GERMANTOWN, Md., Nov. 4, 2021 /PRNewswire/ -- Precigen, Inc.
(Nasdaq: PGEN), a biopharmaceutical company specializing in the
development of innovative gene and cell therapies to improve the
lives of patients, announced a topline summary of the presentations
planned for today's 2021 R&D Day virtual event, which begins at
11:00 AM ET. Participants may
register and access the live webcast through Precigen's investor
relations website in the Events & Presentations section.
Today's event will showcase clinical progress for Precigen's
UltraCAR-T platform, including PRGN-3005 UltraCAR-T, PRGN-3006
UltraCAR-T, PRGN-3007 UltraCAR-T and the AdenoVerse immunotherapy
platform, including PRGN-2009 off-the-shelf (OTS) AdenoVerse
Immunotherapy, and PRGN-2012 OTS AdenoVerse Immunotherapy.
Presentations will be made by Precigen executives and clinical
trial investigators, including:
- Helen Sabzevari, PhD, President
and CEO of Precigen;
- Mary L. (Nora) Disis, MD,
University of Washington (UW) Professor
of Medicine, Director of UW Center for Translational Medicine,
Professor in the Clinical Research Division at the Fred Hutchinson
Cancer Research Center and a lead investigator for the PRGN-3005
clinical trial;
- David Sallman, MD, Assistant
Member in the Department of Malignant Hematology at the H. Lee
Moffitt Cancer Center & Research Institute and a lead
investigator for the PRGN-3006 clinical trial;
- James L. Gulley, MD, PhD, FACP,
Branch Chief and Director of the Medical Oncology Service at the
National Institutes of Health (NIH) and a lead investigator for the
PRGN-2009 clinical trial; and
- Clint T. Allen, MD, Principal
Investigator with the Section on Translational Tumor Immunology at
the NIH and a lead investigator for the PRGN-2012 clinical
trial.
"Today's R&D Day highlights the most significant clinical
data presented for the UltraCAR-T and AdenoVerse platforms to
date," said Helen Sabzevari, PhD,
President and CEO of Precigen, "and we are highly encouraged by the
initial results we are seeing across assets in both platforms. With
UltraCAR-T, initial data for PRGN-3005 and PRGN-3006 continue to
demonstrate favorable safety profiles, dose-dependent expansion,
and durable persistence. The very encouraging clinical responses in
relapsed or refractory AML patients treated with PRGN-3006 at the
two lowest dose levels in the lymphodepletion cohort, which are
administered at significantly lower doses than competing
approaches, highlight the potential of the UltraCAR-T platform. Our
AdenoVerse immunotherapy platform is equally impressive with
initial data for PRGN-2009 and PRGN-2012 showing antigen-specific
immune responses, low neutralizing antibody responses, and
favorable safety profiles highlighting the potential for repeat
administrations. Preliminary data for PRGN-2009 show encouraging
objective responses and suggest an attractive opportunity for
potential combination of PRGN-2009 with checkpoint inhibitors in
multiple HPV-associated cancers. Finally, preliminary data for
PRGN-2012 show encouraging clinical responses in RRP patients,
including a reduction in surgical interventions following PRGN-2012
treatment. We are on track to pursue potentially registrational
trials for therapeutic candidates in both the UltraCAR-T and
AdenoVerse platforms upon dose confirmation and expansion."
PRGN-3006 UltraCAR-T
- Overview: PRGN-3006 is an investigational multigenic,
autologous chimeric antigen receptor T cell (CAR-T) therapy
engineered to simultaneously express a chimeric antigen receptor
(CAR) specifically targeting CD33, membrane bound IL-15 (mbIL15),
and a kill switch. PRGN-3006 UltraCAR-T is under evaluation in a
Phase 1/1b clinical trial for the
treatment of patients with r/r AML or higher-risk myelodysplastic
syndromes (MDS). Trial subjects receive the PRGN-3006 infusion
either without prior lymphodepletion (Cohort 1) or following
lymphodepleting chemotherapy (Cohort 2). PRGN-3006 UltraCAR-T has
been granted Orphan Drug Designation in patients with AML by the US
Food and Drug Administration (US FDA).
- Enrollment: Enrollment in Dose Level 4 of the
non-lymphodepletion cohort and Dose Level 3 of the lymphodepletion
cohort of the Phase 1 dose escalation trial is ongoing
concurrently.
- Dosing: As of the July 25,
2021 data cut-off, 15 r/r AML patients were treated in the
non-lymphodepletion cohort (N=9) and the lymphodepletion cohort
(N=6). Patients were heavily pre-treated with a median of 4 (range:
1 to 6) and 3 (range: 1 to 7) prior regimens in the
non-lymphodepletion and the lymphodepletion cohorts, respectively.
