Celldex Initiates Global Registrational Phase 3 Program of Barzolvolimab in Cold Urticaria and Symptomatic Dermographism

Rhea-AI Summary

Celldex (NASDAQ:CLDX) initiated EMBARQ-ColdU and SD, a global randomized Phase 3 program testing barzolvolimab in adults with cold urticaria (ColdU) and symptomatic dermographism (SD) who remain symptomatic despite H1 antihistamines.

The study will enroll ~240 participants across ~75 sites in 7 countries, randomized 1:1 to barzolvolimab (450 mg loading, then 150 mg Q4W) or placebo for 24 weeks; primary endpoint is complete response at Week 12 by TempTest® (ColdU) or FricTest® (SD). Phase 2 met all primary and secondary endpoints with rapid, durable responses and a well-tolerated safety profile.

Positive

• Global Phase 3 launch across ~75 sites in 7 countries
• Planned enrollment of ~240 participants (120 ColdU; 120 SD)
• Phase 2: primary and secondary endpoints met with high significance
• Phase 2 response rates: up to 75% ColdU, 67% SD at Week 12
• Safety profile described as well-tolerated in Phase 2

Negative

• No approved advanced therapies for ColdU and SD (regulatory path required)
• Open-label extension data and longer-term results are pending Q1 2026

Key Figures

Phase 3 enrollment Approximately 240 participants Planned EMBARQ-ColdU and SD trial size

ColdU cohort size Approximately 120 participants Phase 3 ColdU cohort

SD cohort size Approximately 120 participants Phase 3 SD cohort

Dose regimen 150 mg Q4W, 450 mg loading Barzolvolimab dosing in Phase 3 EMBARQ-ColdU and SD

Partial/complete response ColdU Up to 75% Phase 2 ColdU partial or complete response at 20 weeks

Partial/complete response SD Up to 67% Phase 2 SD partial or complete response at 20 weeks

Disease prevalence More than 533K patients ColdU and SD across US and Europe

Inadequate control on antihistamines More than 80% of patients ColdU and SD patients lacking adequate disease control

Market Reality Check

$28.19 Last Close

Volume Volume 1,089,674 is running at a 1.33x multiple of the 20-day average, indicating elevated interest ahead of this Phase 3 start. normal

Technical Shares at $29.80 are trading above the 200-day MA of $22.36 and sit 2.3% below the 52-week high of $30.50.

Peers on Argus

CLDX is modestly higher while key biotech peers like COGT (-6.43%), ARDX (-2.65%) and AUPH (-2.00%) trade lower, pointing to stock-specific strength rather than a sector-wide move.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 06	CSU Phase 2 data	Positive	-2.0%	Additional CSU Phase 2 data showed strong, durable disease control with barzolvolimab.
Nov 06	ColdU/SD Phase 2	Positive	-2.0%	ColdU and SD Phase 2 results demonstrated high complete and partial response rates vs placebo.
Oct 30	CDX-622 Phase 1	Positive	+0.0%	Initial CDX‑622 Phase 1 data showed favorable safety, PK and sustained mast cell inhibition.
Sep 17	CSU IgE analysis	Positive	+0.0%	Barzolvolimab improved CSU regardless of baseline IgE, with rising complete response rates over time.
Aug 19	EoE Phase 2 miss	Negative	+0.0%	Barzolvolimab met biological but not clinical endpoints in EoE, leading to program discontinuation.

Pattern Detected

Positive barzolvolimab and other clinical readouts have often been followed by flat-to-negative one-day moves, while clearly negative data coincided with a sharp selloff.

Recent Company History

Over the last few months, Celldex has repeatedly highlighted barzolvolimab’s progress, with multiple positive Phase 2 updates in CSU, ColdU and SD on Nov 6, 2025, followed by plans for Phase 3 initiation in Dec 2025. Additional data on CDX‑622 in October showed favorable safety and mast cell inhibition. One major setback came on Aug 19, 2025, when barzolvolimab failed to show clinical benefit in EoE and development in that indication was stopped. Today’s Phase 3 start fits the ongoing pivot toward urticaria and other mast cell–driven diseases.

