- CDX-622 inhibits SCF and TSLP-dependent inflammatory signatures in human skin -- Phase 1 study in healthy volunteers ongoing - HAMPTON, N.J., March 03, 2025 (GLOBE NEWSWIRE) -- Celldex Therapeutics, Inc. (NASDAQ:CLDX) announced today positive preclinical data from CDX-622, a novel bispecific antibody that targets two non-redundant, complementary pathways implicated in inflammation and fibrosis—thymic stromal lymphopoietin (TSLP) and mast cell depletion via stem cell factor (SCF) starvation. The data demon ...

Core Insights - Celldex Therapeutics, Inc. announced positive results from Phase 2 studies of barzolvolimab, showing significant improvements in disease control and quality of life for patients with chronic urticaria [1][2][3] Group 1: Study Results - In the Phase 2 CSU study, 82% of patients reported that symptoms no longer impacted their quality of life at Week 52 [1][7] - In the Phase 2 CIndU study, 60% of patients reported that symptoms no longer impacted their quality of life at Week 12 [1][7] - Up to 71% of CSU patients achieved complete response (UAS7 = 0) at Week 52, the highest rate observed in a well-controlled study [7] - Up to 95% of CSU patients reported meaningful improvement in quality of life based on the Dermatology Life Quality Index (DLQI) at Week 52 [7] - Up to 82% of CSU patients reported well-controlled urticaria based on the Urticaria Control Test (UCT) at Week 52 [7] - In the CIndU study, up to 60% of patients reported that symptoms no longer impacted their quality of life at Week 12, with 69% reporting well-controlled urticaria based on UCT [7] Group 2: Treatment Implications - Barzolvolimab is a humanized monoclonal antibody that targets the receptor tyrosine kinase KIT, crucial for mast cell function and survival [1][14] - The treatment has the potential to change the treatment paradigm for chronic urticaria, allowing patients to live normally again [3] - Current clinical guidelines emphasize complete disease control as the treatment goal, with studies showing minimal or no impact on quality of life when this is achieved [3] Group 3: Future Developments - Global Phase 3 studies for barzolvolimab in patients with CSU are actively enrolling, with plans to advance into Phase 3 development for CIndU in 2025 [6]

Group 1 - Celldex Therapeutics reported a quarterly loss of $0.71 per share, which was better than the Zacks Consensus Estimate of a loss of $0.75, but worse than the loss of $0.57 per share from a year ago, indicating a 24.56% increase in loss year-over-year [1] - The company posted revenues of $1.18 million for the quarter ended December 2024, missing the Zacks Consensus Estimate by 24.19%, and down from $4.13 million in the same quarter last year [2] - Celldex shares have declined approximately 18.4% since the beginning of the year, contrasting with the S&P 500's gain of 1.3% [3] Group 2 - The current consensus EPS estimate for the upcoming quarter is -$0.65 on revenues of $1.3 million, and for the current fiscal year, it is -$3.32 on revenues of $7.5 million [7] - The Medical - Biomedical and Genetics industry, to which Celldex belongs, is currently ranked in the top 28% of over 250 Zacks industries, suggesting a favorable outlook compared to lower-ranked industries [8]

Clinical Development - Barzolvolimab (CDX-0159) achieved primary efficacy endpoints in Phase 2 studies for chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), with statistically significant mean changes from baseline to week 12 compared to placebo [335]. - In the Phase 1b study for CSU, barzolvolimab demonstrated an 82% mean reduction in baseline UAS7 at week 12 for the 4.5 mg/kg dose group, indicating significant symptom improvement [352]. - The ongoing Phase 2 studies for eosinophilic esophagitis (EoE), prurigo nodularis (PN), and atopic dermatitis (AD) are part of the expanded development of barzolvolimab into additional indications [348]. - The company initiated Phase 3 studies in CSU in July 2024, following successful Phase 2 results that showed sustained efficacy and a well-tolerated long-term safety profile [335]. - The first bispecific candidate, CDX-622, targeting chronic inflammation pathways, entered a Phase 1a dose-escalation study in November 2024, with enrollment ongoing [335]. - The Phase 2 study in chronic inducible urticaria (CIndU) achieved its primary efficacy endpoint, with a statistically significant difference in the percentage of patients with a negative provocation test compared to placebo at week 12 [335]. - The company plans to present follow-up data from the CSU study through week 76 in 2025, indicating ongoing commitment to data transparency and patient outcomes [347]. - The Phase 1b trial for chronic inducible urticaria (CIndU) showed a complete response in 95% of patients treated with a single dose of 3 mg/kg of barzolvolimab [369]. - Patients