Drug Act¹; the second is, as of 2025, beginning to be addressed by advances in medicinal chemistry and the increased viability of structure-based drug design.

We were founded in 2019 with the conviction that the molecular biology of myelin maintenance — the cellular machinery by which the nervous system insulates its own electrical signalling — represents a tractable, well-defined target space for a generation of orally-bioavailable therapies in neurodegenerative disease. Our first program, HVTX-104, validates this hypothesis in adult-onset autosomal-dominant leukodystrophy. Our subsequent programs extend the approach into amyotrophic lateral sclerosis, Niemann-Pick type C, and Charcot-Marie-Tooth 1A.

1.1 The disease

Adult-onset autosomal-dominant leukodystrophy (ADLD), the indication for HVTX-104, is caused by a duplication of the LMNB1 gene on chromosome 5q23. The duplication results in elevated levels of lamin B1, which destabilises the nuclear envelope of oligodendrocytes — the cells responsible for producing and maintaining the myelin sheath in the central nervous system. As affected individuals age, the destabilised oligodendrocytes lose their capacity to maintain the integrity of myelin, leading to a progressive demyelinating disease that typically begins between ages forty and fifty-five.

The clinical presentation of ADLD is characteristic. Patients first develop autonomic dysfunction — most commonly orthostatic hypotension, urinary urgency, and impaired sweating — over a period of two to four years. This is followed by progressive cerebellar ataxia, pyramidal motor signs, and ultimately a severe motor and cognitive decline. Median time from symptom onset to dependence on assistive ambulation is approximately nine years; median life expectancy from symptom onset is fourteen years. There is currently no disease-modifying treatment.

1.2 The mechanism

HVTX-104 is a brain-penetrant, orally-bioavailable small molecule that selectively inhibits the principal regulatory pathway by which lamin B1 expression is elevated in ADLD². In preclinical work in transgenic murine models³, treatment with HVTX-104 over twelve weeks normalised oligodendrocyte nuclear morphology, restored myelin basic protein expression to within 12% of wild-type levels, and produced statistically significant improvements in measures of motor function across three independent cohorts.

Crucially, HVTX-104 achieves a free-fraction brain-to-plasma ratio of 0.84 ± 0.09 in non-human primate studies, which compares favourably with marketed CNS small molecules and addresses the principal failure mode of the prior generation of leukodystrophy candidates. The molecule is dosed orally, once daily, at 80 — 120 mg.