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What changed in INOVIO PHARMACEUTICALS, INC.'s 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of INOVIO PHARMACEUTICALS, 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.

+465 added−407 removedSource: 10-K (2025-03-18) vs 10-K (2024-03-06)

Top changes in INOVIO PHARMACEUTICALS, INC.'s 2024 10-K

465 paragraphs added · 407 removed · 310 edited across 9 sections

Item 1. Business

Business — how the company describes what it does

134 edited+94 added−39 removed153 unchanged
Biggest changeThese risk factors include, but are not limited to, the following: • We have incurred significant losses in recent years, expect to incur significant net losses in the foreseeable future and may never become profitable. • We have limited sources of revenue and our success is dependent on our ability to develop our DNA medicines and proprietary device technology. • We will need substantial additional capital to develop our DNA medicines and proprietary device technology, which may prove difficult or costly to obtain. • None of our DNA medicine candidates have been approved for sale, and we may never develop commercially successful DNA medicine products. • DNA medicines are a novel approach to treating and preventing disease, and our CELLECTRA ® delivery devices are a novel approach to administering medicines, and negative perception of the efficacy, safety, or tolerability of any investigational medicines we develop or our devices could adversely affect our ability to conduct our business, advance our investigational medicines, or obtain regulatory approvals. • If we and the contract manufacturers upon whom we rely fail to produce our proprietary devices and DNA medicine candidates in the volumes that we require on a timely basis, or at all, or if these contractors fail to comply with their obligations to us or with stringent regulations, we may face delays in the development and commercialization of our proprietary devices and DNA medicine candidates. • If we lose or are unable to secure collaborators or partners, or if our collaborators or partners do not apply adequate resources to their relationships with us, our product development and potential for profitability will suffer. • We have agreements with government agencies that are subject to termination and uncertain future funding.
Biggest changeNegative perception of the efficacy, safety, or tolerability of any investigational medicines we develop or our devices could adversely affect our ability to conduct our business, advance our investigational medicines, or obtain regulatory approvals. • If we and the contract manufacturers upon whom we rely fail to produce our proprietary devices and DNA medicine candidates in the volumes that we require on a timely basis, or at all, or if these contractors fail to comply with their obligations to us or with stringent regulations, we may face delays in the development and commercialization of our proprietary devices and DNA medicine candidates. 2 • If we lose or are unable to secure collaborators or partners, or if our collaborators or partners do not apply adequate resources to their relationships with us, our product development and potential for profitability will suffer. • We have agreements with government agencies that are subject to termination and uncertain future funding.
Patients in the trial had a median range of 4 surgeries (overall range of 2-8) in the year prior to dosing. After dosing, there was a statistically significant median decrease of 3 surgical interventions (95% confidence interval: -3 to -2).
Patients in the trial had a median of 4 surgeries (overall range of 2-8) in the year prior to dosing. After dosing, there was a statistically significant median decrease of 3 surgical interventions (95% confidence interval: -3 to -2).
The ACA, among other things, increased the minimum level of 18 Medicaid rebates payable by manufacturers of brand name drugs; required collection of rebates for drugs paid by Medicaid managed care organizations; required manufacturers to participate in a coverage gap discount program, under which they must agree to offer point-of-sale discounts (increased to 70 percent, effective as of January 1, 2019) off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; imposed a non-deductible annual fee on pharmaceutical manufacturers or importers who sell certain “branded prescription drugs” to specified federal government programs, implemented a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted, or injected expanded the types of entities eligible for the 340B drug discount program; expanded eligibility criteria for Medicaid programs; created a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; and established a Center for Medicare Innovation at the Centers for Medicare and Medicaid Services, or CMS, to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.
The ACA, among other things, increased the minimum level of Medicaid rebates payable by manufacturers of brand name drugs; required collection of rebates for drugs paid by Medicaid managed care organizations; required manufacturers to participate in a coverage gap discount program, under which they must agree to offer point-of-sale discounts (increased to 70 percent, effective as of January 1, 2019) off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; imposed a non-deductible annual fee on pharmaceutical manufacturers or importers who sell certain “branded prescription drugs” to specified federal government programs, implemented a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted, or injected expanded the types of entities eligible for the 340B drug discount program; expanded eligibility criteria for Medicaid programs; created a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; and established a Center for Medicare Innovation at the Centers for Medicare and Medicaid Services, or CMS, to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.
The process required by the FDA before a biologic may be marketed in the United States generally involves the following: 14 • completion of extensive nonclinical, sometimes referred to as pre-clinical laboratory tests, pre-clinical animal studies and formulation studies in accordance with applicable regulations, including the FDA’s Good Laboratory Practice, or GLP, regulations; • submission to the FDA of an IND, which must become effective before human clinical trials may begin; • performance of adequate and well-controlled human clinical trials in accordance with applicable IND and other clinical trial-related regulations, sometimes referred to as good clinical practices, or GCPs, to establish the safety and efficacy of the proposed product candidate for its proposed indication; • submission to the FDA of a BLA; • satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities where the product is produced to assess compliance with the FDA’s current good manufacturing practice, or cGMP, requirements to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality, purity and potency; • potential FDA audit of the pre-clinical and/or clinical trial sites that generated the data in support of the BLA; and • FDA review and approval of the BLA prior to any commercial marketing or sale of the product in the United States.
The process required by the FDA before a biologic may be marketed in the United States generally involves the following: • completion of extensive nonclinical, sometimes referred to as pre-clinical laboratory tests, pre-clinical animal studies and formulation studies in accordance with applicable regulations, including the FDA’s Good Laboratory Practice, or GLP, regulations; • submission to the FDA of an IND, which must become effective before human clinical trials may begin; • performance of adequate and well-controlled human clinical trials in accordance with applicable IND and other clinical trial-related regulations, sometimes referred to as good clinical practices, or GCPs, to establish the safety and efficacy of the proposed product candidate for its proposed indication; • submission to the FDA of a BLA; • satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities where the product is produced to assess compliance with the FDA’s current good manufacturing practice, or cGMP, requirements to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality, purity and potency; • potential FDA audit of the pre-clinical and/or clinical trial sites that generated the data in support of the BLA; and • FDA review and approval of the BLA prior to any commercial marketing or sale of the product in the United States.
If a pharmaceutical company’s operations are found to be in violation of any of the laws described above or any other governmental regulations that apply to it, it may be subject to significant penalties, including administrative, civil and criminal penalties, damages, fines, disgorgement, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, imprisonment, integrity and/or other oversight obligations, contractual damages, reputational harm and the curtailment or restructuring of operations.
If a pharmaceutical company’s operations are found to be in violation of any of the laws described above or any other governmental regulations that apply to it, it may be 23 subject to significant penalties, including administrative, civil and criminal penalties, damages, fines, disgorgement, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, imprisonment, integrity and/or other oversight obligations, contractual damages, reputational harm and the curtailment or restructuring of operations.
We believe that all of our product candidates will have a biologic primary mode of action. U.S. Biological Product Development In the United States, the FDA regulates biologics under FDCA, and the Public Health Service Act, or PHSA, and their implementing regulations. Biologics are also subject to other federal, state, and local statutes and regulations.
We believe that all of our product candidates will have a biologic primary mode of action. U.S. Biological Product Development 15 In the United States, the FDA regulates biologics under FDCA, and the Public Health Service Act, or PHSA, and their implementing regulations. Biologics are also subject to other federal, state, and local statutes and regulations.
Other Regulations We also are subject to various federal, state and local laws, regulations, and recommendations relating to safe working conditions, laboratory and manufacturing practices, the experimental use of animals, and the use and disposal of hazardous or potentially hazardous substances, including radioactive compounds and infectious disease agents, used in connection with our 20 research.
Other Regulations We also are subject to various federal, state and local laws, regulations, and recommendations relating to safe working conditions, laboratory and manufacturing practices, the experimental use of animals, and the use and disposal of hazardous or potentially hazardous substances, including radioactive compounds and infectious disease agents, used in connection with our research.
Although our patent filings include claims covering various features of our products and product candidates, including composition, methods of manufacture and use, our patents do not provide us with complete protection, or guarantee, against the development of competing products. In addition, some of our know-how and technology are not patentable.
Although our patent filings include claims covering various features of our products and product candidates, including composition, methods of manufacture and use, our 13 patents do not provide us with complete protection, or guarantee, against the development of competing products. In addition, some of our know-how and technology are not patentable.
Furthermore, changes in, or different interpretations of, patent laws 13 in the United States and other countries may result in patent laws that allow others to use our discoveries or develop and commercialize our products. We cannot guarantee that the patents we obtain or the unpatented technology we hold will afford us significant commercial protection.
Furthermore, changes in, or different interpretations of, patent laws in the United States and other countries may result in patent laws that allow others to use our discoveries or develop and commercialize our products. We cannot guarantee that the patents we obtain or the unpatented technology we hold will afford us significant commercial protection.
Phase 3 clinical trials may include comparisons with placebo and/or other 15 comparator treatments. The duration of treatment is often extended to mimic the actual use of a product during marketing. Generally, two adequate and well-controlled Phase 3 clinical trials are required by the FDA for approval of a BLA.
Phase 3 clinical trials may include comparisons with placebo and/or other comparator treatments. The duration of treatment is often extended to mimic the actual use of a product during marketing. Generally, two adequate and well-controlled Phase 3 clinical trials are required by the FDA for approval of a BLA.
A REMS could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products.
A REMS could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. Any of these limitations on approval or marketing could restrict the commercial promotion, 18 distribution, prescription or dispensing of products.
Moreover, the constituent parts of a combination product retain their regulatory status, for example, as a biologic or device, and as such, we may be subject to additional requirements in the Quality System Regulation, or QSR, applicable to 17 medical devices, such as design controls, purchasing controls, and corrective and preventive action.
Moreover, the constituent parts of a combination product retain their regulatory status, for example, as a biologic or device, and as such, we may be subject to additional requirements in the Quality System Regulation, or QSR, applicable to medical devices, such as design controls, purchasing controls, and corrective and preventive action.
There may be significant delays in obtaining coverage and reimbursement as the process of determining coverage and reimbursement is often time consuming and costly which may require the provision of scientific and clinical support for the use of the product to each payor separately, with no assurance that coverage or adequate reimbursement will be obtained.
There 21 may be significant delays in obtaining coverage and reimbursement as the process of determining coverage and reimbursement is often time consuming and costly which may require the provision of scientific and clinical support for the use of the product to each payor separately, with no assurance that coverage or adequate reimbursement will be obtained.
Even if we are able to obtain a license, the license would likely obligate us to pay license fees or royalties or both, and the rights granted to us might be non-exclusive, which could result in our competitors gaining access to the same intellectual property.
Even if we are able to obtain a license, the license would likely obligate us to pay license fees or royalties or both, and the 14 rights granted to us might be non-exclusive, which could result in our competitors gaining access to the same intellectual property.
Defense Advanced Research Projects Agency (DARPA), a research and development agency of the DoD and the JPEO-CBRND, to use our dMAb technology to develop anti-SARS-CoV-2-specific dMAbs that function as both a therapeutic and preventive treatment for COVID-19.
Defense Advanced Research Projects Agency (DARPA), a research and development agency of the DoD and the JPEO-CBRND, to use our DMAb technology to develop anti-SARS-CoV-2-specific DMAbs that function as both a therapeutic and potentially preventive treatment for COVID-19.
The IRB also approves the informed consent form that must be provided to each clinical trial participant or his or her legal representative and must monitor the clinical trial until completed. There are also requirements governing the reporting of ongoing clinical trials and completed clinical trial results to public registries.
The IRB also approves the informed consent form that must be provided to each clinical trial participant or his or her legal representative and must monitor the clinical trial until completed. 16 There are also requirements governing the reporting of ongoing clinical trials and completed clinical trial results to public registries.
We were previously conducting clinical trials of a DNA medicine candidate for the treatment of HPV-related cervical high-grade squamous intraepithelial lesions, or HSIL, but announced in August 2023 that we were ceasing development for this indication in the United States.
We were previously conducting clinical trials of a DNA medicine candidate for the treatment of HPV-related cervical high-grade squamous intraepithelial lesions, or HSIL, but announced in 2023 that we were ceasing development for this indication in the United States.
We communicate frequently and transparently with our employees through a variety of communication methods, including video and written communications, town hall meetings, employee surveys and our company intranet, and 21 acknowledge individual contributions to our company’s success through several rewards and recognition initiatives.
We communicate frequently and transparently with our employees through a variety of communication methods, including video and written communications, town hall meetings, employee surveys and our company intranet, and acknowledge individual contributions to our company’s success through several rewards and recognition initiatives.
PDUFA also imposes an annual program fee for approved products. Fee waivers or reductions are available in certain circumstances, including a waiver of the application fee for the first application filed by a small business or a waiver of fee based on orphan drug status.
PDUFA also imposes an annual program fee for approved products. Fee waivers or 17 reductions are available in certain circumstances, including a waiver of the application fee for the first application filed by a small business or a waiver of fee based on orphan drug status.
Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance. These regulations also impose certain organizational, procedural and documentation requirements with respect to manufacturing and quality assurance activities.
Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance. These regulations 20 also impose certain organizational, procedural and documentation requirements with respect to manufacturing and quality assurance activities.
These work by either increasing uptake of the DNA/RNA into cells or by acting as an adjuvant, alerting the immune system. DNA Immunotherapy Delivery with Electroporation 11 There are other companies with electroporation intellectual property and devices.
These work by either increasing uptake of the DNA/RNA into cells and/or by acting as an adjuvant, alerting the immune system. DNA Immunotherapy Delivery with Electroporation There are other companies with electroporation intellectual property and devices.
To that end, we invest in our employees to be an employer of choice. Employee Engagement As we work to make an impact on how healthcare is delivered, we believe it is critical that our employees are informed and engaged.
To that end, we invest in our employees to be an employer of choice. 24 Employee Engagement As we work to make an impact on how healthcare is delivered, we believe it is critical that our employees are informed and engaged.
The overall incidence of GBM varies worldwide and is highest in North America, Australia and Northern and Western Europe. In the United States, the average age-adjusted incidence rate of GBM is 3.19 cases per 100,000 persons.
The overall incidence of GBM varies worldwide but is highest in North America, Australia and Northern and Western Europe. In the United States, the average age-adjusted incidence rate of GBM is 3.19 cases per 100,000 persons.
The trials are designed to evaluate safety, tolerability and immunogenicity of INO-4800 as a 9 homologous booster where INO-4800 was administered as the primary vaccine and as a heterologous booster where an inactivated vaccine was administered as the primary vaccine.
The trials are designed to evaluate safety, tolerability and immunogenicity of INO-4800 as a homologous booster where INO-4800 was administered as the primary vaccine and as a heterologous booster where an inactivated vaccine was administered as the primary vaccine.
Design and Manufacture: DNA medicines can be rapidly designed and scaled, with ease of manufacturing providing a potential cost advantage. g. Delivery Mechanism: Our proprietary electroporation devices increase cellular uptake and overcome the barrier posed by cell membranes that can hinder the entry of large molecules, such as DNA plasmids.
Design and Manufacture: DNA medicines can be rapidly designed and scaled, with ease of manufacturing providing a potential cost advantage. g. Delivery Mechanism: Our proprietary delivery devices use electroporation to increase cellular uptake and overcome the barrier posed by cell membranes that can hinder the entry of large molecules, such as DNA plasmids.
In the area of HPV-related diseases, for example, the expressed proteins are antigens that elicit antigen-specific T cell responses to fight HPV.
In the area of HPV-related diseases, for example, the expressed proteins are viral antigens that elicit antigen-specific T cell responses to fight HPV.
Ebola can spread through human-to-human transmission by direct contact with the blood, secretions, organs or bodily fluids of an infected individual and with surfaces or materials that contain the contaminated fluids of an infected person, such as bedding and clothing. It is capable of causing death within 2 to 21 days of exposure.
EBOV can spread through human-to-human transmission by direct contact with the blood, secretions, organs or bodily fluids of an infected individual and with surfaces or materials that contain the contaminated fluids of an infected person, such as bedding and clothing. It is capable of causing death within 2 to 21 days of exposure.
Prognosis is extremely poor, and a limited number of new therapies have been approved over the last 10 years; average survival for U.S. patients has been reported as low as 8 months with a five-year survival rate of 6.9% for all ages combined.
Prognosis is extremely poor, and a limited number of new therapies have been approved over the last 10 years; average survival for U.S. patients has been reported to be as low as 8 months with a five-year survival rate of 6.9% for all ages combined.
In the event that VGX-3100 is approved for marketing in Greater China, we will be entitled to receive royalty payments based on a tiered percentage of annual net sales, with such percentage being in the low- to mid-teens, subject to reduction in the event of generic competition in a particular territory.
In the event that VGX-3100 is approved for marketing, we will be entitled to receive royalty payments based on a tiered percentage of annual net sales, with such percentage being in the low- to mid-teens, subject to reduction in the event of generic competition in a particular territory.
We start by identifying one or more antigens that we believe are the best targets for directing the immune system toward HPV and then apply our SynCon design process, which analyzes the genetic make-up of the selected antigens from multiple strains of the virus.
We start by identifying one or more viral antigens that we believe are the best targets for directing the immune system toward HPV and then apply our design process, which analyzes the genetic make-up of the selected antigens from multiple strains of the virus.
Approximately one-half of our workforce is comprised of women and approximately one-half is comprised of individuals with ethnically diverse backgrounds. In addition, four of the eight members of our board of directors are women. None of our employees are subject to collective bargaining agreements. We consider our relationship with our employees to be good.
Approximat ely one-half of our workforce is comprised of women and approximately one-half is comprised of individuals with ethnically diverse backgrounds. In addition, four of the eight members of our board of directors are women. None of our employees are subject to collective bargaining agreements. We consider our relationship with our employees to be good.
However, ERVEBO has not been approved for repeat dosing and there are no approved booster vaccines yet available in the United States. In December 2021, we announced complete enrollment of a 46-participant Phase 1b trial (NCT04906629) in which our DNA medicine candidate INO-4201 was assessed as a heterologous booster in healthy volunteers previously vaccinated with ERVEBO.
