Celldex Therapeutics, Inc. (NASDAQ:CLDX) today reported
interim data from the Company’s ongoing, open label clinical trial
of CDX-0159 in patients with antihistamine refractory cold contact
urticaria (ColdU) and symptomatic dermographism (SD), the two most
common forms of chronic inducible urticaria (CIndU). In all
patients treated and assessed for at least 15 days after treatment
(n=10), 8 of 10 patients (80%) experienced a complete response (CR)
to provocation testing post-treatment and one patient experienced a
partial response (PR). CDX-0159 was generally well tolerated.
CDX-0159 is a humanized monoclonal antibody developed by Celldex
that binds the KIT receptor with high specificity and potently
inhibits its activity. The KIT receptor tyrosine kinase is
expressed in a variety of cells, including mast cells, which
mediate inflammatory responses such as hypersensitivity and
allergic reactions. Enrollment is currently being completed in the
ColdU and SD cohorts (10 per cohort; 20 total). Based on these
compelling results, the study will be expanded to also include 10
patients with cholinergic urticaria. The Company will host a
conference call at 7:45 am ET today to discuss results and will be
joined by Dr. Marcus Maurer, Professor of Dermatology and Allergy
at Charité - Universitätsmedizin in Berlin, who is conducting
the study.
“CDX-0159 is having a profound, beneficial impact for patients
in this study, all of whom entered with significant disease which
was refractory to antihistamines,” said Dr. Maurer. “As a
physician, it is exciting to see such high complete response rates,
which are made even more noteworthy by the fact that the responses
are developing rapidly after treatment and are coupled with a
well-tolerated safety profile to date. Inducible urticarias can
significantly impact a patient’s quality of life, and this is
especially true for cold contact urticaria and symptomatic
dermographism, as avoiding the triggers for these diseases is
extremely difficult. CDX-0159 through its unique ability to impact
mast cells is demonstrating great potential and could be a
much-needed addition to the treatment landscape.”
Data Summary:Fifteen out of 20 planned patients
with antihistamine refractory CIndU have received a single
intravenous infusion of CDX-0159 at 3 mg/kg, including nine
patients with cold contact urticaria (ColdU) and six patients with
symptomatic dermographism (SD). Safety results are reported for all
15 patients; activity results are reported for all patients
assessed for at least 15 days/2 weeks after treatment (n=10; 7
ColdU and 3 SD). Patients had high disease activity as assessed by
provocation threshold testing. In ColdU and SD pts, baseline
critical temperature thresholds were 18.7 +/- 2.7 °C (range:
5-27°C) and FricTest® thresholds were 3.7 +/- 0.3 (range: 3-4) of
4.
- Eight of 10 patients (7 ColdU; 1 SD) experienced a complete
response (CR) as assessed by provocation threshold testing through
their latest assessment. The remaining two patients (both with SD)
were recently treated and have been followed for two weeks. One
patient experienced a partial response (PR) thus far, and one
patient has reported symptomatic improvement (decreased itching).
All patients will continue to be assessed for response through week
12.
- Patient global assessment (Pat-GA) and physician global
assessment (Phy-GA) results are consistent with provocation testing
results.
- Measurements of serum tryptase levels are available for only
the first six patients evaluated for activity, all with ColdU. The
mean baseline was 3.3 +/- 0.2 ng/ml and levels on day 15 after
treatment were at or below the limit of detection. These patients
all experienced complete responses.
- CDX-0159 was generally well tolerated. Six of 15 patients had
mild infusion reactions, generally areas of localized redness and
itching, which resolved rapidly. A single severe infusion reaction
was observed (brief loss of consciousness, followed by shaking and
sweating). The patient was treated with antihistamines and
steroids; no epinephrine was administered. The patient rapidly
recovered and was hospitalized for observation with no further
manifestations of this event. Importantly, there was no evidence of
mast cell activation as measured by decreases in serum tryptase
levels shortly after the infusion and further at a later time
point.
- Through day 15, three patients had transient, mild decreases in
hemoglobin, and no patients had meaningful declines in white blood
cells.
“The interim results reported today further reinforce our
enthusiasm for CDX-0159,” said Anthony S. Marucci, President and
Chief Executive Officer of Celldex Therapeutics. “We look forward
to the completion of the cold contact and symptomatic dermographism
cohorts over the coming weeks and plan to report on the balance of
these patients and longer term follow up that will further
characterize the magnitude and duration of treatment effects, most
likely at a medical meeting this summer. We also hope to see
cholinergic patients begin to enter the study in May. Looking
beyond inducible urticaria, manufacturing activities are also
progressing as planned to support the introduction of the
subcutaneous formulation into the clinical program in the third
quarter. We also anticipate results from the ongoing Phase 1b study
in chronic spontaneous urticaria by the end of this year and are on
track to initiate a third study in prurigo nodularis in the fourth
quarter.”
CIndUs are forms of urticaria that have an attributable cause or
trigger associated with them, typically resulting in wheals (hives)
or angioedema. Approximately 0.5% of the total population suffers
from CIndUs. Celldex is exploring the three most common forms of
CIndU, cold-induced, dermographism (scratch-induced) and
cholinergic (exercise/sweat-induced). People afflicted with ColdU
experience symptoms like itching, burning wheals and angioedema
when their skin is exposed to temperatures below skin temperature.
Symptomatic dermographism is characterized by the development of a
wheal and flare reaction in response to stroking, scratching or
rubbing of the skin and usually occurs within minutes of the
inciting stimulus. Cholinergic urticaria is triggered by the body’s
sweating response to active or passive body warming, and is
characterized by small (1–4 mm) wheals surrounded by bright red
flares. Common triggers include exercise, hot baths/showers, fever,
occlusive dressings, eating spicy foods and emotional stress. For
these diseases, mast cell activation leading to release of soluble
mediators is thought to be the driving mechanism leading to the
wheals and other symptoms. There are currently no approved
therapies for CIndUs other than antihistamines and patients attempt
to manage symptoms associated with their disease through avoidance
of triggers. Celldex believes that CDX-0159 has significant
potential to directly ablate and/or inhibit mast cells and this, in
turn, could benefit patients with CIndU or other mast cell-driven
diseases.
