Phase II year
2019
(last award dollars: 2020)
Phase II Amount
$1,694,818
Ulcerative colitis (UC) is a chronic, relapsing form of Inflammatory Bowel Disease (IBD) characterized by inflammation and ulceration of the colon and rectum. Uncontrolled UC can lead to serious complications, including toxic megacolon and colorectal cancer. The disease affects approximately 700,000 people in the US, with up to 25% of patients diagnosed before age 20. Young UC patients typically present with more severe symptoms, are subject to heavy psycho-social burden, and suffer from growth and development issues. Moreover, the side effect profiles of approved therapies are frequently more severe in children, limiting the therapies available for this vulnerable population. In particular, there is a need for novel, safe therapeutic options suitable for chronic administration in pediatric and adolescent UC patients. To answer this unmet medical need, Thetis proposes to develop magnesium lysicosapentate, or TP-252, an innovative new molecular entity (NME) as a safe, oral therapy to maintain remission of symptoms in children and adolescents with UC. TP-252 delivers eicosapentaenoic acid, (EPA), an Omega-3 polyunsaturated fatty acid (PUFA) shown to have clinical efficacy for treatment of UC. TP-252 overcomes the physico-chemical and commercial deficits inherent in EPA itself to enable development and registration as a prescription drug with an indication for maintenance of remission in pediatric UC patients. Importantly, in a previous preclinical study conducted by Thetis, TP-252 was shown to: (i) deliver therapeutic levels of EPA to colonic tissue and (ii) favorably change colon tissue levels of key eicosanoid mediators that regulate inflammation. Based on these biological findings, along with technical, pharmaceutical and IP advantages of TP-252, Thetis plans to undertake the development of TP-252 to maintain remission in pediatric UC patients. In this SBIR Fast Track project, Thetis will complete the preclinical activities required for IND submission and initiation of clinical studies. This goal will be achieved through three Specific Aims. Phase I will include an efficacy study performed using a dextran sulfate sodium (DSS) mouse model of UC (Specific Aim #1). The efficacy of TP-252 will be evaluated alone (Sub-aim #1a) and in combination with current treatment (Sub-aim #1b). In Phase II, we will determine the juvenile safety profile of TP-252 in support of treatment of pediatric UC patients (Specific Aim #2). Once the efficacy and acceptable toxicity profile of TP-252 are demonstrated, Thetis will conduct the manufacture and testing of GMP Drug Substance (Specific Aim #3), which itself involves two sub-aims including prototype drug product development (Sub-aim #3a), followed by manufacturing scale-up, testing, packaging and release of drug product for clinical supplies (Sub-aim #3b). Upon completion of this project, Thetis will be able to prepare and submit an IND filing as a prerequisite to initiate Phase I clinical studies. This SBIR project is critical to enabling development of the TP-252 program to address the unmet medical need in this vulnerable pediatric population.
Public Health Relevance Statement: NARRATIVE Ulcerative colitis (UC) is a chronic, relapsing form of Inflammatory Bowel Disease (IBD) characterized by inflammation and ulceration of the colon and rectum. Uncontrolled UC can lead to serious complications, including toxic megacolon and colorectal cancer. The disease affects approximately 700,000 people in the US, with up to 25% of patients diagnosed before age 20. Young UC patients typically present with more severe symptoms, are subject to heavy psycho-social burden, and suffer from growth and development issues. Moreover, the side effect profiles of approved therapies are frequently more severe in children, limiting the therapies available for this vulnerable population. In particular, there is a need for novel, safe therapeutic options suitable for chronic administration in pediatric and adolescent UC patients. Thetis Pharmaceuticals proposes to develop TP-252 as a safe, oral therapy to maintain remission of symptoms in children and adolescents with UC.
NIH Spending Category: Autoimmune Disease; Cancer; Colo-Rectal Cancer; Complementary and Integrative Health; Digestive Diseases; Inflammatory Bowel Disease; Nutrition; Orphan Drug; Pediatric; Pediatric Cancer; Rare Diseases; Women's Health
Project Terms: Address; Adolescent; Affect; Age; analytical method; Appearance; base; Biological; Biological Assay; C57BL/6 Mouse; Child; Childhood; Chronic; Clinical; clinical development; clinical efficacy; Clinical Research; Clinical Trials; Colitis; Colon; Colorectal Cancer; Data; Development; Diagnosis; Disease; Disease remission; Dose; Drug Prescriptions; efficacy study; Eicosanoids; Eicosapentaenoic Acid; Enteral; Evaluation; Formulation; Future; Goals; Growth and Development function; Inflammation; Inflammatory Bowel Diseases; innovation; juvenile animal; Laboratories; Lead; Magnesium; Maintenance; manufacturing scale-up; Mediator of activation protein; Medical; method development; Modeling; Molecular; Monitor; mouse model; Nonesterified Fatty Acids; novel; Omega-3 Fatty Acids; Oral; Patients; Pediatric ulcerative colitis ; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Population; pre-clinical; preclinical study; product development; Program Development; programs; protocol development; prototype; psychosocial; Rectum; Relapse; Research; Rivers; Safety; scale up; Severities; side effect; Small Business Innovation Research Grant; Sodium Dextran Sulfate; Specific qualifier value; Symptoms; tablet formulation; Tablets; Testing; Therapeutic; Tissues; Toxic effect; Toxic Megacolon; Toxicokinetics; Toxicology; Treatment Efficacy; treatment group; Ulcer; Ulcerative Colitis; Validation; Vulnerable Populations
