What changed in this filing

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Item 1A. Risk Factors

2026-03-12 compared with 2025-03-06 · 220 added, 87 removed, 715 unchanged (30% of the section changed)

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Additional risks, uncertainties and other factors not presently known to us or that we currently deem immaterial may also impair our business operations.

The risks and uncertainties described below are not the only ones we face.

Our business, financial condition and operating results can be affected by a number of factors, whether currently known or unknown, including but not limited to those described below.

Any one or more of such factors could directly or indirectly cause our actual results of operations and financial condition to vary materially from past or anticipated future results of operations and financial condition.

Any of these factors, in whole or in part, could materially and adversely affect our business, financial condition, results of operations and stock price.

References to past events are provided by way of example only and are not intended to be a complete listing or a representation as to whether or not such factors have occurred in the past or their likelihood of occurring in the future.

Because of the following factors, as well as other factors affecting our financial condition and operating results, past financial performance should not be considered to be a reliable indicator of future performance, and investors should not use historical trends to anticipate results or trends in future periods.

RISKS RELATED TO OUR FINANCIAL POSITION AND CAPITAL REQUIREMENTS

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Our consolidated financial statements as of December 31, 2025 did not include any adjustments that might result from the outcome of this uncertainty.

We expect that our current cash will be able to fund operations into the third quarter of 2025 but will not be sufficient to fund operations for twelve months from the date of the filing of this Annual Report.

We expect that our current cash will be able to fund operations into the first quarter of 2027;

however, the current cash will only be sufficient to run certain clinical trials and no assurances can be provided and our cash could differ materially from our expectations based on various factors, many of which are out of our control.

We will need to raise additional capital to operate our business and our failure to obtain funding when needed may force us to delay, reduce or eliminate certain of our development programs or commercialization efforts .

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As of December 31, 2025, our accumulated deficit totaled approximately $358.7 million on a consolidated basis.

Pursuant to the VCN Purchase Agreement, we have agreed to use reasonable efforts to commercialize VCN-01 and we agreed as a post- closing covenant to commit to fund VCN's research and development programs, including but not limited to VCN-01 PDAC Phase 2 clinical trial, VCN-01 RB pivotal trial and necessary G&A within a budgetary plan of approximately $27.8 million.

Pursuant to the Purchase Agreement entered into in connection with the Acquisition, we have agreed to use reasonable efforts to commercialize VCN-01.

Additionally, pursuant to the Purchase Agreement, we are required to pay up to $70.2 million in contingent consideration upon the achievement of certain milestones, including regulatory filings, of which to date $7.3 million has been paid and an additional $5.0 million has been earned but deferred pending ongoing discussion with Grifols.

If we are required to make the deferred $5.0 million milestone payment to Grifols, it will significantly deplete our cash and cash equivalents, which could materially and adversely affect our liquidity and limit our ability to fund operations or meet other financial obligations.

We expect to incur additional operating losses in the future and therefore expect our cumulative losses to increase.

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The amount of government funding available for grants is dependent upon governmental budgets over which we have no control and which change with new administrations.

Based on our current plans, we expect that our current cash will be able to fund operations into the third quarter of 2025 but will not be sufficient to fund our operations for the next twelve months and will only be sufficient to complete our planned clinical trials of VCN-01 (in PDAC and retinoblastoma), but may not be sufficient for additional trials of VCN-01, SYN-020 or SYN-004, or to complete the last cohort of the Phase 1a/2a clinical trial of SYN-004, which are expected to require significant cash expenditures.

Based on our current plans, we expect that our current cash will be sufficient to fund operations into the first quarter of 2027 and will only be sufficient to cover overhead costs, close out of the VIRAGE Phase 2b clinical trial, commence and complete a potential Phase 2a study evaluating VCN-01 dosing frequency, exploratory VCN-01 manufacturing scale-up activities, regulatory interactions regarding proposed VCN-01 clinical trials in PDAC and retinoblastoma, and preclinical studies supporting VCN-01 and VCN-12, the first candidate from our VCN-X discovery program.

We believe our cash will also be sufficient to fund our committed obligations under the terms of the Purchase Agreement related to the Acquisition, but may not be sufficient for additional trials of VCN-01 or SYN-004, or to complete the last cohort of the Phase 1a/2a clinical trial of SYN-004, which are expected to require significant cash expenditures.

In addition, based on the significant anticipated cost of a Phase 3 clinical program in a broad indication for SYN-004, we expect it will not be feasible for us to initiate and complete this trial at this time without a partner given the capital constraints tied to our current market cap and share price.

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A failure otherwise to secure additional funds when needed in the future whether through an equity or debt financing or a sufficient amount of capital without a strategic partnership could result in us being unable to complete planned preclinical and clinical trials or obtain approval of our product candidates from the FDA and other regulatory authorities.

In addition, we could be forced to delay, discontinue or curtail product development, forego sales and marketing efforts, and forego licensing in attractive business opportunities.

Our ability to raise capital through the sale of securities may be limited by the rules of the SEC and NYSE American LLC (“NYSE American”) that place limits on the number and dollar amount of securities that may be sold.

In addition, we could be forced to delay, discontinue or curtail product development, forgo sales and marketing efforts, and forgo licensing in attractive business opportunities, cease operations, sell or otherwise liquidate our assets or reorganize the Company, or complete a combination of the foregoing.

Our ability to raise capital through the sale of securities may be limited by the rules of the SEC and NYSE American that place limits on the number and dollar amount of securities that may be sold.

There can be no assurances that we will be able to raise the funds needed, especially in light of the fact that our ability to sell securities registered on our registration statement on Form S-3 will be limited until such time the market value of our voting securities held by non-affiliates is $75 million or more.

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We anticipate a need for additional employees as we undertake later stage clinical trials.

We have also incurred certain obligations pursuant to the terms of the VCN Purchase Agreement including the assumption of $2.4 million of liabilities and have agreed to a post-closing covenant to commit to fund research and development of VCN-01 and OV pipeline programs, including but not limited to the VCN-01 PDAC Phase 2 trial, a VCN-01 RB pivotal trial and necessary G&A within a budgetary plan of approximately $27.8 million with $5.0 million remaining as of December 31, 2024.

Further development of VCN-01 and pipeline OV product candidates will require additional expenditures.

We also expect to continue to incur significant operating and capital expenditures and anticipate that our expenses will substantially increase in the foreseeable future as we do the following:

● continue to undertake preclinical development of our OV pipeline and mid and late-stage clinical trials for our product candidates, including VCN-01;

● continue to undertake preclinical development of our OV pipeline and mid and late-stage clinical trials for our product candidates;

● complete a potential Phase 2a study evaluating VCN-01 dosing frequency

● seek regulatory approvals for our product candidates;

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● hire additional personnel, including members of our management team.

We may experience negative cash flow for the foreseeable future as we fund our development and clinical programs with capital expenditures.

We expect to experience negative cash flow for the foreseeable future as we fund our development and clinical programs with capital expenditures.

As a result, we will need to raise additional capital or generate significant revenues in order to achieve and maintain profitability.

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The amount of government funding available for grants is dependent upon governmental budgets over which we have no control and which change with new administrations.

The actual amount of funds we will need to operate is subject to many risk factors, some of which are beyond our control.

The actual amount of funds we will need to operate is subject to many factors, some of which are beyond our control.

These factors include the following:

The actual amount of funds we will need to operate is subject to many factors, some of which are beyond our control.

These factors include, without limitation, the following:

● the progress of our research activities and ability to attract patients;

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We currently have a limited operating history as an oncology company, no products approved for commercial sale, have no significant source of revenue and may never generate significant revenue.

We are a clinical-stage biopharmaceutical company that began to focus on development of oncolytic viruses for treatment of various types of cancer in 2022.

We are a clinical-stage biopharmaceutical company that began to focus on development of OVs for treatment of various types of cancer in 2022.

We have never generated any product revenue, do not expect to generate revenue in the near future and do not have any products approved for sale.

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● our ability to raise additional capital on a timely basis to continue to fund our clinical trials;

● demonstration in current and future clinical trials that our lead product candidate, VCN-01, as well as each of our other product candidates, is safe and effective;and

● demonstration in current and future clinical trials that our lead product candidate, VCN-01 (zabilugene almadenorepvec), as well as each of our other product candidates, is safe and effective;

● our ability to seek and obtain regulatory approvals, including with respect to the indications we are seeking.

