FDA Grants Fast Track Designation to ABD-147 for ES-SCLC

FDA

The FDA has awarded fast track designation to the next-generation precision radiopharmaceutical therapy ABD-147 for the treatment of patients with extensive-stage small cell lung cancer (SCLC) who have progressed on or after platinum-based chemotherapy.¹

ABD-147 is a targeted radiopharmaceutical biologic therapy that is designed to deliver Actinium-225, a potent alpha-emitting radioisotope, to solid tumors that express the protein DLL3 with high affinity. DLL3 is a protein in the Notch pathway that is found on the surface of neuroendocrine tumors but is rarely expressed on the surface of nonmalignant cells or tissues. It plays a critical role in the development and regulation of epithelial cell vs neuroendocrine cell differentiation in the lungs.

In over 80% of cases of some types of high-grade neuroendocrine carcinomas, such as SCLC, DLL3 is upregulated and expressed on the cell surface. Since this protein has highly specific expression on cancer cells and uses a unique mechanism of action, it has been identified as a potential radiotherapy target for the treatment of patients with SCLC and other DLL3-positive solid tumors.

“Aggressive neuroendocrine cancers, such as SCLC, carry a poor prognosis, and new treatment options are urgently needed,” Lori Lyons-Williams, president and chief executive officer of Abdera Therapeutics, Inc., stated in a news release. “These cancers have the most aggressive clinical course of any type of pulmonary tumor and often rapidly metastasize to other parts of the body. We are thrilled the FDA has recognized the potential of ABD-147 to become a transformative treatment option for SCLC, and we are excited to begin clinical development and provide ABD-147 to patients in need.”

Globally, approximately 325,000 patients are reported to have SCLC or large cell neuroendocrine carcinoma (LCNEC), and this incidence is expected to increase by 4% annually through 2029. In the United States, approximately 35,000 new cases of these cancers are reported annually. Furthermore, 15% of all lung cancer cases are high-grade neuroendocrine cancers, which are likely to metastasize to other parts of the body, including the bone, brain, and liver. Patients who do not receive treatment for high-grade neuroendocrine tumors have a median overall survival (OS) of 2 to 4 months. With treatment, the 5-year OS rate is 5% to 10% for patients with SCLC and 15% to 25% for patients with LCNEC.

Targeted radiotherapeutics comprise 3 components: a molecule that targets cancer cells, a chelating agent that binds a radioisotope agent, and a linker that connects the molecule and the radioisotope.² The ABD-147 development program leverages Abdera’s Radio Optimized Vector Engineering platform, which custom engineers targeted radiopharmaceuticals and tunable pharmacokinetic properties that allow them to have high tumor uptake and simultaneously minimize renal exposure and avoid other systemic radiotoxicities, including myelosuppression.¹ The delivery and therapeutic index of these potent radioisotopes, which emit alpha or beta particles, can selectively attack tumor cells, thereby sparing healthy cells. This radiotherapeutic approach can be used to selectively target and kill several high- and low-expressing cancer targets that are expressed on cell surfaces.

In May 2024, the FDA cleared the company’s investigational new drug application for ABD-147, and Abdera Therapeutics plans to initiate a phase 1 trial investigating the agent in the second half of 2024. The first-in-human trial will evaluate the safety and efficacy of ABD-147 in patients with SCLC or LCNEC who have previously received platinum-based therapy, and will also determine the recommended dosing regimen to use for future development.³

References

1. Abdera Therapeutics announces FDA fast track designation for ABD-147, a next-generation precision radiopharmaceutical therapy, for the treatment of patients with extensive-stage small cell lung cancer. News release. Abdera Therapeutics, Inc. June 27, 2024. Accessed July 16, 2024. https://abderatx.com/press-releases/abdera-therapeutics-announces-fda-fast-track-designation-for-abd-147-a-next-generation-precision-radiopharmaceutical-therapy-for-the-treatment-of-patients-with-extensive-stage-small-cell-lung-cancer/
2. Platform. Abdera Therapeutics, Inc. Accessed July 16, 2024. https://abderatx.com/platform/
3. Abdera Therapeutics announces FDA clearance of IND application for ABD-147. News release. Abdera Therapeutics, Inc. May 23, 2024. Accessed July 16, 2024. https://abderatx.com/press-releases/abdera-therapeutics-announces-fda-clearance-of-ind-application-for-abd-147/