-- First in human results demonstrate potent immune system activation
with no serious adverse events or dose limiting toxicity --
SKOKIE, Ill.--(BUSINESS WIRE)--Sep. 20, 2018--
Exicure, Inc. (OTCQB:XCUR), the pioneer in gene regulatory and
immunotherapeutic drugs utilizing three-dimensional spherical nucleic
acid (SNA™) constructs, announced today Phase 1 results for AST-008, an
SNA consisting of toll-like receptor 9 (TLR9) agonists designed for
immuno-oncology applications.
“Phase 1 results for AST-008 demonstrated our desired highly potent
immune system activation without serious adverse events or dose limiting
toxicity. We believe this molecule could lead to better combination
therapies for patients with cancer and, to that end, we expect to
initiate a Phase 1b/2 trial in patients before year end,” said Dr. David
Giljohann, Chief Executive Officer of Exicure. “These data support the
potential of our SNA platform for immuno-oncology and set the stage for
ongoing development of the SNA platform into indications well beyond
cancer.”
Exicure’s Phase 1 Trial Results
The Phase 1 trial of AST-008 was a single ascending subcutaneous dose
trial comprised of 16 healthy volunteers. AST-008 was shown to be safe
and tolerable in all subjects, with no serious adverse events and no
dose limiting toxicity. AST-008 was well tolerated and all
AST-008-related adverse events were of short duration, reversible and
consistent with TLR9 activation.
In addition to the principle safety and tolerability endpoint, the trial
screened for levels of select cytokines and markers of immune cell
activation. AST-008 was shown to elicit high levels of certain cytokines
as well as activate important effector cells of the immune system
including T cells and natural killer cells, the main drivers of
anti-tumor response.
For the four subjects receiving the trial’s top dose of about 20 µg/kg
of AST-008, initial analyses suggest that the average fold-increase
above baseline for these cytokines is approximately as follows:
IFN-gamma: 3 fold; IL-6: 57 fold; IL-12: 2 fold; IP-10: 32 fold; and
MCP-1: 4 fold. At this dose, AST-008 also elicited 9.5 fold and 3.5 fold
increases in the fraction of activated T cells and natural killer cells,
respectively, compared to baseline.
Exicure’s Planned Phase 1b/2 Patient Trial
Exicure intends to begin an open-label Phase 1b/2 trial of
intra-tumorally dosed AST-008 in combination with a checkpoint inhibitor
before year end. The trial will begin with an AST-008 dose finding Phase
1b stage, followed by a Phase 2 expansion stage. In the Phase 1b,
Exicure will enroll patients with superficial injectable tumors and will
prioritize those with Merkel cell carcinoma, cutaneous squamous cell
carcinoma, melanoma, and squamous cell carcinoma of the head and neck.
Preliminary data from the Phase 1b stage are expected in late 2019.
Historical TLR9 Agonist Healthy Volunteer Data
In 2015, Mologen AG published results (European Journal of Cancer,
2015, volume 51, supplement 1, page S12) from a healthy volunteer trial.
In a single cohort, 13 subjects each received one 60 mg dose (equivalent
to 923 µg/kg for a 65 kg subject) of lefitolimod subcutaneously. On
average, across the cohort, there was a 7 fold-increase in IP-10
expression above baseline. No cell activation data were reported.
Lefitolimod is currently in a Phase 3 clinical trial.
In 2004, Coley Pharmaceutical Group (now Pfizer, Inc.) published results
(Journal of Immunotherapy, 2004, Volume 27, pages 460–471) from a
single ascending dose healthy volunteer trial. In that trial, their TLR9
agonist, PF-03512676, was administered subcutaneously to six subjects
per dose level. For the 20 µg/kg dose level, the average fold-increase
above baseline for these cytokines is as follows: IFN-gamma: no change
from baseline; IL-6: 8 fold; IL-12: no change from baseline; IP-10: 9
fold; and MCP-1: 3 fold.
Upcoming Presentations
Exicure management expects to be presenting and available for meetings
at a number of fall investor conferences including:
-
October 2 – Ladenburg Thalmann 2018 Healthcare Conference at the
Sofitel Hotel New York, NY;
-
October 3 – Leerink Partners Roundtable Series: Rare Disease &
Oncology at the Lotte New York Palace, New York, NY;
-
October 9 – Chardan’s 2nd Annual Genetic Medicines
Conference at the Westin Grand Central, New York, NY;
-
October 25 – BTIG Biotech Conference at the Langham Hotel, New York,
NY.
Exicure also intends to present at a variety of scientific conferences
including:
-
September 27 – CEO Dr. David Giljohann at the SMi Immuno-Oncology
conference at the Copthorne Tara Hotel, London;
-
September 30 – CSO Dr. Ekambar Kandimalla will present a poster at the
Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy
Conference at the Marriott Marquis, New York, NY;
-
October 1 – Poster at the Oligonucleotide Therapeutics Society meeting
at the Marriott Waterfront, Seattle, WA;
-
November 9-10 – Poster at the Society for Immunotherapy of Cancer
(SITC) conference, Washington DC.
About Exicure, Inc.
Exicure, Inc. is a clinical stage biotechnology company developing a new
class of immunomodulatory and gene regulating drugs against validated
targets. Exicure's proprietary 3-dimensional, spherical nucleic acid
spherical nucleic acid (SNA™) architecture is designed to unlock the
potential of therapeutic oligonucleotides in a wide range of cells and
tissues. Exicure's lead programs address inflammatory diseases, genetic
disorders and oncology. Exicure is based outside of Chicago, IL.www.exicuretx.com
Forward Looking Statements
This press release contains forward-looking statements (including within
the meaning of Section 21E of the United States Securities Exchange Act
of 1934, as amended, and Section 27A of the United States Securities Act
of 1933, as amended) concerning the Company, the Company’s technology,
potential therapies and other matters. Forward-looking statements
generally include statements that are predictive in nature and depend
upon or refer to future events or conditions, and include words such as
“may,” “will,” “should,” “would,” “expect,” “plan,” “believe,” “intend,”
“look forward,” and other similar expressions among others. Statements
that are not historical facts are forward-looking statements.
Forward-looking statements are based on current beliefs and assumptions
that are subject to risks and uncertainties and are not guarantees of
future performance. Actual results could differ materially from those
contained in any forward-looking statement as a result of various
factors, including, without limitation: unexpected costs, charges or
expenses that reduce cash runway; that Exicure’s pre-clinical programs
do not advance into the clinic or result in approved products on a
timely or cost effective basis or at all; the cost, timing and results
of clinical trials; that many drug candidates that have completed Phase
1 trials do not become approved drugs on a timely or cost effective
basis or at all; possible safety and efficacy concerns; regulatory
developments; and the ability of Exicure to protect its intellectual
property rights. Exicure’s pipeline programs are in various stages of
pre-clinical and clinical development, and the process by which such
pre-clinical or clinical therapeutic candidates could potentially lead
to an approved therapeutic is long and subject to significant risks and
uncertainties. Risks facing the Company and its programs are set forth
in the Company’s filings with the SEC. Except as required by applicable
law, the Company undertakes no obligation to revise or update any
forward-looking statement, or to make any other forward-looking
statements, whether as a result of new information, future events or
otherwise.
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Source: Exicure, Inc.
MacDougall Biomedical Communications
Karen Sharma, 781-235-3060
ksharma@macbiocom.com
or
The
Del Mar Consulting Group, Inc.
Robert Prag, 858-794-9500
President
bprag@delmarconsulting.com