Celldex Therapeutics Inc

Previous wording

During the past five years through December 31, 2023, we incurred an aggregate of $338.8 million in research and development expenses. The following table indicates the amount incurred for each of our significant research programs and for other identified research and development activities during the nine months ended September 30, 2024 and 2023. The amounts disclosed in the following table reflect direct research and development costs, license fees associated with the underlying technology and an allocation of indirect research and development costs to each program.

Current wording

During the past five years through December 31, 2024, we incurred an aggregate of $459.7 million in research and development expenses. The following table indicates the amount incurred for each of our significant research programs and for other identified research and development activities during the three months ended March 31, 2025 and 2024. The amounts disclosed in the following table reflect direct research and development costs and an allocation of indirect research and development costs to each program.

Previous wording

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, we 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, we announced that enrollment was complete in the ongoing Phase 2 CSU study. In November 2023, we 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 April 2024, we announced enrollment was complete in the ongoing Phase 2 CIndU study. In July 2024, we reported that barzolvolimab achieved the primary efficacy endpoint in this study with a statistically significant difference between the percent of patients with a negative provocation test compared to placebo at week 12 and was well tolerated. We plan to report topline 52 week data from the CSU study and full 12 week primary endpoint data from the CIndU study in the second half of 2024.

Current wording

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, we 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, we announced that enrollment was complete in the ongoing Phase 2 CSU study. In November 2023, we 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, we presented 52 week treatment data from the CSU study, demonstrating sustained and deepening disease efficacy and a well tolerated long term safety profile. We plan to present follow up data from this study through week 76 in 2025. In April 2024, we announced enrollment was complete in the ongoing Phase 2 CIndU study. In July 2024, we announced that our 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 of 2024 and all secondary endpoints across the study were also met and were highly statistically significant and clinically meaningful. Patients on study continued to receive barzolvolimab for 20 weeks of treatment and were then followed for up to 24 additional weeks without treatment. We plan to present data from this study through week 44 in 2025. Patients with resumption of symptoms were eligible to enroll into an open label extension.

Previous wording

Based on the positive results reported in urticaria, we expanded development of barzolvolimab into additional indications where mast cells are believed to play an important role. We are conducting an ongoing Phase 2 study in eosinophilic esophagitis (EoE) and initiated a Phase 2 study in prurigo nodularis (PN) in April 2024 after reporting positive data from a Phase 1b study in PN in late 2023. We have selected atopic dermatitis as the next indication for the study of barzolvolimab and are currently planning the design of a Phase 2 study in this indication, including in patients who received prior biologics, and plan to initiate this study by year end 2024. We continue 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.

Current wording

Based on the positive results reported in urticaria, we expanded development of barzolvolimab into additional indications where mast cells are believed to play an important role. We are conducting ongoing Phase 2 studies in eosinophilic esophagitis (EoE), prurigo nodularis (PN) and atopic dermatitis (AD). We continue 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.

Previous wording

Patients on study continued to receive barzolvolimab for up to 52 weeks and these long term treatment data were presented in September at the European Academy of Dermatology & Venereology (EADV) Congress 2024. The data demonstrated a sustained and deepening disease efficacy and a well tolerated safety profile over a 52 week treatment period. Key highlighted included:

Current wording

Patients on study continued to receive barzolvolimab for up to 52 weeks. Long term treatment data were presented in September at the European Academy of Dermatology & Venereology (EADV) Congress 2024 and quality of life data were presented in March at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting 2025. The data demonstrated a sustained and deepening disease efficacy, a well tolerated safety profile, greatly improved urticaria control and reduced disease impact on quality of life over a 52 week treatment period. Key highlighted included:

Previous wording

The randomized, double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of subcutaneous barzolvolimab in patients with active EoE. To optimize potential efficacy signal in this difficult to treat indication, we have recently amended the protocol to dose 300 mg every 4 weeks rather than 8 weeks. Approximately 75 patients will be enrolled in total. In the revised protocol, patients will be randomly assigned on a 1:1 ratio to receive subcutaneous injections of barzolvolimab at 300 mg every 4 weeks or placebo during a 16-week placebo-controlled treatment phase. Patients then enter a 12-week active treatment phase, in which all patients will receive barzolvolimab 300 mg every 4 weeks. Patients then enter a follow-up phase for an additional 16 weeks. The primary endpoint of the study is reducing esophageal intraepithelial infiltration of mast cells as assessed by peak esophageal intraepithelial mast cell count. Secondary endpoints include the reduction of symptoms of dysphagia and esophageal intraepithelial infiltration of eosinophils and safety. The study includes approximately 60 clinical trial centers across 8 countries, including the United States. Enrollment is ongoing.

