Immuneering Reports Data in Two Preclinical Abstracts at the ASCO 2022 Annual Meeting Highlighting Pan-KRAS/NRAS Activity of IMM-1-104
May 26 2022 - 5:26PM
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<1uM), intermediate (1uM≤EC50≤10uM and ≥25%
inhibition at 10uM), or resistant.
Models sensitive to IMM-1-104 were enriched for MAPK driver
mutations, consistent with pathway addiction. Models with a MAPK
driver mutation and compensatory mutations such as PIK3CA or PTEN
deletion were more likely to show intermediate response than those
with a greater addiction to MAPK drivers. Models lacking a clear
MAPK driver mutation but harboring other putative resistance
alterations were more likely to be resistant in the 3D-TGA.
KRAS mutant pancreatic cancer and NRAS mutant melanoma were the
most broadly sensitive patient-aligned models in the 3D-TGA and
thus will be included among the target indications for
Immuneering’s planned Phase 1/2a clinical trial.
A copy of the abstracts can be accessed at:
https://meetings.asco.org/abstracts-presentations
About Immuneering
Corporation Immuneering aims to improve patient
outcomes by advancing a unique pipeline of oncology and
neuroscience product candidates developed using its translational
bioinformatics platform. Immuneering has more than a decade of
experience applying translational bioinformatics to generate
insights into drug mechanism of action and patient treatment
response. Building on this experience, Immuneering’s
disease-agnostic discovery platform enables the company to create
product candidates based on 1) biological insights that are both
counterintuitive and deeply rooted in data, and 2) novel chemistry.
Immuneering’s lead product candidate IMM-1-104 aims to achieve
pan-KRAS/NRAS activity that selectively impacts cancer cells to a
greater extent than healthy cells. It is designed to be a highly
selective dual-MEK inhibitor that further disrupts KSR to modulate
the signaling dynamics of the MAPK pathway by driving deep cyclic
inhibition that deprives tumor cells of the sustained proliferative
signaling required for rapid growth, while providing a cadenced,
moderate level of signaling sufficient to spare healthy cells.
IMM-1-104 is being developed to treat advanced solid tumors in
patients harboring RAS mutations, and is translationally guided by
Immuneering’s proprietary, human-aligned 3D tumor modeling platform
combined with patient-aligned bioinformatics. In addition to
IMM-1-104, Immuneering is evaluating its MEK-io product candidate,
IMM-6-415, in IND-enabling studies, and has five other oncology
programs in the discovery stage that are designed to target
components of the MAPK or mTOR pathway, as well as two discovery
stage neuroscience programs.
Forward-Looking
Statements This press release includes certain
disclosures that contain "forward-looking statements," including,
without limitation, statements regarding Immuneering’s expectations
the treatment potential of IMM-1-104 and IMM-6-415, the timing of
submission of the IND and commencement of clinical trials for
IMM-1-104 and IMM-6-415, the target indications of Immuneering’s
planned Phase 1/2a trial, and Immuneering’s ability to advance its
pipeline and further diversify its portfolio and make progress
towards its longstanding goal of creating better medicines for
cancer patients. Forward-looking statements are based on
Immuneering’s current expectations and are subject to inherent
uncertainties, risks and assumptions that are difficult to predict.
Factors that could cause actual results to differ include, but are
not limited to, the risks inherent in oncology and neuroscience
drug development, including target discovery, target validation,
lead compound identification, lead compound optimization,
preclinical studies and clinical trials. These and other risks and
uncertainties are described more fully in the section titled "Risk
Factors" in Immuneering’s most recent Form 10-Q filed with the U.S.
Securities and Exchange Commission. Forward-looking statements
contained in this announcement are made as of this date, and
Immuneering undertakes no duty to update such information except as
required under applicable law.
Corporate Contact: Rebecca Kusko,
Ph.D. Immuneering
Corporation rkusko@immuneering.com 617-500-8080
Investor Contact: Susan A. NoonanS.A.
Noonan Communicationssusan@sanoonan.com917-513-5303
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