Theratechnologies Announces Publication in Frontiers in Oncology Journal Highlighting SORT1+ Technology™ for Targeting SORT1-Mediated Vasculogenic Mimicry

On October 22, 2021 Theratechnologies Inc. (Theratechnologies, or Company) (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported the publication of a peer-reviewed article demonstrating that the Company’s novel investigational peptide-drug conjugates (PDCs) TH1902 and TH1904, derived from its SORT1+ Technology, are effective in inhibiting vasculogenic mimicry (VM) in in vitro ovarian and triple negative breast cancer (TNBC) models (Press release, Theratechnologies, OCT 22, 2021, View Source [SID1234596236]).

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The article was published in the science journal Frontiers in Oncology and is titled "New Peptide-Drug Conjugates for Precise Targeting of SORT1-Mediated Vasculogenic Mimicry in the Tumor Microenvironment of TNBC-Derived MDA-MB-231 Breast and Ovarian ES-2 Clear Cell Carcinoma Cells."

"The results published in Frontiers in Oncology showcase for the first time that the sortilin receptor plays a role in the formation of VM, which is associated with cancer progression and resistance. By targeting SORT1, TH1902 and TH1904 have the potential to inhibit VM and cancer cell growth," said Dr. Christian Marsolais, Senior Vice President and Chief Medical Officer at Theratechnologies. "This recognition by our scientific peers highlights the great potential of our PDCs as a unique and effective vehicle for the potential treatment of many types of cancers in which SORT1 receptors are overexpressed and provides additional evidence that SORT1 plays a major role in the generation of VM, particularly in TNBC and ovarian cancer."

The article is the first to report that SORT1 plays a key role in VM formation and highlights the novel results from preclinical models evaluating the efficient inhibitory properties of TH1902 and TH1904 against VM in in vitro ovarian and TNBC cell models. These results further support the expectation that TH1902 and TH1904 may alter the VM process by bringing anticancer drugs, like docetaxel and doxorubicin, into SORT1-positive cancer cells.

The article can be accessed online here.

About Vasculogenic Mimicry
The formation of microvascular channels by deregulated cancer cells leads to aggressive, metastatic and resistant cancer cells and is known as vasculogenic mimicry. VM is believed to be associated with tumor growth, resistance and poor prognosis in many types of aggressive cancers including ovarian and TNBC.

About SORT1+ Technology
Theratechnologies is currently developing a platform of new proprietary peptides for cancer drug development targeting SORT1 receptors called SORT1+ TechnologyTM. SORT1 is a receptor that plays a significant role in protein internalization, sorting and trafficking. It is highly expressed in cancer cells compared to healthy tissue making it an attractive target for cancer drug development. Expression has been demonstrated in, but not limited to, ovarian, triple-negative breast, endometrial, skin, lung, colorectal and pancreatic cancers. 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.

The Company’s innovative peptide-drug conjugates (PDCs) generated through its SORT1+ TechnologyTM demonstrate distinct pharmacodynamic and pharmacokinetic properties that differentiate them from traditional chemotherapy. In contrast to traditional chemotherapy, Theratechnologies’ proprietary PDCs are designed to enable selective delivery of certain anticancer drugs within the tumor microenvironment, and more importantly, directly inside SORT1 cancer cells. Commercially available anticancer drugs, like docetaxel, doxorubicin or tyrosine kinase inhibitors are conjugated to Theratechnologies’ PDC to specifically target SORT1 receptors. This could potentially improve the efficacy and safety of those agents.

In preclinical data, the Company’s SORT1+ TechnologyTM has shown to improve anti-tumor activity and reduce neutropenia and systemic toxicity compared to traditional chemotherapy. Additionally, in preclinical models, SORT1+ TechnologyTM has shown to bypass the multidrug resistance protein 1 (MDR1; also known as P-glycoprotein) and inhibit the formation of vasculogenic mimicry – two key resistance mechanisms of chemotherapy treatment.

About TH1902
TH1902 combines Theratechnologies’ proprietary peptide to the cytotoxic drug docetaxel. TH1902 is currently Theratechnologies’ lead investigational PDC candidate for the treatment of cancer derived from its SORT1+ Technology. The 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. TH1902 is currently being evaluated in a Phase 1 clinical trial for the treatment of cancers where the sortilin receptor is expressed.

The Company is also evaluating TH1904 in preclinical research, a second PDC derived from its SORT1+ TechnologyTM TH1904 is conjugated to the cytotoxic drug doxorubicin.

The Canadian Cancer Society and the Government of Quebec, through the Consortium Québécois sur la découverte du médicament (CQDM), contributes a total of 1.4 million