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What changed in Celldex Therapeutics, Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Celldex Therapeutics, Inc.'s 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+441 added−352 removedSource: 10-K (2026-02-25) vs 10-K (2025-02-27)

Top changes in Celldex Therapeutics, Inc.'s 2025 10-K

441 paragraphs added · 352 removed · 308 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

105 edited+49 added−17 removed204 unchanged
Biggest changePatients on study continued to receive barzolvolimab for 20 weeks of treatment; - Prurigo Nodularis (PN): In April 2024, we initiated a Phase 2 study in PN and enrollment is ongoing; positive data from a Phase 1b study in PN was reported in November 2023; - Eosinophilic Esophagitis (EoE): A Phase 2 study in EoE was initiated in June 2023 and is fully accrued; and - Atopic Dermatitis (AD): A Phase 2 study in AD was initiated in December 2024 and enrollment is ongoing. ● Our next generation bispecific antibody platform to support pipeline expansion with additional candidates for inflammatory diseases.
Biggest changePatients on study continued to receive barzolvolimab and, in November 2025, we reported data from 20 weeks of treatment—demonstrating sustained efficacy and a well tolerated safety profile over the longer treatment period; - Prurigo Nodularis (PN): In April 2024, we initiated a Phase 2 study in PN and enrollment was completed in December 2025.
In the 3.0 mg/kg arm, a ≥4-point decrease in WI-NRS reduction was seen as early as the first week and reached a high of 71% of patients at week six which was distinct from both the 1.5 mg/kg barzolvolimab and placebo arms. % of Subjects with ≥4-point decrease in WI-NRS Dose Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 1.5 mg/kg 0 14 29 14 29 29 29 43 3.0 mg/kg 14 29 29 29 57 71 57 57 placebo 0 0 13 13 25 38 38 25 ​ ● At week 8, 29% of patients achieved clear or almost clear skin according to IGA following a single dose of barzolvolimab 3.0 mg/kg.
In the 3.0 mg/kg arm, a ≥4-point decrease in WI-NRS reduction was seen as early as the first week and reached a high of 71% of patients at Week 6 which was distinct from both the 1.5 mg/kg barzolvolimab and placebo arms. % of Subjects with ≥4-point decrease in WI-NRS Dose Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 1.5 mg/kg 0 14 29 14 29 29 29 43 3.0 mg/kg 14 29 29 29 57 71 57 57 placebo 0 0 13 13 25 38 38 25 ​ ● At Week 8, 29% of patients achieved clear or almost clear skin according to IGA following a single dose of barzolvolimab 3.0 mg/kg.
Two-thirds of patients treated with first line systemic therapy (1.7 million patienst in the US) do not achieve complete control of their atopic dermatitis (Simpson, Bieber, Guttman-Yassky, et al. 2016) and new therapies that offer rapid, meaningful relief from the severe itching and breakdown of the skin associated with AD are needed.
Two-thirds of patients treated with first line systemic therapy (1.7 million patients in the US) do not achieve complete control of their atopic dermatitis (Simpson, Bieber, Guttman-Yassky, et al. 2016) and new therapies that offer rapid, meaningful relief from the severe itching and breakdown of the skin associated with AD are needed.
The process required by the FDA before a drug or biological product may be marketed in the United States generally involves the following: ● completion of preclinical studies and formulation studies in compliance with the FDA’s good laboratory practice, or GLP, regulations; ● submission to the FDA of an investigational new drug, or IND, application which must become effective before human clinical trials may begin; 16 Table of Contents ● approval by an independent institutional review board, or IRB, at each clinical site before each trial may be initiated; ● performance of adequate and well-controlled human clinical trials in accordance with good clinical practices, or GCP, to establish the safety and efficacy of the proposed drug or biological product for each indication; ● submission to the FDA of a new drug application, or NDA, or a biologics license application, or BLA, as applicable; ● satisfactory completion of an FDA advisory committee review, if applicable; ● satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is produced to assess compliance with cGMP requirements and to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity; and ● FDA review and approval of the NDA or BLA.
The process required by the FDA before a drug or biological product may be marketed in the United States generally involves the following: ● completion of preclinical studies and formulation studies in compliance with the FDA’s good laboratory practice, or GLP, regulations; ● submission to the FDA of an investigational new drug, or IND, application which must become effective before human clinical trials may begin; ● approval by an independent institutional review board, or IRB, at each clinical site before each trial may be initiated; ● performance of adequate and well-controlled human clinical trials in accordance with good clinical practices, or GCP, to establish the safety and efficacy of the proposed drug or biological product for each indication; ● submission to the FDA of a new drug application, or NDA, or a biologics license application, or BLA, as applicable; ● satisfactory completion of an FDA advisory committee review, if applicable; ● satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is produced to assess compliance with cGMP requirements and to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity; and ● FDA review and approval of the NDA or BLA.
Key highlighted included: ● Improvements in UAS7 (weekly urticaria activity score), previously shown to be statistically significantly vs placebo at Week 12, were noted as early as week 1 and were sustained or deepened at Week 52. ● At Week 16, patients receiving low dose barzolvolimab (75 mg) or placebo were transitioned to barzolvolimab 150 mg or 300 mg; after crossover, these patients experienced similar clinically meaningful disease response as the rest of the study population. ● 71% of patients treated with barzolvolimab 150 mg Q4W and 52% of patients treated with 300 mg Q8W had a complete response (no itch/hives; UAS7=0) at Week 52.
Key highlights included: ● Improvements in UAS7 (weekly urticaria activity score), previously shown to be statistically significantly vs placebo at Week 12, were noted as early as Week 1 and were sustained or deepened at Week 52. ● At Week 16, patients receiving low dose barzolvolimab (75 mg) or placebo were transitioned to barzolvolimab 150 mg or 300 mg; after crossover, these patients experienced similar clinically meaningful disease response as the rest of the study population. ● 71% of patients treated with barzolvolimab 150 mg Q4W and 52% of patients treated with 300 mg Q8W had a complete response (no itch/hives; UAS7=0) at Week 52.
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.
The randomized, double-blind, placebo-controlled, parallel group Phase 2 study evaluated 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.
The primary endpoint of the study was safety; key secondary 8 Table of Contents endpoints include changes from baseline in Worst Itch-Numerical Rating Scale (WI-NRS) & Investigator Global Assessment (IGA). The primary timepoint for evaluation of clinical activity was 8 weeks; patients were followed for safety and efficacy endpoints to 24 weeks.
The primary endpoint of the study was safety; key secondary endpoints include changes from baseline in Worst Itch-Numerical Rating Scale (WI-NRS) & Investigator Global Assessment (IGA). The primary timepoint for evaluation of clinical activity was 8 weeks; patients were followed for safety and efficacy endpoints to 24 weeks.
This confirmed that serum tryptase level is a robust pharmacodynamic biomarker for assessing mast cell burden and clinical activity in inducible urticaria and potentially in other diseases with mast cell driven involvement. 6 Table of Contents ● Barzolvolimab was well tolerated across all cohorts.
This confirmed that serum tryptase level is a robust pharmacodynamic biomarker for assessing mast cell burden and clinical activity in inducible urticaria and potentially in other diseases with mast cell driven involvement. 7 Table of Contents ● Barzolvolimab was well tolerated across all cohorts.
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.
In July 2024, we announced that our Phase 2 study in 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.
In addition to third-party payors, we will also need to negotiate formulary placement with hospitals, health systems and certain independent delivery networks. Such negotiations may be 22 Table of Contents more protracted than anticipated and may be compromised because of similar considerations, relating to insufficient incremental value and/or cost-effectiveness. Pricing and reimbursement schemes vary widely from country to country.
In addition to third-party payors, we will also need to negotiate formulary placement with hospitals, health systems and certain independent delivery networks. Such negotiations may be more protracted than anticipated and may be compromised because of similar considerations, relating to insufficient incremental value and/or cost-effectiveness. Pricing and reimbursement schemes vary widely from country to country.
It is impossible to predict whether further legislative changes will be enacted or whether FDA regulations, guidance, policies or interpretations will change or what the effect of such changes, if any, may be. Third-Party Payor Coverage and Reimbursement Significant uncertainty exists as to the coverage and reimbursement status of any drug products for which we obtain regulatory approval.
It is impossible to predict whether further legislative changes will be enacted or whether FDA regulations, guidance, policies or interpretations will change or what the effect of such changes, if any, may be. 24 Table of Contents Third-Party Payor Coverage and Reimbursement Significant uncertainty exists as to the coverage and reimbursement status of any drug products for which we obtain regulatory approval.
The final histologic analysis and study report were completed in early 2023 and were consistent with previously reported results. We are encouraged with these findings and believe these data strongly support continued development of barzolvolimab. Bispecific Platform Our next generation bispecific antibody platform is supporting the expansion of our pipeline with additional candidates for inflammatory diseases.
The final histologic analysis and study report were completed in early 2023 and were consistent with previously reported results. We are encouraged with these findings and believe these data strongly support continued development of barzolvolimab. 12 Table of Contents Bispecific Platform Our next generation bispecific antibody platform is supporting the expansion of our pipeline with additional candidates for inflammatory diseases.
Pediatric Information Under the Pediatric Research Equity Act of 2003, an NDA, BLA or supplement to an NDA or BLA must contain data that are adequate to assess the safety and effectiveness of the drug or biological product for the claimed indications in all relevant pediatric 19 Table of Contents subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
Pediatric Information Under the Pediatric Research Equity Act of 2003, an NDA, BLA or supplement to an NDA or BLA must contain data that are adequate to assess the safety and effectiveness of the drug or biological product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
Patents have also been issued in Europe, Japan, Canada, China, Australia, New Zealand, Israel, India, the Republic of Korea, the Russian Federation, Singapore, Brazil, Mexico, South Africa and certain other countries. Where issued the foregoing would 14 Table of Contents have estimated normal patent expiry dates ranging from 2032 to 2033.
Patents have also been issued in Europe, Japan, Canada, China, Australia, New Zealand, Israel, India, the Republic of Korea, the Russian Federation, Singapore, Brazil, Mexico, South Africa and certain other countries. Where issued the foregoing would have estimated normal patent expiry dates ranging from 2032 to 2033.
Accordingly, manufacturers must continue to expend time, money and effort in the areas of production and quality control to maintain cGMP compliance. Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.
Accordingly, manufacturers must continue to expend time, money and effort in the areas of production and quality control to maintain cGMP compliance. 22 Table of Contents Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.
Third parties may have or may obtain valid and enforceable patents or proprietary rights that could block us from developing products using our technology, including: ● certain patents and pending patent applications in the United States and foreign countries relating to particular receptors, antigens and antigenic fragments targeted by our current drug candidates; and ● certain patents and pending patent applications in the United States and foreign countries relating to antibodies targeting certain receptors and other targets including anti- SCF antibodies, anti-TSLP antibodies and certain other antibodies and their sequences and uses.
Third parties may have or may obtain valid and enforceable patents or proprietary rights that could block us from developing products using our technology, including: ● certain patents and pending patent applications in the United States and foreign countries relating to particular receptors, antigens and antigenic fragments targeted by our current drug candidates; and 17 Table of Contents ● certain patents and pending patent applications in the United States and foreign countries relating to antibodies targeting certain receptors and other targets including anti- SCF antibodies, anti-TSLP antibodies and certain other antibodies and their sequences and uses.
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). 7 Table of Contents Topline primary endpoint data from this study were reported in July 2024 and 12 week treatment results were presented at the American College of Allergy, Asthma & Immunology’s Annual Scientific Meeting.
Secondary endpoints included safety and other assessments of clinical activity including CTT (Critical Temperature Threshold), CFT (Critical Friction Threshold) and WI-NRS (Worst itch numeric rating scale). 8 Table of Contents Topline primary endpoint data from this study were reported in July 2024 and 12 week treatment results were presented at the American College of Allergy, Asthma & Immunology’s Annual Scientific Meeting.
Omalizumab, an IgE inhibitor, provides relief for roughly half of the remaining antihistamine refractory patients. Consequently, there is a need for additional therapies. We have completed a Phase 1b randomized, double-blind, placebo-controlled multi-center study of barzolvolimab in CSU.
Omalizumab, an IgE inhibitor, provides relief for roughly half of the remaining antihistamine refractory patients. Consequently, there is a need for additional therapies. 2 Table of Contents We have completed a Phase 1b randomized, double-blind, placebo-controlled multi-center study of barzolvolimab in CSU.
Studies that are conducted in multiple countries are reviewed and authorized by additional regional or country specific health authorities in addition to the FDA. The additional international review often is slower than that of the FDA and may result in regulatory opinions that are different than the decisions provided by the FDA.
Studies that are conducted in multiple countries are reviewed and authorized by additional regional or country specific health authorities in addition to the FDA. The 19 Table of Contents additional international review often is slower than that of the FDA and may result in regulatory opinions that are different than the decisions provided by the FDA.
Alternatively, we may borrow funds from commercial lenders, likely at high interest rates, which would increase the risk of any investment in us. Manufacturing We are a research and development company and have limited experience in commercial manufacturing.
Alternatively, we may borrow funds from commercial lenders, likely at high interest rates, which would increase the risk of any investment in us. 15 Table of Contents Manufacturing We are a research and development company and have limited experience in commercial manufacturing.
Failure to conduct required post-approval studies, or confirm a clinical benefit during post-marketing studies, would allow the FDA to withdraw the drug from the market on an expedited basis. All promotional materials for drug candidates approved under accelerated regulations are subject to prior review by the FDA.
Failure to conduct required post-approval studies, or confirm a clinical benefit during post-marketing studies, would allow the FDA to 21 Table of Contents withdraw the drug from the market on an expedited basis. All promotional materials for drug candidates approved under accelerated regulations are subject to prior review by the FDA.
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.
In July 2024, we announced that our Phase 2 study being conducted in two forms of chronic inducible urticaria (CIndU), ColdU and SD, 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.
Sponsors are also obligated to disclose the results of their clinical trials after completion. Disclosure of the results of clinical trials can be 17 Table of Contents delayed in certain circumstances for up to two years after the date of completion of the trial.
Sponsors are also obligated to disclose the results of their clinical trials after completion. Disclosure of the results of clinical trials can be delayed in certain circumstances for up to two years after the date of completion of the trial.
We have manufactured barzolvolimab and CDX-622 drug substance in our Fall River facility for our current and planned Phase 1 and Phase 2 clinical trials. Our barzolvolimab drug product is currently administered subcutaneously. The subcutaneous formulation will allow for potential self-administration at home setting versus the need for intravenous dosing in a hospital or clinic setting.
We have manufactured barzolvolimab and CDX-622 drug substance in our Fall River facility for our current and planned Phase 1 and Phase 2 clinical trials. Our barzolvolimab drug product is currently administered subcutaneously. The subcutaneous formulation allows for potential self-administration at home, eliminating the need for intravenous dosing in a hospital or clinic setting.
If, when and where issued the latter would have estimated normal patent expiry dates in 2042. ● We own a pending international patent application directed to anti-SCF and anti-TSLP antibody sequences used in CDX-622 as compositions of matter.
If, when and where issued the latter would have estimated normal patent expiry dates in 2042. ● We own a portfolio of pending patent applications directed to anti-SCF and anti-TSLP antibody sequences used in CDX-622 as compositions of matter.
Data obtained from clinical activities are not always conclusive and may be susceptible to varying interpretations that could delay, limit or prevent regulatory approval. The FDA may not grant approval on a timely basis, or at all.
Data obtained from clinical activities are not always conclusive and may be susceptible to varying interpretations that could 20 Table of Contents delay, limit or prevent regulatory approval. The FDA may not grant approval on a timely basis, or at all.
After 52 weeks, patients then enter a follow-up period for an additional 24 weeks. The primary endpoint of the study is mean change in baseline to week 12 in UAS7 (weekly urticaria activity score).
After 52 weeks, patients then entered a follow-up period for an additional 24 weeks. The primary endpoint of the study was mean change in baseline to Week 12 in UAS7 (weekly urticaria activity score).
The primary endpoint of the study is the percentage of patients with a negative provocation test at week 12.
The primary endpoint of the study was the percentage of patients with a negative provocation test at Week 12.
In cold urticaria, patients presented with a mean baseline critical temperature threshold of approximately 19°C or 66°F on the TempTest on initial provocation testing. In patients with symptomatic dermographism baseline FricTest thresholds were an average of 3.6 out of 4 pins. UCT scores at baseline reflect poorly controlled disease.
Patients on study had poorly controlled disease on initial provocation testing. In cold urticaria, patients presented with a mean baseline critical temperature threshold of approximately 19°C or 66°F on the TempTest on initial provocation testing. In patients with symptomatic dermographism baseline FricTest thresholds were an average of 3.6 out of 4 pins.
Employees As a mission driven organization, we believe the engagement and dedication of our employees is central to our success and employ talented individuals who have the skills and expertise to help us achieve our goals. As of December 31, 2024, we had 186 full-time employees, 29 of whom have Ph.D. and/or M.D. degrees.
Employees As a mission driven organization, we believe the engagement and dedication of our employees is central to our success and employ talented individuals who have the skills and expertise to help us achieve our goals. As of December 31, 2025, we had 198 full-time employees, 30 of whom have Ph.D. and/or M.D. degrees.
Of these employees, 157 were engaged in or directly support research and development activities. We consider our relationship with our employees to be good. We believe that our success depends in large part on our ability to attract and retain experienced and skilled employees.
Of these employees, 166 were engaged in or directly support research and development activities. We consider our relationship with our employees to be good. 25 Table of Contents We believe that our success depends in large part on our ability to attract and retain experienced and skilled employees.
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 November 2023, we reported that barzolvolimab achieved the primary efficacy endpoint in a Phase 2 study in CSU, with a statistically significant mean change from baseline to Week 12 of UAS7 (weekly urticaria activity score) compared to placebo and was well tolerated.
