Trial Results

• All 19/19 (100%) patients who received a single full dose of CDX-0159 experienced a clinical response to provocation testing.
• 18/19 (95%) experienced a complete response (CT)
• 1/19 (5%) experienced a marked partial response
• CDX-0159 was generally well tolerated
• The responses are described to be rapid, profound, and durable, and correlated with depletion of skin mast cells.

These data were presented by Dr. Marcus Maurer, Professor of Dermatology and Allergy at Charité – Universitätsmedizin, in Berlin during a late-breaking poster discussion session (#1046) as part of the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress 2021.

From the President & CEO of Celldex Therapeutics and More

Commenting on the results, Anthony S. Marucci, President and Chief Executive Officer of Celldex Therapeutics, said,  “The achievement of a 95% complete response rate, rapid onset and sustained durability after a single dose is unprecedented in this patient population and clearly demonstrates that CDX-0159 has the potential to become an important new treatment option for patients suffering with chronic inducible urticaria. We believe these impressive early data show that CDX-0159 safely depletes mast cells which indicates its potential to impact other diseases with mast cell involvement. We continue to make excellent progress across the CDX-0159 development program in urticaria and expect to expand into prurigo nodularis later this year, and additional indications with mast cell involvement in the future.”

Marcus Maurer, M.D., the Professor of Dermatology and Allergy at Charité – Universitätsmedizin in Berlin, who conducts the study said,“These early-stage results are stunning and represent a major breakthrough for patients with inducible urticarias where current treatment options have been unable to provide relief from often severe symptoms.   While individuals with inducible urticaria go to great lengths to avoid disease triggers in their daily lives, many find it impossible to do so and are impacted by severe itching and burning hives that impair all parts of their lives—their work, their concentration, their sleep and their social behavior. CDX-0159 clearly provided a real benefit to these patients and has meaningfully improved their lives. This novel mast cell depleting mechanism is especially exciting because it can provide insights into the involvement of mast cells across many diseases where their role is not yet well understood by the scientific community.” 

Summary of Data from Ongoing Phase 1b Trial of CDX-0159:

As of the data cut-off on June 11, 2021, 20 patients had received a single intravenous infusion of CDX-0159 at 3 mg/kg, including 11 patients with cold urticaria and 9 patients with symptomatic dermographism. Patients had high disease activity.

In patients with cold urticaria and symptomatic dermographism baseline critical temperature thresholds were 18.9°C/66°F (range: 5-27°C/41-80.6°F) and FricTest® thresholds were 3.8 (range: 3-4) of 4.

Safety results are reported for all 20 patients; activity results are reported for the 19 patients who received a full dose of CDX-0159. 14 of 19 patients completed the 12-week study observation period and five were ongoing (range of 2-8 weeks) as of June 11, 2021.

