– PRGN-2009 combined with an
investigational checkpoint inhibitor resulted in a 30% ORR in
patients with heavily pre-treated HPV-associated cancers that were
naïve or resistant to checkpoint blockade with prolonged duration
of responses –
– Recurrent/metastatic HPV-associated
cancers (cervical, anal, oropharyngeal, etc.) are incurable by
current therapies –
– PRGN-2009 was safe and well-tolerated
with only Grade 1 or 2 treatment related adverse events –
– PRGN-2009 treatment induced
HPV-specific T-cell immune responses and subsequently enhanced
T-cell responses with repeat administrations without the
development of neutralizing antibodies in the majority of
patients –
GERMANTOWN, Md., June 3, 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 clinical data from the Phase 1 study of the off-the-shelf
(OTS) PRGN-2009 AdenoVerse™ immunotherapy alone and in
combination with an investigational anti-PDL1/TGF-Beta Trap
checkpoint inhibitor (bintrafusp alfa) in patients with
recurrent/metastatic (R/M) HPV-associated cancers (clinical trial
identifier: NCT04432597) at the 2023 American Society of Clinical
Oncology (ASCO) Annual Meeting (Abstract# 2628).
"Recurrent/metastatic HPV-associated cancers such as cervical,
anal, and oropharyngeal are incurable by current therapies and
there remains significant unmet need for new safe and effective
treatments. Checkpoint inhibitors alone have shown some promise,
but have not produced durable responses and many patients relapse
or become resistant," said Helen
Sabzevari, PhD, President and CEO of Precigen. "In our Phase
1 study, combining PRGN-2009 with checkpoint inhibition
demonstrated a favorable safety profile and resulted in a 30% ORR
with prolonged duration of responses in patients with heavily
pre-treated HPV-associated cancers, including those who were
checkpoint blockade resistant. We are highly encouraged by these
Phase 1 data and, as we announced on May
31, we are moving rapidly to initiate a Phase 2 study to
combine PRGN-2009 with a checkpoint inhibitor to further
investigate safety and efficacy in recurrent or metastatic cervical
cancer. This new trial is the second Phase 2 for PRGN-2009
AdenoVerse, adding to the ongoing Phase 2 in oropharyngeal squamous
cell carcinoma."
PRGN-2009 is an OTS investigational immunotherapy utilizing the
AdenoVerse platform designed to activate the immune system to
recognize and target HPV-positive (HPV+) solid tumors.
PRGN-2009 is a novel, replication-incompetent gorilla adenovirus
targeting HPV 16/18. PRGN-2009 can be administered repeatedly
leading to enhancement of T-cells without increasing neutralizing
antibodies. PRGN-2009 is under development through a Cooperative
Research and Development Agreement, or CRADA, within the Center for
Immuno-Oncology (CIO), Center for Cancer Research (CCR), National
Cancer Institute (NCI), part of the National Institutes of Health
(NIH).
The Phase 1 trial is an open label, single-center study
evaluating safety and response of PRGN-2009 as a monotherapy (Arm
A) and in combination with bintrafusp alfa (Arm B) in
previously treated adult patients with R/M HPV-associated cancers.
In the monotherapy arm, patients (N = 6) enrolled in two sequential
PRGN-2009 dose level cohorts, Dose Level 1 (1x1011
particle units (PU)) and Dose Level 2 (5x1011 PU)
delivered via subcutaneous injection. In the combination arm,
PRGN-2009 was administered at the recommended phase 2 dose (RP2D)
in combination with bintrafusp alfa.
The primary objective of the study was to evaluate safety and
RP2D of PRGN-2009 and safety of PRGN-2009 in combination with a
checkpoint inhibitor. Secondary objectives included Objective
Response Rate (ORR) (per RECIST 1.1), and progression free survival
(PFS).
Patient Characteristics
Seventeen adult patients
were enrolled in the Phase 1 study (Table 1). Patients received up
to 20 doses of PRGN-2009 for a duration of 1.8 to 17.9 months in
the monotherapy arm and 0.5 to 23.0 months in the combination arm.
