NASDAQ: ONCY

Business Strategy

Our business strategy is to develop and seek regulatory approval to market pelareorep in an effective and timely manner, seek partnerships or transactions that allow for faster and more efficient development of pelareorep than we might be able to accomplish on our own, and access additional technologies at a time and in a manner that we believe is best for our development. We intend to achieve our business strategy by focusing on these key areas:

•Continue to assess the safety and efficacy of pelareorep in human subjects through our clinical development program;

•Maintain existing and establish new collaborations with partners and other experts to assist us with scientific and clinical developments of this new potential pharmaceutical product;

•Implement strategic alliances with select biopharmaceutical companies and laboratories, at a time and in a manner whereby such alliances may complement and expand our own research and development efforts. Such alliances may also result in an eventual expansion to include providing additive sales and marketing capabilities;

•Use our broadening patent base and collaborator network as a mechanism to meet our strategic objectives; and

•Develop relationships with companies that could be instrumental in assisting us to access other innovative therapeutics.

As our clinical development program advances, we anticipate pelareorep's ability to enhance innate and adaptive immune responses within the TME will play an increasingly important role. This greatly increases opportunities for expanding our clinical program, business development, and partnering opportunities to address gastrointestinal cancers in combination with various therapies. We believe this approach has the most promise for generating clinically impactful data and offers the most expeditious path to regulatory approval.

Our primary focus is to position pelareorep as a platform immunotherapy for the treatment of gastrointestinal (“GI”) cancers and advance our GI programs to registration-enabled clinical studies. We are exploring opportunities for registrational programs

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and investigator-sponsored trials in metastatic colorectal cancer, second-line or later anal cancer, and metastatic pancreatic cancer.

Our business strategy is based on attaining a number of commercial objectives, which, in turn, are supported by a number of product development goals. In the context of this Annual Report, statements of our “belief” are based primarily upon our results derived to date from our research and development program in animals, early-stage human trials, and our most recent data from mid-stage clinical trials, upon which we believe that we have a reasonable scientific basis to expect the particular results to occur. It is not possible to predict, based upon studies in animals, or early to mid-stage human trials, whether a new therapeutic will ultimately prove to be safe and effective in humans. There are no assurances that the particular result we expect will occur.

We are pursuing a strategy of establishing relationships with larger companies as strategic partners. It is anticipated that future clinical development into large international or pivotal trials would generally occur in conjunction with a strategic partner or partners, who would contribute expertise and financial assistance. In exchange for certain product rights and commitments to market our product, the strategic partners would be expected to share in proceeds from the sale of our product.

Scientific Background and Summary of Research and Development Highlights

Pelareorep’s anti-tumor activity is based on three complementary modes of action:

•Selective viral replication in permissive cancer cells, such as those with RAS mutations, that lead to tumor cell lysis.

•Modification of the tumor microenvironment by upregulating chemokine/cytokine expression, which makes the tumor more visible to the immune system and stimulates innate immunity that can directly target the tumor.

•Induction of adaptive immune responses, including the expansion of anti-viral and anti-tumor-infiltrating lymphocyte populations that can attack tumors by targeting tumor- and virus-specific antigens.

Preclinical and translational research to date indicates the following:

•Pelareorep has anticancer effects in a variety of animal models demonstrating that it can reduce tumor burden and prolong survival in these models.

•The anticancer effects in animal models can be enhanced when pelareorep is given in combination with chemotherapy, immunotherapy (including PD-1 and PD-L1 inhibitors), radiotherapy, and other targeted cancer therapies, highlighting the ability of pelareorep to enhance the anticancer effects of a broad range of cancer therapeutics.

•A toxic dose of pelareorep has not been reached/established in animal models and doses as high as 9.0 x 1010 TCID50 have been well-tolerated in humans. Treatment with pelareorep causes manageable side-effects.

Clinical data to date indicate the following:

•More than 1,600 patients have received at least one dose of study treatment in clinical studies with pelareorep. Of these, more than 1,200 patients received pelareorep, including over 600 patients in Oncolytics-sponsored trials, and over 500 in investigator-sponsored trials.

•Pelareorep has been administered as single or multiple doses (intratumoral or intravenous), either as a monotherapy or in combination with chemotherapy, immunotherapy (e.g., checkpoint inhibitors), and/or radiotherapy.

•Pelareorep is generally well-tolerated and has a manageable side effect profile.