If we become involved in that litigation, we could consume substantial resources. 15 Table of Contents Licenses We have entered into significant license agreements relating to technologies that are being developed by us.
If we become involved in that litigation, we could consume substantial resources. Licenses We have entered into significant license agreements relating to technologies that are being developed by us.
After 16 weeks, patients then enter a 36-week active treatment period, in which patients receiving placebo or the 75 mg dose are randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks; patients already randomized to the 150 mg and 300 mg treatment arms remain on the same regimen as during the placebo-controlled treatment period.
After 16 weeks, patients then entered a 36-week active treatment period, in which patients receiving placebo or the 75 mg dose were randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks; patients already randomized to the 150 mg and 300 mg treatment arms remained on the same regimen as during the placebo-controlled treatment period.
The study is a randomized, double-blind, placebo-controlled, parallel group Phase 2 study evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab to determine the optimal dosing strategy. 208 patients have been randomly assigned on a 1:1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 16-week placebo-controlled treatment phase.
The study was a randomized, double-blind, placebo-controlled, parallel group Phase 2 study that evaluated the efficacy and safety profile of multiple dose regimens of barzolvolimab to determine the optimal dosing strategy. 208 patients were randomly assigned on a 1:1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 16-week placebo-controlled treatment phase.
The following table is a summary of the competitors of which we are aware that have initiated a Phase 3 study or have obtained marketing approval for a potentially competitive drug to barzolvolimab for treatment of CSU, CIndU, PN, EoE and AD. 12 Table of Contents Competitor Competitor Product Indication(s) Abbvie Rinvoq AD Amgen Tezpire EoE Amgen/Kiowa Kirin Rocatinlimab AD and PN Celltrion CT-P39, omalizumab biosimilar CSU Eli Lilly Olumiant and Ebglyss AD Galderma/Chugai Nemluvio PN and AD Incyte Povorcitinib PN Kashiv Biosciences ADL-018 omalizumab biosimilar CSU Leo Pharma Adbry AD Medimetriks Difamilast AD Novartis Remibrutinib CSU and CIndU Pfizer Cibinqo AD Regeneron/Sanofi Dupixent CSU, PN, EoE and AD Regeneron/Sanofi Amlitelimab AD Teva Tev-45779, omalizumab biosimilar CSU Vanda Pharmaceuticals Tradipitant AD ​ Our competitors may utilize discovery technologies and techniques or partner with collaborators in order to develop products more rapidly or successfully than us or our collaborators are able to.
Some of our competitors possess substantially greater financial, technical and human resources than we do. ​ 14 Table of Contents The following table is a summary of the competitors of which we are aware that have initiated a Phase 3 study or have obtained marketing approval for a potentially competitive drug to barzolvolimab for treatment of CSU, CIndU, PN, and AD. ​ ​ Competitor ​ ​ ​ Competitor Product ​ ​ ​ Indication(s) Abbvie ​ Rinvoq ​ AD Akeso Bio ​ AKT120 ​ AD Amgen/Kiowa Kirin ​ Rocatinlimab ​ AD and PN Celltrion ​ CT-P39, omalizumab biosimilar ​ CSU Eli Lilly ​ Olumiant and Ebglyss ​ AD Galderma/Chugai ​ Nemluvio ​ PN and AD Genentech/Novartis ​ Xolair ​ CSU Incyte ​ Povorcitinib ​ PN Kashiv Biosciences ​ ADL-018 omalizumab biosimilar ​ CSU Leo Pharma ​ Adbry ​ AD Medimetriks ​ Difamilast ​ AD Novartis ​ Remibrutinib ​ CSU and CIndU Pfizer ​ Cibinqo ​ AD Regeneron/Sanofi ​ Dupixent ​ CSU, PN, and AD Sanofi ​ Amlitelimab ​ AD Teva ​ Tev-45779, omalizumab biosimilar ​ CSU Vanda Pharmaceuticals ​ Tradipitant ​ AD ​ Our competitors may utilize discovery technologies and techniques or partner with collaborators in order to develop products more rapidly or successfully than us or our collaborators are able to.
Other potential consequences include, among other things: ● restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; ● fines, untitled and warning letters or holds on post-approval clinical trials; ● refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; ● product seizure or detention, or refusal to permit the import or export of products; or ● consent decrees, injunctions or the imposition of civil or criminal prosecution. 20 Table of Contents The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market.
Other potential consequences include, among other things: ● restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; ● fines, untitled and warning letters or holds on post-approval clinical trials; ● refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; ● product seizure or detention, or refusal to permit the import or export of products; or ● consent decrees, injunctions or the imposition of civil or criminal prosecution.
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.
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.
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.
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.
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.
Patients then entered a follow-up phase for an additional 24 weeks. In addition, the study included the option for patients who had symptoms following the treatment phase, including patients who were on placebo, to enroll in an open label extension where all patients received 300 mg of barzolvolimab every 8 weeks.
A single IV dose of 3.0 mg/kg barzolvolimab resulted in rapid and durable reductions in itch and healing of skin lesions in patients with moderate to severe PN and that barzolvolimab was generally well tolerated. ● At week 8, the percentage of patients with ≥4-point decrease in WI-NRS was 57% and 43% for the single dose 3.0 or 1.5 mg/kg barzolvolimab arms, respectively, and 25% for the placebo arm; this level of response generally persisted out to week 16.
Patients on study generally had moderate to severe disease with mean baselines scores across all arms of 8.6 for WI-NRS and 3.3 for IGA. ​ 10 Table of Contents A single IV dose of 3.0 mg/kg barzolvolimab resulted in rapid and durable reductions in itch and healing of skin lesions in patients with moderate to severe PN and that barzolvolimab was generally well tolerated. ● At Week 8, the percentage of patients with ≥4-point decrease in WI-NRS was 57% and 43% for the single dose 3.0 or 1.5 mg/kg barzolvolimab arms, respectively, and 25% for the placebo arm; this level of response generally persisted out to Week 16.
The key patents and patent applications owned by us or licensed to us that we consider important to our current clinical programs include the following (except where stated otherwise, the indicated and estimated patent expiry dates are the estimated normal expirations if all maintenance fees and annuities are paid when due, and do not include any possible additional terms for Patent Term Adjustments (PTAs), Patent Term Extensions (PTEs), other term extensions or Supplementary Protection Certificates (SPCs), if these may be secured in due course): ● We own a portfolio of patents and patent applications directed to barzolvolimab and other anti-KIT receptor antibodies.
We routinely review our patent portfolio and adjust our strategies for prosecution and maintenance of individual cases according to a number of factors, including program priorities, stage of development and patent term. 16 Table of Contents The key patents and patent applications owned by us or licensed to us that we consider important to our current clinical programs include the following (except where stated otherwise, the indicated and estimated patent expiry dates are the estimated normal expirations if all maintenance fees and annuities are paid when due, and do not include any possible additional terms for Patent Term Adjustments (PTAs), Patent Term Extensions (PTEs), other term extensions or Supplementary Protection Certificates (SPCs), if these may be secured in due course): ● We own a portfolio of patents and patent applications directed to barzolvolimab and other anti-KIT receptor antibodies.
Secondary objectives include but are not limited to additional measures of itch response from baseline compared to different timepoints, the assessment of skin lesions as measured by the Investigator Global Assessment (IGA), QoL outcomes and safety. The study will include approximately 50 clinical trial centers worldwide, including the United States.
Secondary objectives include but are not limited to additional measures of itch response from baseline compared to different timepoints, the assessment of skin lesions as measured by the Investigator Global Assessment (IGA), QoL outcomes and safety. The study includes approximately 75 clinical trial centers worldwide, including the United States. Enrollment was completed in December 2025.
Secondary endpoints include safety and other assessments of clinical activity including ISS7 (weekly itch severity score), HSS7 (weekly hive severity score) and AAS7 (weekly angioedema activity score). 3 Table of Contents Topline data from this study were presented in November of 2023 and 12 week treatment results were presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in February 2024.
Secondary endpoints included safety and other assessments of clinical activity including ISS7 (weekly itch severity score), HSS7 (weekly hive severity score) and AAS7 (weekly angioedema activity score). Topline data from this study were presented in November of 2023 and 12 week treatment results were presented at the AAAAI Annual Meeting in February 2024.
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.
At 24 weeks, patients on placebo will be re-randomized to active treatment across both dosing groups. After completion of the 52 week treatment period, patients on study will continue to be followed for 16 weeks. 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.
Patients on study continued to receive barzolvolimab and, in September 2024, we reported data from 52 weeks of treatment—demonstrating sustained and deepening disease efficacy and a well tolerated long term safety profile.
Patients on study continued to receive barzolvolimab and, in September 2024, we reported data from 52 weeks of treatment—demonstrating sustained and deepening disease efficacy and a well tolerated long term safety profile. In June 2025, Celldex presented longer term follow up data from the study.
Barzolvolimab was administered intravenously as add on treatment to H1-antihistamines, either alone or in combination with H2-antihistamines and/or leukotriene receptor agonists. 45 patients with moderate to severe CSU refractory to antihistamines were enrolled and treated [35 barzolvolimab (n=9 in 0.5 mg/kg; n=8 in 1.5 mg/kg; n=9 in 3.0 mg/kg; n=9 in 4.5 mg/kg) and 10 placebo]. 2 Table of Contents At saturating doses (1.5 mg/kg and higher), barzolvolimab resulted in rapid, marked and durable responses in patients with moderate to severe CSU refractory to antihistamines.
Barzolvolimab was administered intravenously as add on treatment to H1-antihistamines, either alone or in combination with H2-antihistamines and/or leukotriene receptor agonists. 45 patients with moderate to severe CSU refractory to antihistamines were enrolled and treated [35 barzolvolimab (n=9 in 0.5 mg/kg; n=8 in 1.5 mg/kg; n=9 in 3.0 mg/kg; n=9 in 4.5 mg/kg) and 10 placebo].
We are focusing our efforts and resources on the continued research and development of ● Barzolvolimab (also referred to as CDX-0159), a monoclonal antibody that specifically binds the KIT receptor and potently inhibits its activity, which is currently being studied across multiple mast cell driven diseases including - Chronic Urticarias: We initiated Phase 3 studies in chronic spontaneous urticaria (CSU) in July 2024.
We are focusing our efforts and resources on the continued research and development of ● Barzolvolimab (also referred to as CDX-0159), a monoclonal antibody that specifically binds the KIT receptor and potently inhibits its activity, which is currently being studied across multiple mast cell driven diseases including - Chronic Spontaneous Urticaria (CSU): In February 2026, we announced that enrollment is complete in our Phase 3 studies in CSU and that topline data will be available in the fourth quarter of 2026.
Secondary endpoints include the evaluation of the clinical efficacy of barzolvolimab, compared to placebo across multiple patient-reported outcomes, including assessing impressions of disease change and severity and improvements in quality of life. When all clinical trial sites are open, the study will include up to 50 clinical trial centers in the United States. Enrollment is ongoing.
Secondary endpoints include the evaluation of the clinical efficacy of barzolvolimab, compared to placebo across multiple patient-reported outcomes, including assessing impressions of disease change and severity and improvements in quality of life. When all clinical trial sites are open, the study includes approximately 40 clinical trial centers in the United States. Enrollment was completed in January 2026.
Barzolvolimab demonstrated significant improvements in AAS7 in patients with angioedema across all doses at week 12. This improvement was rapid (within 2 weeks) and durable (continued through 12 weeks). Barzolvolimab demonstrated strong improvement in AAS7 independent of omalizumab status at Week 12.
This improvement was rapid (within 2 weeks) and durable (continued through 12 weeks). Barzolvolimab demonstrated strong improvement in AAS7 independent of omalizumab status at Week 12.
In many countries, the health care professionals we may interact with may meet the FCPA’s definition of a foreign government official. 21 Table of Contents Foreign Regulation In order to market any therapeutic or diagnostic product outside of the United States, we need to comply with numerous and varying regulatory requirements of other countries regarding safety and efficacy and governing, among other things, clinical trials, marketing authorization, commercial sales and distribution of our products.
Foreign Regulation In order to market any therapeutic or diagnostic product outside of the United States, we need to comply with numerous and varying regulatory requirements of other countries regarding safety and efficacy and governing, among other things, clinical trials, marketing authorization, commercial sales and distribution of our products.
Federal and State Fraud and Abuse, Data Privacy and Security and Transparency Laws In addition to FDA restrictions on marketing and promotion of pharmaceutical products, several other types of federal and state laws have been applied to restrict certain marketing business practices in the biopharmaceutical and medical device industries in recent years.
As a result, the ultimate effect, implementation, and meaning of the BPCIA is subject to uncertainty. 23 Table of Contents Federal and State Fraud and Abuse, Data Privacy and Security and Transparency Laws In addition to FDA restrictions on marketing and promotion of pharmaceutical products, several other types of federal and state laws have been applied to restrict certain marketing business practices in the biopharmaceutical and medical device industries in recent years.
In the past, we have entered into collaborative partnership agreements with pharmaceutical and other companies and organizations that provided financial and other resources, including capabilities in research, development, manufacturing, and sales and marketing, to support our research and development programs and may enter into more of them in the future. 11 Table of Contents Partnership agreements may terminate without benefit to us if the underlying products are not fully developed.
In the past, we have entered into collaborative partnership agreements with pharmaceutical and other companies and organizations that provided financial and other resources, including capabilities in research, development, manufacturing, and sales and marketing, to support our research and development programs and may enter into more of them in the future.
We face competition from companies, major universities and research institutions in the United States and abroad, including a number of large pharmaceutical companies, as well as firms specialized in the development and production of targeted therapies and immune modulators. Some of our competitors possess substantially greater financial, technical and human resources than we do.
We face competition from companies, major universities and research institutions in the United States and abroad, including a number of large pharmaceutical companies, as well as firms specialized in the development and production of targeted therapies and immune modulators.
Barzolvolimab was well tolerated with a favorable safety profile. Most adverse events were mild to moderate in severity; through 12 weeks, the most common treatment emergent adverse events in barzolvolimab treated patients were urticaria/CSU (10%), hair color changes (9%), and neutropenia/ANC decrease (8%).
Most adverse events were mild to moderate in severity; through 12 weeks, the most common treatment emergent adverse events in barzolvolimab treated patients were urticaria/CSU (10%), hair color changes (9%), and neutropenia/ANC decrease (8%). The rate of infections was similar between barzolvolimab treated patients and placebo with no association between neutropenia and infections.
Commercial Organization We have limited commercial experience in marketing, sales, distribution and product reimbursement. We have the capability to provide current and future market insights to our research and development organization regarding our potential drug candidates.
We are currently preparing for the DP PPQ activities and expect to complete these activities in 2026. Commercial Organization We have limited commercial resourcing and experience in marketing, sales, distribution and product reimbursement. We have the capability to provide current and future market insights to our research and development organization regarding our potential drug candidates.
Moreover, any partner could breach its agreement with us or otherwise not use best efforts to promote our products. A partner may choose to pursue alternative technologies or products that compete with our technologies or drug candidates. In either case, if a partner failed to successfully develop one of our drug candidates, we would need to find another partner.
A partner may choose to pursue alternative technologies or products that compete with our technologies or drug candidates. In either case, if a partner failed to successfully develop one of our drug candidates, we would need to find another partner.
Many drug candidates that initially appear promising ultimately do not reach the market because they are found to be unsafe or ineffective when tested. Our inability to commercialize a product would impair our ability to earn future revenues.
Many drug candidates that initially appear promising ultimately do not reach the market because they are found to be unsafe or ineffective when tested.
CSU presents as itchy hives, angioedema or both for at least six weeks without a specific trigger; multiple episodes can play out over years or even decades.
Chronic Spontaneous Urticaria (CSU) Summary of Phase 1 and Phase 2 Data Presented to Date CSU presents as itchy hives, angioedema or both for at least six weeks without a specific trigger; multiple episodes can play out over years or even decades.
Data from this study were reported across multiple medical meetings, including the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in February 2023, the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress in June 2023 and the European Academy of Dermatology & Venereology (EADV) Congress in October 2023.
Data from this study were reported across multiple medical meetings, including the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in February 2023, the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress in June 2023 and the European Academy of Dermatology & Venereology (EADV) Congress in October 2023. 3 Table of Contents We have completed a Phase 2 study in patients with CSU who remained symptomatic despite antihistamine therapy.
After approval, many types of changes to the approved product, such as changes in indications, manufacturing changes and labeling, are subject to further testing requirements and FDA review and approval. 18 Table of Contents Special Regulatory Procedures Fast track designation — The FDA is required to facilitate the development and expedite the review of drugs and biologics that are intended for the treatment of a serious or life-threatening disease or condition and that demonstrate the potential to address unmet medical needs.
Special Regulatory Procedures Fast track designation — The FDA is required to facilitate the development and expedite the review of drugs and biologics that are intended for the treatment of a serious or life-threatening disease or condition and that demonstrate the potential to address unmet medical needs.
The data demonstrated a sustained and deepening disease efficacy and a well tolerated safety profile over a 52 week treatment period.
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.
Additional Barzolvolimab Development Activities In 2023, we completed the transfer of our current barzolvolimab manufacturing process to a Contract Development & Manufacturing Organizations (“CDMO”) and successfully scaled up the drug substance manufacturing process to produce larger cGMP batches in support of late-stage trials and to prepare for potential commercialization.
Additional Barzolvolimab Development Activities The barzolvolimab manufacturing process has been successfully transferred and scaled up to produce larger cGMP batches at both Drug Substance (DS) and Drug Product (DP) commercial Contract Development and Manufacturing Organizations in support of late-stage trials and to prepare for potential commercialization.
CDX-622 was well tolerated in a multi-dose 8 week toxicology study in non-human primates. The No Adverse Event Level (NOAEL) was established to be 75 mg/kg, the highest dose level tested. In November 2024, we initiated a Phase 1 study of CDX-622 in healthy volunteers.
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.
