Our Science

Discovery and Development

The development of HOPO Therapeutics’ flagship active pharmaceutical ingredient HOPO-101 (3,4,3-LI(1,2-HOPO)), began with the aim of creating a pill that could be used to protect and treat people in a nuclear disaster scenario. After extensive investigation and pre-clinical evaluation, HOPO-101 emerged as a promising candidate capable of binding to, or chelating, heavy metals and removing them from the body. It has several properties that make it exceptionally suited to serve as a chelating agent for heavy metal toxicity.

Selectivity

The therapeutic interventions that are currently available for the treatment of heavy metal contamination, including EDTA and DTPA, can deplete the body’s supply of metal ions that are essential for the body’s function, such as iron, zinc, and calcium. Due to its size and molecular shape, HOPO-101 chelates the f-block elements of the periodic table, including gadolinium, but does not chelate any essential ions. Read more

Oral Availability

The most convenient drug delivery route is an oral medication. This allows for easy self-administration, and is ideal for rapid distribution and treatment for a large population. In pre-clinical studies, HOPO-101 shows good oral availability, and it maintains efficacy when formulated as the oral capsule HOPO 14-1. Read more

Prophylactic and Delayed Efficacy

HOPO-101 effectively removes heavy metals from the body when used either as a prophylaxis or when administered days or weeks following contamination. It could be used to provide protection prior to exposure to heavy metals, e.g. to protect first responders in a nuclear disaster scenario, as well as to treat patients that have already been contaminated. Read more

Rapid Clearance

Heavy metals are excreted quickly once bound by HOPO-101, and the highly stable binding prevents redistribution of heavy metals to other locations in the body. This ensures that heavy metals spend a minimal amount of time in the body, which is particularly important in the case of radioactive isotopes.

HOPO 14-1

The investigational drug product HOPO 14-1, our lead drug candidate, is a proprietary oral formulation containing the active pharmaceutical ingredient (API) HOPO-101. It has been designed to optimize absorption of the API from the GI tract into circulation, and formulated for maximum stability and ease-of-use in a range of radiological disaster scenarios. It can serve as a rapid intervention treatment or a prophylactic safeguard for exposure to radioactive material.

HOPO 14-1 has not been approved by the FDA for any use. Please read this disclaimer regarding any statements or implications regarding its safety, efficacy, or regulatory status.

FAQ

  1. What kinds of metals does HOPO 14-1 chelate?
    In preclinical studies it chelates and promotes the removal of a wide range of heavy metals from the body. These include lead, cadmium, and tin, as well most lanthanide and actinide elements. Of particular note are gadolinium and the radioactive elements uranium, plutonium, and americium.

  2. Can HOPO 14-1 treat lead poisoning?
    Based on available data yes, it can remove lead from the body. A central part of our mission is to improve the lives of people affected by lead poisoning and other forms of environmental heavy metal exposure.

  3. Can HOPO 14-1 remove gadolinium deposited from MRI contrast agents?
    Based on available data yes. In published preclinical studies it has proven far more effective than DTPA at removing gadolinium from the body.

  4. Does HOPO 14-1 cross the blood-brain barrier?
    Yes. The preclinical pharmacokinetics and biodistribution of HOPO-101 have been extensively studied and it does cross the blood-brain barrier.

  5. Will HOPO 14-1 chelate deposited gadolinium that is “free” AND gadolinium still bound to a GBCA chelator?
    Based on the available data, yes, however at this point there is insufficient evidence to anticipate how effective it will be in these different scenarios.

  6. How does one drug molecule target so many different metals when other chelators cannot?
    The innovative design principles responsible for the selectivity of HOPO-101 are based not only in an optimized binding site for heavy metals, but the exclusion of physiologically-relevant metal ions. Essential minerals such as calcium, magnesium, and zinc, are always present in the body, at much higher concentrations than heavy metals. Drawing inspiration from Nature, the development team was able to optimize a molecule that would efficiently bind heavy metals and ignore the body’s necessary metal ions. This selectivity is the key to both the safety and broad efficacy profile of HOPO 14-1 observed in preclinical studies.

  7. Can I purchase or obtain HOPO 14-1?
    At the moment, no, it is not available for purchase or distribution. This includes any distribution through the Expanded Access Program (“Compassionate Use”).

  8. What is your timeline for making HOPO 14-1 available?
    As an FDA-regulated drug product, availability of HOPO-101 is subject to approval by regulatory authorities: the FDA in the United States and similar agencies in other countries around the world. Approval and authorization to market HOPO-101 is our primary focus at this time. We will revisit our position on the Expanded Access Program after every possible technical milestone.

Related Publications

Genome-wide toxicogenomic study of the lanthanides sheds light on the selective toxicity mechanisms associated with critical materials
Structural and spectroscopic characterization of an einsteinium complex
Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents
Biodistribution of the Multidentate Hydroxypyridinonate Ligand [ 14 C]-3,4,3-LI(1,2-HOPO), a Potent Actinide Decorporation Agent
In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)