on barzolvolimab experienced rapid responses, with 100% achieving well-controlled disease (UCT>12) by week 4 post-treatment in the ColdU cohort [369]. - The Phase 2 study for EoE will enroll approximately 75 patients, with a primary endpoint of reducing esophageal intraepithelial mast cell count, and data is expected to be presented in the second half of 2025 [386]. - A Phase 2 study for atopic dermatitis (AD) was initiated in December 2024, with approximately 120 patients enrolled to evaluate the efficacy of barzolvolimab at doses of 150 mg and 300 mg [387]. - The primary endpoint for the AD study is the Peak Pruritus Numerical Rating Scale (PP-NRS) at Week 16, with secondary endpoints including various patient-reported outcomes [387]. Financial Performance - The total research and development expenses incurred over the past five years amounted to $459.7 million, with $163.6 million spent in 2024, up from $118.0 million in 2023 [344]. - Total revenues for the year ended December 31, 2024, increased by $137,000, or 2%, to $7,020,000 compared to $6,883,000 in 2023 [409]. - Product development and licensing agreements revenue decreased by $265,000, or 95%, to $13,000 in 2024, while contracts and grants revenue increased by $402,000, or 6%, to $7,007,000 [409]. - The net loss for the year ended December 31, 2024, was $157,863,000, an increase of $16,434,000, or 12%, compared to the net loss of $141,429,000 in 2023 [410]. - Investment and other income, net, increased by $24,102,000, or 184%, to $37,215,000 in 2024, attributed to higher cash levels from public offerings [409]. - General and administrative expenses increased by $7,634,000, or 25%, to $38,548,000 in 2024, primarily due to higher stock-based compensation [409]. - The company expects a decrease in revenue over the next twelve months due to reduced services under contracts with Rockefeller University [411]. - The company incurred a net loss of $157.9 million for the year ended December 31, 2024, with net cash used in operations amounting to $157.8 million, an increase from $107.3 million in 2023 [437][439]. - Total revenues for the year ended December 31, 2024, were $7.02 million, a 2% increase from $6.88 million in 2023 [473]. - The net loss for the year ended December 31, 2024, was $157.86 million, compared to a net loss of $141.43 million in 2023, representing an increase of 11.6% [473]. Research and Development Expenses - Research and development expenses rose by $45,539,000, or 39%, to $163,550,000 in 2024, driven by increased personnel and product development costs [409]. - Personnel expenses within research and development increased by $11,785,000, or 29%, to $51,906,000 in 2024, due to higher stock-based compensation and increased headcount [413]. - Product development expenses surged by $31,285,000, or 53%, to $90,604,000 in 2024, mainly due to barzolvolimab clinical trial expenses [416]. - Total research and development (R&D) expenses for the year ended December 31, 2024, were $163,550,000, an increase of 38.5% from $118,011,000 in 2023 [488]. - The Barzolvolimab/Anti-KIT Program accounted for $123,750,000 of the total R&D expenses in 2024, up from $79,913,000 in 2023, representing a 54.8% increase [488]. Capital and Liquidity - As of December 31, 2024, the company's liquidity sources included cash, cash equivalents, and marketable securities totaling $725.3 million [437]. - The company plans to raise additional capital through various means, including licensing drug candidates, business combinations, and issuing debt or equity [438]. - The company issued 8,538,750 shares in November 2023, resulting in net proceeds of $216.2 million, and 9,798,000 shares in March 2024, yielding net proceeds of $432.3 million [448][450]. - The company maintains that its cash, cash equivalents, and marketable securities are sufficient to meet working capital requirements through 2027, barring any significant changes [437]. - The company believes its cash and marketable securities will be sufficient to meet working capital requirements for at least the next twelve months [482]. Manufacturing and Operations - In 2023, the company successfully scaled up the barzolvolimab manufacturing process to produce larger cGMP batches in support of late-stage trials [388]. - The Company relies on contract development and manufacturing organizations (CDMOs) for the manufacturing of drug substances and products, as well as for future commercial supplies [498]. - The Company operates a cGMP manufacturing facility in Fall River, Massachusetts, to produce drug substance for clinical trials, utilizing excess capacity through contract manufacturing and research arrangements [511]. - Research and development expenses include clinical trial costs, manufacturing of clinical material, and personnel costs, with expenses recognized as incurred [514].

