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 six months ended June 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, 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.

Previous wording

In July 2024, we 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. Both Phase 3 trials are randomized, double-blind, placebo-controlled, parallel group, global studies ( approximately 40 countries; 250 sites per study) where approximately 915 patients per trial will be randomized evenly to barzolvolimab 150 mg every 4 weeks (following 300 mg loading dose), barzolvolimab 300 mg every 8 weeks (following 450 mg loading dose) or placebo for 52 weeks. At 24 weeks, patients on placebo will be re-randomized to active treatment across both dosing groups. The primary endpoint of the studies will evaluate the clinical effect of barzolvolimab in reducing urticaria activity (weekly urticaria activity score; UAS7) at week 12. The studies are designed to detect a clinically meaningful difference between each of the active arms versus placebo in the overall population as well as in the subpopulation of omalizumab refractory participants. Enrollment is ongoing.

Current wording

We believe these results strongly support the further development of barzolvolimab in CSU. In July 2024, we 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. Both Phase 3 trials are randomized, double-blind, placebo-controlled, parallel group, global studies ( approximately 40 countries; 250 sites per study) where approximately 915 patients per trial will be randomized evenly to barzolvolimab 150 mg every 4 weeks (following 300 mg loading dose), barzolvolimab 300 mg every 8 weeks (following 450 mg loading dose) or placebo for 52 weeks. At 24 weeks, patients on placebo will be re-randomized to active treatment across both dosing groups. The primary endpoint of the studies will evaluate the clinical effect of barzolvolimab in reducing urticaria activity (weekly urticaria activity score; UAS7) at week 12. The studies are designed to detect a clinically meaningful difference between each of the active arms versus placebo in the overall population as well as in the subpopulation of omalizumab refractory participants. Enrollment is ongoing.

Previous wording

In July 2022, we 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, we announced that enrollment was complete. The study is being conducted at approximately 85 sites across approximately 12 countries. The 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 CIndU to determine the optimal dosing strategy. 196 patients in 2 cohorts (differentiated by CIndU subtype) including 97 patients with cold urticaria and 99 patients with symptomatic dermographism were randomly assigned on a 1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 20-week treatment phase. Patients then enter a follow-up phase for an additional 24 weeks. In addition, the study includes the option for patients who have symptoms following the treatment phase, including patients who were on placebo, to enroll in an open label extension where all patients receive 300 mg of barzolvolimab every 8 weeks. The primary endpoint of the study is the percentage of patients with a negative provocation test at week 12. Secondary endpoints include safety and other assessments of clinical activity including CTT (Critical Temperature Threshold), CFT (Critical Friction Threshold) and WI-NRS (Worst itch numeric rating scale). Topline primary endpoint data from this study were reported in July 2024 and showed that barzolvolimab achieved the primary efficacy endpoint, a statistically significant difference between the percent of patients with a negative provocation test compared to placebo at week 12 as assessed by the TempTest® in ColdU and the FricTest® in SD. Importantly, barzolvolimab demonstrated rapid, durable and clinically meaningful responses in patients with CIndU refractory to antihistamines. Demographics and baseline disease characteristics were well balanced across treatment groups.

Current wording

In July 2022, we 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, we announced that enrollment was complete. The study is being conducted at approximately 85 sites across approximately 12 countries. The 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 CIndU to determine the optimal dosing strategy. 196 patients in 2 cohorts (differentiated by CIndU subtype) including 97 patients with cold urticaria and 99 patients with symptomatic dermographism were randomly assigned on a 1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 20-week treatment phase. Patients then enter a follow-up phase for an additional 24 weeks. In addition, the study includes the option for patients who have symptoms following the treatment phase, including patients who were on placebo, to enroll in an open label extension where all patients receive 300 mg of barzolvolimab every 8 weeks. The primary endpoint of the study is the percentage of patients with a negative provocation test at week 12. Secondary endpoints include safety and other assessments of clinical activity including CTT (Critical Temperature Threshold), CFT (Critical Friction Threshold) and WI-NRS (Worst itch numeric rating scale).

Previous wording

Barzolvolimab was well tolerated with a favorable safety profile consistent with prior studies. Most adverse events were mild to moderate in severity; through 12 weeks, the most common treatment emergent adverse events in barzolvolimab treated patients were hair color changes (13%) and neutropenia (11%). The rate of infections was similar between barzolvolimab-treated patients and placebo with no association between neutropenia and infections.

Current wording

Barzolvolimab was well tolerated with a favorable safety profile consistent with prior studies. Most adverse events were grade 1 (mild). Through 12 weeks, the most common treatment emergent adverse events in barzolvolimab treated patients were hair color changes (13%; Grade 1, n=15 / Grade 2, n=2) and neutropenia (10%; Grade 1, n=7 / Grade 2, n=6), which are mechanism related (KIT) and expected to be reversible. The rate of infections was similar between barzolvolimab-treated patients and placebo with no association between neutropenia and infections.

Previous wording

Patients on study will continue to receive barzolvolimab for 20 weeks and we plan to report full 12 week primary endpoint data from this study in the fourth quarter of 2024. We believe these results strongly support the further development of barzolvolimab in CIndU and plan to advance CIndU into Phase 3 registrational development.

Current wording

We believe these results strongly support the further development of barzolvolimab in CIndU and plan to advance CIndU into Phase 3 registrational development.

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 in support of Phase 3 trials. We are in the process of scaling up our drug product manufacturing. We believe that barzolvolimab can be scaled up to permit drug product manufacturing in commercial quantities.

Current 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.

Previous wording

Our next generation bispecific antibody platform is supporting the expansion of our pipeline with additional candidates for inflammatory diseases and oncology. Targets are being selected based on new science as well as their compatibility to be used in bispecific antibody formats with our existing antibody programs. Development is focused on emerging, important pathways controlling inflammatory diseases or immunity to tumors.

