Celldex Therapeutics, Inc. (Celldex) operates as a biopharmaceutical company.
The company is dedicated to exploring the science of mast cell biology and developing therapeutic antibodies 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. The company's drug candidates include monoclonal and bispecific antibodies designed to address mast ce...
Celldex Therapeutics, Inc. (Celldex) operates as a biopharmaceutical company.
The company is dedicated to exploring the science of mast cell biology and developing therapeutic antibodies 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. The company's drug candidates include monoclonal and bispecific antibodies designed to address mast cell mediated diseases for which available treatments are inadequate.
The company focuses its efforts and resources on the continued research and development of:
Barzolvolimab (also referred to as CDX-0159), a monoclonal antibody that specifically binds the KIT receptor and potently inhibits its activity, which is being studied across multiple mast cell driven diseases, including:
Chronic Urticarias: The company-initiated Phase 3 studies in chronic spontaneous urticaria (CSU) in July 2024. In November 2023, it announced that its Phase 2 study in CSU achieved the primary efficacy endpoint (statistically significant mean change from baseline to week 12 of urticaria activity score compared to placebo) and was well tolerated. Patients on study continued to receive barzolvolimab, and in September 2024, the company reported data from 52 weeks of treatment, demonstrating sustained and deepening disease efficacy along with a well-tolerated long-term safety profile. In July 2024, it announced that its Phase 2 study in chronic inducible urticaria (CIndU) achieved the primary efficacy endpoint (statistically significant difference between the percent of patients with a negative provocation test compared to placebo at week 12) and was well tolerated. 12-week data from the CIndU study were presented in October 2024, and all secondary endpoints across the study were also met, showing high statistical significance and clinical meaningful. Patients in the study continued to receive barzolvolimab for 20 weeks of treatment.
Prurigo Nodularis (PN): In April 2024, the company initiated a Phase 2 study in PN and enrollment is ongoing; positive data from a Phase 1b study in PN was reported in November 2023;
Eosinophilic Esophagitis (EoE): A Phase 2 study in EoE was initiated in June 2023 and is fully accrued; and
Atopic Dermatitis (AD): A Phase 2 study in AD was initiated in December 2024 and enrollment is ongoing.
The company’s next generation bispecific antibody platform to support pipeline expansion with additional candidates for inflammatory diseases. Targets are being selected based on new science, as well as their compatibility to be used in bispecific antibody formats with its existing antibody programs. Development is focused on emerging, important pathways controlling inflammatory diseases.
CDX-622 (TSLP & SCF): The company’s first bispecific candidate for inflammatory diseases is CDX-622 which targets two complementary pathways that drive chronic inflammation, potently neutralizing the alarmin thymic stromal lymphopoietin (TSLP) and depleting mast cells via stem cell factor (SCF) starvation. In November 2024, a Phase 1a dose-escalation study in healthy volunteers was initiated and enrollment is ongoing.
Clinical Development Programs
Barzolvolimab (also referred to as CDX-0159)
Barzolvolimab is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT and potently inhibits its activity. KIT is expressed in a variety of cells, including mast cells, and its activation by its ligand SCF regulates mast cell growth, differentiation, survival, chemotaxis and degranulation. Barzolvolimab is designed to block KIT activation by disrupting both SCF binding and KIT dimerization. By targeting KIT, barzolvolimab has been shown to inhibit mast cell activity and decrease mast cell numbers.
