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Partnering to Advance Therapy for Radiation Exposure
Exposure to harmful radionuclides as the result of a nuclear accident or terrorist attack can cause devastating human health effects. A number of agents that remove heavy metals from the body (decorporation agents) are approved to treat radiation and radionuclide contamination, but they are highly impractical in mass-casualty situations because they must be delivered intravenously on a daily basis for weeks or months.
SRI has been working collaboratively with the Lawrence Berkeley National Laboratory (Berkeley Lab) to develop new decorporation agents that ideally would treat the broadest possible range of radionuclides and be available in oral formulations.
“HOPO” ligands show promise
Through more than 50 years of discovery effort, Berkeley Lab has identified a number of decorporation ligands that can effectively chelate actinides and lanthanides. Of these, 3,4,3-LI(1,2-HOPO) has been selected as the most promising candidate to treat radionuclide contamination. Early efficacy studies showed the “HOPO” agent demonstrated superior activity across a greater range of radionuclides compared to currently available therapies.
Leveraging its expertise in radiation biology, organizational familiarity with the pre-clinical development pathway, and in-depth experience with regulated studies, SRI has measurably advanced the HOPO discovery program. In collaboration with scientists at Berkeley Lab, our researchers have worked to identify and secure critical program funding from a variety of government agencies including NIH-ARRA, NCI-RAID, NIAID, and BARDA. They have also:
- Completed all the federally required safety studies (including pharmacokinetics, ADME, in vitro and in vivo safety studies);
- Developed the most appropriate analytical methods for dose analysis and stability testing;
- Developed bioanalytical methods in animal and human matrices;
- Managed regulatory filing with U.S. Food and Drug Administration for Investigative New Drug (IND)
- Developed the FDA-approved clinical protocol
- Initiated manufacturing of clinical drug product
As SRI continues to develop the HOPO ligands with Berkeley Lab, we are charting new territory in obtaining regulatory approval for a clinical development plan under the U.S. FDA’s Animal Efficacy Rule. Field trials to define human efficacy of the HOPO product are not feasible, and researchers had no precedent for the approval of any new radionuclide decorporation product under the efficacy rule. SRI has developed well-controlled animal efficacy and safety studies as required by the rule to provide substantial evidence of decorporation effectiveness and safety.
Driving toward clinical development
SRI Biosciences has helped Berkeley Lab achieve critical milestones to move the HOPO compounds toward clinical development:
- Ensuring the feasibility of large-scale compound manufacture
- Generating nonclinical safety and pharmacokinetics data required to support an Investigational New Drug (IND) application
- Developing a Phase 1 clinical trial protocol
- Securing FDA approval to proceed with the Phase 1 single ascending-dose first-in-human clinical trial. This represents Berkeley Lab’s first IND application for this class of compounds
Research and development activities described were supported by Lawrence Berkeley National Lab (Berkeley Lab) Consortium Agreement No. 6920841 as sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Number 1RC2AI087604-01; Berkeley Lab Subcontract No. 7033740; Department of Energy DE-AC02-05CH11231; NIAID/NIH under Contract Number HHSN272201500013I; and Biomedical Advanced Research and Development Authority (BARDA) under Contract Number IPIAA12OS99609 to Berkeley Lab
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