Introducing transformative precision HDAC6 targeting
Our next-gen molecular recognition technology surpasses the limitations of existing molecules to deliver truly disease-modifying treatments.
The Rationale
HDAC6: Multifaceted Therapeutic Target
HDAC6 is a uniquely versatile, mainly cytoplasmic enzyme that both deacetylates proteins such as alpha-tubulin and acts as a ubiquitin-binding adaptor, regulating cilia, cellular transport, cytoskeleton dynamics, misfolded protein clearance and immune responses.
Unlike the HDACs that control gene expression in the nucleus, HDAC6 acts mainly on non-histone proteins, giving it a favourable safety profile that sets it apart from broadly acting HDAC inhibitors.
Combining this target profile with our proprietary chemistry, we are designing medicines that address disease at its root, in the periphery or central nervous system, in chronic or acute settings, alone or in combination.
The Science
Defying challenges and biases
Our innovative binding mechanism allows us to reverse disease phenotypes caused by aberrant HDAC6 activity.
We harness cutting-edge capabilities in rational drug design, by combining the use of structure-activity relationship studies, X-ray crystallography, molecular biology and computer aided drug discovery to engineer life-changing medicines.
By precisely inhibiting dysregulated HDAC6 activity at the epicentre of specific disease pathways, HDAX molecules have demonstrated unparalleled efficacy in several indications. Our innovative treatments with high binding affinity, enabling low effective concentration and long duration of action, providing an intervention strategy for diseases with no or limited existing therapies.
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Target Cardiorenal
Aberrant activity of HDAC6 has been linked to cardiorenal and metabolic dysfunction including hypertrophy, hypertension, fibrosis and insulin resistance. Therapeutic intervention can modulate multiple interconnected pathways which regulate kidney function, metabolism and boost cardiorenal and metabolic well-being.
In autosomal dominant polycystic kidney disease (ADPKD), aims to restore homeostasis of the cilia-dependent cyst activation (CDCA) pathway, a key driver of cyst growth, with the goal of halting and potentially reversing ADPKD progression. Because the approach acts downstream of the underlying mutation, it is designed to be genotype- and disease stage-agnostic, offering holistic benefit to all patients across renal, cardiovascular and metabolic health.
Target Neurological Diseases
HDAC6 plays a pivotal role in pathways that lead to nerve degeneration, impaired axonal transport and inflammation in disease. Its hyperactivity reduces microtubule acetylation, disrupting cargo transport and mitochondrial function, and contributing to neuropathy and neurodegeneration. HDAC6 inhibition restores acetylation homeostasis, offering an avenue for neuroprotection and neuronal regeneration to reverse disease phenotypes.
Target Expansion Potential
Beyond our current focus, HDAC6 inhibition holds broad therapeutic promise across rare and inflammatory diseases. With emerging insights into biological pathways and disease etiology, HDAX therapeutics’ proprietary platform offers opportunities to develop interventive strategies to augment patient outcomes in complex diseases.
The Pipeline
Unlocking the therapeutic potential of HDAC targeting
Our lead candidate is advancing as a disease-modifying oral therapy for autosomal dominant polycystic kidney disease (ADPKD), with heart failure as our next indication. Our discovery engine is building the next wave of HDAC6 programs for diseases with high unmet need.
| Program | Therapeutic Area |
Discovery
Lead Optimization Development Candidate Clinical Entry |
|---|---|---|
| Peripheral inhibitor |
Therapeutic Area
CVRM (Cardiovascular, Renal & Metabolic)
Entry Indication: HFpEF Expansion: CMT |
Bitopic binder
Novel chemotype
|
| BBB-permeable inhibitor |
Therapeutic Area
Neurology
Under exploration |
Bitopic binder
Developable hit validated in vivo
|
At HDAX, we believe in the urgent need to accelerate the development of disease-modifying medicines for patients in need. We are open to partnering opportunities and strategic collaborations to propel the science. Let’s connect if you share our vision.
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