TABLE 2.

Summary of Activities in the Radioprotectors and Radiomitigators Portfolio

Indication	Drug; company	Award type	Year started	Current status	Model	Aims
Enteritis	DFMO (α-difluoromethylornithine); RxBio Inc., Johnson City, TN	Phase I	2011	Complete	Mouse model of pelvis irradiation; HCT116 and H29 cell lines; and mouse model of colon cancer.	Evaluate radioprotecting/radiomitigating effect on gastrointestinal injury. Evaluate the effect on cancer radiosensitivity.
Enteritis	ABC294640 (sphingosine kinase inhibitor); Apogee Biotechnology Corp., Hummelstown, PA	Phase I	2014	Ongoing	In vitro cell lines; mouse model of gastrointestinal acute radiation syndrome.	Perform proof-of-concept studies to show that drug will reduce GI-ARS following abdominal or pelvic radiation.
Proctitis	PAAG-ployglucosamine; Synedgen, Claremont, CA	Phase I	2014	Ongoing	Rat, acute radiation-induced proctitis.	Demonstrate efficacy in mitigation of radiation-induced proctitis. Develop plans to demonstrate that PAAG does not protect cancer cells during radiotherapy.
Mucositis	CBLB502 (TLR-5 agonist); Buffalo Biolabs, Buffalo, NY	Phase I	2012	Complete	Mouse model of head and neck cancer.	Demonstrate protective effect to skin and oral mucosa after single- and fractionated multiple radiation dose regimens. Demonstrate safety and efficacy of the drug in combination with radiotherapy.
Mucositis	RLIP76 (proteoliposome); Terapio Inc., Austin, TX	Phase I	2013	Complete	Hamster cheek.	Develop RLIP as a topical mouthwash. Test efficacy, systemic absorption and demonstrate no tumor protection.
Mucositis	JVRSOD (gene therapeutic); Colby Pharmaceuticals, Menlo Park, CA	Fast track	2013	Ongoing	Mouse model and patients with head and neck cancer.	Perform dose- and schedule- optimization studies for protection from radiation-induced oral mucositis. Identify and qualify a GMP manufacturing site. Submit an IND application for JVRSOD. Perform phase I safety and phase II efficacy clinical trials.
Mucositis	BMX-001a (metalloporphyrin antioxidant); BioMimetix JV, Engelwood, CO	Phase I	2014	Ongoing	Mouse model of head and neck squamous cell carcinoma.	Establish optimum dose schedule to reduce xerostomia and mucositis. Demonstrate that the drug does not interfere with standard of care.
Lung injury	UTL-5g (TNF-α modulator); 21st Century Therapeutics Inc., Detroit, MI	Phase I	2011	Complete	Cell lines and mouse model of lung injury.	Examine whether the drug reduces tumor cell killing in vitro. Demonstrate efficacy in reducing radiation-induced lung injury in vivo. Demonstrate that the drug does not affect tumor cell killing induced by radiation in vivo.
Lung injury	BIO300 (synthetic genistein); Humanetics Corp., Minneapolis, MN	Fast track	2012	Ongoing	Mouse xenograft of NSCLC tumor model and NSCLC patients.	Perform efficacy studies in mouse model to demonstrate inhibition of tumor growth and mitigation of radiation-induced lung damage. File IND for the use of BIO300 in patients receiving radiotherapy for NSCLC. Conduct phase II clinical study to assess safety and effect of BIO300 in improving the morbidity and mortality in patients receiving radiation therapy.
Brain injury	TP508 (biotherapeutic, 23 amino acid peptide); Chrysalis Biotherapeutics, Galveston, TX	Phase I	2011	Transitioned to phase II	Cell lines and mouse xenograft orthotopic model.	Optimize dose and schedule for vascular protection. Demonstrate protection to brain tissue from radiotherapy damage. Determine whether the protection is selective to normal tissue without altering radiation cell killing of cancer cells.
Brain injury	TP508 (biotherapeutic, 23 amino acid peptide); Chrysalis Biotherapeutics, Galveston, TX	Phase II	2013	Ongoing	Mouse orthotopic xenograft model.	Determine the following: 1. Whether the drug protects also cancer stem cells or whether its protective effects are specific to neuroprogenitor cells; 2. Whether the drug reduces radiotherapy-induced neuronal atrophy and cognitive impairment; and 3. How the drug affects neuroprogenitor cells and generation of new neurons.
Brain injury	Fullerene-based radioprotectors; Luna Innovations Inc., Roanoke, VA	Phase I	2014	Ongoing	Cell lines and animals.	Perform preclinical studies to demonstrate safety. Perform preclinical studies to demonstrate effectiveness and improvement in therapeutic ratio.
Thrombocytopenia	CLT009, human allogenic megakaryocyte progenitors	Fast track	2012	Ongoing	Ex vivo cell culture expansion.	Develop culture methods and assays for the expansion, characterization and production of sufficient quantity MKP to initiate and complete IND enabling studies. Optimize media formulations, growth and culturing conditions and scalability of production of MKP for preclinical efficacy, safety and related IND studies.

^aAll information provided here and in the text is publicly accessible at http://projectreporter.nih.gov/reporter.cfm, except for funds distributed in 2015. While this information is accessible on the website, http://projectreporter.nih.gov/reporter.cfm, at the end of FY 2015, the company BioMimetix has kindly agreed to publicly release this information in this article.