Barzolvolimab was initially studied in chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), diseases where mast cell degranulation plays a central role in the onset and progression of the disease. In July 2024, the company initiated two Phase 3 studies in CSU. Phase 1 studies in CSU and CIndU were successfully completed, and Phase 2 studies are ongoing. In July 2023, the company announced that enrollment was complete in the ongoing Phase 2 CSU study. In November 2023, it reported that barzolvolimab achieved the primary efficacy endpoint in this study, with a statistically significant mean change from baseline to week 12 of UAS7 (weekly urticaria activity score) compared to placebo, and was well tolerated. In September 2024, the company presented 52-week treatment data from the CSU study, demonstrating sustained and deepening disease efficacy along with a well-tolerated long-term safety profile. The company plans to present follow-up data from this study through week 76 in 2025. In April 2024, it announced that enrollment was complete in the ongoing Phase 2 CIndU study. In July 2024, the company announced that its Phase 2 study in chronic inducible urticaria (CIndU) achieved the primary efficacy endpoint (statistically significant difference between the percent of patients with a negative provocation test compared to placebo at week 12) and was well tolerated. Twelve-week data from the CIndU study were presented in October 2024, and all secondary endpoints across the study were also met, showing high statistical significance and clinical relevance. Patients in the study continued to receive barzolvolimab for 20 weeks of treatment and were then followed for up to 24 additional weeks without treatment. The company plans to present data from this study through week 44 in 2025. Patients with resumption of symptoms were eligible to enroll in an open-label extension. [1]
Based on the positive results reported in urticaria, the company expanded the development of barzolvolimab into additional indications where mast cells are believed to play an important role. It is conducting ongoing Phase 2 studies in eosinophilic esophagitis (EoE), prurigo nodularis (PN), and atopic dermatitis (AD). The company continues to assess potential opportunities for barzolvolimab in other diseases where mast cells play an important role, such as dermatologic, respiratory, allergic, gastrointestinal, and ophthalmic conditions.
Chronic Spontaneous Urticaria (CSU)
CSU presents as itchy hives, angioedema or both for at least six weeks without a specific trigger; multiple episodes can play out over years or even decades. It is one of the most frequent dermatologic diseases with a prevalence of 0.5-1.0% of the total population or up to approximately 1 to 3 million patients in the United States (Weller et al. 2010. Hautarzt. 61(8), Bartlett et al. 2018. DermNet.Org). Approximately 50% of patients with CSU achieve symptomatic control with antihistamines.
The company has completed a Phase 1b randomized, double-blind, placebo-controlled multi-center study of barzolvolimab in CSU. The study was designed to assess the safety of multiple ascending doses of barzolvolimab in patients with CSU who remain symptomatic despite treatment with antihistamines. Secondary and exploratory objectives included pharmacokinetic and pharmacodynamic assessments, clinical activity outcomes and quality of life assessments. Barzolvolimab was administered intravenously as add on treatment to H1-antihistamines, either alone or in combination with H2-antihistamines and/or leukotriene receptor agonists.
In June 2022, the company-initiated dosing in a Phase 2 study in patients with CSU who remained symptomatic despite antihistamine therapy; in July 2023, the company announced that enrollment was complete.
In June 2024, data on a secondary endpoint from the study, angioedema activity, and additional measures of angioedema control, were presented at the EAACI 2024 Congress.
In July 2024, the company initiated two Phase 3 studies of barzolvolimab in CSU. The studies, EMBARQ-CSU1 and EMBARQ-CSU2, are designed to establish the efficacy and safety of barzolvolimab in adult patients with CSU who remain symptomatic despite H1 antihistamine treatment.
Chronic Inducible Urticaria (CIndU)
The company completed a Phase 1b open label clinical trial in patients with CIndU refractory to antihistamines, conducted in Germany. This study was designed to evaluate the safety of a single intravenous dose (3 mg/kg) of barzolvolimab in patients with cold urticaria (ColdU) or symptomatic dermographism (SD).
In July 2022, the company announced that the first patient had been dosed in a Phase 2 study in patients with CIndU who remain symptomatic despite antihistamine therapy; in April 2024, the company announced that enrollment was complete.
Prurigo Nodularis (PN)
The company has expanded clinical development of barzolvolimab into prurigo nodularis (PN). PN is a chronic skin disease characterized by the development of hard, intensely itchy (pruritic) nodules on the skin. Mast cells through their interactions with sensory neurons and other immune cells are believed to play an important role in amplifying chronic itch and neuroinflammation, both of which are a hallmark of PN.
