TTC-352 / TTC Oncology, Lantern Pharma - LARVOL DELTA

The ER partial agonist TTC-352 inhibits a novel epithelial-mesenchymal transition pathway, and induces DNA damage in endocrine-resistant breast cancer cells (AACR 2025) - "Our lab has previously shown a correlation between protein kinase C α (PKCα) overexpression and tamoxifen resistance (TR) (Tonetti, 2003) and further reported a novel EMT signaling in TR breast cancer cells. Combination with Olaparib enhances E2-induced DNA damage in LTED models (Traphagen, 2023). These findings suggest that TTC-352 with a PARP inhibitor may be a potential combination therapy for endocrine-resistant ER+ breast cancer."

Late-breaking abstract • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CDH1 • CTNND1 • ER • FOXC2 • TP53BP1

Impact of Estrogen Receptor Targeting Drugs on a Novel Epithelial-Mesenchymal Transition Pathway in Endocrine Resistant Breast Cancer: Implications for Metastasis (SABCS 2024) - "Currently, endocrine therapy, including tamoxifen, aromatase inhibitors (letrozole, anastrozole, and exemestane), Selective Estrogen Receptor Degraders (fulvestrant and elacestrant), is the standard of care for patients with estrogen receptor-positive (ER+) breast cancer. E2 and TTC-352 treatment lowered FOXC2 binding on the p120catenin promoter, increased its transcription, and decreased the migration of MCF-7/PKCa and MCF-7:5C breast cancer cells compared to vehicle. E2 and TTC-352 treatment does not activate the PKCa-FOXC2-p120catenin EMT signaling axis and reduces the migratory potential of TR cells. Conclusion and Our findings suggest that patients with endocrine-resistant ER+ breast cancer may benefit from E2 and TTC-352 therapy by inhibiting the activation of the PKCa-FOXC2-p120catenin signaling and cell migration identified in TR cell lines."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDH1 • CTNND1 • ER • FOXC2 • PRKCA

Phase 1 study of TTC-352 in patients with metastatic breast cancer progressing on endocrine therapy (SABCS 2019) - P1; "TTC 352 demonstrates manageable safety and early clinical evidence of antitumor activity in patients with BC progressing on endocrine therapy. Based upon SS TTC-352 plasma concentrations and tolerability, the 180mg BID dose is recommended for further testing."

Clinical • P1 data • CDK4 • CDK6

Lantern Pharma and TTC Oncology Establish AI Collaboration to Expand the Clinical Development of Drug Candidate TTC-352 (Businesswire) - "Lantern Pharma...announced that it has entered into a research and development collaboration with TTC Oncology. The collaboration will focus on leveraging RADR® AI insights to advance TTC Oncology’s first- and best-in-class drug candidate TTC-352 for recurrent ER+ breast cancer patients and additional patient populations potentially identified by RADR®.....Under the terms of the collaboration, Lantern Pharma is receiving an exclusive right to license TTC-352, including any collaboration intellectual property (IP), during an exclusive option period. Additionally, Lantern and TTC will each participate in upfront, milestone, and royalty payments in the event a third party licenses IP resulting from the collaboration. No further financial details were disclosed."

Licensing / partnership • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology

Phase I study of TTC-352 in patients with estrogen receptor-positive metastatic breast cancer (AACR 2019) - P1; "A total of 9 patients have been enrolled to date."

Clinical • P1 data

"Do you know something about TTC-352?" (@GioCap75)

Rapid Induction of the Unfolded Protein Response and Apoptosis by Estrogen Mimic TTC-352 for the Treatment of Endocrine-Resistant Breast Cancer. (PubMed, Mol Cancer Ther) - "Patients with long-term estrogen-deprived breast cancer (BC), after resistance to tamoxifen or aromatase inhibitors develops, can experience tumor regression when treated with estrogens. This study highlights TTC-352's benzothiophene scaffold that yields an H-bond with Glu353, which allows Asp351-to-helix 12 (H12) interaction; sealing ERα's ligand binding domain, recruiting E2-enriched coactivators, and triggering rapid ERα-induced unfolded protein response (UPR) and apoptosis, as the basis of its anti-cancer properties. BPTPE's phenolic OH yields an H-Bond with Thr347, which disrupts Asp351-to-H12 interaction; delaying UPR and apoptosis, and increasing clonal evolution risk."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • ER • PCR

Pharmacology and Molecular Mechanisms of Clinically-Relevant Estrogen Estetrol and Estrogen Mimic BMI-135 for Endocrine-Resistant Breast Cancer Treatment. (PubMed, Mol Pharmacol) - "Long-term estrogen deprivation (LTED) with tamoxifen (TAM) or aromatase inhibitors leads to endocrine-resistance, whereby physiologic levels of estrogen kill breast cancer (BC)...Estetrol and ShERPA TTC-352 are being evaluated in clinical trials...The naturally-occurring estrogen estetrol and Selective Human ER Partial Agonists are being evaluated in endocrine-resistant BC clinical trials. This work provides a comprehensive evaluation of their pharmacology in numerous endocrine-resistant BC models and an endometrial cancer model, and their molecular mechanisms of tumor regression through the unfolded protein response and apoptosis."

Clinical • Journal • Breast Cancer • Endometrial Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

Study of TTC-352 in Patients With Metastatic Breast Cancer Progressing on Endocrine Therapy (clinicaltrials.gov) - P1; N=15; Completed; Sponsor: TTC Oncology, LLC; Active, not recruiting ➔ Completed

Clinical • Trial completion • Breast Cancer • Gastrointestinal Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CDK4

Phase 1 study of TTC-352 in patients with metastatic breast cancer progressing on endocrine and CDK4/6 inhibitor therapy. (PubMed, Breast Cancer Res Treat) - P1 | "TTC-352 demonstrates safety and early clinical evidence of antitumor activity against heavily pretreated hormone-refractory breast cancer. Based upon TTC-352 plasma concentrations and tolerability, the 180 mg twice a day is recommended for further testing. (ClinicalTrials.gov Identifier: NCT03201913)."

Clinical • Journal • P1 data • Breast Cancer • Cardiovascular • Hormone Receptor Breast Cancer • Oncology • Pain • Pulmonary Embolism • Solid Tumor • ER

Study of TTC-352 in Patients With Metastatic Breast Cancer Progressing on Endocrine Therapy (clinicaltrials.gov) - P1; N=15; Active, not recruiting; Sponsor: TTC Oncology, LLC; Recruiting ➔ Active, not recruiting; N=36 ➔ 15

Clinical • Enrollment change • Enrollment closed