TScan Therapeutics, Lyell, SQZ Biotech and others secured clearance from the U.S. Food and Drug Administration for their Investigational New Drug Application.
TScan Therapeutics secured clearance from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug Application to assess TSC-100 in treating patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation (HCT).
Waltham, Mass.-based TScan said the target of TSC-100 is the minor histocompatibility antigen HA-1. That is a “lineage-specific” antigen found on blood cells. The first patient in a multi-arm Phase I study is expected to be dosed in the first half of this year. The trial will evaluate TSC-100 compared to standard-of-care in patients undergoing allogeneic HCT. The company is currently securing locations for its initial study sites.
“FDA clearance of our TSC-100 IND is significant as it allows us to move forward with the umbrella clinical protocol for our hematologic cancer study,” Gavin MacBeath, Ph.D., chief scientific officer of TSCan said in a statement. “This is a great accomplishment for our organization and validation of our TCR discovery platform.”
At the same time the company received the go-ahead to begin clinical studies on TSC-100, the FDA placed a clinical hold on the IND for TSC-101. TSC-101 is targeted to the lineage-specific blood cell antigen HA-2, which, according to the company, is a novel target for cell therapy. The hold is pending an additional risk assessment related to off-tumor reactivity for TSC-101. No timeline was provided for the potential lifting of the hold. TScan said it would work with the regulatory agency to resolve its questions as quickly as possible.
TScan was not the only company this morning to announce clearance to begin a Phase I study.
APS Takes RET Inhibitor into the Clinic
Applied Pharmaceutical Science, Inc. (APS) secured a nod from the FDA to begin clinical studies of its next-generation selective RET inhibitor, APS03118. The China-based company intends to aim the asset at multiple cancer types.
Preclinical data compiled by APS showed that APS03118 is highly selective for RET kinases. Compared to the current first-generation RET inhibitors, APS said APS03118 showed significant nanomolar level potent antitumor activity in inhibition to various RET fusion and mutations, including RET gatekeeper V804M/L/E and solvent frontier G810R/S/C mutations. In a brain tumor model tested on mice, APS03118 completely eliminated brain tumors and all animals survived after dosing. APS said this demonstrated the therapeutic advantages of APS03118 for patients with brain metastases.
APS intends to initiate Phase I studies in the second quarter of 2022.
Tango Therapeutics Guides MTAP Deletion-Aimed Drug into the Clinic
Cambridge, Mass.-based Tango Therapeutics said the FDA cleared the IND for its lead program, TNG908. Tango’s TNG908 is a synthetic lethal small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5). The drug candidate is designed to selectively kill cancer cells with a methylthioadenosine phosphorylase (MTAP) deletion, occurring in 10–15% of all human cancers. Tango highlighted several cancer types that exhibit the MTAP deletion, including non-small cell lung cancer, mesothelioma, pancreatic cancer and cholangiocarcinoma.
Tango expects to initiate a Phase I/II study of TNG908 in the first half of this year. According to the company, preliminary safety and efficacy data are expected in the first half of 2023. Enrollment in the trial will be limited to patients with confirmed MTAP-deleted tumors.
According to Tango, preclinical data showed that TNG908 demonstrated strong selectivity for MTAP-deleted tumors with robust anti-tumor effects in vitro and in vivo.
SQZ Biotech Secures IND for mRNA-Based Cell Therapy
SQZ Biotech will take SQZ-eAPC-HPV into a Phase I/II study after securing IND clearance from the FDA. The Watertown, Mass.-based company will initiate its COMMANDER-001 trial of SQZ-eAPC-HPV in patients with HPV16+ solid tumors, including head and neck, cervical, and anal cancers, and have progressed following standard therapies.
According to SQZ, SQZ-eAPC-HPV was developed by delivering five different mRNAs into a patient’s monocytes, B cells, T cells and NK cells. The company engineered four cell types with five functions in a single step.
In preclinical models, SQZ said its eAPCs had generated robust CD8 T cell responses against multiple antigens, including HPV16 proteins.
Ranok Therapeutics’ RNK05047 Cleared for Phase I/II Study
Ranok Therapeutics received IND clearance from the FDA for RNK05047, a novel treatment for advanced solid tumors and lymphomas. The company anticipates enrollment in a Phase I/II study in the first half of 2022.
RNK05047 is a first-in-class, small-molecule, BRD4-selective protein degrader that was discovered and developed using Ranok’s proprietary approach to targeted protein degradation, CHAMP (Chaperone-mediated Protein Degradation).
Lyell Immunopharma Takes TCR Therapy into the Clinic with GSK
Bay Area-based Lyell received clearance from the FDA to initiate a Phase I study of LYL132, an investigational T-cell receptor (TCR) therapy for patients with solid tumors expressing New York esophageal squamous cell carcinoma 1 (NY-ESO-1). The company is conducting the study in collaboration with GlaxoSmithKline.
Lyell said LYL132 incorporates Epi-R, the company’s epigenetic reprogramming technology. It is under investigation as a potential next-generation enhancement to letetresgene autoleucel (lete-cel), a GSK TCR therapy targeting NY-ESO-1, in pivotal clinical development.
The planned Phase I trial will assess LYL132 in patients with NY-ESO-1+ advanced synovial sarcoma or myxoid/round cell liposarcoma.
