CLDX Celldex Therapeutics Inc

Celldex Therapeutics, Inc. (NASDAQ:CLDX) announced today new data demonstrating sustained and deepening disease efficacy and a well tolerated safety profile over a 52 week treatment period for barzolvolimab in chronic spontaneous urticaria (CSU), an immune-related condition driven by mast cell activation. Barzolvolimab specifically targets mast cells by binding the receptor tyrosine kinase KIT with high specificity and potently inhibiting its activity, which is required for mast cell function and survival. The data are bring presented today by Dr. Martin Metz, Professor of Dermatology and Allergy at Charité - Universitätsmedizin in Berlin in a late breaking oral presentation at the EADV Congress 2024. The Company previously announced that this Phase 2 study of barzolvolimab in patients with moderate to severe CSU refractory to antihistamines, including patients with biologic-refractory disease, met its primary endpoint—a significant improvement in UAS7 compared to placebo at 12 weeks—across all dose groups tested.

“The barzolvolimab data reported today set a new bar for efficacy in CSU—demonstrating the highest rate of complete response observed in a well controlled study,” said Martin Metz, M.D. "By addressing the root driver of chronic spontaneous urticaria, the mast cell, barzolvolimab provides early, durable and, most importantly, the opportunity for complete symptom control for the many patients who do not see meaningful benefit from the current standard of care, including patients with omalizumab refractory disease. Importantly, barzolvolimab was also well tolerated across the 52 week treatment period further supporting barzolvolimab’s significant potential to become a transformative treatment option for patients suffering from this often very severe and debilitating disease."

New long-term data from the Phase 2 study of barzolvolimab assessed at 52 weeks:

• Improvements in UAS7 (weekly urticaria activity score), previously shown to be statistically significantly vs placebo at Week 12, were noted as early as week 1 and were sustained or deepened at Week 52.

• At Week 16, patients receiving low dose barzolvolimab (75 mg) or placebo were transitioned to barzolvolimab 150 mg or 300 mg; after crossover, these patients experienced similar clinically meaningful disease response as the rest of the study population.

• 71% of patients treated with barzolvolimab 150 mg Q4W and 52% of patients treated with 300 mg Q8W had a complete response (no itch/hives; UAS7=0) at Week 52. These responses were observed early and sustained through 52 weeks.

• 74% of patients treated with barzolvolimab 150 mg Q4W and 68% of patients treated with 300 mg Q8W had well controlled (UAS7<6) disease at Week 52.

• These robust responses were observed regardless of prior omalizumab experience.

Barzolvolimab was well tolerated with a favorable safety profile through 52 weeks of treatment. Most adverse events were grade 1 (mild), mechanism related (KIT) and expected to be reversible. The most common treatment emergent adverse events occurring in greater than 10% of barzolvolimab treated patients were hair color changes, neutropenia, urticaria, skin hypopigmentation (areas of skin lightening) and nasopharyngitis (common cold). Neutrophil counts did not decline further with continued dosing and there was no association between infections and neutropenia. The hypopigmentation was observed with longer term exposure and did not lead to treatment discontinuation. Adverse events were not dose dependent.

"We believe this data set is a landmark event for the barzolvolimab program and for the treatment of CSU,” said Diane C. Young, M.D., Senior Vice President and Chief Medical Officer of Celldex Therapeutics. “CSU is a disease of misery that often impacts all aspects of patients’ lives. There is an urgent need for new treatment options and the profound and sustained results observed across all endpoints in this study suggest that barzolvolimab could play a critical role in addressing this unmet need for patients, their families and physicians. Phase 3 studies of barzolvolimab in CSU are actively enrolling patients and progressing on schedule.”

Additional Presentation at EADVAn e-Poster (#P3596) entitled “Barzolvolimab treatment improves quality of life and urticaria control in patients with chronic spontaneous urticaria (CSU): Results from a Phase 2 trial” is available at EADV in the e-poster area. These data are from the 12 week analysis. 67% and 57% of patients treated with 150 mg Q4W or 300 mg Q8W, respectively, reported improvement of CSU and their quality of life (DLQI score of 0 or 1). The majority of patients (>65%) treated with 150 mg Q4W or 300 mg Q8W achieved well-controlled urticaria (UCT≥12). Findings were similar for patients with prior omalizumab experience.

Results presented at the EADV Congress 2024 are available on the "Publications” page of the "Science" section of the Celldex website.

Webcast The Company will host a conference call/webcast today to discuss the results at 12:00 pm ET/6:00 pm CEST. To access the live and archived webcast, please visit the Investor Relations page of Celldex’s website at https://ir.celldex.com/events-presentations. Parties interested in participating via telephone may register here to receive the dial-in numbers and unique PIN to seamlessly access the call. Otherwise please access the listen-only webcast link. The archived webcast will be available for a limited time on the Company’s website.

About BarzolvolimabBarzolvolimab 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), chronic inducible urticaria (CIndU), prurigo nodularis (PN) and eosinophilic esophagitis (EOE) with additional indications planned for the future, including atopic dermatitis (AD).

About the Phase 2 CSU StudyThe randomized, double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab in patients with CSU who remain symptomatic despite antihistamine therapy, to determine the optimal dosing strategy. 208 patients were randomly assigned on a 1:1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 16-week placebo-controlled treatment period. After 16 weeks, patients then entered a 36-week active treatment period, in which patients receiving placebo or the 75 mg dose were randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks; patients already randomized to the 150 mg and 300 mg treatment arms remained on the same regimen as during the placebo-controlled treatment period. After 52 weeks, patients enter a follow-up period for an additional 24 weeks. Barzolvolimab achieved the primary efficacy endpoint of the study—a statistically significant mean change from baseline to week 12 in UAS7 (weekly urticaria activity score) compared to placebo at all dose levels. For additional information on this trial (NCT05368285), please visit www.clinicaltrials.gov.

About the Phase 3 CSU ProgramIn July, Celldex initiated a global Phase 3 Program for barzolvolimab in CSU, consisting of two Phase 3 trials (EMBARQ-CSU1; NCT06445023 and EMBARQ-CSU2; NCT06455202) designed to establish the efficacy and safety of barzolvolimab in adult patients with CSU who remain symptomatic despite H1 antihistamine treatment. The studies also include patients who remain symptomatic after treatment with biologics. Enrollment is underway.

About Chronic Spontaneous Urticaria (CSU)CSU is characterized by the occurrence of hives or wheals for 6 weeks or longer without identifiable specific triggers or causes. The activation of the mast cells in the skin (release of histamines, leukotrienes, chemokines) results in episodes of itchy hives, swelling and inflammation of the skin that can go on for years or even decades. Current therapies provide symptomatic relief only in some patients.

About Celldex Therapeutics, Inc.Celldex is a clinical stage biotechnology company leading the science at the intersection of mast cell biology and the development of transformative therapeutics for patients. 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 severe inflammatory, allergic, autoimmune and other devastating diseases. Visit www.celldex.com.

Forward Looking StatementThis 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), 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 ContactSarah CavanaughSenior Vice President, Corporate Affairs & Administration(508) 864-8337scavanaugh@celldex.com

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