Abdera Therapeutics Reports Promising Early Data for DLL3-Targeted Radiopharmaceutical ABD-147 in Small Cell Lung Cancer
核心洞察
Abdera Therapeutics (搜索) presented initial Phase 1 clinical data for ABD-147, a novel DLL3 (搜索)-targeting radiopharmaceutical delivering Actinium-225 to small cell lung cancer tumors.
The first-in-human trial demonstrated selective tumor uptake, rapid clearance from blood and kidneys, and favorable safety profile with disease stabilization observed in advanced patients.
ABD-147 has received FDA Fast Track designation for extensive stage small cell lung cancer and targets DLL3 (搜索), which is expressed in approximately 85% of SCLC patients.
Abdera Therapeutics (搜索) announced promising initial clinical data from its first-in-human Phase 1 trial of ABD-147, a targeted radiopharmaceutical designed to deliver the potent alpha-emitting isotope Actinium-225 to tumors expressing delta-like ligand 3 (DLL3 (搜索)). The data, presented at the IASLC 2025 World Conference on Lung Cancer in Barcelona, demonstrate selective tumor uptake and favorable safety profile in patients with small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC).
Targeting a Critical Cancer Pathway
ABD-147 represents a novel approach to treating SCLC by targeting DLL3 (搜索), a protein in the Notch pathway that is critical for neuroendocrine versus epithelial cell differentiation in the lungs. In high-grade neuroendocrine carcinomas including SCLC, DLL3 is upregulated and specifically expressed on the cell surface in more than 80% of cases, while being absent or very rarely expressed on nonmalignant cells.
"DLL3 (搜索) is expressed in approximately 85% of patients with SCLC, an intrinsically radiosensitive cancer," according to the company's presentation. This high specificity makes DLL3 a compelling target for treating SCLC and other DLL3-positive solid tumors with targeted radiotherapy.
Encouraging Phase 1 Results
The Phase 1 trial evaluated safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of ABD-147 in patients with locally advanced or metastatic SCLC and LCNEC following platinum-based chemotherapy. Data from six patients enrolled in the first dose cohort as of August 15, 2025, showed several promising findings.
Pharmacokinetic analysis revealed that human PK was consistent with preclinical models across multiple species, with minimal inter-patient variability. Biodistribution studies demonstrated favorable tumor uptake with rapid clearance from blood and key organs, including the kidneys. Dosimetry analysis using Indium-111 tracking showed that projected administered activity of ABD-147 across all planned doses remains within established safety limits for all organs, including kidneys, liver, and bone marrow.
CT imaging confirmed ABD-147 uptake in target lesions, supporting DLL3 (搜索) specificity. Most importantly, preliminary anti-tumor activity showed disease stabilization, including one patient who received multiple cycles of ABD-147 with over four months of follow-up.
Safety Profile Supports Continued Development
ABD-147 demonstrated a favorable safety profile at the initial dose level. The treatment was well tolerated with no infusion-related events, no dose modifications, and no dose-limiting toxicities observed to date. Treatment-related adverse events included one case of paresthesia (tingling sensation) that resolved rapidly and one case of thrombocytopenia.
Five serious adverse events were observed in two patients – three instances of dyspnea and two deaths due to co-morbidities – all of which were deemed unrelated to the study drug. Based on these initial data, the independent safety review committee recommended continuation of dose escalation with ABD-147.
Expert Commentary and Clinical Significance
"These data with ABD-147 validate the mechanistic promise of DLL3 (搜索)-targeted alpha radiotherapy and mark an important step toward a modality that could reshape SCLC treatment," said Lisa Bodei, M.D., Ph.D., Nuclear Medicine Physician and Early Drug Development Specialist at Memorial Sloan Kettering Cancer Center. "While early, at the first dose level, we observed selective tumor uptake, predicted biodistribution without evidence of alteration, and disease stabilization in advanced disease following platinum-based therapy."
Philippe Bishop, M.D., chief medical officer of Abdera Therapeutics (搜索), emphasized the significance of the milestone: "The presentation of our first-in-human data for ABD-147 marks an important milestone for Abdera and reinforces the promise of our precision radiopharmaceuticals for difficult-to-treat cancers. These data highlight the power of our ROVEr™ platform to engineer finely tunable radiopharmaceuticals with optimal tumor accumulation and healthy tissue clearance."
Addressing Critical Medical Need
The global incidence for SCLC and LCNEC represents approximately 325,000 patients and is expected to increase 4% annually through 2029. In the U.S., approximately 35,000 new cases are diagnosed annually, with fifteen percent of all lung cancer cases being high-grade neuroendocrine cancers.
These cancers have the most aggressive clinical course of any type of pulmonary tumor and often metastasize to other parts of the body, including the brain, liver, and bone. Without treatment, median survival from diagnosis is only two to four months. With treatment, overall survival at five years is 5% to 10% for SCLC and 15% to 25% for LCNEC, highlighting the urgent need for new treatment options.
Regulatory Recognition and Next Steps
The U.S. Food and Drug Administration has granted Fast Track designation to ABD-147 for treating patients with extensive stage small cell lung cancer who have progressed on or after platinum-based chemotherapy. The drug has also received Orphan Drug Designation for treating neuroendocrine carcinoma.
ABD-147 is developed using Abdera's proprietary Radio Optimized Vector Engineering (ROVEr™) platform, which enables the company to engineer potential best-in-class therapies for both clinically validated and novel targets that deliver potent radioisotopes capable of emitting alpha or beta particles to selectively destroy cancer cells.