Company to host
conference call today, May 2, at 8:30 am
EDT / 2:30 pm CEST
- Update covers data from 11 heavily
pre-treated, last-line patients in Phase 1b dose expansion Cohort A
treated with IMA203 TCR-T monotherapy against PRAME
- Objective response rate (ORR): 64%
(7/11) initial ORR at week 6 and 67% (6/9) confirmed ORR at month
3
- Median duration of response not
reached at median follow-up time of 8.5 months at data cut-off
- Objective responses independent of
solid tumor type at low, medium and high PRAME expression levels in
checkpoint-refractory cutaneous melanoma, platinum-resistant
ovarian cancer, uveal melanoma, head and neck cancer and synovial
sarcoma
- Cohort A IMA203 monotherapy TCR-T
treatment continues to show manageable tolerability with no
high-grade CRS and no ICANS; no dose dependent increase of CRS
observed
- Proprietary rapid manufacturing
process with 7 days of manufacturing time; manufacturing success
rate of 94% to reach current recommended Phase 2 dose
- Next data update and pathway towards
registration-directed trials planned to be set out in 4Q 2023
- Company well capitalized with cash
position1 of $386m at YE 2022 and reach into 2025 to leverage
multi-cancer PRAME opportunity
Houston, Texas and
Tuebingen, Germany, May 2, 2023 –
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 an
interim clinical data update for 11 patients with recurrent and/or
refractory solid cancers treated with ACTengine® IMA203 TCR-T
monotherapy in the ongoing Phase 1b dose expansion Cohort A. IMA203
TCR-T cells are directed against an HLA-A*02-presented peptide
derived from PRAME, a broadly expressed solid cancer target with
clinical proof-of-concept for IMA203 demonstrated by Immatics in
2022. Overall, IMA203 showed a high rate of deep and durable
objective responses, with a confirmed objective response rate of
67% (6/9), across multiple tumor types, including two confirmed
partial responses (cPR) ongoing at more than 9 months after
treatment and three additional partial responses ongoing at data
cut-off. IMA203 monotherapy continues to be well tolerated in
heavily pre-treated patients at doses of up to approximately 9
billion CD8+ TCR-T cells. No high-grade cytokine release syndrome
(CRS) and no immune effector cell associated neurotoxicity syndrome
(ICANS) were observed in Cohort A at data cut-off.
The data will be presented by Martin Wermke, MD,
Professor at the University Hospital Dresden and Coordinating
Investigator of the ACTengine® IMA203 TCR-T trial during a
conference call today, May 2, at 8:30 am EDT / 2:30 pm CEST.
“The treatment of solid cancer patients who have
exhausted all available standard of care options remains a
significant challenge. These patients typically show fast
progressing disease with very poor prognosis,” said Martin Wermke,
MD, Coordinating Investigator of the ACTengine® IMA203 TCR-T trial.
“It is therefore very encouraging to see that IMA203 is able to
provide durable, clinically relevant responses in a variety of
solid cancer patients.”
“Today marks a significant step in our efforts
towards bringing our ACTengine® IMA203 monotherapy to patients with
solid tumors, as we present for the first time longer-term clinical
data demonstrating deep and durable responses, some of them ongoing
beyond 9 months after treatment,” commented Cedrik Britten, MD,
Chief Medical Officer at Immatics. “Furthermore, we show that these
responses are agnostic of tumor type and that ACTengine® IMA203
achieved objective responses at widely differing PRAME expression
levels. These data further increase our confidence in the success
and broad potential of targeting PRAME, and our product candidate
IMA203. We continue executing and anticipate announcing a potential
fast-to-market pathway for the first 1-2 indications by the end of
the year.”
Safety data for IMA203 TCR-T monotherapy
in Phase 1b Cohort A: Treatment with
IMA203 monotherapy continues to show manageable tolerability at
doses as high as ~9x109 TCR-T cells.
- At data cut-off on April 4, 2023,
11 PRAME-positive patients were infused with IMA203 TCR-T cells at
dose level (DL) 4 or DL5 with a mean total infused dose of 3.67x109
TCR-T cells (range 1.30-8.84x109 TCR-T cells).
- Based on data review of 6 patients
in the exploratory highest DL5, this DL was cleared by the DSMB
(Data and Safety Monitoring Board) for safety, and the updated
provisional recommended Phase 2 dose (RP2D) now includes DL4 and
DL5. The final RP2D will be defined prior to starting Phase 2.