The company has completed a Phase 1b multi-center, randomized, double-blind, placebo-controlled intravenous study in PN. Data from the study, including 24 weeks of follow-up, were presented at the 12th World Congress on Itch (WCI) held in November 2023. 24 adults (evaluable: n=23 safety; n=22 efficacy) with moderate to severe PN were randomized across three arms: (1) barzolvolimab 3.0 mg/kg (n=9), barzolvolimab 1.5 mg/kg (n=7) and placebo (n=8).
In April 2024, the company initiated a Phase 2 subcutaneous study in PN. This randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety profile of 2 dose levels of barzolvolimab compared to placebo in approximately 120 patients with moderate to severe PN who had inadequate response to prescription topical medications, or for whom topical medications are medically inadvisable (such as concerns for safety).
Eosinophilic Esophagitis (EoE)
In July of 2023, the company announced that the first patient had been dosed in a Phase 2 study of eosinophilic esophagitis (EoE). EoE, the most common type of eosinophilic gastrointestinal disease, is a chronic inflammatory disease of the esophagus characterized by the infiltration of eosinophils.
Atopic Dermatitis (AD)
In December of 2024, the company announced the initiation of a Phase 2 study in atopic dermatitis (AD). AD is one of the most common chronic inflammatory skin diseases, with a lifetime prevalence of up to 20% of the U.S. population and a substantial impact on quality of life (Kawakami, et al. 2009).
Additional Barzolvolimab Development Activities
In 2023, the company completed the transfer of its current barzolvolimab manufacturing process to a Contract Development & Manufacturing Organizations (CDMO) and successfully scaled up the drug substance manufacturing process to produce larger cGMP batches in support of late-stage trials and to prepare for potential commercialization. Drug product manufacturing into 1 mL pre-filled syringes has been completed and are actively being used in the ongoing Phase 3 CSU trials.
Bispecific Platform
The company’s next generation bispecific antibody platform is supporting the expansion of its pipeline with additional candidates for inflammatory diseases. Targets are being selected based on new science, as well as their compatibility to be used in bispecific antibody formats with its existing antibody programs. Development is focused on emerging, important pathways controlling inflammatory diseases.
CDX-622
CDX-622 is a bispecific antibody that targets two complementary pathways that drive chronic inflammation, potently neutralizing the alarmin thymic stromal lymphopoietin (TSLP) and depleting mast cells via stem cell factor (SCF) starvation. TSLP has been directly implicated in several respiratory and dermatological disorders, such as asthma, chronic obstructive pulmonary disease (COPD), eosinophilic esophagitis, atopic dermatitis and chronic spontaneous urticaria, and in fibrotic diseases, such as systemic sclerosis and idiopathic pulmonary fibrosis. In these disorders, TSLP is often upregulated and associated with disease severity. Similarly, mast cells drive or contribute to the pathophysiology of allergic, inflammatory, autoimmune and fibrotic disorders and CDX-622 contains a unique SCF neutralizing function that is expected to inhibit and deplete mast cells. Combined neutralization of SCF and TSLP with CDX-622 is expected to simultaneously reduce tissue mast cells and inhibit Type 2 inflammatory responses to potentially offer enhanced therapeutic benefit in inflammatory and fibrotic disorders. In preclinical studies, CDX-622 inhibits TSLP and SCF with similar potency to both its respective parental mAbs and comparator mAbs in vitro. CDX-622 was well tolerated in a multi-dose 8 week toxicology study in non-human primates. The No Adverse Event Level (NOAEL) was established to be 75 mg/kg, the highest dose level tested.
