Abstract A042: Formulation of FLAG-003 Tablets to support Phase I/II Clinical Testing in Children with DIPG

Abstract FLAG-003 is a rationally-created single small molecule which exhibits bi-functional complementary (and clinically relevant) therapeutic responses. The molecule is both anti-angiogenic (inhibiting three specific kinases: EGFR, PDGDR and VEGF-R2) and inhibits tubulin by binding to the colchicine binding site. Both effects play a role in anti-cancer therapy, but the combination is essential to combatting cancer on multiple fronts. FLAG-003 was originally envisioned as a therapeutic against breast cancer, but the finding that the drug freely penetrates the blood brain barrier (BBB) and accumulates in the brain tissue led researchers to consider using FLAG-003 to treat cancers of the brain. Previous studies have demonstrated in vitro proof of concept in GBM and DIPG cell lines, as well as proof of concept in three animal PDX models in premier research institutions. FLAG Therapeutics (the drug sponsor) determined that the greatest need and best clinical application for (first-in-man) clinical testing would be in children with documented (via MRI) tumors of the pons (DIPG). Testing in DIPG children presents several challenges that needed to be addressed. It is essential that (whenever possible) the impact on the clinical subject and the family should be considered when designing a “patient-friendly” dosage form. This includes (1) making an oral formulation instead of an injection, (2) considering the perceived taste of the dosage form, and (3) the route of administration knowing that children often have an NG-feeding tube in place. Lastly, (4) the ability of the drug to be administered at home instead of at a clinic/hospital would ease the burden on the patient and family. FLAG Therapeutics has produced a 30mg tablet (total weight) which delivers 5mg of FLAG-003 per tablet. The tablet is a mini-tablet that is 4mm in diameter and can be easily administered into an NG-tube. The tablet also is formulated with a taste-masking agent to nullify any adverse taste to the dosage form. Additionally, the tablet disintegrates rapidly and can be mixed with a variety of foods for ease of administration. Lastly, the tablets are sufficiently stable (physically and chemically) that they can be dispensed to the patient in bulk for daily administration over 21 or 28 days, only requiring the patient to return to the clinic monthly for routine testing. These “patient-friendly” modifications to the dosage form are meant to ease the burden on the family, minimize any patient discomfort, and contribute to a better “Quality-of-Life” (QoL) during phase I/II clinical testing. Clinical testing will begin at 10mg/day (2 tablets) and dose escalates at 5mg increments using multiple tablets. The same tablets can be used in an adult trial to complete the dose-ranging studies and later formulated into a fixed dose tablet for further testing. By using a common blend approach, the same tablet formulation can be used for multiple strengths (5mg active in 30mg tablet, 50mg active in 300mg tablet, etc.) to provide a consistent patient response and a cleaner regulatory submission. Citation Format: Frank L. Sorgi. Formulation of FLAG-003 Tablets to support Phase I/II Clinical Testing in Children with DIPG [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr A042.