Mr. Robert Andrade reports

FENNEC PHARMACEUTICALS ANNOUNCES INVESTIGATOR-SPONSORED STUDY TO BE CONDUCTED BY UNIVERSITY OF ARIZONA CANCER CENTER

Fennec Pharmaceuticals Inc. has initiated an investigator-sponsored study by University of Arizona Cancer Center to evaluate use of Pedmark (sodium thiosulphate injection) in adolescent and young adult (AYA) and adult patients with head and neck and testicular cancers receiving cisplatin.

Pedmark is currently approved for pediatric patients one month of age and older with localized, non-metastatic solid tumours and is also recognized by the National Comprehensive Cancer Network with a 2A recommendation for use in adolescent and young adult patients.

Fennec recently announced the initiation of two other institution-led clinical studies:

• In March, 2026, Fennec announced that Tampa General Hospital (TGH) Cancer Institute is initiating a study evaluating the real-world clinical utility of Pedmark in reducing the risk of ototoxicity in AYA and adult cancer patients receiving cisplatin-based treatment. Additional investigator-initiated studies supporting the use of Pedmark in additional tumour types and patient populations, including AYA cancer, have been submitted to Fennec and are currently under review.
• In December, 2025, Fennec announced that City of Hope, a United States cancer research and treatment organization, is evaluating Pedmark for the prevention of cisplatin-induced ototoxicity (CIO) in adult men with stage II to III metastatic testicular germ cell tumours.

Additional investigator-initiated studies supporting the use of Pedmark have been submitted to Fennec and are currently under review.

"At Fennec, we are committed to supporting independent research efforts, which help build real-world evidence and expand understanding of how Pedmark may benefit patients beyond the populations studied in our pivotal trials," said Pierre S. Sayad, PhD, MS, chief medical officer of Fennec Pharmaceuticals. "Within the last few months, we have announced the initiation of three new studies with leading and highly respected academic and community oncology centres. We believe that data and insights generated through these studies -- and others to come -- will help support broader clinical adoption of Pedmark to prevent ototoxicity, or permanent hearing loss, in AYA and adult cancer patients receiving cisplatin-based treatment. We look forward to continued dialogue with regulatory authorities regarding the potential pathways for Pedmark label expansion as our growing body of evidence-based data matures."

University of Arizona study details

University of Arizona Cancer Center:  Tucson, Ariz.

Principal investigator:   Lisa Davis/Alejandro Recio-Boiles

Title:  Phase I/II Open-Label Trial of Intravenous Sodium Thiosulfate (Pedmark) as Otoprotectant in Adults Receiving Cisplatin Chemotherapy

Overview:  Phase I/II study to determine the efficacy of intravenous sodium thiosulphate to reduce hearing impairment caused by cisplatin as determined from prior hazard ratio (HR) risk reduction compared with historical control data and determine the systemic elimination of unbound cisplatin up to six hours after infusion.

About cisplatin-induced ototoxicity

Cisplatin and other platinum-based chemotherapies are widely used to treat solid tumours and have been vital in improving survival rates. Unfortunately, these life-saving treatments often result in permanent, irreversible hearing loss, also known as ototoxicity.

Hearing loss from cisplatin treatment is not rare. Studies show that between 60 to 90 per cent of patients treated with cisplatin may develop hearing loss, depending upon the dose and duration of chemotherapy. Many of those treated with cisplatin will require lifelong hearing aids or cochlear implants, which can be helpful for some, but do not reverse the hearing loss and can be costly over time. Treatment-induced hearing loss can reduce quality of survivorship as it impacts many aspects of life, such as speech and language skills, academic performance, social-emotional development, career potential, and the ability to live independently. While audiologic monitoring is recommended to help manage ototoxicity, it is currently underutilized in certain cancer patient populations. Pedmark (sodium thiosulphate injection)

Pedmark is the first and only United States Food and Drug Administration-(FDA)-approved therapy indicated to reduce the risk of ototoxicity associated with cisplatin treatment in pediatric patients one month of age and older with localized, non-metastatic, solid tumours. It is a unique formulation of sodium thiosulphate in single-dose, ready-to-use vials for intravenous use in pediatric patients. Pedmark is also the first and only therapeutic agent with proven efficacy and safety data with an established dosing regimen, across two open-label, randomized phase 3 clinical studies, the Children's Oncology Group (COG) Protocol ACCL0431 and SIOPEL 6.

