Allogeneic cell and gene therapy for neuroendocrine tumors

PROJECT SUMMARY/ABSRACT Neuroendocrine tumors (NETs) are a type of rare neoplasm that originates from cells of the diffuse neuroendocrine system. It is estimated that more than 12,000 people in the U.S. are diagnosed with a NET each year and, in total, approximately 171,000 people in the U.S. are living with NETs in 2023. The number of individuals diagnosed with this type of tumor has been increasing consistently over the past 30 years, from 1.09 per 100,000 persons in 1973 to 6.98 per 100,000 persons by 2012. This observed increase in NET incidence is thought to be the result of improvements in awareness and diagnostics, including better imaging tests and endoscopy. The majority of NETs, and specifically well-differentiated and functional GEPNETs, express the surface protein, somatostatin receptor type 2 (SSTR2), which is the basis for both diagnosis, imaging (including monitoring for progression), and symptomatic therapy. Treatment options for neuroendocrine tumors depend on factors such as tumors size, location, grade, and malignant spread. Approaches include surgical removal (if possible), targeted drug therapy, chemotherapy, and peptide receptor radionuclide therapy (PRRT). Other than rare cases localized, surgically accessible disease, there are no curative therapies for NETs. The primary approved drugs are somatostatin analogs (SSAs), SSA-based PRRT, and a tryptophan hydroxylase inhibitor (blocks serotonin biosynthesis; telotristat ethyl). While these drugs can help alleviate some of the symptoms associated with the secretion of bioactive substances from functional NETs, they demonstrate little to no effect on reducing tumor burden or generating complete remission. Furthermore, PRRT affects organ function and can lead to secondary malignancies. Therefore, other than the limited cases where complete surgical resection is possible, no curative treatment options currently exist. Cell and gene therapy (CGT)-based immuno-oncology (1-0) drugs are transforming cancer outcome expectations. Expression Therapeutics, Inc. (ET) is a fully integrated CGT company with an established executive team that has demonstrated proven success in preclinical execution, clinical development, and GMP manufacturing of transformative therapies in the hemophilia and oncology spaces. ET possesses differentiated, proprietary platform technologies including the LentET gene transfer system, expression Cassette Optimization (eCO), Secreted T cell Actuators (STARs), and Allogeneic Donor Expanded and Programmed T (ADEPT) cells. Expression Therapeutics has developed candidate STAR expressed by ADEPT cells that displays potent cytotoxicity against cancer cell lines. The overall goal of the proposed studies is to advance a promising lead ADEPT-STAR-NET candidate towards clinical testing.