At 3 mg/kg in the ColdU and SD cohorts, safety results were reported for 21 patients and activity results were reported for the 20 patients who received a full dose of barzolvolimab.
Generally patients on study had high disease activity at baseline that was poorly controlled and marked impairment in quality of life. At 3 mg/kg in the ColdU and SD cohorts, safety results were reported for 21 patients and activity results were reported for the 20 patients who received a full dose of barzolvolimab.
Barzolvolimab demonstrated strong improvement in UAS7 independent of omalizumab status at week 12. Approximately 20% (n=41) of enrolled patients received prior treatment with omalizumab and more than half of these patients had omalizumab-refractory disease. These patients experienced a similar clinical benefit as the overall treated population within their individual dosing groups consistent with the barzolvolimab mechanism of action.
Barzolvolimab demonstrated strong improvement in UAS7 independent of omalizumab status at Week 12. Approximately 20% (n=41) of enrolled patients received prior treatment with omalizumab and more than half of these patients had omalizumab-refractory disease.
Neutrophil counts did not decline further with continued dosing and there was no association between infections and neutropenia. The hypopigmentation was observed with longer term exposure and did not lead to treatment discontinuation. Adverse events were not dose dependent. We believe these results strongly support the further development of barzolvolimab in CSU.
Neutrophil counts did not decline further with continued dosing and there was no association between infections and neutropenia. The hypopigmentation was observed with longer term exposure and did not lead to treatment discontinuation.
FDA Approval Process In the United States, the FDA regulates drugs and biological products under the Federal Food, Drug, and Cosmetic Act, or FDCA, the Public Health Service Act, or PHSA, and implementing regulations.
Our inability to commercialize a product would impair our ability to earn future revenues. 18 Table of Contents FDA Approval Process In the United States, the FDA regulates drugs and biological products under the Federal Food, Drug, and Cosmetic Act, or FDCA, the Public Health Service Act, or PHSA, and implementing regulations.
The rate of infections was similar between barzolvolimab treated patients and placebo with no association between neutropenia and infections. In June 2024, data on a secondary endpoint from the study, angioedema activity, and additional measures of angioedema control, were presented at the EAACI 2024 Congress. Approximately 72% of patients on study had angioedema at baseline.
In June 2024, 12 week data on a secondary endpoint from the study, angioedema activity, and additional measures of angioedema control, were presented at the EAACI 2024 Congress. Approximately 72% of patients on study had angioedema at baseline. Barzolvolimab demonstrated significant improvements in AAS7 in patients with angioedema across all doses at Week 12.
Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation. As a result, the ultimate effect, implementation, and meaning of the BPCIA is subject to uncertainty.
Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation.
We believe our program assets provide us with the strategic options to either retain full economic rights to our innovative therapies or seek favorable economic terms through advantageous commercial partnerships.
We believe our program assets provide us with the strategic options to either retain full economic rights to our innovative therapies or seek favorable economic terms through advantageous commercial partnerships. This approach allows us to maximize the overall value of our technology and product portfolio while best ensuring the expeditious development of each individual product.
There are currently no approved therapies for chronic inducible urticarias other than antihistamines and patients attempt to manage symptoms associated with their disease through avoidance of triggers. We are currently exploring cold-induced and dermographism (scratch-induced) urticarias in an ongoing Phase 2 study.
There are currently no approved therapies for chronic inducible urticarias other than antihistamines and patients attempt to manage symptoms associated with their disease through avoidance of triggers. We completed a Phase 1b open label clinical trial in patients with CIndU refractory to antihistamines, conducted in Germany.
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.
We recently completed a Phase 2 study in patients with CIndU who remain symptomatic despite antihistamine therapy. The study was conducted at approximately 85 sites across approximately 12 countries.
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 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.
Combined neutralization of SCF and TSLP with CDX-622 is expected to simultaneously reduce tissue mast cells and inhibit Type 2 inflammatory responses to potentially offer enhanced therapeutic benefit in inflammatory and fibrotic disorders. In preclinical studies, CDX-622 inhibits TSLP and SCF with similar potency to both its respective parental mAbs and comparator mAbs in vitro .
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. CDX-622 has been engineered to disable effector function (AQQ) and reduce clearance (YTE).
Any manufacturing failures or compliance issues at our CDMOs could cause delays in our clinical studies or commercialization of our drug candidates. 13 Table of Contents We currently operate our own cGMP manufacturing facility in Fall River, Massachusetts, to produce drug substance for our current and planned early-stage clinical trials.
We currently operate our own cGMP manufacturing facility in Fall River, Massachusetts, to produce drug substance for our current and planned early-stage clinical trials.
If we fail to meet our obligations under these agreements, they could terminate, and we might need to enter into relationships with other collaborators and to spend additional time, money and other valuable resources in the process. We cannot predict whether our collaborators will continue their development efforts or, if they do, whether their efforts will achieve success.
Partnership agreements may terminate without benefit to us if the underlying products are not fully developed. If we fail to meet our obligations under these agreements, they could terminate, and we might need to enter into relationships with other collaborators and to spend additional time, money and other valuable resources in the process.
Drugs and biologics may be promoted only for the approved indications and in accordance with the provisions of the approved label.
The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs and biologics may be promoted only for the approved indications and in accordance with the provisions of the approved label.
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.
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. The primary endpoint analysis will be performed when all patients have completed the placebo controlled portion of the study at 24 weeks.
Patients on barzolvolimab experienced a > 8 point improvement in AAS7 (considered a clinically meaningful result) across all doses compared to placebo (p 4 Table of Contents 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.
Patients on barzolvolimab experienced a > 8 point improvement in AAS7 (considered a clinically meaningful result) across all doses compared to placebo (p Patients on study continued to receive barzolvolimab for up to 52 weeks.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changePhysicians may elect not to prescribe our drugs, and patients may elect not to request or take them, for a variety of reasons, including: ● limitations or warnings contained in a drug’s FDA-approved labeling; ● changes in the standard of care or the availability of alternative drugs for the targeted indications for any of our drug candidates; ● limitations in the approved indications for our drug candidates; ● the approval, availability, market acceptance and reimbursement for the companion diagnostic, where applicable; ● demonstrated clinical safety and efficacy compared to other drugs; ● significant adverse side effects; ● effectiveness of education, sales, marketing and distribution support; ● timing of market introduction and perceived effectiveness of competitive drugs; ● price and cost-effectiveness; ● adverse publicity about our drug candidates or favorable publicity about competitive drugs; ● convenience and ease of administration of our drug candidates; and ● willingness of third-party payors to reimburse for the cost of our drug candidates.
Biggest changePhysicians may elect not to prescribe our drugs, and patients may elect not to request or take them, for a variety of reasons, including: ● limitations or warnings contained in a drug’s FDA-approved labeling; ● changes in the standard of care or the availability of alternative drugs for the targeted indications for any of our drug candidates; ● limitations in the approved indications for our drug candidates; ● the approval, availability, market acceptance and reimbursement for the companion diagnostic, where applicable; ● demonstrated clinical safety and efficacy compared to other drugs; ● the prevalence and severity of adverse side effects; ● effectiveness of education, sales, marketing and distribution support; ● the ability of the third-party manufacturers we contract with to provide an adequate (in amount and quality) supply of product to support the market demand; ● timing of market introduction and perceived effectiveness of competitive drugs; ● price, cost-effectiveness and the extent to which any government action results in downward pressure on the price that we would receive for our drug candidates; ● acceptance of our drug candidates as safe, effective and well-tolerated by patients and the medical community; 36 Table of Contents ● adverse publicity about our drug candidates or favorable publicity about competitive drugs; ● convenience and ease of administration of our drug candidates; ● our potential involvement in lawsuits in connection with enforcing intellectual property rights in and to our drug candidates; and ● willingness of third-party payors to reimburse for the cost of our drug candidates.
Relying on foreign manufacturers involves peculiar and increased risks, including the risk relating to the difficulty foreign manufacturers may face in complying with cGMP requirements as a result of language barriers, lack of familiarity with cGMP or the FDA regulatory process, supply chain issues or other causes, economic or political instability in or affecting the home countries of our foreign manufacturers, shipping delays, potential changes in foreign regulatory laws governing the sales of our product supplies, fluctuations in foreign currency exchange rates and the imposition or application of trade restrictions.
Relying on foreign manufacturers involves peculiar and increased risks, including the risk relating to the difficulty foreign manufacturers may face in complying with cGMP requirements as a result of language barriers, lack of familiarity with cGMP or the FDA regulatory process, supply chain issues or other causes, economic or political instability in or affecting the home countries of our foreign manufacturers, shipping delays, potential changes in foreign regulatory laws governing the sales of our product supplies, fluctuations in foreign currency exchange rates and the imposition or application of trade restrictions, including tariffs.
Such third-party collaborators: ● may not perform their obligations as expected or as required under our collaboration agreement; ● may encounter production difficulties that could constrain the supply of the companion diagnostic test; ● may have difficulties gaining acceptance of the use of the companion diagnostic test in the clinical community; ● may not pursue commercialization of the companion diagnostic test even if they receive any required regulatory approvals; 38 Table of Contents ● may elect not to continue the development or commercialization of the companion diagnostic test based on changes in the third parties’ strategic focus or available funding, or external factors such as an acquisition, that divert resources or create competing priorities; ● may be susceptible to third party cyber-attacks on our and their information security systems; ● may not commit sufficient resources to the marketing and distribution of the companion diagnostic test; and ● may terminate their relationship with us.
Such third-party collaborators: ● may not perform their obligations as expected or as required under our collaboration agreement; ● may encounter production difficulties that could constrain the supply of the companion diagnostic test; ● may have difficulties gaining acceptance of the use of the companion diagnostic test in the clinical community; ● may not pursue commercialization of the companion diagnostic test even if they receive any required regulatory approvals; 42 Table of Contents ● may elect not to continue the development or commercialization of the companion diagnostic test based on changes in the third parties’ strategic focus or available funding, or external factors such as an acquisition, that divert resources or create competing priorities; ● may be susceptible to third party cyber-attacks on our and their information security systems; ● may not commit sufficient resources to the marketing and distribution of the companion diagnostic test; and ● may terminate their relationship with us.
For example, these transactions may entail numerous operational and financial risks, including: ● exposure to unknown liabilities; ● disruption of our business and diversion of our management’s time and attention in order to develop acquired products, drug candidates or technologies; ● incurrence of substantial debt or dilutive issuances of equity securities to pay for acquisitions; ● higher than expected acquisition and integration costs; 39 Table of Contents ● write-downs of assets or impairment charges; ● increased amortization expenses; ● difficulty and cost in combining the operations and personnel of any acquired businesses with our operations and personnel; ● impairment of relationships with key suppliers or customers of any acquired businesses due to changes in management and ownership; and ● inability to retain key employees of any acquired businesses.
For example, these transactions may entail numerous operational and financial risks, including: ● exposure to unknown liabilities; ● disruption of our business and diversion of our management’s time and attention in order to develop acquired products, drug candidates or technologies; ● incurrence of substantial debt or dilutive issuances of equity securities to pay for acquisitions; ● higher than expected acquisition and integration costs; 43 Table of Contents ● write-downs of assets or impairment charges; ● increased amortization expenses; ● difficulty and cost in combining the operations and personnel of any acquired businesses with our operations and personnel; ● impairment of relationships with key suppliers or customers of any acquired businesses due to changes in management and ownership; and ● inability to retain key employees of any acquired businesses.
If we, our drug candidates or the manufacturing facilities for our drug candidates fail to comply with regulatory requirements of the FDA and/or other non-U.S. regulatory authorities, we could be subject to administrative or judicially imposed sanctions, including the following: ● warning letters; 46 Table of Contents ● civil or criminal penalties and fines; ● injunctions; ● consent decrees; ● suspension or withdrawal of regulatory approval; ● suspension of any ongoing clinical studies; ● voluntary or mandatory product recalls and publicity requirements; ● refusal to accept or approve applications for marketing approval of new drugs; ● restrictions on operations, including costly new manufacturing requirements; or ● seizure or detention of drugs or import bans.
If we, our drug candidates or the manufacturing facilities for our drug candidates fail to comply with regulatory requirements of the FDA and/or other non-U.S. regulatory authorities, we could be subject to administrative or judicially imposed sanctions, including the following: ● warning letters; 50 Table of Contents ● civil or criminal penalties and fines; ● injunctions; ● consent decrees; ● suspension or withdrawal of regulatory approval; ● suspension of any ongoing clinical studies; ● voluntary or mandatory product recalls and publicity requirements; ● refusal to accept or approve applications for marketing approval of new drugs; ● restrictions on operations, including costly new manufacturing requirements; or ● seizure or detention of drugs or import bans.
Further, the risk of cyber-attacks or other privacy or data security incidents may be heightened due to common, external attempts to attack our information technology systems and data using means such as phishing, other social engineering and vulnerability exploitation.
Further, the risk of cyber-attacks or other privacy or data security incidents may be heightened due to common, external attempts to attack our information technology systems and data using means such as phishing, deepfakes, other social engineering and vulnerability exploitation.
The laws that may affect our ability to operate include: ● the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, to induce, or in return for, the purchase or recommendation of an item or service reimbursable under a federal health care program, such as the Medicare and Medicaid programs; ● federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid or other third-party payors that are false or fraudulent; ● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and its implementing regulations, which impose certain requirements relating to the privacy, security and transmission of individually identifiable health information; ● the federal transparency requirements under the Patient Protection and Affordable Care Act of 2010 (“ACA”) requires manufacturers of drugs, devices, biologics and medical supplies to report to the Department of Health and Human Services information related to physician payments and other transfers of value and physician ownership and investment interests; ● state law and foreign law equivalents of each of the above federal laws, such as anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers, and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; and 47 Table of Contents ● state and federal laws, such as the Physician Sunshine Act, directed at generating transparency on financial issues, including drug prices and payments made by drug companies to various entities and individuals involved in healthcare.
The laws that may affect our ability to operate include: ● the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, to induce, or in return for, the purchase or recommendation of an item or service reimbursable under a federal health care program, such as the Medicare and Medicaid programs; ● federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid or other third-party payors that are false or fraudulent; ● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and its implementing regulations, which impose certain requirements relating to the privacy, security and availability of individually identifiable electronic health information; ● the federal transparency requirements under the Patient Protection and Affordable Care Act of 2010 (“ACA”) requires manufacturers of drugs, devices, biologics and medical supplies to report to the Department of Health and Human Services information related to physician payments and other transfers of value and physician ownership and investment interests; ● state law and foreign law equivalents of each of the above federal laws, such as anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers, and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; and 51 Table of Contents ● state and federal laws, such as the Physician Sunshine Act, directed at generating transparency on financial issues, including drug prices and payments made by drug companies to various entities and individuals involved in healthcare.
The risks of a security breach or disruption, particularly through cyber-attacks or cyber intrusion, including by traditional computer “hackers,” threat actors, personnel (such as through theft, inadvertent mistake or misuse), sophisticated nation-state and 40 Table of Contents nation-state-supported actors, sovereign governments and cyber terrorists, have generally increased over time, including for geopolitical reasons and in conjunction with military conflicts and defense activities, along with the number, intensity and sophistication of attempted attacks and intrusions from around the world.
The risks of a security breach or disruption, particularly through cyber-attacks or cyber intrusion, including by traditional computer “hackers,” threat actors, personnel (such as through theft, inadvertent 44 Table of Contents mistake or misuse), sophisticated nation-state and nation-state-supported actors, sovereign governments and cyber terrorists, have generally increased over time, including for geopolitical reasons and in conjunction with military conflicts and defense activities, along with the number, intensity and sophistication of attempted attacks and intrusions from around the world.
These claims can arise at any point in the development, testing, manufacture, marketing or sale of our drug candidates and may be made directly by patients involved in clinical trials of our products, by consumers or health care providers or by individuals, organizations or companies selling our products. 41 Table of Contents Product liability claims can be expensive to defend, even if the drug or drug candidate did not actually cause the alleged injury or harm.
These claims can arise at any point in the development, testing, manufacture, marketing or sale of our drug candidates and may be made directly by patients involved in clinical trials of our products, by consumers or health care providers or by individuals, organizations or companies selling our products. 45 Table of Contents Product liability claims can be expensive to defend, even if the drug or drug candidate did not actually cause the alleged injury or harm.
In connection with the agreement pursuant to which we acquired Kolltan in 2016 (the “Merger Agreement”) as modified by the definitive settlement agreement (the “Settlement Agreement”) we entered on July 15, 2022 related to litigation arising from the Kolltan merger, in the event that regulatory approval by the United States Food and Drug Administration or European Medicines Agency of certain drug candidates are achieved, we will be required to pay to the former stockholders of Kolltan a milestone payment of $52,500,000, which milestone payment may be made, at our sole election, in cash, in shares of our common stock or a combination of both, subject to provisions of the Merger Agreement.
In connection with the agreement pursuant to which we acquired Kolltan in 2016 (the “Merger Agreement”) as modified by the definitive settlement agreement (the “Settlement Agreement”) we entered on July 15, 2022 related to litigation arising from the 29 Table of Contents Kolltan merger, in the event that regulatory approval by the United States Food and Drug Administration or European Medicines Agency of certain drug candidates are achieved, we will be required to pay to the former stockholders of Kolltan a milestone payment of $52,500,000, which milestone payment may be made, at our sole election, in cash, in shares of our common stock or a combination of both, subject to provisions of the Merger Agreement.
The FDA may withdraw fast track designation if it believes that the designation is no longer supported by data from our clinical development program. 44 Table of Contents Any breakthrough therapy designation granted by the FDA for our product candidates may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.
The FDA may withdraw fast track designation if it believes that the designation is no longer supported by data from our clinical development program. 48 Table of Contents Any breakthrough therapy designation granted by the FDA for our product candidates may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.
To the extent we enter into such strategic partnerships, co- promotion or other licensing arrangements, our product revenues are likely to be lower than if we directly marketed and sold such drugs, and some or all of the revenues we receive will depend upon the efforts of third parties, which may not be successful and may not be within our control.