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If we cannot successfully execute on any of the factors listed above, our business may not succeed, we may never generate revenue and your investment will be adversely affected.

We have identified material weaknesses in our internal controls in the past, and we cannot provide assurances that additional material weaknesses will not occur in the future

Although we currently believe that our internal controls are effective, we have identified material weaknesses in our internal controls in the past, and we cannot provide assurances that additional material weaknesses will not occur in the future

If our internal control over financial reporting or our disclosure controls and procedures are not effective, we may not be able to accurately report our financial results, prevent fraud, or file our periodic reports in a timely manner, which may cause investors to lose confidence in our reported financial information and may lead to a decline in our stock price.

Our management is responsible for establishing and maintaining adequate internal control over our financial reporting, as defined in Rule 13a- 15(f) under the Exchange Act.

Based on our assessment, we have concluded that as of December 31, 2024 we have remediated our prior weakness over internal controls.

During 2023 and the first three quarters of 2024, we did not maintain effective review controls at a sufficient level of precision with certain financial statement areas and over unusual transactions involving complex accounting and related disclosure requirements.

We also did not maintain effective information technology general controls over user access, program change management, and segregation of duties, within certain key information systems supporting our accounting and financial reporting processes.

Additionally, many of our business process controls dependent upon the information derived from these information systems were also ineffective, as we did not design and implement controls to validate the completeness and accuracy of underlying data utilized in the operation of those controls.

While we have taken remedial action to address the material weaknesses and we now believe that our internal control over financial reporting is effective, we cannot provide any assurance that such remedial measures, or any other remedial measures we take, will continue to be effective.

Based on our assessment, we have concluded that as of December 31, 2025 our internal control over financial reporting and our disclosure controls and procedures are effective.

However, during 2023 and the first three quarters of 2024, we identified certain material weaknesses in our internal controls, which led to a determination that our controls were not effective during those periods.

While we took remedial action to address the previously identified material weaknesses in 2024 and we believe that our internal control over financial reporting have been, and continue to be, effective since December 31, 2024, we cannot provide any assurance that such remedial measures, or any other remedial measures we take from time to time, will continue to be effective.

If we fail to maintain effective internal control over financial reporting, we may not be able to accurately report our financial results, detect or prevent fraud, or file our periodic reports in a timely manner, which may, among other adverse consequences, cause investors to lose confidence in our reported financial information and lead to a decline in our stock price.

In addition, a material weakness will not be considered remediated until the applicable controls operate for a sufficient period of time and management has concluded, through testing, that these controls are designed and operating effectively.

Although management believes that the material weaknesses have been remediated there can be no assurance that our internal control over financial reporting, as modified, will enable us to identify or avoid material weaknesses in the future.

Although management believes that the previously identified material weaknesses were remediated prior to December 31, 2024, there can be no assurance that our internal control over financial reporting, as modified, will enable us to identify or avoid material weaknesses in the future.

We expect to seek to raise additional capital in the future, which may be dilutive to stockholders or impose operational restrictions.

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We are authorized to issue 350,000,000 shares of Common Stock, of which 45,892,668 shares of Common Stock were outstanding as of March 10, 2026.

If all of the unissued authorized shares were issued stockholders ownership percentage will be diluted.

If all of the unissued authorized shares were issued stockholders ownership percentage will be significantly diluted.

In order to raise additional capital, we may in the future offer additional shares of our Common Stock or other securities convertible into or exchangeable for our Common Stock at prices that may not be the same as the price per share paid by existing stockholders, thereby subjecting such stockholders to dilution.

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Our quarterly and annual operating results may fluctuate significantly in the future, which makes it difficult for us to predict our future operating results.

The VCN Purchase Agreement requires that we make certain cash payments to Grifols upon attainment of certain milestones, which payments may vary significantly from period to period and any such variance could cause a significant fluctuation in our operating results from one period to the next.

The Purchase Agreement entered into in connection with the Acquisition requires that we make certain cash payments to Grifols upon attainment of certain milestones, which payments may vary significantly from period to period and any such variance could cause a significant fluctuation in our operating results from one period to the next.

As discussed elsewhere in this Annual Report, the payment of $5.0 million of contingent consideration earned by Grifols pursuant to the Acquisition has been deferred pending ongoing discussions with Grifols.

From time to time, we may enter into collaboration agreements with other companies that include development funding and significant upfront and milestone payments and/or royalties, which may become an important source of our revenue.

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In addition, our manufacturing and clinical trial expenses, which are anticipated to be significant, may fluctuate significantly quarter to quarter based upon whether or not we are engaged in clinical trials or manufacturing our product candidates, and timing of our process development work.

Furthermore, we measure compensation cost for stock-based awards made to employees at the grant date of the award, based on the fair value of the award as determined by our board of directors, and recognize the cost as an expense over the employee's requisite service period.

Furthermore, we measure compensation cost for stock-based awards made to employees at the grant date of the award, based on the fair value of the award as determined by the Board of Directors, and recognize the cost as an expense over the employee’s requisite service period.

As the variables that we use as a basis for valuing these awards change over time, our underlying stock price and stock price volatility, the magnitude of the expense that we must recognize may vary significantly.

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and sustained decreases in share price.

A prolonged U.S.

federal government shutdown could materially and adversely affect our business and operations.

Any disruption in the operations of the U.S.

government, including as a result of the recent or future temporary or prolonged shutdowns resulting from the failure of Congress to enact appropriations bills or raise the federal debt ceiling, could materially and adversely affect our business, operations and financial condition.

Recently, beginning on October 1, 2025, the U.S.

federal government shut down and remained shut down through November 12, 2025, and again beginning on January 31, 2026 through February 3, 2026, during which times certain regulatory agencies, such as the FDA and the SEC, furloughed critical employees and stopped critical activities.

Additionally, on October 10, 2025, the U.S.

government implemented substantial layoffs and workforce reductions in connection with the federal government shutdown, which resulted in the suspension or delay of various government-funded programs.

Furthermore, the recent federal government shutdown has resulted, and may continue for a prolonged period of time to result, in reduced availability of government services, and suspension or delay of activities by key agencies that regulate, fund, or interact with our business, including the SEC, the FDA, the Department of Health and Human Services, and the U.S.

Patent and Trademark Office.

As a result, the review and approval of our filings, applications, and submissions could be delayed, and we may be unable to access or rely upon certain government data or systems.

In particular, it may lead to disruptions and delays in FDA’s review and oversight of our product candidates and impact the FDA’s ability to provide timely feedback on our development program or pending applications.

Additionally, a prolonged or future shutdown of the U.S.

federal government could materially impact the operations of the SEC.

For example, the SEC announced that during the recent U.S.

federal government shutdowns, it would not review or declare registration statements effective.

In the event of an extended shutdown, the SEC may operate with limited staff or suspend certain functions altogether, which could delay the review or effectiveness of our filings, including registration statements or other financing-related disclosures.

Such delays could adversely affect our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue to fund our operations.

Government shutdowns, if prolonged, can significantly impact the ability of government agencies upon which rely, such as the FDA and SEC, to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

Even the threat of a government shutdown or prolonged budget negotiation uncertainty may adversely affect the broader U.S.

economy, investor confidence, and capital markets.

Such conditions could negatively impact our access to financing, timing of capital-raising transactions, and the liquidity or trading volume of our securities.

Accordingly, the current or future federal government shutdowns, or uncertainty regarding the continuity of government operations, could have a material adverse effect on our business, results of operations, and stock price.

Federal budget and debt-ceiling disputes may adversely affect capital markets and our financing activities.

Moreover, the uncertainty surrounding government funding debates and debt-ceiling negotiations can negatively affect market conditions, investor sentiment, and the liquidity of small-cap and microcap issuers such as ours.

If market volatility or trading disruptions were to occur during the current or future government shutdowns, our ability to execute at-the-market offerings or other financing transactions under our effective shelf registration statement or through private equity offerings could be materially impaired.