The median age in both arms was 61. The median number of prior
lines of therapies in the metastatic setting was 2.5 for the
monotherapy arm and 2 for the combination arm. All patients in the
monotherapy arm (N=6) and 10 of 11 patients in the combination arm
received prior immune checkpoint blockade (ICB) therapy.
Table 1. Patient Demographics and Clinical
Characteristics
|
|
|
Monotherapy
Arm (N=6)
|
Combination
Arm (N=11)
|
Age, years
(median, range)
|
61 (43-70)
|
61 (54-80)
|
Female, n
(%)
|
6 (100)
|
3 (27)
|
Tumor types
(n,%)
Oropharyngeal
Cervical
Anal
Vaginal
|
-
3 (50.0)
2 (33.3)
1 (16.7)
|
7 (63.6)
3 (27.3)
1 (9.1)
-
|
HPV status (n,
%)
HPV16
HPV18
Other
N/A
|
3 (50)
-
2
(33.3)
1 (16.7)
|
9 (81.8)
1 (9.1)
1 (9.1)
-
|
Previous lines of
therapy in metastatic setting, median (range)
|
2.5 (2-3)
|
2 (1-4)
|
ICB exposure, n
(%)
Primary resistance
Secondary resistance
|
6 (100)
4 (66.7)
2 (33.3)
|
10 (90.9)
5 (50)
5 (50)
|
Safety Data
PRGN-2009 treatment in both
monotherapy and combination arms was safe and well-tolerated (Table
2). In both study arms, there was a low incidence of
treatment-related adverse events (TRAEs) with only Grade 1 or 2
TRAEs in the monotherapy arm. The most common TRAEs in the
monotherapy arm were injection site reactions, flu-like symptoms,
fatigue and rash. In addition to these in the combination arm,
patients also experienced Grade 1 or 2 epistaxis, headache,
keratoacanthoma, fever, decreased lymphocyte count, anemia and oral
hemorrhage. TRAEs reported in the combination arm were in line with
the safety profile reported for bintrafusp alfa and only Grade 1 or
2 TRAEs were attributable to PRGN-2009 in the combination arm.
Table 2: Safety Data
|
|
|
Monotherapy Arm
(N=6)
|
Combination Arm
(N=11)
|
Treatment-related
adverse events, n (%)
|
Grade 1-2
(all)
|
Grade 3-4
(all)
|
Grade 1-2
(≥10%)
|
Grade 3-4
(all)
|
Injection site
reactions
|
4 (66.7)
|
0
|
9 (81.8)
|
0
|
Flu-like
symptoms,
|
3 (50.0)
|
0
|
6 (54.5)
|
0
|
Fatigue
|
2 (33.3)
|
0
|
3 (27.3)
|
0
|
Rash,
maculopapular
|
1 (16.7)
|
0
|
3 (27.3)
|
0
|
Epistaxis
|
0
|
0
|
3 (27.3) *
|
0
|
Headache
|
0
|
0
|
3 (27.3)
|
0
|
Keratoacanthoma
|
0
|
0
|
3 (27.3)*
|
0
|
Fever
|
0
|
0
|
2 (18.2)
|
0
|
Lymphocyte count,
decreased
|
0
|
0
|
2 (18.2)*
|
0
|
Anemia
|
0
|
0
|
2 (18.2)*
|
0
|
Oral
hemorrhage
|
0
|
0
|
2 (18.2)*
|
0
|
Duodenal
Hemorrhage
|
0
|
0
|
0
|
2 (18.2)*†‡
|
Pharyngeal
mucositis
|
0
|
0
|
0
|
1 (9.1) *
|
|
*Attributed to
bintrafusp alfa; † both patients concurrently receiving NSAIDs; ‡ 1
patient died following refusal of standard supportive medical
management measures (blood transfusion).
|
Clinical Activity
Tumor responses were observed
in patients after treatment with PRGN-2009 in combination with
bintrafusp alfa (Arm 1B), including in ICB-resistant patients
(Table 3). PRGN-2009 combined with bintrafusp alfa resulted in a
30% ORR in patients with pretreated R/M HPV-associated cancers with
prolonged duration of responses (Table 3, Figure 1). The majority
of patients developed HPV-16 and/or HPV-18 specific immune
responses after treatment with PRGN-2009 in both monotherapy and
combination arms (Table 4) without the development of neutralizing
antibodies (Figure 2).
