– Phase 1/2 pivotal study met the
primary safety and efficacy endpoints –
– 51% (18 out of 35) of patients
achieved Complete Response, requiring no surgeries after treatment
with PRGN-2012; complete responses have been durable beyond 12
months with median duration of follow up of 20 months as of data
cutoff –
– 86% of patients (30 out of 35)
had a decrease in surgical interventions in the year after
PRGN-2012 treatment compared to the year prior to treatment; RRP
surgeries reduced from a median of 4 pre-treatment to 0
post-treatment –
– PRGN-2012 was well-tolerated
with no dose-limiting toxicities and no treatment-related adverse
events greater than Grade 2 –
– PRGN-2012 treatment induced HPV
6/11-specific T cell responses in RRP patients with a significantly
greater expansion of peripheral HPV-specific T cells in responders
compared with non-responders –
– PRGN-2012 significantly (p <
0.0001) improved Derkay and quality of life scores in complete
responders –
– RRP is a rare, devastating
HPV-mediated chronic disease characterized by growth of benign
tumors for which the current standard-of-care is repeated
surgeries; if approved, PRGN-2012 has the potential
to be the first FDA-approved therapeutic for the treatment of
RRP –
– Clinical data associated with
favorable safety, strong efficacy, ease of administration, and
immunological responses, position PRGN-2012 to potentially
be the preferred treatment-of-choice for RRP –
– PRGN-2012 rolling BLA
submission, under an accelerated approval pathway, is anticipated
in the second half of 2024 –
– Precigen to host webcast event
today at 6:00 PM CT / 7:00 PM ET –
GERMANTOWN, Md., June 3, 2024
/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 released positive Phase 1/2 pivotal study results
for the investigational PRGN-2012 off-the-shelf (OTS)
AdenoVerse® gene therapy in patients with
recurrent respiratory papillomatosis (RRP). Results were presented
in a late-breaking oral presentation at the 2024 American Society
of Clinical Oncology (ASCO) Annual Meeting by Scott M. Norberg, DO, Associate Research
Physician, Center for Immuno-Oncology, Center for Cancer Research,
National Cancer Institute and a lead investigator for the PRGN-2012
clinical study. The Company will host a webcast event today at
6:00 PM CT / 7:00 PM ET to detail the results presented at
ASCO.
"We are thrilled with the results of the Phase 1/2 pivotal study
showing more than half of patients were surgery
free–Complete Response–and 86% of patients had a
significant reduction in the need for surgeries after PRGN-2012
treatment. Based on the efficacy, safety, and ease of
administration, we believe PRGN-2012 is a game-changer for RRP
patients and has the potential to be the preferred
treatment-of-choice for RRP," said Helen
Sabzevari, PhD, President and CEO of Precigen. "We look
forward to sharing these results with the FDA as part of a rolling
Biologics License Application submission under an accelerated
approval pathway. We have ramped up our commercial readiness
efforts in anticipation of a potential launch in 2025 and are
excited by the potential to bring a long overdue new treatment
option to the RRP community."
Pivotal Study Design and Endpoints
The Phase 1/2
clinical study (clinical trial identifier: NCT04724980) evaluated
safety and efficacy of PRGN-2012. The study design included an
initial 3+3 dose escalation cohort to identify the recommended
Phase 2 dose (RP2D). Adult RRP patients who had three or more
surgeries in the prior 12 months were eligible for the study. The
Phase 1/2 study enrolled a total of 38 patients. Of these, 3
patients received four administrations of PRGN-2012 at 1x
1011 particle units (PU)/dose and 35 patients received
four administrations of PRGN-2012 at RP2D (5 x 1011
PU/dose) over a 12 week treatment period via subcutaneous
injection.
Primary endpoints included safety and Complete Response rate
defined as the percentage of patients who require no RRP
surgeries in the 12-month period after PRGN-2012 treatment
completion. Key secondary endpoints included HPV-specific immune
responses, extent of papilloma growth as measured by Derkay
scoring, and quality of life measurement as measured by Vocal
Handicap Index-10 (VHI-10).
Patient Characteristics
Baseline patient
characteristics of the 35 adult patients included a median age of
49 years (range: 20-88); 20 of the patients were male and 15 were
female. Patients had a median of 4 surgeries (range: 3-10) in the
12 months before PRGN-2012 treatment initiation. Average years
since RRP diagnosis was 20 (range: 1-65) with 12 and 23 patients
with juvenile and adult onset RRP, respectively.
Clinical Efficacy
Primary efficacy endpoint analysis
demonstrated that 51% (18 out of 35) (95% CI: 34-69) patients
achieved Complete Response, defined as no need for RRP
surgeries in the 12-month period following completion of PRGN-2012
treatment. The Complete Response rate was 50% (6 out of 12) and 52%
(12 out of 23) in the Phase 1 and Phase 2 portions of the study,
respectively (TABLE 1). Complete Responses were durable. Median
durability of response has not yet been reached with median follow
up of 20 months as of the data cutoff date of May 20, 2024. PRGN-2012 treatment significantly
(p < 0.0001) reduced the need for surgeries in RRP patients
compared to pre-treatment history (FIGURE 1). PRGN-2012 treatment
reduced the need for RRP surgeries in 86% (30 out of 35) of
patients compared to their pre-treatment history. RRP surgeries
were reduced from a median of 4 (range: 3-10) in the 12 months
pre-treatment to 0 (range: 0-7) in the 12 months post PRGN-2012
treatment completion.