Accordingly, any federal government shutdown or protracted budget impasse could materially and adversely affect our regulatory compliance, financing options and capabilities, and overall financial condition.

RISKS RELATED TO OUR BUSINESS

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Prior to the VCN Acquisition, our focus was on the microbiome and our research and development was focused primarily on therapeutics for various microbiome related diseases.

Upon the VCN Acquisition, our focus has shifted to the use of oncolytic viruses to treat cancer.

Upon the VCN Acquisition, our focus has shifted to the use of OVs to treat cancer.

Although members of our management and scientific/development teams have experience in the research and development of cancer treatments, we may not be successful as a company with such focus.

In the past Oncolytic Viruses have experienced certain safety and efficacy challenges.

In the past OVs have experienced certain safety and efficacy challenges.

Although current clinical trials of OVs have supported their role as a potential treatment for cancer, there is the risk of virus-related toxicities in vivo and possible transmission to patients’ contacts, such as other patients and health care workers.

In recent years, clinical trials to address these concerns have been conducted.

Any such transmission by VCN-01 or a competitor would have an adverse impact on our future OV research and development efforts.

Any such transmission by VCN-01 (zabilugene almadenorepvec) or a competitor would have an adverse impact on our future OV research and development efforts.

Likewise, a number of OVs have previously failed to meet their primary endpoints in advanced clinical trials, potentially reducing investor and partner interest or confidence in the development of new such therapies, however well differentiated they are from previous products.

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Failure can occur at any point in the process, including after significant funds have been invested.

The success of our business currently depends on our development, approval and commercialization of our lead product candidate, VCN-01.

Our ongoing Phase 1b/2a clinical trial of SYN-004 for the prevention of aGVHD in allogeneic HCT recipients, our completed Phase 1 single ascending and multiple ascending dose studies of SYN-020 and ongoing early-stage clinical trials of VCN-01 are not designed as registrational clinical trials and we currently do not have the necessary funding to complete any late stage registrational clinical trials.

The success of our business currently depends on our development, approval and commercialization of our lead product candidate, VCN-01 (zabilugene almadenorepvec).

Our ongoing Phase 1b/2a clinical trial of SYN-004 for the prevention of aGVHD in allogeneic HCT recipients, and ongoing early-stage clinical trials of VCN-01 are not designed as registrational clinical trials and we currently do not have the necessary funding to complete any late stage registrational clinical trials.

There are many uncertainties known and unknown that may affect the outcome of future clinical trials.

All of our product candidates, including VCN-01, SYN-004 (ribaxamase), and SYN-020 will require additional clinical and non-clinical development, regulatory review and approval in multiple jurisdictions, substantial investment, access to sufficient commercial manufacturing capacity and significant marketing efforts before we can generate any revenue from product sales.

Regardless of whether our clinical trials are deemed to be successful, promising new product candidates may fail to reach the market or may only have limited commercial success because of efficacy or safety concerns, failure to achieve positive clinical outcomes, inability to obtain necessary regulatory approvals or satisfy regulatory criteria, limited scope of approved uses, excessive costs to manufacture, the failure to establish or maintain intellectual property rights, or infringement of the intellectual property rights of others.

Although Rasayana has assumed all responsibility and costs for the development and commercialization of SYN-020, and has committed to use reasonable commercial efforts to develop and commercialize SYN-020 and to meet certain development milestones set forth in the Rasayana License Agreement, no assurances can be made that they will be successful in further developing or obtaining regulatory approval of products related thereto or that we will receive any development milestone payments or sales milestone payments from Rasayana in connection therewith.

Regardless of whether our clinical trials (or, in the case of SYN-020, Rasayana’s clinical trials) are deemed to be successful, promising new product candidates may fail to reach the market or may only have limited commercial success because of efficacy or safety concerns, failure to achieve positive clinical outcomes, inability to obtain necessary regulatory approvals or satisfy regulatory criteria, limited scope of approved uses, excessive costs to manufacture, the failure to establish or maintain intellectual property rights, or infringement of the intellectual property rights of others.

Failure to obtain regulatory approvals of VCN-01, SYN-004 (ribaxamase) or SYN-020 in a timely manner would have a material adverse impact on our business.

Even if we successfully develop VCN-01, SYN-004 (ribaxamase), SYN-020 or other new products or enhancements, they may be quickly rendered obsolete by changing customer preferences, changing industry standards, or competitors’ innovations.

Even if we successfully develop VCN-01, SYN-004 (ribaxamase), or other new products or enhancements, or if Rasayana successfully develops SYN-020 or new products or enhancements covered by the Rasayana License Agreement, they may be quickly rendered obsolete by changing customer preferences, changing industry standards, or competitors’ innovations.

Innovations may not be quickly accepted in the marketplace because of, among other things, entrenched patterns of clinical practice or uncertainty over third-party reimbursement.

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Failure to launch successful new products or new indications for existing products may cause our products to become obsolete, which may limit our ability to achieve profitability.

We may form or seek strategic alliances or enter into additional licensing arrangements in the future, and we may not realize the benefits of such alliances or licensing arrangements.

We have in the past, and may continue to seek to, form or seek strategic alliances or enter into additional licensing arrangements in the future, and we may not realize the benefits of such alliances or licensing arrangements.

As discussed elsewhere in this Annual Report on Form 10-K, on February 17, 2026, we entered into the Rasayana License Agreement with Rasayana, pursuant to which we granted Rasayana an exclusive worldwide license with the right to grant sublicenses to research, develop, manufacture and commercialize any Product (as such term is defined in the Rasayana License Agreement), which includes SYN-020, comprising, containing, or covered by the Licensed IP (as such term is defined in the Rasayana License Agreement) and/or devised, developed, or produced using the Licensed IP.

We are also considering licensing and partnership opportunities for the further development of our SYN-004 (ribaxamase) product candidate, and may consider other strategic opportunities for this product candidate or our other product candidates from time to time.

We may form or seek strategic alliances, create joint ventures or collaborations or enter into additional licensing arrangements with third parties that we believe will complement or augment our development and commercialization efforts with respect to our product candidates and any future product candidates that we may develop.

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In addition to our own patent applications, we also currently rely on licensing agreements with third party patent holders/licensors for our products.

We have entered license agreements upon which our OV technology is dependent.

We have entered into license agreements upon which our OV technology is dependent.

If we breach the terms of any of our license agreements or collaborations, including any failure to make royalty payments required thereunder or failure to reach certain developmental milestones or fulfill our obligations under the agreements could result in a termination of the agreements.

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Due to our small work force, we expect in future years to require additional personnel to support our later stage research and development efforts.

Manufacturing of VCN-01, SYN-004 (ribaxamase) and SYN-020 to support potential future clinical studies will require us to incur additional expenses.

Manufacturing of VCN-01 (zabilugene almadenorepvec) and SYN-004 (ribaxamase) to support potential future clinical studies will require us to incur additional expenses.

Because development activities in our collaborations are sometimes determined pursuant to joint steering committees, future development costs associated with these programs may be difficult to anticipate and may exceed our expectations.

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Developments by competitors may render our products or technologies obsolete or non-competitive.

The pharmaceutical and biotechnology industries, including the oncolytic virus industry and the monoclonal antibody industry, are characterized by rapidly evolving technology and intense competition.

The pharmaceutical and biotechnology industries, including the OV industry and the monoclonal antibody industry, are characterized by rapidly evolving technology and intense competition.

Our competitors include major multi-national pharmaceutical companies and biotechnology companies developing both generic and proprietary therapies to treat serious diseases.

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These competitors will compete with us in product sales as well as recruitment and retention of qualified scientific and management personnel, establishment of clinical trial sites and patient enrollment for clinical trials, as well as in the acquisition of technologies and technology licenses complementary to our programs or advantageous to our business.

Companies pursuing clinical development of modified oncolytic adenoviruses include AdCure Bio LLC, Calidi Biotherapeutics, Inc., Candel Therapeutics, Inc., CG Oncology, Inc., Elicera Therapeutics AB, EpicentRx, Inc., GeneMedicine, Co Ltd., IconOVir Bio, Inc., Lokon Pharma AB, Memgen, Inc., Multivir, Inc., NewGenPharm Incorporation, Oncolys BioPharma, Inc., Orca Therapeutics B.V., Akamis Bio Ltd.

