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. Author manuscript; available in PMC: 2021 May 1.
Published in final edited form as: Radiat Res. 2020 Mar 27;193(5):425–434. doi: 10.1667/RR15545.1

TABLE 2.

NCI SBIR-Funded Grants for Radiation Sensitizers in Chronological Order

Company
Omniox, Inc. NuvOx Pharma, LLC
Drug and mechanism
 OMX-4.80, a H-NOX oxygen carrier: Increases tumor oxygenation. NVX-108, a dodecafluoropentane emulsion (DDFPe): Increases tumor oxygenation.
Organ
 None specified Glioblastoma (GBM)
Award type and year(s)
 Phase I, II grants and Bridge; 2008, 2010, 2012 Phase I, II grants and Bridge; 2010, 2014, 2017
Phase I aims
 To identify leading candidates for therapeutic development, to evaluate penetration of H-NOX into tissue, to evaluate reduction in hypoxia in mice carrying human tumor xenografts treated with H-NOX, and to perform pharmacokinetic and toxicology studies.

  1. Develop an optimized DDFPe radiation sensitizer formulation.

  2. Characterize the formulation in vitro.

  3. Study toxicity/biocompatibility in cell culture.

  4. Conduct toxicity studies in mice.

  5. Perform radiation sensitization studies in cell culture.
Phase I results
 Phase I studies successfully identified a lead candidate that penetrates deep into tumors and raises oxygen levels in hypoxic zones. OMX-4.80 administered I.V. into mice bearing orthotopic glioblastoma penetrated into intracranial tumors and reduced tumor hypoxia in a dose-dependent manner (7). Combination of OMX-4.80 and radiation decreased tumor growth and increased survival. Toxicology studies in rodents and dogs revealed a good safety profile (7). PEGylated version of OMX-4.80 (OMX-4.80P) was developed to improve the circulation half-life, and half-life and was shown to reduce hypoxia in rodent glioblastoma models and was tell tolerated in rodents and dogs (8). NVX-108 increased tumor pO2 up to 400% in mice with pancreatic tumor xenografts (5). The addition of NVX-108 to radiation and carbogen resulted in 2-fold reduction in tumor volume (5).
Phase II aims
 Determine the degree of RT enhancement by lead H-NOX candidates, and refine them for optimal biodistribution, tumor oxygenation, RT enhancement and safety. Phase IIB aims at continued preclinical research, safety testing, and clinical development through phase 1 trials.

  1. To validate tumor re-oxygenation with NVX-108 with imaging biomarkers.

  2. To confirm efficacy of NVX-108 + RT + carbogen in treating GBM in mice.

Phase IIb Aims:

  1. To file an IND for a randomized, prospective placebo-controlled trial of NVX-108 to treat GBM. Specific

  2. Conduct randomized, placebo controlled trial of NVX-108 in chemoradiation of GBM.
Phase II results
 No public data found NVX-108 increased pancreatic tumor xenograft pO2 via fiber-optic probe measurement although no differences were noted on MRI TOLD imaging (6).
Follow-up
 No clinical trials. Phase I clinical trial of NVX-108 with radiation and temozolomide in patients with newly-diagnosed glioblastoma multiforme (NCT02189109). This trial is reportedly completed but not yet published.
Commercialization deal headline and year
 n/a RiboMed Biotech and NuvOx Pharma enter into partnership; 2013.
Deal type and subtype
 n/a Strategic alliances; partnerships.
Drug and deal value (U.S. $M)
 n/a NVX-108; 0
Company
MedVas Concepts, LLC Omniox, Inc. Medical Guidance Systems, LLC
Drug delivery system: Selective delivery of chemotherapy to tumor endothelial cells using cell surface proteins that are upregulated by exposure to ionizing radiation. H-NOX variants with less immunogenicity than OMX-4.80: Increases tumor oxygenation. Tiptuximab, an antibody that binds specifically to radiation inducible TIP1 on cancer: TIP1 is an inducible protein on cancer cells in response to radiation therapy.
None specified None specified None specified
Phase I grant; 2012 Phase I grant; 2014 Phase I grant; 2014
To demonstrate proof-of-concept including selective delivery of a vascular disrupting agent to endothelial cells and effective inhibition of tumor growth in an animal model of disease.

  1. Compare the oxygen affinity, stability and NO reactivity of a panel of 10 candidate drugs to identify a lead candidate.

  2. Perform animal studies to characterize the pharmacokinetic, safety and immunogenicity of the lead candidate drug.

  3. Examine tumor biodistribution and oxygenation using a syngeneic tumor xenograft model in mice and demonstrate reduction in primary tumor growth with repeated H-NOX dosing in conjunction with fractionated radiation.