Financial Performance - Total revenue for Q4 2024 was $1.2 million, a decrease from $4.1 million in Q4 2023, while total revenue for the year was $7.0 million compared to $6.9 million in 2023[13]. - The net loss for Q4 2024 was $47.1 million, or ($0.71) per share, compared to a net loss of $43.3 million, or ($0.83) per share, in Q4 2023; for the year, the net loss was $157.9 million, or ($2.45) per share, compared to $141.4 million, or ($2.92) per share, in 2023[17]. Expenses - Research and development (R&D) expenses increased to $46.9 million in Q4 2024 from $30.4 million in Q4 2023, and for the year, R&D expenses were $163.6 million compared to $118.0 million in 2023[14]. - General and administrative (G&A) expenses rose to $10.3 million in Q4 2024 from $8.8 million in Q4 2023, with annual G&A expenses totaling $38.5 million compared to $30.9 million in 2023[15]. Cash and Assets - Cash, cash equivalents, and marketable securities as of December 31, 2024, were $725.3 million, down from $756.0 million as of September 30, 2024, primarily due to $32.5 million used in operating activities during Q4[11]. - Total assets increased to $792,340 million in December 2024, up from $465,627 million in December 2023, representing a growth of 70%[25]. - Cash, cash equivalents, and marketable securities rose to $725,281 million, compared to $423,598 million in the previous year, indicating a 71% increase[25]. - Stockholders' equity grew significantly to $747,005 million, up from $429,171 million, reflecting a 74% increase year-over-year[25]. - Current liabilities increased to $39,501 million from $31,125 million, marking a rise of 27%[25]. - Long-term liabilities slightly increased to $5,834 million from $5,331 million, showing a growth of 9%[25]. - Other current assets surged to $21,878 million, compared to $8,095 million, which is an increase of 170%[25]. - Intangible and other assets, net, rose to $40,835 million from $29,874 million, representing a 37% increase[25]. - Property and equipment, net, increased to $4,346 million from $4,060 million, showing a growth of 7%[25]. Clinical Development - Barzolvolimab demonstrated a 71% complete response rate at Week 52 in a Phase 2 study for chronic spontaneous urticaria (CSU), marking the highest rate observed in a controlled study[12]. - The global Phase 3 program for CSU is enrolling approximately 915 patients across 40 countries and 500 sites, with ongoing enrollment in the Phase 3 barzolvolimab studies[8]. - A Phase 1 study for CDX-622, a bispecific candidate targeting SCF and TSLP, was initiated in November 2024, with enrollment ongoing in a two-part randomized, double-blind, placebo-controlled study[10]. - The company anticipates multiple important data readouts in 2025, including results from barzolvolimab Phase 2 studies in CSU, CIndU, and eosinophilic esophagitis[7]. Future Outlook - Celldex expects its cash position to be sufficient to meet estimated working capital requirements and fund current planned operations through 2027[18].