(formerly PsiOxus Therapeutics Ltd), Shanghai Sunway Biotech Co., Ltd, Circio Holding ASA (formerly Targovax Oy|Targovax ASA), Tessa Therapeutics, Theolytics Ltd., TILT Biotherapeutics, Ltd., and Valo Therapeutics Oy.

Companies pursuing clinical development of modified oncolytic adenoviruses include AdCure Bio LLC, Calidi Biotherapeutics, Inc., Candel Therapeutics, Inc., CG Oncology, Inc., Elicera Therapeutics AB, EpicentRx, Inc., GeneMedicine, Co Ltd., Lokon Pharma AB, Memgen, Inc., Multivir, Inc., NewGenPharm Incorporation, Oncolys BioPharma, Inc., Orca Therapeutics B.V., Akamis Bio Ltd.

(formerly PsiOxus Therapeutics Ltd), Shanghai Sunway Biotech Co., Ltd, Tessa Therapeutics, Theolytics Ltd., TILT Biotherapeutics, Ltd., Urogen Pharma, and Valo Therapeutics Oy.

OV products have been or are being developed using other virus backbones, including:

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and vaccinia viruses (Genelux Corporation, Imugene Ltd, Joint Biosciences Ltd, KaliVir Immunotherapeutics LLC, SillaJen, Inc., Transgene SA, Turnstone Biologics, Corp.).

In addition, academic research centers may develop technologies that compete with our VCN-01, SYN-004 and SYN-020, products and our other technologies.

In addition, academic research centers may develop technologies that compete with our VCN-01 (zabilugene almadenorepvec), SYN-004 (ribaxamase) and SYN-020 products and our other technologies.

Should clinicians or regulatory authorities view alternative therapeutic regiments as more effective than our products, this might delay or prevent us from obtaining regulatory approval for our products, or it might prevent us from obtaining favorable reimbursement rates from payers, such as Medicare, Medicaid, hospitals and private insurers.

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We rely on suppliers for the substance raw materials of our product candidates and third parties for manufacturing-related services to produce material that meets appropriate content, quality and stability standards and use in clinical trials of our products and, after approval, for commercial distribution.

To succeed, clinical trials require adequate supplies of study material, which may be difficult or uneconomical to procure or manufacture and there can be no assurance that we will successfully procure such study material or even if procured, that we can do so in quantities and in a timely manner to allow our clinical trials to proceed as planned.

To succeed, clinical trials require adequate supplies of study material, which may be difficult or uneconomical to procure or manufacture and there can be no assurance that we will successfully procure such study material when needed, if at all, or even if procured, that we can do so in quantities and in a timely manner to allow our clinical trials to proceed as planned.

Drug supply, once produced, is stored at clinical trial sites and vendor depots and we rely on these locations to maintain and protect the drug supply appropriately.

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If we do find replacement manufacturers and vendors, we may not be able to enter into agreements with them on terms and conditions favorable to us and there could be a substantial delay before a new facility could be qualified and registered with the FDA and foreign regulatory authorities.

The third-party manufacturers of the active pharmaceutical ingredient (API) and drug product for our lead product candidates, VCN-01, SYN-004 (ribaxamase) and SYN-020, are established cGMP manufacturers.

The third-party manufacturers of the active pharmaceutical ingredient (API) and drug product for our lead product candidates, VCN-01 (zabilugene almadenorepvec), and SYN-004 (ribaxamase), are established cGMP manufacturers.

For all other therapeutic areas, we have not yet established cGMP manufacturers for our biologic and drug candidates.

We have used only one API manufacturer for each of our product candidates (VCN-01, SYN-004 or SYN-020) used in clinical trials to date.

We have used only one API manufacturer for each of our product candidates (VCN-01, SYN-004 and SYN-020) (prior to entering into the Rasayana License Agreement) used in clinical trials to date.

Although we believe additional manufacturers are available, if any of our manufacturers were to limit or terminate production or otherwise fail to meet the quality or delivery requirements needed to satisfy the supply commitments, the process of locating and qualifying alternate sources could require up to several months, during which time our production could be delayed.

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Furthermore, if our manufacturers fail to deliver the required commercial quantities on a timely basis and at commercially reasonable prices, we may be unable to meet demand for any approved products and would lose potential revenues.

For our Phase 2 clinical trial of VCN-01 in patients with PDAC, we are administering our clinical product candidate, VCN-01, in combination with other approved standard of care drugs.

Any problems obtaining the standard of care drugs could result in a delay or interruption in our clinical trials.

For our ongoing Phase 2 clinical trial of VCN-01 in patients with PDAC, we are administering VCN-01 in combination with the already approved standard of care drugs, gemcitabine/nab-paclitaxel, for which there has recently been a supply shortage.

Therefore, our success will be dependent upon the continued use of and ability to obtain the standard of care drugs.

For our clinical trials of VCN-01 (zabilugene almadenorepvec), we have or will administer our product candidate, VCN-01, in combination with other cancer drugs.

Any problems obtaining these co-administered drugs could result in a delay or interruption in our clinical trials.

For our proposed pivotal clinical trial of VCN-01 in patients with PDAC, we plan to administer VCN-01 in combination with the already approved standard of care drugs, gemcitabine/nab-paclitaxel, for which there have previously been supply shortages.

A potential clinical trial in refractory retinoblastoma is expected to administer VCN-01 in combination with topotecan.

Our success will be dependent upon the continued use of and ability to obtain the co-administered drugs.

We expect that in any other clinical trials we conduct for additional indications, our clinical product candidate will also be administered in combination with drugs owned by third parties.

If any of the standard of care or third-party drugs that are used in our clinical trials are unavailable while the trials are continuing, the timeliness and commercialization costs could be impacted.

If any of the co-administered drugs that are used in our clinical trials are unavailable while the trials are continuing, the timeliness and commercialization costs could be impacted.

In addition, if any of these other drugs are determined to have safety or efficacy problems, our clinical trials and commercialization efforts would be adversely affected.

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We have limited resources dedicated to designing, conducting and managing our preclinical studies and clinical trials.

We rely on, third parties, including clinical research organizations (CROs), consultants and principal investigators, to assist us in designing, managing, conducting, monitoring and analyzing the data from our preclinical studies and clinical trials.

We rely on, third parties, including CROs, consultants and principal investigators, to assist us in designing, managing, conducting, monitoring and analyzing the data from our preclinical studies and clinical trials.

We rely on these vendors and individuals to perform many facets of the clinical development process on our behalf, including conducting preclinical studies, the recruitment of sites and subjects for participation in our clinical trials, maintenance of good relations with the clinical sites, and ensuring that these sites are conducting our trials in compliance with the trial protocol and applicable regulations.

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Due to our small work force, we expect in future years to require additional personnel to support our later stage research and development efforts.

We have been and may be required to retain additional consultants and employees in order to fulfill our obligations under our licenses and collaborations for our development of VCN-01, SYN-004 (ribaxamase), SYN-020, and our agreements with Washington University and other collaborators.

We have been and may be required to retain additional consultants and employees in order to fulfill our obligations under our licenses and collaborations for our development of VCN-01 (zabilugene almadenorepvec), SYN-004 (ribaxamase), and our agreements with Washington University and other collaborators.

Our future performance will depend in part on our ability to successfully integrate newly hired officers into our management team and our ability to develop an effective working relationship among senior management.

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Such services may not always be available to us on a timely basis when we need them.

Inadequate funding for the FDA, the SEC and other government agencies, including from government shutdowns, or other disruptions to these agencies’ operations, could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business and timelines.

Without appropriation of additional funding to federal agencies, our business operations related to our product development activities for the U.S.

market could be impacted.

The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and other events that may otherwise affect the FDA’s ability to perform routine functions.

Average review times at the agency have fluctuated in recent years as a result.

Disruptions at the FDA and other agencies may also slow the time necessary for new product candidates to be reviewed and/or approved by necessary government agencies, which would adversely affect our business.

In addition, government funding of the SEC and other government agencies on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable.

Disruptions and personnel turnover, as a result of leadership changes, staff reductions or otherwise, at the FDA and other agencies may also slow the time necessary for new drugs and biologics or modifications to approved drugs and biologics to be reviewed and/or approved by necessary government agencies, which would adversely affect our business.