Table 3: Best Response by Arm
|
|
|
Monotherapy
Arm
|
Combination
Arm
|
Evaluable patients,
n
|
6
|
10
|
Best response,
n
|
|
|
CR
|
-
|
1a
|
PR
|
-
|
2c,d
|
SD
|
4b
|
1
|
PD
|
2
|
6
|
ORR, % (95%
CI)
|
-
|
30
(6.7-65.3)
|
a immune
checkpoint blockade (ICB)-resistant; b 1 SD confirmed;
c 1 PR confirmed; d 1 ICB-resistant, 1 TCR
treatment-resistant; 2 patients treated beyond progression without
delayed response; CI: confidence interval
|
Figure 1: Time to
Response and Duration of Response to Treatment
|
Table 4:
HPV-specific T-cell Immune Responses
|
|
|
Monotherapy
Arm
|
Combination
Arm
|
HPV-16, n/N
(%)
|
5/6 (83)
|
7/10 (70)
|
HPV-18, n/N
(%)
|
5/6 (83)
|
7/8 (88)
|
HPV-16 and/or HPV-18
n/N (%)
|
6/6 (100)
|
8/10 (80)
|
N: number of patients
tested
|
Figure 2:
Neutralizing Antibodies
|
Phase 2 Clinical Study in Newly Diagnosed Oropharyngeal
Squamous Cell Carcinoma
The Phase 2 portion of the
study is ongoing at the RP2D and enrollment was completed in the
monotherapy arm with 20 evaluable patients with newly diagnosed
oropharyngeal squamous cell carcinoma (OPSCC). An interim clinical
data presentation from the Phase 2 monotherapy arm is expected in
the second half of 2023.
Phase 2 Randomized Control Study in Recurrent or Metastatic
Cervical Cancer
The Company recently
announced that the US Food and Drug Administration (FDA) has
cleared the Investigational New Drug (IND) application to initiate
a Phase 2 study of the first-in-class PRGN-2009 OTS
AdenoVerse™ immunotherapy in combination with
pembrolizumab in patients with recurrent or metastatic cervical
cancer. The Phase 2 randomized, open-label, two-arm, multicenter
study will evaluate the efficacy and safety of PRGN-2009 in
combination with pembrolizumab versus pembrolizumab monotherapy in
patients with recurrent or metastatic cervical cancer who are
pembrolizumab resistant.
###
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.
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 T-cell immune responses as well as an ability to
boost these responses via repeat administration. Superior
performance characteristics and high yield manufacturing of
AdenoVerse vectors leveraging UltraVector® technology
allows Precigen to engineer cutting-edge investigational gene
therapies to treat complex diseases.
AdenoVerse™ Immunotherapy Clinical
Program
Precigen's AdenoVerse immunotherapy platform
is currently under clinical investigation in a Phase 1/2 study of
PRGN-2009 AdenoVerse immunotherapy alone or in combination with
anti-PDL1/TGF-Beta Trap (bintrafusp alfa) in patients with
HPV-associated cancers (NCT04432597), including oropharyngeal
squamous cell carcinoma (OPSCC), a Phase 2 study of PRGN-2009
AdenoVerse immunotherapy in combination with pembrolizumab in
patients with recurrent or metastatic cervical cancer, and a
Phase 2 study of PRGN-2012 AdenoVerse immunotherapy in patients
with recurrent respiratory papillomatosis (RRP) (NCT04724980).
PRGN-2012 has been granted Orphan Drug Designation in
patients with RRP by the FDA.
For patients interested in enrolling in NCI-led clinical
studies, please call NCI's toll-free number 1-800-4-Cancer
(1-800-422-6237) (TTY: 1-800-332-8615), email
NCIMO_Referrals@mail.nih.gov, and/or visit the website:
https://trials.cancer.gov.
Trademarks
Precigen, AdenoVerse, UltraVector 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 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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