•When combined with chemotherapy or immunotherapy, pelareorep does not appear to enhance either the frequency or severity of the adverse effects of these agents.

•Efficacy results from clinical studies show that treatment with pelareorep can improve the outcome of cancer patients with a variety of different tumors:

•In the GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with peLarEorep and anTi-PD-L1) platform study, the objective response rate (“ORR”) and disease control rate (“DCR”) were 62% and 85%, respectively, in evaluable first-line advanced/metastatic unresectable pancreatic ductal adenocarcinoma (“PDAC”) patients treated with the combination of pelareorep, atezolizumab, and gemcitabine/nab-paclitaxel. The observed ORR is substantially higher than the typical ORR of approximately 25% reported in historical trials of gemcitabine and nab-paclitaxel in metastatic pancreatic cancer. In a single-arm study of gemcitabine plus pelareorep, known as REO 017, first-line patients with metastatic PDAC, had a median OS of 10.2 months with 1-year and 2-year survival rates of 45% and 24%, respectively. These results were encouraging when compared to an average median OS of less than 7 months, and 1-year and 2-year survival rates of approximately 22% and 6%, respectively, for metastatic PDAC patients treated with gemcitabine alone in benchmark studies.

•In a two-arm Phase 2 study (NCI 8601), patients with metastatic PDAC were randomized to receive either carboplatin, paclitaxel and pelareorep (test arm) or carboplatin and paclitaxel alone (control arm). The ORR,

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median progression-free survival (“PFS”) and median overall survival (“OS”) were similar between the test and control arms. However, the overall survival rate at 2 years was higher in the pelareorep-containing arm (20% vs. 9%) suggesting a possible survival benefit associated with the addition of pelareorep to chemotherapy.

•Interim clinical results from the second-line or later squamous cell carcinoma of the anal canal (“SCAC”) cohort of the GOBLET study showed an ORR of 30% from 20 evaluable patients receiving pelareorep and atezolizumab compared to 13.8% for the current approved treatment in the same indication. Additionally, two durable complete responses were recorded, with one ongoing beyond two years, and another lasting 15 months. The median duration of response is 15.5 months for pelareorep-atezolizumab patients compared to 9.5 months for the standard-of-care.

•Interim clinical results from the third-line subset of the SCAC cohort of the GOBLET study showed four of 14 evaluable third-line patients receiving pelareorep and atezolizumab achieved objective responses, resulting in an ORR of approximately 29%. These responses included two complete responses and two partial responses. The median duration of response (“DOR”) is approximately 17 months (67 weeks), indicating both depth and durability of clinical benefit in a heavily pretreated population. In historical third-line SCAC studies, objective response rates are typically approximately 10% or less, with limited durability.

•A study of pelareorep in colorectal cancer showed ORR, PFS, and OS results that exceeded historical control data by a multiple of two to three times. Second-line KRAS (Kristen rat sarcoma)-mutant, microsatellite-stable (“MSS”) metastatic colorectal cancer (“mCRC”) patients from the REO 022 trial receiving pelareorep, bevacizumab (Avastin®), and fluorouracil, leucovorin, irinotecan (“FOLFIRI”) recorded an ORR of 33%, PFS of 16.6 months, and OS of 27 months, compared to approximately 10%, 5.7 months, and 11.2 months, respectively, from historical studies.

•In the randomized Phase 2 IND.213 study, 74 mBC patients were treated with pelareorep plus paclitaxel (“PTX”) versus PTX alone (standard of care control chemotherapy). The patients treated with PTX + pelareorep demonstrated a statistically significant improvement in median overall survival (“OS”) compared to those treated with PTX alone: 17.4 months versus 10.4 months, respectively (HR = 0.65; 80% CI 0.46–0.91; p=0.1). In a post hoc subgroup analysis of patients with HR+/HER2- disease, the median OS benefit from the addition of pelareorep to PTX was even greater compared to PTX alone: 21.0 months versus 10.8 months, respectively (HR = 0.60; p=0.1).

