– PRGN-3005 was well-tolerated with no dose
limiting toxicities, no CRS greater than Grade 2, and no
neurotoxicity –
– PRGN-3005 cells demonstrated expansion
and persistence when delivered via either intraperitoneal or
intravenous infusion without lymphodepletion or via intravenous
infusion after lymphodepletion demonstrating the effectiveness of
mbIL15 –
– A single intravenous infusion following
lymphodepletion decreased tumor burden in 67% of the heavily
pretreated patients (median of 8 or more prior therapies) with 90%
of individual target lesions showing stable disease or partial
response –
– PRGN-3005 UltraCAR-T cells are being
evaluated in the Phase 1b dose
expansion study with intravenous infusion following lymphodepletion
and incorporating repeat infusion –
– Best responder
achieved stable disease for more than 18 months after failing 9
prior lines of treatment; results achieved with two doses of
UltraCAR-T cells in the low millions –
GERMANTOWN, Md., June 5, 2023
/PRNewswire/ -- Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical
company specializing in the development of innovative gene and cell
therapies to improve the lives of patients, today presented
positive data at the 2023 American Society of Clinical Oncology
(ASCO) Annual Meeting from the Phase 1 portion of the Phase
1/1b clinical study evaluating safety
and efficacy of PRGN-3005 UltraCAR-T® in advanced stage
platinum resistant ovarian cancer patients (Abstract# 5590). The
presentation was delivered by John B.
Liao, MD, PhD, Cancer Vaccine Institute, University of Washington Medicine, and a lead
investigator for the PRGN-3005 clinical trial.
"We are pleased with the results of the Phase 1 study which
demonstrate a favorable safety profile for PRGN-3005 UltraCAR-T.
Our UltraCAR-T therapies continue to be well-tolerated with no dose
limiting toxicities across our clinical stage UltraCAR-T
portfolio," said Helen Sabzevari,
PhD, President and CEO of Precigen. "At this early stage, we are
encouraged that patients in the IV plus lymphodepletion arm showed
stable or partial response in 90% of the individual target lesions,
and that the case study presented demonstrated that the repeat
dosing further decreased tumor burden. UltraCAR-T is the only CAR-T
platform that has demonstrated the ability to expand and persist
and show a reduction in tumor burden and lesions with low doses of
UltraCAR-T cells in this heavily pretreated ovarian cancer patient
population. We are currently underway in the Phase 1b dose expansion study at Dose Level 3 via IV
infusion with lymphodepletion and incorporating repeat dosing."
"Ovarian cancer symptoms are not always obvious and it is
frequently diagnosed at an advanced stage where cancer has spread
to distant parts of the body, which results in historically poor
outcomes," said Mary L. (Nora)
Disis, MD, faculty member at the University of Washington and Fred Hutchinson Cancer
Research Center and one of the lead investigators for the PRGN-3005
study. "The patients enrolled were heavily pretreated with a median
of 8 or more prior lines of therapy and had significantly advanced
stage disease with a high baseline tumor burden and distant
metastases. PRGN-3005 resulted in a decrease in tumor burden in 67%
of patients who received just one IV infusion following
lymphodepletion. We are encouraged by the expansion, persistence
and activity of the UltraCAR-T cells manufactured using the
overnight process in this heavily pre-treated population of the
patients, and in view of the favorable safety profile and
preliminary activity, we are looking forward to utilizing PRGN-3005
cells in patients with fewer prior lines of therapy for their
disease."
PRGN-3005 UltraCAR-T is an autologous chimeric antigen receptor
T (CAR-T) cell therapy manufactured using non-viral gene delivery
and is under investigation for the treatment of patients with
advanced, recurrent platinum resistant ovarian, fallopian tube or
primary peritoneal cancer.
PRGN-3005 utilizes Precigen's transformative UltraCAR-T
therapeutic platform, which eliminates ex vivo expansion and
reduces manufacturing time to allow for rapid next day
administration of UltraCAR-T cells following non-viral gene
transfer. PRGN-3005 UltraCAR-T is a multigenic CAR-T cell
investigational therapy utilizing Precigen's advanced non-viral
gene delivery system to co-express a chimeric antigen receptor,
membrane-bound interleukin‐15 (mbIL15), and a kill switch for
better precision and control.
Conducted in collaboration with the University of Washington and Fred Hutchinson Cancer
Research Center, the Phase 1 study has completed dose escalation,
which evaluated the safety and efficacy of PRGN-3005 administered
either via intraperitoneal (IP) or intravenous (IV) infusion, in
the absence of lymphodepletion (LD) or IV following lymphodepletion
with cyclophosphamide only (clinical trial identifier:
NCT03907527).
