10q10k10q10k.net

What changed in Celldex Therapeutics, Inc.'s 10-K — 2023 vs 2024

vs

Paragraph-level year-over-year comparison of Celldex Therapeutics, Inc.'s 2023 and 2024 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 2024 report.

+432 added−369 removedSource: 10-K (2025-02-27) vs 10-K (2024-02-26)

Top changes in Celldex Therapeutics, Inc.'s 2024 10-K

432 paragraphs added · 369 removed · 313 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

100 edited+49 added−22 removed177 unchanged
Biggest changeMean reduction from baseline in UAS7 at week 24 was 80% in the 1.5 mg/kg dose group (n=7), 70% in the 3.0 mg/kg dose group (n=6) and 77% in the 4.5 mg/kg dose group (n=7). ● Complete response (UAS7=0) at week 12 was 57% in the 1.5 mg/kg dose group, 44% in the 3.0 mg/kg dose group and 67% in the 4.5 mg/kg dose group.
Biggest changePhase 1 CSU: Summary of Clinical Activity Assessments at Week 12 & 24 ​ 4.5 mg/kg Q8 3.0 mg/kg Q8 1.5 mg/kg Q4 Mean Reduction Baseline UAS7; % at Week 12 82% (n=9) 67% (n=9) 67% (n=8) Mean Reduction Baseline UAS7; % at Week 24 77% (n=7) 70% (n=6) 80% (n=7) UAS7=0 (Complete Control); % at Week 12 67% 44% 57% UAS7=0 (Complete Control); % at Week 24 43% 67% 57% UAS7≤6 (Well-controlled); % at Week 12 67% 67% 57% UAS7≤6 (Well-controlled); % at Week 24 57% 67% 57% UCT ≥ 12 (Well-controlled); % at Week 12 89% 63% 75% UCT ≥ 12 (Well-controlled); % at Week 24 67% 67% 75% ​ During post-treatment follow up, 71% (10 of 14) of patients who had been treated with doses greater than or equal to 1.5 mg/kg and had a complete response (UAS7=0) at week 12, remained urticaria free at week 24 (patients received last dose of barzolvolimab at week 8).
We completed a Phase 1b open label clinical trial in CIndU in patients refractory to antihistamines, conducted in Germany. This study was designed to evaluate the safety of a single intravenous dose (3 mg/kg) of barzolvolimab in patients with cold urticaria (ColdU) or symptomatic dermographism (SD).
We completed a Phase 1b open label clinical trial in patients with CIndU refractory to antihistamines, conducted in Germany. This study was designed to evaluate the safety of a single intravenous dose (3 mg/kg) of barzolvolimab in patients with cold urticaria (ColdU) or symptomatic dermographism (SD).
On our website, investors can obtain, free of charge, a copy of our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, our Code of Conduct and Business Ethics, including disclosure related to any amendments or waivers thereto, other reports and any amendments thereto filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act of 1934, as amended, as soon as reasonably practicable after we file such material electronically with, or furnish it to, the Securities and Exchange Commission, or the SEC.
On our website, investors can obtain, free of charge, a copy of our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, our Code of Business Conduct and Ethics, including disclosure related to any amendments or waivers thereto, other reports and any amendments thereto filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act of 1934, as amended, as soon as reasonably practicable after we file such material electronically with, or furnish it to, the Securities and Exchange Commission, or the SEC.
Summary of Clinical Activity Assessments at Week 12 ​ 300 mg Q8W (n=51) 150 mg Q4W (n=52) 75 mg Q4W (n=53) Placebo (n=51) UAS7 Changes Baseline UAS7 (mean) 31.33 30.75 30.30 30.09 LS Mean change at Week 12 -23.87 -23.02 -17.06 -10.47 LS Mean difference from placebo (Confidence Interval, p value) -13.41 (CI: -17.47, -9.34) p -12.55 (CI:-16.56, -8.55) p -6.60 (CI:-10.71, -2.49) p=0.0017 ​ HSS7 Changes Baseline HSS7 (mean) 14.92 15.05 14.86 14.47 LS Mean change at Week 12 -12.19 -11.19 -8.25 -4.95 LS Mean difference from placebo (Confidence Interval, p value) -7.24 (CI:-9.36, -5.12) p -6.24 (CI:-8.33, -4.16), p -3.31 (CI:-5.40, -1.22), p=0.0020 ​ ISS7 Changes Baseline ISS7 (mean) 16.42 15.70 15.44 15.61 LS Mean change at Week 12 -11.79 -11.68 -8.62 -5.47 LS Mean difference from placebo (Confidence Interval, p value) -6.32 (CI: -8.50, -4.13), p -6.21 (CI: -8.38, -4.04), p -3.16 (CI: -5.41, -0.91), p=0.0061 ​ Responder Analyses/Clinical Responses UAS7=0 (Complete Control) 37.5% 51.1% 22.9% 6.4% UAS7≤6 (Well-controlled) 62.5% 59.6% 41.7% 12.8% ​ UAS7, HSS7 and ISS7 data were analyzed using ANCOVA model and multiple imputation.
Phase 2 CSU: Summary of Clinical Activity Assessments at Week 12 ​ 300 mg Q8W (n=51) 150 mg Q4W (n=52) 75 mg Q4W (n=53) Placebo (n=51) UAS7 Changes Baseline UAS7 (mean) 31.33 30.75 30.30 30.09 LS Mean change at Week 12 -23.87 -23.02 -17.06 -10.47 LS Mean difference from placebo (Confidence Interval, p value) -13.41 (CI: -17.47, -9.34) p -12.55 (CI:-16.56, -8.55) p -6.60 (CI:-10.71, -2.49) p=0.0017 ​ HSS7 Changes Baseline HSS7 (mean) 14.92 15.05 14.86 14.47 LS Mean change at Week 12 -12.19 -11.19 -8.25 -4.95 LS Mean difference from placebo (Confidence Interval, p value) -7.24 (CI:-9.36, -5.12) p -6.24 (CI:-8.33, -4.16), p -3.31 (CI:-5.40, -1.22), p=0.0020 ​ ISS7 Changes Baseline ISS7 (mean) 16.42 15.70 15.44 15.61 LS Mean change at Week 12 -11.79 -11.68 -8.62 -5.47 LS Mean difference from placebo (Confidence Interval, p value) -6.32 (CI: -8.50, -4.13), p -6.21 (CI: -8.38, -4.04), p -3.16 (CI: -5.41, -0.91), p=0.0061 ​ Responder Analyses/Clinical Responses UAS7=0 (Complete Control) 37.5% 51.1% 22.9% 6.4% UAS7≤6 (Well-controlled) 62.5% 59.6% 41.7% 12.8% ​ UAS7, HSS7 and ISS7 data were analyzed using ANCOVA model and multiple imputation.
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; 13 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; 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 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 6 Table of Contents weeks.
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.
Patients will 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 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.
Sales of any of our drug candidates, if approved, will depend, in part, on the extent to which the costs of the drugs will be covered by third-party payors, including government health programs such as Medicare and Medicaid, as well as commercial health insurers, such as managed care organizations.
Sales of any of our drug candidates, if approved, will depend, in part, on the extent to which the acquisition costs of the drugs will be covered by third-party payors, including government health programs such as Medicare and Medicaid, as well as commercial health insurers, such as managed care organizations.
The containment of health care costs has become a priority of federal, state and foreign governments, and the prices of drugs have been a focus in this effort. Given that the Inflation Reduction Act is now in place, potential implications for the biopharma industry are being assessed.
The containment of health care costs has become a priority of federal, state and foreign governments, and the prices of drugs have been a focus in this effort. Given that the Inflation Reduction Act is now in place, potential implications for the biopharma industry are still being assessed.
Further (later filed) patent applications (relating to Fc sequences used in barzolvolimab and certain uses of barzolvolimab) are pending in the U.S., the European Patent Office, Japan, Canada, China, Australia, New Zealand, Israel, India, the Republic of Korea, the Eurasian Patent Office, Brazil, Mexico and South Africa.
Further (later filed) patent applications (relating to Fc sequences used in barzolvolimab and certain uses of barzolvolimab) are pending in the U.S., the European Patent Office, Japan, Canada, China, Australia, New Zealand, Israel, India, the Republic of Korea, the Eurasian Patent Office, Singapore, Brazil, Mexico and South Africa.
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. 15 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.
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.
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 16 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 19 Table of Contents subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
The subcutaneous form could improve the patient experience if the product becomes available commercially. In 2023, we completed the transfer of our current barzolvolimab manufacturing process to a CMO and successfully scaled up the drug substance manufacturing process to produce larger cGMP batches in support of late-stage trials and to prepare for potential commercialization.
The subcutaneous form could improve the patient experience if the product becomes available commercially. In 2023, we completed the transfer of our current barzolvolimab manufacturing process to a CDMO and successfully scaled up the drug substance manufacturing process to produce larger cGMP batches in support of late-stage trials and to prepare for potential commercialization.
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. 5 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. 6 Table of Contents ● Barzolvolimab was well tolerated across all cohorts.
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-ILT4 antibodies, anti-PD-1 antibodies, 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 ● 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.
For example, certain EU member states may approve a specific price and volume for a drug product after which incremental revenues or profits need to be paid back by way of rebates. They may also institutionalize utilization restrictions, curb physicians’ drug budgets, provide conditional reimbursement schemes that 19 Table of Contents require additional evidence to be generated post-marketing authorization, etc.
For example, certain EU member states may approve a specific price and volume for a drug product after which incremental revenues or profits need to be paid back by way of rebates. They may also institutionalize utilization restrictions, curb physicians’ drug budgets, provide conditional reimbursement schemes that require additional evidence to be generated post-marketing authorization, etc.
Of these employees, 136 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, 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.
Secondary and exploratory objectives included pharmacokinetic and pharmacodynamic assessments, including changes from baseline provocation thresholds, measurement of tryptase and stem cell factor levels, clinical activity outcomes, quality of life assessments and measurement of tissue mast cells through skin biopsies. Generally patients on study had high disease activity at baseline that was poorly controlled and marked impairment in quality of life.
Secondary and exploratory objectives included pharmacokinetic and pharmacodynamic assessments, including changes from baseline provocation thresholds, measurement of tryptase and stem cell factor levels, clinical activity outcomes, quality of life assessments and measurement of tissue mast cells through skin biopsies. 5 Table of Contents Generally patients on study had high disease activity at baseline that was poorly controlled and marked impairment in quality of life.
These license and collaboration agreements generally provide for royalty payments equal to specified percentages of product sales, annual license maintenance fees, continuing patent prosecution costs and potential future milestone payments to third parties upon the achievement of certain development, regulatory and/or commercial milestones. Summarized below are our significant research collaboration and license agreements for our current clinical drug candidates.
These license and collaboration agreements generally provide for royalty payments equal to specified percentages of product sales, annual license maintenance fees, continuing patent prosecution costs and potential future milestone payments to third parties upon the achievement of certain development, regulatory and/or commercial milestones. Summarized below is our significant research collaboration and license agreement for our current clinical drug candidates.
If we become involved in that litigation, we could consume substantial resources. 12 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. 15 Table of Contents Licenses We have entered into significant license agreements relating to technologies that are being developed by us.
The process for determining reimbursement rates is separate from the payor coverage decision. Therefore, despite obtaining coverage, reimbursement rates may be lower than expected, which can result in larger out-of-pocket payments for the patient.
The process for determining reimbursement rates is separate from the payor coverage decision. Therefore, despite obtaining coverage, reimbursement rates may be lower than expected, which can result in significant out-of-pocket payments for the patient.
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.
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.
During the initial 8 week observation period in the 3.0 mg/kg dosing arm, an anaphylactic reaction occurred in a complicated patient with multiple comorbidities; the event fully resolved without sequelae. Generally, AEs seen during the 24-week follow-up period were consistent with comorbidities commonly observed in the PN population.
During the initial 8 week observation period in the 3.0 mg/kg dosing arm, an anaphylactic reaction occurred in a complicated patient with multiple comorbidities; the event fully resolved without sequelae. Generally, adverse events seen during the 24-week follow-up period were consistent with comorbidities commonly observed in the PN population.
None of the information posted on our website is incorporated by reference into this Annual Report. The SEC also maintains a website at http://www.sec.gov that contains reports, proxy and information statements and other information regarding us and other companies that file materials with the SEC electronically. ​ 21 Table of Contents
None of the information posted on our website is incorporated by reference into this Annual Report. The SEC also maintains a website at http://www.sec.gov that contains reports, proxy and information statements and other information regarding us and other companies that file materials with the SEC electronically.
We follow federal, state and local rules and guidelines to ensure the safety of our workforce and provide resources to assist our employees in managing their overall physical and mental health. 20 Table of Contents Research and Development We have dedicated a significant portion of our resources to our efforts to develop our drug candidates.
We follow federal, state and local rules and guidelines to ensure the safety of our workforce and provide resources to assist our employees in managing their overall physical and mental health. Research and Development We have dedicated a significant portion of our resources to our efforts to develop our drug candidates.
Many of the products that we are attempting to develop and commercialize will be competing with existing therapies. Other 9 Table of Contents companies are pursuing the development of new therapies that target the same diseases and conditions that we are targeting and may compete directly with our drug candidates.
Many of the products that we are attempting to develop and commercialize will be competing with existing therapies. Other companies are pursuing the development of new therapies that target the same diseases and conditions that we are targeting and may compete directly with our drug candidates.
This randomized, double-blind, placebo-controlled, parallel group study will evaluate the efficacy and safety profile of 2 dose levels of barzolvolimab compared to placebo in approximately 120 patients with moderate to severe PN who had inadequate response to prescription topical medications, or for whom topical medications are medically inadvisable (such as concerns for safety).
This randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety profile of 2 dose levels of barzolvolimab compared to placebo in approximately 120 patients with moderate to severe PN who had inadequate response to prescription topical medications, or for whom topical medications are medically inadvisable (such as concerns for safety).
Targets are being selected based on new science as well as their compatibility to be used in bispecific antibody formats with our existing antibody programs. Development is focused on emerging, important pathways controlling inflammatory diseases or immunity to tumors.
Targets are being selected based on new science as well as their compatibility to be used in bispecific antibody formats with our existing antibody programs. Development is focused on emerging, important pathways controlling inflammatory diseases.
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.
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.
Additional Barzolvolimab Development Activities In 2023, we completed the transfer of our current barzolvolimab manufacturing process to a CMO and successfully scaled up the drug substance manufacturing process to produce larger cGMP batches in support of late-stage trials and to prepare for potential commercialization.
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.
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 medical benefit 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 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 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. The study is being conducted at approximately 85 sites across approximately 12 countries.
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.
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, 2023, we had 160 full-time employees, 26 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, 2024, we had 186 full-time employees, 29 of whom have Ph.D. and/or M.D. degrees.
To conduct late-stage clinical trials, as well as manufacture and commercialize our drug candidates, we engage Contract Manufacturing Organizations (CMOs) to manufacture our drug candidates on a large scale at a competitive cost and in accordance with current Good Manufacturing Practices (cGMP) and U.S. and foreign regulatory requirements, as applicable.
To conduct late-stage clinical trials, as well as manufacture and commercialize our drug candidates, we engage CDMOs in the U.S and outside the U.S. to manufacture our drug candidates on a large scale at a competitive cost and in accordance with current Good Manufacturing Practices (cGMP) and U.S. and foreign regulatory requirements, as applicable.
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. 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. Phase 1 studies in CSU and CIndU were successfully completed and Phase 2 studies are ongoing.
Our drug candidates may not be considered medically necessary, provide insufficient incremental medical benefit, or may not be deemed cost-effective. A payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved.
Our drug candidates may not be considered medically necessary, provide insufficient incremental value, or may not be deemed cost-effective per payor criteria. A payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved.