Additionally, Pedmark is recommended for the adolescent and young adult (AYA) population by the National Comprehensive Cancer Network, or NCCN, with a 2A endorsement.

Approximately 500,000 patients in the U.S. are diagnosed annually with cancers that could be treated with a platinum-based chemotherapy. The incidence of ototoxicity depends upon the dose and duration of chemotherapy, and many of those treated will require lifelong hearing aids. Until the FDA approval of Pedmark, there were no preventative agents for this hearing loss. Patients with hearing loss resulting from cancer treatment have a statistically significant worse quality of life compared with peers who have no hearing loss.

Pedmark has been studied by co-operative groups in two phase 3 clinical studies of survival and reduction of ototoxicity, COG ACCL0431 and SIOPEL 6. Both studies have been completed. The COG ACCL0431 protocol enrolled childhood cancers typically treated with intensive cisplatin therapy for localized and disseminated disease, including newly diagnosed hepatoblastoma, germ cell tumour, osteosarcoma, neuroblastoma, medulloblastoma, and other solid tumours. SIOPEL 6 enrolled only hepatoblastoma patients with localized tumours.

Indications and usage

Pedmark (sodium thiosulphate injection) is indicated to reduce the risk of ototoxicity associated with cisplatin in pediatric patients one month of age and older with localized, non-metastatic solid tumours.

Limitations of use

The safety and efficacy of Pedmark have not been established when administered following cisplatin infusions longer than six hours. Pedmark may not reduce the risk of ototoxicity when administered following longer cisplatin infusions, because irreversible ototoxicity may have already occurred.

Important safety information

Pedmark is contraindicated in patients with history of a severe hypersensitivity to sodium thiosulfate or any of its components.

Hypersensitivity reactions occurred in 8 per cent to 13 per cent of patients in clinical trials. Monitor patients for hypersensitivity reactions. Immediately discontinue Pedmark and institute appropriate care if a hypersensitivity reaction occurs. Administer antihistamines or glucocorticoids (if appropriate) before each subsequent administration of Pedmark. Pedmark may contain sodium sulphite; patients with sulfite sensitivity may have hypersensitivity reactions, including anaphylactic symptoms and life-threatening or severe asthma episodes. Sulphite sensitivity is seen more frequently in people with asthma.

Pedmark is not indicated for use in pediatric patients less than one month of age due to the increased risk of hypernatremia or in pediatric patients with metastatic cancers.

Hypernatremia occurred in 12 per cent to 26 per cent of patients in clinical trials, including a single Grade 3 case. Hypokalemia occurred in 15 per cent to 27 per cent of patients in clinical trials, with Grade 3 or 4 occurring in 9 per cent to 27 per cent of patients. Monitor serum sodium and potassium levels at baseline and as clinically indicated. Withhold Pedmark in patients with baseline serum sodium greater than 145 mmol/L.

Monitor for signs and symptoms of hypernatremia and hypokalemia more closely if the glomerular filtration rate (GFR) falls below 60 mL/min/1.73 square metres.

Administer antiemetics prior to each Pedmark administration. Provide additional antiemetics and supportive care as appropriate.

The most common adverse reactions (greater than or equal to 25 per cent with difference between arms of greater than 5 per cent compared with cisplatin alone) in SIOPEL 6 were vomiting, nausea, decreased hemoglobin and hypernatremia. The most common adverse reaction (greater than or equal to 25 per cent with difference between arms of greater than 5 per cent compared with cisplatin alone) in COG ACCL0431 was hypokalemia.

About Fennec Pharmaceuticals Inc.

Fennec Pharmaceuticals is a specialty pharmaceutical company committed to the fight against ototoxicity in cancer patients who receive cisplatin-based chemotherapy. Fennec is focused on the commercialization of Pedmark to reduce the risk of platinum-induced ototoxicity in cancer patients. Pedmark received FDA approval in September, 2022, and European Commission approval in June, 2023, and United Kingdom (U.K.) approval in October, 2023, under the brand name Pedmarqsi.

In March, 2024, Fennec entered into an exclusive licensing agreement under which Norgine Pharmaceuticals Ltd., a leading European specialist pharmaceutical company, with rights to commercialize Pedmarqsi in Europe, U.K., Australia and New Zealand. Pedmarqsi is now commercially available in the U.K. and Germany.

Pedmark has received orphan drug exclusivity in the U.S. and Pedmarqsi has received pediatric use marketing authorization in Europe, which includes eight years plus two years of data and market protection.

We seek Safe Harbor.