TP-1454 / Sumitomo Pharma - LARVOL DELTA

Phase 1 Study of Oral TP-1454 (clinicaltrials.gov) - P1 | N=31 | Completed | Sponsor: Sumitomo Pharma America, Inc. | Active, not recruiting ➔ Completed

Trial completion • Anal Carcinoma • Oncology • Solid Tumor • CD4

Phase 1 Study of Oral TP-1454 (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: Sumitomo Pharma America, Inc. | Trial completion date: Oct 2024 ➔ May 2025 | Trial primary completion date: Oct 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Anal Carcinoma • Oncology • Solid Tumor • CD4

Targeting pyruvate kinase M2 for the treatment of kidney disease. (PubMed, Front Pharmacol) - "Interestingly, PKM2 activators (TEPP-46, DASA-58, mitapivat, and TP-1454) and PKM2 inhibitors (shikonin, alkannin, compound 3k and compound 3h) have exhibited potential therapeutic property in kidney disease, which indicates the pleiotropic effects of PKM2 in kidney. In the future, the deep investigation of PKM2 pleiotropic effects in kidney is urgently needed to determine the therapeutic effect of PKM2 activator/inhibitor to benefit patients. The information in this review highlights that PKM2 functions as a potential biomarker and therapeutic target for kidney diseases."

Journal • Review • Acute Kidney Injury • Diabetic Nephropathy • Nephrology • Renal Disease • PKM

Phase 1 Study of Oral TP-1454 (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: Sumitomo Pharma America, Inc. | Recruiting ➔ Active, not recruiting | N=50 ➔ 31 | Trial completion date: Dec 2025 ➔ Oct 2024 | Trial primary completion date: Sep 2025 ➔ Oct 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Anal Carcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4

Phase 1 Study of Oral TP-1454 (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Sumitomo Pharma Oncology, Inc. | Active, not recruiting ➔ Recruiting | Trial completion date: Oct 2023 ➔ Dec 2025 | Trial primary completion date: Apr 2023 ➔ Sep 2025

Enrollment open • Trial completion date • Trial primary completion date • Anal Carcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4

The PKM2 activator and molecular glue TP-1454 modulates tumor-immune responses by destabilizing T-regulatory cells (AACR-NCI-EORTC 2022) - P1 | "These findings suggest a novel mechanism to regulate the TME with a PKM2 activator in preclinical models and should be investigated further in clinical trials."

Oncology • CD4 • FOXP3

[VIRTUAL] Pkm2 activation modulates the tumor-immune microenvironment and enhances response to checkpoint inhibitors in preclinical solid tumor models (AACR 2021) - P1 | "We are currently exploring the effect of TP-1454 treatment on O-GlcNac of Foxp3 and its stability in HEK293 cells, to support the link between PKM2 activation and stabilization of Foxp3.TP-1454 effects on tumor-specific immunity were validated using tumor rechallenge studies. The results of a tumor rechallenge study will be presented using murine MC38 or RENCA xenograft models that are treated with TP-1454 and I/O combination therapies that exhibited a complete response (CR) and were re-implanted.These preclinical studies indicate a unique mechanism modulating tumor metabolism and the TME to improve the response of cancer patients to immunotherapy."

Checkpoint inhibition • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4 • FOXP3

Phase 1 Study of Oral TP-1454 (clinicaltrials.gov) - P1 | N=44 | Active, not recruiting | Sponsor: Sumitomo Pharma Oncology, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • EGFR • MSI • PD-L1

Phase 1 Study of Oral TP-1454 (clinicaltrials.gov) - P1; N=44; Recruiting; Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; Trial completion date: Dec 2022 ➔ Oct 2023; Trial primary completion date: Nov 2022 ➔ Apr 2023

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • EGFR • MSI • PD-L1

Sumitomo Dainippon Pharma Oncology Presents New Data from Investigational Pipeline of Novel Cancer Therapeutics at AACR Virtual Annual Meeting I 2021 (PRNewswire) - "Sumitomo Dainippon Pharma Oncology, Inc...presented new findings on a range of investigational agents from the company's pipeline at the American Association for Cancer Research (AACR) Virtual Annual Meeting I, taking place April 10-15, 2021. The data presented at the meeting include preclinical and Phase 1 clinical data evaluating the potential anti-cancer activity of the PKM2 activator TP-1454, PIM inhibitor TP-3654, TNK1 inhibitor TP-5809 and CDK9 inhibitor alvocidib."

P1 data • Preclinical • Hodgkin Lymphoma • Lymphoma • Oncology • Solid Tumor

Phase 1 Study of Oral TP-1454 (clinicaltrials.gov) - P1; N=44; Recruiting; Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Oncology • Solid Tumor

Sumitomo Dainippon Pharma Oncology Announces First Patient Dosed with TP-1454 in Patients with Advanced Solid Tumors (PRNewswire) - “Sumitomo Dainippon Pharma Oncology, Inc…announced that the first patient has been dosed with TP-1454, an investigational small-molecule pyruvate kinase M2 isoform (PKM2) activator, administered alone and in combination with ipilimumab and nivolumab, in a Phase 1/1b study in patients with advanced metastatic or progressive solid tumors.”

Trial status • Oncology • Solid Tumor

Tolero Pharmaceuticals submits Investigational New Drug Application for experimental PKM2 activator TP-1454 (PRNewswire) - "Tolero Pharmaceuticals, Inc…announced the submission of an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for its investigational small-molecule pyruvate kinase M2 isoform (PKM2) activator, TP-1454. Under this IND, Tolero intends to conduct a Phase 1/1b, first-in-human, open-label, dose‑escalation, safety, pharmacokinetic and pharmacodynamic study, which will evaluate oral TP‑1454 alone, and in combination with ipilimumab and nivolumab, in patients with advanced metastatic or progressive solid tumors."

IND • New P1 trial • Oncology • Solid Tumor

PKM2 activation suppresses cellular ROS scavenging capacity and potentiates doxorubicin antitumor activity (EORTC-NCI-AACR 2017) - "Studies investigating TP-1454-induced glutathione suppression in combination with doxorubicin, in vivo, are currently under way. Taken together, these data support the hypothesis that PKM2 activators may combine well with anthracycline drugs and warrant clinical investigation of PKM2 as a potential therapeutic target for the treatment of multiple cancer types."

Oncology

"#ToleroPharmaceuticals Submits Investigational New Drug Application for Experimental #PKM2Activator #TP1454 https://t.co/XaFps7qf5i" (@1stOncology)

IND

[VIRTUAL] Effect of TP-1454, a PKM2 activator, on the tumor-immune microenvironment in preclinical models as a development path in combination with IO agents. (ASCO 2020) - No abstract available

Combination therapy • Preclinical

Phase 1 Study of Oral TP-1454 (clinicaltrials.gov) - P1; N=44; Not yet recruiting; Sponsor: Tolero Pharmaceuticals, Inc.

Clinical • Combination therapy • New P1 trial • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-1

Tolero Pharmaceuticals presents findings from preclinical studies evaluating investigational agents TP-1287 in prostate cancer models and TP-1454 in colorectal cancer models (PRNewswire) - "Data from a preclinical prostate cancer model, showed TP-1287 as monotherapy and in combination with venetoclax or docetaxel enhanced tumor growth inhibition. Additionally, TP-1287 combined with docetaxel alone showed tumor growth inhibition...In a separate preclinical colorectal cancer model, TP-1454 in combination with anti-PD1 and anti-CTLA4 therapies showed tumor regression, tumor growth inhibition and an acceptable safety profile."

Preclinical