Changes and cuts in FDA staffing also could result in delays in the FDA’s responsiveness or in its ability to review IND submissions or applications, issue regulations or guidance, or implement or enforce regulatory requirements in a timely fashion or at all.

Over the last several years the U.S.

government has shut down several times and certain regulatory authorities, such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical activities.

In addition, the current U.S.

presidential administration has issued certain policies and Executive Orders directed towards reducing the employee headcount and costs associated with U.S.

administrative agencies, including the FDA, and it remains unclear the degree to which these efforts may limit or otherwise adversely affect the FDA’s ability to conduct routine activities.

If a prolonged government shutdown occurs, or if renewed global health concerns, funding shortages or staffing limitations hinder or prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, including formal and informal interactions with product developers, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

Global health crises may adversely affect our planned operations.

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● interruption in global shipping that may affect the manufacture and transport of clinical trial materials, such as investigational drug product used in our clinical trials;

● changes in local regulations as part of a response to the a pandemic outbreak which may require us to change the ways in which our clinical trials are conducted, which may result in unexpected costs, or to discontinue the clinical trials altogether;

● changes in local regulations as part of a response to a pandemic outbreak which may require us to change the ways in which our clinical trials are conducted, which may result in unexpected costs, or to discontinue the clinical trials altogether;

● delays in necessary interactions with local regulators, ethics committees and other important agencies and contractors due to limitations in employee resources or forced furlough of government employees;

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In addition, it could impact economies and financial markets, resulting in an economic downturn that could impact our ability to raise capital or slow down potential partnering relationships.

Our business and the business of the suppliers of our clinical product candidates has been and is expected to continue to be materially and adversely affected by the pandemic and post-pandemic workforce and supply-chain issues.

Our business and the business of the suppliers of our clinical product candidates were materially and adversely affected by the pandemic and post-pandemic workforce and supply-chain issues.

While we are currently not experiencing material delays, such events could result in the delay or complete or partial closure of clinical trial sites or one or more manufacturing facilities which could impact our supply of our clinical product candidates.

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The extent to which a pandemic may impact our business and clinical trials will depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the ultimate geographic spread of the disease, the duration of the outbreak, travel restrictions and social distancing in the United States and Spain, business closures or business disruptions and the effectiveness of actions taken in the United States, Spain, and other countries to contain and treat the disease.

We do not yet know the full extent of potential delays or impacts on our business, operations, or the global economy as a whole.

While the original spread of COVID-19 has been mitigated, the continued emergence of novel virus strains mean there is no guarantee that a future outbreak of this or any other widespread epidemics will not occur, or that the global economy will recover, either of which could seriously harm our business.

Business disruptions could seriously harm our future revenue and financial condition and increase costs and expenses.

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Any of the foregoing could harm our business and we cannot anticipate all of the ways in which the current economic climate and financial market conditions could adversely impact our business.

In addition, the global macroeconomic environment could be negatively affected by, among other things, pandemics or epidemics, instability in global economic markets, instability in the global credit markets, supply chain weaknesses, instability in the geopolitical environment as a result of the withdrawal of the United Kingdom from the European Union, the Russian war with Ukraine, the war in the Middle East and other political tensions, and foreign governmental debt concerns.

In addition, the global macroeconomic environment could be negatively affected by, among other things, pandemics or epidemics, instability in global economic markets, instability in the global credit markets, supply chain weaknesses, instability in the geopolitical environment as a result of the Russian war with Ukraine, the war in the Middle East, military or other action taken by the United States in foreign countries and other political tensions, and foreign governmental debt concerns.

Such challenges have caused, and may continue to cause, uncertainty and instability in local economies and in global financial markets.

Changes to trade policy, including tariff and customs regulations, or failure to comply with such regulations may have an adverse effect on our reputation, business, financial condition and results of operations.

Changes in U.S.

or international social, political, regulatory and economic conditions or in laws and policies governing trade, manufacturing, development and investment in the countries where we currently sell our products or conduct our business, could adversely affect our business, reputation, financial condition and results of operations.

or international social, political, regulatory and economic conditions or in laws and policies governing trade, manufacturing, development and investment in the countries where we currently conduct our business could adversely affect our business, reputation, financial condition and results of operations.

Changes or proposed changes in U.S.

or other countries’ trade policies may result in restrictions and economic disincentives on international trade.

Tariffs, economic sanctions and other changes in U.S.

trade policy have in the past and could in the future trigger retaliatory actions by affected countries, and certain foreign governments have instituted or are considering imposing retaliatory measures on certain U.S.

Changes to U.S.

policy implemented by the U.S.

Congress, the Trump administration or any new administration have impacted and may in the future impact, among other things, the U.S.

and global economy, international trade relations, unemployment, immigration, healthcare, taxation, the U.S.

regulatory environment, inflation and other areas.

government has recently imposed, or is currently considering imposing, tariffs on certain trade partners, including China, where we have engaged a vendor.

Additionally, the United States has recently imposed significant tariffs on imports from other countries, including a baseline tariff of 10% on imports into the United States and higher tariffs on multiple designated countries, such as “reciprocal” tariffs at varying rates.

Such tariffs have prompted retaliatory measures from several countries, which may further escalate.

Certain of these tariffs have been subsequently paused or modified, and the situation remains fluid.

While pharmaceutical products are currently excluded from the baseline and “reciprocal” tariffs imposed by the United States, such tariffs still apply to the raw materials and other products necessary for the manufacture and formulation of our product candidates.

In addition, the U.S.

Department of Commerce has initiated an investigation under Section 232 of the Trade Expansion Act of 1962, as amended, to determine the effects of importing pharmaceuticals and pharmaceutical ingredients on national security.

This investigation may lead to the imposition of tariffs on pharmaceutical imports, consistent with the current U.S.

administration’s stated policy objective of reshoring pharmaceutical manufacturing to the United States.

Further, in July 2025, the United States and the EU announced the framework of a trade agreement that generally imposes a 15% tariff on imports from the EU.

Under this agreement, pharmaceutical products would not be subject to any future Section 232 investigation duties in excess of this 15% rate.

Supreme Court is currently considering legal challenges to tariffs imposed under the International Emergency Economic Powers Act, such as the baseline and reciprocal tariffs discussed above.

The outcome of this decision could impact trade agreements entered into by the United States and the wider tariff environment in which we operate.

Tariffs, reciprocal tariffs, economic sanctions, embargoes, import or export licensing requirements and other changes in U.S.

trade policy have in the past and could in the future trigger additional retaliatory actions by affected countries.

Further, any emerging protectionist or nationalist trends (whether regulatory, or consumer-driven) either in the United States or in other countries could affect the trade environment.

We, like many other multinational corporations, conduct a significant amount of business that would be impacted by changes to the trade policies of the United States and foreign countries (including governmental action related to tariffs, international trade agreements, or economic sanctions).

Our business, like many other corporations, would be impacted by changes to the trade policies of the United States and foreign countries (including governmental action related to tariffs, international trade agreements, or economic sanctions).

Such changes have the potential to adversely impact the U.S.

economy or certain sectors thereof or the economy of another country in which we conduct operations, our industry and the global demand for our products, and as a result, could have a material adverse effect on our business, financial condition and results of operations.

economy or certain sectors thereof, the global economy, and our industry, and as a result, could have a material adverse effect on our business, financial condition and results of operations.

We rely extensively on our information technology systems, and our systems and infrastructure face certain risks, including cybersecurity and data leakage risks.

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● obtaining permission to proceed under an IND application with the FDA or foreign equivalent to commence clinical trials;

● delays in reaching an agreement with FDA or other ergaultory authorities on final trial design, including selection of control dose and efficacy endpoints

● identification of, and acceptable arrangements with, one or more clinical sites;

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Success in preclinical testing and early clinical trials does not ensure that later clinical trials will be successful.

Success in Phase 1 studies of VCN-01 in PDAC or retinoblastoma does not ensure success of VCN-01, especially in light of the small number of patients treated in those trials.