•In the subsequent Phase 2 BRACELET-1 study, 45 patients with HR+/HER2- mBC were randomized to receive one of three treatments: PTX alone, PTX + pelareorep, or PTX + pelareorep + avelumab, a licensed anti-PD-L1 antibody. An additional 3 patients received PTX + pelareorep + avelumab as a safety run-in cohort for a total of 48 patients enrolled. Final efficacy results from the BRACELET-1 study demonstrated that the median OS in the PTX alone control arm was 18.2 months. However, the median OS could not be calculated in the PTX + pelareorep arm due to the number of patients still alive at the time of the analysis. A conservative estimate of median OS for the PTX + pelareorep arm is 32.1 months, indicating that PTX + pelareorep delivered a greater than 12-month survival advantage compared to PTX alone. This survival benefit is further illustrated by the 24-month overall survival rate, which showed that 64% of patients treated with PTX + pelareorep survived at least 2 years compared to 33% of patients treated with PTX alone. In addition, the final median progression free survival (“PFS”) was 12.1 months for PTX + pelareorep compared to 6.4 months for PTX alone, a benefit of 5.7 months. These results substantiated the statistically significant near doubling of median OS observed in the earlier randomized IND-213 study in HR+/HER2- patients treated with PTX + pelareorep compared to PTX alone.

•In the AWARE-1 window-of-opportunity study, most HR+/HER2- early breast cancer patients treated with pelareorep showed an increase in CeLTIL score, a measure of tumor cellularity and tumor infiltrating lymphocytes that is associated with a better prognosis in breast cancer. Importantly, the addition of the immune checkpoint inhibitor atezolizumab to pelareorep increased both the magnitude of the increase in CeLTIL score and the proportion of patients with a positive CelTIL score thereby achieving the study’s primary endpoint. Biomarker data from AWARE-1 further demonstrated that pelareorep treatment modified the TME to make it more visible to the immune system, generated and expanded tumor infiltrating lymphocyte clones in the blood, upregulated PD-L1 expression, and promoted CD8+ T cell infiltration into tumors. Some of these effects were even more prominent when pelareorep was combined with atezolizumab demonstrating synergy between the two agents.

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Mechanism of Action

Figure 1. Proposed mechanism of action for pelareorep

Pelareorep is an intravenously delivered unmodified oncolytic reovirus that selectively infects cancer cells via mutations such as RAS and other and is being developed as an immunotherapy for multiple cancers. Translational data supports the ability of pelareorep to provide benefit to certain cancer patients after failure of CPI therapy.

Upon infection, significant increases in anti-viral and immune gene expression converts the tumor microenvironment from an immunologically silent “cold” tumor to an immunologically responsive “hot” tumor. This conversion is due to the accumulation of reovirus-produced dsRNA which activates toll-like receptor 3 (“TLR3”). Gene expression analysis of tumor biopsies at day 3 post-treatment have shown a significant activation of DDX58/RIG-I (retinoic acid-inducible gene I), a cytosolic pattern recognition receptor (“PRR”) that recognizes short dsRNA in the cytosol. RIG-I can mediate the induction of a type-1 interferon response and is an essential molecule in the innate immune system for recognizing cells that have been infected with a virus. Consistent with this observation, increases in the expression type-1 interferon genes are also observed. These include IRF7, a member of the interferon regulatory transcription factor (“IRF”) family that regulates many interferon-alpha genes. Increases in IRF1/STAT1, a key growth inhibitory and tumor suppressive signaling pathway that prevents cancer formation by maintaining growth control and can activate genes that produce type-I interferons, are observed. IRF1 is also essential for the development and activation of immune cells, such as T cells and natural killer cells. Increases in the expression of PD-L1, a CPI target molecule, and the inflammatory chemokines CXCL10 and CXCL11, which are important for T cell trafficking and migration to the TME and predominantly induced by IFN-gamma, have been observed across all post-treatment tumor types. Another consequence of the activation of TLR3 by pelareorep is the production of CXCL13, a chemokine critical for the formation of tertiary lymphoid structures (“TLS”). TLS formation in breast cancer tumors have been detected by imaging mass cytometry of tumor biopsies following pelareorep treatment. Numerous reports have identified TLS as a biomarker that is superior to PD-L1/PD-1 expression in its ability to predict responsiveness to CPIs. Taken together, these data demonstrate pelareorep’s ability to positively alter the TME to increase responsiveness to immune based therapy.

