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J Biotechnol. 2016 Dec 10;239:115-125. doi: 10.1016/j.jbiotec.2016.10.010. Epub 2016 Oct 13.

Dusquetide: A novel innate defense regulator demonstrating a significant and consistent reduction in the duration of oral mucositis in preclinical data and a randomized, placebo-controlled phase 2a clinical study.

Author information

1
Radiation Oncology, University of Kentucky, 800 Rose Street, Lexington, KY, 40536, USA.
2
Gibbs Cancer Center, Spartanburg Regional Hospital, 101 E Wood, Spartanburg, SC, 29303, USA.
3
Veteran's Affairs Long Beach Hospital, 5901 E 7th Street, Mail Code 114A, Long Beach, CA, 98022, USA.
4
Department of Medicine, University of Michigan Health System, 1500 E Medical Center Drive, Ann Arbor, MI, 48109, USA.
5
Department of Radiation Oncology, Willis-Knighton Cancer Center, 2600 Kings Highway, Shreveport, LA,71103, USA.
6
Division of Hematology and Oncology, Washington University, 660 South Euclid Avenue, Saint Louis, MO, 63110, USA.
7
Department of Hematology and Oncology, Wake Forest Health Sciences Medical Center, 1 Medical Center Blvd., Winston-Salem, NC, 27157, USA.
8
PharPoint Research, 5003S Miami Blvd. #100, Durham, NC, 27703, USA.
9
Division of Oral Medicine, Brigham and Women's Hospital and the Dana-Farber Cancer Institute, Boston MA, USA; Biomodels LLC, 313 Pleasant Street, Watertown, MA 02472, USA.
10
Soligenix Inc., 29 Emmons Drive, Suite C-10, Princeton, NJ, 08540, USA.
11
Soligenix Inc., 29 Emmons Drive, Suite C-10, Princeton, NJ, 08540, USA. Electronic address: odonini@shaw.ca.

Abstract

Dusquetide, a novel Innate Defense Regulator, modulates the innate immune system at a key convergence point in intracellular signaling pathways and has demonstrated activity in both reducing inflammation and increasing clearance of bacterial infection. Innate immunity has also been implicated in the pathogenesis of oral mucositis (OM), a universal toxicity of chemoradiation therapy (CRT). Testing the hypothesis that dusquetide can mitigate the development and duration of OM, preclinical studies have been completed and correlated with interim results from a Phase 2 clinical study in patients undergoing CRT for head and neck cancer. Dusquetide reduced the duration of OM in mouse and hamster models by approximately 50%, which was recapitulated by the 50% reduction of severe OM (SOM) in the Phase 2 trial. A reduction in the clinical rate of infection was also observed, consistent with previously reported preclinical studies. In aggregate, these results not only demonstrate the safety and efficacy of dusquetide in addressing this unmet medical need, but also provide proof of concept for the translation of dusquetide action between animal models and the human clinical setting, and further support the contention that innate immunity is an important driver for the initiation and continued impact of OM.

KEYWORDS:

5-Fluorouracil (PubChem CID: 3385); Cancer supportive care; Dextran sulfate sodium (PubChem CID: 7849109); Dusquetide; Dusquetide (PubChem CID: 71722017); Head and neck cancer; Immune; Innate; Oral mucositis; Paclitaxel (PubChem CID: 36314)

PMID:
27746305
DOI:
10.1016/j.jbiotec.2016.10.010
[Indexed for MEDLINE]
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