Core Insights - Celldex Therapeutics reported strong efficacy data for barzolvolimab in chronic urticarias, with ongoing Phase 3 studies in chronic spontaneous urticaria (CSU) and plans to initiate a Phase 3 program in chronic inducible urticaria (CIndU) in 2025 [2][7][12] - The company has initiated two new programs, including advancing barzolvolimab into atopic dermatitis and introducing a bispecific candidate, CDX-622, targeting inflammatory pathways [2][10] - Financial results showed a net loss of $47.1 million for Q4 2024, with total revenues of $1.2 million for the quarter and $7.0 million for the year, reflecting a decrease in revenue primarily due to reduced services under agreements [11][12][17] Pipeline Developments - Barzolvolimab is a humanized monoclonal antibody targeting the KIT receptor, crucial for mast cell activity, with significant results in Phase 2 studies for CSU and CIndU [3][6] - The Phase 3 program for CSU includes two trials enrolling approximately 915 patients each across 40 countries, aiming to establish the drug's efficacy and safety [7] - CDX-622, a bispecific antibody, is designed to neutralize TSLP and deplete mast cells, with a Phase 1 study in healthy volunteers initiated in November 2024 [10][13] Financial Performance - As of December 31, 2024, the company had cash, cash equivalents, and marketable securities totaling $725.3 million, down from $756.0 million at the end of Q3 2024 [11][25] - Research and development expenses increased to $46.9 million for Q4 2024 and $163.6 million for the year, driven by clinical trial costs for barzolvolimab [14] - General and administrative expenses rose to $10.3 million for Q4 2024, attributed to higher stock-based compensation and commercial planning expenses [15]

Core Viewpoint - Celldex Therapeutics has initiated a Phase 2 study of barzolvolimab for atopic dermatitis, addressing a significant unmet need in the treatment of this common chronic inflammatory skin disease [1][2][3] Group 1: Study Details - The Phase 2 study is randomized, double-blind, and placebo-controlled, evaluating the efficacy and safety of subcutaneous barzolvolimab in patients with moderate to severe atopic dermatitis [2] - Approximately 120 patients will be enrolled, receiving either 150 mg or 300 mg of barzolvolimab or a placebo every 4 weeks after an initial loading dose [2] - The primary endpoint is to assess clinical efficacy using the Peak Pruritus Numerical Rating Scale (PP-NRS) at Week 16, with secondary endpoints including various patient-reported outcomes [2][3] Group 2: Disease Background - Atopic dermatitis affects up to 20% of the US population, with a significant impact on quality of life, as many patients experience severe itching and skin breakdown [1][3] - Up to 50% of adult patients have moderate to severe disease, and 86% experience daily pruritus, with 61% reporting severe or unbearable itching [3] Group 3: Barzolvolimab Overview - Barzolvolimab is a humanized monoclonal antibody that targets the receptor tyrosine kinase KIT, crucial for mast cell function and survival [4] - The drug is also being studied for other conditions, including chronic spontaneous urticaria and eosinophilic esophagitis, indicating its potential versatility in treating mast cell-related diseases [4] Group 4: Company Background - Celldex Therapeutics is a clinical-stage biotechnology company focused on developing therapeutics that engage the immune system and target critical pathways for severe inflammatory and allergic diseases [5]

Financial Performance - Celldex Therapeutics reported a quarterly loss of $0.64 per share, which was better than the Zacks Consensus Estimate of a loss of $0.69, and an improvement from a loss of $0.81 per share a year ago, indicating a 20.99% year-over-year improvement [1] - The company posted revenues of $3.19 million for the quarter ended September 2024, surpassing the Zacks Consensus Estimate by 121.60%, compared to revenues of $1.52 million in the same quarter last year [2] - Over the last four quarters, Celldex has surpassed consensus EPS estimates four times and topped consensus revenue estimates three times [2] Stock Performance - Celldex shares have declined approximately 35.9% since the beginning of the year, contrasting with the S&P 500's gain of 21.2% [3] - The current consensus EPS estimate for the upcoming quarter is -$0.73 on revenues of $1.41 million, and for the current fiscal year, it is -$2.50 on revenues of $4.45 million [7] Industry Outlook - The Medical - Biomedical and Genetics industry, to which Celldex belongs, is currently ranked in the top 38% of over 250 Zacks industries, suggesting a favorable outlook compared to lower-ranked industries [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can be tracked by investors [5]