However, ERVEBO has not been approved for repeat dosing and there are currently no approved booster vaccines available in the United States. In 2021, we announced complete enrollment of a 46-participant Phase 1b trial (NCT04906629) in which our DNA medicine candidate INO-4201 was assessed as a heterologous booster in healthy volunteers previously vaccinated with ERVEBO.
DNA-Launched Nanoparticles (dLNPs) INOVIO and our collaborators at the Wistar Institute are applying our experience in DNA vaccine development toward the development of the next generation of DNA medicine technology, by investigating DNA-launched nanoparticles, or dLNPs, initially targeting infectious diseases vaccines. INO-6172, INOVIO’s first dLNP to enter clinical trials, is in a Phase 1 trial sponsored and funded by NIAID.
DNA-Launched Nanoparticles (DLNPs) We and our collaborators at the Wistar Institute are applying our experience in DNA vaccine development toward the development of the next generation of DNA medicine technology, by investigating DNA-launched nanoparticles, or DLNPs, initially targeting infectious diseases vaccines. INO-6172, our first DLNP to enter clinical trials, is in a Phase 1 trial sponsored and funded by NIAID.
For this trial, adult patients first underwent surgical removal of their papillomas and then received up to four doses of INO-3107, once every three weeks. The primary endpoint of this trial was safety and tolerability.
For this trial, adult patients first underwent surgical removal of their papillomas and then received four doses of INO-3107, once every three weeks. The primary endpoint of this trial was safety and tolerability.
INO-6172 contains two plasmids, one encoding for the dLNP and one encoding for human IL-12. The trial is a randomized, 45-participant, open-label Phase 1 trial that is examining the safety and immunogenicity of INO-6172 in adults without HIV. The trial is ongoing, as is additional preclinical work with dLNP technology and additional vaccine candidates.
INO-6172 contains two plasmids, one encoding for the DLNP and one encoding for human IL-12. The trial is a randomized, 45-participant, open-label Phase 1 trial evaluating the safety and immunogenicity of INO-6172 in adults without HIV. The trial is ongoing, as is additional preclinical work with DLNP technology and additional vaccine candidates.
Occupational injuries at our workplace have historically been very low and are always investigated to determine if any environmental or other changes need to be implemented. 22
Occupational injuries at our workplace have historically been very low and are always investigated to determine if any environmental or other changes need to be implemented. 25
These DNA 3 medicines can generate antigen-targeted humoral and cellular immune responses based on the indication, including antigen-specific cytotoxic, or killer, T cell responses that are important for fighting cancer and viral infections. Characteristics of our DNA medicines include: a.
These DNA medicines can generate antigen-targeted humoral and cellular immune responses based on the indication, including antigen-specific cytotoxic, or killer, T cell responses that are important for fighting cancer and viral infections. Some of the key characteristics of our DNA medicines include: a.
SynCon ® - DNA Plasmid Design Technology Our precisely designed DNA plasmids are circular double-stranded DNA that have been optimized, using our proprietary technology and algorithms, to express a protein.
DNA Plasmid Design Technology Our precisely designed DNA plasmids are circular double-stranded DNA constructs that have been optimized, using our proprietary technology and algorithms, to express a protein.
We have generated immune responses, including CD4+, CD8+, and memory T cells, with SynCon-designed DNA medicines against various tumor-associated antigens, as well as against different strains of certain infectious diseases in human clinical trials. Because the engineered sequences are substantially similar to the original sequences, without matching them exactly, we believe they are patentable.
We have generated immune responses, including CD4+, CD8+, and memory T cells, with our DNA medicines against various tumor-associated antigens, as well as against different strains of certain infectious diseases in human clinical trials. Because the engineered genetic sequences are substantially similar to the original sequences, without matching them exactly, we believe they are patentable.
The primary endpoint of the trial was histologic clearance of the high-grade lesions and virologic clearance of the HPV-16/18 virus in anal/perianal tissue samples. In December 2020, we announced Phase 2 efficacy results from this trial. 8 One-half of participants treated with VGX-3100 (11/22) showed resolution of HPV-16/18-associated anal HSIL at six months following the start of treatment.
The primary endpoint of the trial was histologic clearance of the high-grade lesions and virologic clearance of the HPV-16/18 virus in anal/perianal tissue samples. In 2020, we announced Phase 2 results from this trial. One-half of the 22 participants treated with VGX-3100 showed resolution of HPV-16/18-associated anal HSIL at six months following the start of treatment.
For head and neck cancers, AstraZeneca is developing a bispecific antibody targeting PD-1 and TIGIT for locaregionally advanced head and neck squamous cell carcinoma, while the National Cancer Institute is conducting a Phase 3 study with the immunotherapy nivolumab (Bristol-Myers Squibb’s Opdivo) in HPV-positive oropharynx cancer. Other companies are pursuing different approaches to pre-cancers and cancers we are targeting.
For head and neck cancers, AstraZeneca is developing a bispecific antibody targeting PD-1 and TIGIT for locoregionally advanced head and neck squamous cell carcinoma, while the National Cancer Institute is conducting a Phase 3 study with the immunotherapy nivolumab (Bristol-Myers Squibb’s Opdivo) in HPV-positive oropharyngeal cancer. Other companies are pursuing different approaches to pre-cancers and cancers we are targeting.
Our issued patents directed to our other product candidates expire between about 2027 and 2036 and our pending patent applications, if issued, would expire between about 2027 and 2042. Our issued patents directed to our device delivery systems expire between about 2024 and 2036 and our pending patent applications, if issued, would expire between about 2024 and 2042.
Our issued patents directed to our other product candidates expire between about 2027 and 2036 and our pending patent applications, if issued, would expire between about 2027 and 2042. Our issued patents directed to our device delivery systems expire between about 2025 and 2036 and our pending patent applications, if issued, would expire between about 2025 and 2042.
Our collaborator ApolloBio Corporation is conducting a Phase 3 clinical trial of VGX-3100 for cervical HSIL in China and plans to seek regulatory approval for and potentially commercialize the candidate in that jurisdiction. VGX-3100 for the Treatment of Anal or Perianal HSIL HPV-16 and HPV-18 can cause precancerous lesions of the anus (anal HSIL).
Our collaborator ApolloBio Corporation is conducting a Phase 3 clinical trial of VGX-3100 for cervical HSIL in China and plans to seek regulatory approval for and potentially commercialize the candidate in that jurisdiction. See “Collaborations and Alliances” below. VGX-3100 for the Treatment of Anal or Perianal HSIL HPV-16 and HPV-18 can cause precancerous lesions of the anus (anal HSIL).
INO-6160 is being evaluated in a Phase 1 trial that is externally sponsored and funded by the National Institute of Allergy and Infectious Diseases, or NIAID. The trial is a randomized, 20-participant, open-label Phase 1 trial to examine the safety and immunogenicity of INO-6160.
INO-6160 is being evaluated in a Phase 1 trial that is externally sponsored and funded by the National Institute of Allergy and Infectious Diseases, or NIAID. The trial is a randomized, 20-participant, open-label Phase 1 trial evaluating the safety and immunogenicity of INO-6160.
The potential limitation of the technology stems from problems with unwanted immune responses against components of the viral vector itself, making repeated administration difficult. Lipid Nanoparticle DNA/RNA Delivery A number of lipid formulations have been developed that increase the effect of DNA/RNA immunotherapies, most notably with COVID-19 mRNA vaccines.
A potential limitation of the technology stems from problems with unwanted immune responses against components of the viral vector itself, making repeated administration to boost or maintain immune responses difficult. Lipid Nanoparticle DNA/RNA Delivery A number of lipid formulations have been developed that increase the effect of DNA/RNA immunotherapies, most notably with COVID-19 mRNA vaccines.
INO-3107 is composed of plasmids encoding for HPV-6 and HPV-11 antigens, as well as human interleukin-12 (IL-12).
INO-3107 is an immunotherapy composed of plasmids encoding for HPV-6 and HPV-11 antigens, as well as human interleukin-12 (IL-12).
There are also various development-stage biotechnology companies involved in different vaccine and immunotherapy technologies, including but not limited to Agenus, AIVITA, Barinthus Biotherapeutics (formerly Vaccitech), BL Corp, Entos Pharma, Frantz Viral Therapeutics, Immunocore, Imunon, ImVax, Iovance, Gritstone Bio, Genexine, Hookipa, Mimivax, Nektar, Northwest Therapeutics, Novavax, Nykode, Precigen, and PapiVax.
There are also various development-stage biotechnology companies involved in different immunotherapy and vaccine technologies, including but not limited to Agenus, AIVITA, Barinthus Biotherapeutics (formerly Vaccitech), BL Corp, BlueSphere Bio, Dynavax, Entos Pharma, Flow Pharma, Frantz Viral Therapeutics, Immunocore, Immunome, Imunon, ImVax, Iovance, Genexine, HOOKIPA, Mimivax, Nektar, Northwest Therapeutics, Novavax, Nykode, Precigen, and PapiVax.
In May 2023, results from an open-label, multicenter Phase 1/2 trial (NCT:04398433) evaluating the efficacy, safety, tolerability and immunogenicity of our lead product candidate INO-3107 in 32 patients with HPV 6 and/or HPV 11-associated RRP were presented at the American Broncho-Esophagological Association (ABEA) program at the Combined Otolaryngology Spring Meetings (COSM) in Boston, Massachusetts.
In May 2023, preliminary results from an open-label, multicenter Phase 1/2 trial (RRP-001; NCT:04398433) evaluating the efficacy, safety, tolerability and immunogenicity of INO-3107 in 32 patients with HPV 6 and/or HPV 11-associated RRP were presented at the American Broncho-Esophagological Association (ABEA) program at the Combined Otolaryngology Spring Meetings (COSM) in Boston, Massachusetts.
We are entitled to receive up to an aggregate of $20.0 million, less required income, withholding or other taxes, upon the achievement of specified milestones related to the regulatory approval of VGX-3100 in accordance with the License and Collaboration Agreement.
We are entitled to receive up to an aggregate of $20.0 million, less required income, withholding or other taxes, upon the achievement of specified milestones related to the regulatory approval of VGX-3100 in accordance with the ApolloBio Agreement.
Additionally, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.
Additionally, on March 11, 2021 the American Rescue Plan Act of 2021 was signed into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, effective January 1, 2024.
The extent of government regulation that might result from any future legislation or administrative action cannot be accurately predicted. Significant Customers and Research and Development During the year ended December 31, 2023, we derived 29% of our revenue from ApolloBio.
The extent of government regulation that might result from any future legislation or administrative action cannot be accurately predicted. Significant Customers and Research and Development During the years ended December 31, 2024 and 2023, we derived 100% and 29%, respectively, of our revenue from ApolloBio.
This open-label single-arm trial plans to enroll approximately 90 participants who will receive up to four doses of VGX-3100 delivered by CELLECTRA 5PSP. The primary endpoint of the trial is histological regression of high-grade anal lesions to low-grade SIL or normal histology. This study is ongoing.
This open-label single-arm trial has enrolled approximately 90 participants who will receive up to four doses of VGX-3100 delivered by CELLECTRA 5PSP. The primary endpoint of the trial is histological regression of high-grade anal lesions to low-grade SIL or normal histology.
In early 2023, updated results were published in Clinical Cancer Research from a Phase 1b/2a trial of INO-3112 in combination with AstraZeneca’s PD-L1 immune checkpoint inhibitor, durvalumab, showing an overall response rate, or ORR, of 27.6% (4 complete responses (CR) and 4 partial responses (PR)) in 29 evaluable patients and increased peripheral HPV-specific T cells and tumoral CD8+ T cells.
In early 2023, updated results were published in Clinical Cancer Research from a Phase 1b/2a trial of INO-3112 in combination with AstraZeneca’s PD-L1 immune checkpoint inhibitor, durvalumab, showing an ORR of 27.6% with 4 complete responses and 4 partial responses in the overall group of 29 evaluable patients and increased presence of peripheral HPV-specific T cells and tumoral CD8+ T cells.
Our product candidate INO-5401 is an immunotherapy consisting of three DNA plasmids encoding for three tumor-associated antigens: human Telomerase Reverse Transcriptase (hTERT), Wilms Tumor gene-1 (WT1) and Prostate-Specific Membrane Antigen (PSMA).
Our immunotherapy candidate INO-5401 consists of three DNA plasmids encoding for three tumor-associated antigens: human Telomerase Reverse Transcriptase (hTERT), Wilms Tumor gene-1 (WT1) and Prostate-Specific Membrane Antigen (PSMA).
Corporate Information Our corporate headquarters are located at 660 W. Germantown Pike, Suite 110, Plymouth Meeting, Pennsylvania 19462, and our main telephone number is (267) 440-4200. Available Information Our Internet website address is www.inovio.com. In addition to the information contained in this Annual Report, information about us can be found on our website.
Germantown Pike, Suite 110, Plymouth Meeting, Pennsylvania 19462, and our main telephone number is (267) 440-4200. Available Information Our Internet website address is www.inovio.com. In addition to the information contained in this Annual Report, information about us can be found on our website.
Employees and Human Capital Resources As of February 14, 2024, we employed 122 people on a full-time basis. Of the total, 90 were in product research, which includes research and development, quality assurance, clinical, engineering and manufacturing, and 32 were in general and administrative functions, which includes corporate development, information technology, legal, commercial, investor relations, finance and corporate administration.
Employees and Human Capital Resources As of February 14, 2025, we employed 134 people on a full-time basis. Of the total, 99 were in product research, which includes research and development, quality assurance, clinical, engineering and manufacturing, and 35 were in general and administrative functions, which includes corporate development, information technology, legal, commercial, investor relations, finance and corporate administration.
INO-3112 for the Treatment of HPV-related Oropharyngeal Squamous Cell Carcinoma, or OPSCC INO-3112 is a DNA medicine candidate targeting HPV 16/18 combined with a DNA plasmid encoding for human IL-12 as an immune activator.
INO-3112 for the Treatment of HPV-related Oropharyngeal Squamous Cell Carcinoma, or OPSCC INO-3112 is a DNA immunotherapy consisting of two plasmids targeting HPV 16/18 combined with a DNA plasmid encoding for human IL-12 as an immune activator.
INO-6160 for HIV INO-6160 is a DNA medicine candidate being developed as a prophylactic vaccine against human immunodeficiency virus, or HIV. INO-6160 is composed of one plasmid encoding for an HIV trimer and one encoding for human IL-12.
INO-6160 for HIV We are developing our DNA medicine candidate INO-6160 as a prophylactic vaccine against human immunodeficiency virus, or HIV. INO-6160 is composed of one plasmid encoding for an HIV trimer and one encoding for human IL-12.
In certain instances, FDA may grant conditional approval of a BLA on the sponsor’s agreement to conduct additional clinical trials, such as these post-approval trials, to further assess the biologic’s safety and effectiveness after BLA approval.
In certain instances, FDA may grant conditional approval of a BLA on the sponsor’s agreement to conduct additional clinical trials, such as these post-approval trials, to further assess the biologic’s safety and effectiveness after BLA approval. Under the accelerated approval pathway, FDA may require the conduct of confirmatory trials before full approval.
Further, the efficacy of the combination of INO-3112 with durvalumab resulted in a median overall survival, or OS, of more than 29 months. This is an improvement over historical data for immune-checkpoint blockade therapy alone, or in combination with other HPV therapeutic vaccines.
Further, the efficacy of the combination of INO-3112 with durvalumab resulted in a median overall survival, or OS, of more than 29 months. This is an improvement over historical data for immune-checkpoint blockade therapy alone, or in combination with other HPV therapeutic vaccines and almost three times the historical overall survival period for monotherapy durvalumab in a similar patient population.
In July 2022, Wistar announced the dosing of the first participant in a Phase 1, open-label, single-center, dose escalation trial to evaluate the safety, tolerability and pharmacokinetic profile of two of our mAb product candidates, administered IM followed immediately by electroporation using our CELLECTRA 2000 device in a 1- and 2-dose regimen (Days 0 and 3) in healthy adults (NCT05293249).
In 2022, Wistar announced the dosing of the first participant in a Phase 1, open-label, single-center, dose escalation trial to evaluate the safety, tolerability and pharmacokinetic profile of the mAb product candidates encoded on our DNA plasmid, administered intramuscularly followed immediately by electroporation using our CELLECTRA 2000 device in a 1- dose (Day 0), 2-dose (Days 0 and 3) and 4-dose regimen (Days 0, 3, 28 and 31) in healthy adults (NCT05293249).
Commercialization and Manufacturing Because of the broad potential applications of our technologies, we intend to develop and commercialize products both on our own and through our collaborators and licensees. We intend to develop and commercialize products in well-defined specialty markets, such as HPV-related diseases, infectious diseases, and cancer. Where appropriate, we intend to rely on strategic marketing and distribution alliances.
We intend to develop and commercialize products both on our own and through our collaborators and licensees. We intend to develop and commercialize products in well-defined specialty markets, such as HPV-related diseases, infectious diseases, and cancer. Where appropriate, we intend to rely on strategic marketing and distribution alliances.
Uncertainties regarding the interpretation and enforcement of Chinese laws, rules and regulations, a trade war, political unrest or unstable economic conditions in China could materially adversely affect our business, financial condition and results of operations. • It is difficult and costly to generate and protect our intellectual property and our proprietary technologies, and we may not be able to ensure their protection. • If we are sued for infringing intellectual property rights of third parties, it will be costly and time-consuming, and an unfavorable outcome in that litigation would have a material adverse effect on our business. • Failure or perceived failure to comply with laws, regulations, contracts, self-regulatory schemes, notices and other obligations related to data privacy and security (including security incidents) could harm our business.
Uncertainties regarding the interpretation and enforcement of Chinese laws, rules and regulations, a trade war, political unrest or unstable economic conditions in China could materially adversely affect our business, financial condition and results of operations. • It is difficult and costly to generate and protect our intellectual property and our proprietary technologies, and we may not be able to ensure their protection. • If we are sued for infringing intellectual property rights of third parties, it will be costly and time-consuming, and an unfavorable outcome in that litigation would have a material adverse effect on our business. • We are subject to stringent and evolving U.S. and foreign laws, regulations, and rules, contractual obligations, industry standards, policies and other obligations related to data privacy and security.