Market Pulse Summary

The stock moved -5.7% in the session following this news. A negative reaction despite advancement into Phase 3 would fit past patterns where positive barzolvolimab updates saw weak price follow‑through. Investors have previously reacted strongly to setbacks, such as the EoE discontinuation, so any selloff could reflect concern about trial risk, concentration in mast cell diseases, or future funding needs to support large global studies rather than the specifics of this ColdU/SD protocol.

Key Terms

monoclonal antibody medical

"Barzolvolimab is a humanized monoclonal antibody that specifically binds..."

A monoclonal antibody is a laboratory-made protein designed to recognize and attach to a specific target in the body, such as a disease-causing substance or cell. It functions like a highly precise lock-and-key tool, helping to treat or detect illnesses. For investors, companies developing monoclonal antibodies can represent promising opportunities in the healthcare sector, especially as these treatments often address unmet medical needs.

receptor tyrosine kinase medical

"specifically binds the receptor tyrosine kinase KIT with high specificity..."

A receptor tyrosine kinase is a protein on a cell’s surface that acts like a switch, receiving signals from outside the cell and turning on internal processes by adding small chemical tags (phosphate groups) to other proteins. Investors care because these switches control cell growth, survival and communication, so drugs or tests that block or modify them can become important treatments; their clinical progress, approvals or setbacks often have a major impact on company value and risk.

provocation test medical

"percent of patients with complete response (negative provocation test) at Week 12..."

A provocation test is a medical procedure that intentionally exposes a patient to a suspected trigger—such as a drug, chemical, allergen, or stressor—to see whether it reliably produces symptoms. For investors, these tests matter because they can prove whether a treatment works or causes harm, influence regulatory approval, change product labeling, or reveal safety risks that affect sales, legal exposure, and market trust; think of it as a controlled experiment to confirm cause-and-effect.

open label extension medical

"patients ... were given the option to enter an open label extension (OLE)..."

An open-label extension is a follow-on phase of a clinical trial where participants keep receiving the experimental drug and both doctors and patients know what treatment is being given. It matters to investors because it produces longer-term safety and effectiveness information, helps regulators and companies assess ongoing benefits or risks, and can indicate whether a therapy has staying commercial value — like an extended test drive revealing durability and real-world performance.

Phase 3 medical

"Celldex announced today the initiation of its global Phase 3 trial (EMBARQ-ColdU and SD)..."

Phase 3 is the late-stage clinical testing step for a new drug or medical treatment, where the product is given to large groups of patients to confirm effectiveness, monitor side effects, and compare it to standard care. Successful Phase 3 results are often the final scientific hurdle before regulators decide on approval and market launch—like passing a final exam before graduation—and can sharply change a company's valuation and future revenue prospects.

Phase 2 medical

"all primary and secondary endpoints met ... in Phase 2 study"

Phase 2 is the mid-stage clinical trial where a new drug or treatment is tested in a larger group of patients to see if it works and to keep checking safety after initial human testing. Think of it as a field test that proves whether a product actually delivers its promised benefit. Investors watch Phase 2 closely because its results strongly influence a medicine’s chances of reaching the market, the size of its potential sales, and the company’s valuation.

AI-generated analysis. Not financial advice.

• No advanced therapies approved to treat ColdU and SD—diseases of misery that dramatically impact all aspects of patient life
• Barzolvolimab is the only drug in development to demonstrate clinical benefit in patients in ColdU and SD in a large, randomized, placebo-controlled study--all primary and secondary endpoints met with high statistical significance at 12 weeks and sustained through end of treatment period (20 weeks) in Phase 2 study
• Initiation of EMBARQ-ColdU and SD marks second barzolvolimab Phase 3 program; Phase 3 in CSU ongoing
  

HAMPTON, N.J., Dec. 09, 2025 (GLOBE NEWSWIRE) -- Celldex (NASDAQ:CLDX) announced today the initiation of its global Phase 3 trial (EMBARQ-ColdU and SD) designed to establish the efficacy and safety of barzolvolimab in adult patients with cold urticaria (ColdU) and symptomatic dermographism (SD) who remain symptomatic despite H1 antihistamine treatment. ColdU and SD are characterized by the occurrence of hives or wheals that have an attributable trigger associated with them—exposure to cold temperatures in ColdU and scratching/rubbing of the skin in SD. Mast cell activation is known to be a critical driver in ColdU and SD. Barzolvolimab is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity, which is required for mast cell function and survival. 

