GERMANTOWN, Md., Dec. 13, 2021 /PRNewswire/ -- Precigen,
Inc., a biopharmaceutical company specializing in the development
of innovative gene and cell therapies to improve the lives of
patients, today presented positive interim data at the 63rd ASH
Annual Meeting and Exposition (Abstract# 825) from the ongoing
Phase 1/1b clinical study of
PRGN-3006 UltraCAR-T® in patients with relapsed or
refractory (r/r) acute myeloid leukemia (AML) and higher risk
myelodysplastic syndromes (MDS) (clinical trial identifier:
NCT03927261). The oral presentation was delivered by
David Sallman, MD, Assistant Member
in the Department of Malignant Hematology at the H. Lee Moffitt
Cancer Center & Research Institute (Moffitt) and a lead
investigator for the PRGN-3006 clinical trial.
PRGN-3006 UltraCAR-T is a multigenic autologous CAR-T
simultaneously expressing a CAR specifically targeting CD33;
membrane bound IL-15 (mbIL15) for enhanced in vivo expansion
and persistence; and a kill switch to conditionally eliminate CAR-T
cells for an improved safety profile. CD33 is over-expressed on AML
blasts with lesser expression on normal hematopoietic stem cells.
PRGN-3006 UltraCAR-T has been granted Orphan Drug Designation in
patients with AML by the US Food and Drug Administration (US
FDA).
The Phase 1/1b clinical study is
designed to enroll in two phases, an initial dose escalation phase
followed by a dose expansion phase, to evaluate safety and
determine the maximum tolerated dose of PRGN-3006 delivered via
intravenous (IV) infusion without lymphodepletion (Cohort 1) or
with lymphodepletion (Cohort 2). The study is also evaluating in
vivo persistence and anti-tumor activity of PRGN-3006.
Today's ASH presentation included data from 15 r/r AML patients
treated in the non-lymphodepletion cohort (N=9) and the
lymphodepletion cohort (N=6). Patients were heavily pre-treated
with a median of 4 (range: 1 to 6) and 3 (range: 1 to 7) prior
regimens in the non-lymphodepletion and the lymphodepletion
cohorts, respectively. Additionally, 33% and 50% of the patients
had failed prior allogeneic hematopoietic stem cell transplant
(allo-HSCT) in the non-lymphodepletion and the lymphodepletion
cohorts, respectively. All patients received a single infusion of
PRGN-3006.
Safety Data
PRGN-3006 was well-tolerated with no
dose-limiting toxicities (DLTs) and no neurotoxicity at any dose
level. Overall, there was low incidence of adverse events following
PRGN-3006 infusion and the most common adverse events were
decreased lymphocyte count, anemia and cytokine release syndrome
(CRS). More than 70% of treatment emergent adverse events (TEAEs)
were either Grade 1 or 2 with only one transient Grade 3 CRS
reported (Dose Level 1, Cohort 1), which resolved in less than 24
hours with tocilizumab and dexamethasone. Other cases of CRS were
Grade 1 or 2 and required either no intervention or resolved
following standard CRS management. No subjects experienced a
significant increase in serum IL-15, demonstrating that mbIL15
remains tethered to the UltraCAR-T cells as designed and is not
released.
Clinical Activity
Non-lymphodepletion
Cohort
Excellent dose-dependent expansion and persistence of
PRGN-3006 in peripheral blood and bone marrow was observed
following a single infusion, with detection of UltraCAR-T cells in
blood for more than 7 months post-infusion highlighting the ability
of UltraCAR-T cells to engraft and survive even in the absence of
lymphodepletion. Peak expansion was observed between days 7 and 21
in the peripheral blood (FIGURE 1).
In the non-lymphodepletion cohort at the three dose levels
evaluated, 3 out of 9 (33%) patients had Stable Disease (SD), per
European LeukemiaNet (ELN) criteria, persisting for more than 3
months with one patient experiencing durable SD for more than 7
months with concomitant reduction in peripheral blast levels.
Lymphodepletion Cohort
Excellent dose-dependent
expansion and persistence of PRGN-3006 in peripheral blood and bone
marrow was observed following a single infusion, with detection of
UltraCAR-T cells in blood for more than 3 months post-infusion.
Peak expansion was observed between days 14 and 21 in the
peripheral blood with higher peak expansion (> 10 fold) observed
in the lymphodepletion cohort (FIGURE 2) at the same dose
level.
An ORR of 50% (3 out of 6) was reported in the lymphodepletion
cohort in patients treated at the two lowest dose levels. This
included an ORR of 33% (1 out of 3) at Dose Level 1 and 67% (2 out
of 3) at Dose Level 2 as summarized in TABLE 1. One responder (Dose
Level 1) subsequently received allo-HSCT with ongoing survival
greater than 1 year.