Clinical Development - Barzolvolimab (CDX-0159) is currently in Phase 3 studies for chronic spontaneous urticaria (CSU), with a Phase 2 study achieving primary efficacy endpoints and demonstrating a statistically significant mean change from baseline to week 12[75]. - The company initiated a Phase 2 study in prurigo nodularis (PN) in April 2024, following positive data from a Phase 1b study reported in November 2023[90]. - A Phase 2 study in eosinophilic esophagitis (EoE) was initiated in June 2023, with enrollment ongoing[76]. - The company plans to initiate a Phase 2 study for atopic dermatitis (AD) by the end of 2024, targeting patients who have received prior biologics[76]. - The company initiated two Phase 3 studies of barzolvolimab in Chronic Spontaneous Urticaria (CSU) in July 2024, enrolling approximately 915 patients per trial across 250 sites in about 40 countries[113]. - In a Phase 1b trial for Cold Urticaria (ColdU) and Symptomatic Dermographism (SD), a complete response was achieved in 95% (n=19/20) of patients treated with a single dose of 3 mg/kg barzolvolimab[118]. - In a Phase 2 study for Chronic Inducible Urticaria (CIndU), 196 patients were randomized to receive barzolvolimab at either 150 mg every 4 weeks or 300 mg every 8 weeks, with the primary endpoint being the percentage of patients with a negative provocation test at week 12[128]. - The company has expanded clinical development of barzolvolimab into Prurigo Nodularis (PN), a chronic skin disease with an estimated 154,000 patients in the U.S. who have undergone treatment in the last 12 months[134]. Financial Performance - The total research and development expenses for the nine months ended September 30, 2024, amounted to $116.6 million, compared to $87.6 million for the same period in 2023, reflecting a year-over-year increase of approximately 33%[86]. - The total revenues for the three months ended September 30, 2024, were $3.191 million, a 110% increase from $1.517 million in the same period in 2023[151]. - Research and development expenses increased by 31% to $45.263 million for the three months ended September 30, 2024, compared to $34.535 million in the prior year[151]. - The net loss for the three months ended September 30, 2024, was $42.121 million, a 10% increase from $38.260 million in the same period in 2023[152]. - Revenue from product development and licensing agreements for the three months ended September 30, 2024, was $5.8 million, a 112% increase compared to $2.8 million for the same period in 2023[161]. - Investment and other income increased by 236% to $10.005 million for the three months ended September 30, 2024, compared to $2.979 million in the prior year[151]. - Investment and other income, net, for the nine months ended September 30, 2024, increased by $19.5 million, or 222%, totaling $28.3 million compared to $8.8 million for the same period in 2023[168]. Research and Development Expenses - The company incurred an aggregate of $338.8 million in research and development expenses over the past five years through December 31, 2023[86]. - Product development expenses for the nine months ended September 30, 2024, rose by $19.4 million, or 43%, reaching $64.7 million compared to $45.3 million for the same period in 2023[169]. - General and administrative expenses increased by $6.2 million, or 28%, totaling $28.3 million for the nine months ended September 30, 2024, compared to $22.1 million for the same period in 2023[167]. Cash Flow and Financing - Net cash used in operating activities was $125.3 million for the nine months ended September 30, 2024, compared to $74.8 million for the same period in 2023[174]. - Net cash used in investing activities was $314.2 million for the nine months ended September 30, 2024, compared to net cash provided of $65.4 million for the same period in 2023[176]. - Net cash provided by financing activities was $441.1 million for the nine months ended September 30, 2024, compared to $1.1 million for the same period in 2023[177]. - In March 2024, the company issued 9,798,000 shares of common stock, resulting in net proceeds of $432.3 million after deducting underwriting fees and offering expenses[178]. Clinical Efficacy and Safety - Barzolvolimab demonstrated a mean reduction from baseline in weekly urticaria activity score (UAS7) of 67% at week 12 for both the 1.5 mg/kg and 3.0 mg/kg dose groups, and 82% for the 4.5 mg/kg dose group[94]. - At week 12, complete response (UAS7=0) was achieved by 57% of patients in the 1.5 mg/kg group, 44% in the 3.0 mg/kg group, and 67% in the 4.5 mg/kg group[95]. - Well-controlled disease (UCT≥12) at week 12 was reported in 75% of the 1.5 mg/kg group, 63% of the 3.0 mg/kg group, and 89% of the 4.5 mg/kg group[96]. - At week 12, barzolvolimab achieved a statistically significant mean change from baseline in UAS7 