Immatics Announces First Cancer Patient Treated with Second-Generation ACTengine® TCR-T Candidate IMA203CD8 Targeting PRAME
August 23 2022 - 07:00AM
GlobeNewswire Inc.
- IMA203CD8 is a 2nd-generation product candidate co-expressing
Immatics’ proprietary CD8αβ co-receptor engaging functional CD4 and
CD8 T cells directed against PRAME
- Preclinical data with IMA203CD8 showed enhanced potency and
prolonged anti-tumor activity mediated by activated TCR-engineered
CD4 T cells
- The IMA203CD8 Phase 1b expansion study is the third cohort of
Immatics' multi-cohort strategy to achieve durable high response
rates with TCR-T cells targeting PRAME-positive, hard-to-treat
solid tumors
- First three patients to be treated at dose level 3 with the
intention to advance directly to the recommended Phase 2 dose
Houston, Texas
and Tuebingen,
Germany, August
23, 2022 –
Immatics N.V. (NASDAQ: IMTX, “Immatics”), a clinical-stage
biopharmaceutical company active in the discovery and development
of T cell-redirecting cancer immunotherapies, today announced the
treatment of the first patient in its Phase 1b expansion cohort C
(NCT03686124) evaluating IMA203CD8, the company’s 2nd generation
TCR-T monotherapy approach where a proprietary CD8αβ co-receptor is
added to PRAME-specific IMA203 T cells. The CD8 co-receptor plays
an important role during T cell antigen recognition and T cell
activation, enabling the effective engagement of CD8 and CD4 T
cells in the anti-tumor response. The 2nd generation TCR-T
IMA203CD8 aims to further enhance depth and durability of
anti-tumor responses and clinical outcomes of TCR-T targeting PRAME
in patients with solid cancers. PRAME is highly prevalent across
several indications thereby supporting the program’s potential to
reach a broad patient population.
“IMA203CD8’s unique mode of action has been
validated by preclinical data presented at SITC last year, which
demonstrated sustained suppression of tumor growth in serial
killing experiments. With the initiation of the IMA203CD8 cohort,
we can now test to what extent the interplay of engineered CD8 and
CD4 T cells enhances anti-tumor activity in the clinical setting,”
said Dr. Cedrik Britten, M.D., Chief Medical Officer at Immatics.
“Today’s milestone brings us closer to our goal of achieving
long-lasting responses for a broad range of cancer patients having
solid tumors that express PRAME.”
The importance of CD4 T cells for the duration
of responses has been demonstrated by Immatics in preclinical
assays where IMA203CD8 showed enhanced potency and prolonged
anti-tumor activity compared to IMA203 alone. These findings are in
line with a growing body of literature from CD19 CAR-T cells in
hematological cancers that suggest a relevant role of engineered
CD4 T cells in maintaining durable anti-tumor responses over a long
period. Immatics’ proprietary lentiviral vector enables CD4 and CD8
T cells to be engineered with the PRAME-specific IMA203 TCR and a
CD8αβ construct. In the preclinical studies, this approach showed
functional superiority over multiple other CD8 constructs in
conjunction with the PRAME-specific IMA203 TCR. Immatics has
successfully developed a proprietary 4-in-1 vector that includes
both IMA203 TCRα and TCRβ as well as CD8α and CD8β chains while
maintaining a high transduction rate, circumventing the challenges
associated with increasing the lentiviral vector payload.
The IMA203CD8 Phase 1b dose expansion cohort is
expected to enroll up to 24 patients with different types of solid
tumors across several clinical trial sites in the U.S. and in
Germany. Following personalized manufacturing and lymphodepletion,
patients will receive a single dose of IMA203CD8. Initially, 3
patients will be treated at a dose level 3 (DL3, up to 0.48 billion
total transduced T cells per m² body surface area) before patient
treatment at the provisional recommended Phase 2 dose, DL4 (up to
1.2 billion total transduced cells per m² body surface area). The
primary objective of this Phase 1b cohort is to evaluate the safety
profile of IMA203CD8. Secondary objectives include evaluating
initial anti-tumor and biological activity.
The 2nd generation TCR-T IMA203CD8 is part of
Immatics’ strategy to realize the full clinical potential of IMA203
TCR-T targeting PRAME. This strategy includes three Phase 1b
expansion cohorts, which have all been initiated during the first
half of 2022 and build on the promising early clinical results
during the company’s Phase 1a trial. Interim data showed a 50%
objective response rate (8/16 patients) across several solid tumor
indications including melanoma, head and neck cancer, uveal
melanoma and synovial sarcoma.
- Cohort A – IMA203 as monotherapy at
the provisional, recommended Phase 2 dose (RP2D) plus exploration
of a higher dose level DL5 (up to 4.7 billion transduced CD8 T
cells per m² body surface area)
- Cohort B – IMA203 in combination
with an immune checkpoint inhibitor, Opdivo® (nivolumab)
- Cohort C – IMA203CD8, a 2nd
generation monotherapy in which IMA203 is co-transduced with a CD8
co-receptor
Each Phase 1b expansion cohort is designed to
evaluate the observed objective response rate, demonstrate
durability of response and provide the basis for entering
registration trials. The next data readout for the IMA203
monotherapy cohort at RP2D is expected during 2H 2022 and an
initial data readout for Cohort B and Cohort C is planned for
YE2022.
