Sodium Thiosulfate

– Study, Which Enrolled 27 Patients, Met Primary Endpoint with a Significant Reduction in Hearing Loss in 3-18 Year Old Patients who Received PEDMARK® when Compared with Historically Reported Rates of Hearing Loss in Patients Receiving Cisplatin Alone (16-24% versus 56-63%, Respectively) – – PEDMARK® Showed No Interference with Cisplatin Antitumor Activity as Evidenced by an Approximate 95% Clinical Response Rate – – The Company Plans to Pursue Registration and is Exploring Partnering or Licensing Opportunities for PEDMARK® in Japan Based Upon These Results – RESEARCH TRIANGLE PARK, N.C., Dec. 02, 2025 (GLOBE NEWSWIRE) -- Fennec Pharmaceuticals Inc. (NASDAQ:FENC; TSX: FRX), a specialty pharmaceutical company, today announced positive topline results from the investigator-initiated Phase 2/3 STS-J01 clinical trial evaluating PEDMARK® (sodium thiosulfate injection) for the reduction of cisplatin-induced ototoxicity in pediatric and adolescent and young adult (AYA) patients with non-metastatic solid tumors in Japan. 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 1 month of age and older with localized, non-metastatic, solid tumors. The study, which enrolled 27 patients in the primary cohort (patients aged 3-18 years) and 6 in exploratory cohorts and examined the addition of PEDMARK® administered six hours after cisplatin. The primary endpoint of the study was met and the data showed that 24% and 16% of evaluable patients who were treated with PEDMARK® experienced hearing loss (ototoxicity) as assessed by the American Speech-Language-Hearing Association (ASHA) criteria and Brock grade scaling, respectively. These rates compare favorably to the cisplatin-only arms of PEDMARK®’s pivotal Phase 3 trials, where 56% of children developed clinically significant hearing loss using ASHA criteria (ACCL0431) and 63% developed hearing impairment defined as Brock Grade ≥1 (SIOPEL-6). Further, the study demonstrated that among the largest subgroup of patients aged 7–18 years, hearing loss occurred in only 19% (ASHA) and 14.3% (Brock). Additionally, pharmacokinetic analyses demonstrated no reduction in cisplatin exposure, and there was no evidence of adverse interaction or attenuation of antitumor activity. The overall tumor response rate of approximately 95% confirms that PEDMARK® does not interfere with the antitumor activity of cisplatin. “The STS‑J01 findings add compelling support to the global clinical evidence base for PEDMARK®,” said Pierre S. Sayad, PhD, M.S., chief medical officer of Fennec Pharmaceuticals. “Seeing such low rates of hearing loss in a real‑world, investigator‑initiated setting in Japan reinforces the consistency and magnitude of PEDMARK®’s protective effect, which has now been demonstrated across multiple continents, tumor types and clinical settings. Importantly, the high tumor response rate and the pharmacokinetic data show that PEDMARK® does not interfere with how cisplatin works; by six hours, the active platinum is already bound and inactive. This is a critical and highly reassuring finding for physicians, families and regulators alike.” PEDMARK® was well-tolerated in the study. Across more than 200 treatment-emergent adverse events reported, none were attributed to PEDMARK®. “For decades in Japan, we have witnessed the profound and lifelong burden of cisplatin‑induced hearing loss among the children and young adults,” said Eiso Hiyama, M.D., lead investigator and professor in the Department of Pediatric Surgery at Hiroshima University Hospital in Hiroshima, Japan. “These encouraging results from the first large-scale pediatric and adolescent and young adults (AYA) trial in Japan demonstrate that