Patient Demographics
The study population includes
patients with advanced stage (III/IV) recurrent ovarian, fallopian
tube, and primary peritoneal cancer who are platinum resistant and
have progressed after receiving standard-of-care therapies or are
not eligible to receive available therapies with known clinical
benefit (Table 1). The mean age of patients in the study was 57.4
in the IP arm without lymphodepletion, 67.3 in the IV arm without
lymphodepletion and 62.7 in the IV arm with lymphodepletion.
Patients were heavily pretreated with a median of greater than or
equal to 8 prior lines of therapy across all arms. Patients had
significantly advanced stage disease with a high baseline tumor
burden with most patients having distant metastases, including
liver, spleen, bladder and lung.
Table 1: Phase 1 Dose Escalation Patient Demographics
|
IP
(N=12)
|
IV
(N=6)
|
IV with
LD
(N=9)
|
Age
(years)
|
|
|
|
|
Mean, Median
|
57.4, 59.5
|
67.3, 69.5
|
62.7, 64
|
|
Range
|
38-70
|
54-76
|
47-77
|
ECOG
Status
|
|
|
|
|
0
|
4
(33.3 %)
|
3
(50 %)
|
5
(55.6 %)
|
|
1
|
8
(66.7 %)
|
3
(50 %)
|
4
(44.4 %)
|
Baseline Tumor
Burden (mm)
|
|
|
|
|
Mean, Median
|
71.2, 54.3
|
61.6, 46
|
97.1, 109.5
|
|
Range
|
15.2- 142.8
|
33.7 -145.7
|
44.5 - 149.8
|
Baseline CA
125
|
|
|
|
|
Mean, Median
|
1845.2,
1208.5
|
789.2, 199.5
|
539.3, 486
|
|
Range
|
82-8148
|
42-3035
|
60-1301
|
Prior lines of
therapy
|
|
|
|
Mean, median
(range)
|
8.2, 8.5
(5-11)
|
7.7, 8
(4-10)
|
7.7, 8
(5-11)
|
|
4-5
|
2
(16.7 %)
|
1
(16.7 %)
|
2
(22.2 %)
|
|
6-11
|
10
(83.3 %)
|
5
(83.3 %)
|
7
(77.8 %)
|
Safety Data
PRGN-3005 was well-tolerated with low
incidence of treatment related adverse events (TRAEs), no dose
limiting toxicities (DLTs), and no neurotoxicity (Table 2). The
most common side effects for the IV and IP arms without
lymphodepletion were abdominal pain, fever and decreased absolute
lymphocyte count (ALC). Serious Adverse Events included five
incidences of Cytokine Release Syndrome (CRS), with no incidence of
CRS greater than Grade 2. One patient with CRS required specific
intervention which resolved following standard CRS management after
24 hours. There was no use of tocilizumab or dexamethasone or kill
switch.
Table 2: PRGN-3005 Treatment Related Adverse Events
|
IP
(N=12)
|
IV
(N=6)
|
IV with
LD
(N=9)
|
|
# of
Events
|
Patients
(n, %)
|
# of
Events
|
Patients
(n, %)
|
# of
Event
|
Patients
(n, %)
|
Abdominal
Pain
|
7
|
1 (8 %)
|
0
|
0
|
0
|
0
|
Cytokine Release
Syndrome
|
0
|
0
|
1
|
1
(17 %)
|
5
|
5
(56 %)
|
Grade 1 CRS
|
0
|
0
|
1
|
1 / 1
|
4
|
4 / 5
|
Grade 2 CRS
|
0
|
0
|
0
|
0 / 1
|
1
|
1 / 5
|
Fever
|
1
|
1 (8 %)
|
1
|
1
(17 %)
|
2
|
2
(22 %)
|
Hypotension
|
0
|
0
|
0
|
0
|
1
|
1
(11 %)
|
ALC,
Decreased
|
6
|
2
(17 %)
|
12
|
2
(33 %)
|
0
|
0
|
Nausea
|
0
|
0
|
0
|
0
|
1
|
1
(11 %)
|
Small Intestinal
Obstruction
|
1
|
1 (8 %)
|
0
|
0
|
0
|
0
|
White Blood Cell
Decreased
|
0
|
0
|
1
|
1
(17 %)
|
1
|
1
(11 %)
|
Summary of Events of
Interest
|
DLTs
|
0
|
0
|
0
|
0
|
0
|
0
|
Serious Adverse
Events
|
6
|
5
(41 %)
|
2
|
1
(17 %)
|
4
|
4
(44 %)
|
Neurotoxicity
|
0
|
0
|
0
|
0
|
0
|
0
|
|
|
|
|
|
|
|
|
Clinical Activity
Expansion Kinetics
PRGN-3005 administered either
intraperitoneally or intravenously at doses as low as 2 million
CAR-T cells resulted in a dose-dependent expansion and encouraging
persistence in peripheral blood.