Phase 2 trials are conducted on a limited group of the target patient population; safety, optimal dosage and efficacy are studied. A Phase 3 trial is performed in a large patient population, generally over a wide geographic area to provide evidence for the safety and efficacy of the product.
Phase 2 trials are conducted on a limited group of the target patient population; safety, optimal dosage and efficacy are studied. A Phase 3 trial is performed in a large patient population, generally over a wide geographic area to provide evidence for the safety and efficacy of the product. The FDA maintains and exercises oversight authority throughout the clinical trial.
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.
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.
Drug product manufacturing into 1 mL pre-filled syringes has been completed in support of Phase 3 trials. We are in the process of scaling up our drug product manufacturing. We believe that barzolvolimab can be scaled up to permit drug product manufacturing in commercial quantities.
Drug product manufacturing into 1 mL pre-filled syringes has been completed and are actively being used in the ongoing Phase 3 CSU trials. We are in the process of scaling up our drug product manufacturing. We believe that barzolvolimab can be scaled up to permit drug product manufacturing in commercial quantities.
The marketability of any drugs for which we receive regulatory approval for commercial sale may suffer if third-party payors and/or hospital administrators fail to provide adequate coverage, reimbursement or formulary placement. Coverage policies, third-party reimbursement rates and drug pricing regulations may change in the future.
The marketability of any drugs for which we receive regulatory approval for commercial sale may suffer if third-party payors and/or hospital administrators fail to provide adequate coverage, reimbursement or formulary placement. Coverage policies, third-party reimbursement rates and drug pricing regulations may change in the future. In addition, the States may continue to consider legislation of their own (e.g.
The 1.5 mg/kg, 3.0 mg/kg and 4.5 mg/kg dose groups showed similar markedly improved urticaria symptoms, including rapid onset of responses (as early as 1 week after the first dose) and prolonged disease control with sustained durability up to 24 weeks.
The 1.5 mg/kg, 3.0 mg/kg and 4.5 mg/kg dose groups showed similar markedly improved urticaria symptoms, including rapid onset of responses (as early as 1 week after the first dose) and prolonged disease control with sustained durability up to 24 weeks. Patients with prior omalizumab therapy also had similar symptom improvement as all patients.
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].
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.
If, when and where issued the latter would have estimated normal patent expiry dates in 2042. ● We own a family of patent applications directed to anti-ILT4 antibody sequences used in CDX-585 as compositions of matter.
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 foregoing would have estimated normal patent expiry dates ranging from 2041 to 2042. There can be no assurance that patent applications owned by or licensed to us will result in granted patents or that, if granted, the resultant patents will afford protection against competitors with similar technology.
If, when and where issued any applications in the national and regional phases of this application would have estimated normal patent expiry dates in 2044. There can be no assurance that patent applications owned by or licensed to us will result in granted patents or that, if granted, the resultant patents will afford protection against competitors with similar technology.
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.
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.
By targeting KIT, barzolvolimab has been shown to inhibit mast cell activity and decrease mast cell numbers, which we believe could provide potential clinical benefit in mast cell related diseases.
Barzolvolimab is designed to block KIT activation by disrupting both SCF binding and KIT dimerization. By targeting KIT, barzolvolimab has been shown to inhibit mast cell activity and decrease mast cell numbers, which we believe could provide potential clinical benefit in mast cell related diseases.
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.
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.
In November 2023, we reported that barzolvolimab achieved the primary efficacy endpoint in the ongoing Phase 2 CSU 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. We are currently planning Phase 3 studies in CSU which are expected to initiate in summer 2024.
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 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.
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.
Competitors may use this publicly available information to gain knowledge regarding the progress of clinical development programs as well as clinical trial design. 14 Table of Contents Marketing Approval Assuming successful completion of the required clinical testing, the results of the preclinical and clinical studies, together with detailed information relating to the product’s pharmacology, chemistry, manufacture, controls and proposed labeling, among other things, are submitted to the FDA as part of an NDA or BLA requesting approval to market the product for one or more indications.
Marketing Approval Assuming successful completion of the required clinical testing, the results of the preclinical and clinical studies, together with detailed information relating to the product’s pharmacology, chemistry, manufacture, controls and proposed labeling, among other things, are submitted to the FDA as part of an NDA or BLA requesting approval to market the product for one or more indications.
The FDA has issued several guidance documents outlining an approach to review and approval of biosimilars. Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, can be shown through analytical studies, animal studies, and a clinical study or studies.
Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, can be shown through analytical studies, animal studies, and a clinical study or studies.
Patients will be randomly assigned on a 1:1:1 ratio to receive barzolvolimab injections of 150 mg Q4W after an initial loading dose of 450 mg, 300 mg Q4W after an initial loading dose of 450 mg, or placebo during a 24‑week Treatment Phase.
Approximately 120 patients will be randomly assigned on a 1:1:1 ratio to receive subcutaneous injections of barzolvolimab at either 150 or 300 mg or placebo every 4 weeks after an initial loading dose of 450 mg or placebo during a 16-week placebo-controlled treatment phase.
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.
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.
Whether or not we obtain FDA approval for a product, we 18 Table of Contents need to obtain the necessary approvals by the comparable regulatory authorities of foreign countries before we can commence clinical trials or marketing of the product in those countries.
Whether or not we obtain FDA approval for a product, we need to obtain the necessary approvals by the comparable regulatory authorities of foreign countries before we can commence clinical trials or marketing of the product in those countries. The approval process varies from country to country and can involve additional product testing and additional administrative review periods.
We have the capability to provide current and future market insights to our research and development organization regarding our potential drug candidates.
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 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 and oncology.
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.
This could prevent the product’s widespread use, require its withdrawal from the market or expose us to liability. The FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the patients are being exposed to an unacceptable health risk.
The FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the patients are being exposed to an unacceptable health risk.
Most AEs were mild or moderate in severity and resolved while on study. The most common treatment emergent adverse events were hair color changes, COVID-19, headache, neutropenia and urinary tract infections (UTIs). UTIs and COVID-19 were reported as unrelated to treatment. Generally transient, asymptomatic and mild changes in hematologic parameters were observed, consistent with observations from prior studies.
Barzolvolimab was well tolerated. Most adverse events were mild or moderate in severity and resolved while on study. The most common treatment emergent adverse events were hair color changes, COVID-19, headache, neutropenia and urinary tract infections (UTIs). UTIs and COVID-19 were reported as unrelated to treatment.
In order to secure coverage and reimbursement for any drug that might be approved for sale, we need to conduct analyses and pharmaco-economic studies in order to demonstrate the incremental medical benefit over and above the generally-accepted standard of care and cost-effectiveness of the drug.
In order to secure coverage and reimbursement for any drug that might be approved for sale, we need to conduct analyses and pharmaco-economic studies in order to demonstrate the incremental value over and above the currently available treatment options.
Even if favorable coverage and reimbursement status is attained for one or more drugs for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.
Prescription Drug Afforability Boards) which could further restrict the ability to freely price drugs and/or curb utilization in the U.S. Even if favorable coverage and reimbursement status is attained for one or more drugs for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.
The FDA maintains and exercises oversight authority throughout the clinical trial process. A product’s safety and effectiveness in one clinical trial is not necessarily indicative of its safety and effectiveness in another clinical trial. Moreover, we may not discover all potential problems with a product even after completing clinical trials on it.
A product’s safety and effectiveness in one clinical trial is not necessarily indicative of its safety and effectiveness in another clinical trial. Moreover, we may not discover all potential problems with a product even after completing clinical trials on it. Some of our products and technologies have undergone only preclinical testing.
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: In November 2023, we announced that our Phase 2 study in chronic spontaneous urticaria (CSU) achieved the primary efficacy endpoint (statistically significant mean change from baseline to week 12 of urticaria activity score compared to placebo) and was well tolerated.
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.
Based on the positive results reported in urticaria, we expanded development of barzolvolimab into additional indications where mast cells are believed to play an important role.
Based on the positive results reported in urticaria, we expanded development of barzolvolimab into additional indications where mast cells are believed to play an important role. We are conducting ongoing Phase 2 studies in eosinophilic esophagitis (EoE), prurigo nodularis (PN) and atopic dermatitis (AD).
Risk Factors.” 1 Table of Contents 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.
Risk Factors.” 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. KIT is expressed in a variety of cells, including mast cells, and its activation by its ligand SCF regulates mast cell growth, differentiation, survival, chemotaxis and degranulation.
As we expected, and consistent with previous findings with KIT blocking antibodies, we were pleased to report in December 2022, that during this recovery period spermatogenesis fully recovered in all male animals as measured by both sperm count and motility. The final histologic analysis and study report were completed in early 2023 and were consistent with previously reported results.
Due to the very high concentrations of barzolvolimab at the end of dosing, the recovery period was approximately one year. As we expected, and consistent with previous findings with KIT blocking antibodies, we were pleased to report in December 2022, that during this recovery period spermatogenesis fully recovered in all male animals as measured by both sperm count and motility.
Some of our products and technologies have undergone only preclinical testing. As a result, we do not know whether they are safe or effective for humans. Also, regulatory authorities may decide, contrary to our findings, that a product is unsafe or not as effective in actual use as its clinical trial results indicated.
As a result, we do not know whether they are safe or effective for humans. Also, regulatory authorities may decide, contrary to our findings, that a product is unsafe or not as effective in actual use as its clinical trial results indicated. This could prevent the product’s widespread use, require its withdrawal from the market or expose us to liability.
EoE, the most common type of eosinophilic gastrointestinal disease, is a chronic inflammatory disease of the esophagus characterized by the infiltration of eosinophils. This chronic inflammation can result in trouble swallowing, chest pain, vomiting and impaction of food in the esophagus, a medical emergency.
This chronic inflammation can result in trouble swallowing, chest pain, vomiting and impaction of food in the esophagus, a medical emergency.
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.
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.
Approximately 180 patients in 2 cohorts (differentiated by CIndU subtype) including 90 patients with cold urticaria and 90 patients with symptomatic dermographism will be 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 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.
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.
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.
A Phase 2 study in chronic inducible urticaria (CIndU) is currently enrolling patients and we expect to report data from this study in the second half of 2024; - Prurigo Nodularis (PN): In November 2023, we reported positive data from a Phase 1b study in PN that supports further development of barzolvolimab in this indication and we are currently planning for the initiation of a Phase 2 study in PN in early 2024; - Eosinophilic Esophagitis (EoE): A Phase 2 study in EoE was initiated in June 2023 and enrollment is ongoing. ● Our next generation bispecific antibody platform to support pipeline expansion with additional candidates for inflammatory diseases and oncology.
Patients 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.
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.
Drugs and biologics may be promoted only for the approved indications and in accordance with the provisions of the approved label.
The FDA, the Office of the Inspector General of Health and Human Services and other agencies actively enforce the laws and regulations prohibiting the promotion of off label uses, and a company that is found to have improperly promoted off label uses may be subject to significant liability. 17 Table of Contents Biosimilars and Exclusivity The Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) created an abbreviated approval pathway for biological products shown to be highly similar to, or interchangeable with, an FDA-licensed reference biological product.
The FDA, the Office of the Inspector General of Health and Human Services and other agencies actively enforce the laws and regulations prohibiting the promotion of off label uses, and a company that is found to have improperly promoted off label uses may be subject to significant liability.
Mast cells through their interactions with sensory neurons and other immune cells are believed to play an important role in amplifying chronic itch and neuroinflammation, both of which are a hallmark of PN. There is currently only one FDA approved therapy for PN, representing an area of significant unmet need.
PN is a chronic skin disease characterized by the development of hard, intensely itchy (pruritic) nodules on the skin. Mast cells through their interactions with sensory neurons and other immune cells are believed to play an important role in amplifying chronic itch and neuroinflammation, both of which are a hallmark of PN.
Any manufacturing failures or compliance issues at contract manufacturers could cause delays in our Phase 1 and Phase 2 clinical studies for these drug candidates. 10 Table of Contents 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 will allow for potential self-administration at home setting versus the need for intravenous dosing in a hospital or clinic setting.
As a standard part of toxicology studies, some animals from each group continued to be observed through a recovery period to understand the reversibility of any adverse findings. Due to the very high concentrations of barzolvolimab at the end of dosing, the recovery period was approximately one year.
The only clinically adverse finding at the completion of dosing was a profound impact on spermatogenesis, an expected and well understood effect of KIT inhibition. As a standard part of toxicology studies, some animals from each group continued to be observed through a recovery period to understand the reversibility of any adverse findings.
Industry sources estimate there are approximately 154,000 patients in the United States with PN who have undergone treatment within the last 12 months and, of these, approximately 75,000 would be biologic-eligible. We have completed a Phase 1b multi-center, randomized, double-blind, placebo-controlled intravenous study in PN.
There is currently only one FDA approved therapy for PN, representing an area of significant unmet need. Industry sources estimate there are approximately 154,000 patients in the United States with PN who have undergone treatment within the last 12 months and, of these, approximately 75,000 would be biologic-eligible.
We continue to assess potential opportunities for barzolvolimab in other diseases where mast cells play an important role, such as dermatologic, respiratory, allergic, gastrointestinal and ophthalmic conditions. Chronic Spontaneous Urticaria (CSU) 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.
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.
We incurred research and development expenses of $118.0 million, $82.3 million and $53.3 million during the years ended December 31, 2023, 2022 and 2021, respectively. We anticipate that a significant portion of our operating expenses will continue to be related to research and development in 2024 as we continue to advance our drug candidates through clinical development.
We incurred research and development expenses of $163.6 million, $118.0 million and $82.3 million during the years ended December 31, 2024, 2023 and 2022, respectively.
We also rely on CMOs for labeling and storage for studies inside and outside the U.S. 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.
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.

