Theratechnologies Inc. (Theratechnologies) (TSX:TH) (NASDAQ:THTX), a commercial-stage biopharmaceutical company, today announced new positive results for its investigational Sortilin (SORT1) targeting peptide-drug conjugates (PDCs) which will be presented in three posters during AACR’s virtual annual meeting II on June 22, 2020.
“We are very pleased with the results being presented at AACR. The strong activity of our technology against various cancers is very promising. Furthermore, it has shown a significant impact on vasculogenic mimicry, a process which is known to be associated with treatment resistance, tumor progression and poorer prognosis for patients,” said Dr. Christian Marsolais, Senior Vice President and Chief Medical Officer, Theratechnologies.
Inhibition of Vasculogenic Mimicry
Vasculogenic mimicry (VM) is the formation of microvascular channels in aggressive, metastatic and resistant cancers. Recently published studies indicate that the presence of VM is known to contribute to tumor progression, dissemination of cancer metastases and chemoresistance. It is associated with poorer prognosis in many types of aggressive cancers including ovarian and triple-negative breast cancers.
Results indicate that, in vitro, TH1904 (peptide-doxorubicin conjugate) stopped the formation of VM in an ovarian cancer model at very low doses whereas doxorubicin alone had no effect. Strong inhibition of VM in a triple-negative breast cancer model was also observed with very low doses of TH1902 (peptide-docetaxel conjugate) compared to docetaxel alone.
The abstract “Sortilin receptor-mediated novel cancer therapy: A targeted approach to inhibit VM in ovarian and breast cancers” is now available online at aacr.org
Peptide-Curcumin Conjugate (TH1901)
Various phytochemicals found in plants, such as curcumin, have been shown to have antiproliferative, antiangiogenic and apoptotic properties against various cancers such as colorectal, ovarian and breast cancers.
Curcumin was conjugated to Theratechnologies’ investigational SORT1 targeting peptide. TH1901 was tested for its anti-proliferative effect against various cancer cells in vitro and compared to the effect of unconjugated curcumin.
Results indicate that TH1901 has up to 100 times greater anti-proliferation activity against cancer cells than curcumin. In addition, TH1901 induced cell apoptosis and it had a stronger effect on TNF-induced intracellular signaling pathways involved in pro-inflammation processes compared to curcumin alone.
“Results obtained with the peptide-curcumin conjugate demonstrate the versatility and potential broad applications of Theratechnologies’ SORT1+ technology in cancer,” added Dr. Marsolais.
Theratechnologies is currently evaluating the further development of TH1901.
The abstract “TH1901, a novel Curcumin-peptide conjugate for the treatment of Sortilin-positive (SORT1+) cancer” is now available online at aacr.org
TH1902 induced complete tumor regression in Triple-Negative Breast Cancer with no apparent decrease in neutrophil count
Triple-negative breast cancer (TNBC), which represents approximately 10 to 20% of breast cancers, does not express estrogen receptors, progesterone receptors or human epidermal growth factor receptor 2 (HER2). It is more aggressive than other breast cancers. It has been observed that TNBC overexpresses SORT1 receptors.
TH1902 was tested in vivo to assess its effect on TNBC compared to docetaxel alone.
Results indicate that docetaxel administered alone at one quarter of its maximum tolerated dose (MTD) (3.75 mg/kg/week) had no apparent effect on tumor burden in a mouse model. In contrast, TH1902 administered at a comparable dose led to strong and sustained tumor inhibition.
TH1902 has also demonstrated a better safety profile than the administration of docetaxel alone. While a single 15mg/kg dose of docetaxel induced neutropenia, no apparent change in neutrophil counts was observed in mice treated with equivalent doses of TH1902 for up to 6 cycles.
The abstract “A novel Sortilin-targeted docetaxel peptide conjugate (TH1902), for the treatment of Sortilin-positive (SORT1+) triple-negative breast cancer” is now available online at aacr.org