FDA Grants Safe to Proceed Letter to IND of Ropidoxuridine in GBM

• Ropidoxuridine (IPdR) is an orally available radiation sensitizer for the treatment of glioblastoma.

• The FDA has previously provided Shuttle Therapeutics positive guidance regarding the investigational new drug application (IND)applicationforropidoxuridine in glioblastoma (GBM).

• With a Safe to Proceed letter granted by the FDA, the phase 2 clinical trial of ropidoxuridine may commence.

The FDA has granted a Safe to Proceed letter to the IND application of a phase 2 study evaluating ropidoxuridine as a radiation sensitizing agent during radiotherapy in patients with newly diagnosed IDH-wildtype GBM with unmethylated MGMT promoter status.¹

Ropidoxuridine is a radiation sensitizer candidate being developed in combination with radiation therapy for the treatment of patients with GBM. The agent has previously received an orphan drug designation from the FDA, providing potential marketing exclusivity upon first FDA approval for the disease.

With this Safe to Proceed letter, Shuttle Pharmaceuticals may begin the phase 2 study, which is currently finalizing site enrollment. The study expects to enroll the first patient who will be treated with the first dose in the coming months.

"We are excited to have been granted approval to commence ropidoxuridine's phase 2 clinical trial following the receipt of the FDA's 'Safe to Proceed' letter," stated Shuttle Pharma's chairman and chief executive officer, Anatoly Dritschilo, MD, in a press release. "Radiation therapy is a proven modality for treating cancers. However, there is a significant need in the market to make radiation more effective. The results of this phase 2 clinical trial will be important as we look to leverage radiation sensitizers to increase cancer cure rates, prolong patient survival and improve quality of life for patients suffering from glioblastoma."

Data presented at the 30th EORTC-NCI-AACR Symposium in November 2018 showed that among 18 patients who completed dose-escalation with ropidoxuridine 1200 mg/day for 30 days, 4 patients had partial responses, 9 patients had stable disease, and 1 patient had progressive disease in target lesions.² These patients were treated with the maximum tolerated dose in combination with radiation therapy.

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These findings support the clinical development of ropidoxuridine in combination with radiation and provide the foundation for design of phase 1b/2 trials for the treatment of patients with brain tumors and sarcomas.

In September 2023, the FDA gave positive feedback and guidance on the protocol design and the company's chemistry, manufacturing, and controls for ropidoxuridine combined with radiotherapy to treat brain tumors, including GBM.³

Now with the receipt of the Safe to Proceed letter from the FDA, the phase 2 clinical trial of ropidoxuridine may commence.¹

REFERENCES:

1. Shuttle Pharmaceuticals receives FDA approval to proceed with phase II clinical trial of ropidoxuridine for treatment of patients with glioblastoma. News release. Shuttle Pharmaceuticals Holdings, Inc. January 8, 2024. Accessed January 8, 2024. http://tinyurl.com/yh5dvmj8

2. Kinsella T, Safran H, Breakstone R, et al. Pharmacology of oral (PO) ropidoxuridine in treating patients with advanced gastrointestinal cancer undergoing radiation therapy (RT) (NCT02381561). Presented at: 30th edition of EORTC-NCI-AACR symposium on Molecular Targets and Cancer Therapeutics; November 13-16, 2018; Dublin, Ireland.

3. Shuttle Pharma announces results of pre-IND meeting with FDA for ropidoxuridine phase II clinical trial for patients with glioblastoma. News release. Shuttle Pharmaceuticals Holdings, Inc. September 25, 2023. Accessed January 8, 2024. https://tinyurl.com/44knmumx