We file patent applications to protect our technologies, inventions and improvements to our inventions that we consider important to the development of our business. We file for patent registration extensively in the United States and in key foreign markets.
Intellectual Property Patents and other proprietary rights are essential to our business. We file patent applications to protect our technologies, inventions and improvements to our inventions that we consider important to the development of our business. We file for patent registration extensively in the United States and in key foreign markets.
Termination or cessation of funding would have a negative impact on our ability to develop certain of our pipeline candidates and/or require us to seek alternative funding sources to advance product candidates. • Our operating results may be harmed if our corporate restructuring plans and cost reduction efforts do not achieve the anticipated results or cause undesirable consequences. 2 • We are currently subject to litigation and may become subject to additional litigation, which could harm our business, financial condition and reputation. • We face intense and increasing competition and steps taken by our competitors, such as the introduction of a new, disruptive technology may impede our ability to develop and commercialize our DNA medicines. • We have entered into collaborations with Chinese companies and rely on clinical materials manufactured in China for our development efforts.
Termination or cessation of funding could have a negative impact on our ability to develop some of the product candidates in our pipeline and/or require us to seek alternative funding sources to advance those candidates. • We are currently subject to litigation and may become subject to additional litigation, which could harm our business, financial condition and reputation. • We face intense and increasing competition and steps taken by our competitors, such as the introduction of a new, disruptive technology may impede our ability to develop and commercialize our DNA medicines. • We have entered into collaborations with Chinese companies and may rely on clinical materials manufactured in China for our development efforts.
We can design our plasmids to teach the body’s cells to produce a wide range of proteins, including antigens to elicit a specific immune response and monoclonal antibodies to fight a specific pathogen.
We can design our plasmids to teach the body’s cells to produce a wide range of proteins, including antigens to elicit a specific immune response, monoclonal antibodies to fight a specific pathogen, or therapeutic proteins to replace defective or missing proteins in the body.
In this trial, statistical significance was not achieved in the investigational biomarker-selected population for the endpoint of lesion regression and viral clearance. However, statistical significance was achieved in the all-participants population for the endpoint of lesion regression and viral clearance. 7 REVEAL2 was our second Phase 3 trial with VGX-3100.
This decision followed final analysis of the data from our second Phase 3 trial of VGX-3100. In this trial, statistical significance was not achieved in the investigational biomarker-selected population for the endpoint of lesion 8 regression and viral clearance. However, statistical significance was achieved in the all-participants population for the endpoint of lesion regression and viral clearance.
The study is ongoing. INO-4201 for Ebola Virus Disease The Ebola virus causes one of the most virulent viral diseases, with case fatality rates averaging approximately 50% but approaching up to 90% in past outbreaks in areas with no or under-developed health care.
The study is ongoing and we and our collaborators plan to present and publish the interim clinical data this year. INO-4201 for Ebola Virus Disease The Ebola virus (EBOV) causes one of the most virulent viral diseases, with case fatality rates averaging approximately 50% but approaching up to 90% in past outbreaks in areas with no or under-developed health care.
The FDA and other regulatory agencies may expand current requirements for public disclosure of DNA-based product development data, which may harm our competitive position with foreign and United States companies developing DNA-based products for similar indications.
The FDA and other regulatory agencies may expand current requirements for public disclosure of DNA-based product development data, which may harm our competitive position with foreign and United States companies developing DNA-based products for similar indications. Manufacturing We rely on third parties for the manufacture of clinical supplies for all of our product candidates.
Additional symptoms of RRP can include a hoarse voice, difficulty in sleeping and swallowing, and chronic coughing. RRP symptoms are usually more severe in 6 children than in adults. The standard of care for RRP is surgery.
In approximately 2% of cases, RRP can develop into squamous cell carcinoma. Additional symptoms of RRP can include a hoarse voice, difficulty in sleeping and swallowing, and chronic coughing. RRP symptoms are usually more severe in children than in adults. The standard of care for RRP is repeated surgery.
VGX-3100 delivered by CELLECTRA-5PSP device was well tolerated in the trial. In addition to the Phase 2 anal HSIL trial described above, a separate Phase 2 trial sponsored by the AIDS Malignancy Consortium (AMC-103 study) is evaluating VGX-3100 in participants with histologically confirmed anal or perianal HSIL associated with HPV-16 and/or HPV-18 who are HIV-positive.
Administration of VGX-3100 by our CELLECTRA-5PSP device was also well tolerated in the trial. A separate Phase 2 trial of VGX-3100 is currently being sponsored by the AIDS Malignancy Consortium. The trial is evaluating VGX-3100 in participants with histologically confirmed anal or perianal HSIL associated with HPV-16 and/or HPV-18 who are HIV-positive.
These are comprised, in part, of: • one U.S. patent, 4 U.S. patent applications and approximately 40 counterpart foreign patent applications directed to treatment of RRP; 12 • seven issued U.S. patents and four U.S. patent applications, as well as approximately 80 issued foreign counterpart patents and approximately 30 counterpart foreign patent applications, directed to treatment of GBM; • approximately 100 issued U.S. patents and approximately 80 U.S. patent applications, as well as approximately 850 issued foreign counterpart patents and approximately 590 counterpart foreign patent applications, directed to our other earlier-stage product candidates; and • 4 issued U.S. patents and 6 U.S. patent applications, as well as approximately 160 issued foreign counterpart patents and approximately 50 counterpart foreign patent applications, directed to our device delivery systems.
These are comprised, in part, of: • one issued U.S. patent, three U.S. patent applications and approximately 40 counterpart foreign patent applications directed to treatment of RRP; • eight issued U.S. patents and five U.S. patent applications, as well as approximately 80 issued foreign counterpart patents and approximately 30 counterpart foreign patent applications, directed to treatment of GBM; • approximately 50 issued U.S. patents and approximately 65 U.S. patent applications, as well as approximately 425 issued foreign counterpart patents and approximately 490 counterpart foreign patent applications, directed to our other earlier-stage product candidates; and • three issued U.S. patents and four U.S. patent applications, as well as approximately 160 issued foreign counterpart patents and approximately 45 counterpart foreign patent applications, directed to our device delivery systems.
Further, on August 16, 2022, President Biden signed the Inflation Reduction Act of 2022, or IRA, into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.
There have been amendments to and judicial and Congressional challenges to certain aspects of the ACA. For example, on August 16, 2022, President Biden signed the Inflation Reduction Act of 2022, or IRA, into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.
INO-5401 for the Prevention of Cancer for People with BRCA1/2 Mutation INOVIO is partnering with the University of Pennsylvania to conduct a Phase 1b investigator-sponsored trial to evaluate the tolerability and immunogenicity of INO-5401 alone or INO-5401 in combination with INO-9012 delivered with CELLECTRA in adult cancer and non-cancer patients with BRCA1 or BRCA2 mutations. This trial is ongoing.
INO-5401 for the Prevention of Cancer for People with BRCA1/2 Mutation We are collaborating with researchers at the University of Pennsylvania to conduct a Phase 1b investigator-sponsored trial to evaluate the tolerability and immunogenicity of INO-5401 alone or in combination with INO-9012, in each case delivered with our CELLECTRA device, for adult cancer and non-cancer patients with BRCA1 or BRCA2 mutations.
All humans have BRCA1 and BRCA2 genes, but some people are born with an error, or mutation, in one of these genes. People with a gene mutation in either BRCA1 or BRCA2 are at heightened risk for certain cancers, including breast, ovarian, prostate, and pancreatic cancers. These gene mutations can be passed on to children by either men or women.
This trial is ongoing. All humans have BRCA1 and BRCA2 genes, but some people are born with an error, or mutation, in one of these genes. People with a gene mutation in either BRCA1 or BRCA2 are at heightened risk for certain cancers, including breast, ovarian, prostate, and pancreatic cancers.
ApolloBio’s obligation to pay royalties will continue for 10 years after the first commercial sale in a particular territory or, if later, until the expiration of the last-to-expire patent covering the licensed products in the specified territory. After marketing approval in a territory, the License and Collaboration Agreement, will continue in force until ApolloBio has no remaining royalty obligations.
ApolloBio’s obligation to pay royalties will continue for 10 years after the first commercial sale in a particular territory or, if later, until the expiration of the last-to-expire patent covering the licensed products in the specified territory.
In the fourth quarter of 2023, we received feedback from the U.S. Food and Drug Administration, or FDA, that the data from this completed trial could be used to support the submission of a Biologic License Application, or BLA, for review under the FDA’s accelerated approval program.
Food and Drug Administration, or FDA, that the data from the completed Phase 1/2 trial could be used to support the submission of a Biologic License Application, or BLA, for review under the FDA’s accelerated approval program.
At the state level, legislatures have increasingly passed legislation and implemented 19 regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework. 22 At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
Our research and development expense was $86.7 million in 2023, $187.7 million in 2022 and $249.2 million in 2021. Geographic Information All of our revenue for the years ended December 31, 2023, 2022 and 2021 was earned in the United States. All of our long-lived assets are located in the United States.
Our research and development expense was $75.6 million in 2024 and $86.7 million in 2023. Geographic Information All of our revenue for the years ended December 31, 2024 and 2023 was earned in the United States. All of our long-lived assets are located in the United States. Corporate Information Our corporate headquarters are located at 660 W.
COVID-19 DNA-encoded Monoclonal Antibodies (dMAb ® ) Using our GOAL algorithm technology, we are able to create precisely designed DNA plasmids that encode for specific monoclonal antibodies (mAbs). We refer to these DNA plasmids as our dMAb product candidates to differentiate them from infused recombinant monoclonal antibodies.
COVID-19 DNA-encoded Monoclonal Antibodies (DMAb ® ) Using our GOAL technology, we are able to create precisely designed DNA plasmids that encode for specific monoclonal antibodies (mAbs).

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeConcerns over inflation, rising interest rates, energy costs, geopolitical issues, global pathogen outbreaks or pandemics, and the availability and cost of credit have in the past and may continue to contribute to increased 46 volatility and diminished expectations for the economy and the markets going forward. Market upheavals may have an adverse effect on us.
Biggest changeConcerns due to reasons including, among other things, inflation, rising interest rates, energy costs, geopolitical issues, political changes and trends such as protectionism, economic nationalism resulting in government actions impacting international trade agreements or imposing trade restrictions such as tariffs and retaliatory counter measures, global pathogen outbreaks or pandemics, and the availability and cost of credit have in the past and may continue to contribute to increased volatility and diminished expectations for the economy and the markets going forward.
DNA medicines are a novel approach to treating and preventing disease, and our CELLECTRA ® delivery devices are a novel approach to administering medicines, and negative perception of the efficacy, safety, or tolerability of any investigational medicines we develop or our devices could adversely affect our ability to conduct our business, advance our investigational medicines, or obtain regulatory approvals.
DNA medicines are a novel approach to treating and preventing disease, and our CELLECTRA delivery devices are a novel approach to administering medicines. Negative perception of the efficacy, safety, or tolerability of any investigational medicines we develop or our devices could adversely affect our ability to conduct our business, advance our investigational medicines, or obtain regulatory approvals.
If we are subject to any liability as a result of our or our third-party manufacturers' activities involving hazardous materials, our business and financial condition may be adversely affected. We have entered into collaborations with Chinese companies and rely on clinical materials manufactured in China for our development efforts.
If we are subject to any liability as a result of our or our third-party manufacturers' activities involving hazardous materials, our business and financial condition may be adversely affected. We have entered into collaborations with Chinese companies and may rely on clinical materials manufactured in China for our development efforts.
The following factors, which are not exhaustive, in addition to the other risk factors described in this report, and the potentially low volume of trades in our common stock, may have a significant impact on the market price of our common stock, some of which are beyond our control: • developments concerning any research and development, clinical trials, manufacturing, and marketing efforts or collaborations; • fluctuating public or scientific interest in the potential for our vaccines or other DNA medicine candidates; • our announcement of significant acquisitions, strategic collaborations, joint ventures or capital commitments; • fluctuations in our operating results; • announcements of technological innovations; • new products or services that we or our competitors offer; • changes in the structure of healthcare payment systems; • the initiation, conduct and/or outcome of intellectual property and/or litigation matters; • changes in financial or other estimates by securities analysts or other reviewers or evaluators of our business; • conditions or trends in bio-pharmaceutical or other healthcare industries; • regulatory developments in the United States and other countries; • perceptions of gene-based therapy; • changes in the economic performance and/or market valuations of other biotechnology and medical device companies; • additions or departures of key personnel; • sales or other transactions involving our common stock; • changes in our capital structure; • sales or other transactions by executive officers or directors involving our common stock; • changes in accounting principles; • global unrest including geopolitical risks emanating from countries such as Russia and China, terrorist activities, the conflict between Israel and Hamas, bank failures, and other economic and other external factors; and • catastrophic weather and/or global disease pandemics.
The following factors, which are not exhaustive, in addition to the other risk factors described in this report, and the potentially low volume of trades in our common stock, may have a significant impact on the market price of our common stock, some of which are beyond our control: • developments concerning any research and development, clinical trials, manufacturing, and marketing efforts or collaborations; • fluctuating public or scientific interest in the potential for our vaccines or other DNA medicine candidates; • our announcement of significant acquisitions, strategic collaborations, joint ventures or capital commitments; • fluctuations in our operating results; • announcements of technological innovations; • new products or services that we or our competitors offer; • changes in the structure of healthcare payment systems; • the initiation, conduct and/or outcome of intellectual property and/or litigation matters; • changes in financial or other estimates by securities analysts or other reviewers or evaluators of our business; • conditions or trends in bio-pharmaceutical or other healthcare industries; • regulatory developments in the United States and other countries; • perceptions of gene-based therapy; • changes in the economic performance and/or market valuations of other biotechnology and medical device companies; • additions or departures of key personnel; • sales or other transactions involving our common stock; • changes in our capital structure; 48 • sales or other transactions by executive officers or directors involving our common stock; • changes in accounting principles; • global unrest including geopolitical risks emanating from countries such as Russia and China, terrorist activities, the conflict between Israel and Hamas, bank failures, and other economic and other external factors; and • catastrophic weather and/or global disease pandemics.
For example: • we, or the parties from whom we have acquired or licensed patent rights, may not have been the first to file the underlying patent applications or the first to make the inventions covered by such patents; • the named inventors or co-inventors of patents or patent applications that we have licensed or acquired may be incorrect, which may give rise to inventorship and ownership challenges; • others may develop similar or alternative technologies, or duplicate any of our products or technologies that may not be covered by our patents, including design-arounds; • pending patent applications may not result in issued patents; • the issued patents covering our products and technologies may not provide us with any competitive advantages or have any commercial value; • the issued patents may be challenged and invalidated, or rendered unenforceable; • governments in the United States or abroad may prevent us from enforcing patents on our vaccines, which could prevent us from excluding competitors from those markets; • the issued patents may be subject to reexamination, which could result in a narrowing of the scope of claims or cancellation of claims found unpatentable; • we may not develop or acquire additional proprietary technologies that are patentable; • our trademarks may be invalid or subject to a third party's prior use; or • our ability to enforce our patent rights will depend on our ability to detect infringement, and litigation to enforce patent rights may not be pursued due to significant financial costs, diversion of resources, and unpredictability of a favorable result or ruling.
For example: • we, or the parties from whom we have acquired or licensed patent rights, may not have been the first to file the underlying patent applications or the first to make the inventions covered by such patents; • the named inventors or co-inventors of patents or patent applications that we have licensed or acquired may be incorrect, which may give rise to inventorship and ownership challenges; 46 • others may develop similar or alternative technologies, or duplicate any of our products or technologies that may not be covered by our patents, including design-arounds; • pending patent applications may not result in issued patents; • the issued patents covering our products and technologies may not provide us with any competitive advantages or have any commercial value; • the issued patents may be challenged and invalidated, or rendered unenforceable; • governments in the United States or abroad may prevent us from enforcing patents on our vaccines, which could prevent us from excluding competitors from those markets; • the issued patents may be subject to reexamination, which could result in a narrowing of the scope of claims or cancellation of claims found unpatentable; • we may not develop or acquire additional proprietary technologies that are patentable; • our trademarks may be invalid or subject to a third party's prior use; or • our ability to enforce our patent rights will depend on our ability to detect infringement, and litigation to enforce patent rights may not be pursued due to significant financial costs, diversion of resources, and unpredictability of a favorable result or ruling.
Foreign Corrupt Practices Act, which, among other things, prohibits companies issuing stock in the U.S. from bribing foreign officials for government contracts and other business; • state 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, state and local laws requiring the registration of pharmaceutical sales and medical representatives, 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 often are not preempted by HIPAA, thus complicating compliance efforts; and • additional state and local laws such as laws in California and Massachusetts, which mandate implementation of compliance programs, compliance with industry ethics codes, and spending limits, and other state and local laws, such as laws in Vermont, Maine, and Minnesota which require reporting to state governments of gifts, compensation, and other remuneration to physicians.
Foreign Corrupt Practices Act, which, among other things, prohibits companies issuing stock in the U.S. from bribing foreign officials for government contracts and other business; • state 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, state and local laws requiring the registration of pharmaceutical sales and medical representatives, 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 often are not preempted by HIPAA, thus complicating compliance efforts; and • additional state and local laws such as laws in California and Massachusetts, which mandate implementation of compliance programs, compliance with industry ethics codes, and spending limits, and other state and local laws, 44 such as laws in Vermont, Maine, and Minnesota which require reporting to state governments of gifts, compensation, and other remuneration to physicians.
If a third party claims that we infringe its intellectual property rights, it could cause our business to suffer in a number of ways, including: • we may become involved in time-consuming and expensive litigation, even if the claim is without merit, the third party's patent is invalid or we have not infringed; • we may become liable for substantial damages for past infringement if a court decides that our technologies infringe upon a third party's patent; • we may be enjoined by a court to stop making, selling or licensing our products or technologies without a license from a patent holder, which may not be available on commercially acceptable terms, if at all, or which may require us to pay substantial royalties or grant cross-licenses to our patents; and • we may have to redesign our products so that they do not infringe upon others' patent rights, which may not be possible or could require substantial investment or time.
