GERMANTOWN, Md., Oct. 1, 2021 /PRNewswire/ -- Precigen
ActoBio, an innovative clinical-stage biotechnology company focused
on a new class of microbe-based therapeutic agents and a
wholly-owned subsidiary of Precigen, Inc. (Nasdaq: PGEN), today
announced additional positive interim data from the ongoing Phase
1b/2a clinical study investigating
AG019 ActoBiotics™ for the treatment of recent-onset type 1
diabetes (T1D) (clinical trial identifier: NCT03751007, EudraCT
2017-002871-24). Results were presented in an oral presentation
entitled, "AG019 ActoBiotics as monotherapy or in association
with teplizumab in recent-onset type 1 diabetes was safe and
demonstrated encouraging metabolic and immunological effects"
at the European Association for the Study of Diabetes (EASD) 57th
Annual Meeting by Chantal
Mathieu, MD, PhD, Professor of Medicine at the Katholieke
Universiteit Leuven, Belgium.
The Phase 1b open-label portion of
the study evaluates the safety and tolerability of AG019 as a
monotherapy in adult (age 18-42) and adolescent (age 12-17)
patients. The Phase 2a double-blind portion of the study
investigates the safety and tolerability of AG019 in combination
with an investigational anti-CD3 monoclonal antibody, teplizumab
(PRV-031).
Previously reported Phase 1b/2a topline data showed the potential of oral
AG019 treatment to preserve insulin production in recent-onset T1D
through its capacity to induce antigen-specific immune
modulation:
- The primary endpoint of both the Phase 1b AG019 monotherapy study and the Phase 2a AG019
combination therapy study was met.
- AG019 was well tolerated as a monotherapy and in combination
with teplizumab with no serious adverse events (SAEs)
reported.
- A single 8-week treatment cycle of oral AG019 as a monotherapy
and in combination with teplizumab showed stabilization or increase
of C-peptide levels during the first 6 months post treatment
initiation in recent-onset T1D.
- In an independent analysis performed by the Immune Tolerance
Network (ITN), a leading independent research group sponsored by
the US National Institutes of Health, oral AG019 treatment induced
antigen-specific tolerance in conjunction with the reduction of
disease-specific T-cell responses 6 months post treatment
initiation. The extent of the antigen-specific tolerance was
similar in both the AG019 monotherapy and combination therapy
indicating that this effect may be attributed to the oral AG019
treatment.
New clinical results presented at EASD include:
Phase 1b oral AG019
monotherapy:
Dosing: Patients received a daily dose
of oral AG019 monotherapy for 8 weeks and were evaluated for
pharmacodynamic and metabolic markers. The average time of T1D
diagnosis was 104 days at dosing initiation.
Clinical Activity*: New AG019 monotherapy
data show that glycated hemoglobin (HbA1c) was below the 7% target
for 100% of adult patients (9 of 9) and 92% of the patients aged 17
years and above (11 of 12) up to 12 months after dosing initiation.
An HbA1c level below 7% is an important indicator of long-term
glycemic control as defined by the American Diabetes Association
(ADA). Moreover, insulin-dose adjusted HbA1c (IDAA1c) is a model
that uses both weight-adjusted insulin dose and HbA1c in the same
formula to reduce the influence of the insulin treatment regimen. A
stabilization of IDAA1c below 9 was demonstrated in 78% of adult
patients (7 of 9) and in 75% of patients aged 17 years and above (9
of 12) up to 12 months after dosing initiation. Stable glycemia,
measured as a reduction of HbA1c/IDAA1c, is known to reduce the
long-term risk of developing microvascular complications, including
diabetic retinopathy, nephropathy, and other vascular
complications.
Mechanistic Data: In an independent
analysis performed by the ITN, the AG019 monotherapy showed a
decrease of conventional T-cells with an inflammatory phenotype (%
TNFα+) in 100% of adult patients (4 of 4) analyzed up to 6 months
after dosing initiation, whereas the mean expression of the
inhibitory receptor PD-1 remained overall stable.
Phase 2a AG019 combination therapy:
Dosing: Patients received a daily dose of
oral AG019 monotherapy for 8 weeks in combination with daily
intravenous infusions of teplizumab for 12 days and were evaluated
for pharmacodynamic and metabolic markers. The average time of T1D
diagnosis was 103 days at dosing initiation.
Clinical Activity*: New AG019 combination
therapy data show stabilization of HbA1c below the ADA target (7%)
was demonstrated in 70% of adult patients (7 of 10) up to 12 months
after dosing initiation. HbA1c levels were below target in 75% of
the adolescent patients (3 of 4) up to 6 months after dosing
initiation and remained below target for whom 12-month data is
available (n=2). In addition, a stabilization of IDAA1c was
demonstrated in 100% of adult patients (10 of 10) up to 12 months
after dosing initiation. Stabilization of IDAA1c was demonstrated
in 75% of adolescent patients (3 of 4) up to 6 months after dosing
initiation and remained below target for whom 12-month data is
available (n=2). HbA1c and IDAA1c levels were below the target in
33% of placebo-treated patients (1 of 3) up to 6 months after
dosing initiation.