… 91 more changes not shown on this page.

Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

104 edited+15 added−9 removed282 unchanged
Biggest changeFor 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; ● 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. 37 Table of Contents Accordingly, although there can be no assurance that we will undertake or successfully complete any transactions of the nature described above, any transactions that we do complete could have a material adverse effect on our business, results of operations, financial condition and prospects.
Biggest changeFor 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.
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 legislation or administrative action, either in the United States or in other countries.
Physicians 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; ● 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.
Physicians 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.
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 ● 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 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.
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 three 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.
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.
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; ● 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; 44 Table of Contents ● 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; 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.
We believe that our immunotherapy technology portfolio may offer opportunities to develop immunotherapeutic drugs that treat a variety of cancers and inflammatory and infectious diseases by stimulating a patient’s immune system against those diseases.
We believe that our immunotherapy technology portfolio may offer opportunities to develop immunotherapeutic drugs that treat a variety of inflammatory and infectious diseases by stimulating a patient’s immune system against those diseases.
Any unplanned event, such as flood, fire, explosion, earthquake, extreme weather condition, power shortage, telecommunication failure or other natural or manmade accidents or incidents that result in us being unable to fully utilize our facilities, or the manufacturing facilities of our third-party CMOs, could severely disrupt our operations and have a material adverse effect on our business, results of operations, financial condition and prospects.
Any unplanned event, such as flood, fire, explosion, earthquake, extreme weather condition, power shortage, telecommunication failure or other natural or manmade accidents or incidents that result in us being unable to fully utilize our facilities, or the manufacturing facilities of our third-party CDMOs, could severely disrupt our operations and have a material adverse effect on our business, results of operations, financial condition and prospects.
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. 26 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. 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.
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. 30 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. 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.
CMOs may encounter difficulties in scaling up production, including problems involving supply chain, raw material suppliers, production yields, technical difficulties, scaled-up product characteristics, quality control and assurance, shortage of qualified personnel, capacity constraints, changing priorities within the CMOs, compliance with FDA and foreign regulations, environmental compliance, production costs and development of advanced manufacturing techniques and process controls.
CDMOs may encounter difficulties in scaling up production, including problems involving supply chain, raw material suppliers, production yields, technical difficulties, scaled-up product characteristics, quality control and assurance, shortage of qualified personnel, capacity constraints, changing priorities within the CDMOs, compliance with FDA and foreign regulations, environmental compliance, production costs and development of advanced manufacturing techniques and process controls.
Our computer systems and those of our CROs, CMOs, 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.
Failure to achieve this level of supply can jeopardize and prevent the successful commercialization of the drug. Our leading drug candidates require specialized manufacturing capabilities and processes. We may face difficulty in securing commitments from U.S. and foreign contract manufacturers as these manufacturers could be unwilling or unable to accommodate our needs.
Failure to achieve this level of supply can jeopardize and prevent the successful commercialization of the drug. Our leading drug candidates require specialized manufacturing capabilities and processes. We may face difficulty in securing commitments from U.S. and foreign CDMOs as these manufacturers could be unwilling or unable to accommodate our needs.
The commercial manufacturing facility would also need to be licensed for the production of our drug candidates by the FDA and meet other regulatory standards. We therefore work with CMOs under established manufacturing arrangements that comply with the FDA’s requirements and other regulatory standards, although there is no assurance that the manufacturing will be successful.
The commercial manufacturing facility would also need to be licensed for the production of our drug candidates by the FDA and meet other regulatory standards. We therefore work with CDMOs under established manufacturing arrangements that comply with the FDA’s requirements and other regulatory standards, although there is no assurance that the manufacturing will be successful.
Such third-party collaborators: ● may not perform its 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; ● 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; 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.
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 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 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.
Risks inherent in conducting international clinical trials include, but are not limited to: ● foreign regulatory requirements that could burden or limit our ability to conduct our clinical trials; ● administrative burdens of conducting clinical trials under multiple foreign regulatory schema; ● foreign currency fluctuations which could negatively impact our financial condition since certain payments are paid in local currencies; 43 Table of Contents ● manufacturing, customs, shipment and storage requirements; ● cultural differences in medical practice and clinical research; and ● diminished protection of intellectual property in some countries.
Risks inherent in conducting international clinical trials include, but are not limited to: ● foreign regulatory requirements that could burden or limit our ability to conduct our clinical trials; ● administrative burdens of conducting clinical trials under multiple foreign regulatory schema; ● foreign currency fluctuations which could negatively impact our financial condition since certain payments are paid in local currencies; ● manufacturing, customs, shipment and storage requirements; ● cultural differences in medical practice and clinical research; and ● diminished protection of intellectual property in some countries.
If we cannot enroll patients as needed, our costs may increase, or we may be forced to delay or terminate testing for a product. 27 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. 29 Table of Contents We may have delays in commencing, enrolling and completing our clinical trials, and we may not complete them at all.
In pharmaceutical development, many drugs that initially show promise in early-stage testing are later found to cause side effects that prevent further development of the drug. Currently marketed therapies for the treatment of cancer and inflammatory diseases are generally limited to some extent by their toxicity.
In pharmaceutical development, many drugs that initially show promise in early-stage testing are later found to cause side effects that prevent further development of the drug. Currently marketed therapies for the treatment of inflammatory diseases are generally limited to some extent by their toxicity.
If our future drugs fail to achieve market acceptance, we will not be able to generate significant revenues and may never achieve profitability. 31 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 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 we are not able to maintain regulatory compliance, we may not be permitted to market our future products and our business may suffer. 32 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. 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.
Any of these factors could have a material adverse effect on the sales of any drug candidates that we may commercialize in the future. 33 Table of Contents Failure to obtain regulatory approvals in foreign jurisdictions will prevent us from marketing our products internationally.
Any of these factors could have a material adverse effect on the sales of any drug candidates that we may commercialize in the future. 35 Table of Contents Failure to obtain regulatory approvals in foreign jurisdictions will prevent us from marketing our products internationally.
Any manufacturing failures, supply chain delays or compliance issues at our Fall River facility or at our CMOs could cause delays in our clinical studies for our drug candidates. We may need to rely on third-party collaborators to develop and commercialize companion diagnostic tests for our drug candidates.
Any manufacturing failures, supply chain delays or compliance issues at our Fall River facility or at our CDMOs could cause delays in our clinical studies for our drug candidates. We may need to rely on third-party collaborators to develop and commercialize companion diagnostic tests for our drug candidates.
If such third-party collaborators fail to develop, obtain regulatory approval or commercialize the companion diagnostic test, we may not be able to enter into arrangements with another diagnostic company to obtain supplies of an alternative diagnostic test for use 36 Table of Contents in connection with the development and commercialization of our drug candidates or do so on commercially reasonable terms, which could adversely affect and/or delay the development or commercialization of our drug candidates.
If such third-party collaborators fail to develop, obtain regulatory approval or commercialize the companion diagnostic test, we may not be able to enter into arrangements with another diagnostic company to obtain supplies of an alternative diagnostic test for use in connection with the development and commercialization of our drug candidates or do so on commercially reasonable terms, which could adversely affect and/or delay the development or commercialization of our drug candidates.
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.
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.
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.
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.
We or our third-party collaborators may also experience 29 Table of Contents delays in developing a sustainable, reproducible and scalable manufacturing process or transferring that process to commercial partners or negotiating insurance reimbursement for such companion diagnostic, all of which may prevent us from completing our clinical trials or commercializing our drugs on a timely or profitable basis, if at all.
We or our third-party collaborators may also experience delays in developing a sustainable, reproducible and scalable manufacturing process or transferring that process to commercial partners or negotiating insurance reimbursement for such companion diagnostic, all of which may prevent us from completing our clinical trials or commercializing our drugs on a timely or profitable basis, if at all.
Although we try to ensure that our employees and consultants do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or our employees, consultants or independent contractors have inadvertently or otherwise used or disclosed intellectual property, including trade secrets or other 41 Table of Contents proprietary information, of a former employer or other third parties.
Although we try to ensure that our employees and consultants do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or our employees, consultants or independent contractors have inadvertently or otherwise used or disclosed intellectual property, including trade secrets or other proprietary information, of a former employer or other third parties.
Any unused annual limitation may be carried over to later years, and the amount of the limitation may, under certain circumstances, be subject to adjustment if the fair value of our net assets is determined to be below or in excess of the tax basis of such 47 Table of Contents assets at the time of the ownership change, and such unrealized loss or gain is recognized during the five-year period after the ownership change.
Any unused annual limitation may be carried over to later years, and the amount of the limitation may, under certain circumstances, be subject to adjustment if the fair value of our net assets is determined to be below or in excess of the tax basis of such assets at the time of the ownership change, and such unrealized loss or gain is recognized during the five-year period after the ownership change.
The key difficulty in qualifying more than one source for each product is the duplicated time and expense in doing so without the potential to mitigate these costs if the secondary source is never utilized. Further, contract manufacturers must operate in compliance with cGMP and failure to do so could result in, among other things, the disruption of product supplies.
The key difficulty in qualifying more than one source for each product is the duplicated time and expense in doing so without the potential to mitigate these costs if the secondary source is never utilized. Further, CDMOs must operate in compliance with cGMP and failure to do so could result in, among other things, the disruption of product supplies.
In addition, when used in combination with other marketed therapies, our drug candidates may exacerbate adverse events associated with the marketed therapy. 28 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. 30 Table of Contents Our drug candidates, including barzolvolimab, are monoclonal antibodies, which are biologics.
Our inability to commercialize a drug candidate would impair our ability to earn future revenues. 25 Table of Contents Premarket review of our product candidates by the FDA and/or other regulatory authorities is a lengthy and uncertain process and approval may be delayed, limited or denied, any of which would adversely affect our ability to generate operating revenues.
Our inability to commercialize a drug candidate would impair our ability to earn future revenues. Premarket review of our product candidates by the FDA and/or other regulatory authorities is a lengthy and uncertain process and approval may be delayed, limited or denied, any of which would adversely affect our ability to generate operating revenues.
Additionally, even after granting approval, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for such drug will be subject to extensive and ongoing regulatory requirements.
Additionally, after approval, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for such drug will be subject to extensive and ongoing regulatory requirements.
Moreover, achieving and sustaining compliance with applicable federal and state privacy, security and fraud laws may prove costly. 45 Table of Contents Compliance with laws and regulations pertaining to the privacy and security of health information may be time consuming, difficult and costly, particularly in light of increased focus on privacy issues in countries around the world, including the U.S. and the EU.
Moreover, achieving and sustaining compliance with applicable federal and state privacy, security and fraud laws may prove costly. Compliance with laws and regulations pertaining to the privacy and security of health information may be time consuming, difficult and costly, particularly in light of increased focus on privacy issues in countries around the world, including the U.S. and the EU.
The confidentiality, collection, use and disclosure of personal data, including clinical trial patient-specific information, are subject to governmental regulation generally in the country that the personal data were collected or used.
The confidentiality, collection, use and disclosure of personal data, including clinical trial patient-specific information, are subject to governmental regulation generally in the country that the personal data was collected or used.
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.
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.
Our internal computer systems, or those of our CROs, CMOs, or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our drug development programs.
Our internal computer systems, or those of our CROs, CDMOs, or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our drug development programs.
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.
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.
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 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 45 Table of Contents dialysis, antidotes, or other treatments, if known.
