GERMANTOWN, Md., Oct. 26,
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, today announced that the US Food and Drug Administration
(FDA) has cleared the Investigational New Drug (IND) application to
initiate the Phase 1/1b clinical
trial of PRGN-3007 in advanced receptor tyrosine kinase-like orphan
receptor 1-positive (ROR1+) hematological and solid
tumors. PRGN-3007 is a first-in-class investigational therapy based
on the next generation of Precigen's UltraCAR-T® platform and
incorporates intrinsic programmed cell death protein 1 (PD-1)
blockade. This first-in-human investigator-initiated study of
PRGN–3007 will be conducted in collaboration with the H. Lee
Moffitt Cancer Center & Research Institute.
ROR1 is overexpressed in various cancers with minimal expression
in healthy adult tissues. ROR1 is aberrantly expressed in multiple
hematological tumors, including chronic lymphocytic leukemia (CLL),
mantle cell leukemia (MCL), acute lymphoblastic leukemia (ALL), and
diffuse large B-cell lymphoma (DLBCL) and solid tumors, including
breast adenocarcinomas encompassing triple negative breast cancer
(TNBC), pancreatic cancer, ovarian cancer, and lung
adenocarcinoma.
PRGN-3007 UltraCAR-T is an investigational multigenic,
autologous CAR-T cell therapy utilizing Precigen's clinically
validated advanced non-viral gene delivery system and the
well-established overnight, decentralized manufacturing process.
Precigen has further advanced the UltraCAR-T platform to address
the inhibitory tumor microenvironment by incorporating intrinsic
checkpoint blockade without the need for complex and costly gene
editing techniques. PRGN-3007 is engineered using a single
multicistronic transposon plasmid to simultaneously express a
chimeric antigen receptor (CAR) targeting ROR1, membrane-bound
interleukin–15 (mbIL15), a kill switch, and a novel mechanism for
the intrinsic blockade of PD-1 gene expression.
The PD-1/programmed death ligand 1 (PD-L1) pathway plays a vital
role in how tumor cells evade immune response. While the blockade
of the PD-1/PD-L1 pathway has demonstrated considerable benefit for
treating various cancers, the use of systemic checkpoint inhibitors
can lead to side effects associated with autoimmune response. The
innovative design of PRGN-3007, where the blockade of PD-1
expression is intrinsic and localized to UltraCAR-T cells, is aimed
at avoiding systemic toxicity and the high cost of checkpoint
inhibitors by eliminating the need for combination treatment.
The Phase 1/1b clinical trial is
an open-label study 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 relapsed or refractory CLL, relapsed or refractory
MCL, relapsed or refractory ALL, and relapsed or refractory DLBCL.
The target patient population for Arm 2 includes locally advanced
unresectable or metastatic histologically confirmed TNBC. The study
will enroll in two parts: an initial 3+3 dose escalation in each
arm followed by a dose expansion at the maximum tolerated dose
(MTD). Arm 1 and Arm 2 will enroll in parallel.
"ROR1 is an attractive target for treatment of multiple
hematological and solid tumors due to its high expression in cancer
and minimal expression in healthy adult tissues," said Javier Pinilla-Ibarz, MD, PhD, Senior Member,
Lymphoma Section Head and Director of Immunotherapy, Malignant
Hematology Department, H. Lee Moffitt Cancer Center & Research
Institute, and Principal Investigator for the PRGN-3007 clinical
study. "Preclinical studies of PRGN-3007 UltraCAR-T indicate the
potential for improved efficacy by specific targeting of ROR1
combined with intrinsic blockade of PD-1 expression and we look
forward to investigating the potential in this first-in-human
clinical study."
"ROR1 expression is thought to be a potential adverse prognostic
factor in TNBC patients," said Hatem
Soliman, MD, Medical Director of the Clinical Trials Office,
H. Lee Moffitt Cancer Center & Research Institute, and
Principal Investigator for the TNBC cohort of PRGN-3007 clinical
study. "Given the aggressive nature of TNBC and the need for
additional treatment options, we are eager to investigate PRGN-3007
in this setting."
"This is the first study of our next generation UltraCAR-T,
which adds checkpoint blockade to our non-viral, multigenic
UltraCAR-T platform," said Helen
Sabzevari, PhD, President and CEO of Precigen. "PRGN-3007
eliminates the need to combine an antigen-specific CAR-T with a
separate checkpoint inhibitor, which has the potential to avoid
systemic toxicity and reduce cost. This new study is a big step
toward our UltraCAR-T library approach, which aims to deliver
personalized autologous UltraCAR-T therapies based on
a patient's cancer indication and biomarker profile
using overnight manufacturing at the patient's medical
center."