About
IMA203CD8 and
target PRAMEACTengine® IMA203CD8 T cells are directed
against an HLA-A*02-presented peptide derived from preferentially
expressed antigen in melanoma (PRAME), a protein frequently
expressed in a large variety of solid cancers thereby supporting
the programs’ potential to address a broad cancer patient
population. Immatics’ PRAME peptide is present at a high copy
number per tumor cell and is homogenously and specifically
expressed in tumor tissue. The peptide has been identified and
characterized by Immatics’ proprietary mass spectrometry-based
target discovery platform XPRESIDENT®. Through its proprietary TCR
discovery and engineering platform XCEPTOR®, Immatics has generated
a highly specific T cell receptor (TCR) against this target which
is engineered into CD8 and CD4 T cells alongside a proprietary
CD8αβ co-receptor for its 2nd generation TCR-based cell therapy
approach, ACTengine® IMA203CD8. In preclinical studies, Immatics’
proprietary CD8αβ construct showed functional superiority over
multiple other CD8 constructs in conjunction with the
PRAME-specific IMA203 TCR.
About
ACTengine® ACTengine® is a
personalized cell therapy approach for patients with advanced solid
tumors. The patient’s own T cells are genetically engineered to
express a novel, proprietary TCR directed against a defined cancer
target. The modified T cells are then reinfused into the patient to
attack the tumor. The approach is also known as TCR-engineered cell
therapy (TCR-T). All Immatics’ ACTengine® product candidates can be
rapidly manufactured utilizing a proprietary manufacturing process
designed to enhance T cell engraftment and persistence in vivo.
The ACTengine® T cell products are manufactured
at the Evelyn H. Griffin Stem Cell Therapeutics Research Laboratory
in collaboration with UTHealth.
- END -
About
ImmaticsImmatics combines the discovery of true
targets for cancer immunotherapies with the development of the
right T cell receptors with the goal of enabling a robust and
specific T cell response against these targets. This deep know-how
is the foundation for our pipeline of Adoptive Cell Therapies and
TCR Bispecifics as well as our partnerships with global leaders in
the pharmaceutical industry. We are committed to delivering the
power of T cells and to unlocking new avenues for patients in their
fight against cancer.
For regular updates about Immatics, visit
www.immatics.com. You can also follow us on Instagram, Twitter and
LinkedIn.
Forward-Looking
Statements:Certain statements in this press release may be
considered forward-looking statements. Forward-looking statements
generally relate to future events or Immatics’ future financial or
operating performance. For example, statements concerning the
timing of product candidates and Immatics’ focus on partnerships to
advance its strategy are forward-looking statements. In some cases,
you can identify forward-looking statements by terminology such as
“may”, “should”, “expect”, “intend”, “will”, “estimate”,
“anticipate”, “believe”, “predict”, “potential” or “continue”, or
the negatives of these terms or variations of them or similar
terminology. Such forward-looking statements are subject to risks,
uncertainties, and other factors which could cause actual results
to differ materially from those expressed or implied by such
forward looking statements. These forward-looking statements are
based upon estimates and assumptions that, while considered
reasonable by Immatics and its management, are inherently
uncertain. New risks and uncertainties may emerge from time to
time, and it is not possible to predict all risks and
uncertainties. Factors that may cause actual results to differ
materially from current expectations include, but are not limited
to, various factors beyond management's control including general
economic conditions and other risks, uncertainties and factors set
forth in filings with the SEC. Nothing in this presentation should
be regarded as a representation by any person that the
forward-looking statements set forth herein will be achieved or
that any of the contemplated results of such forward-looking
statements will be achieved. You should not place undue reliance on
forward-looking statements, which speak only as of the date they
are made. Immatics undertakes no duty to update these
forward-looking statements. All the scientific and clinical data
presented within this press release are – by definition prior to
completion of the clinical trial and a clinical study report –
preliminary in nature and subject to further quality checks
including customary source data verification.
For more information, please
contact:
Media and Investor Relations
Contact |
Jacob Verghese or Eva Mulder |
|
Trophic Communications |
|
Phone: +49 89 2070 89831 or +31 65 2331 579 |
|
immatics@trophic.eu |
|
Immatics N.V. |
|
Anja Heuer |
Jordan Silverstein |
Director, Corporate Communications |
Head of Strategy |
Phone: +49 89 540415-606 |
Phone: +1 281 810 7545 |
media@immatics.com |
InvestorRelations@immatics.com |
Immatics NV (NASDAQ:IMTX)
Historical Stock Chart
From Aug 2023 to Sep 2023
Immatics NV (NASDAQ:IMTX)
Historical Stock Chart
From Sep 2022 to Sep 2023