IMM-1-104 strongly inhibits tumor growth in an animal model of KRAS-G12V mutant pancreatic cancer
Preclinical data package now includes animal studies showing the potential for broad activity across tumors driven by MAPK pathway mutations including: KRAS-G12C, KRAS-G12D, KRAS-G12S, KRAS-G12V, NRAS-Q61R, and BRAF-V600E
IMM-1-104 IND expected in Q3 2022; Enrollment of the first patient in Phase 1 testing expected in Q4 2022
CAMBRIDGE, Mass., May 26, 2022 (GLOBE NEWSWIRE) -- Immuneering Corporation (NASDAQ: IMRX), a biopharmaceutical company using translational bioinformatics to advance a pipeline of product candidates designed to benefit large populations of patients with cancer and other diseases, today reported data in two preclinical abstracts at the 2022 ASCO Annual Meeting highlighting the pan-KRAS/NRAS activity of IMM-1-104. “These data underscore IMM-1-104's potential to broadly target solid tumors driven by a wide variety of frequently occurring KRAS and NRAS mutations. We believe IMM-1-104 focuses this pan-KRAS/NRAS activity selectively against malignant cells through its deep cyclic inhibition mechanism, which aims to deprive cancer cells of the sustained signaling they depend on to proliferate, while providing a cadenced release of inhibition that is designed to reduce the impact on healthy cells,” said Ben Zeskind, Ph.D., MBA, chief executive officer of Immuneering Corporation. “We look forward to submitting our IND for IMM-1-104 in the third quarter of 2022 and enrolling our first patient in the Phase 1 trial in the fourth quarter of 2022.”
The abstracts reported are as follows:
Head-to-head comparison of the dual-MEK inhibitor IMM-1-104 versus sotorasib or adagrasib in KRAS mutant pancreatic tumors.Session Title: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary, publication onlyTrack: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and HepatobiliaryFirst author: Peter King, Ph.D.
In this preclinical study, Immuneering researchers tested IMM-1-104 in a head-to-head comparison versus agents including sotorasib and adagrasib, in a series of preclinical models to characterize differential activity of each compound against pancreatic tumors driven by diverse KRAS mutations. Cell-based 2D biochemical and 3D growth assays were performed across nine pancreatic ductal adenocarcinoma (PDAC) models. The Capan-2 PDAC xenograft animal model was used to evaluate single agent activity of IMM-1-104 (75, 100, 150 mg/kg BID p.o. or 150 mg/kg QD p.o.) versus sotorasib or adagrasib (30 and 100 mg/kg QD p.o. each) for 21 days of treatment after tumors had reached volumes of 150 to 200 mm3.
The head-to-head comparison in vivo demonstrated a lack of Tumor Growth Inhibition (TGI) by sotorasib and adagrasib in KRAS-G12V mutant Capan-2 PDAC tumors. In contrast, IMM-1-104 observed TGIs of 49-84% across all doses and schedules tested. Consistent with other IMM-1-104 in vivo studies, median body weight loss was no more than 3-5% at top doses.
“These preclinical findings suggest that IMM-1-104 has the potential to offer a unique advantage over current therapeutic options for pancreatic cancers driven by a broad range of KRAS mutations that occur more commonly than KRAS-G12C,” said Peter King, Ph.D., Vice President and Head of Discovery. “Our dual-MEK inhibitor has been designed to block pathway reactivation and have a short half life with the goal of achieving pan-KRAS/NRAS activity focused against malignant cells.”
Translational modeling for patients with RAS mutant tumors: Profiling the dual-MEK inhibitor IMM-1-104 in a humanized 3D assay.Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology, publication onlyTrack: Developmental Therapeutics—Molecularly Targeted Agents and Tumor BiologyFirst author: Brett Hall, Ph.D.
In this preclinical study, Immuneering researchers characterized IMM-1-104’s pharmacologic activity across 52 tumor cell lines that spanned 11 distinct tumor types in a humanized, Extracellular Matrix (ECM)-based 3D tumor growth assay (3D-TGA). Tumor models were categorized based on in vivo drug PK limits as sensitive to IMM-1-104 (EC50