PRGN-2012 treatment showed significant (p < 0.0001)
improvement in anatomical Derkay scores, a tool used for research
purposes to quantify RRP severity based on involvement of laryngeal
structures, with mean Derkay scores reducing from 9 (range: 5-19)
at baseline to 1 (range: 0-5) at 24 weeks post-treatment in
patients with Complete Response. Quality of life, as evaluated
using the validated VHI-10, significantly (p < 0.0001) improved
from a mean of 25 (range: 12-38) at baseline to 7 (range: 0-30) at
24 weeks post PRGN-2012 treatment in patients with Complete
Response. PRGN-2012 treatment induced HPV 6/11-specific T cell
responses in RRP patients with a significantly greater expansion of
peripheral HPV-specific T cells observed in responders compared
with non-responders.
|
TABLE 1: Clinical
Efficacy Summary
|
|
Total Patients
(N=35)
|
|
|
Phase
1
(N=12)
|
Phase
2
(N=23)
|
Phase 1/2
Total
(N=35)
|
|
Complete
Response
No surgeries needed
during 12 months post-treatment
|
50%
(6/12)
|
52%
(12/23)
|
51%
(18/35)
|
|
Decrease in Rate of
Surgery
12 months
post-treatment compared to 12 months pre-treatment
|
83%
(10/12)
|
87%
(20/23)
|
86%
(30/35)
|
Safety
PRGN-2012 treatment was well-tolerated
with no dose-limiting toxicities and no treatment-related adverse
events (TRAEs) greater than Grade 2 (TABLE 2). All patients
received four administrations of PRGN-2012 at the intended dose
levels. TRAEs were mostly mild with no treatment-related serious
adverse events reported. The most common TRAE was injection site
reaction. Other common TRAEs occurring in more than one subject
were fatigue, chills, and fever. There was no meaningful anti-drug
antibody response with repeat administrations of PRGN-2012.
|
TABLE 2:
Treatment-related Adverse Events Occurring in More Than 1
Patient
|
|
Total Patients
(N=38)
|
|
|
Event
|
1 x 1011 PU
(N =
3)
|
5 x 1011 PU
(N=35)
|
|
Grade
1
|
Grade
2
|
Grade
1
|
Grade
2
|
|
(N,
%)
|
(N,
%)
|
(N,
%)
|
(N,
%)
|
|
Chills
|
-
|
-
|
25
(71 %)
|
-
|
|
Fatigue
|
-
|
-
|
28
(80 %)
|
2 (6 %)
|
|
Fever
|
-
|
-
|
24
(69 %)
|
-
|
|
Headache
|
|
|
2 (6 %)
|
|
|
Hyperhidrosis
|
-
|
-
|
2 (6 %)
|
-
|
|
Injection site
reaction
|
3
(100 %)
|
-
|
34
(97 %)
|
-
|
|
Myalgia
|
-
|
-
|
9
(26 %)
|
2 (6 %)
|
|
Nausea
|
-
|
-
|
8
(23 %)
|
-
|
|
Vomiting
|
-
|
-
|
2 (6 %)
|
-
|
|
|
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. Currently, there is no
cure for RRP and the current standard-of-care is repeated
endoscopic debulking with ablation or excision of papillomatous
lesions.3,4 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. 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.5 Although rare, one to three
percent of RRP cases can transform into invasive squamous cell
carcinoma.6,7
|
|
AdenoVerse®
Precigen's AdenoVerse
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 gene therapies 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.
|
|
About PRGN-2012 AdenoVerse® Gene Therapy
PRGN-2012 is
an investigational off-the-shelf AdenoVerse gene therapy designed
to elicit immune responses directed against cells infected with
human papillomavirus (HPV) 6 or HPV 11 for the treatment of RRP.
PRGN-2012 was the first to receive Breakthrough Therapy Designation
and an accelerated approval pathway for RRP from the US Food and
Drug Administration (FDA). PRGN-2012 received Orphan Drug
Designation from the FDA and from the European Commission. Results
from the Phase 1 portion of the Phase 1/2 study were published in
the peer-reviewed journal, Science Translational
Medicine, a leading publication from the American
Association for the Advancement of Science (AAAS).
|
|
AdenoVerse® Clinical
Programs
Precigen's AdenoVerse platform is currently under
clinical investigation in a Phase 1/2 study of PRGN-2009 alone or
in combination with an anti-PDL1/TGF-Beta Trap in patients with
HPV-associated cancers (NCT04432597), a Phase 2 study of PRGN-2009
in combination with pembrolizumab in newly diagnosed patients with
HPV-associated oropharyngeal squamous cell carcinoma (OPSCC)
(NCT05996523), a Phase 2 study of PRGN-2009 in combination with
pembrolizumab in patients with recurrent or metastatic cervical
cancer (NCT06157151), and a Phase 1/2 study of PRGN-2012 in
patients with recurrent respiratory papillomatosis (RRP)
(NCT04724980). PRGN-2012 has been granted Orphan Drug
Designation and Breakthrough Therapy Designation in
patients with RRP by the FDA and Orphan Drug Designation by the
European Commission.
|
|
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 X @Precigen, LinkedIn or
YouTube.
|
|
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 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
|
|
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 Seedat, RY (2020). "Juvenile-Onset Recurrent
Respiratory Papillomatosis Diagnosis and Management - A Developing
Country Review." Pediatric Health Med Ther 11: 39-46.
6 Dedo, HH et al. (2001). "CO(2) laser treatment in
244 patients with respiratory papillomas." Laryngoscope 111(9):
1639-1644.
7 Silver, RD et al. (2003). "Diagnosis and
management of pulmonary metastasis from recurrent respiratory
papillomatosis." Otolaryngol Head Neck Surg 129(6):
622-629.
|
|
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