Mr. Robert Andrade reports

FENNEC PHARMACEUTICALS ANNOUNCES CLINICAL RESEARCH COLLABORATION WITH TAMPA GENERAL HOSPITAL CANCER INSTITUTE

Fennec Pharmaceuticals Inc. has noted the Tampa General Hospital (TGH) Cancer Institute is initiating a study evaluating the real-world clinical utility of sodium thiosulphate injection (Pedmark) in reducing the risk of ototoxicity in adolescent and young adult (AYA) and adult cancer patients receiving cisplatin-based treatment.

"The TGH Cancer Institute, in collaboration with the USF Health Morsani College of Medicine, is committed to better understanding and advancing otoprotective strategies aimed at preserving auditory function in patients receiving cisplatin chemotherapy," said Gene A. Wetzstein, PharmD, BCOP, director of Supportive Care Research & Scientific Affairs at the TGH Cancer Institute and principal investigator of the initiative. "This evaluation will examine real-world clinical data and audiology monitoring that will help inform future clinical research and quality efforts in assessing, preventing and managing ototoxicity."

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 AYA patients.

"Real-world evidence plays a critical role in demonstrating the clinical utility of Pedmark across diverse patient populations and tumour types," said Dr. Pierre S. Sayad, PhD, MS, chief medical officer of Fennec Pharmaceuticals. "As more institutions generate data on its use outside of controlled trials, clinicians will gain a clearer picture of the important role of Pedmark in providing hearing loss protection for patients receiving cisplatin."

The following sections provide general background information and labeling approved by the United States' Food and Drug Administration for Pedmark and are not intended to solicit participation in any research activity.

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 U.S. 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 1 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 thiosulphate 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 sulphite sensitivity may have hypersensitivity reactions, including anaphylactic symptoms and life-threatening or severe asthma episodes. Sulfite 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, will commercialize pedmarqsi in Europe, United Kingdom, 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. Further, Fennec has patents providing protection for Pedmark until 2039 in both the U.S. and internationally.

We seek Safe Harbor.