Success in Phase 1 and Phase 2 studies of VCN-01 (zabilugene almadenorepvec) in PDAC or retinoblastoma does not ensure success of VCN-01, especially in light of the small number of patients treated in those trials.

Success of our predecessor P1A clinical product or positive topline data from our previous SYN-004 (ribaxamase) Phase 1 and Phase 2 clinical trials, does not ensure success of SYN-004 (ribaxamase).

Furthermore, the FDA could determine that VCN-01 or SYN-004 (ribaxamase) have not demonstrated appropriate safety and thus require additional clinical trials and safety data, despite prior positive clinical trial results.

Furthermore, the FDA could determine that VCN-01 (zabilugene almadenorepvec) or SYN-004 (ribaxamase) have not demonstrated appropriate safety and thus require additional clinical trials and safety data, despite prior positive clinical trial results.

We cannot be sure that the results of later clinical trials would replicate the results of prior clinical trials and preclinical testing nor that they would satisfy the requirements of the FDA or other regulatory agencies.

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In addition, the FDA or other regulatory agencies may order the temporary or permanent discontinuation of our clinical trials at any time if they believe that the clinical trials are not being conducted in accordance with applicable regulatory requirements or that they present an unacceptable safety risk to the clinical trial subjects.

For example, the FDA or foreign equivalents could determine that VCN-01 or SYN-004 has not demonstrated appropriate safety, that adverse events are drug related and require additional clinical trials and safety data, despite positive results from Phase 1 clinical trials of VCN-01 or our SYN-004 Phase 2b clinical trial.

For example, the FDA or foreign equivalents could determine that VCN-01 (zabilugene almadenorepvec) or SYN-004 (ribaxamase) has not demonstrated appropriate safety, that adverse events are drug related and require additional clinical trials and safety data, despite positive results from Phase 1 and Phase 2 clinical trials of VCN-01 or our SYN-004 Phase 2b clinical trial.

Administering any product candidate to humans may produce undesirable side effects.

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Under the Orphan Drug Act of 1983, the (“Orphan Drug Act”), the FDA may designate a product as an orphan drug if it is a drug intended to treat a rare disease or condition, which is defined as a patient population of fewer than 200,000 individuals in the United States.

We have received orphan drug designation from both the FDA and EMA for VCN-01 for the treatment of retinoblastoma and for the treatment of pancreatic cancer.

We have received orphan drug designation from both the FDA and EMA for VCN-01 (zabilugene almadenorepvec) for the treatment of retinoblastoma and for the treatment of pancreatic cancer.

If a product with an orphan drug designation subsequently receives the first marketing approval for the indication for which it has such designation, the product is entitled to a seven-year period of marketing exclusivity in the United States, which precludes the FDA from approving another marketing application for the same drug for the same indication during that time period with some exceptions.

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Fast Track designation by the FDA may not actually lead to a faster development or regulatory review or approval process, and does not assure FDA approval of our product candidate and, even if we obtain FDA approval, we may not receive marketing approval, marketing exclusivity or other expected benefits.

In May 2024, the FDA granted Fast Track designation to VCN-01 for the treatment of pancreatic cancer.

In May 2024, the FDA granted Fast Track designation to VCN-01 (zabilugene almadenorepvec) for the treatment of pancreatic cancer.

However, the receipt of such a designation for a product candidate may not result in a faster development process, review or approval compared to drugs considered for approval under conventional regulatory procedures and does not assure that the product will ultimately be approved by the regulatory authority or that approval will be granted within any particular timeframe.

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Fast Track designation alone does not guarantee qualification for the FDA’s priority review procedures.

Although we have obtained rare pediatric disease designation for VCN-01 for the treatment of retinoblastoma, we may not be eligible to receive a priority review voucher in the event the FDA determines we no longer meet the criteria for designation, revokes the designation or FDA approval of a BLA for VCN-01 for retinoblastoma does not occur prior to September 30, 2026.

Although we have obtained rare pediatric disease designation for VCN-01 (zabilugene almadenorepvec) for the treatment of retinoblastoma, we may not be eligible to receive a priority review voucher in the event the FDA determines we no longer meet the criteria for designation, revokes the designation or FDA approval of a BLA for VCN-01 for retinoblastoma does not occur prior to September 30, 2029.

The FDA grants rare pediatric disease designation for rare diseases (fewer than 200,000 affected persons in the United States) that are serious and life-threatening and primarily affect children ages 18 years or younger.

The sponsor of an application for a rare pediatric disease drug product may be eligible for a voucher that can be used or sold to obtain a priority review for a subsequent application submitted under section 505(b)(1) of the FDCA or section 351 of the PHS Act.

The rare pediatric disease priority review voucher program was most recently reauthorized by Congress through December 20, 2024, with the potential for priority review vouchers to be granted through September 30, 2026.

We received rare pediatric disease designation from the FDA for VCN-01 on July 30, 2024.

Legislative authorization for the rare pediatric disease priority review voucher (PRV) program was most recently authorized by Congress through September 30, 2029.

We received rare pediatric disease designation from the FDA for VCN-01 (zabilugene almadenorepvec) on July 30, 2024.

Vouchers for rare pediatric disease drugs are awarded for qualifying applications when the drug receives approval.

Although VCN-01 has received rare pediatric disease designation for the treatment of retinoblastoma, VCN-01 may not receive a priority review voucher for a number of reasons:

VCN-01 may not receive approval for retinoblastoma prior to September 30, 2026;

Although VCN-01 has received rare pediatric disease designation for the treatment of retinoblastoma, VCN-01 may not receive a PRV for a number of reasons:

VCN-01 may not receive approval for retinoblastoma prior to the required deadline;

VCN-01 may receive approval in adults, but not pediatric patients;

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Finally, a rare pediatric disease designation does not necessarily lead to faster development or regulatory review of the product or increase the likelihood that it will receive marketing approval.

The failure to maintain rare pediatric disease designation for VCN-01 or if FDA approval does not occur prior to September 30, 2026 could result in the inability to receive a priority review voucher which could adversely affect our business, financial condition and results of operations.

The failure to maintain rare pediatric disease designation for VCN-01 or if FDA approval does not occur prior to the required deadline could result in the inability to receive a priority review voucher which could adversely affect our business, financial condition and results of operations.

Our product candidates, if approved for sale, may not gain acceptance among physicians, patients and the medical community, thereby limiting our potential to generate revenues.

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Our collaborators assisting our competitors could harm our competitive position.

We have in the past, and expect to have in the future, agreements with third-party contract research organizations (CROs) under which we have delegated to the CROs the responsibility to coordinate and monitor the conduct of our VCN-01, SYN-004 and SYN-020 clinical trials and to manage data for our clinical programs.

We have in the past, and expect to have in the future, agreements with third-party CROs under which we have delegated to the CROs the responsibility to coordinate and monitor the conduct of our VCN-01 (zabilugene almadenorepvec), SYN-004 (ribaxamase) and SYN-020 (prior to entering into the Rasayana License Agreement) clinical trials and to manage data for our clinical programs.

We also rely upon CROs to monitor and manage data for our clinical programs, as well as the execution of future nonclinical studies.

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Reimbursement may not be available for our product candidates, which would impede sales.

Market acceptance and sales of our product candidates may depend on coverage and reimbursement policies and health care reform measures.

Market acceptance and sales of our product candidates may depend in part on coverage and reimbursement policies from third-party payors, such as government insurance programs, including Medicare and Medicaid, private health insurers, health maintenance organizations and other health care related organizations, who are increasingly challenging the price of medical products and services.

Accordingly, there is significant uncertainty related to the insurance coverage and reimbursement of newly approved products.

Adoption of any drug by the medical community may be limited if third-party payers will not offer adequate coverage.

In the United States, the principal decisions about reimbursement for new products are typically made by CMS.

Private payors tend to follow CMS to a substantial degree.

However, no uniform or consistent policy of coverage and reimbursement for drug products exists among third-party payors.

Therefore, coverage and reimbursement for drug products can differ significantly from payor to payor as well as from state to state.

Consequently, the coverage determination process is often a time-consuming and costly process that must be played out across many jurisdictions and different entities.

Further, a payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved.

Furthermore, coverage policies and third-party reimbursement rates may change at any time.