If a third party claims that we infringe its intellectual property rights, it could cause our business to suffer in a number of ways, including: 47 • we may become involved in time-consuming and expensive litigation, even if the claim is without merit, the third party's patent is invalid or we have not infringed; • we may become liable for substantial damages for past infringement if a court decides that our technologies infringe upon a third party's patent; • we may be enjoined by a court to stop making, selling or licensing our products or technologies without a license from a patent holder, which may not be available on commercially acceptable terms, if at all, or which may require us to pay substantial royalties or grant cross-licenses to our patents; and • we may have to redesign our products so that they do not infringe upon others' patent rights, which may not be possible or could require substantial investment or time.
If we (or a third party upon whom we rely) experience a security incident or are perceived to have experienced a security incident, we may experience adverse consequences, such as government enforcement actions (for example, investigations, fines, penalties, audits, and 38 inspections); additional reporting requirements and/or oversight; restrictions on processing sensitive information (including personal data); litigation (including class claims); indemnification obligations; negative publicity; reputational harm; monetary fund diversions; diversion of management attention; interruptions in our operations (including availability of data); financial loss; and other similar harms.
If we (or a third party upon whom we rely) experience a security incident or are perceived to have experienced a security incident, we may experience adverse consequences, such as government enforcement actions (for example, investigations, fines, penalties, audits, and inspections); additional reporting requirements and/or oversight; restrictions on processing sensitive information (including personal data); litigation (including class claims); indemnification obligations; negative publicity; reputational harm; monetary fund diversions; diversion of management attention; interruptions in our operations (including availability of data); financial loss; and other similar harms.
In addition, future acquisitions 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 to develop acquired products or technologies; • incurrence of substantial debt or dilutive issuances of securities to pay for acquisitions; • higher than expected acquisition and integration costs; • 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.
In addition, future acquisitions 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 to develop acquired products or technologies; • incurrence of substantial debt or dilutive issuances of securities to pay for acquisitions; • higher than expected acquisition and integration costs; • increased amortization expenses; 40 • 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.
Similar to the federal healthcare program Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and related regulations, which impose certain requirements relating to the privacy, security and transmission of individually identifiable health information on certain individuals and entities; • the Physician Payments Sunshine Act, created under the ACA, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with certain exceptions, to report annually to CMS, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), other healthcare professionals (such as physicians assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; • the FDCA, which among other things, strictly regulates drug product marketing, prohibits manufacturers from marketing drug products for off-label use and regulates the distribution of drug samples; • the U.S.
Similar to the federal healthcare program Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and related regulations, which impose certain requirements relating to the privacy, security and transmission of individually identifiable health information on certain individuals and entities; • the Physician Payments Sunshine Act, created under the ACA, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with certain exceptions, to report annually to CMS, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), other healthcare professionals (such as physicians assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; • the Federal Food, Drug and Cosmetic Act (FDCA), which among other things, strictly regulates drug product marketing, prohibits manufacturers from marketing drug products for off-label use and regulates the distribution of drug samples; • the U.S.
The laws that may affect our ability to operate include: • the federal healthcare program Anti-Kickback Statute, which prohibits, among other things, people from soliciting, receiving or providing remuneration, directly or indirectly, to induce or reward either the referral of an individual, or ordering, or leasing of an item, good, facility or service, for which payment may be made by a federal healthcare 40 program such as Medicare or Medicaid.
The laws that may affect our ability to operate include: • the federal healthcare program Anti-Kickback Statute, which prohibits, among other things, people from soliciting, receiving or providing remuneration, directly or indirectly, to induce or reward either the referral of an individual, or ordering, or leasing of an item, good, facility or service, for which payment may be made by a federal healthcare program such as Medicare or Medicaid.
Coupled with the expansion of social media platforms and similar devices that allow individuals access to a broad audience, these claims have had a significant negative impact on some businesses. Certain companies that have faced employment- or harassment-related lawsuits have had to 42 terminate management or other key personnel, and have suffered reputational harm that has negatively impacted their business.
Coupled with the expansion of social media platforms and similar devices that allow individuals access to a broad audience, these claims have had a significant negative impact on some businesses. Certain companies that have faced employment- or harassment-related lawsuits have had to terminate management or other key personnel, and have suffered reputational harm that has negatively impacted their business.
However, companies may in certain circumstances share truthful and not misleading information that is otherwise consistent with the product’s FDA approved labeling. In addition, manufacturers of drug products and their facilities are subject to continual review and periodic inspections by the FDA and other regulatory authorities for compliance with current good manufacturing practices, or cGMP, regulations.
However, companies may in certain circumstances share truthful and not misleading information that is otherwise consistent with the product’s FDA approved labeling. In addition, manufacturers of drug products and devices and their facilities are subject to continual review and periodic inspections by the FDA and other regulatory authorities for compliance with current good manufacturing practices, or cGMP, regulations.
In addition, regardless of merit or eventual outcome, product liability claims may result in: • decreased demand for our DNA medicine candidates; • impairment of our business reputation; • withdrawal of clinical trial participants; • costs of related litigation; • distraction of management's attention from our primary business; • substantial monetary awards to patients or other claimants; • loss of revenues; and • inability to commercialize our products.
In addition, regardless of merit or eventual outcome, product liability claims may result in: • decreased demand for our DNA medicine candidates; • impairment of our business reputation; • withdrawal of clinical trial participants; 42 • costs of related litigation; • distraction of management's attention from our primary business; • substantial monetary awards to patients or other claimants; • loss of revenues; and • inability to commercialize our products.
The commencement and completion of clinical trials can be delayed for a number of reasons, including delays related to: • obtaining regulatory approval to commence a clinical trial; • adverse results from third-party clinical trials involving gene-based therapies and the regulatory response thereto; • reaching agreement on acceptable terms with prospective CROs and trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; • future bans or stricter standards imposed on clinical trials of gene-based therapy; • manufacturing sufficient quantities of our proprietary device and DNA medicine candidates for use in clinical trials; • obtaining Internal Review Board, or IRB, approval to conduct a clinical trial at a prospective site; • slower than expected recruitment and enrollment of patients to participate in clinical trials for a variety of reasons, including competition from other clinical trial programs for similar indications; • conducting clinical trials with sites internationally due to regulatory approvals and meeting international standards; 26 • retaining patients who have initiated a clinical trial but may be prone to withdraw due to side effects from the therapy, lack of efficacy or personal issues, or who are lost to further follow-up; • collecting, reviewing and analyzing our clinical trial data; and • global unrest, including geopolitical risks emanating from countries such as Russia and China, global pathogen outbreaks or pandemics, terrorist activities, the conflict between Israel and Hamas, bank failures and other economic and other external factors beyond our control.
The commencement and completion of clinical trials can be delayed for a number of reasons, including delays related to: • obtaining regulatory approval to commence a clinical trial; • adverse results from third-party clinical trials involving gene-based therapies and the regulatory response thereto; • reaching agreement on acceptable terms with prospective CROs and trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; • future bans or stricter standards imposed on clinical trials of gene-based therapy; • manufacturing sufficient quantities of our proprietary device and DNA medicine candidates for use in clinical trials; • obtaining Institutional Review Board, or IRB, approval to conduct a clinical trial at a prospective site; • slower than expected recruitment and enrollment of patients to participate in clinical trials for a variety of reasons, including competition from other clinical trial programs for similar indications; • conducting clinical trials with sites internationally due to regulatory approvals and meeting international standards; • retaining patients who have initiated a clinical trial but may be prone to withdraw due to side effects from the therapy, lack of efficacy or personal issues, or who are lost to further follow-up; • collecting, reviewing and analyzing our clinical trial data; and • global unrest, including geopolitical risks emanating from countries such as Russia and China, global pathogen outbreaks or pandemics, terrorist activities, the conflict between Israel and Hamas, bank failures and other economic and other external factors beyond our control.
If our information technology systems or those of third parties upon which we rely or our data, are or were compromised, we could experience adverse consequences resulting from such compromise, including but not limited to, regulatory 37 investigations and actions; litigation; fines and penalties; disruptions of our business operations; reputational harm; loss of revenue and profits; and other adverse consequences.
If our information technology systems or those of third parties upon which we rely or our data, are or were compromised, we could experience adverse consequences resulting from such compromise, including but not limited to, regulatory investigations and actions; litigation; fines and penalties; disruptions of our business operations; reputational harm; loss of revenue and profits; and other adverse consequences.
Data Privacy Framework and the UK extension thereto (which allows for transfers to relevant U.S.-based organizations who self-certify compliance and participate in the Framework), these mechanisms are subject to legal challenges, and there is no assurance that we can satisfy or rely on these measures to lawfully transfer personal data to the United States.
Data Privacy Framework and the UK extension thereto (which allows for 52 transfers to relevant U.S.-based organizations who self-certify compliance and participate in the Framework), these mechanisms are subject to legal challenges, and there is no assurance that we can satisfy or rely on these measures to lawfully transfer personal data to the United States.
If these third parties do not successfully carry out their contractual duties or meet expected deadlines, we and our collaborators may not be able to obtain regulatory approval for or commercialize our DNA medicine candidates. We and our collaborators have entered into agreements with CROs to provide monitors for and to manage data for our on-going clinical programs.
If these third parties do not successfully carry out their contractual duties or meet expected deadlines, we and our collaborators may not be able to obtain regulatory approval for or commercialize our DNA medicine candidates. 36 We and our collaborators have entered into agreements with CROs to provide monitors for and to manage data for our on-going clinical programs.
Following an assessment of the current global demand for COVID-19 vaccines, changes in regulatory timelines and requirements, diminishing government financial support, and the overall growing uncertainty related to opportunities for 27 heterologous booster vaccines, in the fourth quarter of 2022 we discontinued our internally funded efforts to develop INO-4800 as a COVID-19 heterologous booster vaccine.
Following an assessment of the current global demand for COVID-19 vaccines, changes in regulatory timelines and requirements, diminishing government financial support, and the overall growing uncertainty related to opportunities for heterologous booster vaccines, in the fourth quarter of 2022 we discontinued our internally funded efforts to develop INO-4800 as a COVID-19 heterologous booster vaccine.
There may be significant 34 delays in obtaining coverage and reimbursement as the process of determining coverage and reimbursement is often time-consuming and costly which will require us to provide scientific and clinical support for the use of our products to each payor separately, with no assurance that coverage or adequate reimbursement will be obtained.
There may be significant delays in obtaining coverage and reimbursement as the process of determining coverage and reimbursement is often time-consuming and costly which will require us to provide scientific and clinical support for the use of our products to each payor separately, with no assurance that coverage or adequate reimbursement will be obtained.
Remote work has also become more common and increased risks to our information technology systems and data. Future or past business transactions (such as acquisitions or integrations) could expose us to additional cybersecurity risks and vulnerabilities as our systems could be negatively affected by vulnerabilities resent in acquired or integrated entities’ systems and technologies.
Remote work has also become more common and increased risks to our information technology systems and data. Future or past business transactions (such as acquisitions or integrations) could expose us to additional cybersecurity risks and vulnerabilities as our systems could be negatively affected by vulnerabilities resent in acquired or integrated entities’ 41 systems and technologies.
More restrictive statutory regimes, government regulations, or negative public opinion would have an adverse effect on our business, financial condition, results of operations, and prospects and may delay or impair the development of our investigational medicines and commercialization of any approved products or demand for any products we may develop.
More restrictive statutory regimes, government regulations, or negative public opinion would have an adverse effect on our 31 business, financial condition, results of operations, and prospects and may delay or impair the development of our investigational medicines and commercialization of any approved products or demand for any products we may develop.
While we seek to maintain adequate inventory of the single-source components and materials used in 29 our product candidates, any interruption or delay in the supply of components or materials, or our inability to obtain components or materials from alternate sources at acceptable prices in a timely manner, could impair our ability to supply our investigational medicines.
While we seek to maintain adequate inventory of the single-source components and materials used in our product candidates, any interruption or delay in the supply of components or materials, or our inability to obtain components or materials from alternate sources at acceptable prices in a timely manner, could impair our ability to supply our investigational medicines.
On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.
On December 8, 43 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.
We will also have to compete with other pharmaceutical and biotechnology companies to recruit, hire, train and 33 retain marketing and sales personnel. To the extent we rely on third parties to commercialize our approved products, if any, we will receive lower revenues than if we commercialized these products ourselves.
We will also have to compete with other pharmaceutical and biotechnology companies to recruit, hire, train and retain marketing and sales personnel. To the extent we rely on third parties to commercialize our approved products, if any, we will receive lower revenues than if we commercialized these products ourselves.
The FDA also weighs the benefits of a product against its risks and the FDA may view the efficacy results in the context of safety as not being supportive of licensure. Other regulatory authorities in Europe and other countries may make similar findings with respect to these endpoints.
The FDA also weighs the benefits of a product against its risks and the FDA may view the efficacy results in the context of safety as not 34 being supportive of licensure. Other regulatory authorities in Europe and other countries may make similar findings with respect to these endpoints.
For drugs that have been 31 designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens.
For drugs that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens.
For example, the California Consumer Privacy Act of 2018 (“CCPA”), applies to personal data of 48 consumers, business representatives, and employees who are California residents, and requires certain businesses to provide specific disclosures in privacy notices and honor requests of such individuals to exercise certain privacy rights.
For example, the California Consumer Privacy Act of 2018 (“CCPA”), applies to personal data of consumers, business representatives, and employees who are California residents, and requires certain businesses to provide specific disclosures in privacy notices and honor requests of such individuals to exercise certain privacy rights.
We and our manufacturers are subject to federal, state and local laws and regulations governing the use, manufacture, storage, handling and disposal of these hazardous materials. In the event of an accident, state or federal authorities may curtail the use of these 41 materials and interrupt our business operations.
We and our manufacturers are subject to federal, state and local laws and regulations governing the use, manufacture, storage, handling and disposal of these hazardous materials. In the event of an accident, state or federal authorities may curtail the use of these materials and interrupt our business operations.
Social media is increasingly being used to communicate about our research, development candidates, investigational medicines, and the diseases our development candidates and investigational medicines are being developed to treat. Social media practices in the biopharmaceutical industry continue to evolve and regulations relating to such use are not always clear.
Social media is increasingly being used to communicate about our research, development candidates, investigational medicines, and the diseases our development candidates and investigational medicines are being developed to treat. Social 51 media practices in the biopharmaceutical industry continue to evolve and regulations relating to such use are not always clear.
Any decline in available funding or access to our cash and liquidity resources could, among other risks, limit our ability to meet our capital needs and fund future growth or fulfill our other obligations, or result in breaches of our financial and/or contractual obligations.
Any decline in available funding or access to our cash and liquidity resources could, among other risks, limit our ability to meet our capital needs and fund future growth or fulfill our 50 other obligations, or result in breaches of our financial and/or contractual obligations.
There has been limited clinical trial experience for the development of pharmaceuticals to treat these rare diseases in general, and we are not aware of a registrational trial that led to approval of a 30 drug to treat these diseases.
There has been limited clinical trial experience for the development of pharmaceuticals to treat these rare diseases in general, and we are not aware of a registrational trial that led to approval of a drug to treat these diseases.
If the FDA does not consider or approve our application, it may require that we conduct additional clinical, preclinical or manufacturing validation studies and submit that data before it will reconsider our application.
If the FDA does not consider or approve our application, it may 27 require that we conduct additional clinical, preclinical or manufacturing validation studies and submit that data before it will reconsider our application.
If we, our DNA medicine candidates, or the manufacturing facilities for our DNA medicine candidates fail to comply with applicable regulatory requirements, a regulatory agency may: • issue Warning Letters or untitled letters; • impose civil or criminal penalties; • suspend regulatory approvals; • suspend any ongoing clinical trials; • refuse to approve pending applications or supplements to applications filed by us; • impose restrictions on operations, including costly new manufacturing requirements; or • seize or detain products or require us to initiate a product recall.
If we, our DNA medicine candidates, or the manufacturing facilities for our DNA medicine candidates fail to comply with applicable regulatory requirements, a regulatory agency may: • issue Warning Letters or untitled letters; • initiate injunction actions; • impose civil or criminal penalties; • suspend regulatory approvals; • suspend any ongoing clinical trials; • refuse to approve pending applications or supplements to applications filed by us; • impose restrictions on operations, including costly new manufacturing requirements; or • seize or detain products or require us to initiate a product recall.
For example, we may be approved only for a very limited indication, we may not successfully complete required post-approval trials, such trials may not confirm the clinical benefit of our drug, or approval of the drug may be withdrawn.
For example, we may be approved only for a very limited indication, we may not successfully complete required post-approval trials, such trials may not confirm the clinical benefit of our drug, or approval 35 of the drug may be withdrawn.
Delays in the commencement, conduct or completion of clinical testing could result in increased costs to us and delay or limit our ability to generate revenues. Delays in the commencement, conduct or completion of clinical testing could significantly affect our product development costs.
Delays in the commencement, conduct or completion of clinical testing could result in increased costs to us and delay or limit our ability to generate revenues. 29 Delays in the commencement, conduct or completion of clinical testing could significantly affect our product development costs.
Although the FDA and other regulatory agencies do not regulate a physician’s choice of drug treatment made in the physician’s independent medical judgment, they do restrict promotional communications from companies or their sales force with respect to off-label uses of products for which marketing clearance has not been issued.
Although the FDA and other regulatory authorities do not regulate a physician’s choice of drug treatment made in the physician’s independent medical judgment, they do restrict promotional communications from companies or their sales force with respect to off-label uses of products for which marketing clearance has not been issued.
Such threats are prevalent and continue to rise, are increasingly difficult to detect and come from a variety of sources such as traditional computer “hackers,” threat actors, “hactivists,” organized criminal threat actors, personnel (such as through error or malfeasance), sophisticated national states and nation-state support actors (for example, in conjunction with military conflicts).
Such threats are prevalent and continue to rise, are increasingly difficult to detect and come from a variety of sources such as traditional computer “hackers,” threat actors, “hacktivists,” organized criminal threat actors, personnel (such as through error or malfeasance), sophisticated national states and nation-state support actors (for example, in conjunction with military conflicts).