About Receptor Tyrosine Kinase-like Orphan Receptor 1
(ROR1)
ROR1 is a type I orphan-receptor that is expressed
during embryogenesis and by certain hematological and solid tumors
but is undetectable on normal adult tissues.1-3
ROR1 plays an important role in oncogenesis by activating
cell survival signaling events, particularly the non-canonical WNT
signaling pathway.4 Aberrant expression of ROR1 is
detected in multiple hematological malignancies including
CLL5, MCL6, ALL7, and
DLBCL.8 Elevated ROR1 expression is detected in
various solid tumors, including breast adenocarcinoma encompassing
TNBC, pancreatic cancer, ovarian cancer, Ewing's sarcoma and lung
adenocarcinoma.9-14 Many human breast adenocarcinomas
express high levels of ROR1, which is not expressed by normal
breast tissue.15
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 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.
Trademarks
Precigen, UltraCAR-T 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
1 Balakrishnan, A., et al.,
Analysis of ROR1 Protein Expression in Human Cancer and Normal
Tissues. Clin Cancer Res, 2017. 23(12): p.
3061-3071.
|
2 Green, J.L., et al., ROR
receptor tyrosine kinases: orphans no more. Trends in Cell
Biology, 2008. 18(11): p. 536-544.
|
3 Rebagay, G., et al., ROR1
and ROR2 in Human Malignancies: Potentials for Targeted Therapy.
Front Oncol, 2012. 2(34).
|
4 Zhao Y, et al., Tyrosine
Kinase ROR1 as a Target for Anti-Cancer Therapies. Front.
Oncol, 2021.
|
5 Baskar, S., et al., Unique
Cell Surface Expression of Receptor Tyrosine Kinase ROR1 in Human
B-Cell Chronic Lymphocytic Leukemia. Clin Cancer Res, 2008.
14(2): p. 396-404.
|
6 Hudecek, M., et al., The
B-cell tumor–associated antigen ROR1 can be targeted with T cells
modified to express a ROR1-specific chimeric antigen receptor.
Blood, 2010. 116(22): p. 4532-4541.
|
7 Enayati H, et al.,
Expression of ROR1 Gene in Patients with Acute Lymphoblastic
Leukemia. IJBC 2019; 11(2): 57-62.
|
8 Ghaderi, A., et al., ROR1 Is
Expressed in Diffuse Large B-Cell Lymphoma (DLBCL) and a Small
Molecule Inhibitor of ROR1 (KAN0441571C) Induced Apoptosis of
Lymphoma Cells. Biomedicines, 2020. 8(6).
|
9 Zhang, S., et al., The
onco-embryonic antigen ROR1 is expressed by a variety of human
cancers. Am J Pathol, 2012. 181(6): p. 1903-10.
|
10 Zhang, S., et al., ROR1 is
expressed in human breast cancer and associated with enhanced
tumor-cell growth. PLoS One, 2012.7(3): p.
e31127.
|
11 Potratz, J., et al.,
Receptor tyrosine kinase gene expression profiles of Ewing sarcomas
reveal ROR1 as a potential therapeutic target in metastatic
disease. Mol Oncol, 2016. 10(5): p. 677-92.
|
12 Zheng, Y.Z., et al., ROR1
is a novel prognostic biomarker in patients with lung
adenocarcinoma. Sci Rep, 2016. 6: p. 36447.
|
13 Choi, M.Y., et al.,
Pre-clinical Specificity and Safety of UC-961, a First-In-Class
Monoclonal Antibody Targeting ROR1. Clin Lymphoma Myeloma
Leuk, 2015. 15 Suppl: p. S167-9.
|
14 Balakrishnan, A., et al.,
Analysis of ROR1 Protein Expression in Human Cancer and Normal
Tissues. Clin Cancer Res, 2017. 23(12): p.
3061-3071.
|
15 Zhang S. et al., ROR1 is
expressed in human breast cancer and associated with enhanced
tumor-cell growth. PLoS One, 2012, 7:e31127.
|
For more information, contact:
Investor
Contact:
|
Media
Contacts:
|
Steven
Harasym
|
Donelle M.
Gregory
|
Vice President,
Investor Relations
|
press@precigen.com
|
Tel: +1 (301)
556-9850
|
|
investors@precigen.com
|
Glenn
Silver
|
|
Lazar-FINN
Partners
|
|
glenn.silver@finnpartners.com
|
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SOURCE Precigen, Inc.