zavondemstat (TACH101) / Tachyon - LARVOL DELTA

Phase 1 study of zavondemstat (TACH101), a first-in-class KDM4 inhibitor, in patients with advanced solid tumors: Results on safety, pharmacokinetics, and anti-tumor activity. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT05076552 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • P1 data • PK/PD data • Oncology • Solid Tumor

Histone methylation changes of H3K9 and H3K36 in PBMCs as pharmacodynamic biomarkers for Zavondemstat (TACH101), a pan-inhibitor of KDM4 histone lysine demethylase (EORTC-NCI-AACR 2024) - P1 | "Zavondemstat is the only inhibitor of KDM4 histone demethylase in clinical development. Modifications in histone methylation at H3K9 and H3K36 in PBMCs may serve as pharmacodynamic biomarkers for zavondemstat activity in conjunction with clinical safety and efficacy assessments. The ongoing Phase 1 trial (NCT05076552) will further investigate these changes in patient samples."

Biomarker • Epigenetic controller • PK/PD data • Oncology

A Phase 1 dose escalation study of zavondemstat (TACH101), a first-in-class KDM4 inhibitor for advanced solid tumors (ESMO 2024) - No abstract available

Metastases • P1 data • Oncology • Solid Tumor

A Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral TACH101 in Participants With Advanced or Metastatic Cancer (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Tachyon Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | N=70 ➔ 30

Enrollment change • Enrollment closed • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI

A Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral TACH101 in Participants With Advanced or Metastatic Cancer (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Tachyon Therapeutics, Inc. | Phase classification: P1a/1b ➔ P1

Metastases • Phase classification • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI

A Phase 1 dose escalation study of TACH101, a first-in-class KDM4 inhibitor for advanced solid tumors. (AACR-NCI-EORTC 2023) - No abstract available

Metastases • P1 data • Oncology • Solid Tumor

TACH101, a first-in-class pan-inhibitor of KDM4 histone demethylase. (PubMed, Anticancer Drugs) - "A reduction in the population of tumor-initiating cells was observed following TACH101 treatment. Overall, these observations demonstrate the broad applicability of TACH101 as a potential anticancer agent and support its advancement into clinical trials."

Epigenetic controller • Journal • Hematological Disorders • Hematological Malignancies • Oncology • Pancreatic Cancer • DRD

Tachyon Receives Funding from CIRM for a Phase 1 Clinical Study of TACH101, a First-in-Class KDM4 Inhibitor, in Patients with Advanced Solid Tumors (Businesswire) - "Tachyon Therapeutics, Inc...announced that the California Institute for Regenerative Medicine (CIRM) has awarded the company a $7.1 million grant to support a Phase 1 clinical study of TACH101 in patients with advanced solid tumors, with an expansion phase planned for gastrointestinal cancers, including microsatellite instability high (MSI-H) colorectal cancer (CRC)."

Financing • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor

Tachyon Announces Financing and Start of Clinical Study of First-in-Class KDM4 Inhibitor for Advanced Cancers (Businesswire) - "Tachyon Therapeutics...announced the closing of a financing that brings the Company’s total equity financing raises to $11.6 million and, together with a recently announced CIRM grant of $7.1 million, brings total funding in the Company to $18.7 million since the Company started operations in 2020....Proceeds from the financing are being used to run the Phase 1 clinical study in advanced solid tumors for TACH101, a first-in-class, small molecule, KDM4 histone demethylase inhibitor, as well as to advance the Company’s pipeline of emerging oncology drug candidates targeting previously unexplored mechanisms of tumorigenesis....The Company recently received clearance of the Company’s Investigational New Drug (IND) application for TACH101 and enrolled its first patient in a Phase 1 clinical study in patients with advanced or metastatic solid tumors (ClinicalTrials.gov Identifier NCT05076552)."

Financing • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor

A Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral TACH101 in Participants With Advanced or Metastatic Cancer (clinicaltrials.gov) - P1a/1b | N=70 | Recruiting | Sponsor: Tachyon Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2024 ➔ Jul 2025 | Trial primary completion date: Jul 2023 ➔ Jul 2025

Enrollment open • Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI

A Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral TACH101 in Participants With Advanced or Metastatic Cancer (clinicaltrials.gov) - P1a/1b | N=70 | Not yet recruiting | Sponsor: Tachyon Therapeutics, Inc. | Phase classification: P1 ➔ P1a/1b | Trial primary completion date: Nov 2023 ➔ Jul 2023

Metastases • Phase classification • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI

Tachyon Receives IND Clearance from FDA to Develop Novel KDM4 Inhibitor TACH101 for Advanced Solid Tumors (Businesswire) - "Tachyon Therapeutics...announced that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application to develop TACH101 for the treatment of advanced solid tumors....The first-in-human clinical study of TACH101 is expected to commence in Q4 2022 and will include a Phase 1a open-label, single-arm, dose escalation portion to evaluate the safety and tolerability of orally administered TACH101 in subjects with advanced and metastatic solid tumors."

IND • New P1 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Inhibition of cancer stem cells with TACH101, a first-in-class inhibitor of KDM4 histone lysine demethylase. (ASCO 2022) - "TACH101 inhibited proliferation of and tumor initiation by CSCs. As therapy resistance and metastatic dissemination are grave consequences of CSC activity, TACH101 provides a novel approach to eradicating this population and shows broad applicability as a potential therapeutic agent. Preparations to advance TACH101 into clinical trials are underway."