Tumor Responses
Best responses in patients treated
without lymphodepletion were stable disease with complete responses
in individual target lesions. Incorporating lymphodepletion prior
to IV infusion led to an encouraging efficacy signal as
demonstrated by a decrease in tumor burden in 67% (6/9) of patients
(Figure 1), with concurrent decreases in CA125 at Day 35 in 89%
(8/9) of patients and stable or partial response in 90% of the
individual target lesions (Figure 2).
Figure 1: Target Tumor Burden
Figure 2: CA125 Levels and Target Lesion Response in the IV
Administration with Lymphodepletion Arm
Case Study
The best response was observed in a 73 year
old female patient who was heavily pretreated with more than 9
prior lines of therapy. The patient received two infusions of
PRGN-3005, one year apart. The first infusion of 2 million
UltraCAR-T cells was administered via IV without lymphodepletion,
after which the patient had durable stable disease for about 1
year. Subsequent to the increase in tumor burden, UltraCAR-T cells
in the blood also expanded. The patient also received a second
infusion of cells this time following lymphodepletion and
demonstrated a 28% decrease in tumor burden. After the second
infusion there was a significant increase in MUC16-specific T-cell
activity and ongoing survival for more than 18 months (Figures 3,
4).
Figure 3: Repeat Dosing and Tumor Response for Best
Responder
Figure 4: Expansion and Tumor Burden/Sum of Lesions for Best
Responder
PRGN-3005 UltraCAR-T cells are currently being evaluated in the
Phase 1b dose expansion study at Dose
Level 3 via IV infusion with lymphodepletion and incorporating
repeat dosing.
About Ovarian Cancer
Worldwide, nearly 300,000 women
are diagnosed with ovarian cancer every year1 with
approximately 22,000 of them in the US2. Since early
ovarian cancer is often without obvious symptoms, the disease is
frequently diagnosed at an advanced stage where cancer has spread
to distant parts of the body, such as the liver or
lungs2,3. Five-year survival rates depend on stage and
type of ovarian cancer with rates decreasing for advanced stage
cancers that have spread to distant parts of the body3.
Precigen: Advancing Medicine with
Precision™
Precigen (Nasdaq: PGEN) is a dedicated
discovery and clinical stage biopharmaceutical company advancing
the next generation of gene and cell therapies using precision
technology to target the most urgent and intractable diseases in
our core therapeutic areas of immuno-oncology, autoimmune
disorders, and infectious diseases. Our technologies enable us to
find innovative solutions for affordable biotherapeutics in a
controlled manner. Precigen operates as an innovation engine
progressing a preclinical and clinical pipeline of
well-differentiated therapies toward clinical proof-of-concept and
commercialization. For more information about Precigen, visit
www.precigen.com or follow us on Twitter @Precigen,
LinkedIn or YouTube.
UltraCAR-T®
UltraCAR-T is a multigenic
autologous CAR-T platform that utilizes Precigen's advanced
non-viral Sleeping Beauty system to simultaneously express an
antigen-specific CAR to specifically target tumor cells, mbIL15 for
enhanced in vivo expansion and persistence, and a kill switch to
conditionally eliminate CAR-T cells for a potentially improved
safety profile. Precigen has advanced the UltraCAR-T platform to
address the inhibitory tumor microenvironment by incorporating a
novel mechanism for intrinsic checkpoint blockade without the need
for complex and expensive gene editing techniques. UltraCAR-T
investigational therapies are manufactured via Precigen's overnight
manufacturing process using the proprietary
UltraPorator® electroporation system at the medical
center and administered to patients only one day following gene
transfer. The overnight UltraCAR-T manufacturing process does not
use viral vectors and does not require ex vivo activation and
expansion of T cells, potentially addressing major limitations of
current T cell therapies.