TABLE 1: Summary Objective Response Data for
the Lymphodepletion Cohort
Dose Level
(DL)
|
AML
Subtype
|
Dose
Received
|
Age
|
Sex
|
Prior
Regimens*
|
Safety**
|
Objective
Response***
|
DL 1
|
Persistent
AML
|
8.7 x
106
|
60
|
F
|
2 prior:
CLAG and
HiDAC
|
No incidence
of CRS,
neurotoxicity
or DLT
|
CRh at Day
84
|
DL 2
|
Extramedullary
AML
|
28 x
106
|
53
|
M
|
7 prior: intensive
chemo,
vidasia, venetoclax, FLAG,
anti-IDH1, allo-HSCT
|
No incidence
of CRS,
neurotoxicity
or DLT
|
PR#
|
AML
|
20 x
106
|
61
|
F
|
4 prior:
vyxeos,
HMA+venetoclax,
allo-HSCT
|
CRS Grade 1,
with SAE skin
rash,
(possible
GVHD)
|
CRi at Day
28
CRh at Day
60
|
*CLAG=cladribine,
cytarabine, and granulocyte-stimulating factor; HiDAC=high-dose
cytarabine; FLAG=fludarabine, cytarabine and filgrastim;
anti-IDH1=isocitrate dehydrogenases 1 inhibitor;
HMA=hypomethylating agents (HMA); allo-HSCT= allogeneic
hematopoietic stem cell transplant
**SAE=small ubiquitin-like modifier activating enzyme; GVHD=graft
versus host disease
***Per ELN criteria; Complete Response with incomplete hematologic
recovery (CRi); Complete response with hematologic recovery
(CRh)
#Per RECIST v1.1; PR=partial response
|
Analysis of peripheral blood samples post PRGN-3006 infusion
showed gene expression changes consistent with improvement in the
immune compartment function for anti-tumor effect in responders.
There was an increase in cytotoxicity, costimulatory signaling, and
lymphoid compartment and decreased apoptosis pathway scores in the
lymphodepletion cohort on Days 14 and 28 post PRGN-3006 treatment
compared to baseline.
The study is anticipated to progress to the multicenter
expansion phase with the plan to evaluate the potential of repeated
dosing of PRGN-3006.
"The interim data for PRGN-3006 showed excellent, dose-dependent
expansion and persistence of PRGN-3006 in peripheral blood and bone
marrow following a single infusion, with detection of UltraCAR-T
cells in blood more than 3 months post-infusion in the
non-lymphodepletion and lymphodepletion cohorts," said David A. Sallman, MD, of Moffitt and lead
investigator for the PRGN-3006 clinical study. "An ORR of 50% in
patients treated at the two lowest dose levels in the
lymphodepletion cohort is highly encouraging and the specifics of
the responding patients suggest the potential for PRGN-3006 as a
bridge to allo-HSCT, which is a very important potential treatment
pathway for these patients."
"We are excited by these interim data, which clearly highlight
the extraordinary potential and flexibility of the UltraCAR-T
platform to deliver precision medicine to patients at any time, at
any place and as many times as needed," said Helen Sabzevari, PhD, President and CEO of
Precigen. "Based on the favorable safety profile and excellent
expansion observed for both the lymphodepletion and the
non-lymphodepletion cohorts, we believe UltraCAR-T cells have the
potential to improve outcomes for cancer patients."
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 unique 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.
About Acute Myeloid Leukemia (AML)
AML is a cancer
that starts in the bone marrow, but most often moves into the
blood.1 Though considered rare, AML is among the
most common types of leukemia in adults.2 In 2019, it
was estimated that 21,450 new cases of AML would be diagnosed in
the US.2 AML is uncommon before the age of 45 and the
average age of diagnosis is about 68.2 The prognosis for
patients with AML is poor with an average 5–year survival rate of
approximately 25 percent overall, and less than a 5 percent 5–year
survival rate for patients older than 65.3 Amongst
elderly AML patients (≥ 65 years of age), median survival
is short, ranging from 3.5 months for patients 65 to 74
years of age to 1.4 months for patients ≥ 85 years of
age.3
About Myelodysplastic Syndrome (MDS)
MDS are diseases
of the bone marrow generally found in adults in their
70s.4 Incidence in the US is not known for sure, but
estimates range from 10,000 each year and higher.4 Using
International Prognostic Scoring System (IPSS-R), median survival
for MDS patients can vary from less than one year for the "very
high" IPSS-R risk group to more than eight years for the "very low"
IPSS-R group.4
UltraCAR-T®
UltraCAR-T is a multigenic autologous CAR-T platform that utilizes
Precigen's advanced non-viral Sleeping Beauty system to
simultaneously express an antigen-specific CAR to specifically
target tumor cells, mbIL15 for enhanced in vivo expansion
and persistence, and a kill switch to conditionally eliminate CAR-T
cells for a potentially improved safety profile. Precigen has
advanced the UltraCAR-T platform to address the inhibitory tumor
microenvironment by incorporating a novel mechanism for intrinsic
checkpoint blockade without the need for complex and expensive gene
editing techniques. UltraCAR-T investigational therapies are
manufactured via Precigen's overnight manufacturing process using
the proprietary UltraPorator electroporation system at the medical
center and administered to patients only one day following gene
transfer. The overnight UltraCAR-T manufacturing process does not
use viral vectors and does not require ex vivo activation
and expansion of T cells, potentially addressing major limitations
of current T cell therapies.
UltraPorator™
The UltraPorator system is an
exclusive device and proprietary software solution for the scale-up
of rapid and cost-effective manufacturing of UltraCAR-T therapies
and potentially represents a major advancement over current
electroporation devices by significantly reducing the processing
time and contamination risk. The UltraPorator device is a
high-throughput, semi-closed electroporation system for modifying T
cells using Precigen's proprietary non-viral gene transfer
technology. UltraPorator is being utilized for clinical
manufacturing of Precigen's investigational UltraCAR-T therapies in
compliance with current good manufacturing practices.
Trademarks
Precigen, UltraCAR-T, UltraPorator 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 American Cancer Society. What is
Acute Myeloid Leukemia (AML)?
|
2 American Cancer Society. Key
Statistics for Acute Myeloid Leukemia (AML)
|
3 Thein, M., et al., Outcome of older
patients with acute myeloid leukemia: an analysis of SEER data over
3 decades. Cancer, 2013. 119(15): p.2720-7
|
4 American Cancer Society. Key
Statistics for Myelodysplastic Syndromes
|
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
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