On October 26, 2022 Theratechnologies Inc. ("Theratechnologies" or the "Company") (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies reported that data from a tissue microarrays (TMAs) study demonstrating high expression of sortilin 1 (SORT1) in several solid tumors when compared to normal tissues, to be presented as a poster at the 34th European Organisation for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI), and the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Symposium on molecular targets and cancer therapeutics being held October 26-28, 2022, in Barcelona, Spain (Press release, Theratechnologies, OCT 26, 2022, View Source [SID1234622408]). The data highlight the potential of SORT1 as a new target for internalization of anticancer therapy and will be used to support the ongoing preclinical and clinical programs of Theratechnologies’ SORT1+ Technology platform.
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SORT1 is a receptor protein that binds to circulating proteins and peptides prior to their intracellular internalization. It is involved in the rapid transport of molecules across the cell membrane. SORT1 internalization function can be exploited to internalize a peptide-drug conjugate (PDC) to which docetaxel is attached and potentially inhibit the proliferation of cancer cells . Up to now, the pattern and prevalence of SORT1 expression in different healthy tissues have not been well understood, but SORT1 has been shown to be highly expressed in certain malignancies such as breast and ovarian cancers.
"Our study, the first to assess SORT1 expression across a variety of tissue microarrays representing several malignancies, shows that this receptor is highly expressed in cancer compared to normal tissues," said Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer, Theratechnologies. "To our knowledge, no other group has conducted such an extensive screening of tumor or normal tissue biopsies to evaluate the level of SORT1 expression, which is elevated in multiple tumor types and maintained in stages 1 to 4. That makes SORT1 an attractive receptor for targeted delivery and rapid internalization of cancer therapeutic agents."
Researchers reported data on a total of 1,446 cancer cores, using the same immunohistochemistry (IHC) method and scored them using an H-score (an accurate method of describing reactivity in homogeneous tissue such as cancer) ranging from 0 to 300, whereby 0 corresponds to no cell stained for SORT1 and 300 corresponds to strong SORT1 staining in all cells.
The investigators observed high SORT1 expression in multiple solid tumors, as illustrated in the following table:
Interestingly, across 257 normal or adjacent tissue evaluable cores, SORT1 staining was either negative (null) or low for most healthy tissues including lung, stomach, liver, ovary, prostate, lymph node, esophagus, small intestine, cervix, skin, spleen, bone marrow, and thymus. Some healthy tissues had moderate or strong staining in >10% of cells, including the colonic mucosa, rectal epithelium, pancreatic islets and vessels, breast lobules, testicular spermatids and Sertoli cells, kidney tubules, and cerebral neuronal cells and astrocytes. The full poster can be found on Theratechnologies’ website.
"These findings further strengthen the evidence to support the development of our SORT1+ Technology platform, including our ongoing first-in-human study of TH1902, a SORT1-targeted PDC, currently in eight solid tumor types," added Dr. Marsolais. "They could also lay the groundwork for additional PDCs that are in early development."
The Company intends to further evaluate additional tissue microarrays to increase the biopsy sample size and to broaden the range of tumor types and sub-types that may be susceptible to SORT1, such as in prostate, small-cell lung carcinoma and thyroid cancers.
About TH1902 and SORT1+ Technology
Theratechnologies is currently developing a platform of proprietary peptides called SORT1+ TechnologyTM for cancer drug development targeting SORT1 receptors. The SORT1 receptor plays a significant role in protein internalization, sorting and trafficking. It is highly expressed in cancer cells compared to healthy tissue, which makes SORT1 an attractive target for cancer drug development. Expression of SORT1 is associated with aggressive disease, poor prognosis and decreased survival. It is estimated that the SORT1 receptor is expressed in 40% to 90% of cases of endometrial, ovarian, colorectal, triple-negative breast and pancreatic cancers.
TH1902 is currently Theratechnologies’ lead investigational PDC candidate for the treatment of cancer derived from its SORT1+ Technology. It is the Company’s proprietary peptide linked to docetaxel – a commonly used cytotoxic agent used to treat many cancers. The U.S. FDA granted fast track designation to TH1902 as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy.