On April 8, 2022 Theratechnologies Inc. ("Theratechnologies" or "the Company") (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported the Company’s participation in three poster presentations at the 2022 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) to be held April 8-13, 2022 at the Ernest N. Morial Convention Center in New Orleans, Louisiana (Press release, Theratechnologies, APR 8, 2022, View Source [SID1234611681]).

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Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer, Theratechnologies commented, "The exciting new data in triple negative breast and ovarian cancer demonstrate remarkable promise of TH1902 in preclinical studies as a potential treatment for these sortilin expressing cancers. The presence of cancer stem cells (CSCs) is associated with aggressive disease, unregulated tumor growth, increased migration of cancer cells, invasion, self renewal and resistance to standard chemotherapy and radiation. Failure to eliminate these cells with current treatments leads to resistance and progression and there are few therapies that have been shown to target CSCs. In preclinical models treated with TH1902, there was marked tumor growth inhibition of cancer stem-like cells with no impact on healthy tissue. This further validates our hypothesis that TH1902 may be effective in hard-to-treat, resistant cancers."

Highlights of the poster presentations included:

AACR Poster #1853 – TH1902, a SORT1 docetaxel peptide-drug conjugate, inhibits tumor growth of human cancer stem-like cells (CD133+) from both triple-negative breast cancers and ovarian cancers

Cancer stem cells, typically associated with CD133 expression, represent a small proportion of cells residing within most tumors and which have high metastatic potential and enhanced drug resistance. In cancer indications such as triple negative breast and ovarian cancers, CSC have also been shown to be involved in vasculogenic mimicry. The study examined the efficacy of TH1902 against cancer stem-like cells and its ability to circumvent some of the known drug resistance phenotypes associated with CSCs. Results included:

The proprietary peptide TH19P01 – Uptake of TH19P01 was exhibited in both cancer stem-like cell lines, but was inhibited by either sortilin ligands or gene silencing, suggesting that the peptide is highly targeted to sortilin expression which is absent in healthy cells.

In vitro – TH1902 induced a marked increase in cell apoptosis – In contrast to docetaxel alone, not only did TH1902 induce cell apoptosis but also produced cell cycle arrest but did not affect healthy tissue.

In vitro — TH1902 bypasses the P-gp efflux pump – Where P-gp inhibitors can restore cell cycle arrest induced by docetaxel, TH1902 was unaffected.

In vivo — triple negative breast and ovarian cancer models – TH1902 significantly inhibited growth of cancer stem-like cell tumor when administered weekly for 3 cycles at a dose equivalent to the MTD of docetaxel and TH1902 treated mice exhibited an increased tolerability when compared to those treated with docetaxel alone.

TH1902 demonstrated better efficacy at doses equivalent to docetaxel – As a single agent in breast and ovarian cancer stem-like cell xenograft tumor models, TH1902 showed better efficacy as compared to docetaxel alone. Better efficacy was also observed in the ovarian tumor model for the TH1902-carboplatin combination as compared to paclitaxel- or docetaxel-carboplatin combinations.

An 80% decrease in tumor growth was observed in TH1902 treated models while tumor volumes diminished about 35% in docetaxel mouse models – The results demonstrated that TH1902 exerts superior anticancer activity as compared to docetaxel alone in CD133+ triple negative breast and ovarian cancer stem-like cell animal models.

AACR Poster #1076 – The peptide-drug conjugate TH1902 inhibits growth of subcutaneous melanoma xenografts and formation of lung metastases in a syngeneic mouse model

Highlights of the study demonstrated Theratechnologies’ proprietary peptide-drug conjugate, TH1902, demonstrated better and sustained efficacy in melanoma subcutaneous xenograft models at doses equivalent to the MTD of docetaxel. Mice treated with TH1902 showed prolonged survival by up to 263%, whereas docetaxel alone increased survival by only 19%.

In a lung B16-F10 metastasis model, different regimens of TH1902 significantly reduced the number of lung metastatic nodules when compared to docetaxel alone.

AACR Poster #1079 – Anti-cancer efficacy of TH1902, a SORT1 docetaxel peptide-drug conjugate, against ovarian and endometrial cancers xenografts alone or in combination with carboplatin

Highlights of the poster detailed efficacy of TH1902 against SORT1+ ovarian (ES-2, SKOV-3. A-2780) and endometrial (AN3-CA) tumor models. In vitro, TH1902 enabled a more than twofold increase in apoptosis (cell death) as compared to docetaxel alone. In vivo xenograft tumor models, mice treated with TH1902 over two weeks exhibited a statistically significant 78% decrease in tumor size. Highlights demonstrated TH1902 treated mice showed prolonged tumor regression as compared to mice treated with docetaxel alone.

Mice treated with TH1902 in combination with carboplatin demonstrated better efficacy than other combinations. Results indicated that TH1902 possesses an in-vivo efficacy superior to that of docetaxel against ovarian and endometrial cancers in the animals tested and that TH1902 can be safely combined with carboplatin to reach optimal inhibition of tumor growth.

All three posters will be available on our website following the conclusion of the meeting.