– Repeated administrations of PRGN-2012
were well-tolerated with no dose-limiting toxicities and no
treatment-related adverse events greater than Grade 2 –
– Clinical data show strong response in
RRP patients with 50% of patients in Complete Response, requiring
no post-treatment surgeries, following PRGN-2012 treatment at Dose
Level 2; All complete responders remain surgery-free post-treatment
with a minimum follow up of 12 months –
– PRGN-2012 treatment at Dose Level 2
significantly reduced the need for surgeries in severe, aggressive
RRP patients; Median number of RRP surgeries in 12-month period
reduced from 6.5 pre-treatment to 0.5 post-treatment –
– Phase 2 study is enrolling patients
with a total of 32 patients enrolled at Dose Level 2 to date
–
– Company to outline regulatory strategy
in RRP as US Food and Drug Administration (FDA)
discussions advance –
– Precigen to host R&D Day virtual
event today at 4:30 PM ET –
GERMANTOWN, Md., Jan. 24,
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 announces positive Phase 1 dose
escalation and expansion cohort data as of the January 12, 2023 cutoff for the investigational,
potential first-in-class PRGN-2012 off-the-shelf (OTS)
AdenoVerse™ immunotherapy in patients with recurrent
respiratory papillomatosis (RRP).
The company will host an R&D Day virtual event today at
4:30 PM ET to showcase the data and
will feature presentations by Clint T.
Allen, MD, Senior Investigator, Surgical Oncology Program,
Center for Cancer Research, National Cancer Institute (NCI) and
lead associate investigator for the PRGN-2012 clinical trial, and
Precigen's President and CEO, Helen
Sabzevari, PhD. Participants may register and access the
live webcast through Precigen's investor relations website in the
Events & Presentations section.
"As a patient and an advocate on behalf of the RRP community,
the potential for a therapeutic alternative to surgical
intervention would be nothing short of life changing," said
Kim McClellan, President, Recurrent
Respiratory Papillomatosis Foundation (RRPF). "There has never been
a therapeutic option for the RRP patient community and we are
incredibly hopeful that this will change in the near future. Our
community faces ongoing risks from hospitalizations and repeat
surgeries, coupled with daily quality-of-life challenges, such as
obstructed breathing, difficulties swallowing, and impaired speech,
and our community bears a tremendous financial burden from the
significant lifetime costs to patients and their families
affiliated with this disease."
"RRP is a rare disease with no cure. The current
standard-of-care is repeated surgery to treat symptoms, which
exposes patients to surgical risks, emotional distress and poses a
significant economic burden to families and the healthcare system
overall. We are thrilled to present these Phase 1 results today as
PRGN-2012 has the potential to improve the lives of patients with
severe, aggressive RRP through reduced surgeries," said
Helen Sabzevari, PhD, President and
CEO of Precigen. "Any treatment that reduces the burden of
surgeries in RRP is considered meaningful and in the PRGN-2012
Phase 1 study, 50% of patients had a Complete Response, requiring
no surgeries as of the data cutoff with a minimum of 12 months
following treatment."
About RRP
RRP is a rare, difficult-to-treat and
sometimes fatal neoplastic disease of the upper and lower
respiratory tracts that is caused by infection with HPV 6 or HPV
11.1-4 RRP is classified based on age of onset as
juvenile or adult. There is no approved therapeutic treatment for
RRP and the current standard-of-care is repeated endoscopic
debulking with ablation or excision of papillomatous
lesions.3,4 Surgeries are not curative and
recurrence of papilloma after surgical removal is very common and
repeated procedures are required to debulk and monitor the disease,
which exposes patients to anesthetic and surgical risks, and
emotional distress. Patients with aggressive RRP can undergo
hundreds of lifetime surgeries to control their
disease.5 RRP morbidity and mortality results from the
effects of papilloma mass on the vocal cords, trachea, and lungs,
which may cause voice changes, stridor, airway occlusion, loss of
lung volume, and/or post-obstructive
pneumonia.6 Although rare, RRP has potential for
malignant transformation in three to seven percent of adult
patients.7
About PRGN-2012
AdenoVerse Immunotherapy
PRGN-2012 is an
innovative therapeutic vaccine with optimized antigen design that
uses Precigen's gorilla adenovector technology, part of Precigen's
proprietary AdenoVerse platform, to elicit immune responses
directed against cells infected with HPV 6 or HPV 11. Gorilla
adenovectors have numerous advantages, including the ability for
repeat administration, the inability to replicate in
vivo, which may improve safety, and the ability to deliver
large payload capacity. In preclinical models, PRGN-2012 has
demonstrated strong and specific immune response against HPV 6 and
HPV 11. PRGN-2012 has been granted Orphan Drug
Designation in patients with RRP by the FDA.
