title: 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.
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.
authors.affiliation: Radiation Oncology, University of Kentucky, 800 Rose Street, Lexington, KY, 40536, USA.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Kudrimoti
authors.affiliation: Gibbs Cancer Center, Spartanburg Regional Hospital, 101 E Wood, Spartanburg, SC, 29303, USA.
authors.forename: Amarintha
authors.initials: A
authors.lastname: Curtis
authors.affiliation: Veteran's Affairs Long Beach Hospital, 5901 E 7th Street, Mail Code 114A, Long Beach, CA, 98022, USA.
authors.forename: Samar
authors.initials: S
authors.lastname: Azawi
authors.affiliation: Department of Medicine, University of Michigan Health System, 1500 E Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Worden
authors.affiliation: Department of Radiation Oncology, Willis-Knighton Cancer Center, 2600 Kings Highway, Shreveport, LA,71103, USA.
authors.forename: Sanford
authors.initials: S
authors.lastname: Katz
authors.affiliation: Division of Hematology and Oncology, Washington University, 660 South Euclid Avenue, Saint Louis, MO, 63110, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Adkins
authors.affiliation: Department of Hematology and Oncology, Wake Forest Health Sciences Medical Center, 1 Medical Center Blvd., Winston-Salem, NC, 27157, USA.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Bonomi
authors.affiliation: PharPoint Research, 5003S Miami Blvd. #100, Durham, NC, 27703, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Elder
authors.affiliation: 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.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Sonis
authors.affiliation: Soligenix Inc., 29 Emmons Drive, Suite C-10, Princeton, NJ, 08540, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Straube
authors.affiliation: Soligenix Inc., 29 Emmons Drive, Suite C-10, Princeton, NJ, 08540, USA. Electronic address: odonini@shaw.ca.
authors.forename: Oreola
authors.initials: O
authors.lastname: Donini
mesh_terms: D000368:Aged; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013280:Stomatitis / Q000188:drug therapy*
chemical_list: D000893:Anti-Inflammatory Agents; D009842:Oligopeptides; C000614919:dusquetide
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)