Evidence of pelareorep’s ability to activate anti-viral and anti-tumor specific immune responses comes from the analysis pre- and post-treatment peripheral blood mononuclear cells (“PBMCs”). Increases in anti-viral cytotoxic T cells have been confirmed by ELISPOT analysis of serial blood samples from a cohort of pelareorep-treated pancreatic cancer patients. In addition, the expansion of TIL clones in the blood has been observed and appears to correlate with reductions in tumor volume. Further analyses of TCR sequences for antigen specificity have confirmed the expansion of mKRAS clones in samples from patients treated with pelareorep, supporting the ability of pelareorep to induce anti-tumor specific T cell responses.

Patents and Trade Secrets

We rely on our patent portfolio to protect the development of pelareorep. At December 31, 2025, we had 137 patents, including 11 U.S. and 7 Canadian patents, and issuances in other jurisdictions. We have an extensive patent portfolio covering pelareorep and formulations that we use in our clinical trial program. We also have patents covering methods for manufacturing pelareorep and screening for susceptibility to pelareorep. These patent rights extend to at least the end of 2031. We are continuing to

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analyze additional patent protections and have placed an emphasis on patent extension strategy. In addition, we have submitted new patent applications that we expect to extend certain patent protections and grant new rights into the 2040’s.

We are not currently aware of competing intellectual property relating to our pelareorep project. While we believe that we have the necessary freedom to operate in these areas, there can be no assurance that others will not challenge our position in the future. Litigation to defend our position could be costly and time-consuming and we cannot be certain we will be successful.

We also rely on unpatented trade secrets and improvements, unpatented know-how, and continuing technological innovation to develop and maintain our competitive position. No assurance can be given that others will not independently develop substantially equivalent proprietary information and techniques or otherwise gain access to our trade secrets or disclose such technology, or that we can meaningfully protect our rights to our unpatented trade secrets.

We require our employees and consultants to execute confidentiality agreements upon the commencement of employment and consulting relationships with us. These agreements provide that all confidential information developed by or made known to an individual during the course of their employment or consulting relationship generally must be kept confidential. In the case of employees, the agreements provide that all inventions conceived by the individual, while employed by us, relating to our business are our exclusive property. While we have implemented reasonable business processes and agreements with which to protect confidential information, these actions may not provide meaningful protection for our trade secrets in the event of unauthorized use or disclosure of such information.

Regulatory Requirements

The development of new pharmaceuticals is strongly influenced by a country's regulatory environment. The primary regulatory body in the U.S. is the FDA and in Europe is the European Medicines Agency (the “EMA”). Similar processes are conducted in specific countries by equivalent regulatory bodies. Regulations in each jurisdiction require the licensing of manufacturing facilities and mandate strict research and product testing standards. Companies must establish the safety and efficacy of their products, comply with current good manufacturing practice (“cGMP”) and potentially submit marketing materials before being allowed to market pharmaceutical products. While we plan to pursue or support the pursuit of the approval of our product, success in acquiring regulatory approval for any product is not assured.

In order to market our pharmaceutical product in the U.S., Europe, and other jurisdictions, we must successfully meet the requirements of those jurisdictions. The requirements of the appropriate regulatory authority will generally include the following stages as part of the regulatory process:

•completion of certain preclinical laboratory tests, animal studies and formulation studies, in accordance with Good Laboratory Practice regulations and other applicable requirements;

•submission to the FDA of an investigational new drug application (“IND”), or of a comparable submission to foreign regulatory authorities which must become effective or be approved before human clinical trials may begin;

•approval by an independent institutional review board, or ethics committee at each clinical site before each trial may be initiated;

•performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practice (“GCP”), requirements to establish the safety, purity and potency and/or efficacy of the proposed biologic for its intended use;

•preparation and submission to the FDA of a biologics license application (“BLA”), or comparable application in other jurisdictions;

•satisfactory completion of an FDA advisory committee review, if applicable;

•a determination by the FDA within 60 days of its receipt of a BLA to file the application for review, or decision by the EMA to validate the application;

•satisfactory completion of inspections of the manufacturing facility or facilities at which the biological product is produced to assess compliance with current cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity, and potential inspection of selected clinical investigation sites and/or the trial sponsor to assess compliance with GCP; and

•FDA review and approval of the BLA, to permit commercial marketing of the product for particular indications for use in the United States, or similar review and approval of a marketing application to permit marketing of the product in the relevant non-U.S. jurisdiction.