compared to placebo across all dose levels, with a mean difference of -13.41 for 300 mg Q8W[105]. - 71% of patients treated with barzolvolimab 150 mg Q4W and 52% treated with 300 mg Q8W had a complete response (UAS7=0) at week 52[110]. - 74% of patients treated with barzolvolimab 150 mg Q4W and 68% treated with 300 mg Q8W had well-controlled disease (UAS7<6) at week 52[111]. - Barzolvolimab was well tolerated, with most adverse events being mild to moderate; common events included hair color changes (9%) and neutropenia (8%)[100]. - Approximately 72% of patients had angioedema at baseline, with significant improvements in angioedema activity score (AAS7) observed across all doses at week 12[108]. - Patients in the 300 mg cohort experienced angioedema-free days 77% of the time over the 12-week period[108]. - The studies confirmed that serum tryptase level is a robust pharmacodynamic biomarker for assessing mast cell burden and clinical activity in inducible urticaria[122]. - The Phase 1b study of barzolvolimab showed a 57% reduction in Worst Itch Numerical Rating Scale (WI-NRS) at week 8 for the 3.0 mg/kg dose, compared to 25% for placebo[137]. - At week 8, 29% of patients in the 3.0 mg/kg group achieved clear or almost clear skin according to Investigator Global Assessment (IGA), with no patients in the 1.5 mg/kg or placebo groups achieving this[138]. Future Outlook - The ongoing clinical trials and development programs are subject to various uncertainties, including regulatory approvals and the ability to raise sufficient capital for continued operations[72]. - The company expects revenue to decrease over the next twelve months primarily due to a decrease in services under contract manufacturing and research agreements[153]. - The company anticipates that cash used in operating activities will increase over the next twelve months due to expanded development of barzolvolimab[174]. - The company plans to initiate a Phase 1 study of CDX-622, a bispecific antibody, in healthy volunteers by the end of 2024[147]. - The company successfully scaled up the barzolvolimab manufacturing process to produce larger cGMP batches in support of late-stage trials[144].

Financial Performance - Total revenue for Q3 2024 was $3.2 million, up from $1.5 million in Q3 2023, representing a 113.3% increase[15] - Net loss for Q3 2024 was $42.1 million, or ($0.64) per share, compared to a net loss of $38.3 million, or ($0.81) per share in Q3 2023[18] - Research and development expenses increased to $45.3 million in Q3 2024 from $34.5 million in Q3 2023, a rise of 31.8%[16] - General and administrative expenses rose to $10.1 million in Q3 2024 compared to $8.2 million in Q3 2023, an increase of 23.2%[17] Cash and Assets - Cash, cash equivalents, and marketable securities as of September 30, 2024, were $756.0 million, down from $802.3 million as of June 30, 2024[14] - Total assets increased to $823,179 million as of September 30, 2024, up from $465,627 million on December 31, 2023, representing a growth of 76.7%[25] - Cash, cash equivalents, and marketable securities reached $755,999 million, significantly up from $423,598 million, marking an increase of 78.5%[25] - Intangible and other assets grew to $40,107 million, up from $29,874 million, which is an increase of 34.1%[25] - Other current assets increased to $22,843 million from $8,095 million, representing a substantial growth of 182.5%[25] - Property and equipment, net, saw a slight increase to $4,230 million from $4,060 million, reflecting a growth of 4.2%[25] Liabilities and Equity - Current liabilities slightly increased to $32,093 million from $31,125 million, reflecting a rise of 3.1%[25] - Long-term liabilities decreased marginally to $5,181 million from $5,331 million, showing a decline of 2.8%[25] - Stockholders' equity rose to $785,905 million, compared to $429,171 million at the end of 2023, indicating an increase of 83.2%[25] - Total liabilities and stockholders' equity remained consistent at $823,179 million, matching the total assets[25] Clinical Developments - Barzolvolimab demonstrated a 71% complete response rate at Week 52 in the Phase 2 CSU study, the highest rate observed in a controlled study[7] - In the Phase 2 CIndU study, 53.1% of patients with cold urticaria achieved a complete response compared to 12.5% in the placebo group (p=0.0011)[8] - The company plans to initiate a global Phase 3 program in chronic inducible urticaria (CIndU) in 2025[5] - Celldex expects to initiate a Phase 2 study in atopic dermatitis (AD) by the end of 2024[11] Financial Outlook - The company believes its cash position is sufficient to fund operations through 2027[19] - The overall financial position indicates strong growth and improved liquidity, positioning the company favorably for future investments and expansions[25]