Phase 1b CIndU Study Design
The Phase 1b study (NCT04548869) is an open label clinical trial
designed to evaluate the safety of a single dose of CDX-0159 in up
to 20 patients with cold contact urticaria (n=10) or symptomatic
dermographism (n=10) who are refractory to antihistamines. The
study has been amended to also add a cohort of 10 patients with
cholinergic urticaria. Patients' symptoms are induced via
provocation testing that resembles real life triggering situations.
Secondary and exploratory objectives include pharmacokinetic and
pharmacodynamic assessments, including changes from baseline
provocation thresholds, measurement of tryptase and stem cell
factor levels, clinical activity outcomes (impact on urticaria
symptoms, disease control, clinical response), quality of life
assessments and measurement of tissue mast cells through skin
biopsies. CDX-0159 is administered intravenously (3.0 mg/kg) as add
on treatment to H1-antihistamines and patients are followed for 12
weeks after dosing.
Webcast and Conference CallCelldex executives
will host a conference call/webcast along with Dr. Marcus Maurer to
discuss the results at 7:45 a.m. ET today. The event will
be webcast live over the internet and can be accessed by going to
the "Events & Presentations" page under the "Investors &
Media" section of the Celldex Therapeutics website
at www.celldex.com. The call can also be accessed by dialing
1-760-298-5103 (within the United States) or 1-866-743-9666
(outside the United States). The conference ID is 5399769. A
replay of the call will be archived on the Company's website or can
be accessed by dialing 1-404-537-3406 (within the United
States) or 1-855-859-2056 (outside the United States). The
conference ID is 5399769.
About CDX-0159CDX-0159 is a humanized
monoclonal antibody developed by Celldex that binds the KIT
receptor with high specificity and potently inhibits its activity.
The KIT receptor tyrosine kinase is expressed in a variety of
cells, including mast cells, which mediate inflammatory responses
such as hypersensitivity and allergic reactions. KIT signaling
controls the differentiation, tissue recruitment, survival and
activity of mast cells. In a Phase 1a single dose, healthy
volunteer study, CDX-0159 demonstrated a favorable safety profile
as well as profound and durable reductions of plasma tryptase,
indicative of systemic mast cell ablation or suppression. Based on
these data, Celldex has initiated two Phase 1b studies in the mast
cell-driven disease chronic spontaneous urticaria (CSU) and the
three most common forms of chronic inducible urticaria (CIndU)—cold
contact urticaria, symptomatic dermographism and cholinergic
urticaria. The Company is also planning a third study in prurigo
nodularis (PN), where mast cells through their interactions with
sensory neurons and other immune cells are believed to play an
important role in amplifying chronic itch and neurogenic
inflammation.
About Celldex Therapeutics, Inc.Celldex is a
clinical stage biotechnology company dedicated to developing
monoclonal and bispecific antibodies that address devastating
diseases for which available treatments are inadequate. Our
pipeline includes antibody-based therapeutics which have the
ability to engage the human immune system and/or directly affect
critical pathways to improve the lives of patients with
inflammatory diseases and many forms of cancer. Visit
www.celldex.com.
Forward Looking Statement This release contains
"forward-looking statements" made pursuant to the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995.
These statements are typically preceded by words such as
"believes," "expects," "anticipates," "intends," "will," "may,"
"should," or similar expressions. These forward-looking statements
reflect management's current knowledge, assumptions, judgment and
expectations regarding future performance or events. Although
management believes that the expectations reflected in such
statements are reasonable, they give no assurance that such
expectations will prove to be correct or that those goals will be
achieved, and you should be aware that actual results could differ
materially from those contained in the forward-looking statements.
Forward-looking statements are subject to a number of risks and
uncertainties, including, but not limited to, our ability to
successfully complete research and further development and
commercialization of Company drug candidates; the effects of the
outbreak of COVID-19 on our business and results of operations; the
uncertainties inherent in clinical testing and accruing patients
for clinical trials; our limited experience in bringing programs
through Phase 3 clinical trials; our ability to manage and
successfully complete multiple clinical trials and the research and
development efforts for our multiple products at varying stages of
development; the availability, cost, delivery and quality of
clinical materials produced by our own manufacturing facility or
supplied by contract manufacturers, who may be our sole source of
supply; the timing, cost and uncertainty of obtaining regulatory
approvals; the failure of the market for the Company's programs to
continue to develop; our ability to protect the Company's
intellectual property; the loss of any executive officers or key
personnel or consultants; competition; changes in the regulatory
landscape or the imposition of regulations that affect the
Company's products; our ability to continue to obtain capital to
meet our long-term liquidity needs on acceptable terms, or at all,
including the additional capital which will be necessary to
complete the clinical trials that we have initiated or plan to
initiate; and other factors listed under "Risk Factors" in our
annual report on Form 10-K and quarterly reports on Form 10-Q.
All forward-looking statements are expressly qualified in their
entirety by this cautionary notice. You are cautioned not to place
undue reliance on any forward-looking statements, which speak only
as of the date of this release. We have no obligation, and
expressly disclaim any obligation, to update, revise or correct any
of the forward-looking statements, whether as a result of new
information, future events or otherwise.
Company ContactSarah CavanaughSenior Vice
President, Corporate Affairs & AdministrationCelldex
Therapeutics, Inc.(508) 864-8337scavanaugh@celldex.com
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