A new pathway
against cancer
HPlus Therapeutics is developing first-in-class inhibitors of the Hv1 proton channel, a novel therapeutic approach built on years of pioneering research at the University of Geneva.
HPlus Therapeutics is developing first-in-class inhibitors of the Hv1 proton channel, a novel therapeutic approach built on years of pioneering research at the University of Geneva.
Our mission is to translate the biology of tumor pH regulation into transformative cancer therapies. By targeting Hv1, a validated but historically undrugged ion channel, we are creating a new class of precision medicines with the potential to address multiple solid tumors.
Our discovery platform has screened over 60,000 compounds, yielding 8 lead candidates with very promising potency.
Hv1 enables cancer cells to maintain intracellular pH homeostasis by exporting the excess protons generated during their heightened metabolism. At the same time, it acidifies the tumor microenvironment, promoting invasion, metastasis, immune evasion, and resistance to therapy. Hv1 overexpression has been implicated in numerous cancers, including breast, colorectal, glioma, and glioblastoma.
Recognizing the therapeutic potential of this mechanism, we established a dedicated discovery platform focused exclusively on Hv1. Screening more than 60,000 compounds has yielded 8 lead candidates, with multiple molecules already demonstrating low-micromolar potency. Our program is now advancing through hit-to-lead optimization toward clinical development.
Hv1 is consistently overexpressed in aggressive cancers and is associated with poor patient outcomes, including reduced overall and recurrence-free survival. Across multiple preclinical models, genetic deletion or pharmacological inhibition of Hv1 suppresses tumor growth, reduces invasion and metastasis, and disrupts the acidic microenvironment required for tumor progression.
Although Hv1 has long been recognized as an attractive oncology target, its highly selective proton-conducting architecture has made it exceptionally difficult to inhibit with small molecules. As a result, decades of compelling biological evidence have remained largely inaccessible to drug development.
HPlus Therapeutics is overcoming this challenge. Our proprietary discovery platform has generated the first generation of selective Hv1 inhibitors, enabling therapeutic modulation of a target previously considered undruggable. Current hit-to-lead optimization is focused on maximizing potency, selectivity, and pharmacokinetic performance to advance best-in-class development candidates.
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