UltraCAR-T® Clinical Program
The UltraCAR-T
platform has shifted the autologous CAR-T manufacturing paradigm
using an advanced non-viral multigene delivery system and an
overnight, decentralized manufacturing process for administration
of autologous CAR-T cells one day after gene transfer to reduce
vein-to-vein time. Precigen's UltraCAR-T platform is currently
under clinical investigation for hematological and solid tumors,
including a Phase 1/1b study of
PRGN-3005 UltraCAR-T in patients with advanced, recurrent platinum
resistant ovarian, fallopian tube or primary peritoneal cancer
(NCT03907527), a Phase 1/1b study of
PRGN-3006 UltraCAR-T in patients with relapsed or refractory acute
myeloid leukemia (AML) or higher risk myelodysplastic syndrome
(MDS) (NCT03927261) and a Phase 1/1b study of PRGN-3007 UltraCAR-T incorporating
PD-1 checkpoint inhibition in patients with ROR1-positive
(ROR1+) hematologic chronic lymphocytic leukemia (CLL),
mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL),
diffuse large B-cell lymphoma (DLBCL) and solid tumor triple
negative breast cancer (TNBC) malignancies (NCT05694364). PRGN-3006
UltraCAR-T has been granted Orphan Drug Designation and Fast
Track Designation in patients with AML by the US Food and Drug
Administration (FDA).
UltraCAR-T® Library
Approach
Precigen's UltraCAR-T library approach is designed
to transform the personalized cell therapy landscape for cancer
patients. Precigen's goal is to develop and validate a library of
non-viral plasmids to target tumor-associated antigens. Enabled by
design and manufacturing advantages of UltraCAR-T, coupled with the
capabilities of the UltraPorator® system, Precigen
is working to empower cancer centers to deliver personalized,
autologous UltraCAR-T treatment with overnight manufacturing to any
cancer patient. Based on the patient's cancer indication and
biomarker profile, one or more non-viral plasmids would be selected
from the library to build a personalized UltraCAR-T treatment.
After initial treatment, this approach has the potential to allow
for redosing of UltraCAR-T targeting the same or new
tumor-associated antigen(s) based on the treatment response and the
changes in antigen expression of the patient's tumor. Precigen
believes that the combination of the advanced
UltraVector® DNA construction platform and the ease
of overnight manufacturing gives this library approach a
proprietary advantage over traditional T-cell therapies.
UltraPorator®
The UltraPorator system is an
exclusive device and proprietary software solution for the scale-up
of rapid and cost-effective manufacturing of UltraCAR-T therapies
and potentially represents a major advancement over current
electroporation devices by significantly reducing the processing
time and contamination risk. The UltraPorator device is a
high-throughput, semi-closed electroporation system for modifying T
cells using Precigen's proprietary non-viral gene transfer
technology. UltraPorator is being utilized for clinical
manufacturing of Precigen's investigational UltraCAR-T therapies in
compliance with current good manufacturing practices.
Trademarks
Precigen, UltraCAR-T, UltraVector,
UltraPorator, and Advancing Medicine with Precision are trademarks
of Precigen and/or its affiliates. Other names may be
trademarks of their respective owners.
Cautionary Statement Regarding Forward-Looking
Statements
Some of the statements made in this press release
are forward-looking statements. These forward-looking statements
are based upon the Company's current expectations and projections
about future events and generally relate to plans, objectives, and
expectations for the development of the Company's business,
including the timing and progress of preclinical studies, clinical
trials, discovery programs and related milestones, the promise of
the Company's portfolio of therapies, and in particular its CAR-T
and AdenoVerse therapies. Although management believes that the
plans and objectives reflected in or suggested by these
forward-looking statements are reasonable, all forward-looking
statements involve risks and uncertainties, including the
possibility that the timeline for the Company's clinical trials
might be impacted by the COVID-19 pandemic, and actual future
results may be materially different from the plans, objectives and
expectations expressed in this press release. The Company has no
obligation to provide any updates to these forward-looking
statements even if its expectations change. All forward-looking
statements are expressly qualified in their entirety by this
cautionary statement. For further information on potential risks
and uncertainties, and other important factors, any of which could
cause the Company's actual results to differ from those contained
in the forward-looking statements, see the section entitled "Risk
Factors" in the Company's most recent Annual Report on Form 10-K
and subsequent reports filed with the Securities and Exchange
Commission.
References
1World Health Organization,
International Agency for Research on Cancer, Global Cancer
Observatory. Cancer Today, Estimated number of new cases in 2018.
Accessed via WHO IARC GCO website.
2American Cancer Society Ovarian Cancer Special Section.
Accessed via ACS website.
3American Cancer Society. Survival Rates for Ovarian
Cancer. Accessed via ACS website.
Investor Contact:
Steven M.
Harasym
Vice President, Investor Relations
Tel: +1 (301) 556-9850
investors@precigen.com
Media Contacts:
Donelle M.
Gregory
press@precigen.com
Glenn Silver
Lazar-FINN Partners
glenn.silver@finnpartners.com
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