Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage T-cell
reprogramming company dedicated to developing curative cell
therapies for patients with solid tumors, is presenting preclinical
data at the 37th Annual Meeting of the Society for Immunotherapy of
Cancer (SITC) on its product candidates and new genetic and
epigenetic reprogramming technologies. This includes new
preclinical research on the potential to generate more potent T
cells to provide durable anti-tumor functions against certain
aggressive solid tumor cancers.
“Our SITC presentations showcase compelling
preclinical data underlying our lead TIL product candidate, LYL845,
as well as the exciting progress Lyell’s research team is making to
advance our understanding of how to counter T-cell exhaustion and
generate T cells with properties of durable stemness,” said Gary
Lee, Ph.D., chief scientific officer at Lyell. “We are applying
this research to grow our pipeline by creating new stackable
reprogramming technologies as we continue to work toward our
mission of developing adoptive T-cell therapies that deliver
consistent, reliable and durable responses in solid tumors.”
Preclinical Data on LYL845
Two presentations on Friday, Nov. 11 highlight
preclinical data on LYL845, Lyell’s tumor-infiltrating lymphocyte
(TIL) product candidate being evaluated for safety, tolerability
and anti-tumor activity in a first-in-human Phase 1 clinical trial
(NCT05573035). (Abstract Nos. 370 and 340).
The first presentation, titled “The
Epi-R™ technology produces a polyclonal TIL product (LYL845)
with a greater expansion success rate across hot and cold tumors,
improved product phenotype, and maintenance of TCR diversity,”
showcases the ability of Epi-R technology to successfully expand
TIL across three tumor types as compared to the standard (control)
process. In this study, expanding TIL with Epi-R technology
resulted in 100 percent success rate vs. 70 percent with control,
including tumor samples collected from checkpoint inhibitor
experienced melanoma patients. The study also includes colorectal
tumor samples which have been considered more challenging to expand
with standard processes. Further, in this study Epi-R technology
yielded a product (LYL845) with a greater proportion of CD8+
T-cells and enriched for T-cells with stem-like profiles, better
metabolic fitness, and preserved polyclonality compared to control
TIL. These qualities have been linked with anti-tumor functionality
and improved outcomes in previous TIL clinical trials.
The second presentation, titled “The Epi-R
technology produces a polyclonal TIL product (LYL845) with diverse
tumor-reactive clones that have stem-like qualities and anti-tumor
function,” highlights bioinformatic analyses demonstrating that
LYL845 products expanded using Epi-R technology were highly
polyclonal and retained putative tumor reactive clones with
increased stemness and reduced exhaustion-associated genes compared
to TIL products derived from the standard process. Moreover,
tumor-specific reactivities of LYL845 were confirmed, and
anti-tumor functions, including dose-dependent cytolytic activities
and cytokine secretion, in tumor cell specific co-culture assays
were demonstrated.
Stackable Genetic and Epigenetic
Reprogramming Technologies in LYL119, a Second-Generation CAR
T-cell therapy targeting ROR1+ solid tumors
Two presentations describe preclinical data on
Lyell’s new, stackable reprogramming technologies – NR4A3 knockout
and Stim-R™ – being incorporated in LYL119, a second-generation
ROR1 targeting CAR T-cell product candidate.
An abstract titled “NR4A3 gene editing and c-Jun
overexpression synergize to limit exhaustion and enhance functional
activity of ROR1 CAR T cells in vitro and in vivo” being presented
on Thursday, Nov. 10 demonstrates that the combination of two
genetic reprogramming technologies, NR4A3 gene knockout and c-Jun
overexpression, enhances the functional activity of ROR1 CAR T
cells. This is demonstrated by higher levels of cytokine
production, increased CAR T-cell persistence and reduced surface
expression of inhibitory receptors after repetitive antigen
stimulation, as well as significant improvement in tumor control in
vivo (Abstract No. 243). NR4A3 and c-Jun both function within the
activator protein 1 (AP-1) transcription factor pathway, which
plays a key role in regulating T-cell function. This new research
furthers the hypothesis that reprogramming of AP-1 transcription
factor pathway in T cells may delay exhaustion and improve
anti-tumor function. Lyell plans to incorporate these two stackable
genetic reprogramming technologies in its new product candidate,
LYL119, currently in preclinical development.
