GERMANTOWN, Md., June 10, 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 positive topline results for 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 from the primary analysis were presented
at the Federation of Clinical Immunology Societies (FOCIS) 2021
Virtual Annual Meeting by Kevan
Herold, MD, Professor of Immunobiology and of Medicine at
the Yale University.
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.
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 insulin production.
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 primary endpoint for assessing safety and
tolerability is treatment-emerging adverse events (TEAEs) reported
up to 6 months post treatment initiation. 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).
The primary endpoint of both the Phase 1b AG019 monotherapy and the Phase 2a AG019
combination therapy was met. AG019 was well tolerated and safe when
administered to adults and adolescents either as monotherapy or in combination with
teplizumab. No serious adverse events (SAEs) were reported and no
AG019 treatment discontinuation occurred due to TEAEs. No severe
TEAEs were reported in patients treated with AG019 monotherapy. The
TEAEs reported for both the mono- and combination therapy were
mostly mild and sometimes moderate severity. The TEAEs reported in
the combination cohorts are in line with the safety profile
reported for teplizumab and no
unexpected TEAEs were identified. In addition, pharmacokinetic
analyses demonstrated localized intestinal delivery of AG019 and no
systemic exposure of hPINS, hIL-10 and of AG019 bacteria in the
blood of the patients, confirming the safety profile of AG019.
Key clinical results for pharmacodynamic and metabolic markers
include:
Phase 1b oral AG019
monotherapy:
- Dosing: Patients who received a daily dose of oral AG019
monotherapy for 8 weeks were evaluated for pharmacodynamic and
metabolic markers.
- Clinical Activity*: Following a single 8-week treatment
cycle of oral AG019, 56% of adult patients (5 of 9) showed
stabilization or increase of C-peptide levels during the first 6
months post treatment initiation (defined as
responders1). The highest percentage of responders (58%,
7 of 12) was seen in patients 17 years and above, indicating a
potential target population for the monotherapy. A sustained
treatment effect may be achieved by prolonging AG019 treatment,
which could be examined in a subsequent clinical trial.
- Mechanistic Data: In an independent analysis performed
in a subset of adult and adolescent patients by the Immune
Tolerance Network (ITN), a leading independent research group
sponsored by the US National Institutes of Health, AG019
monotherapy induced antigen-specific tolerance in conjunction with
the reduction of disease-specific T cell responses 6 months post
treatment initiation.
-
- Preproinsulin (PPI)-specific CD8+ T
cells in circulation were reduced in 87% of patients (7 of
8) at 3 months and in 83% of
patients (5 of 6) at 6 months.
- A trend towards a correlation between PPI-specific CD8+
T cells reduction and C-peptide
preservation was observed at 6 months.
- An increase in the frequency of PPI-specific memory Tregs was
observed in 75% of adult patients (3 of 4) at 6 months and an
increase of PPI-specific CD4+ Tr1 cells was observed in 100% of
adult patients (4 of 4) at 3 months after treatment initiation. An
increase in the frequency of PPI-specific memory Tregs was observed
in 60% of adolescent patients (3 of 5) up to 3 months.
- Results indicated the potential of oral AG019 monotherapy to preserve insulin
production in recent-onset T1D through its capacity to reduce
autoreactive T cells and increase the frequency of memory Tregs to
induce antigen-specific immune modulation.
Phase 2a AG019 combination therapy:
- Dosing: Patients who received a daily dose of oral AG019
monotherapy for 8 weeks in combination with daily intravenous
infusions of teplizumab for 12 days were evaluated for
pharmacodynamic and metabolic markers.
- Clinical Activity*: Following treatment with the
combination of AG019 and teplizumab, 70% of adult patients (7 of
10) and 100% of adolescent patients (4 of 4) showed stabilization
or increase of C-peptide levels at 6 months post treatment
initiation (defined as responders1). 79% of all patients
(11 of 14) showed stabilization of C-peptide levels at 6 months
post treatment initiation. C-peptide levels of the responders for
whom 12-month data is available (n=8) remained above placebo
levels.
- Mechanistic Data: In an independent analysis performed
in adult and a subset of adolescent patients by the ITN, the
combination of AG019 and teplizumab showed the induction of
antigen-specific tolerance in conjunction with reduction of
disease-specific T cell responses for adult and adolescent patients
6 months post treatment initiation.
-
- PPI-specific CD8+ T cells in
circulation were reduced in 63% of patients (7 of 11) at 3 months
and in 67% of patients (6 of 9) at 6 months post treatment
initiation.
- An increase in the frequency of PPI-specific CD4+ Tr1 cells was
observed at 3 months in 40% of adult patients (2 of 5) (analysis of PPI-specific memory Tregs
ongoing).
- The extent of these antigen-specific immune modulatory effects
in the combination therapy patients is similar to what was seen in
AG019 monotherapy patients indicating that this effect may be
attributed to the single 8-week treatment cycle of oral AG019.
"The primary analysis shows that AG019 can be administered
safely, either as a monotherapy or in combination with teplizumab
and provides an opportunity for chronic treatment of T1D," said
Kevan Herold, MD, Professor of
Immunobiology and of Medicine at Yale University and Principal
Investigator for the AG019 Phase 1b/2a clinical study. "The stabilization of
C-peptide in the monotherapy with a single 8-week treatment cycle
of AG019 is encouraging in addition to the synergistic effect
observed between AG019 and teplizumab. There may be an opportunity
for sustained treatment effect following prolonged AG019
treatment."
"We are encouraged by the Phase 1b/2a primary analysis results and the
implications for the potential of AG019 as an easy-to-take oral
monotherapy or combination therapy with teplizumab. The
stabilization of C-peptide levels and induced antigen-specific
tolerance in conjunction with the reduction of disease-specific T cell response suggest the
ability of AG019 to modulate a patient's immune system in a
precise, antigen-specific manner to address the underlying cause of
T1D," said Pieter Rottiers, PhD, CEO
of Precigen ActoBio. "We are excited about advancing AG019 to
assess the efficacy of prolonged treatment of oral AG019."
* 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 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. 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
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
Contact:
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
|
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