Current wording

The randomized, double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of subcutaneous barzolvolimab in patients with active EoE. To optimize potential efficacy signal in this difficult to treat indication, we have recently amended the protocol to dose 300 mg every 4 weeks rather than 8 weeks. Approximately 75 patients will be enrolled in total. In the revised protocol, patients will be randomly assigned on a 1:1 ratio to receive subcutaneous injections of barzolvolimab at 300 mg every 4 weeks or placebo during a 16-week placebo-controlled treatment phase. Patients then enter a 12-week active treatment phase, in which all patients will receive barzolvolimab 300 mg every 4 weeks. Patients then enter a follow-up phase for an additional 16 weeks. The primary endpoint of the study is reducing esophageal intraepithelial infiltration of mast cells as assessed by peak esophageal intraepithelial mast cell count. Secondary endpoints include the reduction of symptoms of dysphagia and esophageal intraepithelial infiltration of eosinophils and safety. The study includes approximately 60 clinical trial centers across 8 countries, including the United States. The study is fully accrued and we plan to present data from the study in the second half of 2025.

Previous wording

In 2023, we completed the transfer of our current barzolvolimab manufacturing process to a CMO 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.

Current wording

In 2023, we completed the transfer of our current barzolvolimab manufacturing process to a 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.

Previous wording

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 mAbsin 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. We have completed manufacturing and IND-enabling activities and plan to initiate a Phase 1 study of CDX-622 in healthy volunteers by the end of 2024.

Current wording

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 mAbsin vitro and preferentially inhibits the soluble over the membrane form of SCF, which may lead to differential impact on KIT-dependent processes. CDX-622 was well tolerated in a multi-dose 8 week toxicology study in non-human primates and led to a profound mast cell depletion in several tissues. The No Adverse Event Level (NOAEL) was established to be 75 mg/kg, the highest dose level tested.

Previous wording

The $3.9 million increase in net loss for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to an increase in research and development expenses, partially offset by an increase in investment and other income, net.

Current wording

The $21.0 million increase in net loss for the three months ended March 31, 2025, as compared to the three months ended March 31, 2024, was primarily due to an increase in research and development and general and administrative expenses, partially offset by an increase in investment and other income, net.

Previous wording

Revenue from product development and licensing agreements for the three months ended September 30, 2024 was relatively consistent with the three months ended September 30, 2023. The $1.7 million increase in contracts and grants revenue for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to an increase in revenue from our contract manufacturing and research and development agreements with Rockefeller University. We expect revenue to decrease over the next twelve months primarily due to a decrease in services expected to be performed under our contract manufacturing and research and development agreements with Rockefeller University.

Current wording

Revenue from product development and licensing agreements for the three months ended March 31, 2025 was relatively consistent with the three months ended March 31, 2024. The $0.5 million increase in contracts and grants revenue for the three months ended March 31, 2025, as compared to the three months ended March 31, 2024, was primarily due to an increase in revenue from our contract manufacturing and research and development agreements with Rockefeller University. We expect revenue to decrease over the next twelve months primarily due to a decrease in services expected to be performed under our contract manufacturing and research and development agreements with Rockefeller University.

Previous wording

Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes. The $3.3 million increase in personnel expenses for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to higher stock-based compensation expense and an increase in employee headcount. We expect personnel expenses to increase over the next twelve months as a result of additional headcount to support the expanded development of barzolvolimab.

Current wording

Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes. The $2.2 million increase in personnel expenses for the three months ended March 31, 2025, as compared to the three months ended March 31, 2024, was primarily due to higher stock-based compensation expense and an increase in employee headcount. We expect personnel expenses to increase over the next twelve months as a result of additional headcount to support the expanded development of barzolvolimab.

Previous wording

Laboratory supplies expenses include laboratory materials and supplies, services, and other related expenses incurred in the development of our technology. Laboratory supply expenses for the three months ended September 30, 2024 were relatively consistent with the three months ended September 30, 2023. We expect laboratory supplies expenses to remain relatively consistent over the next twelve months, although there may be fluctuations on a quarterly basis.

Current wording

Laboratory supplies expenses include laboratory materials and supplies, services, and other related expenses incurred in the development of our technology. The $0.9 million increase in laboratory supply expenses for the three months ended March 31, 2025, as compared to the three months ended March 31, 2024, was primarily due to higher laboratory materials and supplies purchases. We expect laboratory supplies expenses to remain relatively consistent over the next twelve months, although there may be fluctuations on a quarterly basis.

Previous wording

Product development expenses include clinical investigator site fees, external trial monitoring costs, data accumulation costs, contracted research and outside clinical drug product manufacturing. The $7.1 million increase in product development expenses for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to an increase in barzolvolimab clinical trial expenses, partially offset by a decrease in barzolvolimab contract manufacturing expenses. We expect product development expenses to increase over the next twelve months as a result of the expanded development of barzolvolimab, although there may be fluctuations on a quarterly basis.