“Across studies in cold urticaria and symptomatic dermographism, barzolvolimab has demonstrated a unique and profound ability to offer rapid, sustained, complete disease response, providing hope for patients who are impacted by severe itching and hives that dramatically impact all aspects of their lives despite constant vigilance to avoid disease triggers,” said Diane C. Young, MD, Senior Vice President and Chief Medical Officer of Celldex. “Advancing a promising agent that addresses the root driver of the disease—the mast cell—into a registrational study is a significant step forward for patients and physicians who desperately need better treatment options.”

EMBARQ-ColdU and SD is designed to establish the efficacy and safety of barzolvolimab in adult participants with ColdU and SD who remain symptomatic despite H1 antihistamine treatment. Participants who remain symptomatic after treatment with biologics are also eligible for the study. The randomized, double-blind, placebo-controlled, parallel group Phase 3 study will recruit participants from approximately 75 clinical trial sites across 7 countries. Approximately 240 participants will be enrolled to 2 separate cohorts (differentiated by subtype) to include approximately 120 participants with ColdU and 120 participants with SD. Participants in each cohort will be randomized in a 1:1 ratio to one of two treatment arms: cohort 1: barzolvolimab 150 mg every 4 weeks (Q4W) following a loading dose of 450 mg on Day 1 or cohort 2: matching placebo for 24 weeks. The primary endpoint of the study will evaluate the percent of patients with complete response (negative provocation test) at Week 12 as assessed by the TempTest® in ColdU and the FricTest® in SD. After completing the treatment period, participants will continue to be followed for 16 weeks.

“Barzolvolimab is now advancing across five indications demonstrating its significant potential to treat a broad array of mast cell driven diseases with Phase 3 studies ongoing in chronic spontaneous urticaria, cold urticaria and symptomatic dermographism and Phase 2 studies in prurigo nodularis and atopic dermatitis,” said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex. “We remain focused on executing these trials seamlessly and achieving our goal of making barzolvolimab available to meet the needs of patients.”

There are no advanced therapies approved to treat the more than 533K patients impacted by ColdU and SD across the United States and Europe. Patients are typically treated with up to four times the labeled dose of antihistamines, but more than 80% continue to report inadequate disease control. ColdU and SD are diseases of misery and despite best efforts, patients often find it impossible to avoid disease triggers and are impacted by severe itching and burning hives that dramatically impact all aspects of their lives. More than 60% of patients report moderate to severe impact on their mental/emotional well-being, daily activities, and social/intimate relationships, suffering from social stigma, including being asked if they are contagious, being stared at in public, and people refusing to shake hands or touch them.¹ Not surprisingly, patients with ColdU and SD also report high rates of anxiety and depression.²

Results from a placebo controlled Phase 2 study in ColdU and SD demonstrated that barzolvolimab met the primary endpoint of the study, a statistically significant difference between the percent of participants with a negative provocation test compared to placebo at Week 12 as assessed by the TempTest^® in ColdU and the FricTest^® in SD. Importantly, barzolvolimab demonstrated rapid, durable and clinically meaningful responses with up to 75% of patients with ColdU and 67% of patients with SD obtaining a partial or complete response. Secondary endpoints in the study were also achieved at week 12 and strongly supported the primary endpoint results, including responder analyses, improvements in Critical Temperature and Critical Friction Thresholds (CFT and CFT), changes in WI-NRSprovo (itch associated with provocation test) and Urticaria Control Test. These effects were sustained through the end of the treatment period (20 weeks) with up to 78% of patients with ColdU and 58% of patients with SD obtaining a partial or complete response. Barzolvolimab demonstrated a well-tolerated safety profile over the course of the study. Patients were followed for up to 24 weeks after treatment completion and patients with returning or continuing symptoms were given the option to enter an open label extension (OLE) during this follow up period. Consistent with the clinical endpoint results at Week 20, placebo-treated patients entered the OLE at a faster rate compared to barzolvolimab-treated patients. Data from the OLE are expected to be presented in Q1 2026.