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Clinical Trials

Once a pharmaceutical candidate is identified for development, it enters the preclinical testing stage. Preclinical tests include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies, in an effort to support subsequent clinical testing. The conduct of preclinical studies is subject to regulations and requirements, including GLP regulations for certain studies. In addition, prior to beginning the first clinical trial with a product candidate in the United States, the trial sponsor must submit an IND to the FDA. An IND is a request for allowance from the FDA to introduce an investigational drug into interstate commerce and administer the product to humans, and must become effective before human trials may begin.

Clinical trials involve the administration of the investigational drug product to human subjects under the supervision of one or more qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with GCP regulations. Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

•Phase 1: The product candidate is initially introduced into healthy human volunteers or patients with the target disease or condition. These studies are designed to test for safety, dosage tolerance, absorption, metabolism, distribution and excretion and, if possible, to gain an early indication of its effectiveness.

•Phase 2: The product candidate is administered to a limited patient population with a specified disease or condition to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and appropriate dosage. Multiple Phase 2 trials may be conducted to obtain information prior to beginning larger and more expensive Phase 3 trials.

•Phase 3: The product candidate is administered to an expanded patient population to further evaluate dosage, to provide substantial evidence of clinical efficacy, and to further test for safety in an expanded patient population, generally at geographically dispersed clinical study sites. These clinical trials are intended to establish the overall risk-benefit ratio of the product candidate and provide, if appropriate, an adequate basis for product labeling.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and biological characteristics of the product and finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, the manufacturer must develop methods for testing the identity, strength, quality and purity of the final drug. In addition, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

Marketing Approvals

The results of the preclinical and clinical testing, together with manufacturing and controls information, are submitted to regulatory agencies in order to obtain approval to commence commercial sales. In responding to such an application, regulatory agencies may grant marketing approval, request additional information or further research, or deny the application if they determine that the application does not satisfy their regulatory approval criteria. For example, in the United States, regulatory approval requires submission and approval by the FDA of a BLA. FDA reviews a BLA to determine, among other things, whether a product candidate is safe, pure and potent and the facility in which it is manufactured, processed, packed or held meets standards designed to assure the product’s continued safety, purity and potency. Before approving a BLA, the FDA will inspect the facility or facilities where the product is manufactured. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving a BLA, the FDA may inspect one or more clinical trial sites as well as the trial sponsor to assure compliance with GCP requirements. After the FDA evaluates a BLA and conducts any required inspections, it will issue an approval letter or a Complete Response Letter (“CRL”). An approval letter authorizes commercial marketing of the biologic with prescribing information for specific indications. A CRL indicates that the review cycle of the application is complete and the application will not be approved in its present form. If a CRL is issued, the sponsor must resubmit the BLA, addressing all of the deficiencies identified in the letter, or withdraw the application. Even if such data and information are submitted, the FDA may decide that the BLA does not satisfy the criteria for approval.

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FDA Expedited Development and Review Programs

In the United States, a sponsor may seek approval of its product candidate under programs designed to expedite FDA’s review and approval of biological products that meet certain criteria. For example, product candidates are eligible for Fast Track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition. A product candidate can also receive Breakthrough Therapy designation if preliminary clinical evidence indicates that the product candidate, alone or in combination with one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. In addition, a BLA is eligible for priority review if the underlying product candidate is designed to treat a serious condition and, if approved, would provide a significant improvement in safety or effectiveness compared to available therapy. Also, depending on the design of the applicable clinical trials, product candidates studied for their safety and effectiveness in treating serious or life-threatening diseases or conditions may receive accelerated approval upon a determination that the product candidate has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

These programs do not change the standards for approval but may expedite the development or approval process. Even if a product candidate qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

Post-Marketing Regulations

Once approved, pharmaceutical products are subject to pervasive and continuing regulation by the FDA and comparable foreign regulatory authorities, including, among other things, requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product. After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior regulatory review and approval. Regulatory agencies may withdraw a product approval if compliance with pre- and/or post-marketing regulatory standards is not maintained or if problems occur after the product reaches the marketplace. In addition, they may require post-marketing studies, sometimes referred to as Phase 4 studies, to monitor the effect of an approved product, and may limit further marketing of the product based on the results of these post-market studies. The FDA and other foreign regulatory agencies have broad post-market regulatory and enforcement powers, including the ability to levy fines and penalties, suspend or delay issuance of approvals, seize or recall products, or withdraw approvals.