  1. Image the radiolabeled antibody in mouse models of lung cancer.

  2. Study the immune response activated by tiptuximab in human cancers.
No public data found No public data found Conjugating the anti-TIP1 antibody to radio-isotopes was effective for in vivo imaging (9, 10). Anti-TIP1 antibodies activated immune effector cells in mouse models of cancer (9, 11).
n/a n/a n/a
n/a n/a n/a
No clinical trials No clinical trials No clinical trials
n/a n/a n/a
n/a n/a n/a
n/a n/a n/a
Company
Biomimetix JV, LLC Apogee Biotechnology Corp. Medical Guidance Systems, LLC
BMX-001: Metalloporphyrin antioxidant compound with radioprotector and radiosensitizer properties. ABC294640, a SK2 inhibitor: Sphingosine kinases (SK1 and SK2) are frequently overexpressed in many human cancers and inhibition of SK activity has anti-proliferative effects on tumor cells. GIRLRG, a peptide ligand: Binds to radiation-inducible stress proteins and can specifically deliver cytotoxic agents to cancer cells.
Glioblastoma Prostate cancer None specified
Fast-Track I and II grants; 2015, 2016 Phase I grant; 2015 Phase I grant; 2016

  1. Perform a Phase 1 clinical trial of BMX-001 with standard RT and TMZ in high-grade glioma patients.

  2. Perform a randomized open-label Phase 2 clinical trial of BMX-001 with standard RT and TMZ versus standard RT and TMZ alone in patients with high-grade gliomas.

  1. To analyze the in vitro capability of ABC294640 to sensitize PCa cells to radiation therapy.

  2. To determine the mechanism for ABC294640-mediated radiosensitization

  3. To evaluate the ability of ABC294640 to modify radiation therapy for PCa in vivo.

 Test the hypothesis that inducible cell-surface proteins on cancer can be exploited to achieve cancer specific drug delivery in patients. To conjugate the lead peptide to PEG and chelators that will serve to image the spatial and temporal distribution of peptides in planned clinical trials.
Phase I/II randomized clinical trial of patients with high grade glioma receiving radiation therapy and temozolomide (NCT02655601). ABC294640 decreased castration-resistant prostate cancer cell viability in vitro and diminished the growth of TRAMP-C2 xenografts in vivo (12). The inhibition of both SK2 and dihydroceramide desaturase may account for these effects (12). ABC294640 downregulate Myc and AR expression and activity (13). Related publications: (14, 15).
No public data found n/a n/a
n/a n/a n/a
Phase I clinical trials in anal cancer and with head and neck cancer (NCT03386500; NCT02990468). No trials specific to prostate cancer. Clinical trials for various cancers (NCT03377179; NCT02939807; NCT02757326). No clinical trials
(Pre-SBIR funding: BioMimetix enters into licensing agreement with Duke University, 2011). n/a n/a
Strategic alliances; licensing agreement. n/a n/a
BMX-001; 0 n/a n/a
Company
Medical Guidance Systems, LLC DEKK-TEC, Inc. NERx Biosciences, Inc.
Antibodies that are specific to the PDZ domain on TIP1: Interrupt cell viability signal transduction pathways. 4-demethyl-4-cholesteryloxycarbonyl-penclomedine (DM-CHOC-PEN): Alkylating agent that may prevent DNA repair and sensitize cancer cells to radiation DNA-PK inhibitor: Inhibits repair of DNA damage which potentiates cellular sensitivity to radiation.
None specified Brain metastases None specified
Phase I grant; 2016 Phase I grant; 2017 Phase I grant; 2017
To determine the efficacy of anti-TIP1/PDZ IgG compared to anti-TIP1/PDZ scFv antibodies in mouse models of cancer and to determine the role of immune effector cells in the cancer response to anti-TIP1 antibodies.

  1. Conduct a phase I clinical trial with DM-CHOC-PEN plus de-escalating doses of WBRT in adults with brain metastases to document safety and to define acceptable minimal effective doses (MED) for the WBRT.

  2. Study the pharmacokinetic profiles for DM-CHOC-PEN and metabolites in the presence of WBRT.

  3. Determine anticancer activity and prepare for a Phase II clinical trial.

 Expand upon identified DNA-PK inhibitors and dvance the development of these molecules for use as anti-cancer therapeutics and to increase the efficacy of radiation and chemotherapy.
Anti-PDZ antibodies enhanced the effects of radiotherapy in mice models of glioma and lung cancer (16). Ongoing phase I clinical trial of DM-CHOC-PEN with WBRT in patients with brain mets: NCT03371004 No public data found
n/a n/a n/a
n/a n/a n/a
No clinical trials Trial is ongoing in collaboration with Tulane University Medical Center. No clinical trials
n/a n/a n/a
n/a n/a n/a
n/a n/a n/a