Cancer stem cells • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • CD44

TACH101, a first-in-class inhibitor of KDM4 histone lysine demethylase for the treatment of diffuse large B-cell lymphoma (AACR 2022) - "The KDM4 inhibitor, TACH101, had compelling activity in preclinical DLBCL models, suggesting that TACH101 could be an effective therapy for DLBCL. Preparations to advance the drug into clinical trials are underway."

Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • LY9

Tachyon Presents Preclinical Data on the Company’s Novel KDM4 inhibitor, TACH101, at the 2022 AACR Annual Meeting (Businesswire) - "Tachyon Therapeutics...shared preclinical data for TACH101, the Company’s first-in-class KDM4 inhibitor, at the American Association for Cancer Research ('AACR') Annual Meeting 2022. TACH101 is an investigational agent for the potential treatment of adult patients with diffuse large B-cell lymphoma (DLBCL)....TACH101 demonstrated favorable pharmacologic and ADME profile without significant off-target activity and low probability of drug-drug interactions."

Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

TACH101, a first-in-class pan-inhibitor of KDM4 for treatment of gastrointestinal cancers. (ASCO-GI 2022) - "Preclinical work on TACH101 KDM4 inhibitor demonstrates compelling data and applicability as a potential therapy for gastrointestinal cancers. Preparations to advance TACH101 into clinical trials are underway."

Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI

Tachyon Presents New Data Supporting the Development of TACH101, a Novel KDM4 Inhibitor, as a Potential Therapy for Gastrointestinal Cancers at the 2022 ASCO-GI Conference (Businesswire) - "Tachyon Therapeutics...announced the presentation of data from its TACH101 program in a virtual poster presentation at the American Society of Clinical Oncology Gastrointestinal Cancer Symposium being held from January 20-22, 2022. The data demonstrate the potent anti-cancer activity of TACH101, a first-in-class small molecule inhibitor of KDM4 histone demethylase, in preclinical models of gastrointestinal (GI) cancers....The Company plans to initiate a first-in-human Phase 1 clinical trial in the first half of 2022."

New P1 trial • Preclinical • Gastrointestinal Cancer • Oncology • Solid Tumor

Tachyon Presents TACH101 Data at the 2021 AACR-NCI-EORTC Conference (Businesswire) - "Tachyon Therapeutics...announces the presentation of data from its TACH101 program in a virtual poster presentation at the AACR-NCI-EORTC International Conference On Molecular Targets and Cancer Therapeutics being held virtually from October 7-10, 2021. The data showed potent inhibition of gene expression by TACH101 and an increased sensitivity of TACH101 in colorectal cancer, especially those harboring microsatellite instability high (MSI-H) signature....TACH101 treatment caused 86% repression of PNUTS mRNA, as well as a 51% increase in H3K9me3 (a mark of repressed transcription); a 78% decrease in H3K36me3 at the PNUTS gene was also observed."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology

A Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral TACH101 in Participants With Advanced or Metastatic Cancer (clinicaltrials.gov) - P1; N=70; Not yet recruiting; Sponsor: Tachyon Therapeutics, Inc.

Clinical • New P1 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI

[VIRTUAL] Identification of pharmacodynamic and sensitivity biomarkers for TACH101, a pan- inhibitor of KDM4 histone lysine demethylase (AACR-NCI-EORTC 2021) - No abstract available

Biomarker • PK/PD data • Oncology

[VIRTUAL] TACH101, a first-in-class KDM4 inhibitor for treatment of triple-negative breast cancer (ESMO 2021) - "Extensive preclinical work on TACH101 KDM4 inhibitor indicates compelling data and applicability as a potential therapy for TNBC. The preparations to advance the drug into clinical trials are underway."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • TNS1

Tachyon Announces Presentation at the 2021 ESMO Annual Meeting (Businesswire) - "Tachyon Therapeutics, Inc...announces an abstract presentation of the Company’s lead product candidate, TACH101, at the European Society of Medical Oncology ('ESMO') Annual Meeting....TACH101 was potent in killing a Triple Negative Breast Cancer (TNBC) cell line (MDA-MB-231) with an IC50 of 0.0035 µM; Gene expression analysis of TACH101-treated tumors show that Protein Phosphatase 1 Regulatory subunit 10 (PPP1R10 or PNUTS), a key regulator of the retinoblastoma protein (Rb) and p53, was a direct target of KDM4 and was significant downregulated after 24 hours of treatment."

Preclinical • Breast Cancer • Oncology • Triple Negative Breast Cancer

[VIRTUAL] Pharmacologic characterization of TACH101, a first-in-class KDM4 inhibitor for development as a cancer therapeutic. (ASCO 2021) - "TACH101 is a potent KDM4 specific inhibitor without significant off-target activity in in vitro and in vivo studies . It did not show inhibition or induction of CYP enzymes suggesting low probability of CYP mediated drug-drug interaction . The exposure from oral administration in rats and dogs was dose proportional and was not significantly affected by food intake in dogs ."

Oncology

[VIRTUAL] Inhibition of histone lysine demethylases with TACH101, a first-in-class pan-inhibitor of KDM4. (ASCO 2021) - "Extensive preclinical work on TACH101 KDM4 inhibitor shows compelling data and broad applicability as a potential anti-cancer agent . Further evaluation is ongoing to advance the molecule into clinical trials."

Breast Cancer • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD44 • MSI

Tachyon Announces Presentations at the ASCO Annual Meeting (Businesswire) - "Data presented at ASCO show favorable pharmacologic properties for TACH101, compelling efficacy data in animal models, and broad applicability as a potential anti-cancer agent. We look forward to advancing this molecule into first-in-human trials later this year.”"

New trial • Preclinical • Oncology