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Theratechnologies outlines Sortilin data

2020-05-15 09:02 ET - News Release

Mr. Denis Boucher reports


Theratechnologies Inc. has provided new positive results for its investigational Sortilin (Sort1) targeting peptide-drug conjugates (PDCs) which will be presented in three posters during American Association for Cancer Research's virtual annual meeting II on June 22, 2020.

  • Significant inhibition of vasculogenic mimicry observed with TH1902 and TH1904;
  • New peptide-curcumin conjugate, TH1901, shows 100 times greater anti-cancer cell proliferation activity than unconjugated curcumin in vitro;
  • Results to be presented at American Association for Cancer Research (AACR) virtual annual meeting II.

"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, tumour 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 tumour 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 with docetaxel alone.

The abstract "Sortilin receptor-mediated novel cancer therapy: A targeted approach to inhibit VM in ovarian and breast cancers" is now available on-line at the AACR website.

Peptide-curcumin conjugate (TH1901)

Various phytochemicals found in plants, such as curcumin, have been shown to have anti-proliferative, anti-angiogenic 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 with 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 signalling pathways involved in pro-inflammation processes compared with 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 on-line at the AACR website.

TH1902 induced complete tumour regression in triple-negative breast cancer with no apparent decrease in neutrophil count.

Triple-negative breast cancer (TNBC), which represents approximately 10 to 20 per cent 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 with docetaxel alone.

Results indicate that docetaxel administered alone at one-quarter of its maximum tolerated dose (MTD) (3.75 milligrams per kilogram per week) had no apparent effect on tumour burden in a mouse model. In contrast, TH1902 administered at a comparable dose led to strong and sustained tumour inhibition.

TH1902 has also demonstrated a better safety profile than the administration of docetaxel alone. While a single 15 mg/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 six 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 on-line at the AACR website.

About Theratechnologies' Sort1+ technology

Theratechnologies has developed a peptide which specifically targets Sortilin (Sort1) receptors. Sort1 is overexpressed in ovarian, triple-negative breast, skin, lung, colorectal and pancreatic cancers, among others. Sort1 plays a significant role in protein internalization, sorting and trafficking, making it an attractive target for drug development.

Commercially available anti-cancer drugs, like docetaxel, doxorubicin or tyrosine kinase inhibitors, are conjugated to Theratechnologies' investigational novel peptide to specifically target Sortilin receptors. This could potentially improve the efficacy and safety of those agents.

Theratechnologies intends to submit an investigational new drug application to the Food and Drug Administration for a first-in-human clinical trial for TH1902 before the end of 2020.

The Canadian Cancer Society and the government of Quebec, through the Consortium Quebecois sur la decouverte du medicament (CQDM), will contribute a total of $1.4-million toward some of the research currently being conducted for the development of Theratechnologies' targeted oncology platform.

About Theratechnologies Inc.

Theratechnologies is a commercial-stage biopharmaceutical company addressing unmet medical needs by bringing to market specialized therapies for people with orphan medical conditions, including those living with HIV.

We seek Safe Harbor.

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