There are limited data regarding the efficacy of DNA medicine candidates compared with conventional vaccines, and we must conduct a substantial amount of additional research and development before the FDA or any comparable foreign regulatory authority will approve any of our DNA medicine candidates.
There are limited data regarding the efficacy of DNA medicine candidates compared with conventional therapies, including vaccines, and we must conduct a substantial amount of additional research and development before the FDA or any comparable foreign regulatory authority will approve any of our DNA medicine candidates.
Further, the ACA codified case law that a claim including items or services resulting from a violation of the federal healthcare program Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act; • federal civil and criminal false claims laws, including the civil False Claims Act, 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; • HIPAA, which prohibits, among other things, executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters.
Further, the ACA codified case law that a claim including items or services resulting from a violation of the federal healthcare program Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act; • federal civil and criminal false claims laws, including the civil False Claims Act, 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 Health Insurance Portability and Accountability Act (HIPAA), which prohibits, among other things, executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters.
Our product candidates could fail to complete the clinical trial process for many reasons, including the following: • we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that our proprietary device or product candidate is safe and effective for any indication; • the results of clinical trials may not meet the level of clinical or statistical significance required by the FDA or comparable foreign regulatory authorities for approval; • the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials; • we may not be successful in enrolling a sufficient number of participants in clinical trials; • we may be unable to demonstrate that our proprietary device or DNA medicine candidates' clinical and other benefits outweigh their safety risks; • we may be unable to demonstrate that our proprietary device or product candidate presents an advantage over existing therapies, or over placebo in any indications for which the FDA requires a placebo-controlled trial; • the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials; • the data collected from clinical trials of our DNA medicine candidates may not be sufficient to support the submission of a new drug application or other submission or to obtain regulatory approval in the United States or elsewhere; • the FDA or comparable foreign regulatory authorities may fail to approve our manufacturing processes or facilities or that of third-party manufacturers with which we or our collaborators contract for clinical and commercial supplies; and • the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
Our product candidates could fail to complete the clinical trial process for many reasons, including the following: • we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that our proprietary device meets the standard of reasonable assurance of safety and effectiveness or that our product candidate is safe and effective for any indication; • the results of clinical trials may not meet the level of clinical or statistical significance required by the FDA or comparable foreign regulatory authorities for approval; • the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials; • we may not be successful in enrolling a sufficient number of participants in clinical trials; • we may be unable to demonstrate that our proprietary device or DNA medicine candidates' clinical and other benefits outweigh their safety risks; • we may be unable to demonstrate that our proprietary device or product candidate presents an advantage over existing therapies, or over placebo in any indications for which the FDA requires a placebo-controlled trial; • the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials; • the data collected from clinical trials of our DNA medicine candidates may not be sufficient to support the submission of a new drug application or other submission or to obtain regulatory approval in the United States or elsewhere; • the FDA or comparable foreign regulatory authorities may fail to approve our manufacturing processes or facilities or that of third-party manufacturers with which we or our collaborators contract for clinical and commercial supplies; and • the regulations or marketing authorization and approval policies of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for marketing authorization or approval.
Any of these events could have a material adverse effect on our reputation, business, or financial 49 condition, including but not limited to: inability to process personal data or to operate in certain jurisdictions; limited ability to develop or commercialize our products; expenditure of time and resources to defend any claim or inquiry; adverse publicity; or substantial changes to our business model or operations. 50 ITEM 1B.
Any of these events could have a material adverse effect on our reputation, business, or financial condition, including but not limited to: inability to process personal data or to operate in certain jurisdictions; limited ability to develop or commercialize our products; expenditure of time and resources to defend any claim or inquiry; adverse publicity; or substantial changes to our business model or operations. 53 ITEM 1B.
If we fail to obtain FDA approval to market our proprietary device and DNA medicine candidates, we will be unable to sell our products in the United States, which will significantly impair our ability to generate any revenues.
If we fail to obtain FDA approval to market our proprietary device and DNA medicine candidates as combination products, we will be unable to sell our products in the United States, which will significantly impair our ability to generate any revenues.
For example, in 2021 the DoD discontinued funding for the planned Phase 3 trial of our COVID-19 product candidate, which resulted in increased expenditures by us. 32 Government agencies may fail to perform their responsibilities under these agreements, which may cause them to be terminated by the government agencies.
For example, in 2021 the DoD discontinued funding for the planned Phase 3 trial of our COVID-19 product candidate, which resulted in increased expenditures by us. Government agencies may fail to perform their responsibilities under these agreements, which may cause them to be terminated by the government agencies. In addition, we may fail to perform our responsibilities under these agreements.
For example, we previously relied on VGXI to manufacture DNA plasmids for our DNA medicine candidates before they became unable to produce the necessary plasmids due to a lack of manufacturing capacity. As a result, we had to engage several additional third-party contract manufacturers.
In addition, we previously relied on VGXI to manufacture DNA plasmids for our DNA medicine candidates before they became unable to produce the necessary plasmids due to a lack of manufacturing capacity. As a result, we had to engage several additional third-party contract manufacturers.
The IRA also eliminates the "donut hole" under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program. It is unclear how such challenges, and the healthcare reform measures of the Biden administration will impact the ACA and our business.
The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program. It is unclear how such challenges, and the healthcare reform measures of the Biden administration will impact the ACA and our business.
Our future capital requirements will depend on many factors, including, among others: • the progress of our current and new product development programs; • the progress, scope and results of our pre-clinical and clinical testing; • the time and cost involved in obtaining regulatory approvals; • the cost of manufacturing our DNA medicine candidates; • the cost of prosecuting, enforcing and defending against patent infringement claims and other intellectual property rights; • debt service obligations; • competing technological and market developments; and 23 • our ability and the related costs to establish and maintain collaborative and other arrangements with third parties to assist in potentially bringing our products to market.
Our future capital requirements will depend on many factors, including, among others: • the progress of our current and new product development programs; • the progress, scope and results of our pre-clinical and clinical testing; • the time and cost involved in obtaining regulatory approvals; • the cost to commercialize any product that obtains regulatory approval; • the cost of manufacturing our DNA medicine candidates; • the cost of prosecuting, enforcing and defending against patent infringement claims and other intellectual property rights; 26 • debt service obligations; • competing technological and market developments; and • our ability and the related costs to establish and maintain collaborative and other arrangements with third parties to assist in potentially bringing our products to market.
This regulatory review and approval process, which includes evaluation of preclinical studies and clinical trials of our products as well as the evaluation of our manufacturing processes and our third-party contract manufacturers' facilities, is lengthy, expensive and uncertain.
This regulatory review and approval process, which includes evaluation of preclinical studies and clinical trials of our combination products as well as the evaluation of our device design, manufacturing processes and our third-party contract manufacturers' facilities, is lengthy, expensive and uncertain.
Even if United States regulatory approval is obtained, regulators may still impose significant restrictions on a product's indicated uses or marketing or impose ongoing requirements for potentially costly post-approval studies. This governmental oversight may be particularly strict with respect to gene-based therapies.
Even if FDA regulatory approval is obtained, regulators may still impose significant restrictions on a product's indicated uses or marketing or impose ongoing requirements for potentially costly post-approval studies. This governmental 33 oversight may be particularly strict with respect to gene-based therapies.
Period to period comparisons are not 44 indicative of future performance.
Period to period comparisons are not indicative of future performance.
Third-party manufacturers may not be able to comply with cGMP regulations, regulations applicable to biologic/device combination products, including applicable provisions of the FDA’s drug cGMP regulations, device cGMP requirements embodied in the quality system regulations or similar regulatory requirements outside the United States.
Third-party manufacturers may not be able to comply with cGMP regulations, regulations applicable to biologic/device combination products, including applicable provisions of the FDA’s drug cGMP regulations, device cGMP requirements embodied in the quality system regulations, and any amendments thereto, or similar regulatory requirements outside the United States.
We are not permitted to market or promote our proprietary device and DNA medicine candidates before we receive regulatory approval from the FDA or comparable foreign regulatory authorities.
We are not permitted to market or promote our proprietary device and DNA medicine candidates as combination products before we receive regulatory approval from the FDA or comparable foreign regulatory authorities.
We have experienced significant operating losses over the last several years. As of December 31, 2023 our accumulated deficit was $1.6 billion. We have generated limited revenues, primarily consisting of license revenue, grant funding and interest income.
We have experienced significant operating losses over the last several years. As of December 31, 2024 our accumulated deficit was $1.7 billion. We have generated limited revenues, primarily consisting of license revenue, grant funding and interest income.
Additionally, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.
Additionally, on March 11, 2021, the American Rescue Plan Act of 2021 was signed into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, effective January 1, 2024.
If the safety of any product is compromised due to our or our manufacturers' failure to adhere to applicable laws or for other reasons, we may not be able to obtain regulatory approval for or successfully commercialize our products, and we may be held liable for any injuries sustained as a result.
If the safety of any product is compromised due to our or our manufacturers' failure to adhere to applicable laws or for other reasons, we may not be able to pass preapproval inspection of our manufacturing facilities and obtain regulatory approval for or successfully commercialize our products, and we may be held liable for any injuries sustained as a result.
Risks Related to Product Development, Manufacturing and Regulatory Approval If we are unable to obtain FDA approval of our product candidates, we will not be able to commercialize them in the United States. We need FDA approval prior to marketing our proprietary device and DNA medicine candidates in the United States.
Risks Related to Product Development, Manufacturing and Regulatory Approval If we are unable to obtain FDA approval of our proprietary devices and DNA medicine candidates, we will not be able to commercialize them in the United States.
Furthermore, because our product candidates are combination products comprising an electroporation device for delivery of a biologic, additional time may be required to obtain regulatory approval for our product candidates because of the complexity involved with co-packaging a drug-device combination product.
Furthermore, because our product candidates are drug-device combination products comprising an electroporation device for delivery of a biologic, additional time may be required to obtain regulatory approval for our product candidates because of the complexity involved with developing and manufacturing a drug-device combination product.
If we pursue accelerated approval for INO-3107 or any of our other product candidates, it may not lead to a faster development or regulatory review or approval process and does not increase the likelihood that our product candidates will receive marketing approval.
Pursuing accelerated approval for INO-3107 or any of our other product candidates may not lead to a faster development or regulatory review or approval process and does not increase the likelihood that our product candidates will receive marketing approval.
Some companies are seeking to treat early HPV infections or low-grade cervical dysplasia. Loop Electrosurgical Excision Procedure, commonly known as LEEP, is a surgical procedure and is the current standard of care for treating high-grade cervical dysplasia.
Some companies are seeking to treat early HPV infections or low-grade cervical dysplasia. Loop Electrosurgical Excision Procedure, commonly known as LEEP, is a surgical procedure and is the current standard of care in the United States and other high income countries for treating high-grade cervical dysplasia.
We have entered into agreements with government agencies, such as the National Institutes of Health’s National Institute of Allergy and Infectious Diseases, DARPA, Medical CBRN Defense Consortium and the Department of Defense (DoD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, and we intend to continue entering into these types of agreements with government agencies in the future.
We have entered into agreements with government agencies, such as the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIH NIAID), Defense Advanced Research Projects Agency (DARPA), Medical CBRN Defense Consortium (MCDC) and the Department of Defense (DoD) Joint Program Executive Office (JPEO) for Chemical, Biological, Radiological and Nuclear Defense (CBRN), and we intend to continue entering into these types of agreements with government agencies in the future.
In addition, there is also a risk that due to changes in laws and regulations, such as alternative minimum taxes or suspensions on the use of net operating losses, or other unforeseen reasons, our existing net operating losses could expire or otherwise become unavailable to offset future income tax liabilities. General Risk Factors Our quarterly operating results may fluctuate significantly.
In addition, there is also a risk that due to changes in laws and regulations, such as alternative minimum taxes or suspensions on the use 49 of net operating losses, or other unforeseen reasons, our existing net operating losses could expire or otherwise become unavailable to offset future income tax liabilities.
We have agreements with government agencies that are subject to termination and uncertain future funding. Termination or cessation of funding would have a negative impact on our ability to develop certain of our pipeline candidates and/or require us to seek alternative funding sources to advance product candidates.
We have agreements with government agencies that are subject to termination and uncertain future funding. Termination or cessation of funding could have a negative impact on our ability to develop some of the product candidates in our pipeline and/or require us to seek alternative funding sources to advance those candidates.
As a result, Precigen could receive marketing approval for its RRP product candidate before we can obtain regulatory approval for INO-3107, which could put us at a competitive disadvantage in this indication. Advaxis, Genexine, and Gilead Sciences have therapeutic cervical cancer product candidates under development.
As a result, Precigen could receive marketing approval for its RRP product candidate before we can obtain regulatory approval for INO-3107, which could put us at a competitive disadvantage in this indication. Advaxis, Genexine, and Gilead Sciences have therapeutic cervical cancer product candidates under development. Many companies are pursuing different approaches to pre-cancers and cancers we are targeting.
The time required to obtain approval by the FDA and similar foreign authorities is unpredictable but typically takes many years following the commencement of clinical trials, depending upon numerous factors. In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change. We have not obtained regulatory approval for any human-use products.
The time required to obtain approval by the FDA and similar foreign authorities is unpredictable but typically takes many years following the commencement of clinical trials, depending upon numerous factors. In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change.
Many companies are pursuing different approaches to pre-cancers and cancers we are targeting. 36 We also compete more specifically with companies seeking to utilize antigen-encoding DNA delivered with electroporation or other delivery technologies such as viral vectors or lipid vectors to induce in vivo generated antigen production and immune responses to prevent or treat various diseases.
We also compete more specifically with companies seeking to utilize antigen-encoding DNA delivered with electroporation or other delivery technologies such as viral vectors or lipid vectors to induce in vivo generated antigen production and immune responses to prevent or treat various diseases.
In addition, if the FDA and similar 24 regulatory agencies do not approve our delivery devices, then we will not be able to bring to market our DNA medicines that rely on delivery by such a device. Such delays or failure to obtain approval of our devices would result in significant harm to our business.
In addition, if the FDA and similar regulatory authorities do not provide marketing authorization for our delivery devices, then we will not be able to bring to market our DNA medicines that rely on delivery by such a device. Such delays or failure to obtain marketing authorization for our devices would result in significant harm to our business.
Our products, even if they are deemed to be safe and effective by regulatory authorities, could be difficult to manufacture on a large scale or uneconomical to market, or our competitors could develop superior products more quickly and efficiently or more effectively market their competing products.
Our products, even if they are deemed to be safe and effective by regulatory authorities, could be difficult to manufacture on a large scale, particularly given the complexity concerning the manufacturing of combination products, or uneconomical to 30 market, or our competitors could develop superior products more quickly and efficiently or more effectively market their competing products.
Human-use equipment and DNA medicine candidates in later stages of clinical trials may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical testing.
Results of an animal study may not be indicative of results achievable in human studies. Human-use equipment and DNA medicine candidates in later stages of clinical trials may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical testing.
We are dependent on single-source suppliers for some of the components and materials used in, and the processes required to develop, our product candidates and investigational medicines. We currently depend on single-source suppliers for some of the components and materials used in, and manufacturing processes required to develop and commercialize, our product candidates and investigational medicines.
We are dependent on single-source suppliers for some of the components and materials used in, and the processes required to develop, our proprietary device and DNA medicine candidates. We currently depend on single-source suppliers for some of the components and materials used in, and manufacturing processes required to develop and commercialize, our proprietary device and DNA medicine candidates.
Moreover, the U.S. government, state legislatures and foreign governmental entities have shown significant interest in implementing cost containment programs to limit the growth of government-paid healthcare costs, including price controls, restrictions on reimbursement and coverage and requirements for substitution of generic products for branded prescription drugs.
Third-party payors are increasingly challenging the effectiveness of and prices charged for medical products and services. 38 Moreover, the U.S. government, state legislatures and foreign governmental entities have shown significant interest in implementing cost containment programs to limit the growth of government-paid healthcare costs, including price controls, restrictions on reimbursement and coverage and requirements for substitution of generic products for branded prescription drugs.
Manufacturers often encounter difficulties in production, particularly in scaling up for commercial production. 28 These problems include difficulties with production costs and yields, quality control, including stability of the equipment and DNA medicine candidates and quality assurance testing, shortages of qualified personnel, as well as compliance with strictly enforced federal, state and foreign regulations.
These problems include difficulties with production costs and yields, quality control, including stability of the equipment and DNA medicine candidates and quality assurance testing, shortages of qualified personnel, as well as compliance with strictly enforced federal, state and foreign regulations.
In addition, the novelty of our CELLECTRA ® delivery devices may make it difficult to demonstrate to physicians and third-party payors that this delivery system is an appropriate approach for DNA medicines and provides advantages compared to the current standards of care.
In addition, even if our product candidates receive regulatory approval from the FDA and similar regulatory authorities, the novelty of our CELLECTRA delivery devices may make it difficult to demonstrate to physicians and third-party payors that this delivery system is an appropriate approach for DNA medicines and provides advantages compared to the current standards of care.
Additionally, these obligations may be subject to differing applications and interpretations, which may be inconsistent or conflict among jurisdictions. Preparing for and complying with these obligations requires us to devote significant resources and may necessitate changes to our services, information technologies, systems, and practices and to those of any third parties that process personal data on our behalf.
Preparing for and complying with these obligations requires us to devote significant resources and may necessitate changes to our services, information technologies, systems, and practices and to those of any third parties that process personal data on our behalf.
To the extent we are able to raise additional capital through the sale of equity securities, or we issue securities in connection with another transaction in the future, the ownership position of existing stockholders could be substantially diluted.
In particular, biotech and small-cap companies tend to feel these difficulties acutely. To the extent we are able to raise additional capital through the sale of equity securities, or we issue securities in connection with another transaction in the future, the ownership position of existing stockholders could be substantially diluted.
In RRP caused by HPV subtypes 6 and 11, Precigen is developing a potential treatment for RRP based on a gorilla adenovirus vector and has publicly stated its plans to submit a BLA in 2024 based on a completed Phase 1/2 study.