• All 19/19 (100%) patients experienced a clinical response as assessed by provocation threshold testing; 18/19 (95%) experienced a complete response and 1/19 (5%) experienced a partial response. 
• 10/10 (100%) patients with cold urticaria experienced a complete response.
• 8/9 (89%) patients with symptomatic dermographism experienced a complete response and 1/9 (11%) experienced a partial response.
• Compete responses were observed in all 3 patients (1 cold urticaria; 2 symptomatic dermographism) with prior Xolair® (omalizumab) experience, including two who were Xolair refractory.
• Rapid onset of responses after dosing and sustained durability were observed. 
• Most patients with cold urticaria and symptomatic dermographism experienced a complete response by week 1 and by week 4, respectively.
• The median duration of response for patients was 77+ days for cold urticaria and 57+ days for symptomatic dermographism.
• Improvements in disease activity as reported by physician’s and patient’s global assessment of disease severity were consistent with the complete responses as measured by provocation testing.
• A single 3 mg/kg dose of CDX-0159 resulted in rapid, marked and durable suppression of serum tryptase and depletion of skin mast cells (87% depletion) as measured through biopsy. 
• The kinetics of serum tryptase and skin mast cell depletion mirrored clinical activity.
• This confirmed that serum tryptase level is a robust pharmacodynamic biomarker for assessing mast cell burden and clinical activity in inducible urticaria and potentially in other diseases with mast cell-driven involvement.
• CDX-0159 was generally well tolerated. The most common adverse events were hair color changes, mild infusion reactions, and transient changes in taste perception. 
• Hair color changes (generally small areas of hair color lightening) and taste disorders (generally partial changes of ability to taste salt) are consistent with inhibiting KIT signaling in other cell types and are expected to be fully reversible.
• As previously reported, a single severe infusion reaction of brief loss of consciousness was observed in a patient with a history of fainting. The patient rapidly recovered. Importantly, no evidence of mast cell activation as measured by serum tryptase monitoring was observed.
• There was no evidence of clinically significant decreases in hematology parameters—an important finding for a KIT inhibitor.
• One patient with symptomatic dermographism enrolled in the study also had a diagnosis of prurigo nodularis. After a single dose of CDX-0159, this patient experienced both a complete response of symptomatic dermographism and notable improvement of the prurigo nodularis.

Celldex plans to initiate a study in prurigo nodularis in the fourth quarter of 2021.

The Study

The Phase 1b study is an open-label clinical trial designed to evaluate the safety of a single dose of CDX-0159 in patients with cold urticaria or symptomatic dermographism who are refractory to antihistamines. The study was recently amended to also add a cohort of 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.

For additional information on this trial (NCT04548869), please visit www.clinicaltrials.gov.

A pre-recorded poster discussion at EAACI was made available on July 9, Yet, a Q&A with the session chair will also take place on Monday, July 12, 2021 at 12:30-13:30 p.m. CET (6:30-7:30 a.m. ET). 

• A subcutaneous formulation of CDX-0159 is planned to enter the clinic in the third quarter of 2021.
• Celldex plans to initiate a study in prurigo nodularis in the fourth quarter of 2021.
• Celldex remains on track to initiate Phase 2 trials in both spontaneous and inducible urticaria in the first half of 2022.
• Initial results from the cholinergic cohort are planned for presentation at a scientific congress in the first quarter of 2022.
• Treatment results from the Phase 1b study in chronic spontaneous urticaria are planned for presentation at a scientific congress in early summer of 2022.
• The Company plans to expand development into a fourth indication by year-end 2022.

Webcast and Conference Call

The Company will host a conference call/webcast along with Dr. Marcus Maurer to discuss the results at 8:15 a.m. ET on Monday, July 12. The event will be webcast live 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 (866) 743-9666 (within the United States) or (760) 298-5103 (outside the United States). The conference ID is 4493642. A replay of the call will be archived on the Company’s website or can be accessed by dialing (855) 859-2056 (within the United States) or (404) 537-3406 (outside the United States). The conference ID is 4493642. 

About Chronic Inducible Urticaria

Chronic inducible urticarias are forms of urticaria that have an attributable trigger associated with them, typically resulting in wheals (hives) or angioedema. Approximately 0.5% of the total population suffers from chronic inducible urticarias.

Celldex is exploring the three most common forms: cold-induced, dermographism (scratch-induced) and cholinergic (exercise/sweat-induced).

People afflicted with cold urticaria experience 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 the 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 chronic inducible urticarias. Patients use antihistamines and attempt to manage the symptoms associated with their disease by avoiding the triggers.

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.

Prohost Observations 

Celldex was almost buried after the failure of one product in a clinical trial. We kept the firm in the Prohost Aggressive Portfolio (Table #7), knowing, for certain, that a firm with solid scientific fundamentals, excellent management,  excellent researchers and promising product pipeline does not die easily. As a matter of fact, the firm resurrected, its stock rebounded and soared.

Celldex is indeed a member of the Prohost Portfolio.  

Click here to read more about Celldex Therapeutics.