- Most frequent treatment-emergent
adverse events (TEAEs) were as expected for cell therapies.
- All 11 patients experienced
expected cytopenia (Grade 1-4) associated with lymphodepletion. 10
patients (91%) had a low to moderate (Grade 1-2) cytokine release
syndrome (CRS), of which 5 patients (45%) had Grade 1, and 5
patients (45%) had Grade 2 CRS. No high-grade (Grade 3 or higher)
CRS and no immune effector cell associated neurotoxicity syndrome
(ICANS) were observed in any of these 11 patients. No
dose-dependent increase of CRS was observed across Phase 1a and
Phase 1b Cohort A (N=38 patients infused with IMA203 in
total).
- No additional dose limiting
toxicities (DLT) were observed in Cohort A since the initial Phase
1a dose escalation.
Clinical activity for IMA203 TCR-T
monotherapy in Phase 1b Cohort A: IMA203
monotherapy demonstrates a high rate of deep objective responses
with ongoing durability of more than 9 months after treatment in
some patients.
- At data cut-off on April 4, 2023,
11 patients were infused with IMA203 TCR-T cells and evaluable for
at least one tumor response assessment post treatment.
- Objective responses were observed
in last-line solid cancer patients including cutaneous melanoma,
ovarian cancer, uveal melanoma, head and neck cancer, synovial
sarcoma.
- Patients were heavily pre-treated
with a mean of ~4 lines of prior systemic treatments and had
exhausted all available standard of care treatments.
- All cutaneous melanoma patients
were checkpoint inhibitor-refractory, all ovarian cancer patients
were platinum-resistant.
- Initial objective response rate
(ORR) of 64% (7/11) was observed at ~week 6 (partial responses, PR,
according to RECIST 1.1).
- Confirmed ORR of 67% (6/9) was
observed at ~month 3; initial responses at week 6 were confirmed
for all 6 responders with available subsequent 3-month scan.
- Median duration of response2 was
not reached (min 1.3+ months, max 8.8+ months) at a median
follow-up3 of 8.5 months.
- At data cut-off, 5 of 7 responses
remain ongoing:
- 2 cPRs (cut. & uveal melanoma)
ongoing at 9+ months
- 1 cPR (cut. melanoma) ongoing at 6+
months
- 1 cPR (ovarian cancer) ongoing at
~3 months
- 1 PR (synovial sarcoma) ongoing at
6+ weeks
- Objective responses were observed
in patients independent of tumor type at all PRAME expression
levels above Immatics’ mass spectrometry-guided RNA threshold
including expression levels at or just above this threshold.
- IMA203 T cells were found in all
evaluable tumor tissues and the level of tumor infiltration was
associated with objective responses.
Best Overall Response – Phase 1b Cohort A
1 Ovarian cancer patient A-DL5-04 erroneously received one dose
of nivolumab and is part of intent-to-treat population (shown here)
but not per-protocol population; NET: Neuroendocrine Tumor; PD:
Progressive disease; SD: Stable disease; PR: Partial response; cPR:
Confirmed partial response; BL: Baseline; BOR: Best Overall
Response
Response over Time – Phase 1b Cohort A
Manufacturing of IMA203 TCR-T cells
- Immatics’ proprietary manufacturing
process has a manufacturing time of 7 days (+7-day expedited
release testing), with a success rate of 94% in achieving the
provisional RP2D.
- Manufacturing improvements
(including monocyte depletion) and higher applied cell doses
implemented for the Phase 1b part of the trial led to significantly
increased levels of IMA203 T cells in the blood of patients in
Phase 1b Cohort A compared to patients in the Phase 1a dose
escalation.
- Immatics is currently building a
state-of-the-art facility designed to manufacture ACTengine® IMA203
TCR-T products, as well as other cell therapy candidates, for
registration-directed trials and initial commercial supply. Built
with flexibility and cost-efficiency in mind, the facility is
designed to be scalable via a modular design to accommodate
manufacturing demands. The facility is expected to be operational
in 2024.
Development strategy to realize the
multi-cancer opportunity PRAME
Immatics believes, the results presented today
further validate PRAME as one of the most promising solid tumor
targets for TCR-based therapies. Immatics’ IMA203 development
strategy is based on two pillars aimed initially at a (1)
fast-to-market approach and, later at a (2) broad development.