These risks become more acute as we scale up for commercial quantities, where reliable sources of drug substance and drug product become critical to commercial success. The commercial viability of any of our drug candidates, if approved, will depend on the ability of our contract manufacturers to produce drug substance and drug product on a large scale.
These risks become more acute as we scale up for commercial quantities, where reliable sources of drug substance and drug product become critical to commercial success. The commercial viability of any of our drug candidates, if approved, will depend on the ability of our CDMOs to produce drug substance and drug product on a large scale.
To the extent that any disruption or security breach were to result in a loss of or damage to our data or 38 Table of Contents applications or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development or commercialization of our drug candidates could be delayed.
To the extent that any disruption or security breach were to result in a loss of or damage to our data or applications or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development or commercialization of our drug candidates could be delayed.
For example, our operations are located primarily on the east coast 48 Table of Contents of the United States, and any adverse weather event or natural disaster, such as a hurricane or heavy snowstorm, could have a material adverse effect on a substantial portion of our operations.
For example, our operations are located primarily on the east coast of the United States, and any adverse weather event or natural disaster, such as a hurricane or heavy snowstorm, could have a material adverse effect on a substantial portion of our operations.
While we believe that there is currently sufficient capacity worldwide for the production of our potential products through CMOs, establishing long-term relationships with CMOs and securing multiple sources for the necessary quantities of clinical and commercial materials required can be a challenge due to increasing industry demand for CMO services.
While we believe that there is currently sufficient capacity worldwide for the production of our potential products through CDMOs, establishing long-term relationships with CDMOs and securing multiple sources for the necessary quantities of clinical and commercial materials required can be a challenge due to increasing industry demand for CDMO services.
The impacts of a potential resurgence of COVID-19 could pose the risk that we or our employees, suppliers, customers and others may be restricted or prevented from conducting business activities for indefinite or intermittent periods of time, including as a result of employee health and safety concerns, shutdowns, shelter in place orders, travel restrictions and other actions and restrictions that may be prudent or required by governmental authorities.
A potential resurgence of an epidemic could pose the risk that we or our employees, suppliers, customers and others may be restricted or prevented from conducting business activities for indefinite or intermittent periods of time, including as a result of employee health and safety concerns, shutdowns, shelter in place orders, travel restrictions and other actions and restrictions that may be prudent or required by governmental authorities.
Moreover, a product recall, if required, could generate substantial 39 Table of Contents negative publicity about our products and business and inhibit or prevent development of our drug candidates and, if approval is obtained, commercialization of our future drugs.
Moreover, a product recall, if required, could generate substantial negative publicity about our products and business and inhibit or prevent development of our drug candidates and, if approval is obtained, commercialization of our future drugs.
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.
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.
We have not undertaken a study to assess whether an ownership change or multiple ownership changes have occurred for (i) acquired businesses with NOLs prior to being acquired by the Company, (ii) the Company on the state level, (iii) the Company since March 2015 or (iv) research and development credits.
We have not undertaken a study to assess whether an ownership change or multiple ownership changes have occurred for (i) acquired businesses with NOLs prior to being acquired by the Company, (ii) the Company on the state level, (iii) the Company since June 2024 or (iv) research and development credits.
During the years ended December 31, 2023, 2022 and 2021, we incurred $32.4 million, $23.8 million and $8.0 million in clinical trial expense and $24.1 million, $4.5 million and $1.7 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, 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.
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 $1.4 billion as of December 31, 2023.
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.
Side effects from biologics may include hypersensitivity; severe reactions such as anaphylaxis or cytokine release syndrome; immune-mediated adverse reactions that may occur in any organ system or tissue, such as pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic reactions; as well as infusion-related reactions, cellulitis, sepsis, pneumonia, urinary tract infection, fatigue, rash, and diarrhea.
Side effects from biologics may include but are not limited to hypersensitivity; severe reactions such as anaphylaxis or cytokine release syndrome; immune-mediated adverse reactions that may occur in any organ system or tissue, such as pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic reactions; as well as infusion-related reactions, cellulitis, sepsis, pneumonia, urinary tract infection, fatigue, rash, and diarrhea.
The approval of a companion diagnostic as part of the product label will limit the use of the drug candidate to only 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 31 Table of Contents those patients who express the specific biomarker it was developed to detect.
Drugs designated as breakthrough therapies by the FDA may also be eligible for accelerated approval if the relevant criteria are met. 42 Table of Contents Designation as a breakthrough therapy is within the discretion of the FDA.
Drugs designated as breakthrough therapies by the FDA may also be eligible for accelerated approval if the relevant criteria are met. Designation as a breakthrough therapy is within the discretion of the FDA.
Risks Related to Business Operations ● Risks related to strategic transactions. 22 Table of Contents ● 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. ● Risks related to hazardous materials. ● Risks related to product liability claims.
We have incurred operating losses of $154.5 million, $115.2 million and $71.2 million during 2023, 2022 and 2021, respectively, and expect to incur an operating loss in 2024 and beyond. We believe that operating losses will continue in 2024 and beyond because we are planning to incur significant costs associated with the development of our drug candidates.
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.
Until, and unless, we complete clinical trials and other development activity, and receive approval from the FDA and other regulatory authorities, for our drug candidates, we cannot sell our drugs and 23 Table of Contents will not have product revenue.
Until, and unless, we complete clinical trials and other development activity, and receive approval from the FDA and other regulatory authorities, for our drug candidates, we cannot sell our drugs and will not have product revenue.
Use of third-party manufacturers also limits our control over and ability to monitor the manufacturing process. As a result, we may not be able to detect a variety of problems that may arise and may face additional costs in the process of interfacing with and monitoring the progress of our contract manufacturers.
Use of CDMOs also limits our control over and ability to monitor the manufacturing process. As a result, we may not be able to detect a variety of problems that may arise and may face additional costs in the process of interfacing with and monitoring the progress of our CDMOs.
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. In October 2007, June 2009, December 2009 and December 2013, 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. 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.
Disease outbreaks, epidemics and pandemics, including COVID-19, 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.
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.
We face risks related to health epidemics and outbreaks, including COVID-19, which could significantly disrupt our preclinical studies and clinical trials.
We face risks related to health epidemics and outbreaks, which could significantly disrupt our preclinical studies and clinical trials.
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. ● We may enter collaboration agreements for our lead drug candidates that may not meet our expectations.
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.
As of December 31, 2023, we had cash, cash equivalents and marketable securities of $423.6 million. During the next twelve months and beyond, we will take further steps to raise additional capital to fund our long-term liquidity needs.
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.
A future disease outbreak, epidemic or pandemic adversely affects our business, financial condition, results of operations and growth prospects. The future progression of the COVID-19 epidemic and its effects on our business and operations are uncertain.
A future disease outbreak, epidemic or pandemic adversely affects our business, financial condition, results of operations and growth prospects. The progression of an epidemic and the related effects on our business and operations are uncertain.
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. 34 Table of Contents Risks Related to Reliance on Third Parties We rely on third parties to plan, conduct and monitor our clinical tests, and their failure to perform as required would interfere with our product development.
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.
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. 35 Table of Contents There can be no assurances that contract manufacturers will be able to meet our timetable and requirements.
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.
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, 2023, we had net operating loss carryforwards, or NOLs, of approximately $618.4 million for federal income tax purposes, and $1.0 billion 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, 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.
We cannot predict our success in hiring or retaining the personnel we require for continued growth. 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.
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.
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.
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.
We also rely on CMOs for labeling and storage for studies inside and outside the US. In order for us to establish our own commercial manufacturing facility, we would require substantial additional funds and would need to make facility modifications, hire and retain significant additional personnel and comply with extensive cGMP regulations applicable to such a facility.
In order for us to establish our own commercial manufacturing facility, we would require substantial additional funds and would need to make facility modifications, hire and retain significant additional personnel and comply with extensive cGMP regulations applicable to such a facility.
If we are unable to raise the funds necessary to meet our liquidity needs, we may have to delay or discontinue the development of one or more programs, discontinue or delay ongoing or anticipated clinical trials, discontinue or delay our commercial manufacturing efforts, discontinue or delay our efforts to expand into additional indications for our drug product candidates, license out programs earlier than expected, raise funds at significant discount or on other unfavorable terms, if at all, or sell all or part of our business. 24 Table of Contents Our stockholders may be subject to substantial dilution if we elect to pay future milestone consideration to the former Kolltan stockholders in shares of common stock.
If we are unable to raise the funds necessary to meet our liquidity needs, we may have to delay or discontinue the development of one or more programs, discontinue or delay ongoing or anticipated clinical trials, discontinue or delay our commercial manufacturing efforts, discontinue or delay our efforts to expand into additional indications for our drug product candidates, license out programs earlier than expected, raise funds at significant discount or on other unfavorable terms, if at all, or sell all or part of our business.
Should the cost, delivery and quality of clinical materials manufactured by us in our Fall River facility or supplied by contract manufacturers vary to our disadvantage, our business operations could suffer significant harm. We have limited experience in commercial manufacturing.
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.
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.
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.
We routinely enter into consulting agreements with our scientific and clinical collaborators and advisors, key opinion leaders and heads of academic departments in the ordinary course of our business.
We routinely enter into consulting agreements with our scientific and clinical collaborators and advisors, key opinion leaders and heads of academic departments in the ordinary course of our business. We also enter into contractual agreements with physicians and institutions who recruit patients into our clinical trials on our behalf in the ordinary course of our business.
This could disrupt our ability to operate our business, including producing drug product and administering our preclinical and clinical studies. In addition, fluctuations in demand and other implications associated with the COVID-19 pandemic have resulted in, and could continue resulting in, certain supply chain constraints and challenges.
This could disrupt our ability to operate our business, including producing drug product and administering our preclinical and clinical studies. In addition, fluctuations in demand and other implications associated with an epidemic could result in supply chain constraints and challenges.
In anticipation of FDA approval of these products, we will need to make substantial investments to establish sales, marketing, quality control, regulatory compliance capabilities and commercial manufacturing alliances. These investments will increase if and when any of these drug candidates receive FDA approval. We cannot predict how quickly our lead drug candidates will progress through the regulatory approval process.
We expect to spend substantial funds to continue the research and development testing of our drug candidates. In anticipation of FDA approval of these products, we will need to make substantial investments to establish sales, marketing, quality control, regulatory compliance capabilities and commercial manufacturing alliances. These investments will increase if and when any of these drug candidates receive FDA approval.
Subsequent ownership changes, as defined in Section 382, could further limit the amount of net operating loss carryforwards and research and development credits that can be utilized annually to offset future taxable income.
Subsequent ownership changes, as defined in Section 382, could further limit the amount of net operating loss carryforwards and research and development credits that can be utilized annually to offset future taxable income. Refer to Note 16, “Income Taxes,” in the accompanying notes to the financial statements for additional discussion on income taxes.
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.
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.
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.
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.
We rely on third parties to conduct a significant portion of our clinical development activities. These activities include clinical patient recruitment and observation, clinical trial monitoring, clinical data management and analysis, safety monitoring and project management.
These activities include clinical patient recruitment and observation, clinical trial monitoring, clinical data management and analysis, safety monitoring and project management. We conduct project management and medical and safety monitoring in-house for some of our programs and rely on third parties for the remainder of our clinical development activities.
Our success depends upon our ability to develop and maintain a competitive position in the product categories and technologies on which we focus. Many of our competitors have greater capabilities, experience and financial resources than we do. Competition is intense and is expected to increase as new products enter the market and new technologies become available.
Many of our competitors have greater capabilities, experience and financial resources than we do. Competition is intense and is expected to increase as new products enter the market and new technologies become available.
From January 2022 through December 2023, the market price of our common stock has fluctuated from a high of $48.40 per share in the first quarter of 2023, to a low of $19.85 per share in the second quarter of 2022.
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.