About the Phase 1 Clinical Trial
The Phase 1 clinical
trial (clinical trial identifier: NCT04724980) evaluated safety and
efficacy of PRGN-2012 as an immunotherapy following
standard-of-care RRP surgery. Trial design included initiation of a
3+3 dose escalation cohort followed by a dose expansion cohort to
enroll additional patients at the recommended Phase 2 dose (RP2D).
Adult patients with severe, aggressive RRP, defined as greater than
or equal to three surgeries in the prior 12 months, were enrolled
to the clinical trial. A total of 15 patients were enrolled in the
Phase 1 dose escalation and expansion cohorts at Dose Level 1: 1 x
1011 viral particles (vp)/dose (N=3) or Dose Level 2: 5
x 1011 vp/dose (N=12) with patients receiving four
PRGN-2012 administrations (on days 1, 15, 43 and 85) via
subcutaneous injection.
Patient Characteristics
Baseline patient
characteristics of the 15 adult patients included a median age of
51 years (range: 30-73). Ten patients were male and 5 were female.
Patients had an average of 6.2 surgeries (range: 3-10) in the last
12 months before enrolling in the trial. Patients were diagnosed
with RRP for an average of 15 years prior to enrollment.
Safety Summary
Repeated administrations of PRGN-2012
were well-tolerated with no dose-limiting toxicities and no
treatment-related adverse events (TRAEs) greater than Grade 2
(TABLE 1). All patients received four administrations of PRGN-2012
at the intended dose level. TRAEs were all mild and reduced in
frequency over the treatment interval. The most common TRAE was
injection site reaction, which occurred in all of the patients.
Most other TRAEs occurring in more than one subject were similar to
seasonal vaccines and the most common were fatigue, fever, and
chills (TABLE 2). The lack of a significant neutralizing antibody
response to gorilla adenovector over time with subsequent
additional vaccinations highlights the ability to deliver repeated
administrations of PRGN-2012, a differentiating feature of the
AdenoVerse platform.
TABLE 1:
Treatment-related Adverse Events
|
Total Patients
(N=15)
|
|
|
Dose Level
1
1 x
1011 vp (N=3)
|
Dose Level
2
5 x
1011 vp (N=12)
|
All
Subjects
(N=15)
|
|
Subjects
(N,
%)
|
Events
(N)
|
Subjects
(N,
%)
|
Events
(N)
|
Subjects
(N,
%)
|
Events
(N)
|
Grade
1
|
3
(100 %)
|
7
|
12
(100 %)
|
105
|
15
(100 %)
|
112
|
Grade
2
|
0 (0 %)
|
0
|
2
(16.7 %)
|
4
|
2
(13.3 %)
|
4
|
Grades 3 -
5
|
0 (0 %)
|
0
|
0 (0 %)
|
0
|
0 (0 %)
|
0
|
TABLE 2:
Treatment-related Adverse Events by Grade
|
Total Patients
(N=15)
|
|
|
Grade
1
|
Grade
2
|
|
Subjects
(N,
%)
|
Events
(N)
|
Subjects
(N,
%)
|
Events
(N)
|
Chills
|
10/15
(66.7%)
|
14
|
0 (0 %)
|
0
|
Diarrhea
|
1/15
(6.7%)
|
1
|
0 (0 %)
|
0
|
Shortness of breath
(Dyspnea)
|
1/15
(6.7%)
|
1
|
0 (0 %)
|
0
|
Excessive sweating
(Hyperhidrosis)
|
2/15
(13.3%)
|
2
|
0 (0 %)
|
0
|
Fatigue
|
9/15
(60.0%)
|
20
|
2/15
(13.3%)
|
2
|
Fever
|
9/15
(60.0%)
|
17
|
0 (0 %)
|
0
|
Injection site
reaction
|
15/15
(100%)
|
46
|
0 (0 %)
|
0
|
Muscle aches
(Myalgia)
|
2/15
(13.3%)
|
2
|
2/15
(13.3%)
|
2
|
Nausea
|
4/15
(26.7%)
|
6
|
0 (0 %)
|
0
|
Skin itching
(Pruritus)
|
1/15
(6.7%)
|
1
|
0 (0 %)
|
0
|
Vomiting
|
2/15
(13.3%)
|
2
|
0 (0 %)
|
0
|
Clinical Efficacy Summary
Clinical data show PRGN-2012
treatment significantly reduced the need for surgeries for severe,
aggressive RRP patients treated at Dose Level 2. At Dose Level 2,
50% (6 out of 12) patients had a Complete Response, which is
defined as no surgeries needed during the 12-month period following
PRGN-2012 treatment completion (TABLE 3). All complete responders
remained surgery-free post PRGN-2012 treatment as of the cutoff
date. Patients in Dose Level 2 had a 58% (7 out of 12) Overall
Response Rate, defined as greater than or equal to 50% reduction in
the surgeries in 12-months post PRGN-2012 treatment completion
compared to 12-months pre-treatment. 83% (10 out of 12) of patients
treated at Dose Level 2 had reduced surgeries post PRGN-2012
treatment. The number of RRP surgeries in the patients (N=12) in
Dose Level 2 reduced from a median of 6.5 surgeries (range: 3-10)
in the 12-months pre-treatment to 0.5 surgeries (range: 0-6) in
12-months post PRGN-2012 treatment completion.