Mechanistic Data: In an independent analysis
performed by the ITN, the combination of AG019 and teplizumab
showed a decrease of conventional T-cells with an inflammatory
phenotype (% TNFα+) in 67% of adult patients (2 of 3) analyzed up
to 6 months after dosing initiation, while an increase was shown in
100% of placebo-treated adult patients (2 of 2). Moreover, an
increase in the expression of inhibitory receptor PD-1 in PPI and
islet-reactive conventional T-cells was demonstrated in 67% of
adult patients (2 of 3) analyzed up to 6 months after dosing
initiation. This effect was not shown for placebo-treated
adult patients (n=2) at 6 months after dosing initiation.
In the AG019 combination therapy study, the expansion of the
exhausted phenotype in total CD8+ T-cells in adult and adolescent
patients (n=12) was in line with previously reported anti-CD3
specific effects indicating an attenuation of the effector
function. This effect was not shown for placebo-treated adult
patients (n=2).
"AG019 showed stabilization of the long-term glycemic control
markers, HbA1c and IDAA1c, for the majority of patients treated
with the AG019 monotherapy and AG019 combination therapy," said
Chantal Mathieu, MD, PhD, Professor
of Medicine at the Katholieke Universiteit Leuven, Belgium, and principal investigator for the
AG019 Phase 1b/2a clinical study.
"Antigen-specific immune modulation, which is the keystone for the
mechanism of action of AG019 as demonstrated in preclinical
studies, is now translated into the immunological clinical data in
the Phase 1b/2a clinical study."
"The new data presented at EASD strengthens previously reported
findings on C-peptide and antigen-specific immune modulation, and
the exciting data for the AG019 monotherapy reinforces our belief
that AG019 is promising as a standalone therapy. We look forward to
further investigating the potential of AG019 in type 1 diabetes."
Said Pieter Rottiers, PhD, CEO of
Precigen ActoBio.
*Per Protocol Analysis Set: All data from patients who received
at least 75% of the scheduled doses of AG019 and at least one dose
of teplizumab in the combination cohorts and had no major protocol
deviations affecting the main pharmacodynamic endpoints at the time
point of data collection.
About AG019 ActoBiotics™
AG019 is formulated as an
oral capsule of engineered Lactococcus lactis specifically
modified to deliver autoantigen human proinsulin (hPINS) and the
tolerance-enhancing cytokine human interleukin-10 (hIL-10) to the
mucosal lining of the gastrointestinal tissues. Administration of
AG019 is designed to induce specific regulatory T cells (Tregs)
that could reduce or eliminate the destruction of insulin-producing
cells, potentially stabilizing or improving endogenous insulin
production.
About Type 1 Diabetes (T1D)
T1D is an autoimmune
disease in which the immune system destroys insulin-producing beta
cells in the pancreas, resulting in a blood glucose imbalance.
There is no approved disease-modifying treatment for T1D, which is
currently managed through lifestyle modification and diet combined
with exogenous insulin. Replacement insulin therapy is associated
with a variety of near- and long-term adverse events, as is failure
to properly control glucose levels within a narrow range. As of
2019, more than 463 million adults (20-79 years, diagnosed and
undiagnosed) globally are living with diabetes with T1D estimated
to account for 23 million to 46 million (5 to 10%) of all diabetes
cases. Over 1.1 million below 20 years of age have T1D with an
estimated 128,900, under age 20 years, expected to develop T1D
worldwide annually.2
About Precigen ActoBio™
Precigen ActoBio is
a clinical stage biotechnology company and a wholly-owned
subsidiary of Precigen (Nasdaq: PGEN) pioneering a new class of
therapeutic agents created on the ActoBiotics™ platform. The
ActoBiotics™ platform provides a new class of therapeutic agent, a
unique delivery platform precisely tailored for specific disease
modification, with the potential for superior efficacy and safety
via local delivery directly to the relevant tissue. ActoBiotics are
targeted, microbe-based, specifically designed agents that express
and locally deliver potential disease-modifying therapeutics at
disease sites including the intestine, the mouth and the
nasopharynx, to treat a range of disorders. Precigen ActoBio has a
strong R&D pipeline and an extensive portfolio of candidates
advancing toward clinical development across a number of potential
indications. Learn more about Precigen ActoBio at
http://www.precigen.com/actobio.
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, Precigen ActoBio, ActoBiotics,
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 Precigen's current expectations and
projections about future events and generally relate to plans,
objectives, and expectations for the development
of Precigen's business and the business of Precigen
ActoBio, including the timing and progress of preclinical and
clinical trials and discovery programs, and the promise
of their portfolio of 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 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. Precigen 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 Precigen's actual results to differ from those
contained in the forward-looking statements, see the section
entitled "Risk Factors" in Precigen's most recent Annual
Report on Form 10-K and subsequent reports filed with the
Securities and Exchange Commission.
For more information, contact:
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
|
References 1 Greenbaum et al.,
Diabetes 2012
2 International Diabetes Foundation, Diabetes Atlas
Ninth Edition 2019. IDF website
|
View original content to download
multimedia:https://www.prnewswire.com/news-releases/precigen-actobio-announces-additional-positive-interim-data-from-phase-1b2a-study-of-ag019-actobiotics-a-novel-therapy-designed-to-address-the-underlying-cause-of-type-1-diabetes-301389445.html
SOURCE Precigen ActoBio