… 48 more changes not shown on this page.

Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

5 edited+1 added−1 removed5 unchanged
Biggest changeFor certain vendors, we request System and Organization Controls (SOC) reports or similar documents to provide assurance that the vendors have audited practices or practices in keeping with our legal requirements even if SOC audit documentation does not exist.
Biggest changeWe have a self-attestation form to assess cybersecurity readiness that is sent to select vendors based on a risk assessment. For certain vendors, we request System and Organization Controls (SOC) reports or similar documents to provide assurance that the vendors have audited practices or practices in keeping with our legal requirements even if SOC audit documentation does not exist.
IT 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.
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.
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.
Governance; Board Oversight Our Audit Committee is responsible for reviewing our information security programs, including cybersecurity. IT 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.
We 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.
We also engage separate third parties to provide penetration testing, risk consulting, cybersecurity incident assessment and forensics, as necessary and in addition to IT’s internal risk assessment processes. We work with many companies that provide hosted software or support for software systems.
We also engage separate third parties to provide penetration testing, risk consulting, cybersecurity incident assessment and forensics, as necessary and in addition to IT’s internal risk assessment processes. We work with many companies that provide hosted software or support for software systems. It is important for these companies to also have effective cybersecurity measures to protect data and systems.
Removed
It is important for these 50 Table of Contents companies to also have effective cybersecurity measures to protect data and systems. We have a self-attestation form to assess cybersecurity readiness that is sent to select vendors based on a risk assessment.
Added
Our IT head has more than 25 years of IT experience in the biopharmaceutical industry where she has been responsible for technology leadership and digital transformation across core operations.

Item 2. Properties

Properties — owned and leased real estate

2 edited+0 added−0 removed0 unchanged
Biggest changePROPERTIES As of December 31, 2023, 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 2025 (1) Fall River, Massachusetts 33,900 Manufacturing, Office and Laboratory July 2025 (2) New Haven, Connecticut 17,700 Office and Laboratory April 2025 (1) Lease includes one renewal option of two years followed by one renewal option of three years.
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.
(2) Lease includes one renewal option of two years followed by 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. ​ 51 Table of Contents PART II
(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

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

6 edited+0 added−0 removed0 unchanged
Biggest changeBenchmark TR Index ​ $ 100 ​ $ 131 ​ $ 159 ​ $ 200 ​ $ 161 ​ $ 203 NASDAQ Pharmaceutical (Subsector) Index ​ $ 100 ​ $ 115 ​ $ 127 ​ $ 157 ​ $ 175 ​ $ 182 ​ ​ Item 6. [Reserved] ​ 52 Table of Contents
Biggest changeBenchmark 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
The comparison assumes investment of $100 on December 31, 2018 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, 2019 in our common stock and in each of the indices and, in each case, assumes reinvestment of all dividends.
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, 2024, there were approximately 133 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 14, 2025, there were approximately 136 shareholders of record of our common stock.
AND PEER GROUP INDICES The graph below compares the cumulative total stockholder return on the common stock for the period from December 31, 2018 through December 31, 2023, 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, 2019 through December 31, 2024, with the cumulative return on (i) NASDAQ U.S. Benchmark TR Index and (ii) NASDAQ Pharmaceutical (Subsector) Index.
On February 14, 2024 the closing price of our common stock, as reported by NASDAQ, was $36.26 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 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.
The points on the graph are as of December 31 of the year indicated. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ 2018 2019 2020 2021 2022 2023 Celldex Therapeutics, Inc. ​ $ 100 ​ $ 75 ​ $ 590 ​ $ 1,302 ​ $ 1,501 ​ $ 1,336 NASDAQ U.S.
The 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.