In RRP caused by HPV subtypes 6 and 11, Precigen is developing a potential treatment for RRP based on a gorilla adenovirus vector and announced in late 2024 that it has submitted a BLA based on a completed Phase 1/2 study.
If we or our licensors fail to obtain or maintain patent protection or trade secret protection for our DNA medicine candidates or our technologies, third parties could use our proprietary information, which could impair our ability to compete in the market and adversely affect our ability to generate revenues and attain profitability. 43 From time to time, U.S. and other policymakers have proposed reforming the patent laws and regulations of their countries.
If we or our licensors fail to obtain or maintain patent protection or trade secret protection for our DNA medicine candidates or our technologies, third parties could use our proprietary information, which could impair our ability to compete in the market and adversely affect our ability to generate revenues and attain profitability.
Such effects include the risks that our DNA medicine candidates may not be approved for all indications requested, which could limit the uses of our DNA medicine candidates and have an adverse effect on their commercial potential or require costly, post-marketing follow-up studies. 25 Clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results.
Such effects include the risks that our DNA medicine candidates may not be approved for all indications requested, which could limit the uses of our DNA medicine candidates and have an adverse effect on their commercial potential or require costly, post-marketing follow-up studies.
In addition, we may fail to perform our responsibilities under these agreements. Many of our government agreements are subject to audits, which may occur several years after the period to which the audit relates. If an audit identifies significant unallowable costs, we could incur a material charge to our earnings or reduction in our cash position.
Many of our government agreements are subject to audits, which may occur several years after the period to which the audit relates. If an audit identifies significant unallowable costs, we could incur a material charge to our earnings or reduction in our cash position. As a result, we may be unsuccessful entering, or ineligible to enter, into future government agreements.
To the extent that our DNA medicine candidates are manufactured at multiple sites or using different processes, we will also need to demonstrate comparability across the manufacturing batches in order to obtain regulatory approval.
This includes how the constituent parts may interact and interrelate and is a complex process. To the extent that our DNA medicine candidates are manufactured at multiple sites or using different processes, we will also need to demonstrate comparability across the manufacturing batches in order to obtain regulatory approval.
The commercial success of our proprietary device and DNA medicine candidates for which we obtain marketing approval from the FDA or other regulatory authorities will depend upon the acceptance of these products by both the medical community and patient population.
If products for which we receive regulatory approval do not achieve broad market acceptance, the revenues that we generate from their sales will be limited. 37 The commercial success of our proprietary device and DNA medicine candidates for which we obtain marketing approval from the FDA or other regulatory authorities will depend upon the acceptance of these products by both the medical community and patient population.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeOur Information Technology department (“IT Department”) (including its Senior Director), with support from service providers, helps identify, assess and manage the Company’s cybersecurity threats and risks. The IT Department identifies and assesses risks from cybersecurity threats by monitoring and evaluating our threat environment and the Company’s risk profile using various methods.
Biggest changeOur Information Technology department (“IT Department”) (including its Senior Director), with support from service providers, helps identify, assess and manage our cybersecurity threats and risks. The IT Department identifies and assesses risks from cybersecurity threats by monitoring and evaluating our threat environment and our risk profile using various methods.
This individual has previously held roles as a head of cybersecurity, cybersecurity consultant and information security specialist for other organizations. This individual holds several certifications related to cybersecurity including as a Certified Information Systems Security Professional.
This individual has previously held roles as a head of cybersecurity, cybersecurity consultant and information security specialist for other organizations. This individual holds several certifications related to cybersecurity including Certified Information Systems Security Professional (CISSP).
The Senior Director of IT and the CFO work with our incident response team to help mitigate and remediate cybersecurity incidents of which they 51 are notified. In addition, our incident response and vulnerability management processes include reporting to the audit committee of the board of directors for certain cybersecurity incidents.
The Senior Director of IT and the CFO work with our incident response team to help mitigate and remediate cybersecurity incidents of which they 54 are notified. In addition, our incident response and vulnerability management processes include reporting to the audit committee of the board of directors for certain cybersecurity incidents.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeIn November 2023, we extended the term of the First San Diego Lease until February 29, 2024. In 2016, we entered into an office lease, or the Second San Diego Lease, for a second property in San Diego, California. The total space under the Second San Diego Lease is approximately 51,000 square feet.
Biggest changeThe total space under the New San Diego Lease is approximately 5,600 square feet and the initial term continues through June 2028.We have also entered into an office lease, or the First San Diego Lease, for other property in San Diego, California that we use for office, manufacturing and research and development purposes.
ITEM 2. PROPERTIES We own no real property and have no plans to acquire any real property in the future. San Diego Leases In November 2023, we entered into a lease agreement, or the New San Diego Lease, for research and development space in San Diego, California.
ITEM 2. PROPERTIES We own no real property and have no plans to acquire any real property in the future. San Diego Leases We have entered into a lease agreement, or the New San Diego Lease, for research and development space in San Diego, California.
Rent payments under the New San Diego Lease will include base rent with an annual increase of approximately three percent, and additional monthly fees to cover our share of certain facility expenses, including utilities, property taxes, insurance and maintenance. In addition, we have paid a security deposit of $33,000.
Rent payments under the Plymouth Meeting Lease include base rent with an annual increase of approximately two percent, and additional monthly fees to cover our share of certain facility expenses, including utilities, property taxes, insurance and maintenance. In addition, we have paid security deposits totaling $124,000.
Plymouth Meeting Lease In 2014, we entered into a lease, or the Plymouth Meeting Lease, for our corporate headquarters in Plymouth Meeting, Pennsylvania. We have amended the Plymouth Meeting Lease on multiple occasions to increase the total leased space to 57,361 square feet and extend the lease term through December 31, 2029.
We have amended the Plymouth Meeting Lease on multiple occasions to increase the total leased space to approximately 57,400 square feet and extend the lease term through December 31, 2029.
As of December 31, 2023, rent payments under the Second San Diego Lease include base rent with an annual increase of approximately three percent, and additional monthly fees to cover our share of certain facility expenses, including utilities, property taxes, insurance and maintenance. In addition, we have paid a security deposit of $95,000.
The total space under the First San Diego Lease is approximately 51,000 square feet and the term continues through May 2027. Rent payments under both leases include base rent with an annual increase of approximately three percent, and additional monthly fees to cover our share of certain facility expenses, including utilities, property taxes, insurance and maintenance.
In addition, we have paid security deposits totaling $124,000. We have entered into four agreements to sublease a total of approximately 25,000 square feet in our Plymouth Meeting headquarters, with one sublease term through March 31, 2025, two terms through December 31, 2026, and one month-to-month.
We have entered into four agreements to sublease a total of approximately 25,000 square feet in our Plymouth Meeting headquarters, with two sublease terms through December 31, 2026, one through December 31, 2027 and one through December 31, 2029. We believe our current and future planned facilities will be adequate to meet our operating needs for the foreseeable future.
We believe our current and future planned facilities will be adequate to meet our operating needs for the foreseeable future. Should we need additional space, we believe we will be able to secure additional space at commercially reasonable rates.
Should we need additional space, we believe we will be able to secure additional space at commercially reasonable rates.
Removed
The total space under the New San Diego Lease is approximately 5,563 square feet. The term of the New San Diego Lease commenced on February 10, 2024 and the initial term is 4.3 years. The base rent adjusts periodically throughout the term of the New San Diego Lease.
Added
In addition, we have paid a security deposit of $95,000 in connection with the First San Diego Lease. Plymouth Meeting Lease We have entered into a lease, or the Plymouth Meeting Lease, for our corporate headquarters in Plymouth Meeting, Pennsylvania.
Removed
In 2013, we entered into a lease, or the First San Diego Lease, for office space in San Diego, California. The initial term of the First San Diego Lease was through November 2023. In June 2015, we amended the First San Diego Lease to increase the total leased space to 31,207 square feet and occupy the entire building.
Removed
We are using the facility for office, manufacturing and research and development purposes. The term of the Second San Diego Lease commenced in June 2017 and continues through May 2027. The base rent adjusts periodically throughout the term of the Second San Diego Lease.
Removed
The base rent adjusts periodically throughout the term of the Plymouth Meeting Lease. As of December 31, 2023, rent payments under the Plymouth Meeting Lease include base rent with an annual increase of approximately two percent, and additional monthly fees to cover our share of certain facility expenses, including utilities, property taxes, insurance and maintenance.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeThe complaint seeks injunctive relief, an accounting, damages, 53 disgorgement of profits, attorneys’ fees, interest, and other relief from us. We filed preliminary objections to the complaint, which were overruled. In September 2021, we filed an answer to the complaint, new matter, and counterclaims.
Biggest changeThe complaint asserts claims for breach of contract, declaratory judgment, unfair competition, and unjust enrichment. The complaint seeks injunctive relief, an accounting, damages, disgorgement of profits, attorneys’ fees, interest, and other relief from us. We filed preliminary objections to the complaint, which were overruled. In September 2021, we filed an answer to the complaint, new matter, and counterclaims.
The complaint seeks declaratory judgments, specific performance of the agreement, injunctive relief, an accounting, damages, attorneys’ fees, interest, costs and other relief from VGXI. In June 2020, the Company filed a petition for preliminary injunction, which was denied.
The complaint seeks declaratory judgments, specific performance of the agreement, injunctive relief, an accounting, damages, attorneys’ fees, interest, costs and other relief from VGXI. In June 2020, we filed a petition for preliminary injunction, which was denied.
VGXI Litigation In June 2020, we filed a complaint in the Court of Common Pleas of Montgomery County, Pennsylvania against VGXI, Inc. and GeneOne Life Science, Inc., or GeneOne, and together with VGXI, Inc. collectively referred to as VGXI, alleging that VGXI had materially breached our supply agreement with them.
ITEM 3. LEGAL PROCEEDINGS VGXI Litigation In June 2020, we filed a complaint in the Court of Common Pleas of Montgomery County, Pennsylvania against VGXI, Inc. and GeneOne Life Science, Inc., or GeneOne, and together with VGXI, Inc. collectively referred to as VGXI, alleging that VGXI had materially breached our supply agreement with them.
VGXI also filed a third-party complaint against Ology Bioservices, Inc., a contract manufacturing organization that we had engaged to provide services similar to those that were being provided by VGXI. We filed an answer to VGXI’s counterclaims, disputing the allegations and the claims raised in VGXI’s filing.
VGXI also filed a third-party complaint against Ology Bioservices, Inc., a contract manufacturing organization that we had engaged to provide services similar to those that were being provided by VGXI, but VGXI later discontinued its third-party claims. We filed an answer to VGXI’s counterclaims, disputing the allegations and the claims raised in VGXI’s filing.
We intend to aggressively prosecute the claims set forth in our counterclaims against GeneOne and to vigorously defend ourselves against the claims in GeneOne’s complaint. ITEM 4. MINE SAFETY DISCLOSURES Not applicable. 54 PART II
A trial date for this litigation has not been set. We intend to aggressively prosecute the claims set forth in our counterclaims against GeneOne and to vigorously defend ourselves against the claims in GeneOne’s complaint. ITEM 4. MINE SAFETY DISCLOSURES Not applicable. 56 PART II
GeneOne Litigation In December 2020, GeneOne filed a complaint in the Court of Common Pleas of Montgomery County, Pennsylvania against us, alleging that we had breached the CELLECTRA Device License Agreement, or the Agreement, between us and GeneOne. We terminated the Agreement in October 2020. The complaint asserts claims for breach of contract, declaratory judgment, unfair competition, and unjust enrichment.
GeneOne Litigation In December 2020, GeneOne filed a complaint in the Court of Common Pleas of Montgomery County, Pennsylvania against us, alleging that we had breached the CELLECTRA Device License Agreement, or the Agreement, between us and 55 GeneOne. We terminated the Agreement in October 2020.
Our counterclaims allege that GeneOne breached the Agreement, and assert claims for breach of contract and declaratory judgment. The counterclaims seek damages, interest, expenses, attorney’s fees, and costs. On October 18, 2021, GeneOne filed its answer to our counterclaims and new matter. A trial date for this litigation has not been set.
Our counterclaims allege that GeneOne breached the Agreement and assert claims for breach of contract and declaratory judgment. The counterclaims seek damages, interest, expenses, attorney’s fees, and costs. In October 2021, GeneOne filed its answer to our counterclaims and new matter. In 2024, we filed a motion for summary judgment, which was denied.
Removed
ITEM 3. LEGAL PROCEEDINGS Securities Litigation Securities Class Action Litigation In March 2020, a purported shareholder class action complaint, McDermid v. Inovio Pharmaceuticals, Inc. and J. Joseph Kim, was filed in the United States District Court for the Eastern District of Pennsylvania, naming the Company and its former President and Chief Executive Officer as defendants.
Removed
The lawsuit alleged that the Company made materially false and misleading statements in violation of certain federal securities laws. The plaintiffs sought unspecified monetary damages on 52 behalf of the putative class and an award of costs and expenses, including reasonable attorneys’ fees. The plaintiffs’ complaint was later amended to include certain of the Company’s other officers as defendants.
Removed
After additional motions were filed in the case, in June 2022 the parties negotiated an agreement in principle to settle the shareholder class action complaint, which was approved by the court in January 2023. Under the settlement, we agreed to pay $30.0 million in cash and $14.0 million in shares of its common stock to settle all outstanding claims.
Removed
Our insurance carriers paid the $30.0 million cash component of the settlement. During the three months ended March 31, 2023, we issued 760,083 shares of common stock pursuant to the securities class action settlement. Shareholder Derivative Litigation In April 2020, a purported shareholder derivative complaint, Behesti v.
Removed
Kim, et al., was filed in the United States District Court for the Eastern District of Pennsylvania, naming eight current and former directors of the Company as defendants. The lawsuit asserted state and federal claims and was based on the same alleged misstatements as the shareholder class action complaint described above.
Removed
The lawsuit accused the Company’s board of directors of failing to exercise reasonable and prudent supervision over our management, policies, practices, and internal controls. The plaintiff sought unspecified monetary damages on behalf of the Company as well as governance reforms. Between June 2020 and August 2020, additional shareholder derivative complaints were filed and later consolidated by the court.
Removed
In March 2022, an additional shareholder derivative complaint was filed in the Delaware Court of Chancery, asserting substantially similar claims as those in the consolidated derivative action. In May 2022, the Delaware Court of Chancery entered a stay of the litigation.
Removed
In March 2023, the parties submitted a joint status report to the Court of Chancery reporting that the parties agreed to a settlement in principle, which also provided for the resolution of the consolidated derivative action and certain stockholder demands.
Removed
In April 2023, the plaintiffs in the consolidated derivative action filed a motion for preliminary approval of settlement with the United States District Court for the Eastern District of Pennsylvania. The proposed settlement provided for resolution of the consolidated derivative action, the derivative action pending in the Delaware Court of Chancery, and certain stockholder demands.
Removed
In June 2023, the court entered an order preliminarily approving the proposed settlement of the derivative claims, in accordance with a Stipulation of Settlement. The Stipulation of Settlement contemplated that, following the settlement hearing and the final approval of the settlement by the court, we would implement certain corporate governance reforms described in the Stipulation of Settlement.
Removed
The preliminary order also approved the form and manner of the notice of the Settlement. As part of the Settlement, in July 2023 we paid $1.2 million to plaintiffs’ counsel for their fees and expenses. In October 2023, the court entered an order and final judgment approving the Settlement, which became effective in November 2023.
Removed
The Company has implemented the corporate governance reforms in response to the provisions of the Stipulation of Settlement.

Item 4. Mine Safety Disclosures

Mine Safety Disclosures — required of mining issuers

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Biggest changeITEM 4. MINE SAFETY DISCLOSURES 54 PART II 55 ITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES 55 ITEM 6. [RESERVED] 56 ITEM 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS 57 ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 63 ITEM 8.
Biggest changeITEM 4. MINE SAFETY DISCLOSURES 56 PART II 57 ITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES 57 ITEM 6. [RESERVED] 58 ITEM 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS 59 ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 65 ITEM 8.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeFiscal year ended December 31. 55 12/18 12/19 12/20 12/21 12/22 12/23 Inovio Pharmaceuticals, Inc. 100.00 82.50 221.25 124.75 39.00 12.75 NYSE American 100.00 110.19 104.83 134.55 129.34 131.60 Nasdaq Composite 100.00 136.69 198.10 242.03 163.28 236.17 S&P SuperCap Biotechnology Index 100.00 116.98 128.56 142.49 161.98 167.26 The stock price performance included in this graph is not necessarily indicative of future stock price performance.
Biggest changeFiscal year ended December 31. 57 12/19 12/20 12/21 12/22 12/23 12/24 Inovio Pharmaceuticals, Inc. 100.00 268.18 151.21 47.27 15.45 4.62 NYSE American 100.00 95.14 122.10 117.38 119.42 120.04 Nasdaq Composite 100.00 144.92 177.06 119.45 172.77 223.87 S&P SuperCap Biotechnology Index 100.00 109.90 121.80 138.47 142.98 144.54 The stock price performance included in this graph is not necessarily indicative of future stock price performance.
Performance Graph The graph below compares the performance of our common stock with the performance of the NYSE American Index, the S&P SuperCap Biotechnology index and the Nasdaq Composite Index for the five years ended December 31, 2023.
Performance Graph The graph below compares the performance of our common stock with the performance of the NYSE American Index, the S&P SuperCap Biotechnology index and the Nasdaq Composite Index for the five years ended December 31, 2024.
On November 2, 2023, the listing of our common stock was transferred to the Nasdaq Capital Market. On January 24, 2024, we implemented a 1-for-12 reverse stock split of our common stock. As of March 1, 2024, we had approximately 58 common stockholders of record.
On November 2, 2023, the listing of our common stock was transferred to the Nasdaq Capital Market. On January 24, 2024, we implemented a 1-for-12 reverse stock split of our common stock. As of March 12, 2025, we had approximately 65 common stockholders of record.
The graph assumes a $100 investment on December 31, 2018 in our common stock and in each index, with the reinvestment of all dividends, if any. *$100 invested on 12/31/18 in stock or index, including reinvestment of dividends.