The first objective is to deliver the
PRAME-targeted TCR-T cell therapy in 1-2 last-line solid cancer
types as fast as possible with a focus on indications with PRAME
prevalence above 80% and where clinical proof-of-concept has been
demonstrated, such as cutaneous melanoma (potentially bundled with
uveal melanoma) and/or ovarian cancer. The buildout of the
manufacturing facility will support Immatics’ efforts to maximize
speed to market. Immatics plans to start a first Phase 2 trial in
1H 2024, which is intended to be designed as a
registration-directed trial.
As a second step, Immatics plans to also expand
development to other cancer types, such as uterine cancer, lung
cancer, breast cancer, head and neck cancer and other tumor types
having a broad patient reach.
An update on all three IMA203 Phase 1b Cohorts
and clinical development path for PRAME TCR-T monotherapy towards
registration-directed trials and potential commercialization is
planned for 4Q 2023.
In addition to ACTengine® TCR-T, Immatics is
addressing PRAME-positive cancers with a second therapeutic
modality, TCR Bispecifics (TCER®), to leverage the full potential
of the multi-cancer opportunity PRAME. Immatics’ TCER® IMA402 is a
next-generation, half-life extended TCR Bispecific for which
Immatics submitted a clinical trial application (CTA4) to the
Paul-Ehrlich-Institute (PEI) on April 14, 2023, to initiate the
Phase 1/2 trial. The trial is expected to commence in 2H 2023 with
first clinical data planned in 2024.
Both approaches, ACTengine® and TCER®, are
distinct therapeutic modalities that have the potential to provide
innovative treatment options for a variety of cancer patient
populations with different medical needs. Immatics will continue to
evaluate which of these therapeutic modalities (ACTengine® vs.
TCER® or both) is best suited for each cancer type.
Immatics conference call
Immatics will host a conference call today, May 2nd, 2023, at 8:30
am EDT / 2:30 pm CEST to discuss the clinical data. The webcast and
presentation can be accessed directly through this link.
Participants may also access the slides presented in the webcast on
the Immatics website in the Investors section under “Presentations”
at www.investors.immatics.com/events-presentations. A replay of the
webcast will be made available shortly after the conclusion of the
call and archived on Immatics website for at least 90 days.
About IMA203 and target
PRAMEACTengine® IMA203 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 program’s
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 for its TCR-based cell therapy
approach, ACTengine® IMA203.
ACTengine® IMA203 TCR-T is currently being
evaluated in three ongoing Phase 1b dose expansion cohorts in
last-line patients: Cohort A IMA203 TCR-T monotherapy, Cohort B
IMA203 in combination with an immune checkpoint inhibitor; Cohort B
is focused on generating safety data for potential further
investigation of a combination approach as a front-line therapy,
and Cohort C IMA203CD8 TCR-T monotherapy, where IMA203 engineered T
cells are co-transduced with a CD8αβ co-receptor. IMA203CD8 is
currently being explored in DL4a (up to 0.8x109 TCR-T cells/m2
BSA).
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. The ACTengine® Programs are
co-funded by the Cancer Prevention and Research Institute of Texas
(CPRIT).
- 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.
Immatics intends to use its website
www.immatics.com as a means of disclosing material non-public
information. For regular updates you can also follow us on Twitter,
Instagram 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 press release 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 |
Eva Mulder or Charlotte Spitz |
|
Trophic Communications |
|
Phone: +31 65 2331 579 |
|
immatics@trophic.eu |
|
Immatics N.V. |
|
Anja Heuer |
Jordan Silverstein |
Senior Director, Corporate Communications |
Head of Strategy |
Phone: +49 89 540415-606 |
Phone: +1 281 810 7545 |
media@immatics.com |
InvestorRelations@immatics.com |
1 Cash position includes cash and cash equivalents as well as
other financial assets and was €362.2 million as of December 31,
2022 ($386.3 million using the exchange rate published by the
European Central Bank in effect as of December 31, 2022 (1 EUR =
1,0666 USD).2 Duration of response (DOR) in confirmed responders is
defined as time from first documented response until disease
progression/death. Patients with ongoing response will be censored
at date of data cut-off. Median DOR is analyzed by using the
Kaplan-Meier method.3 Median follow-up is analyzed by using the
reverse Kaplan-Meier method.4 Clinical Trial Application (CTA) is
the European equivalent of an Investigational New Drug (IND)
application.
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