Item 6. [Reserved]

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

1 edited+0 added−0 removed0 unchanged
Biggest changeItem 6. ​ [Reserved] ​ 52 Item 7. ​ Management’s Discussion and Analysis of Financial Condition and Results of Operations ​ 53 Item 7A. ​ Quantitative and Qualitative Disclosures About Market Risk ​ 70 Item 8. ​ Financial Statements and Supplementary Data ​ 71
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

Item 7. Management's Discussion & Analysis

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

94 edited+54 added−24 removed100 unchanged
Biggest changeMean reduction from baseline in UAS7 at week 24 was 80% in the 1.5 mg/kg dose group (n=7), 70% in the 3.0 mg/kg dose group (n=6) and 77% in the 4.5 mg/kg dose group (n=7). ● Complete response (UAS7=0) at week 12 was 57% in the 1.5 mg/kg dose group, 44% in the 3.0 mg/kg dose group and 67% in the 4.5 mg/kg dose group.
Biggest changePhase 1 CSU: Summary of Clinical Activity Assessments at Week 12 & 24 ​ 4.5 mg/kg Q8 3.0 mg/kg Q8 1.5 mg/kg Q4 Mean Reduction Baseline UAS7; % at Week 12 82% (n=9) 67% (n=9) 67% (n=8) Mean Reduction Baseline UAS7; % at Week 24 77% (n=7) 70% (n=6) 80% (n=7) UAS7=0 (Complete Control); % at Week 12 67% 44% 57% UAS7=0 (Complete Control); % at Week 24 43% 67% 57% UAS7≤6 (Well-controlled); % at Week 12 67% 67% 57% UAS7≤6 (Well-controlled); % at Week 24 57% 67% 57% UCT ≥ 12 (Well-controlled); % at Week 12 89% 63% 75% UCT ≥ 12 (Well-controlled); % at Week 24 67% 67% 75% ​ During post-treatment follow up, 71% (10 of 14) of patients who had been treated with doses greater than or equal to 1.5 mg/kg and had a complete response (UAS7=0) at week 12, remained urticaria free at week 24 (patients received last dose of barzolvolimab at week 8).
We completed a Phase 1b open label clinical trial in CIndU in patients refractory to antihistamines, conducted in Germany. This study was designed to evaluate the safety of a single intravenous dose (3 mg/kg) of barzolvolimab in patients with cold urticaria (ColdU) or symptomatic dermographism (SD).
We completed a Phase 1b open label clinical trial in patients with CIndU refractory to antihistamines, conducted in Germany. This study was designed to evaluate the safety of a single intravenous dose (3 mg/kg) of barzolvolimab in patients with cold urticaria (ColdU) or symptomatic dermographism (SD).
Investing Activities 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.
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.
Financing Activities Net cash provided by financing activities was $218.5 million for the year ended December 31, 2023 compared to $4.1 million for the year ended December 31, 2022. The increase in net cash provided by financing activities was primarily due to an increase in net proceeds from stock issuances.
Net cash provided by financing activities was $218.5 million for the year ended December 31, 2023 compared to $4.1 million for the year ended December 31, 2022. The increase in net cash provided by financing activities was primarily due to an increase in net proceeds from stock issuances.
Patients will 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 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.
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. 58 Table of Contents ● 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.
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.
We estimate that clinical trials of the type we generally conduct are typically completed over the following timelines: ​ ​ ​ ​ ​ Estimated ​ ​ Completion Clinical Phase Period Phase 1 1 – 2 Years Phase 2 1 – 5 Years Phase 3 1 – 5 Years ​ 53 Table of Contents The duration and the cost of clinical trials may vary significantly over the life of a project as a result of differences arising during the clinical trial protocol, including, among others, the following: ● the number of patients that ultimately participate in the trial; ● the duration of patient follow-up that seems appropriate in view of results; ● the number of clinical sites included in the trials; ● the length of time required to enroll suitable patient subjects; and ● the efficacy and safety profile of the drug candidate.
We estimate that clinical trials of the type we generally conduct are typically completed over the following timelines: ​ ​ ​ ​ ​ Estimated ​ ​ Completion Clinical Phase Period Phase 1 1 – 2 Years Phase 2 1 – 5 Years Phase 3 1 – 5 Years ​ The duration and the cost of clinical trials may vary significantly over the life of a project as a result of differences arising during the clinical trial protocol, including, among others, the following: ● the number of patients that ultimately participate in the trial; ● the duration of patient follow-up that seems appropriate in view of results; ● the number of clinical sites included in the trials; ● the length of time required to enroll suitable patient subjects; and ● the efficacy and safety profile of the drug candidate.
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) ​ 2023 2022 $ % ​ ​ (In thousands) ​ ​ ​ ​ ​ Personnel ​ $ 40,121 ​ $ 32,674 ​ $ 7,447 ​ 23 % Laboratory supplies ​ 5,358 ​ ​ 6,310 ​ ​ (952) ​ (15) % Facility ​ 4,970 ​ ​ 4,764 ​ ​ 206 ​ 4 % Product development ​ 59,319 ​ ​ 32,156 ​ ​ 27,163 ​ 84 % ​ 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) ​ ​ 2023 2022 $ % ​ ​ ​ (In thousands) ​ ​ ​ ​ ​ ​ Personnel ​ $ 40,121 ​ $ 32,674 ​ $ 7,447 ​ 23 % Laboratory supplies ​ 5,358 ​ 6,310 ​ (952) (15) % Facility ​ 4,970 ​ 4,764 ​ 206 4 % Product development ​ 59,319 ​ 32,156 ​ 27,163 84 % ​ 72 Table of Contents Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes.
Omalizumab, an IgE inhibitor, provides relief for roughly half of the remaining antihistamine refractory patients. Consequently, there is a need for additional therapies. 55 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. 58 Table of Contents We have completed a Phase 1b randomized, double-blind, placebo-controlled multi-center study of barzolvolimab in CSU.
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.
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.
During the initial 8 week observation period in the 3.0 mg/kg dosing arm, an anaphylactic reaction occurred in a complicated patient with multiple comorbidities; the event fully resolved without sequelae. Generally, AEs seen during the 24-week follow-up period were consistent with comorbidities commonly observed in the PN population.
During the initial 8 week observation period in the 3.0 mg/kg dosing arm, an anaphylactic reaction occurred in a complicated patient with multiple comorbidities; the event fully resolved without sequelae. Generally, adverse events seen during the 24-week follow-up period were consistent with comorbidities commonly observed in the PN population.
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, 2023, 2022 and 2021.
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 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, 68 Table of Contents 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; and consulting, legal and other professional fees.
This randomized, double-blind, placebo-controlled, parallel group study will evaluate the efficacy and safety profile of 2 dose levels of barzolvolimab compared to placebo in approximately 120 patients with moderate to severe PN who had inadequate response to prescription topical medications, or for whom topical medications are medically inadvisable (such as concerns for safety).
This randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety profile of 2 dose levels of barzolvolimab compared to placebo in approximately 120 patients with moderate to severe PN who had inadequate response to prescription topical medications, or for whom topical medications are medically inadvisable (such as concerns for safety).
We expect personnel expenses to increase over the next twelve months as a result of additional headcount to support the expanded development of barzolvolimab. 65 Table of Contents Laboratory supplies expenses include laboratory materials and supplies, services and other related expenses incurred in the development of our technology.
We expect personnel expenses to increase over the next twelve months as a result of additional headcount to support the expanded development of barzolvolimab. Laboratory supplies expenses include laboratory materials and supplies, services and other related expenses incurred in the development of our technology.
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 69 Table of Contents sales and maturities of marketable securities of $91.7 million for the year ended December 31, 2022.
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.
Summary of Clinical Activity Assessments at Week 12 ​ 300 mg Q8W (n=51) 150 mg Q4W (n=52) 75 mg Q4W (n=53) Placebo (n=51) UAS7 Changes Baseline UAS7 (mean) 31.33 30.75 30.30 30.09 LS Mean change at Week 12 -23.87 -23.02 -17.06 -10.47 LS Mean difference from placebo (Confidence Interval, p value) -13.41 (CI: -17.47, -9.34) p -12.55 (CI:-16.56, -8.55) p -6.60 (CI:-10.71, -2.49) p=0.0017 ​ HSS7 Changes ​ ​ ​ ​ Baseline HSS7 (mean) 14.92 15.05 14.86 14.47 LS Mean change at Week 12 -12.19 -11.19 -8.25 -4.95 LS Mean difference from placebo (Confidence Interval, p value) -7.24 (CI:-9.36, -5.12) p -6.24 (CI:-8.33, -4.16), p -3.31 (CI:-5.40, -1.22), p=0.0020 ​ ISS7 Changes ​ ​ ​ ​ Baseline ISS7 (mean) 16.42 15.70 15.44 15.61 LS Mean change at Week 12 -11.79 -11.68 -8.62 -5.47 LS Mean difference from placebo (Confidence Interval, p value) -6.32 (CI: -8.50, -4.13), p -6.21 (CI: -8.38, -4.04), p -3.16 (CI: -5.41, -0.91), p=0.0061 ​ Responder Analyses/Clinical Responses UAS7=0 (Complete Control) 37.5% 51.1% 22.9% 6.4% UAS7≤6 (Well-controlled) 62.5% 59.6% 41.7% 12.8% ​ UAS7, HSS7 and ISS7 data were analyzed using ANCOVA model and multiple imputation. 57 Table of Contents Barzolvolimab demonstrated strong improvement in UAS7 independent of omalizumab status at Week 12.
Phase 2 CSU: Summary of Clinical Activity Assessments at Week 12 ​ 300 mg Q8W (n=51) 150 mg Q4W (n=52) 75 mg Q4W (n=53) Placebo (n=51) UAS7 Changes Baseline UAS7 (mean) 31.33 30.75 30.30 30.09 LS Mean change at Week 12 -23.87 -23.02 -17.06 -10.47 LS Mean difference from placebo (Confidence Interval, p value) -13.41 (CI: -17.47, -9.34) p -12.55 (CI:-16.56, -8.55) p -6.60 (CI:-10.71, -2.49) p=0.0017 ​ HSS7 Changes ​ ​ ​ ​ Baseline HSS7 (mean) 14.92 15.05 14.86 14.47 LS Mean change at Week 12 -12.19 -11.19 -8.25 -4.95 LS Mean difference from placebo (Confidence Interval, p value) -7.24 (CI:-9.36, -5.12) p -6.24 (CI:-8.33, -4.16), p -3.31 (CI:-5.40, -1.22), p=0.0020 ​ ISS7 Changes ​ ​ ​ ​ Baseline ISS7 (mean) 16.42 15.70 15.44 15.61 LS Mean change at Week 12 -11.79 -11.68 -8.62 -5.47 LS Mean difference from placebo (Confidence Interval, p value) -6.32 (CI: -8.50, -4.13), p -6.21 (CI: -8.38, -4.04), p -3.16 (CI: -5.41, -0.91), p=0.0061 ​ Responder Analyses/Clinical Responses UAS7=0 (Complete Control) 37.5% 51.1% 22.9% 6.4% UAS7≤6 (Well-controlled) 62.5% 59.6% 41.7% 12.8% ​ UAS7, HSS7 and ISS7 data were analyzed using ANCOVA model and multiple imputation.
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.
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.
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. The study is being conducted at approximately 85 sites across approximately 12 countries.
In July 2022, we announced that the first patient had been dosed in a Phase 2 study in patients with CIndU who remain symptomatic despite antihistamine therapy; in April 2024, we announced that enrollment was complete. The study is being conducted at approximately 85 sites across approximately 12 countries.
The 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, 2023, our principal sources of liquidity consisted of cash, cash equivalents and marketable securities of $423.6 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, 2024, our principal sources of liquidity consisted of cash, cash equivalents and marketable securities of $725.3 million.
Eosinophilic Esophagitis (EoE) In July of 2023, we announced that the first patient had been dosed in a Phase 2 study of eosinophilic esophagitis (EoE). EoE, the most common type of eosinophilic gastrointestinal disease, is a chronic inflammatory disease of the esophagus characterized by the infiltration of eosinophils.
Enrollment is ongoing. 65 Table of Contents Eosinophilic Esophagitis (EoE) In July of 2023, we announced that the first patient had been dosed in a Phase 2 study of eosinophilic esophagitis (EoE). EoE, the most common type of eosinophilic gastrointestinal disease, is a chronic inflammatory disease of the esophagus characterized by the infiltration of eosinophils.
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, 2023, the 62 Table of Contents 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, 2024, the fair value of our contingent consideration was $0.0 million.
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 manufacturing organization, or CMO, 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. 69 Table of Contents Clinical trial expenses include expenses associated with clinical research organization, or CRO, services.
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. 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. Phase 1 studies in CSU and CIndU were successfully completed and Phase 2 studies are ongoing.
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 $103.7 million for the year ended December 31, 2022 compared to $60.9 million for the year ended December 31, 2021.