Further, PRGN-2012 treatment showed significant improvement in
anatomical Derkay scores, a tool used for research purposes to
quantify RRP severity based on involvement of laryngeal structures,
and voice quality, evaluated using the validated Vocal Handicap
Index-10 (VHI-10), at 24-weeks post PRGN-2012 treatment completion
compared to baseline.
Phase 1 data show that PRGN-2012 treatment resulted in an
increase in HPV 6/11-specific T-cell response in the peripheral
blood of RRP patients. Furthermore, the T-cells infiltrating
papillomas from patients who had an objective response and a biopsy
sample available showed an increase in HPV 6/11-specifc T-cells in
papillomas after PRGN-2012 treatment.
TABLE 3: Clinical
Efficacy Summary
|
Total Patients
(N=15)
|
|
|
Dose Level
1
(N=3)
|
Dose Level
2
(N=12)
|
Complete Response
(CR)
No surgeries needed
during 12-months post-treatment
|
0%
(0/3)
|
50%
(6/12)
|
Overall Response
Rate (ORR)
≥ 50% reduction in
surgeries during 12-months post-treatment compared to 12-months
pre-treatment
|
33%
(1/3)
|
58%
(7/12)
|
Decrease in Rate of
Surgery
12-months
post-treatment compared to 12-months pre-treatment
|
100%
(3/3)
|
83%
(10/12)
|
Case Studies
Case studies will be presented for three
of the six complete responders. An example case study included
subject #5, a 40 year old male who required eight surgeries in the
12-months prior to treatment to control papilloma growth. This
patient has been in Complete Response after completing PRGN-2012
treatment, and has been surgery-free up to 18-months as of the
cutoff date (FIGURE 1). Consistent with the disease response, the
patient's Derkay score and VHI-10 index showed significant
reduction at 24-weeks post treatment compared to baseline
indicating improvement in disease severity and vocal function,
respectively. The patient showed improvement in HPV-specific immune
response in peripheral blood and papilloma post PRGN-2012
treatment.
Phase 2 Study
Precigen initiated dosing in the Phase 2
trial at Dose Level 2 and is rapidly enrolling patients, with 20
patients enrolled to date in the Phase 2 trial, bringing the total
number of enrolled patients to 32 at Dose Level 2. The Phase 2
clinical trial evaluates PRGN-2012 as an immunotherapy following
standard-of-care surgery in adult patients with RRP.
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.
About 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.
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.
References
1 Mounts, P et
al. (1982). "Viral etiology of juvenile- and adult-onset
squamous papilloma of the larynx." Proc Natl Acad
Sci U S A 79(17): 5425-5429.
2 Smith, E et al. (1993). "Human
papillomavirus infection in papillomas and nondiseased respiratory
sites of patients with recurrent respiratory papillomatosis using
the polymerase chain reaction." Arch Otolaryngol Head Neck
Surg 119(5): 554-557.
3 Derkay, CS et al. (2008).
"Recurrent respiratory papillomatosis: a
review." Laryngoscope 118(7): 1236-1247.
4 Derkay, CS et al. (2019).
"Update on Recurrent Respiratory
Papillomatosis." Otolaryngol Clin North Am 52(4):
669-679.
5 Allen, CT et al. (2019). "Safety and
clinical activity of PD-L1 blockade in patients with aggressive
recurrent respiratory papillomatosis." J. Immunotherapy Cancer 7,
119.
6 Seedat, RY (2020). "Juvenile-Onset Recurrent
Respiratory Papillomatosis Diagnosis and Management - A Developing
Country Review." Pediatric Health Med Ther 11:
39-46.
7 Katsenos S, et al. (2011). "Recurrent
respiratory papillomatosis: a rare chronic disease, difficult to
treat, with potential to lung cancer transformation: apropos of two
cases and a brief literature review." Case Rep Oncol. 2011
Mar 23;4(1):162-71.
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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