Additionally, 33% and 50% of the patients had failed prior
allogeneic hematopoietic stem cell transplant (allo-HSCT) in the
non-lymphodepletion and the lymphodepletion cohorts, respectively.
Patients received a single PRGN-3006 administration at one of the
following dose levels:
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Non-lymphodepletion Cohort (Cohort
1)
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Dose Level
(DL)
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Subjects
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Dose
Range
(UltraCAR-T
Cells/kg)
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Total UltraCAR-T
Dose
Administered
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DL1
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N=3
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>3x104 to
≤1x105
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1.8 to 7.1
x106 cells
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DL2
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N=3
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>1x105 to ≤
3x105
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24 to 29
x106 cells
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|
|
|
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DL3
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N=3
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>3x105 to ≤
1x106
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34 to 50
x106 cells
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|
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Lymphodepletion
Cohort (Cohort 2)
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Dose Level
(DL)
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Subjects
|
Dose
Range
(UltraCAR-T
Cells/kg)
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Total UltraCAR-T
Dose
Administered
|
|
|
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DL1
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N=3
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>3x104 to
≤1x105
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4.4 to 10
x106 cells
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|
|
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DL2
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N=3
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>1x105 to ≤
3x105
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18 to 28
x106 cells
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- Safety data: Data from the first three dose levels in
Cohort 1 (non-lymphodepletion) and the first two dose levels in
Cohort 2 (lymphodepletion) show that PRGN-3006 was well-tolerated
with no dose-limiting toxicities (DLTs) and no neurotoxicity. Only
one transient Grade 3 cytokine release syndrome (CRS) was reported
(DL1, Cohort 1), which resolved in less than 24 hours with
tocilizumab and dexamethasone. Remaining cases of CRS were Grade 1
or 2 that either required no specific intervention or resolved
following standard CRS management.
- Clinical activity: Dose-dependent expansion and
persistence in both the non-lymphodepletion and the lymphodepletion
cohorts was observed.
-
- An ORR of 50% (3 out of 6) was reported in the lymphodepletion
cohort (Cohort 2) in patients treated at the two lowest dose
levels. This included an ORR of 33% (1 out of 3) at Dose Level 1
and 67% (2 out of 3) at Dose Level 2.
- Objective responses included one partial response (PR) in a
patient with extramedullary AML, one complete response with
incomplete hematologic recovery (CRi) which was bridged to
allo-HSCT, and one complete response with hematologic recovery
(CRh).
- Upcoming presentation: An abstract for the PRGN-3006
Phase 1 trial (Abstract# 825) titled, "Phase 1/1b Safety Study of PRGN-3006 UltraCAR-T in
Patients with Relapsed or Refractory CD33-Positive Acute Myeloid
Leukemia and Higher Risk Myelodysplastic Syndromes," was selected
for oral presentation at the 63rd ASH Annual Meeting and Exposition
on December 13, 2021 at 5:00 PM ET.
PRGN-3005 UltraCAR-T
- Overview: PRGN-3005 UltraCAR-T is an investigational
multigenic, autologous CAR-T cell therapy engineered to express a
CAR specifically targeting the unshed portion of MUC16, which is
highly expressed on ovarian tumors with limited normal tissue
expression, mbIL15, and a kill switch. PRGN-3005 UltraCAR-T is
under evaluation in a Phase 1/1b
clinical trial for the treatment of patients with advanced,
recurrent platinum resistant ovarian cancer. Trial subjects
receive PRGN-3005 either via intraperitoneal (IP) (Arm A) or
intravenous (IV) (Arm B) infusion.
- Enrollment: Doses are currently being administered
without lymphodepletion. Dose escalation in the IP arm and IV arm
is ongoing concurrently.
- Dosing: Ten heavily pretreated, advanced, platinum
resistant ovarian cancer patients with aggressive disease were
treated with a single IP infusion of PRGN-3005 without prior
lymphodepletion at one of the following dose levels:
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Dose Level
(DL)
|
Subjects
|
Dose
Range
(UltraCAR-T
Cells/kg)
|
Total UltraCAR-T
Dose
Administered
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DL1
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N=3
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>3x104 to
≤1x105
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6 to 7.6
x106 cells
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DL2
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N=3
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>1x105 to ≤
3x105
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12 to 21
x106 cells
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DL3
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N=4
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>3x105 to ≤
5x106
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33 to 321
x106 cells
|
- Manufacturing: Precigen's UltraPorator™
system has enabled escalation to higher doses, as evidenced by the
successful infusion of greater than 320 million UltraCAR-T cells,
through the decentralized UltraCAR-T manufacturing process.
