TABLE 1.
NCI SBIR-Funded Contracts for Radiation Sensitizers in Chronological Order
| Company | |
|---|---|
| Celldex | Suvica, Inc. |
| Drug and mechanism | |
| CDX-301 (Flt3L): Hematopoietic growth factor that increases the number of dendritic cells in blood. | SVC 112 (Bouvardin analog): Inhibits protein synthesis at the level of translation elongation. |
| Organ | |
| NSCLC | Head and neck cancer (HNC) |
| Award type and year(s) | |
| Phase I contract and phase II grant; 2012, 2015 | Phase I and II contracts; 2013, 2015 |
| Phase I aims | |
| Combine RT with two powerful immune modulators, Fms-like tyrosine kinase ligand (Flt3L) and an antibody that activates CD27 and investigate the benefits of these immune modulators when combined with RT in mouse models to provide the basis for future clinical studies. | To perform preliminary pharmacokinetic and toxicity studies and to test the efficacy of the drug on preclinical models of human HNC. |
| Phase I results | |
| No public data found | Bouvardin and radiation-enhanced clonogenic death in HNC cell lines and augmented antitumor effects in HNC tumor xenografts in mice (4). There were no clinical signs of toxicity in mice treated with bouvardin such as loss of >10% body weight, lethargy, or loss of appetite (4). |
| Phase II aims | |
| Manufacture clinical grade Fltr3L and to determine the safety, feasibility, and efficacy of combining lung stereotactic radiation therapy and Fltr3L therapy in patients with NSCLC. | Improve synthesis of SVC112, perform toxicity in rat and dogs, show differential activity of SVC112 in cancer cells versus normal cells and perform efficacy studies in human xenografts in mice. |
| Phase II results | |
| Phase II clinical trial underway for stereotactic radiotherapy and Fltr3L therapy in patients with advanced NSCLC; NCT02839265. | No public data found |
| Follow-up | |
| Publications (but unrelated): http://www.celldex.com/science/publications.php#cdx301 | No clinical trials. |
| Commercialization deal headline and year | |
| (Pre-SBR funding: Celldex Therapeutics acquires rights to immune stimulatory molecules from Amgen; 2009.) | n/a |
| Deal type and subtype | |
| Mergers and acquisitions; asset transactions | n/a |
| Drug and deal value (U.S. $M) | |
| CDX-301; 0.9 | n/a |
| Company | |
| Omm Scientific | Shuttle |
| SaliPhe (saliphenylhalamide): Inhibitor of the V-ATPase pump responsible for acidification. | IPdR (5-iodo-2pyrimidinone-2′-deoxyribose), a prod rug of the radiosensitizer IUdR (5-iodo-2′-deoxyuridine): Increased susceptibility of TdR analog-substituted DNA to the generation of highly reactive uracil free radicals by radiation. |
| NSCLC | GI cancer |
| Phase I contract; 2013 | Phase I and II contracts; 2014, 2015 |
| To prepare stable dosing solutions of the drug, perform preclinical efficacy and safety experiments using NSCLC cell lines and normal human bronchial epithelial cell lines, and to conduct genomic expression and metabolism studies on untreated and treated cells. | To produce GMP manufactured IPdR capsules, submit a letter of intent (LOI) to CTEP, and to prepare a protocol and IRB approval for a phase I clinical trial. |
| No public data found | No public data found |
| n/a | To determine the safety and feasibility of oral IPdR in the phase I dose-escalation clinical trial. |
| n/a | Phase I clinical trial is underway for patients with advanced GI cancers receiving radiotherapy; NCT02381561 |
| No clinical trials. | No public data found |
| n/a | n/a |
| n/a | Strategic alliances; licensing agreement |
| n/a | Doranidazole; 0 |
phase IIb bridge awards. phase IIb bridge awards.