Decisions about formulary coverage as well as levels at which government authorities and third-party payers, such as private health insurers and health maintenance organizations, reimburse patients for the price they pay for our products as well as levels at which these payors pay directly for our products, where applicable, could affect whether we are able to commercialize these products.

We cannot be sure that reimbursement will be available for any of our products.

We cannot be sure that reimbursement will be available for any of our product candidates.

Even if favorable coverage and reimbursement status is attained for one or more of our product candidates for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

Also, we cannot be sure that coverage or reimbursement amounts will not reduce the demand for, or the price of, our products.

If coverage and reimbursement are not available or are available only at limited levels, we may not be able to commercialize our products.

If coverage and reimbursement are not available or are available only at limited levels, we may not be able to commercialize our product candidates that we develop and that may be approved.

Thus, even if we succeed in bringing a product to market, it may not be considered medically necessary or cost-effective, and the amount reimbursed for any products may be insufficient to allow us to sell our products on a competitive basis.

In recent years, officials have made numerous proposals to change the health care system in the United States.

These proposals include measures that would limit or prohibit payments for certain medical treatments or subject the pricing of drugs to government control.

These proposed legislative and/or regulatory changes may negatively impact the reimbursement for our products, following approval.

The availability of numerous generic treatments may also substantially reduce the likelihood of reimbursement for our future products.

In addition, in many foreign countries, particularly the countries of the European Union, the pricing of prescription drugs is subject to government control.

If our products are or become subject to government regulation that limits or prohibits payment for our products, or that subjects the price of our products to governmental control, we may not be able to generate revenue, attain profitability or commercialize our products.

If our products are or become subject to government regulation that limits or prohibits payment for our products,

or that subjects the price of our products to governmental control, we may not be able to generate revenue, attain profitability or commercialize our products.

As a result of legislative proposals and the trend towards managed health care in the United States, third-party payors are increasingly attempting to contain health care costs by limiting both coverage and the level of reimbursement of new drugs.

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As a result, significant uncertainty exists as to whether and how much third-party payors will reimburse patients for their use of newly-approved drugs, which in turn will put pressure on the pricing of drugs.

The downward pressure on healthcare costs in general, and prescription drugs in particular, has and is expected to continue to increase in the future.

Healthcare reform measures could hinder or prevent our product candidates’ commercial success.

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Any government-adopted reform measures could adversely impact the pricing of healthcare products and services in the United States or internationally and the amount of reimbursement available from governmental agencies or other third-party payors.

Changes in applicable laws, rules, and regulations or the interpretation of existing laws, rules, and regulations could impact our business in the future by requiring, for example:

(i) changes to our manufacturing arrangements;

(ii) additions or modifications to product labeling;

(iii) the recall or discontinuation of our products;

or (iv) additional record-keeping requirements.

If any such changes were to be imposed, they could adversely affect the operation of its business.

The continuing efforts of the U.S.

and foreign governments, insurance companies, managed care organizations and other payors of health care services to contain or reduce health care costs may adversely affect our ability to set prices for our products which we believe are fair, and our ability to generate revenues and achieve and maintain profitability.

In August 2022, the Inflation Reduction Act (“IRA”) was enacted, which, among other things, requires the U.S.

Department of Health and Human Services (“HHS”) to directly negotiate the selling price of a statutorily specified number of drugs and biologics each year that CMS reimburses under Medicare Part B and Part D.

The negotiated price may not exceed a statutory ceiling price.

Only high-expenditure single-source biologics that have been approved for at least 11 years (seven years for single-source drugs) are eligible to be selected by CMS for negotiation, with the negotiated price taking effect two years after the selection year.

For 2026, the first year in which negotiated prices become effective, CMS selected 10 high-cost Medicare Part D products in 2023, negotiations began in 2024, and the negotiated maximum fair price for each product has been announced.

In addition, CMS has selected and announced the negotiated maximum fair price for 15 additional Medicare Part D drugs which will become effective in 2027.

For 2028, CMS has selected an additional 15 drugs, comprised of drugs covered under Medicare Part D and, for the first time, drugs payable under Medicare Part B.

For 2029 and subsequent years, 20 Part B or D drugs will be selected.

The negotiated prices have represented, and will continue to represent, a significant discount from average prices to wholesalers and direct purchasers.

The IRA also imposes rebates on Medicare Part B and Part D drugs whose prices have increased at a rate greater than the rate of inflation, and in 2024, CMS finalized regulations for the Medicare Part B and Part D inflation rebates.

The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

Manufacturers that fail to comply with the IRA may be subject to various penalties, including civil monetary penalties.

These provisions have been, and may continue to be, subject to legal challenges.

Although full economic effect of the IRA on our business and the pharmaceutical industry in general is unknown at this time, it will likely have a significant impact on the pharmaceutical industry and the pricing of our products and product candidates.

Similarly, the adoption of restrictive price controls in new jurisdictions, more restrictive controls in existing jurisdictions or the failure to obtain or maintain timely or adequate pricing could also reduce our profitability.

We expect pricing pressures will continue globally.

Additionally, on April 15, 2025, the Trump Administration published Executive Order 14273, “Lowering Drug Prices by Once Again Putting Americans First,” which generally directs the federal government to take measures to reduce drug prices.

On May 12, 2025, the Trump Administration published Executive Order 14297, “Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients” which generally, among other things, directs the federal government to establish and communicate most-favored-nation price targets to pharmaceutical manufacturers to bring prices for American patients in line with comparably developed nations.

Further, the Executive Order directs the federal government to support regulatory paths to allow direct-to-patient sales for companies that meet these targets.

It also states that the administration will take additional aggressive action (for example, examining whether marketing approvals should be modified or rescinded or opening the door for individual drug importation waivers) should manufacturers fail to offer American consumers the most-favored-nation lowest price.

It also directs the Secretary of Commerce and the U.S.

Trade Representative to “take all necessary and appropriate action to ensure foreign countries are not engaged in any act, policy, or practice that may be unreasonable or discriminatory or that may impair United States national security including by suppressing the price of pharmaceutical products below fair market value in foreign countries.” Recently, on December 23, 2025, CMS issued proposed regulations to establish, under the Center for Medicare and Medicaid Innovation, two mandatory Most-Favored-Nation demonstration models under Medicare

Parts B and D, respectively.

If these rules or other Most-Favored-Nation pricing rules are finalized, they are likely to reduce prices of at least some drugs in the United States, if they are also sold in comparator countries.

Even if we do not market drugs in such countries, we will be indirectly affected if our drugs competed with drugs whose prices were reduced as a result of Most-Favored-Nation pricing initiatives.

In addition, at the state level, legislatures have increasingly passed legislation and implemented regulations similar to those under consideration at the federal level, as well as laws designed to control pharmaceutical and biotherapeutic product pricing, including restrictions on pricing or reimbursement at the state government level, limitations on discounts to patients, marketing cost disclosure and transparency measures, restrictions or other limitations on patient assistance, and, in some cases, policies to encourage importation from other countries (subject to federal approval) and bulk purchasing.

Certain states are also pursuing cost containment efforts through Prescription Drug Affordability Boards (“PDABs”) and similar entities.

New laws, regulations and judicial decisions, or new interpretations of existing laws, regulations and decisions, that relate to healthcare availability, methods of delivery or payment for products and services, or sales, marketing or pricing, may limit our potential revenue, and we may need to revise our research and development programs.

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If we obtain approval to commercialize our clinical product candidates outside of the United States, a variety of risks associated with international operations could harm our business.

If our clinical product candidate is approved for commercialization, we intend to enter into agreements with third parties to market them in certain jurisdictions outside the United States.

If our lead clinical product candidate is approved for commercialization, we intend to enter into agreements with third parties to market them in certain jurisdictions outside the United States.

We expect that we will be subject to additional risks related to international operations or entering into international business relationships, including:

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In addition, because of the increasing costs of insurance coverage, we may not be able to maintain insurance coverage at a reasonable cost or obtain insurance coverage that will be adequate to satisfy liabilities that may arise.

We and our subsidiaries are subject to U.S.

and foreign tax laws, and changes to such tax laws or differing interpretation of those laws by the relevant governmental authorities could adversely affect our business and operating results.