Manufacturing Regulations

Biologic manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP, which impose certain procedural and documentation requirements. Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting requirements upon application holders and any third-party manufacturers that they may decide to use. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance. We are economically dependent on our toll manufacturers. We primarily use one toll manufacturer in the U.S. to produce the clinical grade pelareorep active ingredient and to formulate finished product required for our clinical trial program. Any significant disruption of the services provided by our primary toll manufacturers has the potential to delay the progress of our clinical trial program. We have attempted to mitigate this risk by identifying an alternative toll manufacturer, establishing stability profiles for long-term storage of pelareorep, and producing sufficient pelareorep in advance of patient enrollment in a particular clinical trial.

Manufacturers of biologics also must comply with general biological product standards. Failure to comply with the statutory and regulatory requirements subjects the manufacturer to possible legal or regulatory action, such as suspension of manufacturing, seizure of product, or mandatory or voluntary recall of a product. Adverse experiences with the product must be reported to the FDA and foreign agencies and could result in the imposition of market restrictions through labeling changes or in product removal. Product approvals may be withdrawn if compliance with regulatory requirements is not maintained or if problems concerning safety or efficacy of the product occur following approval.

Advertising and Promotion Regulations

With respect to both pre- and post-market product advertising and promotion, the FDA and similar foreign agencies impose a number of complex regulations on entities that advertise and promote pharmaceuticals and biologics, which include, among

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other things, standards and regulations relating to direct-to-consumer advertising, on versus off-label promotion, industry-sponsored scientific and educational activities, and promotional activities involving the internet. These agencies have very broad enforcement authority and failure to abide by these regulations can result in penalties including the issuance of a warning letter directing the entity to correct deviations from requisite standards, a requirement that future advertising and promotional materials be pre-cleared by the FDA or relevant foreign agencies. Foreign, state, and federal civil and criminal investigations, fines, and prosecutions are also possible if advertising and promotion regulations are breached.

Other Government Regulations

We are subject to various laws and regulations regarding laboratory practices, the experimental use of animals, and the use and disposal of hazardous or potentially hazardous substances in connection with our research. In each of these areas, as above, the government has broad regulatory and enforcement powers, including the ability to levy fines and civil penalties, suspend or delay issuance of approvals, seize or recall products, and withdraw approvals, any one or more of which could have a material adverse effect upon us.

Market and Competition

According to estimates for 2026 from the American Cancer Society, more than 2.1 million Americans are expected to be diagnosed with cancer in the year, and approximately 626,140 Americans are expected to die of cancer. In the U.S., the relative lifetime risk of developing cancer, for both males and females, is approximately 1 in 3. The costs of this disease state are also significant. In the U.S., the National Cancer Institute estimated that the 2020 cancer-related medical costs were $208.9 billion.1

While pelareorep has not been approved yet by the FDA, we believe there is significant addressable market opportunity within pelareorep’s targeted indications. GI cancer is the fastest growing cancer in the world in people under 50 years old.2

According to estimates from the World Cancer Research Fund (“WCRF”), colorectal cancer (“CRC”) is the third most common cancer worldwide, and there were more than 1.9 million new cases in 2022. Globally, the WCRF estimates there were more than 900,000 deaths attributable to CRC in 2022.3 Market.us Media indicates an addressable market of nearly $20 billion by 2033 from $13 billion in 2024, representing a CAGR of 4.7% during the forecast period from 2025 to 2033.4

We believe the RAS-mutant patient population has a high unmet medical need. Specifically, KRAS-mutant MSS mCRC represents one of the most challenging diseases in GI oncology, as few effective treatment options exist following first-line progression, and available immune-based therapies provide little benefit. The 5-year relative survival rate for mCRC is 15%.5

According to the International Agency for Research on Cancer (“IARC”), there are more than 54,000 global patients with anal cancer in 20226. Market Research Future analysis indicates that the anal cancer market was estimated at over $1 billion in 2025 and it is projected to grow to $2.3 billion by 2035, representing a CAGR of 7.7% during the forecast period from 2025 to 2035.7 At present, there are few available treatment options for unresectable SCAC in the second-line and greater progression, which we believe creates an opportunity to grow this market exponentially in the event we create a new treatment for this patient population.

