On November 6, 2024 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported financial results for the third quarter ended September 30, 2024 and provided a corporate update (Press release, Celldex Therapeutics, NOV 6, 2024, View Source [SID1234647805]).

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"Celldex recently presented best-in-disease data across both our Phase 2 studies of barzolvolimab in CSU and CIndU," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "The data demonstrated barzolvolimab’s unique potential to provide a rapid, durable treatment option and complete disease control for patients suffering from these severe, debilitating diseases. These are transformative results for patients with CSU, many whom do not see meaningful benefit from the current standard of care, and CIndU, where there are currently no approved therapies other than antihistamines. We continue to make strong progress across our entire pipeline, with enrollment ongoing in global Phase 3 CSU trials and our Phase 2 PN and EOE studies. As we look to the end of this year, we remain excited for our Phase 2 study in AD to initiate and our first bispecific for inflammatory diseases, CDX-622, to enter the clinic."

Recent Program Highlights

Barzolvolimab – KIT Inhibitor Program

Barzolvolimab 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.

Chronic Urticarias

Phase 3 Development

A global Phase 3 program in chronic spontaneous urticaria (CSU) was initiated in July, consisting of two Phase 3 trials (EMBARQ-CSU1 and EMBARQ-CSU2) 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. The studies will enroll approximately 915 patients each across 40 countries and 500 sites and are actively enrolling patients.
The Company is currently planning a global Phase 3 program in chronic inducible urticaria (CIndU), which is expected to initiate in 2025.
Phase 2 Development

Barzolvolimab met all primary and secondary endpoints at 12 weeks across the Company’s Phase 2 studies in CSU and CIndU. Results were highly statistically significant and clinically meaningful. Patients continue to be followed on both studies.

52 week long term follow up data from the Phase 2 study in CSU (n=208) were presented in a late breaking oral presentation at the EADV Congress 2024 in September. A deepening of response was observed over the 52 week treatment period and barzolvolimab demonstrated the highest rate of complete response observed in a well controlled study in CSU with 71% of patients (150 mg Q4W) achieving a complete response at Week 52. Importantly, barzolvolimab was also well tolerated through 52 weeks.

12 week primary endpoint data from the Phase 2 study in CIndU (n=196) were presented in a late breaking oral presentation at ACAAI 2024 in October. Barzolvolimab is the first drug to demonstrate clinical benefit in patients with cold urticaria (ColdU) in a large, randomized, placebo-controlled study. Per provocation test, up to 53.1% of patients with ColdU and 57.6% of patients with symptomatic dermographism (SD) treated with barzolvolimab experienced a complete response compared to placebo rates of only 12.5% (p=0.0011) in ColdU and 3.2% (p<0.0001) in SD—the primary endpoint of the study. Secondary and exploratory endpoints were highly supportive of the primary endpoint. Patients on study continued to receive barzolvolimab or placebo for up 20 weeks and are being followed for an additional 24 weeks. The study also includes an Open Label Extension that allows patients with symptoms during the follow-up phase (including patients who were on placebo) to receive active study drug.
Additional Indications

A Phase 2 study in eosinophilic esophagitis (EoE) was initiated in July 2023 and enrollment is ongoing. This randomized, double-blind, placebo-controlled study is evaluating the efficacy and safety profile of barzolvolimab in approximately 75 patients with active EoE. Data from this study is expected in the second half of 2025.
A Phase 2 study in prurigo nodularis (PN) was initiated in early 2024 and enrollment is ongoing. This randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety profile of barzolvolimab 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, including patients who received prior biologics.
In May 2024, Celldex announced that atopic dermatitis (AD) has been selected as the fifth indication for the development of barzolvolimab. Barzolvolimab’s novel mast cell depleting mechanism could play an important role in addressing patients with moderate to severe AD who do not achieve complete disease control on currently available systemic therapies. Celldex plans to initiate a Phase 2 study in AD by year end.
Bispecific Antibody Platform

CDX-622 – Bispecific SCF & TSLP

CDX-622 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. 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.

Celldex has completed preclinical, manufacturing and IND-enabling activities for CDX-622 and plans to initiate a Phase 1 study in healthy volunteers by the end of 2024. 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 and the No Adverse Event Level (NOAEL) was established to be 75 mg/kg, the highest dose level tested. In inflammatory and fibrotic disorders, TSLP is often upregulated and associated with disease severity. Similarly, mast cells drive or contribute to the pathophysiology of many of these disorders and CDX-622 contains a unique SCF neutralizing function that is expected to inhibit and deplete mast cells.
CDX-585 – Bispecific ILT4 & PD-1

The dose-escalation portion of this open-label, multi-center Phase 1 study of CDX-585 in patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy has been completed. We are prioritizing our expanding clinical development program in the inflammatory space and will not advance CDX-585.
Third Quarter 2024 Financial Highlights and 2024 Guidance

Cash Position: Cash, cash equivalents and marketable securities as of September 30, 2024 were $756.0 million compared to $802.3 million as of June 30, 2024. The decrease was primarily driven by third quarter cash used in operating activities of $55.3 million. From June 30, 2024 to September 30, 2024, prepaid and other current assets increased $13.9 million and other assets increased $9.6 million as a result of non-recurring advance payments related to our Phase 3 studies in CSU and late-stage barzolvolimab commercial manufacturing batches. At September 30, 2024, Celldex had 66.3 million shares outstanding.

Revenues: Total revenue was $3.2 million in the third quarter of 2024 and $5.8 million for the nine months ended September 30, 2024, compared to $1.5 million and $2.8 million for the comparable periods in 2023. The increase in revenue was primarily due to an increase in services performed under our manufacturing and research and development agreements with Rockefeller University.

R&D Expenses: Research and development (R&D) expenses were $45.3 million in the third quarter of 2024 and $116.6 million for the nine months ended September 30, 2024, compared to $34.5 million and $87.6 million for the comparable periods in 2023. The increase in R&D expenses was primarily due to an increase in barzolvolimab clinical trial and personnel expenses, partially offset by a decrease in barzolvolimab contract manufacturing expenses.

G&A Expenses: General and administrative (G&A) expenses were $10.1 million in the third quarter of 2024 and $28.3 million for the nine months ended September 30, 2024, compared to $8.2 million and $22.1 million for the comparable periods in 2023. The increase in G&A expenses was primarily due to an increase in stock-based compensation and barzolvolimab commercial planning expenses.

Net Loss: Net loss was $42.1 million, or ($0.64) per share, for the third quarter of 2024, and $110.8 million, or ($1.74) per share, for the nine months ended September 30, 2024, compared to a net loss of $38.3 million, or ($0.81) per share, for the third quarter of 2023, and $98.1 million, or ($2.08) per share, for the nine months ended September 30, 2023.

Financial Guidance: Celldex believes that the cash, cash equivalents and marketable securities at September 30, 2024 are sufficient to meet estimated working capital requirements and fund current planned operations through 2027.