Phase II year
2020
(last award dollars: 2021)
Phase II Amount
$1,680,879
Summary Radiodermatitis is skin tissue damage that occurs in 95% of cancer patients receiving radiotherapy (RT). Although modern RT, e.g., intensity-modulated RT (IMRT) or stereotactic body RT (SBRT), spares more skin areas from RT damage than regular RT, radiodermatitis is still the major toxicity in skin cancer patients treated with SBRT as well as in other cancer patients treated with regular RT where IMRT/SBRT are either unavailable or not suitable, e.g., breast cancer patients. Severe radiodermatitis causes skin erosion, opiate-resistant pain and long-term fibrosis. Current treatments largely aim to ameliorate skin burn rather than promoting healing. Allander Biotechnologies, LLC. has developed a proprietary drug to treat radiodermatitis via anti-inflammation, anti-fibrosis, promoting DNA damage repair, and promoting re-epithelialization. To date, we have established a drug production platform, feasibility for efficacy, safety, and pharmacodynamics (PD) markers to develop our drug into a topically applied drug product. In this Phase II application, we will develop Good Manufacturing Practice (GMP)-scalable production and establish reference standards for our drug substance and drug product. We will perform IND (investigational new drug)-enabling PD and pharmacokinetics (PK) studies. We will evaluate potential toxicity of our drug during topical treatment of radiodermatitis in mice and dogs. We will also perform Good Laboratory Practice (GLP) compliant systemic toxicology studies in rodents via intentional systemic delivery of our drug. By the end of Phase II funding, we will have IND data for CMC (Chemistry, Manufacturing and Controls), preclinical PD/PK, potential cutaneous and systemic toxicities in mice and dogs resulted from topical treatment doses, and GLP systemic toxicology in rodents. These data will allow us to design GLP toxicology studies in a larger species, which will be completed with additional funding for IND filing before initiating a Phase I clinical trial.
Public Health Relevance Statement: Narrative Radiodermatitis manifests as very painful skin damage caused by radiotherapy in cancer patients. Severe radiodermatitis causes skin erosion, opiate-resistant pain and long-term fibrosis. Radiodermatitis is one of the most severe toxic side effects of cancer therapy and is a radiation dose-limiting factor compromising cancer therapy. Current treatments largely aim to ameliorate skin burn rather than promote healing. This application will develop our drug candidate into a drug product to effectively treat radiodermatitis. Our drug will be a topical form allowing patients to self-treat. We propose to produce our drug with robust quality controls, and produce drug efficacy and safety data to apply for an IND application to initiate a clinical trial to treat radiodermatitis.
Project Terms: absorption; Antibodies; Area; Biological Assay; Biotechnology; Breast Cancer Patient; cancer cell; Cancer Patient; cancer radiation therapy; cancer therapy; Canis familiaris; Cells; Chemistry; chronic wound; Clinical Trials; Complex; Cutaneous; cytokine; Data; design; DNA Repair; Dose; Dose-Limiting; drug candidate; drug efficacy; Drug Kinetics; drug production; Drug Stability; Epithelial; Epithelium; Exhibits; Fibrosis; Formulation; Frequencies; Funding; good laboratory practice; Guidelines; healing; HIV-1; Human; immunogenic; immunogenicity; Inflammation; Inflammatory; Intensity-Modulated Radiotherapy; Investigational Drugs; Investigational New Drug Application; keratinocyte; Lead; Length; Malignant Neoplasms; manufacturing scale-up; Maximum Tolerated Dose; Measures; medication safety; meetings; migration; Modeling; Modernization; mouse model; Mus; New Drug Approvals; Oncogenic; Opioid; oral mucositis; Pain; Pathogenesis; Pathway interactions; Patients; Peptides; Pharmaceutical Preparations; pharmacodynamic biomarker; Pharmacodynamics; pharmacokinetics and pharmacodynamics; Phase; Phase I Clinical Trials; pre-clinical; Procedures; Production; Property; Proteins; Quality Control; Radiation; Radiation Dose Unit; Radiation therapy; Radiodermatitis; Rattus; Reference Standards; Regimen; Resistance; Rodent; Safety; side effect; Skin; skin burn; Skin Cancer; Skin Tissue; skin wound; Smad7 protein; subcutaneous; systemic toxicity; tat Protein; Testing; Therapeutic; therapeutic protein; Tissues; Topical application; Toxic effect; Toxicokinetics; Toxicology; Transforming Growth Factor beta; Ulcer