PEDMARK® can protect hearing without compromising cisplatin’s efficacy or introducing any concerning side effects. As a clinician, and with the current unmet medical need of cancer patients in Japan, these findings give me confidence in the effectiveness and safety of PEDMARK® which may offer patients the chance for both survival and preserved quality of life.” Fennec intends to pursue registration in Japan and will also explore partnering or licensing opportunities for PEDMARK®. Full results from the study will be shared in a future scientific presentation and submitted for publication in a peer-reviewed journal. About the STS-J01 Study STS-J01 is a Phase 2/3, 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 3-18 years (primary cohort), 6 infants ≥1 month to <3 years (exploratory cohort), all with localized-stage solid tumors, including neuroblastoma, hepatoblastoma, germ cell tumors, bone and soft tissue sarcomas, medulloblastoma, and atypical teratoid rhabdoid tumors. Patients received PEDMARK intravenously six hours after cisplatin infusion, with dosing adjusted by body weight. The primary endpoint was the incidence of hearing impairment at the end of treatment in the 3- to 18-year-old cohort, assessed according to American Speech-Language-Hearing Association (ASHA) criteria. Secondary endpoints included safety, antitumor 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 tumors and have been vital in improving survival rates. Unfortunately, these life-saving treatments often result in permanent, irreversible hearing loss, also known as ototoxicity.i Hearing loss from cisplatin treatment is not rare. Studies show that between 60-90% of patients treated with cisplatin may develop hearing loss, depending upon the dose and duration of chemotherapyii. 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.iii 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.iv,v While audiologic monitoring is recommended to help manage ototoxicity, it is currently underutilized in certain cancer patient populations. PEDMARK® (sodium thiosulfate 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 1 month of age and older with localized, non-metastatic, solid tumors. It is a unique formulation of sodium thiosulfate 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.vi,vii 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.viii,ix 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 tumor, osteosarcoma, neuroblastoma, medulloblastoma, and other solid tumors. SIOPEL 6 enrolled only hepatoblastoma patients with localized tumors. Indications and UsagePEDMARK® (sodium thiosulfate 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 tumors. Limitations of UseThe safety and efficacy of PEDMARK have not been established when administered following cisplatin infusions longer than 6 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% to 13% 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 sulfite; patients with sulfite 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 1 month of age due to the increased risk of hypernatremia or in pediatric patients with metastatic cancers. Hypernatremia occurred in 12% to 26% of patients in clinical trials, including a single Grade 3 case. Hypokalemia occurred in 15% to 27% of patients in clinical trials, with Grade 3 or 4 occurring in 9% to 27% 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/1.73m2. Administer antiemetics prior to each PEDMARK administration. Provide additional antiemetics and supportive care as appropriate. The most common adverse reactions (≥25% with difference between arms of >5% compared to cisplatin alone) in SIOPEL 6 were vomiting, nausea, decreased hemoglobin, and hypernatremia. The most common adverse reaction (≥25% with difference between arms of >5% compared to cisplatin alone) in COG ACCL0431 was hypokalemia. Please see full Prescribing Information for PEDMARK® at: www.PEDMARK.com. About Fennec PharmaceuticalsFennec Pharmaceuticals Inc. 