To the extent we enter into such strategic partnerships, co- promotion or other licensing arrangements, our product revenues may be lower than if we directly marketed and sold such drugs, and some or all of the revenues we receive will depend upon the efforts of third parties, which may not be successful and may not be within our control.
Risks Related to Our Capital Stock ● Risks related to our history of losses and uncertainty of future profitability. ● Risks relates to the volatility of our common stock. ● Risks related to our use of our net operating loss carryforwards.
Risks Related to Our Capital Stock ● Risks related to our history of losses and uncertainty of future profitability. ● Risks related to the volatility of our common stock. ● Risks related to our use of our net operating loss carryforwards.
In addition, such clinical trials would be subject to the applicable local laws of the foreign jurisdictions where the clinical trials are conducted. A description of any studies related to overdosage is also required, including information on 45 Table of Contents dialysis, antidotes, or other treatments, if known.
In addition, such clinical trials would be subject to the applicable local laws of the foreign jurisdictions where the clinical trials are conducted. A description of any studies related to overdosage is also required, including information on 49 Table of Contents dialysis, antidotes, or other treatments, if known.
If we cannot enroll patients as needed, our costs may increase, or we may be forced to delay or terminate testing for a product. 29 Table of Contents We may have delays in commencing, enrolling and completing our clinical trials, and we may not complete them at all.
If we cannot enroll patients as needed, our costs may increase, or we may be forced to delay or terminate testing for a product. 32 Table of Contents We may have delays in commencing, enrolling and completing our clinical trials, and we may not complete them at all.
However, there can be no assurance that we will not encounter difficulties in scaling up the manufacturing processes. Significant scale-up of 37 Table of Contents manufacturing may result in unanticipated technical challenges and may require additional validation studies that the FDA must review and approve.
However, there can be no assurance that we will not encounter difficulties in scaling up the manufacturing processes. Significant scale-up of 41 Table of Contents manufacturing may result in unanticipated technical challenges and may require additional validation studies that the FDA must review and approve.
Risks Related to Commercialization of Our Drug Candidates ● Risks related to delays, difficulties or unanticipated costs in establishing sales, marketing and distribution capabilities. ● Risks related to the acceptance of our drug candidates by physicians, patients and third-party payors. ● Risks related to reimbursement decisions by third-party payors. ● Risks, including the terms of FDA approval, that could affect the demand for and sales and profitability of any of our drug candidates. 24 Table of Contents ● Risks related to the failure to obtain regulatory approvals in foreign jurisdictions and risks related to international operations if we do obtain regulatory approval in foreign jurisdictions.
Risks Related to Commercialization of Our Drug Candidates ● Risks related to delays, difficulties or unanticipated costs in establishing sales, marketing and distribution capabilities. ● Risks related to the acceptance of our drug candidates by physicians, patients and third-party payors. ● Risks related to reimbursement decisions by third-party payors. ● Risks, including the terms of FDA approval, that could affect the demand for and sales and profitability of any of our drug candidates. ● Risks related to the failure to obtain regulatory approvals in foreign jurisdictions and risks related to international operations if we do obtain regulatory approval in foreign jurisdictions.
Our computer systems and those of our CROs, CDMOs, and other contractors and consultants are vulnerable to damage from cyberattacks, malicious intrusion, computer viruses, unauthorized access, data breaches, phishing attacks, cybercriminals, natural disasters, terrorism, war and telecommunication, electrical failures or other significant disruption even with a cybersecurity risk mitigation program developed by our enterprise.
Our computer systems and those of our CROs, CDMOs, and other contractors and consultants are vulnerable to damage from cyberattacks, malicious intrusion, computer viruses, unauthorized access, data breaches, phishing attacks, cybercriminals, natural disasters, terrorism, war and telecommunication, electrical failures or other significant disruption even with a cybersecurity risk mitigation program developed by our enterprise, including management of our vendors.
If any event occurred that prevented us from using all or a significant portion of our manufacturing and lab facilities, damaged critical infrastructure, such as third-party manufacturing facilities, or otherwise disrupted operations and travel, it may be difficult or, in certain cases, impossible for us to continue our business for a substantial period of time.
If any event occurred that prevented us from using all or a significant portion 54 Table of Contents of our manufacturing and lab facilities, damaged critical infrastructure, such as third-party manufacturing facilities, or otherwise disrupted operations and travel, it may be difficult or, in certain cases, impossible for us to continue our business for a substantial period of time.
In addition, when used in combination with other marketed therapies, our drug candidates may exacerbate adverse events associated with the marketed therapy. 30 Table of Contents Our drug candidates, including barzolvolimab, are monoclonal antibodies, which are biologics.
In addition, when used in combination with other marketed therapies, our drug candidates may exacerbate adverse events associated with the marketed therapy. 33 Table of Contents Our drug candidates, including barzolvolimab, are monoclonal antibodies, which are biologics.
The approval of a companion diagnostic as part of the product label will limit the use of the drug candidate to only 31 Table of Contents those patients who express the specific biomarker it was developed to detect.
The approval of a companion diagnostic as part of the product label will limit the use of the drug candidate to only 34 Table of Contents those patients who express the specific biomarker it was developed to detect.
The regulatory requirements and policies may change and additional government regulations may be enacted with which we may also be required to comply. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or in other countries.
The regulatory requirements and policies may change, and additional government regulations may be enacted with which we may also be required to comply. We cannot predict the likelihood, nature or extent of government regulation that may arise from future 37 Table of Contents legislation or administrative action, either in the United States or in other countries.
Inferior internal controls could also cause investors to lose confidence in our reported financial information, which could have a negative effect on the trading price of our common stock. 50 Table of Contents We have many competitors in our field, and they may develop technologies that make ours obsolete.
Inferior internal controls could also cause investors to lose confidence in our reported financial information, which could have a negative effect on the trading price of our common stock. We have many competitors in our field, and they may develop technologies that make ours obsolete.
We have not submitted a marketing application such as BLA or NDA to the FDA or any similar application to any other regulatory authority in any jurisdiction. The FDA has substantial discretion in the drug approval process, including the ability to delay, limit or deny approval of a product candidate for many reasons.
We have not submitted a marketing application such as BLA or NDA to the FDA or any similar application to any other regulatory authority in any jurisdiction. 30 Table of Contents The FDA has substantial discretion in the drug approval process, including the ability to delay, limit or deny approval of a product candidate for many reasons.
HIPAA imposes specified requirements relating to the privacy, security and transmission of individually identifiable health information, and mandates, among other things, the adoption of uniform standards for the electronic exchange of information in common health care transactions, as well as standards relating to the privacy and security of individually identifiable health information, which require the adoption of administrative, physical and technical safeguards to protect such information.
HIPAA imposes specified requirements relating to the privacy, security and availability of individually identifiable electronic health information, and mandates, among other things, the adoption of uniform standards for the electronic exchange of information in common health care transactions, as well as standards relating to the privacy and security of personal health information, which require the adoption of administrative, physical and technical safeguards to protect such information.
These entities regulate, among other things, the manufacture, testing, safety, effectiveness, labeling, documentation, advertising and sale of drugs and drug candidates. We or our partners must obtain regulatory approval for a drug candidate in all of these areas before we can 27 Table of Contents commercialize any of our drug candidates.
These entities regulate, among other things, the manufacture, testing, safety, effectiveness, labeling, documentation, advertising and sale of drugs and drug candidates. We or our partners must obtain regulatory approval for a drug candidate in all of these areas before we can commercialize any of our drug candidates.
We may not succeed in developing such sales and distribution capabilities, the cost of establishing such sales and distribution capabilities may exceed any product revenue, or our direct marketing and sales efforts may be unsuccessful. We may find it necessary to enter into strategic partnerships, co-promotion or other licensing arrangements.
We may not succeed in developing these new capabilities, the cost of establishing such capabilities may exceed any product revenue, or our direct marketing and sales efforts may be unsuccessful. We may find it necessary to enter into strategic partnerships, co-promotion or other licensing arrangements.
The new framework may increase both the frequency of such challenges and their odds of success by eliminating one way in which the government previously prevailed in such cases. As a result, significant regulatory policies could be subject to increased litigation and judicial scrutiny.
The new framework may increase both the frequency of such challenges and their odds of success by eliminating one way in which the government previously prevailed in such cases. As a result, significant regulatory policies could be 40 Table of Contents subject to increased litigation and judicial scrutiny.
If our drug candidates are approved for commercialization outside of the United States, we expect that we will be subject to additional risks related to international operations and entering into international business relationships, including: ● different regulatory requirements for drug approvals; ● reduced protection for intellectual property rights, including trade secret and patent rights; ● unexpected changes in tariffs, trade barriers and regulatory requirements; ● economic weakness, including inflation, uncertain interest rate environments or political instability in particular foreign economies and markets; ● compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; ● foreign taxes, including withholding of payroll taxes; ● foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations incident to doing business in another country; ● workforce uncertainty in countries where employment regulations are different than, and labor unrest is more common than, in the United States; ● production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; ● business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters, including earthquakes, hurricanes, floods and fires; and ● difficulty in importing and exporting clinical trial materials and study samples. 36 Table of Contents The biopharmaceutical industry is subject to extensive regulatory obligations and policies that may be subject to change, including due to judicial challenges.
If our drug candidates are approved for commercialization outside of the United States, we expect that we will be subject to additional risks related to international operations and entering into international business relationships, including: ● different regulatory requirements for drug approvals; ● reduced protection for intellectual property rights, including trade secret and patent rights; ● unexpected changes in tariffs, trade barriers and regulatory requirements; ● economic weakness, including inflation, uncertain interest rate environments or political instability in particular foreign economies and markets; ● compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; ● foreign taxes, including withholding of payroll taxes; ● foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations incident to doing business in another country; ● workforce uncertainty in countries where employment regulations are different than, and labor unrest is more common than, in the United States; ● production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; ● business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters, including earthquakes, hurricanes, floods and fires; and 39 Table of Contents ● difficulty in importing and exporting clinical trial materials and study samples.
If we are not able to maintain regulatory compliance, we may not be permitted to market our future products and our business may suffer. 34 Table of Contents Reimbursement decisions by third-party payors may have an adverse effect on pricing and market acceptance of any of our drug candidates.
If we are not able to maintain regulatory compliance, we may not be permitted to market our future products and our business may suffer. Reimbursement decisions by third-party payors may have an adverse effect on pricing and market acceptance of any of our drug candidates.
We are subject to various domestic and international privacy and security regulations related to personal information, including health information, that are appliable to our business and associated data processing activities.
We are subject to various domestic and international privacy and security regulations related to personal information, including health information, that are applicable to our business and associated data processing activities.
Disease outbreaks, epidemics and pandemics in regions where we have concentrations of clinical trial sites and other business operations, could adversely affect our business, including by causing significant disruptions in our operations and/or in the operations 51 Table of Contents of manufacturers and CROs upon whom we rely.
Disease outbreaks, epidemics and pandemics in regions where we have concentrations of clinical trial sites and other business operations, could adversely affect our business, including by causing significant disruptions in our operations and/or in the operations of manufacturers and CROs upon whom we rely.
We have designed, implemented and tested the internal control over financial reporting required to comply with this obligation, which was and is time consuming, costly, and complicated. A control system, no matter how well designed and operated, can provide only reasonable, not absolute, assurance that the control system’s objectives will be met.
We have designed, 53 Table of Contents implemented and tested the internal control over financial reporting required to comply with this obligation, which was and is time consuming, costly, and complicated. A control system, no matter how well designed and operated, can provide only reasonable, not absolute, assurance that the control system’s objectives will be met.
Risks Related to Business Operations ● Risks related to strategic transactions. ● Risks related to managing our growth. ● Risks related to our ability to integrate and modify our technologies to create new drugs. ● Risks related to computer systems that we and third parties use and potential security breaches. ● Risks related to hazardous materials. ● Risks related to product liability claims.
Risks Related to Business Operations ● Risks related to strategic transactions. ● Risks related to managing our growth. ● Risks related to our ability to integrate and modify our technologies to create new drugs. ● Risks related to computer systems that we and third parties use and potential security breaches or operational impairment. ● Risks related to hazardous materials. ● Risks related to product liability claims.
Even if we were able to obtain a license, it could be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. We could be forced, including by court order, to cease developing the infringing technology or product. In addition, we could be found liable for monetary damages.
Even if we were able to obtain a license, it could be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. We could be forced, including by court order, to cease developing the infringing technology or product. In addition, we could be found 47 Table of Contents liable for monetary damages.
Claims that we have misappropriated the confidential information or trade secrets of third parties can have a similar negative impact on our business. 43 Table of Contents Third parties may assert that our employees or consultants have wrongfully used or disclosed confidential information or misappropriated trade secrets.
Claims that we have misappropriated the confidential information or trade secrets of third parties can have a similar negative impact on our business. Third parties may assert that our employees or consultants have wrongfully used or disclosed confidential information or misappropriated trade secrets.
Risks Related to Our Capital Stock Our history of losses and uncertainty of future profitability make our common stock a highly speculative investment. We have had no commercial revenue to date from sales of our drug candidates. We had an accumulated deficit of $1.6 billion as of December 31, 2024.
Risks Related to Our Capital Stock Our history of losses and uncertainty of future profitability make our common stock a highly speculative investment. We have had no commercial revenue to date from sales of our drug candidates. We had an accumulated deficit of $1.8 billion as of December 31, 2025.
Risks Related to Our Financial Condition and Capital Requirements We currently have no product revenue and will need to raise capital to operate our business. To date, we have generated no product revenue and cannot predict when and if we will generate product revenue. We had an accumulated deficit of $1.6 billion as of December 31, 2024.
Risks Related to Our Financial Condition and Capital Requirements We currently have no product revenue and will need to raise capital to operate our business. To date, we have generated no product revenue and cannot predict when and if we will generate product revenue. We had an accumulated deficit of $1.8 billion as of December 31, 2025.
Failure to achieve profitability could diminish our ability to sustain operations, pay dividends on our common stock, obtain additional required funds and make required payments on our present or future indebtedness. We expect to incur future losses and we may never become profitable.
Failure to achieve profitability could diminish our ability to sustain operations, pay dividends on our common stock, obtain additional required funds and make required payments on our present or future indebtedness. 28 Table of Contents We expect to incur future losses and we may never become profitable.
In general, other factors that could affect the demand for and sales and profitability of our future drugs include, but are not limited to: ● the timing of regulatory approval, if any, of competitive drugs; ● our or any other of our partners’ pricing decisions, as applicable, including a decision to increase or decrease the price of a drug, and the pricing decisions of our competitors; ● government and third-party payor reimbursement and coverage decisions that affect the utilization of our future drugs and competing drugs; ● negative safety or efficacy data from new clinical studies conducted either in the U.S. or internationally by any party, which could cause the sales of our future drugs to decrease or a future drug to be recalled; ● the degree of patent protection afforded our future drugs by patents granted to or licensed by us and by the outcome of litigation involving our or any of our licensor’s patents; ● marketing exclusivity, if any, awarded by the FDA to our drugs; ● the outcome of litigation involving patents of other companies concerning our future drugs or processes related to production and formulation of those drugs or uses of those drugs; ● the increasing use and development of alternate therapies; ● the rate of market penetration by competing drugs; and ● the termination of, or change in, existing arrangements with our partners.
In general, other factors that could affect the demand for and sales and profitability of our future drugs include, but are not limited to: ● the timing of regulatory approval, if any, of competitive drugs; ● our or any other of our partners’ pricing decisions, as applicable, including a decision to increase or decrease the price of a drug, and the pricing decisions of our competitors; ● government and third-party payor reimbursement and coverage decisions that affect the utilization of our future drugs and competing drugs; ● negative safety or efficacy data from new clinical studies conducted either in the U.S. or internationally by any party, which could cause the sales of our future drugs to decrease or a future drug to be recalled; ● the degree of patent protection afforded our future drugs by patents granted to or licensed by us and by the outcome of litigation involving our or any of our licensor’s patents; ● marketing exclusivity, if any, awarded by the FDA to our drugs; ● the outcome of litigation involving patents of other companies concerning our future drugs or processes related to production and formulation of those drugs or uses of those drugs; ● the increasing use and development of alternate therapies; ● the rate of market penetration by competing drugs; and ● the termination of, or change in, existing arrangements with our partners. 38 Table of Contents Any of these factors could have a material adverse effect on the sales of any drug candidates that we may commercialize in the future.
During the years ended December 31, 2024, 2023 and 2022, we incurred $73.0 million, $32.4 million and $23.8 million in clinical trial expense and $16.4 million, $24.1 million and $4.5 million in contract manufacturing expense. Our net losses have had and will continue to have an adverse effect on, among other things, our stockholders’ equity, total assets and working capital.
During the years ended December 31, 2025, 2024 and 2023, we incurred $111.8 million, $73.0 million and $32.4 million in clinical trial expense and $47.1 million, $16.4 million and $24.1 million in contract manufacturing expense. Our net losses have had and will continue to have an adverse effect on, among other things, our stockholders’ equity, total assets and working capital.
However, there can be no assurance that we will be able to prove these advantages or that the advantages will be sufficient to support the successful commercialization of our drug candidates. 32 Table of Contents Risks Related to Commercialization of Our Drug Candidates We may face delays, difficulties or unanticipated costs in establishing sales, marketing and distribution capabilities or seeking a partnership for the commercialization of our drug candidates, even if regulatory approval is obtained.
However, there can be no assurance that we will be able to prove these advantages or that the advantages will be sufficient to support the successful commercialization of our drug candidates. 35 Table of Contents Risks Related to Commercialization of Our Drug Candidates We may face delays, difficulties or unanticipated costs in establishing and maintaining sales, marketing, market access, patient services and distribution capabilities or seeking a partnership for the commercialization of our drug candidates, even if regulatory approval is obtained.