In November 2024, the company initiated a Phase 1 study of CDX-622 in healthy volunteers. The Phase 1a clinical trial is a two-part, randomized, double-blind, placebo-controlled, dose escalation study designed to assess the safety, pharmacokinetics, and pharmacodynamics of single ascending doses (Part 1) and multiple ascending doses (Part 2) of CDX-622 in up to 56 healthy participants. A single dose of CDX-622 or placebo will be administered intravenously once during Part 1. In Part 2, CDX-622 or placebo will be administered every 3 weeks (Q3W) for up to 6 weeks following the first dose, for a total of 3 doses. Participants will be followed for 12 weeks in both Parts 1 and 2 following the last dose of the study drug. The pharmacodynamic biomarkers from blood and skin will provide highly informative data on the ability of CDX-622 to engage and neutralize stem cell factor (SCF) and Thymic Stromal Lymphopoietin (TSLP). A subcutaneous formulation is being manufactured and will be added to this study in 2025.
License Agreements
Yale University (Yale)
Under a license agreement with Yale, the company may be required to make a one-time payment with respect to barzolvolimab upon achievement of a specified commercial milestone. In addition, the company may be required to pay a low single-digit royalty on annual worldwide net sales of barzolvolimab. Unless earlier terminated by it or Yale, the Yale license agreement is due to expire no later than May 2038 but may expire earlier on a country-by-country basis under specified circumstances.
Competition
The competitors of which the company is aware that have initiated a Phase 3 study or have obtained marketing approval for a potentially competitive drug to barzolvolimab for the treatment of CSU, CIndU, PN, EoE and AD: Abbvie; Amgen; Kiowa Kirin; Celltrion; Eli Lilly; Galderma/Chugai; Incyte; Kashiv Biosciences; Medimetriks; Leo Pharma; Novartis; Pfizer; Regeneron/Sanofi; Teva; and Vanda Pharmaceuticals.
Patents, Licenses and Proprietary Rights
Patents
The company owns a portfolio of patents and patent applications directed to barzolvolimab and other anti-KIT receptor antibodies. These patents and patent applications include claims directed to particular anti-KIT antibody compositions of matter, including barzolvolimab compositions of matter, and methods of using such antibodies. A composition of matter patent has been issued in the U.S. which would have an estimated patent expiry date in 2034 (this includes additional term due to PTA, but does not include any PTE if this may be secured in due course) and further U.S. patent applications are pending. Patents have also been issued in Europe, Japan, Canada, China, Australia, New Zealand, Israel, India, the Republic of Korea, the Russian Federation, Singapore, Brazil, Mexico, South Africa and certain other countries.
Where issued the foregoing would have estimated normal patent expiry dates ranging from 2032 to 2033. Further (later filed) patent applications (relating to Fc sequences used in barzolvolimab and certain uses of barzolvolimab) are pending in the U.S., the European Patent Office, Japan, Canada, China, Australia, New Zealand, Israel, India, the Republic of Korea, the Eurasian Patent Office, Singapore, Brazil, Mexico and South Africa. If, when and where issued the latter would have estimated normal patent expiry dates in 2042.
The company owns a pending international patent application directed to anti-SCF and anti-TSLP antibody sequences used in CDX-622 as compositions of matter. If, when and where issued any applications in the national and regional phases of this application would have estimated normal patent expiry dates in 2044.
Licenses
The company has entered into significant license agreements relating to technologies that are being developed by it. Typically, institutions have granted the company an exclusive worldwide license (with right to sublicense) to make, use and sell products embodying the licensed technology, subject to the reservation by the licensor of a non-exclusive right to use the technologies for non-commercial research purposes.
Research and Development
The company incurred research and development expenses of $163.6 million during the year ended December 31, 2024.
Government Regulation
The company must obtain regulatory approval from the U.S. Food and Drug Administration (FDA) and comparable authorities in other countries, as applicable, for its drug candidates before it can commercialize such drugs in the U.S. and foreign jurisdictions.
The company expects that all of its clinical drug candidates will be subject to review as biological products under BLA standards.
Any drug or biological products manufactured or distributed by the company pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including among other things, requirements relating to recordkeeping, periodic reporting, product sampling and distribution, advertising and promotion and reporting of adverse experiences with the product.
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