Current wording

Our next generation bispecific antibody platform is supporting the expansion of our 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 our existing antibody programs. Development is focused on emerging, important pathways controlling inflammatory diseases.

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 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. 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.

Previous wording

The $5.3 million increase in net loss for the three months ended June 30, 2024, as compared to the three months ended June 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 $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.

Previous wording

Revenue from product development and licensing agreements for the three months ended June 30, 2024 was relatively consistent with the three months ended June 30, 2023. The $2.2 million increase in contracts and grants revenue for the three months ended June 30, 2024, as compared to the three months ended June 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 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.

Previous wording

Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes. The $2.9 million increase in personnel expenses for the three months ended June 30, 2024, as compared to the three months ended June 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 $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.

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 $10.1 million increase in product development expenses for the three months ended June 30, 2024, as compared to the three months ended June 30, 2023, was primarily due to an increase in barzolvolimab clinical trial 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 $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.

Previous wording

The $1.9 million increase in general and administrative expenses for the three months ended June 30, 2024, as compared to the three months ended June 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 $1.8 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.

Previous wording

The $7.8 million increase in investment and other income, net for the three months ended June 30, 2024, as compared to the three months ended June 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 $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.

Previous wording

The $8.8 million increase in net loss for the six months ended June 30, 2024, as compared to the six months ended June 30, 2023, was primarily due to increases in research and development and general and administrative expenses, partially offset by an increase in investment and other income, net.

Current wording

The $12.6 million increase in net loss for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to increases 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 six months ended June 30, 2024 was relatively consistent with the six months ended June 30, 2023. The $1.4 million increase in contracts and grants revenue for the six months ended June 30, 2024, as compared to the six months ended June 30, 2023, was primarily due to an increase in revenue from our contract manufacturing and research and development agreements with Rockefeller University.

Current wording

Revenue from product development and licensing agreements for the nine months ended September 30, 2024 was relatively consistent with the nine months ended September 30, 2023. The $3.1 million increase in contracts and grants revenue for the nine months ended September 30, 2024, as compared to the nine 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.

Previous wording

Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes. The $5.3 million increase in personnel expenses for the six months ended June 30, 2024, as compared to the six months ended June 30, 2023, was primarily due to higher stock-based compensation expense and an increase in employee headcount.

Current wording

Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes. The $8.6 million increase in personnel expenses for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to higher stock-based compensation expense and an increase in employee headcount.

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 six months ended June 30, 2024 were relatively consistent with the six months ended June 30, 2023.

Current 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 nine months ended September 30, 2024 were relatively consistent with the nine months ended September 30, 2023.

Previous wording

Facility expenses include depreciation, amortization, utilities, rent, maintenance and other related expenses incurred at our facilities. Facility expenses for the six months ended June 30, 2024 were relatively consistent with the six months ended June 30, 2023.

Current wording

Facility expenses include depreciation, amortization, utilities, rent, maintenance and other related expenses incurred at our facilities. Facility expenses for the nine months ended September 30, 2024 were relatively consistent with the nine months ended September 30, 2023.

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 $12.3 million increase in product development expenses for the six months ended June 30, 2024, as compared to the six months ended June 30, 2023, was primarily due to an increase in barzolvolimab clinical trial expenses, partially offset by a decrease in barzolvolimab contract manufacturing expenses.

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 $19.4 million increase in product development expenses for the nine months ended September 30, 2024, as compared to the nine 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.

Previous wording

The $4.4 million increase in general and administrative expenses for the six months ended June 30, 2024, as compared to the six months ended June 30, 2023, was primarily due to higher stock-based compensation and barzolvolimab commercial planning expenses.

Current wording

The $6.2 million increase in general and administrative expenses for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to higher stock-based compensation and barzolvolimab commercial planning expenses.

Previous wording

The $12.5 million increase in investment and other income, net for the six months ended June 30, 2024, as compared to the six months ended June 30, 2023, was primarily due to higher levels of cash as a result of our November 2023 and March 2024 underwritten public offerings.

Current wording

The $19.5 million increase in investment and other income, net for the nine months ended September 30, 2024, as compared to the nine 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.

Previous wording

At June 30, 2024, our principal sources of liquidity consisted of cash, cash equivalents and marketable securities of $802.3 million. We have had recurring losses and incurred a loss of $68.7 million for the six months ended June 30, 2024. Net cash used in operations for the six months ended June 30, 2024 was $70.0 million. We believe that the cash, cash equivalents and marketable securities at June 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 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.

Previous wording

Net cash used in operating activities was $70.0 million for the six months ended June 30, 2024 as compared to $55.8 million for the six months ended June 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, 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 $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.

Previous wording

Net cash used in investing activities was $361.9 million for the six months ended June 30, 2024 compared to net cash provided by investing activities of $53.7 million for the six months ended June 30, 2023. The increase in net cash used in investing activities was primarily due to net purchases of marketable securities of $361.3 million for the six months ended June 30, 2024 as compared to net sales and maturities of marketable securities of $54.7 million for the six months ended June 30, 2023.

Current 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.

Previous wording

Net cash provided by financing activities was $439.8 million for the six months ended June 30, 2024 as compared to $0.8 million for the six months ended June 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 $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.

Previous wording

In March 2024, we issued 9,798,000 shares of common stock in an underwritten public offering, resulting in net proceeds of $ 432.3 million, after deducting underwriting fees and offering expenses.

Current wording

In March 2024, we issued 9,798,000 shares of common stock in an underwritten public offering, resulting in net proceeds of $432.3 million, after deducting underwriting fees and offering expenses.