Current wording

Product development expenses include clinical investigator site fees, external trial monitoring costs, data accumulation costs, contracted research and outside clinical drug product manufacturing. The $16.6 million increase in product development expenses for the three months ended March 31, 2025, as compared to the three months ended March 31, 2024, was primarily due to an increase in barzolvolimab clinical trial and contract manufacturing expenses. We expect product development expenses to increase over the next twelve months as a result of the expanded development of barzolvolimab, although there may be fluctuations on a quarterly basis.

Previous wording

The $1.8 million increase in general and administrative expenses for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to higher stock-based compensation and barzolvolimab commercial planning expenses. We expect general and administrative expenses to increase over the next twelve months as a result of the expanded development of barzolvolimab and an increase in commercial planning efforts, although there may be fluctuations on a quarterly basis.

Current wording

The $1.7 million increase in general and administrative expenses for the three months ended March 31, 2025, as compared to the three months ended March 31, 2024, was primarily due to higher stock-based compensation expense. We expect general and administrative expenses to increase over the next twelve months as a result of the expanded development of barzolvolimab and an increase in commercial planning efforts, although there may be fluctuations on a quarterly basis.

Previous wording

The $7.0 million increase in investment and other income, net for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to higher levels of cash as a result of our November 2023 and March 2024 underwritten public offerings. We expect investment and other income to remain relatively consistent over the next twelve months, although there may be fluctuations on a quarterly basis.

Current wording

The $1.1 million increase in investment and other income, net for the three months ended March 31, 2025, as compared to the three months ended March 31, 2024, was primarily due to higher levels of cash as a result of our March 2024 underwritten public offering. We expect investment and other income to decrease over the next twelve months due to lower levels of cash and investment balances, although there may be fluctuations on a quarterly basis.

Previous wording

At September 30, 2024, our principal sources of liquidity consisted of cash, cash equivalents and marketable securities of $756.0 million. We have had recurring losses and incurred a loss of $110.8 million for the nine months ended September 30, 2024. Net cash used in operations for the nine months ended September 30, 2024 was $125.3 million. We believe 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. This could be impacted if we elect to pay the future milestone under the Settlement Agreement with SRS in cash, in the event that we achieve the milestone related to that payment.

Current wording

At March 31, 2025, our principal sources of liquidity consisted of cash, cash equivalents and marketable securities of $673.3 million. We have had recurring losses and incurred a loss of $53.8 million for the three months ended March 31, 2025. Net cash used in operations for the three months ended March 31, 2025 was $54.4 million. We believe that the cash, cash equivalents and marketable securities at March 31, 2025 are sufficient to meet estimated working capital requirements and fund current planned operations through 2027. This could be impacted if we elect to pay the future milestone under the Settlement Agreement with SRS in cash, in the event that we achieve the milestone related to that payment.

Previous wording

Net cash used in operating activities was $125.3 million for the nine months ended September 30, 2024 as compared to $74.8 million for the nine months ended September 30, 2023. The increase in net cash used in operating activities was primarily due to increases in research and development and general and administrative expenses and an increase in advance payments to clinical research and contract manufacturing organizations, partially offset by an increase in investment income as a result of higher levels of cash. We expect that cash used in operating activities will increase over the next twelve months as a result of the expanded development of barzolvolimab.

Current wording

Net cash used in operating activities was $54.4 million for the three months ended March 31, 2025 as compared to $40.6 million for the three months ended March 31, 2024. The increase in net cash used in operating activities was primarily due to increases in research and development and general and administrative expenses, partially offset by an increase in investment income as a result of higher levels of cash. We expect that cash used in operating activities will increase over the next twelve months as a result of the expanded development of barzolvolimab.

Previous wording

Net cash used in investing activities was $314.2 million for the nine months ended September 30, 2024 compared to net cash provided by investing activities of $65.4 million for the nine months ended September 30, 2023. The increase in net cash used in investing activities was primarily due to net purchases of marketable securities of $313.0 million for the nine months ended September 30, 2024 as compared to net sales and maturities of marketable securities of $66.5 million for the nine months ended September 30, 2023.

Current wording

Net cash provided by investing activities was $43.0 million for the three months ended March 31, 2025 compared to net cash used in investing activities of $315.2 million for the three months ended March 31, 2024. The increase in net cash provided by investing activities was primarily due to net sales and maturities of marketable securities of $43.2 million for the three months ended March 31, 2025 as compared to net purchases of marketable securities of $314.9 million for the three months ended March 31, 2024.

Previous wording

Net cash provided by financing activities was $441.1 million for the nine months ended September 30, 2024 as compared to $1.1 million for the nine months ended September 30, 2023. The increase in net cash provided by financing activities was primarily due to an increase in net proceeds from stock issuances.

Current wording

Net cash provided by financing activities was $0.2 million for the three months ended March 31, 2025 as compared to $436.1 million for the three months ended March 31, 2024. The decrease in net cash provided by financing activities was primarily due to a decrease in net proceeds from stock issuances.