Congress, the Organization for Economic Co-operation and Development and other government agencies in jurisdictions where we do business have had an extended focus on issues related to the taxation of multinational corporations.

One example is in the

area of “base erosion and profit shifting,” where payments are made between affiliates from a jurisdiction with high tax rates to a jurisdiction with lower tax rates.

Additionally, changes proposed by the current U.S.

administration, including significant tax reform, could significantly change the U.S.

federal income tax rules and regulations applicable to us and our subsidiaries, although the prospect of tax reform, and the nature of any such reform, remains highly uncertain.

Thus, the tax laws in the United States, Spain and other countries in which we and our subsidiaries do business could change on a prospective or retroactive basis, and any such changes could adversely affect us.

In addition, the tax laws and regulations in the United States, the EU and the various other jurisdictions in which we and our subsidiaries operate or may in the future operate are inherently complex, and we and our subsidiaries will be obligated to make judgments and interpretations about the application of these laws and regulations to us and our subsidiaries and our and their operations and businesses.

The interpretation and application of these laws and regulations could be challenged by the relevant governmental authorities, which could result in material administrative or judicial procedures, actions or sanctions.

INTELLECTUAL PROPERTY RISKS

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We, or our licensors, may also need to participate in interference proceedings involving our issued patents and pending applications of another entity.

The European Patent Office and some national patent authorities have formal patent opposition processes where the validity of issued patents may be challenged.

The European Patent Office and some national patent authorities have formal patent opposition processes where the

validity of issued patents may be challenged.

If a patent opposition is filed, we, or our licensors, may also need to participate in opposition proceedings involving our issued patents.

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The NYSE American Company Guide also states that the NYSE normally will not consider removing from listing securities of an issuer if it is in compliance with all of the following:

a total value of market capitalization of at least $50.0 million;

a total value of market

capitalization of at least $50.0 million;

1,100,000 publicly-held shares;

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In addition, the NYSE American has informed us that it can commence delisting proceedings and immediately suspend trading in the event that our Common Stock trades at levels viewed to be abnormally low and no longer suitable for listing pursuant to Section 1003(f)(v) of the NYSE American Company Guide.

Generally the NYSE American views trading at or below a price of $0.10 to be abnormally low.

Currently, the NYSE American views trading at or below a price of $0.10 to be abnormally low.

New reverse stock split rules implemented by the NYSE American in January 2025 limit the circumstances under which reverse stock splits can be used in order to cure low trading price deficiencies, including the immediate suspension and delisting of any company that has effected one or more reverse stock splits over the prior two year period with a cumulative ratio of 200 shares or more to one.

Based on these rules, due to the reverse stock split effected in August 2024, we would be limited in effecting a reverse stock split to cure a low price deficiency.

As stated above, in the event that we were to fail to meet the requirements of NYSE American per share price requirement the NYSE American could commence delisting proceedings and immediately suspend trading of our Common Stock o the NYSE American or if we fail to meet other requirements such as the stockholders’ equity requirement and we could not timely cure such deficiency, our listing could become subject to NYSE American continued listing evaluation and follow-up procedures, which could result in delisting procedures.

As stated above, in the event that we were to fail to meet the requirements of NYSE American per share price requirement the NYSE American could commence delisting proceedings and immediately suspend trading of our Common Stock on the NYSE American or if we fail to meet other requirements such as the stockholders’ equity requirement and we could not timely cure such deficiency, our listing could become subject to NYSE American continued listing evaluation and follow-up procedures, which could result in delisting procedures.

We previously received notification from the NYSE American citing failure to comply with the minimum stockholders’ equity continued listing standard as set forth in Part 10, Section 1003 of the Company Guide.

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The market price of our Common Stock has been and may continue to be volatile and adversely affected by various factors.

Our stock price has fluctuated in the past, has recently been volatile and may be volatile in the future.

By way of example, on March 19, 2024, the price of our common stock closed at $11.00 per share while on March 20, 2024, our stock price closed at $15.50 per share with no discernable announcements or developments by the company or third parties.

Our stock price has fluctuated in the past, has been volatile and may be volatile in the future.

We may incur rapid and substantial decreases in our stock price in the foreseeable future that are unrelated to our operating performance or prospects.

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● general economic, industry and market conditions;

● other events or factors, including those resulting from such events, or the prospect of such events, including war, terrorism and other international conflicts, which restrict a wide range of trade and financial dealings, public health issues including health epidemics or pandemics, such as the outbreak of the novel coronavirus (COVID-19), and natural disasters such as fire, hurricanes, earthquakes, tornados or other adverse weather and climate conditions, whether occurring in the United States or elsewhere, could disrupt our operations, disrupt the operations of our suppliers or result in political or economic instability.

● other events or factors, including those resulting from such events, or the prospect of such events, including war, terrorism and other international conflicts, which restrict a wide range of trade and financial dealings, public health issues including health epidemics or pandemics, and natural disasters such as fire, hurricanes, earthquakes, tornados or other adverse weather and climate conditions, whether occurring in the United States or elsewhere, could disrupt our operations, disrupt the operations of our suppliers or result in political or economic instability.

These broad market and industry factors may seriously harm the market price of our Common Stock, regardless of our operating performance.

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While we have no reason to believe our shares would be the target of a short squeeze, there can be no assurance that we won’t be in the future, and you may lose a significant portion or all of your investment if you purchase our shares at a rate that is significantly disconnected from our underlying value.

Our articles of incorporation and bylaws and Nevada law may have anti-takeover effects that could discourage, delay or prevent a change in control, which may cause our stock price to decline.

Our articles of incorporation, as amended, our second amended and restated bylaws and Nevada law could make it more difficult for a third party to acquire us, even if closing such a transaction would be beneficial to our stockholders.

Our Charter and bylaws and Nevada law may have anti-takeover effects that could discourage, delay or prevent a change in control, which may cause our stock price to decline.

Our Charter, our second amended and restated bylaws and Nevada law could make it more difficult for a third party to acquire us, even if closing such a transaction would be beneficial to our stockholders.

The Board of Directors could authorize the issuance of an additional series of preferred stock that would grant holders preferred rights to our assets upon liquidation, special voting rights, the right to receive dividends before dividends would be declared to common stockholders, and the right to the redemption of such shares, possibly together with a premium, prior to the redemption of the Common Stock.

To the extent that we do issue additional preferred stock, the rights of holders of Common Stock could be impaired thereby, including without limitation, with respect to liquidation.

Provisions of our articles of incorporation, as amended, and our second amended and restated bylaws may also prevent or frustrate attempts by our stockholders to replace or remove our management.

In particular, our articles of incorporation, as amended, and second amended and restated bylaws, among other things:

Provisions of our Charter, and our second amended and restated bylaws may also prevent or frustrate attempts by our stockholders to replace or remove our management.

In particular, our Charter, and second amended and restated bylaws, among other things:

● provide the board of directors with the ability to alter the bylaws without stockholder approval;

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Resales of our Common Stock in the public market by our stockholders may cause the market price of our common stock to fall.

We may issue common stock from time to time in connection with future offerings.

We may issue shares of Common Stock or securities convertible into or exercisable for shares of Common Stock from time to time in connection with future offerings.

Any issuance from time to time of new shares of our Common Stock, or our ability to issue shares of Common Stock in future offerings, could result in resales of our Common Stock by our current stockholders concerned about the potential dilution of their holdings.

In turn, these resales could have the effect of depressing the market price for our Common Stock.

The shares of common stock offered under our current Amended and Restated At The Market Issuance Sales Agreement may be sold in “at the market” offerings, and investors who buy shares at different times will likely pay different prices.

Investors who purchase shares that are sold under our current Amended and Restated At The Market Issuance Sales Agreement at different times will likely pay different prices, and so may experience different outcomes in their investment results.

The shares of Common Stock offered under our current ATM Sales Agreement may be sold in “at the market” offerings, and investors who buy shares at different times will likely pay different prices.

Investors who purchase shares that are sold under our current ATM Sales Agreement at different times will likely pay different prices, and so may experience different outcomes in their investment results.

We will have discretion, subject to market demand, to vary the timing, prices, and numbers of shares sold, and there is no minimum or maximum sales price.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1A. Risk Factors