Endoscopy Clinical Trials

• Diagnosis of familial adenomatous polyposis (FAP), defined as at least one of the following:

‣ Genetic diagnosis with confirmed APC mutation (clinical CLIA \[clinical laboratory improvement amendments\] certified lab or research testing)

⁃ Obligate carrier

⁃ Clinical diagnosis of classic FAP with ≥ 100 colorectal adenomas status post colectomy or a sub-total colectomy and a family history of FAP

⁃ Clinical diagnosis of FAP, based on personal and family history. Note: This criterion requires documented review and agreement from either the study chair or the MW consortium lead investigator

• Previously underwent prophylactic colectomy or sub-total colectomy with IRA (ileo-rectal or ileo-colonic anastomosis) or IPAA at least 12 months before pre-registration evaluation and without ongoing surgical complication

• Willing to discontinue taking non-steroidal anti-inflammatory drugs (NSAIDs) 5 days prior to initiation of study treatment and limit frequency of NSAID dosing during study treatment

• Age ≥ 18. Because no dosing or adverse event (AE) data are currently available on the use of TPST-1495 in participants \< 18 years of age, children and adolescents are excluded from this study but will be eligible for future pediatric trials, if applicable

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)

• Leukocytes (white blood count \[WBC\]) ≥ 3,000/uL (≥ 2,500/uL for African American participants)

• Platelet count ≥ 100 x 10\^9/L

• Hemoglobin ≥ 11.5 g/dL

• Total bilirubin ≤ 1.5 x institutional upper limit normal (ULN) (unless patient has Gilbert's)

• Alkaline phosphatase ≤ 1.5 x institutional ULN

• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) ≤ 2 x institutional ULN

• Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) ≤ 2 x institutional ULN

• Creatinine ≤ institutional ULN

• Urinary testing results within institutional limits of normal or deemed clinically insignificant

• Individuals on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible

• Presence of Spigelman 2 or 3 duodenal polyposis stage assessed by endoscopy

• Not pregnant: The effects of TPST-1495 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation or for 90 days after stopping study agent. Additionally, men should not donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study agent. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately

• Not currently breastfeeding

• Ability to understand and the willingness to sign a written informed consent document

• Helicobacter (H.) pylori negative confirmed with gastric biopsy (at time of screening EGD). If positive for H. pylori the patient can be offered full course of approved therapy with confirmation of eradication and re-assessment for trial participation with likely need to repeat baseline endoscopies if \> 45 days since date of baseline procedures