The graph assumes a $100 investment on December 31, 2019 in our common stock and in each index, with the reinvestment of all dividends, if any. *$100 invested on 12/31/19 in stock or index, including reinvestment of dividends.
The closing price per share of our common stock on March 1, 2024 was $9.55, as reported on the Nasdaq Capital Market. Dividends The payment of any dividends on our common stock is within the discretion of our board of directors.
The closing price per share of our common stock on March 12, 2025 was $2.05, as reported on the Nasdaq Capital Market. Dividends The payment of any dividends on our common stock is within the discretion of our board of directors.

Item 7. Management's Discussion & Analysis

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

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Biggest changeThe $101.0 million overall decrease in research and development expenses year over year was primarily the result of: • $61.4 million in lower drug manufacturing, clinical study expenses, outside services and expensed inventory related to INO-4800 after we discontinued this program in the fourth quarter of 2022; • $17.9 million in lower drug manufacturing and clinical study expenses related to other COVID-19 studies that ceased after we discontinued development of INO-4800; • $15.0 million in lower employee and consultant compensation, including stock-based compensation, primarily due to reductions in headcount in 2023; • $9.4 million in lower expensed inventory and outside services related to our CELLECTRA 3PSP device and array automation project; • $8.4 million in lower immunology, clinical study expenses and outside services related to VGX-3100 as we discontinued development of this product candidate in the third quarter of 2023; and • $4.4 million in lower drug manufacturing related to the sub-grant through Wistar for COVID-19 dMAbs These decreases were partially offset by: • $17.7 million of lower contra-research and development expense recorded from grant agreements; and • $5.8 million of higher other drug manufacturing costs.
Biggest changeThe $11.1 million overall decrease in research and development expenses year over year was primarily the result of: • $12.3 million in lower employee compensation, including stock-based compensation, due to lower headcount following our corporate restructuring undertaken in 2023; • $8.1 million in lower drug manufacturing expenses for other programs; • $7.5 million in lower drug manufacturing and clinical study expenses related to INO-4800 after we discontinued this program in 2022; • $3.4 million in lower drug manufacturing and engineering services related to other COVID-19 studies that we ceased after we discontinued development of INO-4800; • $2.0 million related to the impairment charge on intangible assets in 2023 which did not recur; • $1.9 million in lower immunology and clinical study expenses related to INO-3107; • $1.3 million in lower clinical study expenses related to VGX-3100 as we discontinued development of this product candidate in the third quarter of 2023; and • $1.3 million in lower clinical study and subcontractor expenses related to our CEPI LASSA and MERS grants.
We base our estimates on experience and on various assumptions that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from those estimates.
We base our estimates on experience and on various assumptions that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the 60 carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from those estimates.
We were previously conducting clinical trials of a DNA medicine candidate for the treatment of HPV-related cervical high-grade squamous intraepithelial lesions, or HSIL, but announced in August 2023 that we were ceasing development for this indication in the United States.
We were previously conducting clinical trials of a DNA medicine candidate for the treatment of HPV-related cervical high-grade squamous intraepithelial lesions, or HSIL, but announced in 2023 that we were ceasing development for this indication in the United States.
We utilize a labor reporting system to record employee 59 compensation on a project-by-project basis. Unallocated research and development expenses include engineering and device-related expenses that are not allocable to a specific project, as well as stock-based compensation, other employee-related expenses that are not related to a specific project, and facilities and depreciation expenses.
We utilize a labor reporting system to record employee compensation on a project-by-project basis. Unallocated research and development expenses include engineering and device- 61 related expenses that are not allocable to a specific project, as well as stock-based compensation, other employee-related expenses that are not related to a specific project, and facilities and depreciation expenses.
Contractual Obligations As of December 31, 2023, future minimum payments due under our contractual obligations are set forth in the table below. We expect to be able to satisfy these obligations, both in the short-term and in the longer-term, with cash on hand.
Contractual Obligations As of December 31, 2024, future minimum payments due under our contractual obligations are set forth in the table below. We expect to be able to satisfy these obligations, both in the short-term and in the longer-term, with cash on hand.
Overview We are a clinical-stage biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from diseases associated with human papillomavirus (HPV), cancer, and infectious diseases. Our platform harnesses the power of in vivo protein production, featuring optimized design and delivery of DNA medicines that teach the body to manufacture its own disease-fighting tools.
Overview We are a clinical-stage biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-associated diseases, cancer and infectious diseases. Our platform harnesses the power of in vivo protein production, featuring optimized design and delivery of DNA medicines that teach the body to manufacture its own disease-fighting tools.
Recent Accounting Pronouncements Information regarding recent accounting pronouncements is contained in Note 2 to the consolidated financial statements, included elsewhere in this report. Results of Operations The consolidated financial data for the years ended December 31, 2023, 2022 and 2021 is presented in the following table and the results of these periods are used in the discussion thereafter.
Recent Accounting Pronouncements Information regarding recent accounting pronouncements is contained in Note 2 to the consolidated financial statements, included elsewhere in this report. Results of Operations The consolidated financial data for the years ended December 31, 2024 and 2023 is presented in the following table and the results of these periods are used in the discussion thereafter.
Gain (Loss) on Investment in Affiliated Entity The gain (loss) on investment in affiliated entity resulted from the change in the fair market value of our investment in PLS of $773,000 and $(1.9) million for the years ended December 31, 2023 and 2022, respectively.
(Loss) Gain on Investment in Affiliated Entity The (loss) gain on investment in affiliated entity resulted from the change in the fair market value of our investment in PLS of $(1.2) million and $773,000 for the years ended December 31, 2024 and 2023, respectively.
We may not be successful in our research and development efforts, and we may never generate sufficient product revenue to be profitable. As of December 31, 2023, we had an accumulated deficit of $1.6 billion.
We may not be successful in our research and development efforts, and we may never generate sufficient product revenue to be profitable. As of December 31, 2024, we had an accumulated deficit of $1.7 billion.
Funding Requirements 62 As of December 31, 2023, we had an accumulated deficit of $1.6 billion and we expect to continue to operate at a loss in the near term. The amount of our accumulated deficit will continue to increase, as it will be expensive to continue research and development efforts.
Funding Requirements As of December 31, 2024, we had an accumulated deficit of $1.7 billion and we expect to continue to operate at a loss in the near term. The amount of our accumulated deficit will continue to increase, as it will be expensive to continue research and development efforts.
As of December 31, 2023, we expect to receive aggregate future minimum lease payments totaling $1.3 million (non-discounted) over the duration of the sublease agreements, which expected payments are not included in the table above. (3) Purchase obligations from supply agreements with contract manufacturers.
As of December 31, 2024, we expect to receive aggregate future minimum lease payments totaling $2.4 million (non-discounted) over the duration of the sublease agreements, which expected payments are not included in the table above. (2) Purchase obligations from supply agreements with contract manufacturers.
Cash Flows Operating Activities Net cash used in operating activities was $124.4 million and $216.2 million for the years ended December 31, 2023 and 2022, respectively. The variance was primarily due to the timing and changes in working capital balances, offset by decreased operating expenses.
Cash Flows Operating Activities Net cash used in operating activities was $104.1 million and $124.4 million for the years ended December 31, 2024 and 2023, respectively. The variance was primarily due to the timing and changes in working capital balances, offset by decreased operating expenses.
Total employee stock-based compensation cost for the years ended December 31, 2023 and 2022 was $10.4 million and $22.2 million, of which $4.5 million and $8.8 million was included in research and development expenses and $5.9 million and $13.4 million was included in general and administrative expenses, respectively.
Total employee stock-based compensation cost for the years ended December 31, 2024 and 2023 was $6.4 million and $10.4 million, of which $2.8 million and $4.5 million was included in research and development expenses and $3.6 million and $5.9 million was included in general and administrative expenses, respectively.
Investing Activities Net cash provided by investing activities was $87.4 million and $109.6 million for the years ended December 31, 2023 and 2022, respectively. The variance was primarily the result of timing differences in short-term investment purchases, sales and maturities.
Investing Activities Net cash provided by investing activities was $104.1 million and $87.4 million for the years ended December 31, 2024 and 2023, respectively. The variance was primarily the result of timing differences in short-term investment purchases, sales and maturities.
(b) Includes impairment of intangible assets of $2.0 million recorded in the second quarter of 2023.
(b) Includes impairment of intangible assets of $2.0 million recorded in 2023.
Net Unrealized Gain (Loss) on Available-for-Sale Equity Securities The net unrealized gain (loss) on available-for-sale equity securities for the years ended December 31, 2023 and 2022 was $5.9 million and $(7.8) million, respectively, which resulted from a change in the fair market value of the investments. Other (Expense) Income , net.
Net Unrealized Gain on Available-for-Sale Equity Securities The net unrealized gain on available-for-sale equity securities for the years ended December 31, 2024 and 2023 was $2.1 million and $5.9 million, respectively, which resulted from a change in the fair market value of the investments.
During the year ended December 31, 2023 , we sold 875,305 shares of our common stock under the Sales Agreement at a weighted average price of $6.33 per share, resulting in aggregate net proceeds of $5.5 million.
During the year ended December 31, 2023 , we sold 875,305 shares of our common stock under the 2021 Sales Agreement at a weighted 64 average price of $6.33 per share, resulting in aggregate net proceeds of $5.5 million. We terminated the 2021 Sales Agreement in August 2024 in connection with the entry into the 2024 Sales Agreement described above.
Issuances of Common Stock On November 9, 2021, we entered into an ATM Equity Offering SM Sales Agreement, or the Sales Agreement, with outside sale s agents, or collectively, the Sales Agents, under which we may offer and sell, from time to time at our sole discretion, shares of our common stock with aggregate gross proceeds of up to $300.0 million, through the Sales Agents.
On November 9, 2021, we entered into an ATM Equity Offering Sales Agreement, or the 2021 Sales Agreement, with outside sale s agents, under which we were able to offer and sell shares of our common stock with aggregate gross proceeds of up to $300.0 million.
As of December 31, 2023, we had net operating loss carry forwards for U.S. federal, California and Pennsylvania income tax purposes of $1,013.3 million, $251.4 million and $102.6 million, respectively, net of the net operating losses that will expire due to IRC Section 382 61 limitations.
As of December 31, 2024, we had net operating loss carry forwards for U.S. federal, California and Pennsylvania income tax purposes of $1.1 billion, $259.9 million and $88.6 million, respectively, net of the net operating losses that will expire due to IRC Section 382 limitations.
We also had U.S. federal and state research and development tax credits of $41.6 million and $6.1 million, respectively, net of the federal research and development credits that will expire due to IRC Section 383 limitations. The net operating losses and credits began to expire during 2023.
We also had U.S. federal and state research and development tax credits of $46.1 million and $7.9 million, respectively, net of the federal research and development credits that will expire due to IRC Section 383 limitations.
We use proprietary technology to design DNA plasmids which are small circular DNA molecules that work like software the body’s cells can download to produce specific proteins to target and fight disease. Our proprietary investigational CELLECTRA ® delivery devices help our DNA medicines enter the body’s cells for optimal effect.
We use proprietary technology to design DNA plasmids, which are small circular DNA molecules that work like software the body’s cells can download to produce specific proteins to target and fight disease.
Working Capital and Liquidity As of December 31, 2023, we had cash and short-term investments of $145.3 million and working capital of $110.5 million, as compared to $253.0 million and $218.4 million as of December 31, 2022, respectively.
Working Capital and Liquidity As of December 31, 2024, we had cash and short-term investments of $94.1 million and working capital of $62.5 million, as compared to $145.3 million and $110.5 million as of December 31, 2023, respectively.
General and Administrative Expenses General and administrative expenses, which include business development expenses, the amortization of intangible assets and patent expenses, were $47.6 million for the year ended December 31, 2023 as compared to $90.2 million in 2022.
General and Administrative Expenses General and administrative expenses, which include business development expenses and patent expenses, were $37.0 million for the year ended December 31, 2024 as compared to $47.6 million in 2023.
We have four active subleases for portions of our Plymouth Meeting corporate headquarters facility with periods through March 31, 2025, two through December 31, 2026 and the other month-to-month.
We have four active subleases for portions of our Plymouth Meeting corporate headquarters facility with two sublease periods through December 31, 2026, one through December 31, 2027 and one through December 31, 2029.
Food and Drug Administration, or FDA, that the data from this completed trial could be used to support the submission of a Biologic License Application, or BLA, for review under the FDA’s accelerated approval program.
The standard of care for RRP is repeated invasive surgery. 59 In 2023, we received feedback from the U.S. Food and Drug Administration, or FDA, that the data from this completed trial could be used to support the submission of a Biologic License Application, or BLA, for review under the FDA’s accelerated approval program.
Our current cash resources, including amounts that we may be able to obtain through sales of common stock under the S ales Agreement, will not be sufficient to complete the clinical development of any of our product candidates, and we anticipate that additional financing will be required in order to complete the development of and to commercialize and generate revenues from the sale of any product candidates that receive regulatory approval.
Our current cash resources will not be sufficient to complete the clinical development of our product candidates beyond INO-3107, and we anticipate that additional financing will be required in order to complete the development of and to commercialize and generate revenues from the sale of INO-3107 or any other product candidates that may receive regulatory approval.
Income Taxes Since inception, we have incurred operating losses and accordingly have not recorded a provision for U.S. income taxes for any of the periods presented. Utilization of net operating losses and tax credits are subject to a substantial annual limitation due to ownership change limitations provided by the Internal Revenue Code of 1986, as amended, or IRC.
Utilization of net operating losses and tax credits are subject to a substantial annual limitation due to ownership change limitations provided by the Internal Revenue Code of 1986, as amended, or IRC.
During the year ended December 31, 2022, stock options to purchase 9,891 shares of common stock were exercised for aggregate net proceeds of $283,000, which proceeds were offset by tax payments made related to net share settlement of RSU awards of $1.4 million.
Other Issuances of Common Stock During the year ended December 31, 2024, stock options to purcha se 8,159 shares of common stock were exercised for aggregate net proceeds to us of $68,000, which proceeds were offset by tax payments made related to net share settlement of RSU awards of $421,000.
Department of Defense (DoD), HIV Vaccines Trial Network, International Vaccine Institute (IVI), Kaneka Eurogentec, National Cancer Institute (NCI), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), Plumbline Life Sciences, Regeneron Pharmaceuticals, Richter-Helm BioLogics, Thermo Fisher Scientific, the University of Pennsylvania, the Walter Reed Army Institute of Research, and The Wistar Institute.
Our partners and collaborators include Advaccine Biopharmaceuticals Suzhou Co, ApolloBio Corporation, AstraZeneca, Coherus Biosciences, Defense Advanced Research Projects Agency (DARPA), HIV Vaccines Trial Network, International Vaccine Institute (IVI), Kaneka Eurogentec, National Cancer Institute (NCI), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), Plumbline Life Sciences, Regeneron Pharmaceuticals, Richter BioLogics, the University of Pennsylvania, the Walter Reed Army Institute of Research, and The Wistar Institute.
In addition to the potential issuance of equity or debt securities in order to raise capital, we are also evaluating potential collaborations as an additional way to fund our operations.
In addition to the potential issuance of equity or debt securities in order to raise capital, we are also evaluating potential collaborations as an additional way to fund our operations. We expect our cash runway to extend through the fourth quarter of 2025, without giving effect to any further capital raising activities that we may undertake.
In addition to our development efforts with INO-3107, we are actively developing or planning to develop DNA medicines for other indications, including HPV-related anal dysplasia and oropharyngeal squamous cell carcinoma, or OPSCC; glioblastoma multiforme, or GBM, a deadly form of brain cancer; and a potential vaccine booster to protect against the Ebola virus.
In addition to our development efforts with the product candidates described above, we are actively developing or planning to develop DNA medicines for other indications, including HPV-related anal dysplasia; cancers in people with certain gene mutations; and a potential vaccine booster to protect against the Ebola virus.
Interest Income The $3.4 million increase in interest income for the year ended December 31, 2023 as compared to 2022 was primarily due to higher interest rates earned on our cash balance. Interest Expense There was a $31,000 decrease in interest expense for the year ended December 31, 2023 as compared to 2022.
Interest Income The $3.4 million decrease in interest income for the year ended December 31, 2024 as compared to 2023 was primarily due to a lower short-term investment balance.
We will pay the Sales Agents a commission of up to three percent (3.0%) of the gross sales proceeds of any common stock sold through the Sales Agents under the Sales Agreement, and we have provided the Sales Agents with certain indemnification rights.
The 2024 Sales Agreement provides that the Sales Agent is entitled to compensation in an amount equal to up to 3.0% of the gross sales proceeds of any common stock sold through the Sales Agent under the 2024 Sales Agreement, and we have provided the Sales Agent with certain indemnification rights.
Accrued clinical trial costs are subject to revisions as trials progress. Revisions are charged to expense in the period in which the facts that give rise to the revision become known.
For clinical trial expenses, judgments used in estimating accruals rely on estimates of total costs incurred based on participant enrollment, completion of studies and other events. Accrued clinical trial costs are subject to revisions as trials progress. Revisions are charged to expense in the period in which the facts that give rise to the revision become known.
Liquidity and Capital Resources Our primary uses of cash are to finance research and development activities, including clinical trial activities for the advancement of our DNA medicine candidates. We have satisfied our cash requirements principally from proceeds from the sale of equity securities, indebtedness and grants and government contracts.
The net operating losses and credits began to expire during 2025. 63 Liquidity and Capital Resources Our primary uses of cash are to finance research and development activities, including clinical trial activities for the advancement of our DNA medicine candidates.
Research and Development Expenses - Clinical Trial Accruals 58 Our activities have largely consisted of research and development efforts related to developing proprietary device technologies, DNA medicine candidates and dMABs. For clinical trial expenses, judgments used in estimating accruals rely on estimates of total costs incurred based on participant enrollment, completion of studies and other events.
We believe the following accounting policies to be critical to the judgments and estimates used in the preparation of our consolidated financial statements: Research and Development Expenses - Clinical Trial Accruals Our activities have largely consisted of research and development efforts related to developing proprietary device technologies, DNA medicine candidates and dMABs.