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, 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. Further, Fennec has patents providing protection for PEDMARK until 2039 in both the U.S. and internationally. For more information, please visit www.fennecpharma.com and follow on LinkedIn. Forward Looking StatementsExcept for historical information described in this press release, all other statements are forward-looking. Words such as “believe,” “anticipate,” “plan,” “expect,” “estimate,” “intend,” “may,” “will,” or the negative of those terms, and similar expressions, are intended to identify forward-looking statements. These forward-looking statements include statements about our business strategy, timeline and other goals, plans and prospects, including our commercialization plans respecting PEDMARK®/PEDMARQSI®, the market opportunity for and market impact of PEDMARK®/ PEDMARQSI®, its potential impact on patients and anticipated benefits associated with its use, and future commercial and regulatory milestones, and potential access to further funding after the date of this release. Forward-looking statements are subject to certain risks and uncertainties inherent in the Company’s business that could cause actual results to vary, including the risks and uncertainties that regulatory and guideline developments may change, scientific data and/or manufacturing capabilities may not be sufficient to meet regulatory standards or receipt of required regulatory clearances or approvals, clinical results may not be replicated in actual patient settings, unforeseen global instability, including political instability, or instability from an outbreak of pandemic or contagious disease, such as the novel coronavirus (COVID-19), or surrounding the duration and severity of an outbreak, protection offered by the Company’s patents and patent applications may be challenged, invalidated or circumvented by its competitors, the available market for the Company’s products will not be as large as expected, the Company’s products will not be able to penetrate one or more targeted markets, revenues will not be sufficient to fund further development and clinical studies, our ability to obtain necessary capital when needed on acceptable terms or at all, the Company may not meet its future capital requirements in different countries and municipalities, and other risks detailed from time to time in the Company’s filings with the Securities and Exchange Commission including its Annual Report on Form 10-K for the year ended December 31, 2024. Fennec disclaims any obligation to update these forward-looking statements except as required by law. For a more detailed discussion of related risk factors, please refer to our public filings available at www.sec.gov and www.sedar.com. PEDMARK® PEDMARQSI® and Fennec® are registered trademarks of Fennec Pharmaceuticals Inc. ©2025 Fennec Pharmaceuticals Inc. All rights reserved. FEN-1604-v1 For further information, please contact: Investors:Robert AndradeChief Financial OfficerFennec Pharmaceuticals Inc.+1 919-246-5299 Corporate and Media:Lindsay Rocco Elixir Health Public Relations+1 862-596-1304lrocco@elixirhealthpr.com_________________ i Rybak L. Mechanisms of Cisplatin Ototoxicity and Progress in Otoprotection. Current Opinion in Otolaryngology & Head and Neck Surgery. 2007, Vol. 15: 364-369.ii Langer T, am Zehnhoff-Dinnesen A, Radtke S, Meitert J, Zolk O. Trends Pharmacol Sci. 2013;34(8):458-469iii Landier W. Ototoxicity and Cancer Therapy. Cancer. June 2016 Vol. 122, No.11: 1647-1658.iv Clemens E, van den Heuvel-Eibrink MM, Mulder RL, et al. Recommendations for ototoxicity surveillance for childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCare Consortium. Lancet Oncol. 2019;20(1):e29-e41v Bass JK, Knight KR, Yock TI, Chang KW, Cipkala D, Grewal SS. Evaluation and management of hearing loss in survivors of childhood and adolescent cancers: a report from the children’s oncology group. Pediatr Blood Cancer. 2016;63(7):1152-1162.vi Chattaraj A et al. Cisplatin-Induced Ototoxicity: A Concise Review of the Burden, Prevention, and Interception Strategies. JCO Oncol Pract. 2023;19vii Freyer DR et al. Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017;18(1):63-74.viii Rajput K, Edwards L, Brock P, Abiodun A, Simpkin P, Al-Malky G. Ototoxicity-induced hearing loss and quality of life in survivors of paediatric cancer. Int J Pediatr Otorhinolaryngol. 2020;138:110401. doi:10.1016/j.ijporl.2020.110401ix Bass JK, Knight KR, Yock TI, Chang KW, Cipkala D, Grewal SS. Evaluation and management of hearing loss in survivors of childhood and adolescent cancers: a report from the children’s oncology group. Pediatr Blood Cancer. 2016;63(7):1152-1162.

倍特药业火速腾飞 ！35个新品获批了，60亿生物药来袭米内网本月初第十一批集采结果官宣，倍特药业9大产品中标，实力非凡。今年以来，倍特药业获批了35个新产品，顺利开拓了3个新市场，首款生物药申报上市，剑指60亿爆款。近几年，公司的研发创新加速推进，73个高端仿制药报产在审，其中7大产品将冲击国内首仿；公司已布局了20多款新药，其中1类新药BT-114143注射液、BPR-101胶囊、注射用HC010均已进入II期临床。35个重磅新品获批，第十一批集采大丰收倍特药业是一家专业从事医药创新和高品质药物研发、生产及销售的高新技术企业，重点聚焦创新药、特色原料药、高端仿制药和新型给药系统四大方向，实现从中间体、原料药到制剂，覆盖化学药（含核素药）、生物药、中成药的全生态医药产业链布局。近几年公司的新品研发陆续进入丰收期：2021年获批了13个新品，2022年获批了16个新品，2023年获批了22个新品，2024年获批了34个新品（含1个2.2类新药），2025年至今已拿下35个新品……今年只剩下最后1个月，全年获批数量能否再创新高，值得期待。表1：2025年至今倍特药业获批的新产品（按大类统计）来源：米内网中国申报进度（MED）数据库截至目前，倍特药业拥有的产品数量升至370多个（按现有批文统计，不含原料药），2025年公司成功开拓了3个新亚类市场，巴氯芬口服溶液是公司首款肌肉松弛药，硫代硫酸钠注射液是公司首款其它所有治疗用药品，枸橼酸托瑞米芬片是公司首款内分泌治疗用药。内分泌治疗用药是抗肿瘤和免疫调节剂（化+生）市场的热销亚类之一，在中国三大终端六大市场（统计范围见文末）的市场规模持续正增长，2023年突破200亿元关口，2024年涨至208亿元新峰值，2025上半年增长率高达4.15%，市场空间巨大。枸橼酸托瑞米芬片是内分泌治疗用药内服TOP8产品，倍特药业是该产品国产第五家获批企业。表2：倍特药业中标第十一批集采的产品情况来源：米内网中国上市药品（MID）数据库截至2025年11月28日，倍特药业过评/视同过评的产品数量达到了175个。刚结束的第十一批集采（11月7日官宣中选结果），公司有9大产品顺利中标，其中包括了7个近两年获批的“光脚产品”，涉及富马酸福莫特罗吸入溶液、钆布醇注射液、罗沙司他胶囊、盐酸去氧肾上腺素注射液、注射用丁二磺酸腺苷蛋氨酸、法莫替丁注射液、碳酸氢钠注射液，上述产品将借集采之力迎来新一波爆发期。首个生物药即将面世，73个高端仿制药在路上据米内网统计，2024年至今倍特药业报产在审的仿制药新品还有73个，涉及11个大类（32个亚类），其中将参与争夺阿糖胞苷注射液、佩玛贝特片、螺内酯口服混悬液、瑞维那新吸入溶液、苯磺酸美洛加巴林片、磷霉素氨丁三醇颗粒、盐酸头孢卡品酯颗粒7个产品的国内首仿。表3：2024年至今倍特药业部分报产在审的重磅新品来源：米内网中国申报进度（MED）数据库值得注意的是，倍特药业在性激素及生殖系统调节剂、影响骨结构及其矿化的药物、诊断用药、诊断用放射性药物、其它呼吸系统制剂5个亚类市场将迎来首个获批产品。2024年在中国三大终端六大市场，性激素及生殖系统调节剂（化+生）的市场规模在150亿元以上。图1：倍特药业2024年至今报产在审的新药来源：米内网中国申报进度（MED）数据库今年9月，倍特药业提交了司美格鲁肽注射液的3.3类新药上市申请获得CDE承办，该产品是公司首个报产的生物药，具有里程碑意义。司美格鲁肽是全球重磅产品，2024年Ozempic+Rybelsus+Wegovy在全球的销售额合计超过了2018亿丹麦克朗（按即时汇率约为310亿美元），而在中国三大终端六大市场，司美格鲁肽的销售额也超过了60亿元。20多款化生新药来势汹汹，3款1类新药风驰电掣今年以来，倍特药业有7款1类新药获批临床，其中PRT-064040鼻喷雾剂、BPR-102胶囊、SNH-119014片、BPR-6023021注射液为首次获批。今年6月，PRT-064040鼻喷雾剂完成了偏头痛I期临床首例受试者入组，SNH-119014片完成了治疗血红蛋白病（包括但不限于地中海贫血、镰状细胞病）I期临床首例受试者入组。此外，化药2类新药（含2.2、2.4类）PRT-062鼻喷雾剂在10月底获批临床，生物药3.3类新药帕博利珠单抗注射液的临床申请也于近日获批了。表4：倍特药业部分在研的重磅新药来源：米内网中国临床试验数据库整体来看，倍特药业在化生市场已布局了超过20款新药，其中12款已在临床阶段。目前进度较快的是BT-114143注射液、BPR-101胶囊、注射用HC010、盐酸(R)-氯胺酮鼻喷雾剂，均已进入II期临床。化药1类新药BT-114143注射液是一款全新小分子纤溶酶原活化抑制剂，拟用于治疗和预防纤维蛋白溶解亢进引起的各种出血和疾病，该新药的膝关节置换围术期出血II期临床在今年7月正式启动。生物药1类新药BPR-101胶囊是一款针对细菌性阴道病（BV）的新型治疗药物，其试验原理基于通过调节阴道微生态环境，抑制有害菌群的过度生长，从而恢复阴道的正常菌群平衡，该新药的细菌性阴道病II期临床在今年5月完成。生物药1类新药注射用HC010是一款全球首创的靶向人PD-1、CTLA-4和VEGF的三特异性抗体，可同时抑制两个免疫检查点和血管新生，该新药用于晚期实体瘤治疗II期临床在今年10月完成了首例受试者入组。资料来源：米内网数据库注：米内网《中国三大终端六大市场药品竞争格局》，统计范围：城市公立医院和县级公立医院、城市社区中心和乡镇卫生院、城市实体药店和网上药店，不含民营医院、私人诊所、村卫生室，不含县乡村药店；上述销售额以产品在终端的平均零售价计算。数据统计截至11月28日，如有疏漏，欢迎指正！