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.
General and Administrative Expense The $6.7 million increase in general and administrative expenses for the year ended December 31, 2022, as compared to the year ended December 31, 2021, was primarily due to higher stock-based compensation, legal and barzolvolimab commercial planning expenses.
General and Administrative Expense The $7.6 million increase in general and administrative 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 and barzolvolimab commercial planning expenses.
Compensation expense for all stock-based awards is recognized using the straight-line method over the term of vesting or performance. 64 Table of Contents RESULTS OF OPERATIONS Year Ended December 31, 2023 compared with Year Ended December 31, 2022 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ Increase/ ​ Increase/ ​ ​ December 31, ​ (Decrease) ​ (Decrease) ​ 2023 2022 $ % ​ ​ (In thousands) Revenues: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Product development and licensing agreements ​ $ 278 ​ $ 56 ​ $ 222 ​ 396 % Contracts and grants ​ 6,605 ​ ​ 2,301 ​ ​ 4,304 ​ 187 % Total revenues ​ $ 6,883 ​ $ 2,357 ​ $ 4,526 ​ 192 % Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Research and development ​ 118,011 ​ ​ 82,258 ​ ​ 35,753 ​ 43 % General and administrative ​ 30,914 ​ ​ 27,195 ​ ​ 3,719 ​ 14 % Gain on fair value remeasurement of contingent consideration ​ — ​ ​ (6,862) ​ ​ (6,862) ​ (100) % Litigation settlement related loss ​ ​ 12,500 ​ ​ 15,000 ​ ​ (2,500) ​ (17) % Total operating expenses ​ 161,425 ​ ​ 117,591 ​ ​ 43,834 ​ 37 % Operating loss ​ (154,542) ​ ​ (115,234) ​ ​ 39,308 ​ 34 % Investment and other income, net ​ 13,113 ​ ​ 2,909 ​ ​ 10,204 ​ 351 % Net loss ​ $ (141,429) ​ $ (112,325) ​ $ 29,104 ​ 26 % ​ Net Loss The $29.1 million increase in net loss for the year ended December 31, 2023, as compared to the year ended December 31, 2022, was primarily due to an increase in research and development expenses and a decrease in the gain on fair value remeasurement of contingent consideration, partially offset by increases in contracts and grants revenue and investment and other income, net.
Year Ended December 31, 2023 compared with Year Ended December 31, 2022 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ Increase/ ​ Increase/ ​ ​ ​ December 31, ​ (Decrease) ​ (Decrease) ​ ​ 2023 2022 $ % ​ ​ ​ (In thousands) Revenues: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Product development and licensing agreements ​ $ 278 ​ $ 56 ​ $ 222 ​ 396 % Contracts and grants ​ ​ 6,605 ​ ​ 2,301 ​ ​ 4,304 ​ 187 % Total revenues ​ $ 6,883 ​ $ 2,357 ​ $ 4,526 ​ 192 % Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ Research and development ​ 118,011 ​ 82,258 ​ 35,753 43 % General and administrative ​ 30,914 ​ 27,195 ​ 3,719 14 % Gain on fair value remeasurement of contingent consideration ​ — ​ (6,862) ​ (6,862) (100) % Litigation settlement related loss ​ ​ 12,500 ​ ​ 15,000 ​ ​ (2,500) ​ (17) % Total operating expenses ​ 161,425 ​ 117,591 ​ 43,834 37 % Operating loss ​ (154,542) ​ (115,234) ​ 39,308 34 % Investment and other income, net ​ 13,113 ​ 2,909 ​ 10,204 351 % Net loss ​ $ (141,429) ​ $ (112,325) ​ $ 29,104 26 % ​ Net Loss The $29.1 million increase in net loss for the year ended December 31, 2023, as compared to the year ended December 31, 2022, was primarily due to an increase in research and development expenses and a decrease in the gain on fair value remeasurement of contingent consideration, partially offset by increases in contracts and grants revenue and investment and other income, net.
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. We expect laboratory supplies expenses to remain relatively consistent over the next twelve months, although there may be fluctuations on a quarterly basis.
The $0.3 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.
Our inability to raise additional capital, or to do so on terms reasonably acceptable to us, would jeopardize the future success of our business. 54 Table of Contents During the past five years through December 31, 2023, we incurred an aggregate of $338.8 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. 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.
The $0.3 million increase in laboratory supply expenses for the year ended December 31, 2022, as compared to the year ended December 31, 2021, 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 $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.
Targets are being selected based on new science as well as their compatibility to be used in 61 Table of Contents bispecific antibody formats with our existing antibody programs. Development is focused on emerging, important pathways controlling inflammatory diseases or immunity to tumors.
Targets are being selected based on new science as well as their compatibility to be used in bispecific antibody formats with our existing antibody programs. Development is focused on emerging, important pathways controlling inflammatory diseases.
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.
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.
Additional Barzolvolimab Development Activities In 2023, we completed the transfer of our current barzolvolimab manufacturing process to a CMO and successfully scaled up the drug substance manufacturing process to produce larger cGMP batches in support of late-stage trials and to prepare for potential commercialization.
Enrollment is ongoing. 66 Table of Contents Additional Barzolvolimab Development Activities In 2023, we completed the transfer of our current barzolvolimab manufacturing process to a CDMO and successfully scaled up the drug substance manufacturing process to produce larger cGMP batches in support of late-stage trials and to prepare for potential commercialization.
The $6.3 million increase in personnel expenses for the year ended December 31, 2022, as compared to the year ended December 31, 2021, was primarily due to higher stock-based compensation expense and an increase in employee headcount. 67 Table of Contents Laboratory supplies expenses include laboratory materials and supplies, services and other related expenses incurred in the development of our technology.
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 1.5 mg/kg, 3.0 mg/kg and 4.5 mg/kg dose groups showed similar markedly improved urticaria symptoms, including rapid onset of responses (as early as 1 week after the first dose) and prolonged disease control with sustained durability up to 24 weeks.
The 1.5 mg/kg, 3.0 mg/kg and 4.5 mg/kg dose groups showed similar markedly improved urticaria symptoms, including rapid onset of responses (as early as 1 week after the first dose) and prolonged disease control with sustained durability up to 24 weeks. Patients with prior omalizumab therapy also had similar symptom improvement as all patients.
Revenue is recognized based on the costs incurred to date as a percentage of the total estimated costs to fulfill the contract. Incurred cost represents work performed, which corresponds with, and thereby best depicts, the transfer of control to the customer.
Under product development agreements, revenue is generally recognized using a cost-to-cost measure of progress. Revenue is recognized based on the costs incurred to date as a percentage of the total estimated costs to fulfill the contract. Incurred cost represents work performed, which corresponds with, and thereby best depicts, the transfer of control to the customer.
Operating Activities 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.
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.
Litigation Settlement Related Loss We recorded a loss of $15.0 million in the second quarter of 2022 related to the Initial Payment due under the binding settlement term sheet entered with SRS, which was subsequently memorialized in a Settlement Agreement with SRS.
Litigation Settlement Related Loss We recorded a loss of $15.0 million in the second quarter of 2022 related to the Initial Payment due under the Settlement Agreement with SRS.
In November 2023, we reported that barzolvolimab achieved the primary efficacy endpoint in the ongoing Phase 2 CSU 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. We are currently planning Phase 3 studies in CSU which are expected to initiate in summer 2024.
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.
We have had recurring losses and incurred a loss of $141.4 million for the year ended December 31, 2023. Net cash used in operations for the year ended December 31, 2023 was $107.3 million.
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.
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.
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 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 and oncology.
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.
For consultant and non-employee director grants, we may elect to use the contractual term as the expected term in the option-pricing model. Actual volatility and lives of options may be significantly different from our estimates.
For consultant and non-employee director grants, we may elect to use the contractual term as the expected term in the option-pricing model. Actual volatility and lives of options may be significantly different from our estimates. Compensation expense for all stock-based awards is recognized using the straight-line method over the term of vesting or performance.
Most AEs were mild or moderate in severity and resolved while on study. The most common treatment emergent adverse events were hair color changes, COVID-19, headache, neutropenia and urinary tract infections (UTIs). UTIs and COVID-19 were reported as unrelated to treatment. Generally transient, asymptomatic and mild changes in hematologic parameters were observed, consistent with observations from prior studies.
Barzolvolimab was well tolerated. Most adverse events were mild or moderate in severity and resolved while on study. The most common treatment emergent adverse events were hair color changes, COVID-19, headache, neutropenia and urinary tract infections (UTIs). UTIs and COVID-19 were reported as unrelated to treatment.
Patients will be randomly assigned on a 1:1:1 60 Table of Contents ratio to receive barzolvolimab injections of 150 mg Q4W after an initial loading dose of 450 mg, 300 mg Q4W after an initial loading dose of 450 mg, or placebo during a 24‑week Treatment Phase.
Approximately 120 patients will be randomly assigned on a 1:1:1 ratio to receive subcutaneous injections of barzolvolimab at either 150 or 300 mg or placebo every 4 weeks after an initial loading dose of 450 mg or placebo during a 16-week placebo-controlled treatment phase.
The amounts disclosed in the following table reflect direct research and development costs, license fees associated with the underlying technology and an allocation of indirect research and development costs to each program. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended Year Ended Year Ended ​ December 31, 2023 December 31, 2022 December 31, 2021 ​ ​ (In thousands) ​ ​ ​ Barzolvolimab/Anti-KIT Program ​ $ 79,913 ​ $ 51,220 ​ $ 24,395 CDX-585 ​ 6,357 ​ ​ 9,793 ​ ​ 7,133 Other Programs ​ 31,741 ​ ​ 21,245 ​ ​ 21,783 Total R&D Expense ​ $ 118,011 ​ $ 82,258 ​ $ 53,311 ​ 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, 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 $19.9 million increase in product development expenses for the year ended December 31, 2022, as compared to the year ended December 31, 2021, was primarily due to an increase in barzolvolimab clinical trial and contract manufacturing expenses.
The $31.3 million increase in product development expenses for the year ended December 31, 2024, as compared to the year ended December 31, 2023, was primarily due to an increase in barzolvolimab clinical trial expenses, partially offset by a decrease in barzolvolimab contract manufacturing expenses.
Net cash provided by financing activities was $4.1 million for the year ended December 31, 2022 compared to $272.4 million for the year ended December 31, 2021. The decrease in net cash provided by financing activities was primarily due to a decrease in net proceeds from stock issuances.
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.
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: In November 2023, we announced that our Phase 2 study in chronic spontaneous urticaria (CSU) achieved the primary efficacy endpoint (statistically significant mean change from baseline to week 12 of urticaria activity score compared to placebo) and was well tolerated.
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.
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.
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 $2.3 million decrease in contracts and grants revenue for the year ended December 31, 2022, as compared to the year ended December 31, 2021, was primarily related to a decrease in services performed under our manufacturing and research and development agreements with Rockefeller University and Gilead Sciences.
Revenue The $0.4 million increase in contracts and grants revenue for the year ended December 31, 2024, as compared to the year ended December 31, 2023, was primarily due to an increase in services performed under our manufacturing and research and development agreements with Rockefeller University.
Based on the positive results reported in urticaria, we expanded development of barzolvolimab into additional indications where mast cells are believed to play an important role.