An abstract titled “Engineering potent CAR
T-cell therapies by controlling T-cell activation signaling
parameters using the Stim-R™ technology, a programmable synthetic
cell-signaling platform” being presented on Friday, Nov. 11
describes Stim-R, Lyell’s new epigenetic reprogramming technology.
Stim-R is a synthetic cell mimic that mediates precise signal
molecule presentation to generate arrays of diverse ROR1-targeted
CAR T-cell products (Abstract No. 252). This research demonstrates
that Stim-R generates potent CAR T-cell products with increased
polyfunctionality, persistence, anti-tumor activity, and reduced
exhaustion following repeated antigen stimulation in vitro. These
cells also showed greater CAR T-cell proliferation and persistence
in vivo, as well as improved tumor control. Lyell also plans to
incorporate this technology in LYL119.
About Lyell Immunopharma,
Inc.
Lyell is a clinical-stage T-cell reprogramming
company dedicated to developing curative cell therapies for
patients with solid tumors. The Company is advancing a pipeline of
therapies designed to address what it believes are the primary
barriers that limit consistent, reliable and curative responses to
adoptive T-cell therapy: T cell exhaustion and lack of durable
stemness, which includes the ability to proliferate, persist and
self-renew, as well as generate differentiated effector cell
progenies to provide durable anti-tumor functionality. Lyell is
applying its proprietary ex vivo genetic and epigenetic
reprogramming technologies to address these barriers in order to
develop new medicines with improved, durable and potentially
curative clinical outcomes. Lyell is based in South San Francisco,
California with facilities in Seattle and Bothell, Washington. To
learn more, please visit www.lyell.com.
Forward Looking Statements
This press release contains forward-looking
statements within the meaning of the Private Securities Litigation
Reform Act of 1995. Forward-looking statements expressed or implied
in this press release include, but are not limited to, statements
regarding: Lyell’s anticipated progress, business plans, business
strategy, planned research and clinical trials and plans to present
at SITC; the growing pipeline of T-cell reprogramming technologies
and product candidates and the potential clinical benefits and
therapeutic potential of such product candidates; Lyell’s plans to
apply its research to grow its pipeline and its mission to develop
adoptive T-cell therapies that deliver consistent, reliable and
durable responses in solid tumors; the potential of Lyell’s
reprogramming technologies to overcome primary barriers to
successful adoptive cell therapy in solid tumors, including the
ability for Lyell’s genetic reprogramming technologies to limit T
cell exhaustion and improve anti-tumor function and for its new
epigenetic reprogramming technology, Stim-R, to generate a more
potent T-cell product, and Lyell’s plans for such reprogramming
technologies; and other statements that are not historical fact.
These statements are based on Lyell’s current plans, objectives,
estimates, expectations and intentions, are not guarantees of
future performance and inherently involve significant risks and
uncertainties. Actual results and the timing of events could differ
materially from those anticipated in such forward-looking
statements as a result of these risks and uncertainties, which
include, but are not limited to, risks and uncertainties related
to: the effects of the COVID-19 pandemic; geopolitical instability;
macroeconomic conditions; Lyell’s ability to submit planned INDs or
initiate or progress clinical trials on the anticipated timelines,
if at all; Lyell’s lack of experience as a company in enrolling,
conducting or completing clinical trials; Lyell’s ability to
manufacture and supply its product candidates for its clinical
trials; the preclinical profiles of Lyell’s product candidates not
translating in clinical trials; the potential for results from
clinical trials to differ from preclinical, early clinical,
preliminary or expected results; significant adverse events,
toxicities or other undesirable side effects associated with
Lyell’s product candidates; the significant uncertainty associated
with Lyell’s product candidates ever receiving any regulatory
approvals; Lyell’s ability to obtain, maintain or protect
intellectual property rights related to its product candidates;
implementation of Lyell’s strategic plans for its business and
product candidates; the sufficiency of Lyell’s capital resources
and need for additional capital to achieve its goals; and other
risks, including those described under the heading “Risk Factors”
in Lyell’s most recently filed quarterly report on Form 10-Q
and subsequent filings with the Securities and Exchange Commission.
Forward-looking statements contained in this press release are made
as of this date, and Lyell undertakes no duty to update such
information except as required under applicable law.
Contact:
Ellen RoseSenior Vice President, Communications
and Investor Relationserose@lyell.com
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