The following tables summarize our research and development expense by product candidate for the years ended December 31, 2023 and 2022 : Years Ended December 31, Increase (Decrease) (dollars in thousands) 2023 2022 $ % INO-4800 and other Covid-19 $ 8,869 $ 93,464 $ (84,595) (91) % VGX-3100 4,748 15,989 (11,241) (70) INO-3107 17,841 8,133 9,708 119 INO-5401 and other Immuno-oncology 8,372 2,775 5,597 202 Other research and development programs (a) 8,472 6,227 2,245 36 Engineering and device-related 8,863 25,187 (16,324) (65) Stock-based compensation 4,606 9,059 (4,453) (49) Other unallocated expenses (b) 24,906 26,817 (1,911) (7) Research and development expense $ 86,677 $ 187,651 $ (100,974) (54) % (a) Net of contributions received from grant agreements and recorded as contra-research and development expense.
The following tables summarize our research and development expense by product candidate for the years ended December 31, 2024 and 2023 : Years Ended December 31, Increase (Decrease) (dollars in thousands) 2024 2023 $ % INO-3107 $ 29,930 $ 17,841 $ 12,089 68 % INO-5401 and other Immuno-oncology 6,293 11,759 (5,466) (46) Other research and development programs (a) (77) 18,702 (18,779) (100) Engineering and device-related 19,394 8,863 10,531 119 Stock-based compensation 2,821 4,606 (1,785) (39) Other unallocated expenses (b) 17,259 24,906 (7,647) (31) $ 75,620 $ 86,677 $ (11,057) (13) % (a) Net of contributions received from grant agreements and recorded as contra-research and development expense.
Contributions received from current grant agreements and recorded as contra-research and development expense were $6.8 million and $24.5 million for the years ended December 31, 2023 and 2022, respectively.
Contributions received from current grant agreements and recorded as contra-research and development expense were $2.1 million and $6.8 million for the years ended December 31, 2024 and 2023, respectively. The decrease was primarily due to decreases of $3.6 million and $553,000, respectively, in reimbursements from Advaccine and expenses earned under the sub-grants through Wistar.
Our lead candidate is INO-3107 for the treatment of recurrent respiratory papillomatosis, or RRP, a rare and debilitating disease of the respiratory tract caused by HPV infection.
Our lead candidate is INO-3107 for the treatment of recurrent respiratory papillomatosis, or RRP, a chronic, rare and debilitating disease characterized by the growth of small tumors, or papillomas, in the respiratory tract primarily caused by HPV-6 and/or HPV-11 genotypes. Although mostly benign, these papillomas can cause severe, sometimes life-threatening airway obstruction and respiratory complications.
Other (expense) income, net, for the years ended December 31, 2023 and 2022 was $(4.7) million and $(3.9) million, respectively, related primarily to the realized loss on short-term investments sold during the periods. Share in Net Loss of Geneos The share in net loss of Geneos represents our share of Geneos' losses during 2022.
Other expense, net, of $4.7 million for the year ended December 31, 2023 was primarily the result of realized losses on short-term investments sold during the year. Income Taxes Since inception, we have incurred operating losses and accordingly have not recorded a provision for U.S. income taxes for any of the periods presented.
Financing Activities Net cash provided by financing activities was $5.0 million and $81.8 million for the years ended December 31, 2023 and 2022, respectively. The variance was primarily due to net proceeds of $5.5 million from the sale of common stock under the Sales Agreement (defined below) in 2023 compared to net proceeds of $83.0 million received during 2022.
Financing Activities Net cash provided by financing activities was $51.5 million and $5.0 million for the years ended December 31, 2024 and 2023, respectively.
We expect interest expense to decrease materially in 2024 due to the maturity and repayment in full of our convertible senior notes on March 1, 2024.
Interest Expense The $1.0 million decrease in interest expense for the year ended December 31, 2024 as compared to 2023 was primarily due to our senior convertible promissory notes that were repaid in full on March 1, 2024.
During the year ended December 31, 2022, we sold 2,870,478 shares of common stock under the Sales Agreement for aggregate net proceeds of $83.0 million. From January 1, 2024 through the date of this report, we sold an additional 543,620 shares of common stock under the Sales Agreement for net proceeds of $5.2 million.
During the three months ended March 31, 2024 , we sold 543,620 shares of our common stock under the 2021 Sales Agreement at a weighted average price of $9.76 per share, resulting in aggregate net proceeds of $5.2 million.
Payments Due by Period Total Less than 1 year 1 – 3 years 3 – 5 years More than 5 years Convertible senior notes (1) $ 16,948,000 $ 16,948,000 $ — $ — $ — Operating lease obligations (2) $ 17,665,000 $ 3,247,000 $ 7,021,000 $ 5,265,000 $ 2,132,000 Manufacturing commitments (3) $ 4,489,000 $ 4,489,000 $ — $ — $ — (1) On March 1, 2024 these Convertible Senior Notes matured and we satisfied the obligation in full from existing cash.
Payments Due by Period Total Less than 1 year 1 – 3 years 3 – 5 years More than 5 years Operating lease obligations (1) $ 14,435,000 $ 3,483,000 $ 6,510,000 $ 4,442,000 $ — Manufacturing commitments (2) $ 269,000 $ 269,000 $ — $ — $ — (1) We have entered into operating leases for our facilities, which expire from 2027 to 2029, and operating leases for office equipment, which expire in 2025.
Removed
In our completed Phase 1/2 clinical trial of INO-3107 for the treatment of HPV-6 and HPV-11-associated RRP, 81.3% of patients experienced a reduction in the number of surgical interventions in the year following administration of INO-3107, when compared with the year prior to treatment.
Added
INOVIO, CELLECTRA, the INOVIO logo, and our other trademarks or service marks appearing in this Annual Report are our property.
Removed
In February 2023, we announced data from the second cohort of our Phase 1/2 clinical trial, which followed the announcement of the first cohort in October 2022.
Added
Solely for convenience, the trademarks and trade names in this report are referred to without the ® and TM symbols, but such references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto.
Removed
In the second cohort of 11 patients who were administered INO-3107 via an exploratory side port injection needle, 10 of the 11 patients (91%) saw a reduction in surgical interventions in the year following initial treatment, with the measurement beginning on Day 0, the start of trial therapy. Of these 10 patients, four did not require surgery.
Added
Products or service names of other companies mentioned in this Annual Report may be trademarks, trade names or service marks of their respective owners. References herein to “we,” “our,” “us,” “INOVIO” or the “Company” refer to INOVIO Pharmaceuticals, Inc. and its consolidated subsidiaries. References herein to “DNA medicines” refers to our product candidates in development.
Removed
There was a statistically significant median decrease of three surgical interventions when comparing the year following treatment to the year prior to treatment. INO-3107 was well-tolerated and immunogenic among patients in the second cohort.
Added
Our proprietary investigational CELLECTRA ® devices are designed to deliver the plasmids into the body’s cells for optimal effect, without the use of chemical adjuvants, lipid nanoparticles or viral vectors.
Removed
The safety and efficacy results for the second cohort were consistent with results announced for the first cohort in October 2022. 57 In the fourth quarter of 2023, we received feedback from the U.S.
Added
We previously expected to be able to submit our BLA by the end of 2024; however, during our device testing process we identified a manufacturing issue involving the single-use disposable administration component of the CELLECTRA 5PSP device that we plan to use in the confirmatory trial and that will be submitted for approval for commercial use.
Removed
Our partners and collaborators include Advaccine Biopharmaceuticals Suzhou Co, ApolloBio Corporation, AstraZeneca, The Bill & Melinda Gates Foundation (Gates), Coalition for Epidemic Preparedness Innovations (CEPI), Coherus Biosciences, Defense Advanced Research Projects Agency (DARPA), The U.S.
Added
We resolved the manufacturing issue in the first quarter of 2025 and are currently on track to begin a rolling submission of the BLA in mid-2025 and to request priority review, with a goal of receiving file acceptance by the FDA by the end of 2025.
Removed
We believe the following accounting policies to be critical to the judgments and estimates used in the preparation of our consolidated financial statements: Collaboration Agreements and Revenue Recognition We assess whether our collaboration agreements are subject to Accounting Standards Codification ("ASC") Topic 808: Collaborative Arrangements (“Topic 808”) based on whether they involve joint operating activities and whether both parties have active participation in the arrangement and are exposed to significant risks and rewards.
Added
We are developing INO-3112, a DNA medicine candidate targeting HPV 16/18 combined with a DNA plasmid encoding for human IL-12 as an immune activator, for the treatment of oropharyngeal squamous cell carcinoma, or OPSCC, a type of head and neck cancer commonly known as throat cancer.
Removed
To the extent that the arrangement falls within the scope of Topic 808 and we conclude that our collaboration partner is not a customer, we present such payments as a reduction of research and development expense.
Added
We have entered into a clinical collaboration and supply agreement with Coherus BioSciences, Inc. to evaluate the combination of INO-3112 and LOQTORZI (toripalimab-tpzi) in a clinical trial for patients with locoregionally advanced, high-risk, HPV16/18 positive OPSCC. Under the terms of the supply agreement, Coherus will provide LOQTORZI for a planned Phase 3 clinical trial.
Removed
If payments from our collaboration partner to us represent consideration from a customer, then we account for those payments within the scope of Accounting Standards Update (“ASU”) 2014-09, Revenue from Contracts with Customers (“Topic 606”).
Added
We have also gained alignment with FDA on the design of the planned Phase 3 trial in the United States and received initial feedback from European regulatory authorities on the proposed design of the trial in Europe.
Removed
Year Ended December 31, Increase/(Decrease) 2023 vs. 2022 Increase/(Decrease) 2022 vs. 2021 2023 2022 2021 $ % $ % Revenue from collaborative arrangements and other contracts, including affiliated entity $ 832,010 $ 10,262,268 $ 1,774,758 $ (9,430,258) (92) % $ 8,487,510 478 % Operating expenses: Research and development 86,676,563 187,650,503 249,240,324 (100,973,940) (54) (61,589,821) (25) General and administrative 47,582,104 90,185,285 53,752,353 (42,603,181) (47) 36,432,932 68 Impairment of Goodwill 10,513,371 — — 10,513,371 100 — — Total operating expenses 144,772,038 277,835,788 302,992,677 (133,063,750) (48) (25,156,889) (8) Loss from operations (143,940,028) (267,573,520) (301,217,919) 123,633,492 46 33,644,399 11 Interest income 8,133,290 4,782,030 3,363,080 3,351,260 70 1,418,950 42 Interest expense (1,222,789) (1,253,952) (1,936,447) 31,163 (2) 682,495 (35) Gain (loss) on investment in affiliated entity 773,145 (1,899,654) (553,570) 2,672,799 * (1,346,084) * Net unrealized gain (loss) on available-for-sale equity securities 5,850,626 (7,846,172) (3,222,838) 13,696,798 * (4,623,334) * Other (expense) income, net (4,711,596) (3,861,584) 343,371 (850,012) * (4,204,955) * Net loss before share in net loss of Geneos (135,117,352) (277,652,852) (303,224,323) 142,535,500 51 25,571,471 8 Share in net loss of Geneos — (2,165,213) (434,387) 2,165,213 * (1,730,826) * Net loss $ (135,117,352) $ (279,818,065) $ (303,658,710) $ 144,700,713 (52) % $ 23,840,645 (8) % *Not meaningful Comparison of Years Ended December 31, 2023 and 2022 Revenue Revenue was primarily derived under collaborative arrangements and other contracts, including arrangements with affiliated entities, for the years ended December 31, 2023 and 2022 .
Added
We are also developing INO-5401, an immunotherapy consisting of three DNA plasmids encoding for three tumor associated antigens, for the treatment of glioblastoma multiforme, or GBM, an aggressive type of brain cancer that accounts for more than 50% of all primary malignant brain tumors. GBM is one of the most complex, deadly, and treatment-resistant cancers.
Removed
The $9.4 million decrease in revenue was primarily due to no revenue from our Procurement Contract with the DoD as all performance obligations were satisfied during 2022.
Added
Year Ended December 31, Increase/(Decrease) 2024 vs. 2023 2024 2023 $ % Revenue from collaborative arrangements and other contracts, including affiliated entity $ 217,756 $ 832,010 $ (614,254) (74) % Operating expenses: Research and development 75,620,340 86,676,563 (11,056,223) (13) General and administrative 36,996,338 47,582,104 (10,585,766) (22) Impairment of goodwill — 10,513,371 (10,513,371) 100 Total operating expenses 112,616,678 144,772,038 (32,155,360) (22) Loss from operations (112,398,922) (143,940,028) 31,541,106 22 Interest income 4,766,993 8,133,290 (3,366,297) (41) Interest expense (177,833) (1,222,789) 1,044,956 (85) Change in fair value of common stock warrant liability 2,808,608 — 2,808,608 100 (Loss) gain on investment in affiliated entity (1,166,443) 773,145 (1,939,588) * Net unrealized gain on available-for-sale equity securities 2,077,182 5,850,626 (3,773,444) * Other expense, net (3,163,711) (4,711,596) 1,547,885 * Net loss $ (107,254,126) $ (135,117,352) $ 27,863,226 21 % *Not meaningful Revenue Revenue was primarily derived under collaborative arrangements and other contracts, including arrangements with affiliated entity, for the years ended December 31, 2024 and 2023 .
Removed
The decrease year over year was primarily due to decreases of $7.7 million earned under the sub-grant through Wistar primarily for DARPA COVID-19 dMAb, $6.1 million from the DoD 3PSP device development grant and $5.0 million earned under the CEPI Lassa and MERS grants. These decreases were offset by an increase of $2.4 million in reimbursements from Advaccine.
Added
We derived 100% and 29%, respectively, of our revenue from a single collaborator, ApolloBio, in those years.
Removed
The $42.6 overall decrease year over year was primarily the result of: 60 • $14.0 million in net expense related to the class action securities litigation settlement, which was accrued in 2022 but paid in 2023; • $11.3 million in lower legal expenses, primarily the result of the conclusion of litigation in 2023; • $6.9 million in one-time severance expenses related to the separation of our former President and Chief Executive Officer in 2022, including $4.2 million of stock-based compensation expense related to equity award modifications, that did not recur in 2023; • $5.9 million in lower employee compensation, including employee and consultant stock-based compensation, as a result of headcount reductions in 2023; • $1.9 million in lower insurance expenses; and • $1.4 million in lower other outside services related to our discontinued INO-4800 and VGX-3100 programs.
Added
These decreases were offset by: • $10.6 million in higher drug manufacturing related to INO-3107; • $6.8 million in higher engineering professional and outside services related to our device development; • $4.7 million of lower contra-research and development expense recorded from grant agreements; and • $4.6 million of higher expensed inventory.
Removed
As described in Note 15 to the consolidated financial statements in this report, we reduced the carrying value of our investment in Geneos to zero in March 2022 and will not record our share of further net losses of Geneos as we have no obligation to fund its operations.
Added
The $10.6 million overall decrease was primarily the result of: 62 • $5.4 million in lower employee compensation, including employee and consultant stock-based compensation, as a result of lower headcount and lower weighted average grant date fair value for the awards granted during 2024; and • $4.7 million in lower legal expenses related to litigation matters settled in 2023 that did not recur in 2024.
Removed
Comparison of Years Ended December 31, 2022 and 2021 For a comparison of the years ended December 31, 2022 and 2021, you may refer to Part II, Item 7 of our Annual Report on Form 10-K for the year ended December 31, 2022 filed with the SEC on March 1, 2023.
Added
Change in Fair Value of Common Stock Warrant Liability We recognized a gain of $2.8 million from a decrease in the fair value of our common stock warrant liability for the year ended December 31, 2024.
Removed
Subject to the terms and conditions of the Sales Agreement, the Sales Agents may sell the common stock by any method permitted by law deemed to be an “at the market" offering.
Added
This change was related to the revaluation of the liability associated with the Warrants, as defined below, we issued in December 2024 and was primarily the result of a decrease in our stock price during the period between the issuance date and December 31, 2024.
Removed
The Sales Agents will use commercially reasonable efforts to sell the common stock from time to time, based upon instructions from us, including any price, time or size limits or other customary parameters or conditions we may impose.
Added
We will continue to estimate the fair value of these Warrants at each balance sheet date and will record gain or loss on the statement of operations for changes between balance sheet dates.
Removed
During the year ended December 31, 2021, stock options to purchase 109,188 shares of common stock were exercised for aggregate net proceeds of $6.7 million, which proceeds were offset by tax payments made related to net share settlement of RSU awards of $4.6 million.
Added
Other Expense, net Other expense, net, of $3.2 million for the year ended December 31, 2024 was primarily due to a realized loss on our short-term investments sold during the year, as well as the financing costs we incurred in connection with the issuance of the Warrants, as defined below, in December 2024.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeThe interest rate on our indebtedness at December 31, 2023 was fixed and not subject to fluctuations in interest rates. As of March 1, 2024, we have no indebtedness. Foreign Currency Risk 63 We operate primarily in the United States and most transactions during the year ended December 31, 2023 were made in United States dollars.
Biggest changeForeign Currency Risk We operate primarily in the United States and most transactions during the year ended December 31, 2024 were made in United States dollars.
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK Interest Rate Risk Our primary exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates. Under our current policies, we do not use interest rate derivative instruments to manage exposure to interest rate changes.
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK Interest Rate Risk 65 Our primary exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates. Under our current policies, we do not use interest rate derivative instruments to manage exposure to interest rate changes.
Although inflation has increased generally in the United States in recent years, we do not believe that inflation has had a material effect on our business, financial condition or results of operations during the year ended December 31, 2023.
Although inflation has increased generally in the United States in recent years, we do not believe that inflation has had a material effect on our business, financial condition or results of operations during the year ended December 31, 2024.
During much of 2022 and into the year ended December 31, 2023, there was a pronounced overall increase in prevailing interest rates in the United States compared to the first half of 2022, which contributed to the unrealized loss of $3.9 million in the market value of our investment portfolio as of December 31, 2023.
Over the past several years, there has been a pronounced overall increase in prevailing interest rates in the United States, which has contributed to the accumulated unrealized loss of $1.9 million in the market value of our investment portfolio as of December 31, 2024.

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