Risks Related to Intellectual Property ● Risks related to intellectual property. Regulatory Risks ● Risks related to the regulatory approval process for our drugs. ● Risks related to changes in product candidate manufacturing or formulation. ● Risks related to our compliance with laws and regulations.
Risks Related to Intellectual Property ● Risks related to intellectual property. Regulatory Risks ● Risks related to the regulatory approval process for our drugs. 27 Table of Contents ● Risks related to changes in product candidate manufacturing or formulation. ● Risks related to our compliance with laws and regulations.
Our ability to use our net operating loss carryforwards will be subject to limitation and, under certain circumstances, may be eliminated. As of December 31, 2024, we had net operating loss carryforwards, or NOLs, of approximately $566.0 million for federal income tax purposes, and $888.8 million for state income tax purposes.
Our ability to use our net operating loss carryforwards will be subject to limitation and, under certain circumstances, may be eliminated. As of December 31, 2025, we had net operating loss carryforwards, or NOLs, of approximately $842.9 million for federal income tax purposes, and $1.0 billion for state income tax purposes.
If we, or a company that licenses technology to us, were not the first creator of an invention that we use, and/or if inventorship were to be decided against us (or our licensor) in any relevant litigation, our use of the underlying product or technology will face restrictions, including elimination, and our ability to defend and/or enforce any affected patent rights could also be materially harmed. 42 Table of Contents If we must defend against suits brought against us or prosecute suits against others involving intellectual property rights, we will incur substantial costs.
If we, or a company that licenses technology to us, were not the first creator of an invention that we use, and/or if inventorship were to be 46 Table of Contents decided against us (or our licensor) in any relevant litigation, our use of the underlying product or technology will face restrictions, including elimination, and our ability to defend and/or enforce any affected patent rights could also be materially harmed.
We rely on CDMOs over whom we have limited control. Should the cost, delivery and quality of clinical materials manufactured by us in our Fall River facility or supplied by CDMOs vary to our disadvantage, our business operations could suffer significant harm. We are a research and development company and have limited experience in commercial manufacturing.
We rely on CDMOs, some of whom are our single source manufacturers, over whom we have limited control. Should the cost, delivery and quality of clinical materials manufactured by us in our Fall River facility or supplied by CDMOs vary to our disadvantage, our business operations could suffer significant harm.
We may retain full economic rights to our drug candidates or seek favorable economic terms through advantageous commercial partnerships. As a result, we may have full responsibility for commercialization of one or more of our drug candidates if and when they are approved for sale. We currently lack sufficient marketing, sales and distribution capabilities to carry out this strategy.
We may retain full economic rights to our drug candidates or seek favorable economic terms through advantageous commercial partnerships. As a result, we may have full responsibility for commercialization of one or more of our drug candidates if and when they are approved for sale.
Failure to achieve profitability could diminish our ability to sustain operations, pay dividends on our common stock, obtain additional required funds and make required payments on our present or future indebtedness. Our share price has been and could remain volatile. The market price of our common stock has historically experienced and may continue to experience significant volatility.
Failure to achieve profitability could diminish our ability to sustain operations, pay dividends on our common stock, obtain additional required funds and make required payments on our present or future indebtedness. 52 Table of Contents Our share price has been and could remain volatile.
Our employees may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have a material adverse effect on our business. We are exposed to the risk of employee fraud or other misconduct.
We cannot predict our success in hiring or retaining the personnel we require for continued growth. 55 Table of Contents Our employees may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have a material adverse effect on our business. We are exposed to the risk of employee fraud or other misconduct.
In addition to any potential liability for significant monetary damages, a decision against us may require us to obtain licenses to patents or other intellectual property rights of others on potentially unfavorable terms.
If we must defend against suits brought against us or prosecute suits against others involving intellectual property rights, we will incur substantial costs. In addition to any potential liability for significant monetary damages, a decision against us may require us to obtain licenses to patents or other intellectual property rights of others on potentially unfavorable terms.
Approval by the FDA does not ensure approval by regulatory authorities in other countries, and approval by one or more foreign regulatory authorities does not ensure approval by regulatory authorities in other foreign countries or by the FDA.
Clinical studies conducted in one country may not be accepted by regulatory authorities in other countries. Approval by the FDA does not ensure approval by regulatory authorities in other countries, and approval by one or more foreign regulatory authorities does not ensure approval by regulatory authorities in other foreign countries or by the FDA.
Specifically, in the EEA, medicinal products can only be commercialized after obtaining a Marketing Authorization, or MA. Before granting the MA, the European Medicines Agency or the competent authorities of the member states of the EEA make an assessment of the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy.
Before granting the MA, the European Medicines Agency or the competent authorities of the member states of the EEA make an assessment of the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy.
Competitor Competitor Product Indication(s) Abbvie Rinvoq AD Amgen Tezpire EoE Amgen/Kiowa Kirin Rocatinlimab AD and PN Celltrion CT-P39, omalizumab biosimilar CSU Eli Lilly Olumiant and Ebglyss AD Galderma/Chugai Nemluvio PN and AD Incyte Povorcitinib PN Kashiv Biosciences ADL-018 omalizumab biosimilar CSU Leo Pharma Adbry AD Medimetriks Difamilast AD Novartis Remibrutinib CSU and CIndU Pfizer Cibinqo AD Regeneron/Sanofi Dupixent CSU, PN, EoE and AD Regeneron/Sanofi Amlitelimab AD Teva Tev-45779, omalizumab biosimilar CSU Vanda Pharmaceuticals Tradipitant AD ​ Our success depends upon our ability to develop and maintain a competitive position in the product categories and technologies on which we focus.
The following table is a summary of the competitors of which we are aware that have initiated a Phase 3 study or have obtained marketing approval for a potentially competitive drug to barzolvolimab for treatment of CSU, CIndU, PN and AD. ​ ​ Competitor ​ ​ ​ Competitor Product ​ ​ ​ Indication(s) Abbvie ​ Rinvoq ​ AD Akeso Bio ​ AKT120 ​ AD Amgen/Kiowa Kirin ​ Rocatinlimab ​ AD and PN Celltrion ​ CT-P39, omalizumab biosimilar ​ CSU Eli Lilly ​ Olumiant and Ebglyss ​ AD Galderma/Chugai ​ Nemluvio ​ PN and AD Genentech/Novartis ​ Xolair ​ CSU Incyte ​ Povorcitinib ​ PN Kashiv Biosciences ​ ADL-018 omalizumab biosimilar ​ CSU Leo Pharma ​ Adbry ​ AD Medimetriks ​ Difamilast ​ AD Novartis ​ Remibrutinib ​ CSU and CIndU Pfizer ​ Cibinqo ​ AD Regeneron/Sanofi ​ Dupixent ​ CSU, PN, and AD Sanofi ​ Amlitelimab ​ AD Teva ​ Tev-45779, omalizumab biosimilar ​ CSU Vanda Pharmaceuticals ​ Tradipitant ​ AD ​ Our success depends upon our ability to develop and maintain a competitive position in the product categories and technologies on which we focus.
General Risk Factors ● Risks related to internal controls over financial reporting. ● Risks that our competitors may develop technologies that make ours obsolete. ● Risks related to health epidemics and outbreaks. ● Risks related to the global economy and supply chain disruptions. ● Risks related to the loss of our key executives and scientists. 25 Table of Contents ● Risks that our employees may engage in misconduct or other improper activities. ● Risks related to our compliance with the Nasdaq Listing Rules.
General Risk Factors ● Risks related to internal controls over financial reporting. ● Risks that our competitors may develop technologies that make ours obsolete. ● Risks related to health epidemics and outbreaks. ● Risks related to the global economy and supply chain disruptions. ● Risks related to the loss of our key executives and scientists. ● Risks that our employees may engage in misconduct or other improper activities. ● Risks related to our compliance with the Nasdaq Listing Rules. ● Risks related to private industries’ increased use of artificial intelligence, machine learning and certain automated decision-making technologies (“AI Technologies”) in business that may expand our limited use of these technologies.
There is continued uncertainty about the implementation of ACA, including the potential for further amendments to the ACA and legal challenges to or efforts to repeal the ACA. 48 Table of Contents In addition, the Inflation Reduction Act of 2022, enacted in August 2022, empowers the Centers for Medicare and Medicaid Services to negotiate directly with pharmaceutical companies to set the prices for a limited set of high-cost drugs covered by Medicare, and puts penalties in place for drug manufacturers who increase their Medicare prices by more than the rate of inflation.
In addition, the Inflation Reduction Act of 2022, enacted in August 2022, empowers the Centers for Medicare and Medicaid Services to negotiate directly with pharmaceutical companies to set the prices for a limited set of high-cost drugs covered by Medicare, and puts penalties in place for drug manufacturers who increase their Medicare prices by more than the rate of inflation.
In general, an ownership change, as defined by Section 382, results from transactions increasing the ownership of certain shareholders or public groups in the stock of a corporation by more than 50 percentage points over a three-year period. 49 Table of Contents In October 2007, June 2009, December 2009, December 2013, November 2016 and June 2020, we experienced a change in ownership as defined by Section 382.
In general, an ownership change, as defined by Section 382, results from transactions increasing the ownership of certain shareholders or public groups in the stock of a corporation by more than 50 percentage points over a three-year period.
Moreover, our patents may not afford effective protection against competitors with similar technology. A successful challenge to any one of our patents could result in a third party’s ability to use the technology covered by the patent. We also face the risk that others will infringe, avoid or circumvent our patents.
A successful challenge to any one of our patents could result in a third party’s ability to use the technology covered by the patent. We also face the risk that others will infringe, avoid or circumvent our patents. Technology that we license from others is subject to similar risks and this could harm our ability to use that technology.
Notwithstanding these arrangements, we face significant competition for this type of personnel from other companies, research and academic institutions, government entities and other organizations. We cannot predict our success in hiring or retaining the personnel we require for continued growth.
Notwithstanding these arrangements, we face significant competition for this type of personnel from other companies, research and academic institutions, government entities and other organizations.
Risks Related to Development and Regulatory Approval of Drug Candidates ● Risks related to our ability to fund and complete the research and development activities and obtain regulatory approval for our program assets. ● Risks related to the extensive and lengthy regulatory scrutiny to which we are subject. ● Risks related to our ability to commence, enroll, manage and complete our clinical trials. ● Risk of serious adverse or unacceptable side effects identified related to our drug candidates. ● Risk related to showing that our drug candidates are effective and competitive with other therapies and approved products. ● We may enter into collaboration agreements for our lead drug candidates that may not meet our expectations.
FDA and other government agencies caused by funding shortages or global health concerns. ● Risks related to our ability to commence, enroll, manage and complete our clinical trials. ● Risk of serious adverse or unacceptable side effects identified related to our drug candidates. ● Risk related to showing that our drug candidates are effective and competitive with other therapies and approved products. ● We may enter into collaboration agreements for our lead drug candidates that may not meet our expectations.
As of December 31, 2024, we had cash, cash equivalents and marketable securities of $725.3 million. During the next twelve months and beyond, we will take further steps to raise additional capital to fund our long-term liquidity needs.
During the next twelve months and beyond, we will take further steps to raise additional capital to fund our long-term liquidity needs.
Additionally, even after receipt of FDA approval, such drug would be subject to substantial, ongoing regulatory requirements. The FDA has complete discretion over the approval of our drug candidates. If the FDA grants approval, the scope of the approval may limit our ability to commercialize such drug, and in turn, limit our ability to generate substantial product revenue.
Even if any of our drug candidates receive FDA approval, the terms of the approval may limit such drug’s commercial potential. Additionally, even after receipt of FDA approval, such drug would be subject to substantial, ongoing regulatory requirements. The FDA has complete discretion over the approval of our drug candidates.
We cannot predict whether the patents we or our licensors seek will issue. If such patents are issued, a competitor may challenge them and may potentially have them revoked or limit their scope, for example based on existing or newly identified prior art or other issues of validity.
If such patents are issued, a competitor may challenge them and may potentially have them revoked or limit their scope, for example based on existing or newly identified prior art or other issues of validity. Moreover, our patents may not afford effective protection against competitors with similar technology.
From January 2023 through December 2024, the market price of our common stock has fluctuated from a high of $53.18 per share in the first quarter of 2024, to a low of $22.11 per share in the fourth quarter of 2023.
The market price of our common stock has historically experienced and may continue to experience significant volatility. From January 2024 through December 2025, the market price of our common stock has fluctuated from a high of $53.18 per share in the first quarter of 2024, to a low of $14.40 per share in the second quarter of 2025.
We may seek approval for our drug candidates outside the United States and may market future products in international markets. In order to market our future products in the European Economic Area, or EEA, and many other foreign jurisdictions, we must obtain separate regulatory approvals.
Failure to obtain regulatory approvals in foreign jurisdictions will prevent us from marketing our products internationally. We may seek approval for our drug candidates outside the United States and may market future products in international markets.
We expect that losses will fluctuate from quarter to quarter and year to year, and that such fluctuations may be substantial. We cannot predict when we will become profitable, if at all. We will need additional capital to fund our operations, including the development, manufacture and potential commercialization of our drug candidates.
We cannot predict when we will become profitable, if at all. We will need additional capital to fund our operations, including the development, manufacture and potential commercialization of our drug candidates. If we do not have or cannot raise additional capital when needed, we may be unable to develop and ultimately commercialize our drug candidates successfully.
Reductions in NIH grants to us or our third-party collaborators may adversely impact our ability to develop our existing product candidates and our ability to identify new product candidates. In addition, on June 28, 2024, the U.S.
Although these reductions are the subject of legal challenges, they may remain in place. Reductions in NIH grants to us or our third-party collaborators may adversely impact our ability to develop our existing product candidates and our ability to identify new product candidates.
The approval procedures vary among countries and can involve additional clinical testing, and the time required to obtain approval may differ from that required to obtain FDA approval. Clinical studies conducted in one country may not be accepted by regulatory authorities in other countries.
Similar regulatory review and risk-benefit assessments may apply to other regulatory authorities and payer bodies in markets around the world. The approval procedures vary among countries and can involve additional clinical testing, and the time required to obtain approval may differ from that required to obtain FDA approval.
We have adopted a Code of Business Conduct and Ethics and launched a Health Care Compliance program, but it is not always possible to identify and deter employee misconduct.
Employee misconduct could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation. We have adopted a Code of Business Conduct and Ethics and launched a Health Care Compliance program, but it is not always possible to identify and deter employee misconduct.
If any of our drug candidates are approved by the FDA, we will need a drug sales force with technical expertise prior to the commercialization of any of our drug candidates.
We currently lack sufficient sales, marketing, market access, patient services and distribution capabilities to carry out this strategy. If any of our drug candidates are approved by the FDA, we will need a drug sales force with technical expertise and commercial-scale manufacturing capabilities prior to the commercialization of any of our drug candidates.
Historically, we have raised capital through the issuance of capital stock on several occasions which, combined with shareholders’ subsequent disposition of those shares, has resulted in changes of control, as defined by Section 382. As a result of these ownership changes, utilization of at least some of our federal NOL carryforwards is subject to an annual limitation.
In October 2007, June 2009, December 2009, December 2013, November 2016 and June 2020, we experienced a change in ownership as defined by Section 382. Historically, we have raised capital through the issuance of capital stock on several occasions which, combined with shareholders’ subsequent disposition of those shares, has resulted in changes of control, as defined by Section 382.
Biotechnology patents involve complex legal, scientific and factual questions and are highly uncertain and may also result in different outcomes in different territories. To date, there is no consistent policy regarding the breadth of claims allowed in biotechnology patents, particularly in regard to patents for technologies for human uses like those we use in our business.
To date, there is no consistent policy regarding the breadth of claims allowed in biotechnology patents, particularly in regard to patents for technologies for human uses like those we use in our business. We cannot predict whether the patents we or our licensors seek will issue.
Since its enactment, there have been judicial and Congressional challenges and amendments to certain aspects of ACA.
Since its enactment, there have been judicial and Congressional challenges and amendments to certain aspects of ACA. There is continued uncertainty about the implementation of ACA, including the potential for further amendments to the ACA and legal challenges to or efforts to repeal the ACA.
Our capital raising activities may include, but may not be limited to, one or more of the following: ● licensing of drug candidates with existing or new collaborative partners; ● possible business combinations; ● issuance of debt; or ● issuance of common stock or other securities via private placements or public offerings. 26 Table of Contents While we may seek capital through a number of means, there can be no assurance that additional financing will be available on acceptable terms, if at all, and our negotiating position in capital-raising efforts may worsen as existing resources are used.
Our capital raising activities may include, but may not be limited to, one or more of the following: ● licensing of drug candidates with existing or new collaborative partners; ● possible business combinations; ● issuance of debt; or ● issuance of common stock or other securities via private placements or public offerings.
Changes in the regulatory approval process, or substantial reductions in the personnel who oversee that process, could affect our ability to obtain regulatory approval for our product candidates or the timeline in which we can obtain that approval.
Changes in the regulatory approval process, or substantial reductions in the personnel who oversee that process, increase the difficulty and cost for us to progress our clinical programs, obtain marketing approval of and commercialize our product candidates and may affect the prices we may set.
We have incurred operating losses of $195.1 million, $154.5 million and $115.2 million during 2024, 2023 and 2022, respectively, and expect to incur an operating loss in 2025 and beyond. We believe that operating losses will continue in 2025 and beyond because we are planning to incur significant costs associated with the development of our drug candidates.
We have incurred operating losses of $287.4 million, $195.1 million and $154.5 million during 2025, 2024, and 2023, respectively, and expect to incur an operating loss in 2026 and beyond.
In such case, we may also not have the resources to conduct new clinical trials and/or we may determine that further clinical development of any such drug candidate is not justified and may discontinue any such programs. 28 Table of Contents If our drug candidates do not pass required tests for safety and effectiveness, we will not be able to obtain regulatory approval and derive commercial revenue from them.
In such case, we may also not have the resources to conduct new clinical trials and/or we may determine that further clinical development of any such drug candidate is not justified and may discontinue any such programs. Disruptions at the U.S.
We also rely on CDMOs for filling, labeling and storage for studies inside and outside the U.S. Any manufacturing failures or compliance issues at our CDMOs could cause delays in our clinical studies or commercialization of our drug candidates.
To date, we have no qualified alternative sources for these single source CDMOs. Any manufacturing failures or compliance issues at our CDMOs could cause delays in our clinical studies or commercialization of our drug candidates.
If our future drugs fail to achieve market acceptance, we will not be able to generate significant revenues and may never achieve profitability. 33 Table of Contents Even if any of our drug candidates receive FDA approval, the terms of the approval may limit such drug’s commercial potential.
If our future drugs, if any, fail to achieve market acceptance or we fail to secure and maintain adequate coverage and reimbursement for our future drugs, if any, we will not be able to generate significant revenues and may never achieve profitability.
If we do not have or cannot raise additional capital when needed, we may be unable to develop and ultimately commercialize our drug candidates successfully. We expect to incur significant costs as we develop our drug candidates. The continuing development and commercialization of our drug candidates requires additional capital beyond our current resources.
We expect to incur significant costs as we develop our drug candidates. The continuing development and commercialization of our drug candidates requires additional capital beyond our current resources. As of December 31, 2025, we had cash, cash equivalents and marketable securities of $518.6 million.
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There is also no assurance that we will be able to enter into further collaborative relationships.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeWe maintain a cybersecurity risk insurance policy. 53 Table of Contents Governance; Board Oversight Our Audit Committee is responsible for reviewing our information security programs, including cybersecurity. Our IT team provides regular updates to the Audit Committee on our IT security strategy, secure score assessments, penetration testing results, and status of risk mitigation activities, where applicable.
Biggest changeGovernance; Board Oversight Our Audit Committee is responsible for reviewing our information security programs, including cybersecurity. Our IT team provides regular updates to the Audit Committee on our IT security strategy, secure score assessments, penetration testing results, and status of risk mitigation activities, where applicable. In 2025, our IT team met with the Audit Committee 4 times.
We engage with consultants to help develop and evidence the policies, standards, and processes in a manner consistent with applicable legal requirements, and also evaluate and adopt cybersecurity software from reputable vendors in cybersecurity, some that provide software as a service solutions backed by a Security Operations Center.
We engage with consultants to help develop and evidence the policies, standards, and processes in a manner consistent with applicable legal requirements. We also evaluate and adopt cybersecurity software from reputable vendors in cybersecurity, including software as a service solutions backed by a Security Operations Center.
Our IT team also notifies the Audit Committee and Executive Committee of any cybersecurity incidents (suspected or actual) and provides updates on the incidents as well as cybersecurity risk mitigation activities, as appropriate.
Our IT team also notifies the Audit Committee and Executive Committee of any cybersecurity incidents (suspected or actual) and provides updates on the incidents as well as cybersecurity risk mitigation activities, as appropriate. ​ 57 Table of Contents
The training engages personnel on how to identify potential cybersecurity risks and protect our resources and information. This training is mandatory for all employees on a periodic basis, and it is supplemented by testing initiatives, including periodic phishing tests.
The training engages personnel on how to identify potential cybersecurity risks and protect our resources and information. This training is mandatory for all employees on a periodic basis, and it is supplemented by testing initiatives, including periodic phishing tests. We maintain a cybersecurity risk insurance policy.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changePROPERTIES As of December 31, 2024, our significant leased properties are described below. ​ ​ ​ ​ ​ ​ ​ ​ Approximate ​ ​ Property Location Square Feet Use Lease Expiration Date Hampton, New Jersey 33,400 Headquarters, Office and Laboratory July 2027 (1) Fall River, Massachusetts 36,300 Manufacturing, Office and Laboratory July 2027 (2) New Haven, Connecticut 17,700 Office and Laboratory October 2026 (1) Lease includes two renewal options of two years.
Biggest changePROPERTIES As of December 31, 2025, our significant leased properties are described below. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Approximate ​ ​ ​ ​ ​ ​ ​ ​ Property Location ​ ​ ​ Square Feet ​ ​ ​ Use ​ ​ ​ Lease Expiration Date Hampton, New Jersey 33,400 Headquarters, Office and Laboratory July 2027 (1) Fall River, Massachusetts 36,300 Manufacturing, Office and Laboratory July 2027 (2) New Haven, Connecticut 17,700 Office and Laboratory October 2026 (3) (1) Lease includes two renewal options of two years.
(2) Lease includes one renewal option of three years. Item 3. LEGAL PROCEEDINGS We are not currently a party to any material legal proceedings. ​ Item 4. MINE SAFETY DISCLOSURES Not applicable. ​ 54 Table of Contents PART II
The initial lease term is 5.5 years with three renewal options of five years each. Item 3. LEGAL PROCEEDINGS We are not currently a party to any material legal proceedings. ​ Item 4. MINE SAFETY DISCLOSURES Not applicable. ​ 58 Table of Contents PART II
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(2) Lease includes one renewal option of three years. (3) In September 2025, we signed a new lease in New Haven, Connecticut to which we will relocate our existing New Haven operations to in 2026. The lease covers approximately 40,400 square feet of office and laboratory space and is scheduled to commence in 2026.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeThe points on the graph are as of December 31 of the year indicated. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ 2019 2020 2021 2022 2023 2024 Celldex Therapeutics, Inc. ​ $ 100 ​ $ 786 ​ $ 1,733 ​ $ 1,999 ​ $ 1,778 ​ $ 1,133 NASDAQ U.S.
Biggest changeThe points on the graph are as of December 31 of the year indicated. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ 2020 ​ ​ ​ 2021 ​ ​ ​ 2022 ​ ​ ​ 2023 ​ ​ ​ 2024 ​ ​ ​ 2025 Celldex Therapeutics, Inc. ​ $ 100 ​ $ 221 ​ $ 254 ​ $ 226 ​ $ 144 ​ $ 155 NASDAQ U.S.
The comparison assumes investment of $100 on December 31, 2019 in our common stock and in each of the indices and, in each case, assumes reinvestment of all dividends.
The comparison assumes investment of $100 on December 31, 2020 in our common stock and in each of the indices and, in each case, assumes reinvestment of all dividends.
AND PEER GROUP INDICES The graph below compares the cumulative total stockholder return on the common stock for the period from December 31, 2019 through December 31, 2024, with the cumulative return on (i) NASDAQ U.S. Benchmark TR Index and (ii) NASDAQ Pharmaceutical (Subsector) Index.
AND PEER GROUP INDICES The graph below compares the cumulative total stockholder return on the common stock for the period from December 31, 2020 through December 31, 2025, with the cumulative return on (i) NASDAQ U.S. Benchmark TR Index and (ii) NASDAQ Pharmaceutical (Subsector) Index.
Item 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES Our common stock currently trades on the Nasdaq Capital Market (NASDAQ) under the symbol “CLDX.” As of February 14, 2025, there were approximately 136 shareholders of record of our common stock.
Item 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES Our common stock currently trades on the Nasdaq Capital Market (NASDAQ) under the symbol “CLDX.” As of February 13, 2026, there were approximately 120 shareholders of record of our common stock.
On February 14, 2025 the closing price of our common stock, as reported by NASDAQ, was $22.70 per share. We have not paid any dividends on our common stock since our inception and do not intend to pay any dividends in the foreseeable future. ​ CELLDEX THERAPEUTICS, INC., NASDAQ MARKET INDEX — U.S.
On February 13, 2026 the closing price of our common stock, as reported by NASDAQ, was $23.00 per share. We have not paid any dividends on our common stock since our inception and do not intend to pay any dividends in the foreseeable future. ​ CELLDEX THERAPEUTICS, INC., NASDAQ MARKET INDEX — U.S.
Benchmark TR Index ​ $ 100 ​ $ 121 ​ $ 153 ​ $ 123 ​ $ 155 ​ $ 193 NASDAQ Pharmaceutical (Subsector) Index ​ $ 100 ​ $ 111 ​ $ 137 ​ $ 153 ​ $ 159 ​ $ 173 ​ ​ Item 6. [Reserved] ​ 55 Table of Contents
Benchmark TR Index ​ $ 100 ​ $ 126 ​ $ 101 ​ $ 128 ​ $ 159 ​ $ 187 NASDAQ Pharmaceutical (Subsector) Index ​ $ 100 ​ $ 124 ​ $ 139 ​ $ 144 ​ $ 156 ​ $ 201 ​ ​ Item 6. [Reserved] 59 Table of Contents

Item 6. [Reserved]

Selected Financial Data — reserved (removed by SEC in 2021)

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Biggest changeItem 6. ​ [Reserved] ​ 55 Item 7. ​ Management’s Discussion and Analysis of Financial Condition and Results of Operations ​ 56 Item 7A. ​ Quantitative and Qualitative Disclosures About Market Risk ​ 75 Item 8. ​ Financial Statements and Supplementary Data ​ 76
Biggest changeItem 6. ​ [Reserved] ​ 59 Item 7. ​ Management’s Discussion and Analysis of Financial Condition and Results of Operations ​ 60 Item 7A. ​ Quantitative and Qualitative Disclosures About Market Risk ​ 81 Item 8. ​ Financial Statements and Supplementary Data ​ 82

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

110 edited+44 added−19 removed119 unchanged
Biggest changePatients on study continued to receive barzolvolimab for 20 weeks of treatment; - Prurigo Nodularis (PN): In April 2024, we initiated a Phase 2 study in PN and enrollment is ongoing; positive data from a Phase 1b study in PN was reported in November 2023; - Eosinophilic Esophagitis (EoE): A Phase 2 study in EoE was initiated in June 2023 and is fully accrued; and - Atopic Dermatitis (AD): A Phase 2 study in AD was initiated in December 2024 and enrollment is ongoing. ● Our next generation bispecific antibody platform to support pipeline expansion with additional candidates for inflammatory diseases.
Biggest changePatients on study continued to receive barzolvolimab and, in November 2025, we reported data from 20 weeks of treatment—demonstrating sustained efficacy and a well tolerated safety profile over the longer treatment period; - Prurigo Nodularis (PN): In April 2024, we initiated a Phase 2 study in PN and enrollment was completed in December 2025.
In June 2024, data on a secondary endpoint from the study, angioedema activity, and additional measures of angioedema control, were presented at the EAACI 2024 Congress. Approximately 72% of patients on study had angioedema at baseline. Barzolvolimab demonstrated significant improvements in AAS7 in patients with angioedema across all doses at week 12.
In June 2024, 12 week data on a secondary endpoint from the study, angioedema activity, and additional measures of angioedema control, were presented at the EAACI 2024 Congress. Approximately 72% of patients on study had angioedema at baseline. Barzolvolimab demonstrated significant improvements in AAS7 in patients with angioedema across all doses at Week 12.
Investing Activities Net cash used in investing activities was $290.1 million for the year ended December 31, 2024 compared to $105.8 million for the year ended December 31, 2023.
Net cash used in investing activities was $290.1 million for the year ended December 31, 2024 compared to $105.8 million for the year ended December 31, 2023.
In the 3.0 mg/kg arm, a ≥4-point decrease in WI-NRS reduction was seen as early as the first week and reached a high of 71% of patients at week six which was distinct from both the 1.5 mg/kg barzolvolimab and placebo arms. % of Subjects with ≥4-point decrease in WI-NRS Dose Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 1.5 mg/kg 0 14 29 14 29 29 29 43 3.0 mg/kg 14 29 29 29 57 71 57 57 placebo 0 0 13 13 25 38 38 25 ​ ● At week 8, 29% of patients achieved clear or almost clear skin according to IGA following a single dose of barzolvolimab 3.0 mg/kg.
In the 3.0 mg/kg arm, a ≥4-point decrease in WI-NRS reduction was seen as early as the first week and reached a high of 71% of patients at Week 6 which was distinct from both the 1.5 mg/kg barzolvolimab and placebo arms. % of Subjects with ≥4-point decrease in WI-NRS Dose Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 1.5 mg/kg 0 14 29 14 29 29 29 43 3.0 mg/kg 14 29 29 29 57 71 57 57 placebo 0 0 13 13 25 38 38 25 ​ ● At Week 8, 29% of patients achieved clear or almost clear skin according to IGA following a single dose of barzolvolimab 3.0 mg/kg.
Two-thirds of patients treated with first line systemic therapy (1.7 million patienst in the US) do not achieve complete control of their atopic dermatitis (Simpson, Bieber, Guttman-Yassky, et al. 2016) and new therapies that offer rapid, meaningful relief from the severe itching and breakdown of the skin associated with AD are needed.
Two-thirds of patients treated with first line systemic therapy (1.7 million patients in the US) do not achieve complete control of their atopic dermatitis (Simpson, Bieber, Guttman-Yassky, et al. 2016) and new therapies that offer rapid, meaningful relief from the severe itching and breakdown of the skin associated with AD are needed.
UCT scores at baseline reflect poorly controlled disease. ​ Summary of Clinical Assessments at Week 12 ​ Cold Urticaria Symptomatic Dermographism All measurements at Week 12 150 mg q4w (n=32) 300 mg q8w (n=32) Placebo (n=32) ​ 150 mg q4w (n=33) 300 mg q8w (n=33) Placebo (n=31) Primary endpoint: % of patients with negative provocation test (complete response) 46.9% p=0.0023 53.1% p=0.0011 12.5% ​ 57.6% p 42.4% p=0.0003 3.2% % of patients with complete or partial response per provocation test 62.5% p=0.0118 75% p=0.0006 31.3% ​ 66.6% p 57.5% p=0.0002 12.9% Improvement in Critical Temperature (CTT) and Critical Friction (CFT) Thresholds -8.82°C p -9.61°C p -0.30°C ​ -2.46 pins p -2.27 pins p=0.0002 -0.82 pins % of patients with Urticaria Control Test > 12 58.6% p=0.0048 68.8% p 31.0% ​ 54.8% p=0.0015 65.5% p 32.0% ​ Patients experienced rapid disease improvement as early as two weeks (the first assessment) after receiving the initial dose of barzolvolimab as demonstrated by reductions in critical temperature and friction thresholds resulting in hives and rapid reduction in itch at the time of provocation testing (WI-NRSprovo).
UCT scores at baseline also reflected poorly controlled disease. ​ Summary of Clinical Assessments at Week 12 ​ Cold Urticaria ​ ​ ​ Symptomatic Dermographism All measurements at Week 12 150 mg q4w (n=32) 300 mg q8w (n=32) Placebo (n=32) ​ 150 mg q4w (n=33) 300 mg q8w (n=33) Placebo (n=31) Primary endpoint: % of patients with negative provocation test (complete response) 46.9% p=0.0023 53.1% p=0.0011 12.5% ​ 57.6% p 42.4% p=0.0003 3.2% % of patients with complete or partial response per provocation test 62.5% p=0.0118 75% p=0.0006 31.3% ​ 66.6% p 57.5% p=0.0002 12.9% Improvement in Critical Temperature (CTT) and Critical Friction (CFT) Thresholds -8.82°C p -9.61°C p -0.30°C ​ -2.46 pins p -2.27 pins p=0.0002 -0.82 pins % of patients with Urticaria Control Test > 12 58.6% p=0.0048 68.8% p 31.0% ​ 54.8% p=0.0015 65.5% p 32.0% ​ Patients experienced rapid disease improvement as early as two weeks (the first assessment) after receiving the initial dose of barzolvolimab as demonstrated by reductions in critical temperature and friction thresholds resulting in hives and rapid reduction in itch at the time of provocation testing (WI-NRSprovo).
Key highlighted included: ● Improvements in UAS7 (weekly urticaria activity score), previously shown to be statistically significantly vs placebo at Week 12, were noted as early as week 1 and were sustained or deepened at Week 52. ● At Week 16, patients receiving low dose barzolvolimab (75 mg) or placebo were transitioned to barzolvolimab 150 mg or 300 mg; after crossover, these patients experienced similar clinically meaningful disease response as the rest of the study population. ● 71% of patients treated with barzolvolimab 150 mg Q4W and 52% of patients treated with 300 mg Q8W had a complete response (no itch/hives; UAS7=0) at Week 52.
Key highlights included: ● Improvements in UAS7 (weekly urticaria activity score), previously shown to be statistically significantly vs placebo at Week 12, were noted as early as Week 1 and were sustained or deepened at Week 52. ● At Week 16, patients receiving low dose barzolvolimab (75 mg) or placebo were transitioned to barzolvolimab 150 mg or 300 mg; after crossover, these patients experienced similar clinically meaningful disease response as the rest of the study population. ● 71% of patients treated with barzolvolimab 150 mg Q4W and 52% of patients treated with 300 mg Q8W had a complete response (no itch/hives; UAS7=0) at Week 52.
Our estimates of employee, consultant and non-employ director stock option values rely on estimates of future uncertain events. Significant assumptions include the use of historical volatility to estimate the expected stock price volatility. We also estimate expected term based on historical exercise patterns.
Our estimates of employee, consultant and non-employee director stock option values rely on estimates of future uncertain events. Significant assumptions include the use of historical volatility to estimate the expected stock price volatility. We also estimate expected term based on historical exercise patterns.
Importantly, no evidence of mast cell activation as measured by serum tryptase monitoring was observed in this patient. Barzolvolimab was also generally well tolerated by patients in the 1.5 mg/kg ColdU cohort and the 3.0 mg/kg cholinergic cohort with a similar safety profile to that reported previously.
The patient rapidly recovered. Importantly, no evidence of mast cell activation as measured by serum tryptase monitoring was observed in this patient. Barzolvolimab was also generally well tolerated by patients in the 1.5 mg/kg ColdU cohort and the 3.0 mg/kg cholinergic cohort with a similar safety profile to that reported previously.