According to estimates from the WCRF there were more than 510,000 new cases of pancreatic cancer globally in 2022.8 Fortune Business Insights indicates an addressable market of $14.4 billion by 2034 from $3.8 billion in 2025, representing a CAGR of nearly 16% during the forecast period from 2025 to 2034.9 Pancreatic cancer is one of the leading causes of cancer death globally. According to estimates for 2026 from the American Cancer Society, the 5-year relative survival rate for metastatic pancreatic cancer is 3%.10

The biotechnology industry emphasizes the importance of proprietary rights and is typically defined by fast-paced advancements in technologies with intense competition. We do business in an extremely competitive oncology market and face significant competition from many sources, including pharmaceutical, biopharmaceutical, and biotechnology companies as well

1 American Cancer Society’s Cancer Facts and Figures 2026

2 https://jamanetwork.com/journals/jama/article-abstract/2836671#google_vignette (accessed February 12, 2026)

3 https://www.wcrf.org/preventing-cancer/cancer-statistics/colorectal-cancer-statistics/ (accessed February 12, 2026)

4 https://media.market.us/colorectal-cancer-therapeutics-market-news/ (accessed February 12, 2026)

5 https://www.cancer.org/cancer/types/colon-rectal-cancer/detection-diagnosis-staging/survival-rates.html (accessed February 12, 2026)

6 https://gco.iarc.who.int/media/globocan/factsheets/cancers/10-anus-fact-sheet.pdf (accessed February 12, 2026)

7 https://www.marketresearchfuture.com/reports/anal-cancer-market-1530 (accessed February 12, 2026)

8 https://www.wcrf.org/preventing-cancer/cancer-statistics/pancreatic-cancer-statistics/ (accessed February 12, 2026)

9 https://www.fortunebusinessinsights.com/pancreatic-cancer-treatment-market-101989 (accessed February 12, 2026)

10 https://www.cancer.org/cancer/types/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html (accessed February 12, 2026)

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as universities and private and public research institutions. Many of our competitors have significantly greater financial, manufacturing, marketing, and drug development resources than we do. Large biopharmaceutical companies in particular have extensive experience in clinical development and in obtaining regulatory approvals for drugs and biologicals. These companies also have significantly greater research capabilities than we do. Smaller or early-stage companies may also prove to be significant competitors, particularly those with collaborative arrangements with large and established companies or universities and research institutions.

Our competitors fall primarily into the following groups of treatment:

•traditional cancer therapies, including chemotherapy, surgery, radiation therapy, and targeted therapies;

•approved immunotherapy antibodies and immunotherapy antibodies in clinical trials;

•other approved oncolytic virus-based immunotherapies and those in clinical trials;

•cancer vaccines including personalized vaccines and those targeting tumor neo-antigens; and

•cell-based therapies, such as CAR-T, T cell receptor-based, and NK cell therapies.

Our business opportunity will be limited, or possibly eliminated if our competitors develop and commercialize products in our selected indications that are safer, more effective, have fewer side effects, or are less expensive alone or in combination with other therapies than pelareorep especially if these get to market sooner than our product. Our competitors also compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and patient enrollment for clinical trials, as well as in acquiring technologies and technology licenses complementary to our programs or advantageous to our business.

Pelareorep, if and when sold, will compete with a number of drugs that are currently marketed or in development that also target cancer but utilize different mechanisms of action. To compete effectively with these agents, pelareorep will need to show improved clinical efficacy and/or safety compared to competing products. We believe that pelareorep, if and when ultimately marketed, will likely be used in combination with other existing cancer treatments like checkpoint inhibitors, surgery, chemotherapy, radiation therapy and other biological therapies. Consequently, we believe pelareorep, if and when marketed, would largely complement rather than compete directly with these existing treatment options.

We do, however, expect to face direct and increasing competition from a number of companies that are also seeking to develop cancer therapies based on oncolytic viruses and other ways to prime the immune system. We believe that our ability to successfully compete will depend, among other things, on our ability to:

•effectively advance the development of pelareorep;

•design, enroll patients in and successfully complete appropriate clinical trials in an efficient manner;

•gain regulatory approval for pelareorep;

•establish collaborations and partnerships for the development of pelareorep;

•commercialize successfully, including demonstrating the safety and efficacy of pelareorep over currently approved therapies to physicians, insurers, and third-party payors;

•secure sufficient coverage from insurers and other payors;

•secure, maintain, and protect intellectual property rights based on our innovations; and

•manufacture and sell commercial quantities of pelareorep to the market.