- Safety data: New data continue to show a favorable
safety profile with no DLTs, no neurotoxicity, and no CRS
reported.
- Clinical activity: Data show dose-dependent expansion
and persistence in the peripheral blood for more than 3 months
after PRGN-3005 treatment without lymphodepletion, and clinical
activity as evidenced by a decrease or stabilization of total
target tumor burden at the first restaging in a majority of
patients.
- Next steps: Complete dose escalation in the IP and IV
arms and, subsequently, incorporate lymphodepletion prior to
PRGN-3005 infusion, which was cleared by the US FDA. Additionally,
based on the favorable safety profile, the potential for repeat
dosing is being evaluated.
PRGN-3007 Next Generation UltraCAR-T with Intrinsic PD-1
Inhibition
- Overview: PRGN-3007, based on the next generation of
UltraCAR-T platform, is an investigational multigenic, autologous
CAR-T cell therapy engineered to simultaneously express a CAR
targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1),
mbIL15, a kill switch, and a novel mechanism for the intrinsic
blockade of PD-1 gene expression. ROR1 is aberrantly expressed in
multiple hematological and solid tumors with minimal expression in
healthy adult tissues.
- Trial design: As recently announced, the US FDA cleared
the investigational new drug (IND) application to initiate a Phase
1/1b open-label trial designed to
evaluate the safety and efficacy of PRGN-3007 in patients with
advanced ROR1+ hematological (Arm 1) and solid (Arm 2)
tumors. The target patient population for Arm 1 includes
r/r chronic lymphocytic leukemia (CLL), r/r mantle cell
leukemia (MCL), r/r acute lymphoblastic leukemia (ALL), and
r/r diffuse large B-cell lymphoma (DLBCL). The target patient
population for Arm 2 includes locally advanced unresectable or
metastatic histologically confirmed triple negative breast cancer
(TNBC). The trial will enroll in two parts: an initial 3+3 dose
escalation in each arm followed by a dose expansion at the maximum
tolerated dose. Arm 1 and Arm 2 will enroll in parallel.
- Preclinical data: An abstract highlighting PRGN-3007
preclinical data (Abstract# 1694) titled, "Preclinical evaluation
of PRGN-3007, a non-viral, multigenic, autologous ROR1
UltraCAR-T® cell therapy with novel mechanism of
intrinsic PD-1 blockade for treatment of hematological and solid
cancers," will be presented as a poster presentation at the 63rd
ASH Annual Meeting and Exposition.
PRGN-2012 OTS AdenoVerse Immunotherapy
- Overview: PRGN-2012 is an investigational OTS AdenoVerse
immunotherapy designed to elicit immune responses directed against
cells infected with HPV 6 or HPV 11 for treatment of recurrent
respiratory papillomatosis (RRP). PRGN-2012 is currently under
evaluation in a Phase 1 clinical trial under a Cooperative Research
and Development Agreement (CRADA) with the National Cancer
Institute (NCI). The Phase 1 trial is designed to follow 3+3 dose
escalation of PRGN-2012 as an adjuvant immunotherapy following
standard-of-care surgical removal of visible papillomas in adult
patients with RRP. PRGN-2012 has been granted Orphan Drug
Designation in patients with RRP by the US FDA.
- Enrollment: Enrollment in the Phase 1 dose escalation
portion of the trial is complete and enrollment in the expansion
cohort is ongoing.
- Dosing: Six patients have been enrolled in the Phase 1
dose escalation arm at one of the following dose levels with
patients receiving four PRGN-2012 administrations (on days 1, 15,
43 and 85) via subcutaneous injection:
-
-
- Dose Level 1: 1 x 1011 viral particles (vp)/dose;
N=3
- Dose Level 2: 5 x 1011 vp/dose; N=3
- Additionally, 8 patients have been enrolled in the Phase 1
dose expansion arm to receive four PRGN-2012 administrations (on
days 1, 15, 43 and 85) at 5 x 1011 vp/dose via
subcutaneous injection.
- Baseline patient characteristics (N=14) included an average of
51 lifetime surgeries (range: 9 to > 800), and an average of 5.5
surgeries (range: 2 to 9) in the last 2 months before enrolling in
the trial.
- Safety data: Repeated administrations of PRGN-2012 were
well-tolerated with no DLTs and no treatment-related adverse events
greater than Grade 2. The lack of a significant neutralizing
antibody response over time with subsequent additional vaccinations
highlights the ability to deliver repeated administrations of
PRGN-2012, a differentiating feature of the AdenoVerse
platform.