The Company determines revenue recognition through the following steps: ● Identification of the contract, or contracts, with a customer; ● Identification of the performance obligations in the contract; ● Determination of the transaction price; ● Allocation of the transaction price to the performance obligations in the contract; and ● Recognition of revenue when, or as, the Company satisfies a performance obligation. 68 Table of Contents Revenue for the Company is derived from product development agreements with collaborative partners for the research and development of therapeutic drug candidates.
The Company determines revenue recognition through the following steps: ● Identification of the contract, or contracts, with a customer; ● Identification of the performance obligations in the contract; ● Determination of the transaction price; ● Allocation of the transaction price to the performance obligations in the contract; and ● Recognition of revenue when, or as, the Company satisfies a performance obligation. 74 Table of Contents Revenue for the Company is derived from product development agreements with collaborative partners for the research and development of therapeutic drug candidates.
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.
The randomized, double-blind, placebo-controlled, parallel group Phase 2 study evaluated 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.
Most responses remained durable through to week 12. 63% (5/8) patients reported well controlled disease (UCT ≥12) at week 8 and 50% (4/8) at week 12, respectively. ● Patients also reported improvements in quality of life outcomes as assessed by the Dermatology Life Quality Index (DLQI) which surveys patients’ perceptions of symptoms and feelings, daily activities, leisure, work and school performance, personal relationships and treatment. 62 Table of Contents ● A single dose of barzolvolimab led to marked decreases in tryptase and in skin mast cells.
Most responses remained durable through to Week 12. 63% (5/8) patients reported well controlled disease (UCT ≥12) at Week 8 and 50% (4/8) at Week 12, respectively. ● Patients also reported improvements in quality of life outcomes as assessed by the Dermatology Life Quality Index (DLQI) which surveys patients’ perceptions of symptoms and feelings, daily activities, leisure, work and school performance, personal relationships and treatment. ● A single dose of barzolvolimab led to marked decreases in tryptase and in skin mast cells.
(“Cantor”) to allow us to issue and sell shares of our common stock from time to time through Cantor, acting as agent. At December 31, 2024, we had registered $300.0 million of our common stock to be sold pursuant to the ATM Agreement, all of which remained unsold as of that date.
(“Cantor”) to allow us to issue and sell shares of our common stock from time to time through Cantor, acting as agent. At December 31, 2025, we had registered $300.0 million of our common stock to be sold pursuant to the ATM Agreement, all of which remained unsold as of that date.
The use of our cash flows for operations has primarily consisted of salaries and wages for our employees; facility and facility-related costs for our offices, laboratories and manufacturing facility; fees paid in connection with preclinical studies, clinical studies, contract manufacturing, laboratory supplies and services; and consulting, legal and other professional fees.
The use of our cash flows for operations has primarily consisted of salaries and wages for our employees; facility and facility-related costs for our offices, laboratories and manufacturing facility; fees paid in connection with preclinical studies, clinical studies, contract manufacturing, laboratory supplies and services; commercial planning; and consulting, legal and other professional fees.
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.
In July 2024, we announced that our Phase 2 study in 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.
On a quarterly basis, we revalue these obligations and record increases or decreases in their fair value as an adjustment to operating earnings. As of December 31, 2024, the fair value of our contingent consideration was $0.0 million.
On a quarterly basis, we revalue these obligations and record increases or decreases in their fair value as an adjustment to operating earnings. As of December 31, 2025, the fair value of our contingent consideration was $0.0 million.
These patients experienced a similar clinical benefit as the overall treated population within their individual dosing groups consistent with the barzolvolimab mechanism of action. 60 Table of Contents Barzolvolimab was well tolerated with a favorable safety profile.
These patients experienced a similar clinical benefit as the overall treated population within their individual dosing groups consistent with the barzolvolimab mechanism of action. 64 Table of Contents Barzolvolimab was well tolerated with a favorable safety profile.
The final histologic analysis and study report were completed in early 2023 and were consistent with previously reported results. We are encouraged with these findings and believe these data strongly support continued development of barzolvolimab. Bispecific Platform Our next generation bispecific antibody platform is supporting the expansion of our pipeline with additional candidates for inflammatory diseases.
The final histologic analysis and study report were completed in early 2023 and were consistent with previously reported results. We are encouraged with these findings and believe these data strongly support continued development of barzolvolimab. 72 Table of Contents Bispecific Platform Our next generation bispecific antibody platform is supporting the expansion of our pipeline with additional candidates for inflammatory diseases.
Mast cells are strongly implicated in all facets of AD pathophysiology and the fundamental processes that characterize AD, including epithelial barrier dysfunction, immune cell recruitment, neuroinflammation (Keith, et al. 2023) and multiple other mast cell-associated factors that correlate with disease severity. Activated mast cells are also found in increased numbers in lesional biopsies.
Mast cells are strongly implicated in all facets of AD pathophysiology and the fundamental processes that characterize AD, including epithelial barrier dysfunction, immune cell recruitment, neuroinflammation (Keith, et al. 2023) and 71 Table of Contents multiple other mast cell-associated factors that correlate with disease severity. Activated mast cells are also found in increased numbers in lesional biopsies.
The primary endpoint of the study was safety; key secondary 64 Table of Contents endpoints include changes from baseline in Worst Itch-Numerical Rating Scale (WI-NRS) & Investigator Global Assessment (IGA). The primary timepoint for evaluation of clinical activity was 8 weeks; patients were followed for safety and efficacy endpoints to 24 weeks.
The primary endpoint of the study was safety; key secondary endpoints include changes from baseline in Worst Itch-Numerical Rating Scale (WI-NRS) & Investigator Global Assessment (IGA). The primary timepoint for evaluation of clinical activity was 8 weeks; patients were followed for safety and efficacy endpoints to 24 weeks.
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). 63 Table of Contents Topline primary endpoint data from this study were reported in July 2024 and 12 week treatment results were presented at the American College of Allergy, Asthma & Immunology’s Annual Scientific Meeting.
Secondary endpoints included safety and other assessments of clinical activity including CTT (Critical Temperature Threshold), CFT (Critical Friction Threshold) and WI-NRS (Worst itch numeric rating scale). 68 Table of Contents Topline primary endpoint data from this study were reported in July 2024 and 12 week treatment results were presented at the American College of Allergy, Asthma & Immunology’s Annual Scientific Meeting.
We believe that the cash, cash equivalents and marketable securities at December 31, 2024 are sufficient to meet estimated working capital requirements and fund current planned operations through 2027.
We believe that the cash, cash equivalents and marketable securities at December 31, 2025 are sufficient to meet estimated working capital requirements and fund current planned operations through 2027.
Omalizumab, an IgE inhibitor, provides relief for roughly half of the remaining antihistamine refractory patients. Consequently, there is a need for additional therapies. 58 Table of Contents We have completed a Phase 1b randomized, double-blind, placebo-controlled multi-center study of barzolvolimab in CSU.
Omalizumab, an IgE inhibitor, provides relief for roughly half of the remaining antihistamine refractory patients. Consequently, there is a need for additional therapies. We have completed a Phase 1b randomized, double-blind, placebo-controlled multi-center study of barzolvolimab in CSU.
The following table indicates the amount incurred for each of our significant research programs and for other identified research and development activities during the years ended December 31, 2024, 2023 and 2022.
The following table indicates the amount incurred for each of our significant research programs and for other identified research and development activities during the years ended December 31, 2025, 2024 and 2023.
The Company has the option to assess qualitative factors to determine if it is more likely than not that the IPR&D asset is impaired and whether it is necessary to perform a quantitative impairment test. Research and Development Expenses Research and development costs, including internal and contract research costs, are expensed as incurred.
The Company has the option to assess qualitative factors to determine if it is more likely than not that the IPR&D asset is impaired and whether it is necessary to perform a quantitative impairment test. 75 Table of Contents Research and Development Expenses Research and development costs, including internal and contract research costs, are expensed as incurred.
The increase in net cash used in investing activities was primarily due to net purchases of marketable 74 Table of Contents securities of $288.2 million for the year ended December 31, 2024 as compared to $104.0 million for the year ended December 31, 2023.
The increase in net cash used in investing activities was primarily due to net purchases of marketable securities of $288.2 million for the year ended December 31, 2024 as compared to $104.0 million for the year ended December 31, 2023.
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.
In July 2024, we announced that our Phase 2 study being conducted in two forms of chronic inducible urticaria (CIndU), ColdU and SD, 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.
The $0.3 million increase in laboratory supply expenses for the year ended December 31, 2024, as compared to the year ended December 31, 2023, was primarily due to higher laboratory services, 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.
The $0.4 million increase in laboratory supply expenses for the year ended December 31, 2025, as compared to the year ended December 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.
After 52 weeks, patients then enter a follow-up period for an additional 24 weeks. The primary endpoint of the study is mean change in baseline to week 12 in UAS7 (weekly urticaria activity score).
After 52 weeks, patients then entered a follow-up period for an additional 24 weeks. The primary endpoint of the study was mean change in baseline to Week 12 in UAS7 (weekly urticaria activity score).
The primary endpoint of the study is the percentage of patients with a negative provocation test at week 12.
The primary endpoint of the study was the percentage of patients with a negative provocation test at Week 12.
In cold urticaria, patients presented with a mean baseline critical temperature threshold of approximately 19°C or 66°F on the TempTest on initial provocation testing. In patients with symptomatic dermographism baseline FricTest thresholds were an average of 3.6 out of 4 pins.
Patients on study had poorly controlled disease on initial provocation testing. In cold urticaria, patients presented with a mean baseline critical temperature threshold of approximately 19°C or 66°F on the TempTest on initial provocation testing. In patients with symptomatic dermographism baseline FricTest thresholds were an average of 3.6 out of 4 pins.
We anticipate that our cash 73 Table of Contents flows from operations will continue to be focused in these areas as we progress our current drug candidates through the clinical trial process and develop additional drug candidates.
We anticipate that our cash flows from operations will continue to be focused in these areas as we progress our current drug candidates through the clinical trial process and develop additional drug candidates.
Hair color changes (generally small areas of hair color lightening) and taste disorders (generally partial changes of ability to taste salt or umami) are consistent with inhibiting KIT signaling in other cell types and completely resolved over time during follow-up. One patient with a history of fainting experienced loss of consciousness during infusion. The patient rapidly recovered.
Hair color changes (generally small areas of hair color lightening) and taste disorders (generally partial changes of ability to taste salt or umami) are consistent with inhibiting KIT signaling in other cell types and completely resolved over time during follow-up. One 67 Table of Contents patient with a history of fainting experienced loss of consciousness during infusion.
The timing of any new contract manufacturing and research and development agreements, collaboration agreements, government contracts or grants and any payments under these agreements, contracts or grants cannot be easily predicted and may vary significantly from quarter to quarter. At December 31, 2024, our principal sources of liquidity consisted of cash, cash equivalents and marketable securities of $725.3 million.
The timing of any new contract manufacturing and research and development agreements, collaboration agreements, government contracts or grants and any payments under these agreements, contracts or grants cannot be easily predicted and may vary significantly from quarter to quarter. At December 31, 2025, our principal sources of liquidity consisted of cash, cash equivalents and marketable securities of $518.6 million.
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 November 2023, we reported that barzolvolimab achieved the primary efficacy endpoint in a Phase 2 study in CSU, with a statistically significant mean change from baseline to Week 12 of UAS7 (weekly urticaria activity score) compared to placebo and was well tolerated.
The $7.4 million increase in personnel expenses for the year ended December 31, 2023, as compared to the year ended December 31, 2022, was primarily due to higher stock-based compensation expense and an increase in employee headcount. Laboratory supplies expenses include laboratory materials and supplies, services and other related expenses incurred in the development of our technology.
The $11.8 million increase in personnel expenses for the year ended December 31, 2024, as compared to the year ended December 31, 2023, was primarily due to higher stock-based compensation expense and an increase in employee headcount. Laboratory supplies expenses include laboratory materials and supplies, services and other related expenses incurred in the development of our technology.
After 16 weeks, patients then enter a 36-week active treatment period, in which patients receiving placebo or the 75 mg dose are randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks; patients already randomized to the 150 mg and 300 mg treatment arms remain on the same regimen as during the placebo-controlled treatment period.
After 16 weeks, patients then entered a 36-week active treatment period, in which patients receiving placebo or the 75 mg dose were randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks; patients already randomized to the 150 mg and 300 mg treatment arms remained on the same regimen as during the placebo-controlled treatment period.
The study is a randomized, double-blind, placebo-controlled, parallel group Phase 2 study evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab to determine the optimal dosing strategy. 208 patients have been randomly assigned on a 1:1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 16-week placebo-controlled treatment phase.
The study was a randomized, double-blind, placebo-controlled, parallel group Phase 2 study that evaluated the efficacy and safety profile of multiple dose regimens of barzolvolimab to determine the optimal dosing strategy. 208 patients were randomly assigned on a 1:1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 16-week placebo-controlled treatment phase.
Research and development expenses consist mainly of clinical trial costs, manufacturing of clinical material, toxicology and other preclinical studies, personnel costs, depreciation, license fees and funding of outside contracted research. 69 Table of Contents Clinical trial expenses include expenses associated with clinical research organization, or CRO, services.
Research and development expenses consist mainly of clinical trial costs, manufacturing of clinical material, toxicology and other preclinical studies, personnel costs, depreciation, license fees and funding of outside contracted research. Clinical trial expenses include expenses associated with clinical research organization, or CRO, services. Contract manufacturing expenses include expenses associated with contract development & manufacturing organization, or CDMO, services.
We expect that cash used in operating activities will increase over the next twelve months as a result of the expanded development of barzolvolimab. Net cash used in operating activities was $107.3 million for the year ended December 31, 2023 compared to $103.7 million for the year ended December 31, 2022.
We expect that cash used in operating activities will increase over the next twelve months as a result of the expanded development of barzolvolimab. Net cash used in operating activities was $157.8 million for the year ended December 31, 2024 compared to $107.3 million for the year ended December 31, 2023.
Secondary endpoints include safety and other assessments of clinical activity including ISS7 (weekly itch severity score), HSS7 (weekly hive severity score) and AAS7 (weekly angioedema activity score). Topline data from this study were presented in November of 2023 and 12 week treatment results were presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in February 2024.
Secondary endpoints included safety and other assessments of clinical activity including ISS7 (weekly itch severity score), HSS7 (weekly hive severity score) and AAS7 (weekly angioedema activity score). Topline data from this study were presented in November of 2023 and 12 week treatment results were presented at the AAAAI Annual Meeting in February 2024.
We have had recurring losses and incurred a loss of $157.9 million for the year ended December 31, 2024. Net cash used in operations for the year ended December 31, 2024 was $157.8 million.
We have had recurring losses and incurred a loss of $258.8 million for the year ended December 31, 2025. Net cash used in operations for the year ended December 31, 2025 was $210.9 million.
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.
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.
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.
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.
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.
Patients then entered a follow-up phase for an additional 24 weeks. In addition, the study included the option for patients who had symptoms following the treatment phase, including patients who were on placebo, to enroll in an open label extension where all patients received 300 mg of barzolvolimab every 8 weeks.
The $1.0 million decrease in laboratory supply expenses for the year ended December 31, 2023, as compared to the year ended December 31, 2022, was primarily due to lower laboratory services, materials and supplies purchases. Facility expenses include depreciation, amortization, utilities, rent, maintenance and other related expenses incurred at our facilities.
The $0.3 million increase in laboratory supply expenses for the year ended December 31, 2024, as compared to the year ended December 31, 2023, was primarily due to higher laboratory services, materials and supplies purchases. Facility expenses include depreciation, amortization, utilities, rent, maintenance and other related expenses incurred at our facilities.
The $11.8 million increase in personnel expenses for the year ended December 31, 2024, as compared to the year ended December 31, 2023, was primarily due to higher stock-based compensation expense and an increase in employee headcount.
The $5.3 million increase in personnel expenses for the year ended December 31, 2025, as compared to the year ended December 31, 2024, was primarily due to higher stock-based compensation expense and an increase in employee headcount.
RESULTS OF OPERATIONS Year Ended December 31, 2024 compared with Year Ended December 31, 2023 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ Increase/ ​ Increase/ ​ ​ December 31, ​ (Decrease) ​ (Decrease) ​ 2024 2023 $ % ​ ​ (In thousands) Revenues: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Product development and licensing agreements ​ $ 13 ​ $ 278 ​ $ (265) ​ (95) % Contracts and grants ​ 7,007 ​ ​ 6,605 ​ ​ 402 ​ 6 % Total revenues ​ $ 7,020 ​ $ 6,883 ​ $ 137 ​ 2 % Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Research and development ​ 163,550 ​ ​ 118,011 ​ ​ 45,539 ​ 39 % General and administrative ​ 38,548 ​ ​ 30,914 ​ ​ 7,634 ​ 25 % Litigation settlement related loss ​ ​ — ​ ​ 12,500 ​ ​ (12,500) ​ (100) % Total operating expenses ​ 202,098 ​ ​ 161,425 ​ ​ 40,673 ​ 25 % Operating loss ​ (195,078) ​ ​ (154,542) ​ ​ 40,536 ​ 26 % Investment and other income, net ​ 37,215 ​ ​ 13,113 ​ ​ 24,102 ​ 184 % Net loss ​ $ (157,863) ​ $ (141,429) ​ $ 16,434 ​ 12 % ​ Net Loss The $16.4 million increase in net loss for the year ended December 31, 2024, as compared to the year ended December 31, 2023, was primarily due to increases in research and development and general and administrative expenses, partially offset by the $12.5 million litigation settlement related loss recorded in 2023 and an increase in investment and other income, net.
