TH-1904 / Theratechnologies - LARVOL DELTA

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. (PubMed, Front Oncol) - "In contrast, VM was unaffected by unconjugated Doxorubicin or Doxil (liposomal Doxorubicin) up to μM concentrations. Overall, current data evidence for the first time that 1) SORT1 itself exerts a crucial role in both ES-2 and MDA-MB-231 VM, and that 2) VM in these cancer cell models can be efficiently inhibited by the peptide-drug conjugates TH1902/TH1904. These new findings also indicate that both peptide-drug conjugates, in addition to their reported cytotoxicity, could possibly inhibit VM in SORT1-positive TNBC and ovarian cancer patients."

Biomarker • Journal • Tumor microenvironment • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • CD133 • CD31 • MMP9 • SORT1

Theratechnologies Announces Fourth Quarter and Fiscal Year 2020 Financial Results (GlobeNewswire) - "In December 2020, the Company filed an IND application with the FDA for the Phase 1 first-in-human development of TH1902, its lead peptide-drug conjugate, or PDC, (docetaxel conjugate), for the treatment of various cancers. The proposed Phase 1 clinical trial design includes a dose escalation study to evaluate the safety, pharmacokinetics, maximum tolerated dose, or MTD, and preliminary anti-tumor activity of TH1902 administered once every three weeks in patients with advanced solid tumors refractory to available anti-cancer therapies; In January 2021, the Company received a 'Study May Proceed' letter from the FDA for the Phase 1 clinical trial of TH1902. The Phase 1 clinical trial is expected to be initiated in the second quarter of calendar year 2021 and is designed to identify a recommended dose for Phase 2 development; preclinical research activities are being conducted using TH1904..."

FDA event • IND • New P1 trial • Preclinical • Oncology • Solid Tumor

[VIRTUAL] Sortilin receptor-mediated novel cancer therapy: A targeted approach to inhibit vasculogenic mimicry in ovarian and breast cancers (AACR-II 2020) - "In fact, the Doxorubicin-peptide conjugate (TH1904) abolished the formation of 3D-tubular structures of ovarian cancer cells in an in vitro model, whereas unconjugated Doxorubicin or liposomal Doxorubicin (up to 20 µM) had no effect on the formation of the VM structure. Moreover, a Docetaxel-peptide conjugate (TH1902) also showed very potent in vitro activity against the formation of VM in TNBC...Targeting this receptor’s functions with peptide-drug conjugates may provide an efficient strategy to increase the binding/internalization of cancer drugs within tumor cells, thereby improving the efficacy of standard anticancer treatments. Our results indicate that peptide-drug conjugates targeting SORT1 strongly inhibit the formation of VM, a phenomenon associated with a more aggressive tumor phenotype and poor prognosis in patients with TNBC or ovarian cancer."

Breast Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • SORT1

[VIRTUAL] Increasing potency of anticancer drugs through Sortilin receptor-mediated cancer therapy: A new targeted approach for the treatment of ovarian cancer (AACR-I 2020) - "As a proof-of-concept, doxorubicin and docetaxel were conjugated to a Sortilin-binding proprietary peptide (TH19P01).Results : In vitro, significant intracellular delivery of the doxorubicin-TH19P01 conjugate (TH1904) and docetaxel-TH19P01 conjugate (TH1902) were observed in a ES-2 ovarian cancer cell line model while preserving efficient doxorubicin or docetaxel cytotoxic mechanism. TH19P01 and drug conjugate uptake in ovarian cancer cells assays were reduced when SORT1 expression was specifically silenced using siRNA or upon competition with the SORT1 ligands neurotensin and progranulin. Importantly, drug-TH19P01 conjugates were found to bypass the P-glycoprotein (P-gp) efflux pump in MDCK-MDR1 cells overexpressing P-gp as the uptake of conjugates was unaffected by the P-gp inhibitor Cyclosporin A. In vivo, TH1904 and TH1902 caused a more potent inhibition of human ovarian tumor xenografts grown in mice and were better tolerated than their unconjugated parent..."

Breast Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Theratechnologies to make oral presentation on oncology platform during AACR Virtual Annual Meeting (GlobeNewswire) - "Theratechnologies Inc...announced that it will make an oral presentation on new results from its sortilin targeting oncology platform during a virtual session of the annual meeting of the American Association for Cancer Research (AACR)....Theratechnologies intends to initiate, by the end of 2020, a phase I clinical trial with TH-1902, a conjugate of Docetaxel and TH-19P01, for the treatment of triple-negative breast cancer, followed shortly thereafter by TH-1904, a conjugate of Doxorubicin and TH-19P01, for the treatment of ovarian cancer."

New P1 trial • Preclinical • Oncology

Theratechnologies announces new positive results for two investigational peptide-drug conjugates targeting sortilin positive ovarian cancer (GlobeNewswire) - “Theratechnologies Inc…announced that new positive results about its two investigational peptide-drug conjugates (PDC) TH1902 and TH1904 will be presented tomorrow during an oral presentation at a virtual session of the Annual Meeting of the American Association for Cancer Research (AACR)…In vivo results obtained with TH1902 and TH1904 demonstrate a high accumulation of the conjugates in ovarian tumors with low accumulation in healthy ovary tissue. Compared to treatments using doxorubicin or docetaxel, two commonly used treatments for ovarian cancer, TH1902 and TH1904 were both found to have better efficacy, at equivalent dose, while not inducing weight loss nor decreasing lymphocytes, two common side effects observed with current treatments.”

Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor