Mr. Robert Andrade reports

FENNEC PHARMACEUTICALS ANNOUNCES ORAL PRESENTATION OF DETAILED RESULTS FROM INVESTIGATOR-INITIATED PHASE 2 STS-J01 CLINICAL STUDY OF PEDMARK® IN JAPAN AT SIOP 2026

Fennec Pharmaceuticals Inc. will provide an oral presentation of detailed results from the investigator-initiated phase 2 STS-J01 clinical trial evaluating Pedmark (sodium thiosulphate injection) for the reduction of cisplatin-induced ototoxicity in pediatric and adolescent and young adult (AYA) patients with non-metastatic solid tumours in Japan. The data will be presented today during the 58th Annual International Society of Pediatric Oncology (SIOP) Annual Meeting in San Antonio, Tex.

• Primary end point met: American Speech-Language-Hearing Association-(ASHA)-defined hearing loss occurred in 24.0 per cent of patients versus the prespecified historical benchmark of 56.4 per cent (P equals 0.001);
• 84 per cent of patients had grade 0 hearing loss by brock criteria; no grade 3 or grade 4 hearing loss was observed;
• Objective responses observed in 23 of 24 evaluable patients (95.8 per cent); prospective pharmacokinetic analyses provide new mechanistic insight supporting the six-hour Pedmark administration interval for pediatric and adolescent and young adult (AYA) patients;
• Building upon the pivotal children's oncology group (COG) protocol ACCL0431 and Siopel 6 studies, STS-J01 represents third study to demonstrate that Pedmark showed no interference with cisplatin antitumour activity.

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 and is also recognized by the National Comprehensive Cancer Network with a 2A endorsement for use in AYA patients.

The study enrolled 33 patients across 11 institutions in Japan, including 27 patients in the primary cohort and six in exploratory cohorts. Key study findings include:

• Among the 25 patients comprising the primary efficacy population, ASHA-defined hearing loss occurred in 24.0 per cent (six/25), significantly lower than the prespecified historical benchmark of 56.4 per cent (P equals 0.001).
• Nineteen of 25 patients (76.0 per cent) remained free of ASHA-defined hearing loss. By Brock criteria, 84.0 per cent of patients had Grade 0 hearing loss, and no patient experienced Grade 3 or Grade 4 hearing loss.
• Objective tumour responses were observed in 23 of 24 evaluable patients (95.8 per cent), providing reassuring clinical context for delayed Pedmark administration six hours following cisplatin.
• Prospective pharmacokinetic analyses further characterized the interaction between Pedmark and cisplatin-derived platinum and provide mechanistic support for the six-hour administration strategy for pediatric and adolescent and young adult (AYA) patients.

"The clinical and pharmacologic findings of STS-J01 are compelling. We observed a significant reduction in hearing loss, with no Grade 3 or Grade 4 hearing loss by Brock criteria, alongside a 95.8-per-cent objective response rate in evaluable patients. The prospective pharmacokinetic analyses further provide important mechanistic insight into why the six-hour interval matters, supporting a model in which Pedmark acts on residual circulating and exchangeable platinum after cisplatin has had time to distribute and initiate its antitumour activity. Together, these findings add an important independent body of evidence supporting the clinical rationale for delayed Pedmark administration," said Pierre S. Sayad, PhD, MS, chief medical officer of Fennec Pharmaceuticals.

The safety profile was consistent with the known tolerability profile of Pedmark and the expected toxicities of cisplatin-containing chemotherapy. No serious adverse event was attributed to Pedmark, and no Grade 4 Pedmark-related toxicity was observed.

"For patients navigating cancer in Japan, the ability to successfully treat their tumours while preserving hearing can have a profound impact on their lives long after treatment ends. Cisplatin remains an important and effective treatment, but the risk of permanent hearing loss represents a significant unmet need, particularly for children and young people who may live with its consequences for the rest of their lives," said Eiso Hiyama, MD, PhD, lead investigator and professor in the Department of Pediatric Surgery at Hiroshima University Hospital in Hiroshima, Japan. "The results from STS-J01 are encouraging because they demonstrate significant hearing protection and provide reassuring clinical context regarding antitumour activity with delayed Pedmark administration. We believe that these results provide further support and confidence in Pedmark for health care professionals."

Fennec is pursuing registration in Japan and is currently exploring partnering or licensing opportunities for Pedmark.

About the STS-J01 study

STS-J01 is a phase 2, investigator-initiated, open-label, single-arm clinical trial designed to evaluate Pedmark for the prevention of cisplatin-induced ototoxicity. The study enrolled 33 patients in two cohorts: 27 children ages three to 18 years (primary cohort), and six patients in exploratory cohorts, all with localized-stage solid tumours, including neuroblastoma, hepatoblastoma, germ cell tumours, bone and soft tissue sarcomas, medulloblastoma, and atypical teratoid rhabdoid tumours. Patients received Pedmark intravenously six hours after cisplatin infusion, with dosing adjusted by body weight. The primary end point was the incidence of hearing impairment at the end of treatment in the three- to 18-year-old cohort, assessed according to American Speech-Language-Hearing Association (ASHA) criteria. Secondary end points included safety, antitumour efficacy, pharmacokinetics and incidence of hearing loss as measured by Brock grading. Exploratory measures included longitudinal audiometric follow-up and validation of surrogate hearing tests.

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 United States 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.

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 multiple countries.

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.