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. 77 Table of Contents Year Ended December 31, 2024 compared with Year Ended December 31, 2023 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ Increase/ ​ Increase/ ​ ​ ​ December 31, ​ (Decrease) ​ (Decrease) ​ ​ ​ ​ ​ 2024 ​ ​ ​ 2023 ​ ​ ​ $ ​ ​ ​ % ​ ​ ​ (In thousands) Revenues: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Product development and licensing agreements ​ $ 13 ​ $ 278 ​ $ (265) ​ (95) % Contracts and grants ​ ​ 7,007 ​ ​ 6,605 ​ ​ 402 ​ 6 % Total revenues ​ $ 7,020 ​ $ 6,883 ​ $ 137 ​ 2 % Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Research and development ​ 163,550 ​ 118,011 ​ 45,539 39 % General and administrative ​ 38,548 ​ 30,914 ​ 7,634 25 % Litigation settlement related loss ​ ​ — ​ ​ 12,500 ​ ​ (12,500) ​ (100) % Total operating expenses ​ 202,098 ​ 161,425 ​ 40,673 25 % Operating loss ​ (195,078) ​ (154,542) ​ 40,536 26 % Investment and other income, net ​ 37,215 ​ 13,113 ​ 24,102 184 % Net loss ​ $ (157,863) ​ $ (141,429) ​ $ 16,434 12 % ​ Net Loss The $16.4 million increase in net loss for the year ended December 31, 2024, as compared to the year ended December 31, 2023, was primarily due to increases in research and development and general and administrative expenses, partially offset by the $12.5 million litigation settlement related loss recorded in 2023 and an increase in investment and other income, net.
Our inability to raise additional capital, or to do so on terms reasonably acceptable to us, would jeopardize the future success of our business. 57 Table of Contents During the past five years through December 31, 2024, we incurred an aggregate of $459.7 million in research and development expenses.
Our inability to raise additional capital, or to do so on terms reasonably acceptable to us, would jeopardize the future success of our business. During the past five years through December 31, 2025, we incurred an aggregate of $662.2 million in research and development expenses.
A single IV dose of 3.0 mg/kg barzolvolimab resulted in rapid and durable reductions in itch and healing of skin lesions in patients with moderate to severe PN and that barzolvolimab was generally well tolerated. ● At week 8, the percentage of patients with ≥4-point decrease in WI-NRS was 57% and 43% for the single dose 3.0 or 1.5 mg/kg barzolvolimab arms, respectively, and 25% for the placebo arm; this level of response generally persisted out to week 16.
Patients on study generally had moderate to severe disease with mean baselines scores across all arms of 8.6 for WI-NRS and 3.3 for IGA. 70 Table of Contents A single IV dose of 3.0 mg/kg barzolvolimab resulted in rapid and durable reductions in itch and healing of skin lesions in patients with moderate to severe PN and that barzolvolimab was generally well tolerated. ● At Week 8, the percentage of patients with ≥4-point decrease in WI-NRS was 57% and 43% for the single dose 3.0 or 1.5 mg/kg barzolvolimab arms, respectively, and 25% for the placebo arm; this level of response generally persisted out to Week 16.
Secondary objectives include but are not limited to additional measures of itch response from baseline compared to different timepoints, the assessment of skin lesions as measured by the Investigator Global Assessment (IGA), QoL outcomes and safety. The study will include approximately 50 clinical trial centers worldwide, including the United States.
Secondary objectives include but are not limited to additional measures of itch response from baseline compared to different timepoints, the assessment of skin lesions as measured by the Investigator Global Assessment (IGA), QoL outcomes and safety. The study includes approximately 75 clinical trial centers worldwide, including the United States. Enrollment was completed in December 2025.
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.
At 24 weeks, patients on placebo will be re-randomized to active treatment across both dosing groups. After completion of the 52 week treatment period, patients on study will continue to be followed for 16 weeks. 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.
Patients on study continued to receive barzolvolimab and, in September 2024, we reported data from 52 weeks of treatment—demonstrating sustained and deepening disease efficacy and a well tolerated long term safety profile.
Patients on study continued to receive barzolvolimab and, in September 2024, we reported data from 52 weeks of treatment—demonstrating sustained and deepening disease efficacy and a well tolerated long term safety profile. In June 2025, Celldex presented longer term follow up data from the study.
Data from this study were reported across multiple medical meetings, including the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in February 2023, the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress in June 2023 and the European Academy of Dermatology & Venereology (EADV) Congress in October 2023. 59 Table of Contents In June 2022, we initiated dosing in a Phase 2 study in patients with CSU who remained symptomatic despite antihistamine therapy; in July 2023, we announced that enrollment was complete.
Data from this study were reported across multiple medical meetings, including the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in February 2023, the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress in June 2023 and the European Academy of Dermatology & Venereology (EADV) Congress in October 2023. 63 Table of Contents We have completed a Phase 2 study in patients with CSU who remained symptomatic despite antihistamine therapy.
Financing Activities Net cash provided by financing activities was $441.4 million for the year ended December 31, 2024 compared to $218.5 million for the year ended December 31, 2023. The increase in net cash provided by financing activities was primarily due to an increase in net proceeds from stock issuances.
The decrease in net cash provided by financing activities was primarily due to a decrease in net proceeds from stock issuances. 80 Table of Contents Net cash provided by financing activities was $441.4 million for the year ended December 31, 2024 compared to $218.5 million for the year ended December 31, 2023.
Secondary endpoints include the evaluation of the clinical efficacy of barzolvolimab, compared to placebo across multiple patient-reported outcomes, including assessing impressions of disease change and severity and improvements in quality of life. When all clinical trial sites are open, the study will include up to 50 clinical trial centers in the United States.
Secondary endpoints include the evaluation of the clinical efficacy of barzolvolimab, compared to placebo across multiple patient-reported outcomes, including assessing impressions of disease change and severity and improvements in quality of life. When all clinical trial sites are open, the study includes approximately 40 clinical trial centers in the United States. Enrollment was completed in January 2026.
The study is being conducted at approximately 75 sites across 9 countries.
The study was conducted at approximately 75 sites across 9 countries.
We are focusing our efforts and resources on the continued research and development of ● Barzolvolimab (also referred to as CDX-0159), a monoclonal antibody that specifically binds the KIT receptor and potently inhibits its activity, which is currently being studied across multiple mast cell driven diseases including - Chronic Urticarias: We initiated Phase 3 studies in chronic spontaneous urticaria (CSU) in July 2024.
We are focusing our efforts and resources on the continued research and development of ● Barzolvolimab (also referred to as CDX-0159), a monoclonal antibody that specifically binds the KIT receptor and potently inhibits its activity, which is currently being studied across multiple mast cell driven diseases including - Chronic Spontaneous Urticaria (CSU): In February 2026, we announced that enrollment is complete in our Phase 3 studies in CSU and that topline data will be available in the fourth quarter of 2026.
Operating Activities Net cash used in operating activities was $157.8 million for the year ended December 31, 2024 compared to $107.3 million for the year ended December 31, 2023.
Operating Activities Net cash used in operating activities was $210.9 million for the year ended December 31, 2025 compared to $157.8 million for the year ended December 31, 2024.
Although we have been successful in raising capital in the past, there can be no assurance that additional financing will be available on acceptable terms, if at all, and our negotiating position in capital raising efforts may worsen as existing resources are used. There is also no assurance that we will be able to enter into further collaborative relationships.
Although we have been successful in raising capital in the past, there can be no assurance that additional financing will be available on acceptable terms, if at all, and our negotiating position in capital raising efforts may worsen as existing resources 79 Table of Contents are used.
The $27.2 million increase in product development expenses for the year ended December 31, 2023, as compared to the year ended December 31, 2022, was primarily due to an increase in barzolvolimab clinical trial and contract manufacturing expenses.
The $70.5 million increase in product development expenses for the year ended December 31, 2025, as compared to the year ended December 31, 2024, was primarily due to increases in barzolvolimab clinical trial and contract manufacturing expenses.
We expect revenue to decrease over the next twelve months as a result of a decrease in services expected to be performed under our contract manufacturing and research and development agreements with Rockefeller University, although there may be fluctuations on a quarterly basis. 70 Table of Contents Research and Development Expense Research and development expenses consist primarily of (i) personnel expenses, (ii) laboratory supply expenses relating to the development of our technology, (iii) facility expenses and (iv) product development expenses associated with our drug candidates as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ Increase/ ​ ​ December 31, ​ (Decrease) ​ 2024 2023 $ % ​ ​ (In thousands) ​ ​ ​ ​ ​ Personnel ​ $ 51,906 ​ $ 40,121 ​ $ 11,785 ​ 29 % Laboratory supplies ​ 5,611 ​ ​ 5,358 ​ ​ 253 ​ 5 % Facility ​ 5,094 ​ ​ 4,970 ​ ​ 124 ​ 2 % Product development ​ 90,604 ​ ​ 59,319 ​ ​ 31,285 ​ 53 % ​ Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes.
Research and Development Expense Research and development expenses consist primarily of (i) personnel expenses, (ii) laboratory supply expenses relating to the development of our technology, (iii) facility expenses and (iv) product development expenses associated with our drug candidates as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ Increase/ ​ ​ ​ December 31, ​ (Decrease) ​ ​ ​ ​ ​ 2024 ​ ​ ​ 2023 ​ ​ ​ $ ​ ​ ​ % ​ ​ ​ (In thousands) ​ ​ ​ ​ ​ ​ Personnel ​ $ 51,906 ​ $ 40,121 ​ $ 11,785 ​ 29 % Laboratory supplies ​ 5,611 ​ 5,358 ​ 253 5 % Facility ​ 5,094 ​ 4,970 ​ 124 2 % Product development ​ 90,604 ​ 59,319 ​ 31,285 53 % ​ Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes.
Equity Offerings In November 2023, we filed an automatic shelf registration statement with the SEC to register for sale any combination of the types of securities described in the shelf registration statement, including shares of our common stock.
The increase in net cash provided by financing activities was primarily due to an increase in net proceeds from stock issuances. Equity Offerings In November 2023, we filed an automatic shelf registration statement with the SEC to register for sale any combination of the types of securities described in the shelf registration statement, including shares of our common stock.
As a result of the uncertainties discussed above, among others, it is difficult to accurately estimate the duration and completion costs of our research and development projects or when, if ever, and to what extent we will receive cash inflows from the commercialization and sale of a product.
Our programs may also benefit from subsidies, grants, contracts or government or agency-sponsored studies that could reduce our development costs. 61 Table of Contents As a result of the uncertainties discussed above, among others, it is difficult to accurately estimate the duration and completion costs of our research and development projects or when, if ever, and to what extent we will receive cash inflows from the commercialization and sale of a product.
During the fourth quarter of 2023, we paid the $12.5 million milestone in cash and recorded a litigation settlement related loss of $12.5 million. 71 Table of Contents Investment and Other Income, Net The $24.1 million increase in investment and other income, net for the year ended December 31, 2024, as compared to the year ended December 31, 2023, was primarily due to higher levels of cash as a result of our November 2023 and March 2024 underwritten public offerings.
Investment and Other Income, Net The $24.1 million increase in investment and other income, net for the year ended December 31, 2024, as compared to the year ended December 31, 2023, was primarily due to higher levels of cash as a result of our November 2023 and March 2024 underwritten public offerings.
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. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended Year Ended Year Ended ​ December 31, 2024 December 31, 2023 December 31, 2022 ​ ​ (In thousands) Barzolvolimab/Anti-KIT Program ​ $ 123,750 ​ $ 79,913 ​ $ 51,220 CDX-622 ​ 17,341 ​ ​ 16,299 ​ ​ 5,613 CDX-585 ​ ​ 2,813 ​ ​ 6,357 ​ ​ 9,793 Other Programs ​ 19,646 ​ ​ 15,442 ​ ​ 15,632 Total R&D Expense ​ $ 163,550 ​ $ 118,011 ​ $ 82,258 ​ Clinical Development Programs Barzolvolimab (also referred to as CDX-0159) Barzolvolimab is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT and potently inhibits its activity.
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. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ ​ Year Ended ​ ​ ​ Year Ended ​ ​ ​ ​ December 31, 2025 ​ ​ ​ December 31, 2024 ​ ​ ​ December 31, 2023 ​ ​ (In thousands) Barzolvolimab/Anti-KIT Program ​ $ 198,329 ​ $ 123,750 ​ $ 79,913 CDX-622 ​ 18,958 ​ ​ 17,341 ​ ​ 16,299 Other Programs ​ 27,787 ​ ​ 22,459 ​ ​ 21,799 Total R&D Expense ​ $ 245,074 ​ $ 163,550 ​ $ 118,011 ​ Clinical Development Programs Barzolvolimab (also referred to as CDX-0159) Barzolvolimab is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT and potently inhibits its activity.
Completion of clinical trials may take several years or more, and the length of time generally varies substantially according to the type, complexity, novelty and intended use of a drug candidate.
The expenditures that will be necessary to execute our business plan are subject to numerous uncertainties. Completion of clinical trials may take several years or more, and the length of time generally varies substantially according to the type, complexity, novelty and intended use of a drug candidate.
We cannot forecast with any degree of certainty which proprietary products, if any, will be subject to future collaborative arrangements, in whole or in part, and how such arrangements would affect our development plan or capital requirements. Our programs may also benefit from subsidies, grants, contracts or government or agency-sponsored studies that could reduce our development costs.
We cannot forecast with any degree of certainty which proprietary products, if any, will be subject to future collaborative arrangements, in whole or in part, and how such arrangements would affect our development plan or capital requirements.
Revenue The $4.3 million increase in contracts and grants revenue for the year ended December 31, 2023, as compared to the year ended December 31, 2022, was primarily related to an increase in services performed under our manufacturing and research and development agreements with Rockefeller University.
Revenue The $5.6 million decrease in contracts and grants revenue for the year ended December 31, 2025, as compared to the year ended December 31, 2024, was primarily due to a decrease in services performed under our manufacturing and research and development agreements with Rockefeller University.
Contract manufacturing expenses include expenses associated with contract development & manufacturing organization, or CDMO, services. The invoicing from CROs and CDMOs for services rendered can lag several months. We accrue the cost of services rendered in connection with CRO and CDMO activities based on our estimate of costs incurred.
The invoicing from CROs and CDMOs for services rendered can lag several months. We accrue the cost of services rendered in connection with CRO and CDMO activities based on our estimate of costs incurred. We maintain regular communication with our CROs and CDMOs to assess the reasonableness of our estimates.
The data demonstrated a sustained and deepening disease efficacy and a well tolerated safety profile over a 52 week treatment period.
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.
CDX-622 was well tolerated in a multi-dose 8 week toxicology study in non-human primates. The No Adverse Event Level (NOAEL) was established to be 75 mg/kg, the highest dose level tested. In November 2024, we initiated a Phase 1 study of CDX-622 in healthy volunteers.
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.
At 3 mg/kg in the ColdU and SD cohorts, safety results were reported for 21 patients and activity results were reported for the 20 patients who received a full dose of barzolvolimab.
Generally patients on study had high disease activity at baseline that was poorly controlled and marked impairment in quality of life. At 3 mg/kg in the ColdU and SD cohorts, safety results were reported for 21 patients and activity results were reported for the 20 patients who received a full dose of barzolvolimab.
The increase in net cash used in investing activities was primarily due to net purchases of marketable securities of $104.0 million for the year ended December 31, 2023 as compared to net sales and maturities of marketable securities of $91.7 million for the year ended December 31, 2022.
The increase in net cash provided by investing activities was primarily due to net sales and maturities of marketable securities of $211.8 million for the year ended December 31, 2025 as compared to net purchases of marketable securities of $288.2 million for the year ended December 31, 2024.
Net cash used in investing activities was $105.8 million for the year ended December 31, 2023 compared to net cash provided by investing activities of $89.9 million for the year ended December 31, 2022.
Investing Activities Net cash provided by investing activities was $209.1 million for the year ended December 31, 2025 compared to net cash used in investing activities of $290.1 million for the year ended December 31, 2024.
Neutrophil counts did not decline further with continued dosing and there was no association between infections and neutropenia. The hypopigmentation was observed with longer term exposure and did not lead to treatment discontinuation. Adverse events were not dose dependent. We believe these results strongly support the further development of barzolvolimab in CSU.
Neutrophil counts did not decline further with continued dosing and there was no association between infections and neutropenia. The hypopigmentation was observed with longer term exposure and did not lead to treatment discontinuation.
We maintain regular communication with our CROs and CDMOs to assess the reasonableness of our estimates. Differences between actual expenses and estimated expenses recorded have not been material and are adjusted for in the period in which they become known.
Differences between actual expenses and estimated expenses recorded have not been material and are adjusted for in the period in which they become known.
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.
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. The primary endpoint analysis will be performed when all patients have completed the placebo controlled portion of the study at 24 weeks.
We believe our program assets provide us with the strategic options to either retain full economic rights to our innovative therapies or seek favorable economic terms through advantageous commercial partnerships.
We believe our program assets provide us with the strategic options to either retain full economic rights to our innovative therapies or seek favorable economic terms through advantageous commercial partnerships. This approach allows us to maximize the overall value of our technology and product portfolio while best ensuring the expeditious development of each individual product.
There are currently no approved therapies for chronic inducible urticarias other than antihistamines and patients attempt to manage symptoms associated with their disease through avoidance of triggers. We are currently exploring cold-induced and dermographism (scratch-induced) urticarias in an ongoing Phase 2 study.
There are currently no approved therapies for chronic inducible urticarias other than antihistamines and patients attempt to manage symptoms associated with their disease through avoidance of triggers. We completed a Phase 1b open label clinical trial in patients with CIndU refractory to antihistamines, conducted in Germany.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeWe do not utilize derivative financial instruments. The carrying amounts reflected in the balance sheet of cash and cash equivalents, accounts receivables and accounts payable approximates fair value at December 31, 2024 due to the short-term maturities of these instruments. ​ 75 Table of Contents
Biggest changeWe do not utilize derivative financial instruments. The carrying amounts reflected in the balance sheet of cash and cash equivalents, accounts receivables and accounts payable approximates fair value at December 31, 2025 due to the short-term maturities of these instruments. ​ 81 Table of Contents

Other CLDX 10-K year-over-year comparisons