- Clinical activity: Preliminary data from three RRP
patient case studies demonstrate very encouraging clinical activity
of PRGN-2012 with reduction or elimination in the need for surgical
interventions at the most recent follow-up, up to 12 weeks after
PRGN-2012 treatment, compared to the recent history of surgical
interventions for these patients before enrolling in the
trial.
PRGN-2009 OTS AdenoVerse Immunotherapy
- Overview: PRGN-2009 is an OTS investigational
immunotherapy utilizing the AdenoVerse platform that has been
designed to activate the immune system to recognize and target
HPV-positive solid tumors. PRGN-2009 is currently under evaluation
in a Phase 1/2 clinical trial under a CRADA with the NCI. The Phase
1 trial is evaluating safety and response of PRGN-2009 as
monotherapy (Arm A) and in combination with bintrafusp alfa (Arm B)
in previously treated patients with recurrent or metastatic
HPV-associated cancers.
- Enrollment: Enrollment in the Phase 1 monotherapy dose
escalation arm is complete and enrollment in the Phase 1
combination arm is ongoing. In addition, enrollment in the
monotherapy arm of the Phase 2 trial, which evaluates PRGN-2009 as
a neoadjuvant therapy for newly diagnosed oropharyngeal or
sinonasal squamous cell cancer patients (OPSCC) is ongoing.
- Dosing: Six patients (all with prior anti-PD-1/PD-L1
treatment) have been treated in the Phase 1 monotherapy dose
escalation arm at one of the following dose levels with patients
receiving three PRGN-2009 administrations (on days 1, 15 and 29),
followed by PRGN-2009 administration once every 4
weeks for up to 1 year:
-
-
- Dose Level 1: 1 x 1011 vp/dose; N=3
- Dose Level 2: 5 x 1011 vp/dose; N=3
- Additionally, 6 patients (all with prior anti-PD-1/PD-L1
treatment) were treated in the Phase 1 combination arm with
patients receiving three PRGN-2009 administrations (5 x
1011 vp/dose on days 1, 15 and 29) in combination with
bintrafusp alfa (1200 mg) once every 2 weeks, followed by
PRGN-2009 administration once every 4 weeks in combination
with bintrafusp alfa administrations once every 2 weeks for up
to 1 year. Five patients with at least one post-treatment scan were
evaluable for disease response.
- Safety data: Phase 1 data show that repeated
administrations of PRGN-2009 demonstrated a favorable safety
profile as monotherapy and in combination therapy with no DLTs. The
lack of a significant neutralizing antibody response over time with
subsequent additional vaccinations highlights the ability to
deliver repeated administrations of PRGN-2009.
- Clinical activity: Patient case studies show encouraging
increases in the HPV16 and/or HPV18-specific immune response with
repeated administrations of PRGN-2009.
-
- In the Phase 1 monotherapy arm, a DCR of 50% (3 out of 6 with
stable disease (SD)) at the first restaging was observed. This
includes a patient with durable (>1 year) SD who has received 16
PRGN-2009 monotherapy administrations.
- In the Phase 1 combination therapy arm, an ORR of 40% (2 out of
5) per RECIST v1.1 was observed. Objective responses included one
ongoing CR at approximately 6 months after treatment initiation and
one ongoing PR at approximately 7 months after treatment
initiation. Additionally, a DCR of 60% (3 out of 5) at first
restaging was observed.
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 unique therapies toward clinical
proof-of-concept and commercialization. For more information about
Precigen, visit www.precigen.com or follow us on Twitter @Precigen
and LinkedIn.
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.
AdenoVerse Immunotherapy
Precigen's AdenoVerse
immunotherapy platform utilizes a library of proprietary
adenovectors for the efficient gene delivery of therapeutic
effectors, immunomodulators, and vaccine antigens designed to
modulate the immune system. Precigen's gorilla adenovectors, part
of the AdenoVerse library, have potentially superior performance
characteristics as compared to current competition. AdenoVerse
immunotherapies have been shown to generate high-level and durable
antigen-specific neutralizing antibodies and effector T cell immune
responses as well as an ability to boost these antibody and T cell
responses via repeat administration. Superior performance
characteristics and high yield manufacturing of AdenoVerse vectors
combined with UltraVector® technology allows Precigen to
engineer cutting-edge investigational gene therapies to treat
complex diseases.
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, AdenoVerse,
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.
Investor
Contact:
Steven
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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SOURCE Precigen, Inc.