Based on the positive results reported in urticaria, we expanded development of barzolvolimab into additional indications where mast cells are believed to play an important role. We are conducting ongoing Phase 2 studies in eosinophilic esophagitis (EoE), prurigo nodularis (PN) and atopic dermatitis (AD).
Differences between actual expenses and estimated expenses recorded have not been material and are adjusted for in the period in which they become known.
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.
As we expected, and consistent with previous findings with KIT blocking antibodies, we were pleased to report in December 2022, that during this recovery period spermatogenesis fully recovered in all male animals as measured by both sperm count and motility. The final histologic analysis and study report were completed in early 2023 and were consistent with previously reported results.
Due to the very high concentrations of barzolvolimab at the end of dosing, the recovery period was approximately one year. As we expected, and consistent with previous findings with KIT blocking antibodies, we were pleased to report in December 2022, that during this recovery period spermatogenesis fully recovered in all male animals as measured by both sperm count and motility.
Chronic Inducible Urticaria (CIndU) CIndUs are forms of urticaria that have an attributable cause or trigger associated with them, typically resulting in hives or wheals. The prevalence of CIndU is estimated at 0.5% of the total population and is reported to overlap in up to 36% of CSU patients (Weller et al. 2010. Hautarzt. 61(8), Bartlett et al. 2018. DermNet.Org).
The prevalence of CIndU is estimated at 0.5% of the total population and is reported to overlap in up to 36% of CSU patients (Weller et al. 2010. Hautarzt. 61(8), Bartlett et al. 2018. DermNet.Org).
Facility expenses for the year ended December 31, 2022 were relatively consistent with the year ended December 31, 2021. Product development expenses include clinical investigator site fees, external trial monitoring costs, data accumulation costs, contracted research and outside clinical drug product manufacturing.
Product development expenses include clinical investigator site fees, external trial monitoring costs, data accumulation costs, contracted research and outside clinical drug product manufacturing.
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 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. 60 Table of Contents Barzolvolimab was well tolerated with a favorable safety profile.
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.
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.
Approximately 180 patients in 2 cohorts (differentiated by CIndU subtype) including 90 patients with cold urticaria and 90 patients with symptomatic dermographism will be 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 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 invoicing from CROs and CMOs for services rendered can lag several months. We accrue the cost of services rendered in connection with CRO and CMO activities based on our estimate of costs incurred. We maintain regular communication with our CROs and CMOs to assess the reasonableness of our estimates.
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.
If a project is completed, the carrying value of the related intangible asset is amortized over the remaining estimated life of the asset beginning in the period in which the project is completed.
These assets are capitalized on our balance sheets until either the project underlying them is completed or the assets become impaired. If a project is completed, the carrying value of the related intangible asset is amortized over the remaining estimated life of the asset beginning in the period in which the project is completed.
During the third quarter of 2021, we issued 6,845,238 shares of common stock in an underwritten public offering resulting in net proceeds of $269.9 million, after deducting underwriting fees and offering expenses.
In March 2024, we issued 9,798,000 shares of our common stock in an underwritten public offering resulting in net proceeds of $432.3 million, after deducting underwriting fees and offering expenses.
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. 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.
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. On February 26, 2024, we entered into a controlled equity offering sales agreement with Cantor Fitzgerald & Co.
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.
A Phase 2 study in chronic inducible urticaria (CIndU) is currently enrolling patients and we expect to report data from this study in the second half of 2024; - Prurigo Nodularis (PN): In November 2023, we reported positive data from a Phase 1b study in PN that supports further development of barzolvolimab in this indication and we are currently planning for the initiation of a Phase 2 study in PN in early 2024; - Eosinophilic Esophagitis (EoE): A Phase 2 study in EoE was initiated in June 2023 and enrollment is ongoing. ● Our next generation bispecific antibody platform to support pipeline expansion with additional candidates for inflammatory diseases and oncology.
Patients 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.
Mast cells through their interactions with sensory neurons and other immune cells are believed to play an important role in amplifying chronic itch and neuroinflammation, both of which are a hallmark of PN. There is currently only one FDA approved therapy for PN, representing an area of significant unmet need.
PN is a chronic skin disease characterized by the development of hard, intensely itchy (pruritic) nodules on the skin. Mast cells through their interactions with sensory neurons and other immune cells are believed to play an important role in amplifying chronic itch and neuroinflammation, both of which are a hallmark of PN.
We expect revenue to remain relatively consistent over the next twelve months, although there may be fluctuations on a quarterly basis.
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.
Revenue for the Company is derived from product development agreements with collaborative partners for the research and development of therapeutic drug candidates. The terms of the agreements may include nonrefundable signing and licensing fees, funding for research, development and manufacturing, milestone payments and royalties on any product sales derived from collaborations.
The terms of the agreements may include nonrefundable signing and licensing fees, funding for research, development and manufacturing, milestone payments and royalties on any product sales derived from collaborations. The Company assesses the multiple obligations typically within product development contracts to determine the distinct performance obligations and how to allocate the arrangement consideration to each distinct performance obligation.
During the fourth quarter of 2023, we issued 8,538,750 shares of common stock in an underwritten public offering resulting in net proceeds of $216.2 million, after deducting underwriting fees and offering expenses.
Also in November 2023, we issued 8,538,750 shares of our common stock in an underwritten public offering resulting in net proceeds of $216.2 million, after deducting underwriting fees and offering expenses. On February 26, 2024, we entered into a controlled equity offering sales agreement (“ATM Agreement”) with Cantor Fitzgerald & Co.
As a standard part of toxicology studies, some animals from each group continued to be observed through a recovery period to understand the reversibility of any adverse findings. Due to the very high concentrations of barzolvolimab at the end of dosing, the recovery period was approximately one year.
The only clinically adverse finding at the completion of dosing was a profound impact on spermatogenesis, an expected and well understood effect of KIT inhibition. As a standard part of toxicology studies, some animals from each group continued to be observed through a recovery period to understand the reversibility of any adverse findings.
The increase in net cash provided by investing activities was primarily due to net sales and maturities of marketable securities of $91.7 million for the year ended December 31, 2022 as compared to net purchases of $214.9 million for the year ended December 31, 2021.
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.
We believe that the cash, cash equivalents and marketable securities at December 31, 2023 are sufficient to meet estimated working capital requirements and fund current planned operations into 2026. This could be impacted if we elect to pay the future milestone under the Settlement Agreement with SRS, if any, in cash.
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.
In order to utilize excess capacity, the Company has, from time to time, entered into contract manufacturing and research and development arrangements in which services are provided on a time-and-material basis or at a negotiated fixed- price. Revenue from time-and-material contracts is generally recognized on an output basis as labor hours and/or direct expenses are incurred.
The Company operates a cGMP manufacturing facility in Fall River, Massachusetts, to produce drug substance for its current and planned early-stage clinical trials. In order to utilize excess capacity, the Company has, from time to time, entered into contract manufacturing and research and development arrangements in which services are provided on a time-and-material basis or at a negotiated fixed- price.
Net cash provided by investing activities was $89.9 million for the year ended December 31, 2022 compared to net cash used in investing activities of $216.2 million for the year ended December 31, 2021.
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.
Industry 59 Table of Contents sources estimate there are approximately 154,000 patients in the United States with PN who have undergone treatment within the last 12 months and, of these, approximately 75,000 would be biologic-eligible. We have completed a Phase 1b multi-center, randomized, double-blind, placebo-controlled intravenous study in PN.
There is currently only one FDA approved therapy for PN, representing an area of significant unmet need. Industry sources estimate there are approximately 154,000 patients in the United States with PN who have undergone treatment within the last 12 months and, of these, approximately 75,000 would be biologic-eligible.
Facility expenses include depreciation, amortization, utilities, rent, maintenance and other related expenses incurred at our facilities. The $0.2 million increase in facility expenses for the year ended December 31, 2023, as compared to the year ended December 31, 2022, was primarily due to higher repairs and depreciation expense.
The $0.2 million increase in facility expenses for the year ended December 31, 2023, as compared to the year ended December 31, 2022, was primarily due to higher repairs and depreciation expense. Product development expenses include clinical investigator site fees, external trial monitoring costs, data accumulation costs, contracted research and outside clinical drug product manufacturing.
We continue to assess potential opportunities for barzolvolimab in other diseases where mast cells play an important role, such as dermatologic, respiratory, allergic, gastrointestinal and ophthalmic conditions. Chronic Spontaneous Urticaria (CSU) 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.
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.
The increase in net cash used in operating activities was primarily due to increases in research and development and general and administrative expenses and the $15.0 million Initial Payment made to SRS under the Settlement Agreement.
The increase in net cash used in operating activities was primarily due to increases in research and development and general and administrative expenses and an increase in advance payments to clinical research and contract manufacturing organizations, partially offset by an increase in investment income as a result of higher levels of cash and a decrease in payments made under the Settlement Agreement with SRS.
We are currently planning for the initiation of a Phase 2 subcutaneous study in PN in early 2024.
In April 2024, we initiated a Phase 2 subcutaneous study in PN.
Under fixed-price contracts, revenue is generally recognized on an output basis as progress is made toward completion of the performance obligations using surveys of performance completed to date. Intangible and Long-Lived Assets We evaluate the recoverability of our long-lived assets, including property and equipment when circumstances indicate that an event of impairment may have occurred.
Revenue from time-and-material contracts is generally recognized on an output basis as labor hours and/or direct expenses are incurred. Under fixed-price contracts, revenue is generally recognized on an output basis as progress is made toward completion of the performance obligations using surveys of performance completed to date.

… 92 more changes not shown on this page.

Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

1 edited+0 added−0 removed3 unchanged
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, 2023 due to the short-term maturities of these instruments. ​ 70 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, 2024 due to the short-term maturities of these instruments. ​ 75 Table of Contents

Other CLDX 10-K year-over-year comparisons