For additional information on EMBARQ-ColdU and SD (NCT07266402), please visit www.clinicaltrials.gov.

¹Winders et al. Impact of chronic inducible urticaria (CIndU) on patients’ health-related quality of life: Results from Urticaria Voices study; presented at EAACI Congress 2025.
²EADV poster: Prevalence, clinical profile and burden of chronic inducible urticaria in EU5, US and Japan, Sep 2022.

TempTest^® and FricTest^® are registered trademarks of Moxie GmbH.

About Barzolvolimab
Barzolvolimab is a humanized monoclonal antibody that binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity. KIT 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 certain inflammatory diseases, such as chronic urticaria, mast cell activation plays a central role in the onset and progression of the disease. Barzolvolimab is currently being studied in chronic spontaneous urticaria (CSU), two forms of chronic inducible urticaria (CIndU) – cold urticaria (ColdU) and symptomatic dermographism (SD), prurigo nodularis (PN) and atopic dermatitis (AD), with additional indications planned for the future.

About Chronic Inducible Urticaria (CIndU), Cold Urticaria (ColdU) and Symptomatic Dermographism (SD):
Cold Urticaria (ColdU) and Symptomatic Dermographism (SD) are forms of Chronic Inducible Urticaria (CIndU), characterized by the occurrence of hives or wheals that have an attributable trigger associated with them. ColdU symptoms include itching, burning wheals/hives and angioedema when skin is exposed to cold temperatures. SD symptoms include the development of wheals in response to stroking, scratching or rubbing of the skin. Approximately 0.5% of the total population suffers from chronic inducible urticarias. 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 ColdU and SD other than antihistamines and patients attempt to manage symptoms associated with their disease through avoidance of triggers.

About Celldex
Celldex is pioneering new horizons in immunology to deliver life-changing therapies. We are relentless in our pursuit of novel antibody-based treatments that engage the human immune system and directly affect critical pathways to improve the lives of patients with allergic, inflammatory and autoimmune disorders.
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, including barzolvolimab (also referred to as CDX-0159) and CDX-622, in current or future indications; 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 Contact
Sarah Cavanaugh
Senior Vice President, Corporate Affairs & Administration
(508) 864-8337
scavanaugh@celldex.com

Patrick Till
Meru Advisors
(484) 788-8560
ptill@meruadvisors.com

FAQ

What is the design of Celldex's EMBARQ-ColdU and SD Phase 3 study (CLDX)?

Randomized, double-blind, placebo-controlled; ~240 participants across 2 cohorts (120 ColdU; 120 SD), 1:1 randomization, 24-week treatment.

What is the dosing regimen for barzolvolimab in the EMBARQ-ColdU and SD trial (CLDX)?

A loading dose of 450 mg on Day 1 followed by 150 mg every 4 weeks (Q4W).

What is the primary endpoint and timing for CLDX's Phase 3 ColdU and SD study?

Percent of patients with complete response at Week 12 by TempTest® (ColdU) or FricTest® (SD).

What Phase 2 efficacy results support Celldex's CLDX Phase 3 program?

Phase 2 met all primary and secondary endpoints with up to 75% ColdU and 67% SD partial/complete responses at Week 12.

When will additional longer-term or open-label data for barzolvolimab be available for CLDX?

Data from the open-label extension are expected to be presented in Q1 2026.

Who is eligible for the EMBARQ-ColdU and SD trial (CLDX)?

Adults with ColdU or SD who remain symptomatic despite H1 antihistamines; participants symptomatic after biologics are also eligible.