Product Marketing Strategy

The markets for the cancer product being developed by us may be large and could require substantial sales and marketing capability. Before or upon successful completion of the development of a cancer product, we intend to enter into one or more strategic partnerships or other collaborative arrangements with a pharmaceutical company or other company with marketing and distribution expertise to address this need. If necessary, we will establish arrangements with various partners for different geographical areas or specific applications at various times in the development process. Our management and consultants have relevant experience with the partnering process of oncology products.

Raw Materials

We believe that sources of raw material pertinent for manufacturing our pelareorep product are generally available.

Corporate Social Responsibility and ESG

As a rapidly growing, clinical-stage biotech company, we are not yet in a position to implement a broad-based ESG policy and program. However, our corporate goals are inspired by our potential to impact the care of patients with cancer, especially those

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with late-stage breast and pancreatic cancers and are informed by our corporate values of acting with integrity, collaboration, innovation, and embracing diversity. In 2025, our corporate goals focused on certain clinical, manufacturing, and business operations and support our desire to obtain an approval for an innovative cancer treatment that extends patient lives. Each year we work hard to achieve our goals and objectives while maintaining a respectful, collaborative, and caring work environment. While we do not formally report on our ESG policies and compliance, we publicly disclose elements of our ESG activities. Our governance policies, including our board of director (“Board”) mandates, code of ethics and conduct, and our public filings are all on our website at https://oncolyticsbiotech.com/investor-overview/corporate-governance/. Our website is not incorporated herein by reference.

Employees

As of December 31, 2025, we had 29 total and full-time employees. We have never had a work stoppage, and none of our employees are covered by collective bargaining agreements. We believe our employee relations are good.

Smaller Reporting Company

We are a “smaller reporting company” as defined in Rule 12b-2 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). We may take advantage of certain of the scaled disclosures available to smaller reporting companies and will be able to take advantage of these scaled disclosures for so long as our public float is below $250 million (i.e., the public float test) as measured on the last business day of our most recently completed second fiscal quarter, or our annual revenue for the most recently completed fiscal year is less than $100 million and our public float is less than $700 million (i.e., the two-part revenue and public float test) as measured on the last business day of our second fiscal quarter.

Corporate Information

Oncolytics Biotech Inc. was formed under the Business Corporations Act (Alberta) on April 2, 1998 as 779738 Alberta Ltd. On April 8, 1998, we changed our name to Oncolytics Biotech Inc.

Our principal place of business is located at 4350 Executive Drive, Suite 325, San Diego, California, U.S. 92121. Our agent for service in the U.S. is Registered Agent Solutions, Inc., 838 Walker Road Suite 21-2 Delaware 19904. On October 20, 2025, we filed a Registration Statement on Form F-4 with the U.S. Securities and Exchange Commission (as amended by Amendment No. 1 to Form F-4, as filed on December 5, 2025) that included a management circular, prospectus and other relevant documents related to various proposals contained therein. It included plans to hold a Special Meeting of Shareholders to vote on, among other things, a series of transactions that will change the jurisdiction of our company from the Province of Alberta in Canada to the State of Nevada in the United States of America (the “Domestication”). On January 15, 2026, the resolutions described in this registration statement related to the Domestication were passed. On March 17, 2026, as part of the Domestication process, we changed our jurisdiction of incorporation to the Province of British Columbia in Canada. We expect the Domestication to become effective on or around March 31, 2026.

“Oncolytics,” and other trademarks or service marks of Oncolytics Biotech Inc. appearing in this Annual Report are the property of Oncolytics Biotech Inc. Trademarks, trade names, and service marks of other companies appearing in this Annual Report are the property of their respective holders.

Financial and other information about our company is available on our website at https://oncolyticsbiotech.com/. We make available on our website, free of charge, copies of our Annual Report on Form 10-K, Quarterly Reports on Form 10‑Q, Current Reports on Form 8‑K, including exhibits, and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act, as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. We may use our website as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation Fair Disclosure promulgated by the SEC. These disclosures will be included on our website under the “Investors” section. All reports we file with the SEC are available free of charge via EDGAR through the SEC website at www.sec.gov. We have included the web addresses of Oncolytics Biotech Inc. and the SEC as inactive textual references only. Except as specifically incorporated by reference into this Annual Report, information on these websites is not part of this filing.

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SUMMARY OF RISK FACTORS

Investing in our securities, including our common shares, involves a high degree of risk. You should carefully consider the risks summarized below and other risks that we face, a detailed discussion of which can be found under “